Temporal patterns of inflammatory biomarkers measured in the cerebrospinal fluid of patients with aneurysmal subarachnoid hemorrhage using multiplex Proximity Extension Assay technology.

Temporal patterns of inflammatory biomarkers measured in the cerebrospinal fluid of patients with aneurysmal subarachnoid hemorrhage using multiplex Proximity Extension Assay technology. | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Temporal patterns of inflammatory biomarkers measured in the cerebrospinal fluid of patients with aneurysmal subarachnoid hemorrhage using multiplex Proximity Extension Assay technology. Pavlos Vlachogiannis, Lars Hillered, Per Enblad, Elisabeth Ronne-Engström This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-17091/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Neuroinflammation has been extensively studied in the context of subarachnoid hemorrhage (SAH) in recent years. A common approach is correlation of levels of single or few inflammatory biomarkers with clinical parameters such as cerebral vasospasm and outcome. However, the complexity of the inflammatory response post SAH may require a more comprehensive overall approach by analyzing multiple biomarkers simultaneously. Methods Twenty-nine patients with SAH requiring insertion of external ventricular drainage were enrolled and ventricular cerebrospinal fluid was collected at days 1, 4 and 10 after hemorrhage. The levels of 92 inflammatory biomarkers were simultaneously measured in the samples using Proseek Multiplex Inflammation 1® assay (Olink Proteomics, Uppsala, Sweden) based on Proximity Extension Assay (PEA) technology. Thirty-eight proteins were excluded from further analysis due to lack of >10% of measurable values. Temporal patterns for each of the remaining 54 proteins were illustrated on graphs with medians and quartiles. Wilcoxon matched pairs test was used for comparison of the medians between time points. Results Four different patterns were visually observed with an early peak and gradually decreasing trend (9 proteins), middle peak (14 proteins), late peak after a gradually increasing trend (27 proteins) and no specific pattern (4 proteins). Several biomarkers showed statistically significant increasing trends (defined as day 1 < day 4 < day 10 values) and late peaks (day 4 day 4) such as leukemia inhibitor factor (LIF) and macrophage inflammatory factor-1β (MIP-1β). No statistically significant decreasing trends (defined as day 1 > day 4 > day 10) were observed. Two proteins showed statistically significant middle peaks (chemokine CCL28 and Delta and Notch epidermal growth factor-related receptor-DNER). Conclusion The comprehensive data set provided in this study may act as an illustration of an inflammatory profile of the acute phase of SAH showing groups of biomarkers with similar temporal patterns of activation. Further studies can be designed based on these data in order to explore potential implications on early and late clinical events in the disease course. Neurobiology of Disease subarachnoid hemorrhage neuroinflammation biomarkers Proximity Extension Assay (PEA) technology Figures Figure 1 Figure 2 Figure 3 Figure 4 Background: Spontaneous subarachnoid hemorrhage (SAH) comprises approximately 5% of all strokes with an incidence of around 9 cases per 100.000 per year and aneurysm rupture being the cause in 85% of cases.[ 1 ] Brain injury in SAH occurs both at the time of the bleeding itself, termed primary injury, but also during the following days to weeks, a phenomenon known as secondary injury. Despite advances in the critical care of SAH patients and aneurysm treatment methods, mortality and morbidity rates among the survivals from the initial bleeding remain high, reflecting a lack of effective treatments targeting the pathophysiological mechanisms that underlie the secondary injury. Delayed cerebral ischemia (DCI) develops in approximately 30–40% of SAH patients and is considered to be a major cause of unfavorable outcome.[ 2 ] For decades the condition was attributed to cerebral vasospasm (CV), i.e. the narrowing of basal cerebral arteries seen early on angiography and persisting for up to two weeks post SAH leading to decreased cerebral blood flow (CBF) and infarctions in the affected territories.[ 3 ] However, about 20% of SAH patients develop DCI without evidence of CV and only 30% of patients with CV actually suffer from DCI.[ 4 ] Moreover, the randomized multicenter CONCSIOUS-1 trial with the endothelin receptor antagonist Clazosentan failed to show any effect on functional outcome or incidence of cerebral ischemia despite significant decrease of CV.[ 5 , 6 ] Thus, an uncoupling of angiographic vasospasm and DCI became apparent and new concepts emerged as potential underlying mechanisms of delayed brain injury.[ 7 , 8 ] Early brain injury (EBI) refers to the events occurring within the first 72 h from ictus and includes the primary injury and its direct consequences. Elevation of intracranial pressure (ICP), global ischemia, impairment of CBF autoregulation, cortical spreading depolarization (CSD), disruption of blood-brain barrier (BBB), cell death, oxidative stress and inflammatory processes are among the mechanisms that are activated shortly after aneurysm rupture and evolve during the following days.[ 9 ] The processes triggered by the EBI are now believed to play an important role in the development of DCI.[ 9 , 10 ] Neuroinflammation may be a mechanistic link between these two conditions and has been studied extensively in the past years.[ 11 – 13 ] Many clinical and experimental studies report levels of single or few inflammatory biomarkers (such as cytokines) in the peripheral blood, cerebrospinal fluid (CSF) and cerebral extracellular fluid through microdialysis (MD) in SAH patients or animal models and further correlate these biomarkers with clinical parameters and outcome.[ 14 – 22 ] Although this strategy provides useful insight in the interplay between inflammation and the disease course it fails to account for the complexity of the involved mechanisms that cannot be adequately described by a single (or few) parameter(s) alone. The aim of the present study was to provide a comprehensive inflammatory profile of the acute phase of SAH by simultaneously measuring the levels of 92 inflammatory biomarkers in the CSF at days 1, 4 and 10 after admission using multiplex Proximity Extension Assay (PEA) technology. The biomarkers were then categorized into different groups according to their temporal expression. Methods: Ethics The study was conducted in accordance with Declaration of Helsinki for human studies and approved by Uppsala University Ethics Committee. All participants or their next of kin gave written consent for participation in the study. Patients Demographic data of the 29 patients included in the study are presented in Table 1 . Inclusion period was between May 2013 and August 2014. Eligibility criteria was spontaneous SAH severe enough to require insertion of an external ventricular drain (EVD) within 24 h from ictus. Patients considered terminally ill from the bleeding were excluded. Brain CT scans were used to establish the diagnosis of SAH and were classified according to Fisher scale (median 4).[ 23 ] World Federation of Neurosurgical societies (WFNS) and Hunt & Hess scores were noted on admission (medians 4 and 3, respectively).[ 24 , 25 ] CT angiography and catheter angiography were performed in all cases and aneurysms were identified in 28 patients. In 26 patients the aneurysms were endovascularly secured and the remaining two were surgically clipped. The patients were treated at the Neurointensive Care Unit of Uppsala University Hospital for at least 10 days after the bleeding. Standardized treatment protocols described in a previous publication were applied.[ 26 ] Functional outcome was assessed by a research nurse at 1 year using Glasgow Outcome Scale.[ 27 ] Table 1 Demographic data of the patient cohort. Number of patients 29 Male vs Female 12 vs 17 Mean age (range) 57 (37–81) Median Hunt & Hess score 3 Median World Federation of Neurosurgical Societies score 4 Median Fisher grade 4 Anterior vs posterior circulation aneurysm 23 vs 5 (1 patient with no aneurysm) Embolization vs surgery 26 vs 2 Favorable vs unfavorable outcome (Glasgow Outcome Scale) 9 vs 20 CSF samples and analysis Ventricular CSF samples were collected through the EVD within 24 h, on day 4 and on day 9–11 after the bleeding, centrifuged directly after collection and frozen in -70 °C. The samples were then analyzed using Proseek Multiplex Inflammation 1®, a multiplex assay panel manufactured by Olink Proteomics AB, Uppsala, Sweden where 92 inflammation-related biomarkers are simultaneously measured using Proximity Extension Assay (PEA) technology (available online at https://www.olink.com/products/inflammation ). The analytical method was previously described in detail.[ 28 ] Values are provided in output unit Normalized Protein Expression (NPX) on log2 scale. NPX values express relative quantification between samples but is not an absolute quantification. Limit of detection (LOD) is determined for each biomarker based on the negative controls analyzed in each run. Biomarkers A list of the 92 biomarkers included in the panel as well as their families is provided in Table 2 . In summary, the panel included 31 cytokines, 20 chemokines, 9 growth factors, 8 tumor necrosis factor (TNF)-family members, 6 membrane glycoproteins, 6 neurotrophic factors, 5 proteases and 7 miscellaneous proteins. A total of 87 NPX values (29 patients x 3 time points) corresponding to protein concentrations were collected for each biomarker. Variations in the detectability of the biomarkers in the samples were noticed; for example, in 44 proteins all samples were successfully analyzed while in 6 proteins all values were below limit of detection. An inclusion criterion was therefore defined that the values needed to be above level of detection (LOD) in at least 90% of the samples for each protein (that is < 9 missing values), which lead to the exclusion of 38 proteins, thus leaving 54 proteins for further analysis. Table 2 List of biomarkers included in the panel Nr PROTEIN FULL NAME FAMILY 1 4E-BP1 Eukaryotic translation initiation factor 4E-binding protein 1 Translation factor 2 ADA Adenosine deaminase Deaminase 3 ARTN Artemin Neurotrophic factor 4 AXIN1 Axin-1 G-protein regulator 5 BDNF Brain-derived neurotrophic factor Neurotrophic factor 6 beta-NGF Beta-nerve growth factor Neurotrophic factor 7 CASP-8 Caspase-8 Cysteine protease 8 CCL11 C-C motif chemokine ligand 11 (Eotaxin) Chemokine 9 CCL13 (MCP-4) C-C motif chemokine ligand 13 (monocyte chemotactic protein 4) Chemokine 10 CCL19 C-C motif chemokine ligand 19 Chemokine 11 CCL2 (MCP-1) C-C motif chemokine ligand 2 (monocyte chemotactic protein 1) Chemokine 12 CCL20 C-C motif chemokine ligand 20 Chemokine 13 CCL23 (MIP-3) C-C motif chemokine ligand 23 (macrophage inflammatory protein-3) Chemokine 14 CCL25 C-C motif chemokine ligand 25 Chemokine 15 CCL28 C-C motif chemokine ligand 28 Chemokine 16 CCL3 (MIP-1α) C-C motif chemokine ligand 3 (macrophage inflammatory protein-1α) Chemokine 17 CCL4 (MIP-1β) C-C motif chemokine ligand 4 (macrophage inflammatory protein-1β) Chemokine 18 CCL7 (MCP-3) C-C motif chemokine ligand 7 (monocyte chemotactic protein 3) Chemokine 19 CCL8 (MCP-2) C-C motif chemokine ligand 8 (monocyte chemotactic protein 2) Chemokine 20 CD244 Natural killer cell receptor 2B4 Membrane glycoprotein 21 CD40 Tumor necrosis factor receptor superfamily member 5 TNF receptor superfamily 22 CD5 T-cell surface glycoprotein CD5 Membrane glycoprotein 23 CD6 T-cell differentiation antigen CD6 Membrane glycoprotein 24 CDCP-1 CUB domain-containing protein 1 Membrane glycoprotein 25 CSF-1 Macrophage colony-stimulating factor 1 Cytokine 26 CST5 Cystatin-D Cysteine proteinase inhibitor 27 CX3CL1 C-X3‐C motif chemokine ligand 1 (Fractalkine) Chemokine 28 CXCL1 C-X‐C motif chemokine ligand 1 Chemokine 29 CXCL10 C-X‐C motif chemokine ligand 10 Chemokine 30 CXCL11 C-X‐C motif chemokine ligand 11 Chemokine 31 CXCL5 C-X‐C motif chemokine ligand 5 Chemokine 32 CXCL6 C-X‐C motif chemokine ligand 6 Chemokine 33 CXCL9 C-X‐C motif chemokine ligand 9 Chemokine 34 DNER Delta and Notch-like epidermal growth factor‐related receptor Growth factor 35 EN-RAGE Protein S100-A12 Calcium-binding protein 36 FGF19 Fibroblast growth factor 19 Growth factor 37 FGF-21 Fibroblast growth factor 21 Growth factor 38 FGF-23 Fibroblast growth factor 23 Growth factor 39 FGF-5 Fibroblast growth factor 5 Growth factor 40 Flt3L Fms-related tyrosine kinase 3 ligand Cytokine 41 GDNF Glial cell line-derived neurotrophic factor Neurotrophic factor 42 HGF Hepatocyte growth factor Growth factor 43 IFN-gamma Interferon gamma Cytokine 44 IL-10 Interleukin-10 Cytokine 45 IL-10RA Interleukin-10 receptor subunit alpha Cytokine 46 IL-10RB Interleukin-10 receptor subunit beta Cytokine 47 IL-12B Interleukin-12 subunit beta Cytokine 48 IL-13 Interleukin-13 Cytokine 49 IL-15RA Interleukin-15 receptor subunit alpha Cytokine 50 IL-17A Interleukin-17A Cytokine 51 IL-17C Interleukin-17C Cytokine 52 IL-18 Interleukin-18 Cytokine 53 IL-18R1 Interleukin-18 receptor 1 Cytokine 54 IL-1α Interleukin-1 alpha Cytokine 55 IL-2 Interleukin-2 Cytokine 56 IL-2RB Interleukin-2 receptor subunit beta Cytokine 57 IL-20 Interleukin-20 Cytokine 58 IL-20RA Interleukin-20 receptor subunit alpha Cytokine 59 IL-22 RA1 Interleukin-20 receptor subunit alpha-1 Cytokine 60 IL-24 Interleukin-24 Cytokine 61 IL-33 Interleukin-33 Cytokine 62 IL-4 Interleukin-4 Cytokine 63 IL-5 Interleukin-5 Cytokine 64 IL-6 Interleukin-6 Cytokine 65 IL-7 Interleukin-7 Cytokine 66 IL-8 Interleukin-8 Cytokine 67 LIF Leukemia inhibitory factor Cytokine 68 LIF-R Leukemia inhibitory factor receptor Cytokine 69 MMP-1 Matrix metalloproteinase-1 Protease 70 MMP-10 Matrix metalloproteinase-10 Protease 71 NRTN Neurturin Neurotrophic factor 72 NT-3 Neurotrophin-3 Neurotrophic factor 73 OPG Osteoprotegerin TNF receptor superfamily 74 OSM Oncostatin-M Cytokine 75 PD-L1 Programmed cell death ligand 1 Membrane glycoprotein 76 SCF Stem cell factor Cytokine 77 SIRT2 SIR2-like protein 2 NAD dependent deacetylase 78 SLAMF1 Signaling lymphocytic activation molecule Membrane glycoprotein 79 ST1A1 Sulfotransferase 1A1 Transferase 80 STAMPB STAM-binding protein Protease 81 TGFA Transforming growth factor alpha Growth factor 82 TGF-β1 Transforming growth factor beta-1 Growth factor 83 TNF Tumor necrosis factor TNF family 84 TNFB Tumor necrosis factor beta (Lymphotoxin-alpha) Cytokine 85 TNFRSF9 Tumor necrosis factor receptor superfamily member 9 TNF receptor superfamily 86 TNFSF14 Tumor necrosis factor superfamily member 14 TNF receptor superfamily 87 TRAIL (TNFSF10) TNF-related apoptosis‐inducing ligand (TNF-superfamily member 10) TNF receptor superfamily 88 TRANCE (TNFSF11) Tumor necrosis factor superfamily member 11 TNF receptor superfamily 89 TSLP Thymic stromal lymphopoietin Cytokine 90 TWEAK (TNFSF12) Tumor necrosis factor superfamily member 12 TNF receptor superfamily 91 uPA Urokinase-type plasminogen activator Protease 92 VEGF-A Vascular endothelial growth factor A Growth factor Alphabetic list of the 92 biomarkers included in Proseek Multiplex Inflammation 1® panel (abbreviations and full names) together with their families. The 54 biomarkers that met the criterion of being above level of detection in at least 90% of the samples (that is < 9 missing values for each protein) to be included for further analysis are marked in bold. Statistics The NPX values of the remaining 54 proteins were converted into linear scale using the formula 2 NPX = linear NPX in order to better visualize the trends of the biomarkers during the observation period. Median values for each day and protein were then calculated from the linear NPX values and their development over time was illustrated in graphs with upper and lower quartiles. Statistical analysis was done on the linear NPX data that were visually not normally distributed. Therefore non-parametric statistical methods were chosen. Wilcoxon matched pairs test was used for the comparison of day 1 vs day 4 vs day 10 median values for each protein. Protein expression levels in graphs were illustrated with medians and upper and lower quartiles. The results were considered statistically significant at the p < 0.05 level. All statistical analyses and graphical presentations were performed using the Statistica® software (Stat Soft, Inc., Tulsa, OK, USA). Results: Visual inspection of the linear NPX graphs revealed four different temporal patterns (Table 3 ): an early peak at day 1 followed by a decreasing trend (Group A: 9 proteins), a middle peak at day 4 (Group B: 14 proteins), an increasing trend with a late peak at day 10 (Group C: 27 proteins) and finally no specific pattern (Group D: 4 proteins). Figures 1 – 4 illustrate typical graphs of median protein expression levels (linear NPX) and upper and lower quartiles over time for each group. Medians were then compared between time points for each protein using Wilcoxon matched pairs test. Table 4 shows the results (p-value