High IL-6/IL-10 ratios indicate sepsis in children with infectious diseases: A retrospective observational study

High IL-6/IL-10 ratios indicate sepsis in children with infectious diseases: A retrospective observational study | 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 Article High IL-6/IL-10 ratios indicate sepsis in children with infectious diseases: A retrospective observational study Lulu Cao, Yi-Qian Ren, Li Zhao, pengpeng Wang, xiaodong Zhu, Yueniu Zhu This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4997373/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 The present study aims to investigate the levels of IL-6 and IL-10, and the ratio of IL-6 to IL-10 in children with or without sepsis, in order to explore the roles of these cytokines in pediatric sepsis. Methods A retrospective observational study was performed between January 1, 2018, and December 31, 2022. Children with infectious diseases were reviewed and assigned to the sepsis and non-sepsis groups, respectively. Information on the demographics, clinical characteristics, laboratory results on IL-6 and IL-10, and treatments were retrieved from the medical records, and compared between the two groups. Results A total of 122 children were analyzed, with 57 and 65 children in the sepsis and non-sepsis groups, respectively. Compared to children in the non-sepsis group, children in the sepsis group had higher IL-6 and IL-10 levels, and IL-6/IL-10 ratios on the first day of hospital admission ( p < 0.05). The further multivariate logistic regression analysis confirmed the statistically significant association between the IL-6/IL-10 ratio, and the presence of sepsis. Conclusions Sepsis children present with higher IL-6 and IL-10 levels, and IL-6/IL-10 ratios, when compared to non-sepsis children. This can be used to evaluate the disease severity in this children population. sepsis interleukin-6 interleukin-10 pediatrics Figures Figure 1 Background Sepsis, particularly severe sepsis, is a significant contributor to mortality in the pediatric population. In infected children, the early identification of high-risk factors for sepsis and prompt treatment are essential to save their lives, and decrease morbidity. Sepsis is multi-organ dysfunction caused by infection [ 1 ]. During the pathogenesis of sepsis, immune dysregulation contributes to the deterioration and unfavorable prognosis of sepsis [ 2 ]. Inflammatory mediators are involved in modulating the immune reaction. Both anti-inflammatory and pro-inflammatory cytokines are released to collectively contribute in maintaining the immune homeostasis, and facilitating infection control. However, the excessive release of these inflammatory cytokines can trigger a cytokine storm, and lead to multi-organ dysfunction. Therefore, conducting studies on these cytokine releases can help to better understand the pathogenesis of sepsis, and recognize patients with a high risk to develop severe illnesses [ 3 , 4 ]. The cytokine interleukin-6 (IL-6) has pro-inflammatory activities [ 3 , 4 ]. Elevated levels of IL-6 are associated to high risk of unfavorable prognosis in sepsis patients [ 3 ]. Although interleukin-10 (IL-10) serves as a crucial anti-inflammatory mediator, high IL-10 level is a risk factor for poor outcomes in sepsis patients [ 3 , 5 ]. Several studies have reported the correlation between IL-6/IL-10, and suggested that the IL-6/IL-10 ratio can be used to predict the severity and prognosis of septic patients [ 6 , 7 ]. A recent publication revealed that the IL-6/IL-10 ratio can indicate the disease severity in pediatric sepsis patients with gram-negative infection in the intensive care unit (ICU)[ 8 ]. However, it remains unknown whether IL-6 and IL-10 can be applied to differentiate sepsis children from non-sepsis children in clinic. Therefore, the present retrospective study was conducted to investigate the significance of IL-6 and IL-10, and the IL-6/IL-10 ratio in pediatric patients with infections, in order to provide a useful clinical tool to facilitate the early identification and management of pediatric sepsis. Materials and Methods Study design and participant selection The present