considered significant at < 0.05). Table 3 Groups of biomarkers by their temporal pattern of protein expression GROUP A (n = 9) EARLY PEAK GROUP B (n = 14) MIDDLE PEAK GROUP C (n = 27) LATE PEAK GROUP D (n = 4) NO PATTERN CCL11 CCL28 4E-BP1 CCL25 CCL20 CSF-1 ADA MCP-1 FGF-19 CST-5 CASP8 TNFRSF9 LIF DNER CCL19 VEGF-A MIP-1α (CCL3) FGF-5 CCL23 MIP-1β (CCL4) Flt3L CD40 MMP10 IL-10 CD5 TGFA IL-10RB CDCP1 TRAIL IL-18R1 CX3CL1 IL-6 CXCL1 LIF-R CXCL10 MCP-3 CXCL11 OSM CXCL5 TGF-β1 CXCL6 CXCL9 EN-RAGE HGF IL-18 IL-7 IL-8 MCP-2 OPG SCF SIRT2 STAMPB TWEAK uPA Four different groups were identified based on visual inspection of the graphs, that is an early peak followed by a decreasing trend (Group A), a middle peak (Group B), a late peak after an increasing trend (Group C) and finally no specific pattern (Group D). Table 4 Expression levels of all proteins and time points. GROUP A DAY 1 1 VS 4 DAY 4 4 VS 10 DAY 10 1 VS 10 CCL11 8,5 (5,2–12) < 0,01 5,2 (3,4–7,8) 0,16 5,1 (4,3–7,2) < 0,01 CCL20 57 (17–176) 0,32 51 (23–108) 0,08 43 (27–97) 0,25 FGF-19 17 (12–21) 0,07 16 (11–20) 0,62 13 (9,2–21) 0,16 LIF 52 (21–148) < 0,01 13 (7,8–22) 0,93 14 (6,1–34) < 0,01 MIP-1α (CCL3) 9,6 (5,2–25) 0,13 8 (5,1–11) 0,99 7,7 (6,6–12) 0,17 MIP-1β (CCL4) 80 (47–404) < 0,01 36 (22–64) 0,44 35 (28–59) < 0,01 MMP-10 17 (9,9–35) 0,20 14 (12–19) 0,06 12 (8,8–18) 0,01 TGFA 7,7 (5,7–11) 0,23 6,9 (5,4–8,5) 0,03 6,5 (5,3–7,3) 0,01 TRAIL 9,4 (6,8–16) 0,01 7,3 (5,2–8,9) 0,99 6,7 (5,3–9,6) 0,04 GROUP B DAY 1 1 VS 4 DAY 4 4 VS 10 DAY 10 1 VS 10 CCL28 1,3 (1,2 − 1,5) < 0,01 1,6 (1,5 − 1,7) 0,02 1,5 (1,3 − 1,6) 0,07 CSF-1 87 (48–126) 0,18 102 (74–131) 0,06 80 (50–111) 0,61 CST5 45 (38–61) < 0,01 60 (54–65) 0,20 57 (48–65) 0,02 DNER 138 (112–216) < 0,01 327 (250–381) 0,01 259 (170–360) < 0,01 FGF-5 3,2 (2,5 − 4,9) < 0,01 6,7 (5,5–11) 0,15 6 (4,2–9,7) 0,01 Flt3L 156 (129–231) < 0,01 267 (185–374) 0,82 285 (166–367) < 0,01 IL-10 5,1 (3,6–8) 0,31 6,3 (4,5–7,9) 0,31 4,9 (3,3–9,5) 0,92 IL-10RB 3,4 (2,9 − 6,2) < 0,01 7,1 (4,7–9,6) 0,26 7,9 (4,3–12) < 0,01 IL-18R1 3,9 (2,3–6,9) 0,12 5,7 (3,3–7,4) 0,34 5,3 (2,8 − 7,5) 0,34 IL-6 927 (267–2037) < 0,01 2715 (537–5589) 0,64 2119 (611–6838) < 0,01 LIF-R 4 (3,3–5,6) < 0,01 5,2 (4,4–7,4) 0,26 5 (4,4–6,4) 0,03 MCP-3 38 (15–78) 0,02 95 (29–172) 0,31 98 (31–290) < 0,01 OSM 11 (8,1–30) 0,02 30 (9,4–53) 0,41 31 (13–61) 0,03 TGF-β1 13 (9–25) < 0,01 30 (19–36) 0,15 29 (17–54) < 0,01 GROUP C DAY 1 1 VS 4 DAY 4 4 VS 10 DAY 10 1 VS 10 4E-BP1 2,3 (1,7 − 3,3) < 0,01 21 (3,5–71) < 0,01 111 (21–102) < 0,01 ADA 16 (10–23) < 0,01 32 (22–64) 0,055 53 (29–107) < 0,01 CASP-8 2,9 (1,7 − 3,6) 0,26 2,8 (2,2–3,9) < 0,01 5,6 (2,9–11) < 0,01 CCL19 177 (115–388) < 0,01 1772 (748–3642) 0,01 2875 (1196–5501) < 0,01 CCL23 12 (7,1–25) < 0,01 63 (31–104) < 0,01 207 (83–331) < 0,01 CD40 64 (43–101) < 0,01 109 (75–189) < 0,01 250 (137–395) < 0,01 CD5 2 (1,5 − 3,5) 0,055 3,2 (2,2–4,2) 0,23 4 (2,2–5,3) 0,01 CDCP1 13 (9–15) < 0,01 17 (15–26) < 0,01 28 (17–42) < 0,01 CX3CL1 6,5 (5,7–8,1) 0,10 9,5 (6,7–11) 0,19 11,7 (6,9–17) 0,07 CXCL1 183 (82–356) < 0,01 830 (127–1066) < 0,01 1037 (437–1973) < 0,01 CXCL10 179 (76–417) < 0,01 1573 (1024–4301) 0,25 2530 (1181–3539) < 0,01 CXCL11 5,7 (3–8) < 0,01 11,8 (8–22) 0,68 19,5 (10–39) < 0,01 CXCL5 252 (144–572) 0,68 271 (160–753) 0,73 437 (185–737) 0,56 CXCL6 21 (8,8–44) < 0,01 204 (22–408) < 0,01 642 (172–959) < 0,01 CXCL9 7,1 (6,2–19) < 0,01 25,9 (15–42) < 0,01 59 (18–116) < 0,01 EN-RAGE 2,9 (2,5 − 4,2) < 0,01 9,8 (5,8–29) 0,11 16 (5,9–39) < 0,01 HGF 36 (27–70) < 0,01 86 (67–116) 0,08 114 (64–188) < 0,01 IL-18 6,3 (4,3–10) 0,33 9,8 (3,5–20) < 0,01 24 (8,3–37) < 0,01 IL-7 2,3 (2–2,5) 0,01 2,4 (2,2–3,4) 0,31 2,8 (2,5 − 3,4) < 0,01 IL-8 6671 (4906–12663) 0,29 10867 (3084–16185) 0,03 15540 (6006–21024) 0,06 MCP-2 107 (53–188) < 0,01 404 (126–644) 0,01 527 (198–1082) < 0,01 OPG 638 (356–1629) 0,24 1076 (646–1584) 0,03 1381 (741–2481) 0,03 SCF 7,2 (5,2–11) 0,19 12 (7,9–15) 0,39 13 (6,1–19) 0,13 SIRT2 4,7 (3,3–8,2) 0,08 6,3 (3,9–10) 0,06 10 (5,2–22) < 0,01 STAMPB 3,6 (2,4–4,2) 0,40 3,5 (2,9 − 6) 0,04 6,3 (3,2–8,9) 0,01 TWEAK 179 (123–246) < 0,01 271 (202–438) 0,16 326 (214–497) < 0,01 uPA 156 (120–227) < 0,01 385 (244–565) < 0,01 1230 (525–2239) < 0,01 GROUP D DAY 1 1 VS 4 DAY 4 4 VS 10 DAY 10 1 VS 10 CCL25 2,5 (2,2–3,6) 0,04 2,2 (2–2,5) 0,04 2,5 (2–3,9) 0,58 MCP-1 9428 (7822–10942) 0,50 9491 (7628–10487) 0,85 8998 (7870–10266) 0,18 TNFRSF9 7 (3,5–10) 0,17 7,2 (5–9,8) 0,96 8,1 (3,7–11) 0,31 VEGF-A 1039 (520–1414) 0,04 689 (493–1007) 0,10 996 (535–1247) 0,38 Comparison of median protein expression levels (linear NPX) with upper and lower quartiles within parentheses between time points for each protein (classified in groups according to Table 3 ); Wilcoxon matched pairs test was used for comparison; p-values were considered significant at < 0.05 level. Group A biomarkers with statistically significant early peak, defined as significantly higher day 1 vs day 4 values, were CCL11, LIF, MIP-1β (CCL4) and TRAIL; no biomarkers in this group showed statistically significant decreasing trend (that is, significant differences between day 1 vs day 4 and day 4 vs day 10 values). Several Group B biomarkers (Table 4 ) showed significantly higher values between day 4 vs day 1 (i.e. CCL28, CST5, DNER, FGF-5, Flt3L, IL-10RB, IL-6, LIF-R, MCP-3, OSM and TGF-β1). Half of these biomarkers showed decreasing NPX values towards day 10 and the rest remained stable. The only biomarkers with statistically significant middle peak (that is, significant difference between day 4 vs day 1 and day 4 vs day 10 values) were CCL28 and DNER. Fifteen of the 27 biomarkers in Group C (Table 4 ) showed statistically significant late peak defined as significantly higher day 10 vs day 4 values (4E-BP1, CASP-8, CCL19, CCL23, CD40, CDCP1, CXCL1, CXCL6, CXCL9, IL-18, IL-8, MCP-2, OPG, STAMPB and uPA). Ten of them also showed statistically significant increasing trend during the entire observation period, that is significantly higher day 10 vs day 4 and day 4 vs day 1 values (i.e. 4E-BP1, CCL19, CCL23, CD40, CDCP1, CXCL1, CXCL6, CXCL9, MCP-2 and uPA). Discussion: In this study we present a concise data set of the sequential production of multiple biomarkers of inflammation in the CSF of patients during the first 10 days post SAH. To our knowledge, this is the largest data set to describe the inflammatory profile of SAH ever reported with 92 inflammatory biomarkers included, many of which never studied in SAH patients previously. This is also the first report of Proximity Extension Assay (PEA) technology being used for measuring biomarker expression levels in the context of SAH. Similar studies were recently published in patients with traumatic brain injury (TBI) and trigeminal neuralgia, as well as numerous other non-neurosurgical conditions (such as neuropathic pain, cardiovascular diseases, gastric cancer, etc.).[ 29 – 31 ] The analyses in the present study were performed in CSF compartment alone (not plasma or cerebral interstitial fluid) as this seems more suitable to describe the disease pathophysiology, given also that major early and late clinical complications (i.e. CV and chronic hydrocephalus) spatially correlate best with this compartment. Many of the included proteins have previously been associated to SAH inflammation, for example IL-1ra, IL-6, IL-8, TNF-a, LIF, MCP-1, and VEGF-A.[ 32 ] On the other hand, there is scarce or non-existing literature on many other proteins, some of which showed interesting temporal patterns and statistically significant peaks and trends, such as LIF, CCL11, CCL28, 4E-BP1, CD40, CXCL6, CXCL9, and IL-18.[ 20 , 33 – 36 ] Group A Nine biomarkers showed higher day 1 values and decreasing trends throughout the observation period (Tables 3 and 4 ). Four of them (CCL11, LIF, MIP-1β and TRAIL) showed statistically significant early peaks with day 1 > day 4 levels but no statistically significant decreasing trends were observed. MIP-1β (also known as CCL4) and CCL11 are members of the chemokine family (C-C motif) and are involved in chemotaxis of macrophages and activated T-cells, respectively, as well as other proinflammatory actions. Their early peak can possibly be associated to the recruitment of leukocytes at the site of the bleeding. LIF is a cytokine involved in activation of signaling pathways that regulate cell growth among other actions. A similar early peak in serum has been observed previously.[ 37 ] TRAIL, a member of the TNF superfamily (also known as TNFSF10) involved in apoptosis, has not been studied in the SAH literature. Group B Among the 14 proteins included in this group only two (CCL28 and DNER) showed statistically significant middle peaks, that is significantly higher day 4 values than both day 1 and day 10. Production of the chemokine CCL28 is induced by other proinflammatory cytokines and its chemotactic actions are exerted on B and T cells and eosinophils. Delta and Notch-like Epidermal growth factor-Receptor (DNER) is an activator of NOTCH1 pathway. None of these biomarkers have been studied in a SAH context earlier and their potential involvement in the SAH complications, mainly CV that coincides temporally with the observed middle peaks, should be examined. It should be noted that the majority of the biomarkers in this group showed a significant increase in their levels between day 1 and day 4 (11/14, Table 4 ). In almost all cases though, with the exception of the two biomarkers named above, these dynamics seemed to wear off between day 4 and day 10. Interestingly, IL-6 was recently studied by our group using a quantitative routine monoclonal antibody-based method in CSF samples from 44 patients with severe SAH. The results showed a very similar temporal IL-6 pattern as in the present study, with increasing values between day 1 and day 4 followed by decreasing values towards day 10, although remaining higher than day 1 values.[ 38 ] Group C Half of the studied biomarkers (n = 27) showed higher levels towards the end of the observation period, reflecting a more prolonged activation post SAH that may indicate an involvement in the healing processes or the development of late complications, such as late vasospasm, posthemorrhagic hydrocephalus, etc. Fifteen biomarkers (4E-BP1, CASP-8, CCL19, CCL23, DC40, CDCP1, CXCL1, CXCL6, CXCL9, IL18, IL8, MCP-2, OPG, STAMPB and uPA) showed statistically significant late peaks, meaning significantly higher day 10 than day 4 values. Apart from CASP-8, IL-18, IL-8, OPG and STAMPB all the remaining proteins in the list showed statistically significant increasing trends throughout the observation period with day 1 < day 4 < day 10 values. Chemokines CCL23, CXCL6 and CXCL9, all potent chemotactic agents for resting T-cells/monocytes, neutrophilic granulocytes and T-cells respectively, have not been studied in SAH patients earlier. Signaling pathway molecule 4E-BP1 has been implicated in the development of vasospasm in a canine SAH-model but no reports on human studied are available.[ 35 ] Protein CD40, a member of TNF family, is found on antigen-presenting cells and mediates multiple inflammatory responses. Elevated serum levels of CD40 have been associated with poor outcome and severity of neurological deficits in SAH patients.[ 36 , 39 ] IL-18, a strong proinflammatory cytokine involved in the synthesis of inflammatory mediators, has recently been shown to be a predictor of early brain injury and clinical prognosis in SAH patients as elevated concentrations correlated to cerebral edema and acute hydrocephalus.[ 20 ] It should be noted that the observed temporal pattern of IL-18 in that study differed from our study as we demonstrated a late peak of this cytokine. Urokinase (or uPA) is a serum protease that activates plasminogen to plasmin which in turn leads to thrombolysis and tissue degradation. Plasma concentrations of its receptor (soluble uPA-receptor) was not shown to correlate with neurological outcome post SAH.[ 40 ] General considerations The great variability of the expression levels and temporal patterns of the measured biomarkers is an indicator of the complexity of the inflammatory response after SAH. Many of the included proteins are well established in the SAH research both in humans and in preclinical animal models while others are novel in the SAH field. Their exact role as well as interplay with each other is not easy to establish, especially considering the fact that many of these substances are described to play both a detrimental and a beneficial role in the disease course depending on the time after bleeding.[ 41 ] This study may offer guidance for further research on groups of biomarkers based either on their families or their pattern of activation (e.g. early vs late peak) to identify potential underlying inflammatory mechanisms of SAH complications as well as novel targets of intervention in order to prevent/treat these conditions and improve outcome. Limitations A limitation with the study is that the PEA analysis method in its presently available form does not give absolute protein concentrations. However, the protein expression levels illustrate the relative concentrations and how these change over time. They also illustrate the relations between the levels of the different biomarkers. The study may be limited by the relatively small number of patients included. Another drawback may be the fact that the study is limited to the CSF compartment. Similar analyses could be performed in the CSF, cerebral interstitial fluid and plasma, giving the opportunity to compare protein levels in the different fluid compartments providing a more thorough inflammatory profile of the acute phase of the disease. Comparisons with healthy individuals could also serve as an indicator of the intensity of activation for each biomarker. Moreover, correlations of the biomarker expression levels with clinical parameters were not performed in this study, as the main goal was to provide general information of as many proteins as possible in order to look for patterns of expression for further investigation. Finally, measurements in more than three time points could possibly describe the temporal patterns of each protein more accurately. Conclusion: The temporal patterns of expression of multiple inflammation-related proteins in the acute phase of SAH are reported in this study providing an inflammatory profile of the disease that facilitates further research in the field of biomarkers. Proximity Extension Assay technology enables the measurement of the expression levels of several biomarkers simultaneously in small amounts of sample, adding a useful tool in the quest of finding relevant biomarkers to better describe and understand the complex pathophysiology of SAH. Abbreviations SAH subarachnoid haemorrhage PEA Proximity Extension Assay DCI delayed cerebral ischemia CV cerebral vasospasm CBF cerebral blood flow EBI early brain injury ICP intracranial pressure CSD cortical spreading depolarization BBB blood-brain barrier CSF cerebrospinal fluid MD microdialysis EVD external ventricular drainage CT computerized tomography WFNS World Federation of Neurosurgical Societies GOS Glasgow outcome scale NPX normalized protein expression LOD limit of detection TNF tumor necrosis factor TBI traumatic brain injury Declarations Ethics approval and consent to participate The Uppsala University Ethical review board for research on humans granted permission for the study. Informed consent for participation was obtained from the patients when feasible or their next of kin. Consent for publication Not applicable. Availability of data and material The datasets used in the current study are available from the corresponding author on reasonable request. Competing interests None. Funding This research project was funded by ALF means (Avtal om läkarutbildning och forskning), that is governmental funding for medical doctors under training for parallel research. Authors' contributions The first and last author were responsible for the study design and data collection and analysis. The first author was responsible for writing the manuscript. All the other authors contributed with critically revising and improving the manuscript. Acknowledgements The authors would like to thank all the nursing staff at the NICU at Uppsala University Hospital, Uppsala, Sweden for their collaboration in the collection of the CSF samples. Authors' information (optional) References Macdonald RL, Schweizer TA: Spontaneous subarachnoid haemorrhage. Lancet 2017, 389: 655-666. 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Lucke-Wold BP, Logsdon AF, Manoranjan B, Turner RC, McConnell E, Vates GE, Huber JD, Rosen CL, Simard JM: Aneurysmal Subarachnoid Hemorrhage and Neuroinflammation: A Comprehensive Review. Int J Mol Sci 2016, 17: 497. Provencio JJ: Inflammation in subarachnoid hemorrhage and delayed deterioration associated with vasospasm: a review. Acta Neurochir Suppl 2013, 115: 233-238. de Oliveira Manoel AL, Macdonald RL: Neuroinflammation as a Target for Intervention in Subarachnoid Hemorrhage. Front Neurol 2018, 9: 292. Mathiesen T, Edner G, Ulfarsson E, Andersson B: Cerebrospinal fluid interleukin-1 receptor antagonist and tumor necrosis factor-alpha following subarachnoid hemorrhage. J Neurosurg 1997, 87: 215-220. Fassbender K, Hodapp B, Rossol S, Bertsch T, Schmeck J, Schutt S, Fritzinger M, Horn P, Vajkoczy P, Kreisel S, et al: Inflammatory cytokines in subarachnoid haemorrhage: association with abnormal blood flow velocities in basal cerebral arteries. 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Lv SY, Wu Q, Liu JP, Shao J, Wen LL, Xue J, Zhang XS, Zhang QR, Zhang X: Levels of Interleukin-1beta, Interleukin-18, and Tumor Necrosis Factor-alpha in Cerebrospinal Fluid of Aneurysmal Subarachnoid Hemorrhage Patients May Be Predictors of Early Brain Injury and Clinical Prognosis. World Neurosurg 2018, 111: e362-e373. Wang Y, Zhong M, Tan XX, Yang YJ, Chen WJ, Liu W, Zheng K: Expression change of interleukin-8 gene in rabbit basilar artery after subarachnoid hemorrhage. Neurosci Bull 2007, 23: 151-155. Hanafy KA: The role of microglia and the TLR4 pathway in neuronal apoptosis and vasospasm after subarachnoid hemorrhage. J Neuroinflammation 2013, 10: 83. Fisher CM, Kistler JP, Davis JM: Relation of cerebral vasospasm to subarachnoid hemorrhage visualized by computerized tomographic scanning. Neurosurgery 1980, 6: 1-9. Hunt WE, Hess RM: Surgical risk as related to time of intervention in the repair of intracranial aneurysms. J Neurosurg 1968, 28: 14-20. Teasdale GM, Drake CG, Hunt W, Kassell N, Sano K, Pertuiset B, De Villiers JC: A universal subarachnoid hemorrhage scale: report of a committee of the World Federation of Neurosurgical Societies. J Neurol Neurosurg Psychiatry 1988, 51: 1457. Johansson M, Cesarini KG, Contant CF, Persson L, Enblad P: Changes in intervention and outcome in elderly patients with subarachnoid hemorrhage. Stroke 2001, 32: 2845-2949. Jennett B, Bond M: Assessment of outcome after severe brain damage. Lancet 1975, 1: 480-484. Assarsson E, Lundberg M, Holmquist G, Bjorkesten J, Thorsen SB, Ekman D, Eriksson A, Rennel Dickens E, Ohlsson S, Edfeldt G, et al: Homogenous 96-plex PEA immunoassay exhibiting high sensitivity, specificity, and excellent scalability. PLoS One 2014, 9: e95192. Dyhrfort P, Shen Q, Clausen F, Thulin M, Enblad P, Kamali-Moghaddam M, Hillered L, Lewen A: Monitoring of Protein Biomarkers of Inflammation in Human Traumatic Brain Injury Using Microdialysis and Proximity Extension Assay Technology in Neurointensive Care. J Neurotrauma 2019. Ericson H, Abu Hamdeh S, Freyhult E, Stiger F, Backryd E, Svenningsson A, Gordh T, Kultima K: Cerebrospinal fluid biomarkers of inflammation in trigeminal neuralgia patients operated with microvascular decompression. Pain 2019, 160: 2603-2611. Backryd E, Lind AL, Thulin M, Larsson A, Gerdle B, Gordh T: High levels of cerebrospinal fluid chemokines point to the presence of neuroinflammation in peripheral neuropathic pain: a cross-sectional study of 2 cohorts of patients compared with healthy controls. Pain 2017, 158: 2487-2495. Zeiler FA, Thelin EP, Czosnyka M, Hutchinson PJ, Menon DK, Helmy A: Cerebrospinal Fluid and Microdialysis Cytokines in Aneurysmal Subarachnoid Hemorrhage: A Scoping Systematic Review. Front Neurol 2017, 8: 379. Hollig A, Remmel D, Stoffel-Wagner B, Schubert GA, Coburn M, Clusmann H: Association of early inflammatory parameters after subarachnoid hemorrhage with functional outcome: A prospective cohort study. Clin Neurol Neurosurg 2015, 138: 177-183. Savarraj JPJ, Parsha K, Hergenroeder GW, Zhu L, Bajgur SS, Ahn S, Lee K, Chang T, Kim DH, Liu Y, Choi HA: Systematic model of peripheral inflammation after subarachnoid hemorrhage. Neurology 2017, 88: 1535-1545. Zhang W, Khatibi NH, Yamaguchi-Okada M, Yan J, Chen C, Hu Q, Meng H, Han H, Liu S, Zhou C: Mammalian target of rapamycin (mTOR) inhibition reduces cerebral vasospasm following a subarachnoid hemorrhage injury in canines. Exp Neurol 2012, 233: 799-806. Kubo Y, Koji T, Yoshida J, Ogawa A, Ogasawara K: Predicting neurological deficit severity due to subarachnoid haemorrhage: soluble CD40 ligand and platelet-derived growth factor-BB. Crit Care Resusc 2016, 18: 242-246. Hollig A, Stoffel-Wagner B, Clusmann H, Veldeman M, Schubert GA, Coburn M: Time Courses of Inflammatory Markers after Aneurysmal Subarachnoid Hemorrhage and Their Possible Relevance for Future Studies. Front Neurol 2017, 8: 694. Vlachogiannis P, Hillered L, Khalil F, Enblad P, Ronne-Engstrom E: Interleukin-6 Levels in Cerebrospinal Fluid and Plasma in Patients with Severe Spontaneous Subarachnoid Hemorrhage. World Neurosurg 2019, 122: e612-e618. Chen XD, Sun J, Lu C, Ba HJ, Chen MH, Lin JH, Cai JY: The prognostic value of plasma soluble CD40 ligand levels following aneurysmal subarachnoid hemorrhage. Thromb Res 2015, 136: 24-29. Kiiski H, Jalkanen V, Ala-Peijari M, Hamalainen M, Moilanen E, Peltola J, Tenhunen J: Plasma Soluble Urokinase-Type Plasminogen Activator Receptor Is Not Associated with Neurological Outcome in Patients with Aneurysmal Subarachnoid Hemorrhage. Front Neurol 2017, 8: 144. Gadani SP, Walsh JT, Lukens JR, Kipnis J: Dealing with Danger in the CNS: The Response of the Immune System to Injury. Neuron 2015, 87: 47-62. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-17091","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research","associatedPublications":[],"authors":[{"id":403751,"identity":"23efae6f-f091-420b-a405-f844b6b03498","order_by":1,"name":"Pavlos Vlachogiannis","email":"data:image/png;base64,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","orcid":"https://orcid.org/0000-0002-8597-8862","institution":"Uppsala Universitet","correspondingAuthor":true,"prefix":"","firstName":"Pavlos","middleName":"","lastName":"Vlachogiannis","suffix":""},{"id":403752,"identity":"1d90f9bd-9698-451c-a974-26c79768cc4e","order_by":2,"name":"Lars Hillered","email":"","orcid":"","institution":"Uppsala Universitet","correspondingAuthor":false,"prefix":"","firstName":"Lars","middleName":"","lastName":"Hillered","suffix":""},{"id":403753,"identity":"6b89dc3a-edbf-41d8-9582-7be4a55b3694","order_by":3,"name":"Per Enblad","email":"","orcid":"","institution":"Uppsala Universitet","correspondingAuthor":false,"prefix":"","firstName":"Per","middleName":"","lastName":"Enblad","suffix":""},{"id":403754,"identity":"5a968ae9-63b3-49be-9505-0b3fe32eb629","order_by":4,"name":"Elisabeth Ronne-Engström","email":"","orcid":"","institution":"Uppsala Universitet","correspondingAuthor":false,"prefix":"","firstName":"Elisabeth","middleName":"","lastName":"Ronne-Engström","suffix":""}],"badges":[],"createdAt":"2020-03-10 15:42:44","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-17091/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-17091/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":641180,"identity":"083cd5dd-7cab-4138-b070-31b2b90475eb","added_by":"auto","created_at":"2020-03-13 01:36:17","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":11968,"visible":true,"origin":"","legend":"Group A example; CC4 (or MIP-1ß): temporal pattern of protein expression level (linear NPX) for C-C motif chemokine ligand 4 (CCL4) or macrophage inflammatory protein-1ß (MIP-1ß). Statistically significant early peak (median day 1 vs day 4 values=80.3 vs 36.4, p\u003c0.01) but no significantly decreasing trend since values seemed to stagnate between day 4 and 10 (36.4 vs 35.1, p=0.44). Of note is the large spread of day 1 values compared to day 4 and day 10 values that were more concentrated.","description":"","filename":"renamed458ab.png","url":"https://assets-eu.researchsquare.com/files/rs-17091/v1/renamed_458ab.png"},{"id":641181,"identity":"584c8192-b3d8-45a6-ae30-f4476d6d9805","added_by":"auto","created_at":"2020-03-13 01:36:17","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":12293,"visible":true,"origin":"","legend":"Group B example; DNER: temporal pattern of protein expression level (linear NPX) for Delta and Notch‐like epidermal growth factor‐related receptor (DNER). Statistically significant peak in the middle of the observation period defined by significantly higher day 4 vs day 1 (327.1 vs 138.8, p\u003c0.01) and day 4 vs day 10 median values (327.1 vs 259.2, p=0.01).","description":"","filename":"Figure2.GroupBexampleDNER.png","url":"https://assets-eu.researchsquare.com/files/rs-17091/v1/Figure 2. Group B example; DNER.png"},{"id":641182,"identity":"f7e2a09f-6232-479b-af91-c0df07d2bb39","added_by":"auto","created_at":"2020-03-13 01:36:17","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":13440,"visible":true,"origin":"","legend":"Group C example; CXCL6: temporal pattern of protein expression level (linear NPX) for C-X-C motif chemokine ligand 6 (CXCL6) showing statistically significant late peak and increasing trend, that is day 1 \u003c day 4 \u003c day 10 median values (21.1 vs 204.3 vs 642.6 respectively, p\u003c0.01). Of note the gradually increasing spread of values towards the end of the observation period.","description":"","filename":"Figure3.GroupCexampleCXCL6.png","url":"https://assets-eu.researchsquare.com/files/rs-17091/v1/Figure 3. Group C example; CXCL6.png"},{"id":641183,"identity":"99bf4f1a-3658-4243-a97b-972bf7aaa78d","added_by":"auto","created_at":"2020-03-13 01:36:17","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":13090,"visible":true,"origin":"","legend":"Group D example; MCP-1: temporal pattern of protein expression level (linear NPX) for monocyte chemotactic protein 1 (MCP-1) or C-C motif chemokine ligand 2 (CCL2) showing essentially stable median values throughout the whole observation period (9428.7 vs 9491.3 vs 8998.3, p=0.50 and p=0.85 respectively).","description":"","filename":"Figure4.GroupDexampleMCP1.png","url":"https://assets-eu.researchsquare.com/files/rs-17091/v1/Figure 4. Group D example; MCP-1.png"},{"id":13493363,"identity":"50288629-ae3c-4ced-b444-f4c988749c2f","added_by":"auto","created_at":"2021-09-16 22:35:21","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1396053,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-17091/v1/a4f0c7bf-c791-468b-95ac-9b7d1972f573.pdf"}],"financialInterests":"","formattedTitle":"Temporal patterns of inflammatory biomarkers measured in the cerebrospinal fluid of patients with aneurysmal subarachnoid hemorrhage using multiplex Proximity Extension Assay technology.","fulltext":[{"header":"Background:","content":" \u003cp\u003eSpontaneous subarachnoid hemorrhage (SAH) comprises approximately 5% of all strokes with an incidence of around 9 cases per 100.000 per year and aneurysm rupture being the cause in 85% of cases.[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e] Brain injury in SAH occurs both at the time of the bleeding itself, termed primary injury, but also during the following days to weeks, a phenomenon known as secondary injury. Despite advances in the critical care of SAH patients and aneurysm treatment methods, mortality and morbidity rates among the survivals from the initial bleeding remain high, reflecting a lack of effective treatments targeting the pathophysiological mechanisms that underlie the secondary injury.\u003c/p\u003e \u003cp\u003eDelayed cerebral ischemia (DCI) develops in approximately 30\u0026ndash;40% of SAH patients and is considered to be a major cause of unfavorable outcome.[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e] For decades the condition was attributed to cerebral vasospasm (CV), i.e. the narrowing of basal cerebral arteries seen early on angiography and persisting for up to two weeks post SAH leading to decreased cerebral blood flow (CBF) and infarctions in the affected territories.[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] However, about 20% of SAH patients develop DCI without evidence of CV and only 30% of patients with CV actually suffer from DCI.[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e] Moreover, the randomized multicenter CONCSIOUS-1 trial with the endothelin receptor antagonist Clazosentan failed to show any effect on functional outcome or incidence of cerebral ischemia despite significant decrease of CV.[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e] Thus, an uncoupling of angiographic vasospasm and DCI became apparent and new concepts emerged as potential underlying mechanisms of delayed brain injury.[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eEarly brain injury (EBI) refers to the events occurring within the first 72\u0026nbsp;h from ictus and includes the primary injury and its direct consequences. Elevation of intracranial pressure (ICP), global ischemia, impairment of CBF autoregulation, cortical spreading depolarization (CSD), disruption of blood-brain barrier (BBB), cell death, oxidative stress and inflammatory processes are among the mechanisms that are activated shortly after aneurysm rupture and evolve during the following days.[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eThe processes triggered by the EBI are now believed to play an important role in the development of DCI.[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] Neuroinflammation may be a mechanistic link between these two conditions and has been studied extensively in the past years.[\u003cspan additionalcitationids=\"CR12\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] Many clinical and experimental studies report levels of single or few inflammatory biomarkers (such as cytokines) in the peripheral blood, cerebrospinal fluid (CSF) and cerebral extracellular fluid through microdialysis (MD) in SAH patients or animal models and further correlate these biomarkers with clinical parameters and outcome.[\u003cspan additionalcitationids=\"CR15 CR16 CR17 CR18 CR19 CR20 CR21\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e] Although this strategy provides useful insight in the interplay between inflammation and the disease course it fails to account for the complexity of the involved mechanisms that cannot be adequately described by a single (or few) parameter(s) alone.\u003c/p\u003e \u003cp\u003eThe aim of the present study was to provide a comprehensive inflammatory profile of the acute phase of SAH by simultaneously measuring the levels of 92 inflammatory biomarkers in the CSF at days 1, 4 and 10 after admission using multiplex Proximity Extension Assay (PEA) technology. The biomarkers were then categorized into different groups according to their temporal expression.\u003c/p\u003e "},{"header":"Methods:","content":" \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eEthics\u003c/h2\u003e \u003cp\u003eThe study was conducted in accordance with Declaration of Helsinki for human studies and approved by Uppsala University Ethics Committee. All participants or their next of kin gave written consent for participation in the study.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003ePatients\u003c/h2\u003e \u003cp\u003eDemographic data of the 29 patients included in the study are presented in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Inclusion period was between May 2013 and August 2014. Eligibility criteria was spontaneous SAH severe enough to require insertion of an external ventricular drain (EVD) within 24\u0026nbsp;h from ictus. Patients considered terminally ill from the bleeding were excluded. Brain CT scans were used to establish the diagnosis of SAH and were classified according to Fisher scale (median 4).[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] World Federation of Neurosurgical societies (WFNS) and Hunt \u0026amp; Hess scores were noted on admission (medians 4 and 3, respectively).[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e] CT angiography and catheter angiography were performed in all cases and aneurysms were identified in 28 patients. In 26 patients the aneurysms were endovascularly secured and the remaining two were surgically clipped. The patients were treated at the Neurointensive Care Unit of Uppsala University Hospital for at least 10\u0026nbsp;days after the bleeding. Standardized treatment protocols described in a previous publication were applied.[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e] Functional outcome was assessed by a research nurse at 1\u0026nbsp;year using Glasgow Outcome Scale.[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cdiv class=\"SimplePara\"\u003eDemographic data of the patient cohort.