retrospective observational study was conducted for children with infectious diseases, who were admitted in Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, China, between January 1, 2018 and December 31, 2022. The study protocol was approved by the hospital ethics committee (Ethics approval number: XHEC-D-2024-136). The inclusion criteria were, as follows: (1) children ≤ 18 years old, and (2) children with an infectious disease, as detailed in the following paragraph. The exclusion criteria were, as follows: (1) children with a history of immunodeficiency; (2) children with malignancy; (3) children with autoimmune diseases; (4) children undergoing long-term glucocorticoid or immunosuppressant therapy; (5) children who received immunotherapy in the past three months; (6) children who have incomplete medical records. If the same child was admitted more than once, all admissions were included in the analysis. Definition of infection Sepsis was defined with reference to the Sepsis-III criteria [ 1 ]. The Sequential Organ Failure Assessment (SOFA) score of children was based on the standard proposed by Matics et al [ 9 ]. The diagnostic criteria for pneumonia, bacterial enteritis, appendiceal abscess, upper urinary tract infection, and cellulitis were established based on the 2005 publication of the ICU infection diagnostic criteria [ 10 ]. The diagnosis of bacterial meningitis required the fulfillment of all the following criteria: (1) fever with rectal temperature of > 38.5°C or axillary temperature of > 38.0°C; (2) meningeal irritation, headache, or altered mental status; (3) severe leukocytosis of > 100×10 6 cells/L or moderate leukocytosis of 10–100×10 6 cells/L, but with a decreased glucose level or an elevated protein of > 100 mg/dL in the cerebrospinal fluid (CSF) examination [ 11 ]. Viral encephalitis was diagnosed according to the clinical presentation of persistent altered mental status for > 24 hours, excluding encephalopathy due to other etiology. The diagnosis required meeting at least three of the following six criteria: (1) fever > 38°C within 72 hours before or after hospital admission; (2) seizures not fully explained by pre-existing epilepsy; (3) CSF white blood cell count of ≥ 5× 10^6/L; (4) new focal neurological signs; (5) new abnormalities in the neurological imaging examination; (6) electroencephalogram suggesting encephalitis [ 12 ]. Cryptococcal meningitis was diagnosed based on the guidelines provided by the Chinese Society of Infection, affiliated with the Chinese Medical Association, with the main criterion being the identification of cryptococcus in the CSF [ 13 ]. Data collection The hospital medical records were reviewed to retrieve the following necessary information: demographics, pediatric risk mortality (PRISM) score, SOFA score, etiology, and treatments. The IL-6 and IL-10 levels were measured on the first day of admission to the pediatric ICU. Then, the serum concentrations of IL-6 and IL-10 were determined using the MesoScale Discovery method (Meso QuickPlex SQ 120, USA) and human cytokines kit (BD, USA), respectively, according to manufacturer’s instructions in the hospital laboratory. Statistical analysis Eligible children were categorized into two groups: sepsis and non-sepsis groups. Continuous data were presented in mean ± standard deviation or median with interquartile range (IQR), and compared by Student t -test or Mann-Whitney test, depending on the normality test results. Categorical data were presented in numbers with percentages, and compared by Chi-square test. Then, multivariate logistic regression analysis was performed to identify the risk factors for sepsis. All statistical analyses were performed using SPSS version 22.0 (SPSS, IBM, NY, USA). A p -value of < 0.05 was considered statistically significant. Results Characteristics of the study participants A total of 412 pediatric patients were admitted during the study period. Among these patients, 185 patients had infections. After excluding 63 pediatric patients, 122 patients were included for the final analysis. These patients had a median age of 32.4 months old (IQR: 16.9 months old, 63.2 months old), and 54.9% (67/122) of