\u003c/div\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eNumber of patients\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e29\u003c/div\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eMale vs Female\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e12 vs 17\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eMean age (range)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e57 (37\u0026ndash;81)\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eMedian Hunt \u0026amp; Hess score\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e3\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eMedian World Federation of Neurosurgical Societies score\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e4\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eMedian Fisher grade\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e4\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eAnterior vs posterior circulation aneurysm\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e23 vs 5 (1 patient with no aneurysm)\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eEmbolization vs surgery\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e26 vs 2\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eFavorable vs unfavorable outcome (Glasgow Outcome Scale)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e9 vs 20\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eCSF samples and analysis\u003c/h2\u003e \u003cp\u003eVentricular CSF samples were collected through the EVD within 24\u0026nbsp;h, on day 4 and on day 9\u0026ndash;11 after the bleeding, centrifuged directly after collection and frozen in -70\u0026nbsp;\u0026deg;C. The samples were then analyzed using Proseek Multiplex Inflammation 1\u0026reg;, a multiplex assay panel manufactured by Olink Proteomics AB, Uppsala, Sweden where 92 inflammation-related biomarkers are simultaneously measured using Proximity Extension Assay (PEA) technology (available online at \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.olink.com/products/inflammation\u003c/span\u003e\u003c/span\u003e). The analytical method was previously described in detail.[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e] Values are provided in output unit Normalized Protein Expression (NPX) on log2 scale. NPX values express relative quantification between samples but is not an absolute quantification. Limit of detection (LOD) is determined for each biomarker based on the negative controls analyzed in each run.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eBiomarkers\u003c/h2\u003e \u003cp\u003eA list of the 92 biomarkers included in the panel as well as their families is provided in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. In summary, the panel included 31 cytokines, 20 chemokines, 9 growth factors, 8 tumor necrosis factor (TNF)-family members, 6 membrane glycoproteins, 6 neurotrophic factors, 5 proteases and 7 miscellaneous proteins. A total of 87 NPX values (29 patients x 3 time points) corresponding to protein concentrations were collected for each biomarker. Variations in the detectability of the biomarkers in the samples were noticed; for example, in 44 proteins all samples were successfully analyzed while in 6 proteins all values were below limit of detection. An inclusion criterion was therefore defined that the values needed to be above level of detection (LOD) in at least 90% of the samples for each protein (that is \u0026lt;\u0026thinsp;9 missing values), which lead to the exclusion of 38 proteins, thus leaving 54 proteins for further analysis.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cdiv class=\"SimplePara\"\u003eList of biomarkers included in the panel\u003c/div\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eNr\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003ePROTEIN\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eFULL NAME\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003eFAMILY\u003c/div\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e1\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e4E-BP1\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eEukaryotic translation initiation factor 4E-binding protein 1\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eTranslation factor\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e2\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eADA\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eAdenosine deaminase\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eDeaminase\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e3\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eARTN\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eArtemin\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003eNeurotrophic factor\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e4\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eAXIN1\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eAxin-1\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003eG-protein regulator\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e5\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eBDNF\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eBrain-derived neurotrophic factor\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003eNeurotrophic factor\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e6\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003ebeta-NGF\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eBeta-nerve growth factor\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003eNeurotrophic factor\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e7\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eCASP-8\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eCaspase-8\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eCysteine protease\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e8\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eCCL11\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eC-C motif chemokine ligand 11 (Eotaxin)\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eChemokine\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e9\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eCCL13 (MCP-4)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eC-C motif chemokine ligand 13 (monocyte chemotactic protein 4)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003eChemokine\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e10\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eCCL19\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eC-C motif chemokine ligand 19\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eChemokine\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e11\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eCCL2 (MCP-1)\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eC-C motif chemokine ligand 2 (monocyte chemotactic protein 1)\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eChemokine\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e12\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eCCL20\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eC-C motif chemokine ligand 20\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eChemokine\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e13\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eCCL23 (MIP-3)\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eC-C motif chemokine ligand 23 (macrophage inflammatory protein-3)\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eChemokine\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e14\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eCCL25\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eC-C motif chemokine ligand 25\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eChemokine\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e15\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eCCL28\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eC-C motif chemokine ligand 28\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eChemokine\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e16\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eCCL3 (MIP-1α)\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eC-C motif chemokine ligand 3 (macrophage inflammatory protein-1α)\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eChemokine\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e17\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eCCL4 (MIP-1β)\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eC-C motif chemokine ligand 4 (macrophage inflammatory protein-1β)\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eChemokine\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e18\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eCCL7 (MCP-3)\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eC-C motif chemokine ligand 7 (monocyte chemotactic protein 3)\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eChemokine\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e19\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eCCL8 (MCP-2)\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eC-C motif chemokine ligand 8 (monocyte chemotactic protein 2)\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eChemokine\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e20\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eCD244\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eNatural killer cell receptor 2B4\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003eMembrane glycoprotein\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e21\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eCD40\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eTumor necrosis factor receptor superfamily member 5\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eTNF receptor superfamily\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e22\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eCD5\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eT-cell surface glycoprotein CD5\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eMembrane glycoprotein\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e23\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eCD6\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eT-cell differentiation antigen CD6\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003eMembrane glycoprotein\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e24\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eCDCP-1\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eCUB domain-containing protein 1\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eMembrane glycoprotein\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e25\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eCSF-1\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eMacrophage colony-stimulating factor 1\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eCytokine\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e26\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eCST5\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eCystatin-D\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eCysteine proteinase inhibitor\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e27\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eCX3CL1\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eC-X3‐C motif chemokine ligand 1 (Fractalkine)\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eChemokine\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e28\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eCXCL1\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eC-X‐C motif chemokine ligand 1\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eChemokine\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e29\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eCXCL10\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eC-X‐C motif chemokine ligand 10\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eChemokine\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e30\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eCXCL11\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eC-X‐C motif chemokine ligand 11\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eChemokine\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e31\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eCXCL5\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eC-X‐C motif chemokine ligand 5\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eChemokine\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e32\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eCXCL6\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eC-X‐C motif chemokine ligand 6\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eChemokine\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e33\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eCXCL9\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eC-X‐C motif chemokine ligand 9\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eChemokine\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e34\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eDNER\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eDelta and Notch-like epidermal growth factor‐related receptor\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eGrowth factor\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e35\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eEN-RAGE\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eProtein S100-A12\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eCalcium-binding protein\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e36\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eFGF19\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eFibroblast growth factor 19\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eGrowth factor\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e37\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eFGF-21\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eFibroblast growth factor 21\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003eGrowth factor\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e38\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eFGF-23\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eFibroblast growth factor 23\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003eGrowth factor\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e39\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eFGF-5\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eFibroblast growth factor 5\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eGrowth factor\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e40\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eFlt3L\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eFms-related tyrosine kinase 3 ligand\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eCytokine\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e41\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eGDNF\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eGlial cell line-derived neurotrophic factor\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003eNeurotrophic factor\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e42\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eHGF\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eHepatocyte growth factor\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eGrowth factor\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e43\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eIFN-gamma\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eInterferon gamma\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003eCytokine\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e44\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eIL-10\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eInterleukin-10\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eCytokine\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e45\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eIL-10RA\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eInterleukin-10 receptor subunit alpha\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003eCytokine\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e46\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eIL-10RB\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eInterleukin-10 receptor subunit beta\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eCytokine\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e47\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eIL-12B\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eInterleukin-12 subunit beta\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003eCytokine\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e48\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eIL-13\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eInterleukin-13\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003eCytokine\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e49\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eIL-15RA\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eInterleukin-15 receptor subunit alpha\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003eCytokine\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e50\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eIL-17A\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eInterleukin-17A\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003eCytokine\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e51\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eIL-17C\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eInterleukin-17C\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003eCytokine\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e52\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eIL-18\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eInterleukin-18\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eCytokine\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e53\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eIL-18R1\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eInterleukin-18 receptor 1\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eCytokine\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e54\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eIL-1α\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eInterleukin-1 alpha\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003eCytokine\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e55\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eIL-2\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eInterleukin-2\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003eCytokine\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e56\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eIL-2RB\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eInterleukin-2 receptor subunit beta\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003eCytokine\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e57\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eIL-20\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eInterleukin-20\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003eCytokine\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e58\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eIL-20RA\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eInterleukin-20 receptor subunit alpha\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003eCytokine\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e59\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eIL-22 RA1\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eInterleukin-20 receptor subunit alpha-1\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003eCytokine\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e60\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eIL-24\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eInterleukin-24\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003eCytokine\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e61\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eIL-33\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eInterleukin-33\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003eCytokine\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e62\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eIL-4\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eInterleukin-4\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003eCytokine\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e63\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eIL-5\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eInterleukin-5\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003eCytokine\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e64\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eIL-6\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eInterleukin-6\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eCytokine\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e65\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eIL-7\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eInterleukin-7\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eCytokine\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e66\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eIL-8\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eInterleukin-8\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eCytokine\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e67\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eLIF\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eLeukemia inhibitory factor\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eCytokine\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e68\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eLIF-R\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eLeukemia inhibitory factor receptor\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eCytokine\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e69\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eMMP-1\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eMatrix metalloproteinase-1\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003eProtease\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e70\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eMMP-10\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eMatrix metalloproteinase-10\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eProtease\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e71\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eNRTN\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eNeurturin\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003eNeurotrophic factor\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e72\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eNT-3\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eNeurotrophin-3\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003eNeurotrophic factor\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e73\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eOPG\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eOsteoprotegerin\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eTNF receptor superfamily\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e74\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eOSM\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eOncostatin-M\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eCytokine\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e75\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003ePD-L1\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eProgrammed cell death ligand 1\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003eMembrane glycoprotein\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e76\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eSCF\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eStem cell factor\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eCytokine\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e77\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eSIRT2\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eSIR2-like protein 2\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eNAD dependent deacetylase\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e78\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eSLAMF1\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eSignaling lymphocytic activation molecule\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003eMembrane glycoprotein\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e79\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eST1A1\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eSulfotransferase 1A1\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003eTransferase\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e80\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eSTAMPB\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eSTAM-binding protein\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eProtease\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e81\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eTGFA\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eTransforming growth factor alpha\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eGrowth factor\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e82\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eTGF-β1\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eTransforming growth factor beta-1\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eGrowth factor\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e83\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eTNF\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eTumor necrosis factor\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003eTNF family\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e84\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eTNFB\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eTumor necrosis factor beta (Lymphotoxin-alpha)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003eCytokine\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e85\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eTNFRSF9\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eTumor necrosis factor receptor superfamily member 9\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eTNF receptor superfamily\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e86\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eTNFSF14\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eTumor necrosis factor superfamily member 14\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003eTNF receptor superfamily\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e87\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eTRAIL (TNFSF10)\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eTNF-related apoptosis‐inducing ligand (TNF-superfamily member 10)\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eTNF receptor superfamily\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e88\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eTRANCE (TNFSF11)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eTumor necrosis factor superfamily member 11\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003eTNF receptor superfamily\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e89\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eTSLP\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eThymic stromal lymphopoietin\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003eCytokine\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e90\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eTWEAK (TNFSF12)\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eTumor necrosis factor superfamily member 12\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eTNF receptor superfamily\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e91\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003euPA\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eUrokinase-type plasminogen activator\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eProtease\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e92\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eVEGF-A\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eVascular endothelial growth factor A\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eGrowth factor\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eAlphabetic list of the 92 biomarkers included in Proseek Multiplex Inflammation 1\u0026reg; panel (abbreviations and full names) together with their families. The 54 biomarkers that met the criterion of being above level of detection in at least 90% of the samples (that is \u0026lt;\u0026thinsp;9 missing values for each protein) to be included for further analysis are marked in bold.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eStatistics\u003c/h2\u003e \u003cp\u003eThe NPX values of the remaining 54 proteins were converted into linear scale using the formula 2\u003csup\u003eNPX\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;linear NPX in order to better visualize the trends of the biomarkers during the observation period. Median values for each day and protein were then calculated from the linear NPX values and their development over time was illustrated in graphs with upper and lower quartiles. Statistical analysis was done on the linear NPX data that were visually not normally distributed. Therefore non-parametric statistical methods were chosen. Wilcoxon matched pairs test was used for the comparison of day 1 vs day 4 vs day 10 median values for each protein. Protein expression levels in graphs were illustrated with medians and upper and lower quartiles. The results were considered statistically significant at the p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 level. All statistical analyses and graphical presentations were performed using the Statistica\u0026reg; software (Stat Soft, Inc., Tulsa, OK, USA).\u003c/p\u003e \u003c/div\u003e "},{"header":"Results:","content":" \u003cp\u003eVisual inspection of the linear NPX graphs revealed four different temporal patterns (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e): an early peak at day 1 followed by a decreasing trend (Group A: 9 proteins), a middle peak at day 4 (Group B: 14 proteins), an increasing trend with a late peak at day 10 (Group C: 27 proteins) and finally no specific pattern (Group D: 4 proteins). Figures\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e illustrate typical graphs of median protein expression levels (linear NPX) and upper and lower quartiles over time for each group. Medians were then compared between time points for each protein using Wilcoxon matched pairs test. Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e shows the results (p-value considered significant at \u0026lt;\u0026thinsp;0.05).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cdiv class=\"SimplePara\"\u003eGroups of biomarkers by their temporal pattern of protein expression\u003c/div\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eGROUP A (n\u0026thinsp;=\u0026thinsp;9)\u003c/div\u003e \u003cdiv class=\"SimplePara\"\u003eEARLY PEAK\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eGROUP B (n\u0026thinsp;=\u0026thinsp;14)\u003c/div\u003e \u003cdiv class=\"SimplePara\"\u003eMIDDLE PEAK\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eGROUP C (n\u0026thinsp;=\u0026thinsp;27)\u003c/div\u003e \u003cdiv class=\"SimplePara\"\u003eLATE PEAK\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003eGROUP D (n\u0026thinsp;=\u0026thinsp;4)\u003c/div\u003e \u003cdiv class=\"SimplePara\"\u003eNO PATTERN\u003c/div\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eCCL11\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eCCL28\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e4E-BP1\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003eCCL25\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eCCL20\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eCSF-1\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eADA\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003eMCP-1\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eFGF-19\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eCST-5\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eCASP8\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003eTNFRSF9\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eLIF\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eDNER\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eCCL19\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003eVEGF-A\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eMIP-1α (CCL3)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eFGF-5\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eCCL23\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eMIP-1β (CCL4)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eFlt3L\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eCD40\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eMMP10\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eIL-10\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eCD5\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eTGFA\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eIL-10RB\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eCDCP1\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eTRAIL\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eIL-18R1\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eCX3CL1\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eIL-6\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eCXCL1\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eLIF-R\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eCXCL10\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eMCP-3\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eCXCL11\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eOSM\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eCXCL5\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eTGF-β1\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eCXCL6\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eCXCL9\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eEN-RAGE\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eHGF\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eIL-18\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eIL-7\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eIL-8\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eMCP-2\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eOPG\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eSCF\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eSIRT2\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eSTAMPB\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eTWEAK\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003euPA\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eFour different groups were identified based on visual inspection of the graphs, that is an early peak followed by a decreasing trend (Group A), a middle peak (Group B), a late peak after an increasing trend (Group C) and finally no specific pattern (Group D).