these pediatric patients were boys. The participant selection flowchart is presented in Fig. 1 . Among these pediatric patients, 18 patients had the following underlying diseases (8 patients from the non-sepsis group and 10 patients from the sepsis group): epilepsy (two cases), congenital esophageal atresia (IIIa) (two cases), cerebral hypoplasia (six cases), methylmalonic acidemia (three cases), asthma (one case), Gaucher disease (one case), bronchopulmonary dysplasia (one case), congenital megacolon (one case), and Reye’s syndrome (one case). There were no statistically significant differences in gender, age, number of underlying diseases, and length of hospital and ICU stays between the two groups. Sepsis children had higher disease severity (higher SOFA and PRISM scores), when compared to non-sepsis children. Furthermore, compared to non-sepsis children, sepsis children received more frequent mechanical ventilation, hemodialysis/hemofiltration, glucocorticoids, and vasopressors ( p < 0.001, Table 1 ). Table 1 Comparison of baseline characteristics and treatments between the two groups. Characteristics Non-sepsis group ( n = 65) Sepsis group ( n = 57) p Gender, n (%) Male 36.00 (55.40%) 31.00 (54.40%) 0.912 Age, months 36.30 (17.60, 60.60) 27.00 (15.50, 80.20) 0.851 Underlying diseases, n (%) Yes 8 (12.30%) 10 (17.50%) 0.452 Infectious diseases, n 0.767 Pneumonia 39 31 Viral encephalitis 15 16 Bacterial meningitis 4 2 Cryptococcal encephalitis 1 1 Bacterial enteritis 3 6 Appendiceal abscess 1 0 Upper urinary tract infection 1 0 Cellulitis 1 1 Disease severity SOFA 1 (0, 1) 6 (2, 10) < 0.001 PRISM 0 (0, 2) 9 (1, 16) < 0.001 Medical treatments, n (%) Invasive mechanical ventilation Yes 4 (6.20%) 31 (54.40%) < 0.001 Hemodialysis/hemofiltration Yes 14 (21.50%) 31 (54.40%) < 0.001 Glucocorticoids Yes 24 (36.90%) 41 (71.90%) < 0.001 Vasopressors Yes 0 (0.00%) 41 (71.90%) < 0.001 Survival, n (%) Yes 65 (100.00%) 40 (17.20%) < 0.001 Length of hospital stay, days 17 (11.00, 25.00) 19 (8.50, 30.00) 0.882 Length of intensive care unit stay, days 7 (5.00, 12.00) 9 (5.50, 19.50) 0.112 Pneumonia was the most common infection in both groups of children, followed by viral encephalitis and bacterial meningitis (Table 1 ). Furthermore, pathogenic microorganisms were isolated from 58 of 122 children, which included viruses in 15 cases, bacteria in 33 cases, Mycoplasma pneumoniae in seven cases, and fungi in three cases (Table 2 ). Table 2 Distribution of pathogenic microorganisms in the two groups of children. Pathogen identified, n Non-sepsis group Sepsis group Virus Cytomegalovirus 1 3 Epstein-Barr virus 1 3 Adenovirus 2 1 Enterovirus 1 1 Parainfluenza virus 0 1 SARS-CoV-2 virus 0 1 Bacteria Escherichia coli 1 2 Klebsiella pneumoniae 1 3 Haemophilus influenzae 3 5 Pseudomonas aeruginosa 1 1 Streptococcus pneumoniae 1 6 Staphylococcus aureus 2 6 Salmonella . 0 1 Others Mycoplasma pneumoniae 4 3 Cryptococcus 1 1 Candida albicans 0 1 Pathogen not detected 46 18 Differences in inflammatory cytokine levels between groups The concentrations of IL-6 and IL-10 in both groups of children are presented in Table 3 . The median levels of IL-6 and IL-10 were significantly higher in the sepsis group, when compared to the non-sepsis group. Similarly, the median IL-6/IL-10 ratio was significantly higher in the sepsis group, when compared to the non-sepsis group. Next, a multivariate logistic regression analysis was further performed, with sepsis as the dependent variable, and demographics, underlying diseases, disease severity, IL-6, IL-10, and the IL-6/IL-10 ratio as independent variables. The association among IL-6, IL-10, and the occurrence of sepsis had no statistical significance in the multiple regression analysis (Tables S1 and S2), while the high IL-6/IL-10 ratio was associated to sepsis occurrence in children with infectious diseases (Table 4 ). Table 3 Comparison of cytokine levels between the two groups. Cytokines Non-sepsis group ( n = 65) Sepsis group ( n = 57) p IQR P 50 IQR P 50 IL-6 (pg/ml) 12.00, 116.00 44.60 13.00, 66.03 89.90 0.020 IL-10 (pg/ml) 6.80, 39.90 20.10 10.80, 227.50 58.90 < 0.001 IL-6/IL-10 0.70, 5.20 1.40 0.90, 8.20 2.40 0.020 Table 4 Results for the multivariate logistic regression analysis. Variables β S.E. Wald df p Exp(β) 95% EXP(β) Lower Upper Gender (male) 1.888 1.580 1.427 1 0.232 6.604 0.298 146.248 Have underlying diseases 6.428 3.014 4.549 1 0.033 619.013 1.683 227,614.702 Age (months) -0.007 0.020 0.137 1 0.711 0.993 0.954 1.032 SOFA 1.822 0.642 8.062 1 0.005 6.182 1.758 21.736 IL-6/IL-10 0.441 0.232 3.605 1 0.040 1.147 1.214 2.450 Constant -11.361 4.312 6.941 1 0.008 0.000 Notes : Dependent variable: sepsis occurrence or no sepsis occurrence. Exp(β) = 1.147, 95% confidence interval = 1.214–2.450. SOFA, Sequential Organ Failure Assessment. Discussion Children with sepsis carry a high mortality rate. In the present study, it was found that children with sepsis had higher levels of IL-6 and IL-10, when compared to children without sepsis. In addition, the ratio of IL-6 to IL-10 was notably higher in sepsis children, when compared to non-sepsis children. These results show that the increase in IL-6/IL-10 ratio can indicate the presence of sepsis in children with infectious diseases. In the present study participants, the most common infection sites included pneumonia, and the central nervous system, which is consistent with the findings of a previous study [ 14 ]. The present study revealed that in children with infectious diseases, both IL-6 and IL-10 were associated to sepsis, which is consistent to the reports of previous studies [ 3 – 5 ]. As an important proinflammatory factor, the high level of IL-6 was found to be a risk factor for poor outcomes in sepsis patients. Thus, IL-6 can be used as a valuable biomarker for sepsis diagnosis [ 15 ]. Compared to non-sepsis patients, the level of IL-6 can be significantly higher in sepsis patients at disease onset [ 16 , 17 ]. In addition, it was reported that IL-6 can be applied to indicate the severity of sepsis, and predict the sepsis prognosis. Among sepsis patients, patients with septic shock presented with significantly higher IL-6 levels, when compared to patients without septic shock[ 16 ]. Furthermore, among sepsis patients, patients with elevated levels of IL-6 presented with a significant increase in mortality within 28 days [ 17 ]. The presence of a ≥ 86% reduction in IL-6 levels within the initial 24 hours of ICU admission would indicate a favorable prognosis [ 18 ]. The level of IL-6 upon discharge can be applied to predicate the all-cause mortality in sepsis patients [ 19 ]. As an anti-inflammatory cytokine, IL-10 is a risk factor for severe sepsis and unfavorable prognosis in sepsis patients [ 5 ]. It was reported that IL-10 is a valuable biomarker to diagnose neonatal sepsis at its early stage [ 20 ]. A higher level of IL-10 can predict the severity of infection in patients with febrile neutropenia [ 21 ]. The persistent elevated levels of IL-10 in septic shock patients might inhibit the release of pro-inflammatory factors, and induce immunosuppression [ 22 , 23 ], finally contributing to the pathogenesis of multiple organ failure (MOF) [ 24 ]. The findings of the present study suggest that elevated IL-6/IL-10 ratios might contribute to sepsis development in pediatric patients with infectious diseases, which is consistent with the reports of previous studies [ 6 , 24 – 26 ]. Loisa et al. reported that a high IL-6/IL-10 ratio might be involved in MOF development in patients with severe sepsis [ 24 ]. In patients with Pneumocystis pneumonia, the severe and non-survival groups presented with high IL-6/IL-10 ratios [ 25 ]. In the present study, it was found that the IL-6/IL-10 ratio can indicate the presence of sepsis in children with infectious diseases. The IL-6/IL-10 ratio can be used to assess the relationship between pro-inflammatory and anti-inflammatory states, with alterations in this relationship closely associated to patient outcomes and disease severity. The early mortality of sepsis patients primarily stems from the exaggerated pro-inflammatory response, resulting in organ dysfunction. During this stage, the body exhibits a hyper-inflammatory state [ 27 ]. An elevated IL-6/IL-10 ratio suggests that the body is experiencing a strong inflammatory reaction, which