\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cdiv class=\"SimplePara\"\u003eExpression levels of all proteins and time points.\u003c/div\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eGROUP A\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003eDAY 1\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e1 VS 4\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003eDAY 4\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e4 VS 10\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003eDAY 10\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e1 VS 10\u003c/div\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eCCL11\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e8,5\u003c/span\u003e (5,2\u0026ndash;12)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;0,01\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e5,2\u003c/span\u003e (3,4\u0026ndash;7,8)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,16\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e5,1\u003c/span\u003e (4,3\u0026ndash;7,2)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;0,01\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eCCL20\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e57\u003c/span\u003e (17\u0026ndash;176)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,32\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e51\u003c/span\u003e (23\u0026ndash;108)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,08\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e43\u003c/span\u003e (27\u0026ndash;97)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,25\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eFGF-19\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e17\u003c/span\u003e (12\u0026ndash;21)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,07\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e16\u003c/span\u003e (11\u0026ndash;20)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,62\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e13\u003c/span\u003e (9,2\u0026ndash;21)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,16\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eLIF\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e52\u003c/span\u003e (21\u0026ndash;148)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;0,01\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e13\u003c/span\u003e (7,8\u0026ndash;22)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,93\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e14\u003c/span\u003e (6,1\u0026ndash;34)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;0,01\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eMIP-1α (CCL3)\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e9,6\u003c/span\u003e (5,2\u0026ndash;25)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,13\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e8\u003c/span\u003e (5,1\u0026ndash;11)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,99\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e7,7\u003c/span\u003e (6,6\u0026ndash;12)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,17\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eMIP-1β (CCL4)\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e80\u003c/span\u003e (47\u0026ndash;404)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;0,01\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e36\u003c/span\u003e (22\u0026ndash;64)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,44\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e35\u003c/span\u003e (28\u0026ndash;59)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;0,01\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eMMP-10\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e17\u003c/span\u003e (9,9\u0026ndash;35)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,20\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e14\u003c/span\u003e (12\u0026ndash;19)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,06\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e12\u003c/span\u003e (8,8\u0026ndash;18)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,01\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eTGFA\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e7,7\u003c/span\u003e (5,7\u0026ndash;11)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,23\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e6,9\u003c/span\u003e (5,4\u0026ndash;8,5)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,03\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e6,5\u003c/span\u003e (5,3\u0026ndash;7,3)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,01\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eTRAIL\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e9,4\u003c/span\u003e (6,8\u0026ndash;16)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,01\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e7,3\u003c/span\u003e (5,2\u0026ndash;8,9)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,99\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e6,7\u003c/span\u003e (5,3\u0026ndash;9,6)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,04\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eGROUP B\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eDAY 1\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e1 VS 4\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eDAY 4\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e4 VS 10\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eDAY 10\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e1 VS 10\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eCCL28\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e1,3\u003c/span\u003e (1,2\u0026thinsp;\u0026minus;\u0026thinsp;1,5)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;0,01\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e1,6\u003c/span\u003e (1,5\u0026thinsp;\u0026minus;\u0026thinsp;1,7)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,02\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e1,5\u003c/span\u003e (1,3\u0026thinsp;\u0026minus;\u0026thinsp;1,6)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,07\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eCSF-1\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e87\u003c/span\u003e (48\u0026ndash;126)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,18\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e102\u003c/span\u003e (74\u0026ndash;131)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,06\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e80\u003c/span\u003e (50\u0026ndash;111)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,61\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eCST5\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e45\u003c/span\u003e (38\u0026ndash;61)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;0,01\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e60\u003c/span\u003e (54\u0026ndash;65)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,20\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e57\u003c/span\u003e (48\u0026ndash;65)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,02\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eDNER\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e138\u003c/span\u003e (112\u0026ndash;216)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;0,01\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e327\u003c/span\u003e (250\u0026ndash;381)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,01\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e259\u003c/span\u003e (170\u0026ndash;360)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;0,01\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eFGF-5\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e3,2\u003c/span\u003e (2,5\u0026thinsp;\u0026minus;\u0026thinsp;4,9)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;0,01\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e6,7\u003c/span\u003e (5,5\u0026ndash;11)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,15\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e6\u003c/span\u003e (4,2\u0026ndash;9,7)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,01\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eFlt3L\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e156\u003c/span\u003e (129\u0026ndash;231)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;0,01\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e267\u003c/span\u003e (185\u0026ndash;374)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,82\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e285\u003c/span\u003e (166\u0026ndash;367)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;0,01\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eIL-10\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e5,1\u003c/span\u003e (3,6\u0026ndash;8)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,31\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e6,3\u003c/span\u003e (4,5\u0026ndash;7,9)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,31\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e4,9\u003c/span\u003e (3,3\u0026ndash;9,5)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,92\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eIL-10RB\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e3,4\u003c/span\u003e (2,9\u0026thinsp;\u0026minus;\u0026thinsp;6,2)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;0,01\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e7,1\u003c/span\u003e (4,7\u0026ndash;9,6)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,26\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e7,9\u003c/span\u003e (4,3\u0026ndash;12)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;0,01\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eIL-18R1\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e3,9\u003c/span\u003e (2,3\u0026ndash;6,9)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,12\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e5,7\u003c/span\u003e (3,3\u0026ndash;7,4)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,34\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e5,3\u003c/span\u003e (2,8\u0026thinsp;\u0026minus;\u0026thinsp;7,5)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,34\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eIL-6\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e927\u003c/span\u003e (267\u0026ndash;2037)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;0,01\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e2715\u003c/span\u003e (537\u0026ndash;5589)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,64\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e2119\u003c/span\u003e (611\u0026ndash;6838)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;0,01\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eLIF-R\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e4\u003c/span\u003e (3,3\u0026ndash;5,6)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;0,01\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e5,2\u003c/span\u003e (4,4\u0026ndash;7,4)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,26\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e5\u003c/span\u003e (4,4\u0026ndash;6,4)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,03\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eMCP-3\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e38\u003c/span\u003e (15\u0026ndash;78)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,02\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e95\u003c/span\u003e (29\u0026ndash;172)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,31\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e98\u003c/span\u003e (31\u0026ndash;290)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;0,01\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eOSM\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e11\u003c/span\u003e (8,1\u0026ndash;30)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,02\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e30\u003c/span\u003e (9,4\u0026ndash;53)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,41\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e31\u003c/span\u003e (13\u0026ndash;61)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,03\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eTGF-β1\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e13\u003c/span\u003e (9\u0026ndash;25)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;0,01\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e30\u003c/span\u003e (19\u0026ndash;36)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,15\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e29\u003c/span\u003e (17\u0026ndash;54)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;0,01\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eGROUP C\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eDAY 1\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e1 VS 4\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eDAY 4\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e4 VS 10\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eDAY 10\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e1 VS 10\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e4E-BP1\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e2,3\u003c/span\u003e (1,7\u0026thinsp;\u0026minus;\u0026thinsp;3,3)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;0,01\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e21\u003c/span\u003e (3,5\u0026ndash;71)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;0,01\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e111\u003c/span\u003e (21\u0026ndash;102)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;0,01\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eADA\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e16\u003c/span\u003e (10\u0026ndash;23)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;0,01\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e32\u003c/span\u003e (22\u0026ndash;64)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,055\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e53\u003c/span\u003e (29\u0026ndash;107)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;0,01\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eCASP-8\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e2,9\u003c/span\u003e (1,7\u0026thinsp;\u0026minus;\u0026thinsp;3,6)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,26\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e2,8\u003c/span\u003e (2,2\u0026ndash;3,9)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;0,01\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e5,6\u003c/span\u003e (2,9\u0026ndash;11)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;0,01\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eCCL19\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e177\u003c/span\u003e (115\u0026ndash;388)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;0,01\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e1772\u003c/span\u003e (748\u0026ndash;3642)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,01\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e2875\u003c/span\u003e (1196\u0026ndash;5501)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;0,01\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eCCL23\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e12\u003c/span\u003e (7,1\u0026ndash;25)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;0,01\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e63\u003c/span\u003e (31\u0026ndash;104)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;0,01\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e207\u003c/span\u003e (83\u0026ndash;331)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;0,01\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eCD40\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e64\u003c/span\u003e (43\u0026ndash;101)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;0,01\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e109\u003c/span\u003e (75\u0026ndash;189)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;0,01\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e250\u003c/span\u003e (137\u0026ndash;395)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;0,01\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eCD5\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e2\u003c/span\u003e (1,5\u0026thinsp;\u0026minus;\u0026thinsp;3,5)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,055\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e3,2\u003c/span\u003e (2,2\u0026ndash;4,2)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,23\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e4\u003c/span\u003e (2,2\u0026ndash;5,3)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,01\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eCDCP1\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e13\u003c/span\u003e (9\u0026ndash;15)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;0,01\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e17\u003c/span\u003e (15\u0026ndash;26)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;0,01\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e28\u003c/span\u003e (17\u0026ndash;42)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;0,01\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eCX3CL1\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e6,5\u003c/span\u003e (5,7\u0026ndash;8,1)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,10\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e9,5\u003c/span\u003e (6,7\u0026ndash;11)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,19\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e11,7\u003c/span\u003e (6,9\u0026ndash;17)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,07\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eCXCL1\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e183\u003c/span\u003e (82\u0026ndash;356)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;0,01\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e830\u003c/span\u003e (127\u0026ndash;1066)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;0,01\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e1037\u003c/span\u003e (437\u0026ndash;1973)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;0,01\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eCXCL10\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e179\u003c/span\u003e (76\u0026ndash;417)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;0,01\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e1573\u003c/span\u003e (1024\u0026ndash;4301)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,25\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e2530\u003c/span\u003e (1181\u0026ndash;3539)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;0,01\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eCXCL11\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e5,7\u003c/span\u003e (3\u0026ndash;8)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;0,01\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e11,8\u003c/span\u003e (8\u0026ndash;22)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,68\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e19,5\u003c/span\u003e (10\u0026ndash;39)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;0,01\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eCXCL5\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e252\u003c/span\u003e (144\u0026ndash;572)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,68\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e271\u003c/span\u003e (160\u0026ndash;753)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,73\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e437\u003c/span\u003e (185\u0026ndash;737)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,56\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eCXCL6\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e21\u003c/span\u003e (8,8\u0026ndash;44)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;0,01\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e204\u003c/span\u003e (22\u0026ndash;408)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;0,01\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e642\u003c/span\u003e (172\u0026ndash;959)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;0,01\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eCXCL9\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e7,1\u003c/span\u003e (6,2\u0026ndash;19)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;0,01\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e25,9\u003c/span\u003e (15\u0026ndash;42)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;0,01\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e59\u003c/span\u003e (18\u0026ndash;116)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;0,01\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eEN-RAGE\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e2,9\u003c/span\u003e (2,5\u0026thinsp;\u0026minus;\u0026thinsp;4,2)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;0,01\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e9,8\u003c/span\u003e (5,8\u0026ndash;29)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,11\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e16\u003c/span\u003e (5,9\u0026ndash;39)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;0,01\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eHGF\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e36\u003c/span\u003e (27\u0026ndash;70)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;0,01\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e86\u003c/span\u003e (67\u0026ndash;116)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,08\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e114\u003c/span\u003e (64\u0026ndash;188)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;0,01\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eIL-18\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e6,3\u003c/span\u003e (4,3\u0026ndash;10)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,33\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e9,8\u003c/span\u003e (3,5\u0026ndash;20)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;0,01\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e24\u003c/span\u003e (8,3\u0026ndash;37)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;0,01\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eIL-7\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e2,3\u003c/span\u003e (2\u0026ndash;2,5)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,01\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e2,4\u003c/span\u003e (2,2\u0026ndash;3,4)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,31\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e2,8\u003c/span\u003e (2,5\u0026thinsp;\u0026minus;\u0026thinsp;3,4)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;0,01\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eIL-8\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e6671\u003c/span\u003e (4906\u0026ndash;12663)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,29\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e10867\u003c/span\u003e (3084\u0026ndash;16185)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,03\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e15540\u003c/span\u003e (6006\u0026ndash;21024)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,06\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eMCP-2\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e107\u003c/span\u003e (53\u0026ndash;188)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;0,01\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e404\u003c/span\u003e (126\u0026ndash;644)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,01\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e527\u003c/span\u003e (198\u0026ndash;1082)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;0,01\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eOPG\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e638\u003c/span\u003e (356\u0026ndash;1629)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,24\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e1076\u003c/span\u003e (646\u0026ndash;1584)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,03\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e1381\u003c/span\u003e (741\u0026ndash;2481)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,03\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eSCF\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e7,2\u003c/span\u003e (5,2\u0026ndash;11)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,19\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e12\u003c/span\u003e (7,9\u0026ndash;15)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,39\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e13\u003c/span\u003e (6,1\u0026ndash;19)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,13\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eSIRT2\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e4,7\u003c/span\u003e (3,3\u0026ndash;8,2)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,08\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e6,3\u003c/span\u003e (3,9\u0026ndash;10)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,06\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e10\u003c/span\u003e (5,2\u0026ndash;22)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;0,01\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eSTAMPB\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e3,6\u003c/span\u003e (2,4\u0026ndash;4,2)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,40\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e3,5\u003c/span\u003e (2,9\u0026thinsp;\u0026minus;\u0026thinsp;6)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,04\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e6,3\u003c/span\u003e (3,2\u0026ndash;8,9)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,01\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eTWEAK\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e179\u003c/span\u003e (123\u0026ndash;246)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;0,01\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e271\u003c/span\u003e (202\u0026ndash;438)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,16\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e326\u003c/span\u003e (214\u0026ndash;497)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;0,01\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003euPA\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e156\u003c/span\u003e (120\u0026ndash;227)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;0,01\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e385\u003c/span\u003e (244\u0026ndash;565)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;0,01\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e1230\u003c/span\u003e (525\u0026ndash;2239)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;0,01\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eGROUP D\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eDAY 1\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e1 VS 4\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eDAY 4\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e4 VS 10\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eDAY 10\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e1 VS 10\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eCCL25\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e2,5\u003c/span\u003e (2,2\u0026ndash;3,6)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,04\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e2,2\u003c/span\u003e (2\u0026ndash;2,5)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,04\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e2,5\u003c/span\u003e (2\u0026ndash;3,9)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,58\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eMCP-1\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e9428\u003c/span\u003e (7822\u0026ndash;10942)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,50\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e9491\u003c/span\u003e (7628\u0026ndash;10487)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,85\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e8998\u003c/span\u003e (7870\u0026ndash;10266)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,18\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eTNFRSF9\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e7\u003c/span\u003e (3,5\u0026ndash;10)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,17\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e7,2\u003c/span\u003e (5\u0026ndash;9,8)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,96\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e8,1\u003c/span\u003e (3,7\u0026ndash;11)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,31\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eVEGF-A\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e1039\u003c/span\u003e (520\u0026ndash;1414)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,04\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e689\u003c/span\u003e (493\u0026ndash;1007)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,10\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e996\u003c/span\u003e (535\u0026ndash;1247)\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cdiv class=\"SimplePara\"\u003e0,38\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"8\"\u003eComparison of median protein expression levels (linear NPX) with upper and lower quartiles within parentheses between time points for each protein (classified in groups according to Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e); Wilcoxon matched pairs test was used for comparison; p-values were considered significant at \u0026lt;\u0026thinsp;0.05 level.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eGroup A biomarkers with statistically significant early peak, defined as significantly higher day 1 vs day 4 values, were CCL11, LIF, MIP-1β (CCL4) and TRAIL; no biomarkers in this group showed statistically significant decreasing trend (that is, significant differences between day 1 vs day 4 \u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eand\u003c/span\u003e day 4 vs day 10 values).\u003c/p\u003e \u003cp\u003eSeveral Group B biomarkers (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e) showed significantly higher values between day 4 vs day 1 (i.e. CCL28, CST5, DNER, FGF-5, Flt3L, IL-10RB, IL-6, LIF-R, MCP-3, OSM and TGF-β1). Half of these biomarkers showed decreasing NPX values towards day 10 and the rest remained stable. The only biomarkers with statistically significant middle peak (that is, significant difference between day 4 vs day 1 \u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eand\u003c/span\u003e day 4 vs day 10 values) were CCL28 and DNER.\u003c/p\u003e \u003cp\u003eFifteen of the 27 biomarkers in Group C (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e) showed statistically significant late peak defined as significantly higher day 10 vs day 4 values (4E-BP1, CASP-8, CCL19, CCL23, CD40, CDCP1, CXCL1, CXCL6, CXCL9, IL-18, IL-8, MCP-2, OPG, STAMPB and uPA). Ten of them also showed statistically significant increasing trend during the entire observation period, that is significantly higher day 10 vs day 4 \u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eand\u003c/span\u003e day 4 vs day 1 values (i.e. 4E-BP1, CCL19, CCL23, CD40, CDCP1, CXCL1, CXCL6, CXCL9, MCP-2 and uPA).\u003c/p\u003e "},{"header":"Discussion:","content":" \u003cp\u003eIn this study we present a concise data set of the sequential production of multiple biomarkers of inflammation in the CSF of patients during the first 10 days post SAH. To our knowledge, this is the largest data set to describe the inflammatory profile of SAH ever reported with 92 inflammatory biomarkers included, many of which never studied in SAH patients previously. This is also the first report of Proximity Extension Assay (PEA) technology being used for measuring biomarker expression levels in the context of SAH. Similar studies were recently published in patients with traumatic brain injury (TBI) and trigeminal neuralgia, as well as numerous other non-neurosurgical conditions (such as neuropathic pain, cardiovascular diseases, gastric cancer, etc.).[\u003cspan additionalcitationids=\"CR30\" citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eThe analyses in the present study were performed in CSF compartment alone (not plasma or cerebral interstitial fluid) as this seems more suitable to describe the disease pathophysiology, given also that major early and late clinical complications (i.e. CV and chronic hydrocephalus) spatially correlate best with this compartment. Many of the included proteins have previously been associated to SAH inflammation, for example IL-1ra, IL-6, IL-8, TNF-a, LIF, MCP-1, and VEGF-A.[\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e] On the other hand, there is scarce or non-existing literature on many other proteins, some of which showed interesting temporal patterns and statistically significant peaks and trends, such as LIF, CCL11, CCL28, 4E-BP1, CD40, CXCL6, CXCL9, and IL-18.[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan additionalcitationids=\"CR34 CR35\" citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]\u003c/p\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eGroup A\u003c/h2\u003e \u003cp\u003eNine biomarkers showed higher day 1 values and decreasing trends throughout the observation period (Tables\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e and \u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). Four of them (CCL11, LIF, MIP-1β and TRAIL) showed statistically significant early peaks with day 1\u0026thinsp;\u0026gt;\u0026thinsp;day 4 levels but no statistically significant decreasing trends were observed. MIP-1β (also known as CCL4) and CCL11 are members of the chemokine family (C-C motif) and are involved in chemotaxis of macrophages and activated T-cells, respectively, as well as other proinflammatory actions. Their early peak can possibly be associated to the recruitment of leukocytes at the site of the bleeding. LIF is a cytokine involved in activation of signaling pathways that regulate cell growth among other actions. A similar early peak in serum has been observed previously.[\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e] TRAIL, a member of the TNF superfamily (also known as TNFSF10) involved in apoptosis, has not been studied in the SAH literature.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eGroup B\u003c/h2\u003e \u003cp\u003eAmong the 14 proteins included in this group only two (CCL28 and DNER) showed statistically significant middle peaks, that is significantly higher day 4 values than \u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eboth\u003c/span\u003e day 1 \u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eand\u003c/span\u003e day 10. Production of the chemokine CCL28 is induced by other proinflammatory cytokines and its chemotactic actions are exerted on B and T cells and eosinophils. Delta and Notch-like Epidermal growth factor-Receptor (DNER) is an activator of NOTCH1 pathway. None of these biomarkers have been studied in a SAH context earlier and their potential involvement in the SAH complications, mainly CV that coincides temporally with the observed middle peaks, should be examined.\u003c/p\u003e \u003cp\u003eIt should be noted that the majority of the biomarkers in this group showed a significant increase in their levels between day 1 and day 4 (11/14, Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). In almost all cases though, with the exception of the two biomarkers named above, these dynamics seemed to wear off between day 4 and day 10. Interestingly, IL-6 was recently studied by our group using a quantitative routine monoclonal antibody-based method in CSF samples from 44 patients with severe SAH. The results showed a very similar temporal IL-6 pattern as in the present study, with increasing values between day 1 and day 4 followed by decreasing values towards day 10, although remaining higher than day 1 values.[\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eGroup C\u003c/h2\u003e \u003cp\u003eHalf of the studied biomarkers (n\u0026thinsp;=\u0026thinsp;27) showed higher levels towards the end of the observation period, reflecting a more prolonged activation post SAH that may indicate an involvement in the healing processes or the development of late complications, such as late vasospasm, posthemorrhagic hydrocephalus, etc. Fifteen biomarkers (4E-BP1, CASP-8, CCL19, CCL23, DC40, CDCP1, CXCL1, CXCL6, CXCL9, IL18, IL8, MCP-2, OPG, STAMPB and uPA) showed statistically significant late peaks, meaning significantly higher day 10 than day 4 values. Apart from CASP-8, IL-18, IL-8, OPG and STAMPB all the remaining proteins in the list showed statistically significant increasing trends throughout the observation period with day 1\u0026thinsp;\u0026lt;\u0026thinsp;day 4\u0026thinsp;\u0026lt;\u0026thinsp;day 10 values.\u003c/p\u003e \u003cp\u003eChemokines CCL23, CXCL6 and CXCL9, all potent chemotactic agents for resting T-cells/monocytes, neutrophilic granulocytes and T-cells respectively, have not been studied in SAH patients earlier. Signaling pathway molecule 4E-BP1 has been implicated in the development of vasospasm in a canine SAH-model but no reports on human studied are available.[\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e] Protein CD40, a member of TNF family, is found on antigen-presenting cells and mediates multiple inflammatory responses. Elevated serum levels of CD40 have been associated with poor outcome and severity of neurological deficits in SAH patients.[\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e, \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e] IL-18, a strong proinflammatory cytokine involved in the synthesis of inflammatory mediators, has recently been shown to be a predictor of early brain injury and clinical prognosis in SAH patients as elevated concentrations correlated to cerebral edema and acute hydrocephalus.[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] It should be noted that the observed temporal pattern of IL-18 in that study differed from our study as we demonstrated a late peak of this cytokine. Urokinase (or uPA) is a serum protease that activates plasminogen to plasmin which in turn leads to thrombolysis and tissue degradation. Plasma concentrations of its receptor (soluble uPA-receptor) was not shown to correlate with neurological outcome post SAH.[\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eGeneral considerations\u003c/h2\u003e \u003cp\u003eThe great variability of the expression levels and temporal patterns of the measured biomarkers is an indicator of the complexity of the inflammatory response after SAH. Many of the included proteins are well established in the SAH research both in humans and in preclinical animal models while others are novel in the SAH field. Their exact role as well as interplay with each other is not easy to establish, especially considering the fact that many of these substances are described to play both a detrimental and a beneficial role in the disease course depending on the time after bleeding.[\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e] This study may offer guidance for further research on groups of biomarkers based either on their families or their pattern of activation (e.g. early vs late peak) to identify potential underlying inflammatory mechanisms of SAH complications as well as novel targets of intervention in order to prevent/treat these conditions and improve outcome.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eLimitations\u003c/h2\u003e \u003cp\u003eA limitation with the study is that the PEA analysis method in its presently available form does not give absolute protein concentrations. However, the protein expression levels illustrate the relative concentrations and how these change over time. They also illustrate the relations between the levels of the different biomarkers. The study may be limited by the relatively small number of patients included. Another drawback may be the fact that the study is limited to the CSF compartment. Similar analyses could be performed in the CSF, cerebral interstitial fluid and plasma, giving the opportunity to compare protein levels in the different fluid compartments providing a more thorough inflammatory profile of the acute phase of the disease. Comparisons with healthy individuals could also serve as an indicator of the intensity of activation for each biomarker. Moreover, correlations of the biomarker expression levels with clinical parameters were not performed in this study, as the main goal was to provide general information of as many proteins as possible in order to look for patterns of expression for further investigation. Finally, measurements in more than three time points could possibly describe the temporal patterns of each protein more accurately.\u003c/p\u003e \u003c/div\u003e "},{"header":"Conclusion:","content":" \u003cp\u003eThe temporal patterns of expression of multiple inflammation-related proteins in the acute phase of SAH are reported in this study providing an inflammatory profile of the disease that facilitates further research in the field of biomarkers. Proximity Extension Assay technology enables the measurement of the expression levels of several biomarkers simultaneously in small amounts of sample, adding a useful tool in the quest of finding relevant biomarkers to better describe and understand the complex pathophysiology of SAH.\u003c/p\u003e "},{"header":"Abbreviations","content":" \u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSAH\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003esubarachnoid haemorrhage\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePEA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eProximity Extension Assay\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eDCI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003edelayed cerebral ischemia\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCV\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ecerebral vasospasm\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCBF\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ecerebral blood flow\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eEBI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eearly brain injury\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eICP\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eintracranial pressure\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCSD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ecortical spreading depolarization\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eBBB\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eblood-brain barrier\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCSF\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ecerebrospinal fluid\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eMD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003emicrodialysis\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eEVD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eexternal ventricular drainage\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ecomputerized tomography\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eWFNS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eWorld Federation of Neurosurgical Societies\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eGOS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eGlasgow outcome scale\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eNPX\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003enormalized protein expression\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eLOD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003elimit of detection\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eTNF\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003etumor necrosis factor\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eTBI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003etraumatic brain injury\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e "},{"header":"Declarations","content":"\u003cp\u003e\u003cem\u003eEthics approval and consent to participate\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp;\u0026nbsp; The Uppsala University Ethical review board for research on humans granted permission for the study. Informed consent for participation was obtained from the patients when feasible or their next of kin.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eConsent for publication\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp;\u0026nbsp; Not applicable.\u0026nbsp;\u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAvailability of data and material\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp;\u0026nbsp; The datasets used in the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eCompeting interests\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp;\u0026nbsp; None.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eFunding\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp;\u0026nbsp; This research project was funded by ALF means (Avtal om l\u0026auml;karutbildning och forskning), that is governmental funding for medical doctors under training for parallel research.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAuthors' contributions\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp;\u0026nbsp; The first and last author were responsible for the study design and data collection and analysis. The first author was responsible for writing the manuscript. All the other authors contributed with critically revising and improving the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAcknowledgements\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u0026nbsp;\u0026nbsp;\u0026nbsp; \u003c/em\u003eThe authors would like to thank all the nursing staff at the NICU at Uppsala University Hospital, Uppsala, Sweden for their collaboration in the collection of the CSF samples.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAuthors' information (optional)\u003c/em\u003e\u003c/p\u003e\n"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eMacdonald RL, Schweizer TA: \u003cstrong\u003eSpontaneous subarachnoid haemorrhage.\u003c/strong\u003e \u003cem\u003eLancet \u003c/em\u003e2017, \u003cstrong\u003e389:\u003c/strong\u003e655-666.\u003c/li\u003e\n\u003cli\u003eBudohoski KP, Guilfoyle M, Helmy A, Huuskonen T, Czosnyka M, Kirollos R, Menon DK, Pickard JD, Kirkpatrick PJ: \u003cstrong\u003eThe 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\u003cstrong\u003e87:\u003c/strong\u003e47-62.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"subarachnoid hemorrhage, neuroinflammation, biomarkers, Proximity Extension Assay (PEA) technology","lastPublishedDoi":"10.21203/rs.3.rs-17091/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-17091/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBackground Neuroinflammation has been extensively studied in the context of subarachnoid hemorrhage (SAH) in recent years. A common approach is correlation of levels of single or few inflammatory biomarkers with clinical parameters such as cerebral vasospasm and outcome. However, the complexity of the inflammatory response post SAH may require a more comprehensive overall approach by analyzing multiple biomarkers simultaneously. \u003c/p\u003e\u003cp\u003eMethods Twenty-nine patients with SAH requiring insertion of external ventricular drainage were enrolled and ventricular cerebrospinal fluid was collected at days 1, 4 and 10 after hemorrhage. The levels of 92 inflammatory biomarkers were simultaneously measured in the samples using Proseek Multiplex Inflammation 1® assay (Olink Proteomics, Uppsala, Sweden) based on Proximity Extension Assay (PEA) technology. Thirty-eight proteins were excluded from further analysis due to lack of \u0026gt;10% of measurable values. Temporal patterns for each of the remaining 54 proteins were illustrated on graphs with medians and quartiles. Wilcoxon matched pairs test was used for comparison of the medians between time points. \u003c/p\u003e\u003cp\u003eResults Four different patterns were visually observed with an early peak and gradually decreasing trend (9 proteins), middle peak (14 proteins), late peak after a gradually increasing trend (27 proteins) and no specific pattern (4 proteins). Several biomarkers showed statistically significant increasing trends (defined as day 1 \u0026lt; day 4 \u0026lt; day 10 values) and late peaks (day 4 \u0026lt; day 10), such as chemokines CXCL6 and CCL23, or significant early peaks (that is, day 1 \u0026gt; day 4) such as leukemia inhibitor factor (LIF) and macrophage inflammatory factor-1β (MIP-1β). No statistically significant decreasing trends (defined as day 1 \u0026gt; day 4 \u0026gt; day 10) were observed. Two proteins showed statistically significant middle peaks (chemokine CCL28 and Delta and Notch epidermal growth factor-related receptor-DNER). \u003c/p\u003e\u003cp\u003eConclusion The comprehensive data set provided in this study may act as an illustration of an inflammatory profile of the acute phase of SAH showing groups of biomarkers with similar temporal patterns of activation. Further studies can be designed based on these data in order to explore potential implications on early and late clinical events in the disease course.\u003c/p\u003e","manuscriptTitle":"Temporal patterns of inflammatory biomarkers measured in the cerebrospinal fluid of patients with aneurysmal subarachnoid hemorrhage using multiplex Proximity Extension Assay technology.","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2020-03-13 01:36:17","doi":"10.21203/rs.3.rs-17091/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"a0abf20a-2519-4a4a-99db-6e03a08fda99","owner":[],"postedDate":"March 13th, 2020","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":69667,"name":"Neurobiology of Disease"}],"tags":[],"updatedAt":"2020-03-31T17:37:20+00:00","versionOfRecord":[],"versionCreatedAt":"2020-03-13 01:36:17","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-17091","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-17091","identity":"rs-17091","version":["v1"]},"buildId":"_2-kVJe1T_tPrBINL-cwx","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}