might contribute to MOF and death. The present study investigated the correlation between IL-6/IL-10 and disease severity, primarily during the stages of the disease. The dynamic balance between anti-inflammatory and pro-inflammatory responses may vary over time. Therefore, the clinical implications of IL-6/IL-10 during the course of sepsis might change with its management. Further studies to monitor the dynamic changes of IL-6/IL-10 are required. Conclusions For children with infectious diseases, high IL-6 and IL-10 levels, and IL-6/IL-10 ratio can indicate the presence of sepsis, requiring prompt management. These present study findings offer novel insights for assessing the severity of infectious diseases in pediatric patients. Abbreviations IL-6：interleukin-6；IL-10：interleukin-10；ICU：intensive care unit; SOFA: Sequential Organ Failure Assessment; CSF: cerebrospinal fluid; PRISM: pediatric risk mortality; IQR：interquartile range; MOF: multiple organ failure Declarations Ethics approval and consent to participate: Ethical approval was provided by the Xinhua Hospital Affiliate, Shanghai Jiao Tong University School of Medicine (XHEC-D-2024-136) Consent to participate: Written informed consent for publication of their clinical details and/or clinical images were obtained from the guardian of the patient. A copy of the consent form is available for review by the Editor of this journal. Consent for publication: NOT applicable Availability of data and materials: The datasets generated during and analyzed during the current study are not publicly available now because the follow-up observation test is still in progress; but are available from the corresponding author or first author on reasonable request. Competing interests The authors declare that they have no competing interests Funding source: No Funding. Authors' contributions: LL C, program design, implementation, data collection and analysis, writing manuscript; YQ R, specimen detection and analysis; L Z, specimen collection, storage and sample preprocessing; PP W, case admission, specimen collection, data collection; XD Z: case admission, data collection; YN Z: quality control, review and editing the manuscript. All authors have read and agreed to the published version of the manuscript. Acknowledgements: We sincerely thank the children and their parents who participated in this study. References Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016;315(8):801–10. Mithal LB, Arshad M, Swigart LR, Khanolkar A, Ahmed A, Coates BM. 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Acta Anaesthesiol Scand. 2003;47(3):319–25. Sun J, Su J, Xie Y, Yin MT, Huang Y, Xu L, Zhou Q, Zhu B. Plasma IL-6/IL-10 Ratio and IL-8, LDH, and HBDH Level Predict the Severity and the Risk of Death in AIDS Patients with Pneumocystis Pneumonia. Journal of immunology research 2016, 2016:1583951. McElvaney OJ, Hobbs BD, Qiao D, McElvaney OF, Moll M, McEvoy NL, Clarke J, O'Connor E, Walsh S, Cho MH et al. A linear prognostic score based on the ratio of interleukin-6 to interleukin-10 predicts outcomes in COVID-19. EBioMedicine 2020, 61:103026. Biron BM, Ayala A, Lomas-Neira JL. Biomarkers for Sepsis: What Is and What Might Be? Biomark insights. 2015;10(Suppl 4):7–17. Additional Declarations No competing interests reported. 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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-4997373","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":362863112,"identity":"b76bdcd3-d0dd-43ae-b1e6-2ab111be1b47","order_by":0,"name":"Lulu Cao","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAzklEQVRIiWNgGAWjYHACxgMMBQw8/MzsBx8kVNQQp+cAgwGDnGQ7T7LBgzPHiNdibHCewUzyYQszYeX87YcPHOYxOJw4s5khrSKxgQ0o0p2AV4vEmbQEsJZ+ZsZjNxJ3yABFzm7Aq8WAIccAbsuNxDNsDAYSuQS08L+BaNlwmMGsILGNmQgtEhBbjA2AWhiI0iJx41nCwTkG6XKSzTzJEglnjvEQ9At/f/LBB28qrHn4+Y8f/PijokaOv70XvxYMwEOa8lEwCkbBKBgFWAEA6uVJxbvYbiMAAAAASUVORK5CYII=","orcid":"","institution":"XinHua Hospital","correspondingAuthor":true,"prefix":"","firstName":"Lulu","middleName":"","lastName":"Cao","suffix":""},{"id":362863114,"identity":"e6a988c4-bc47-4e17-a073-ec5b0d06d12e","order_by":1,"name":"Yi-Qian Ren","email":"","orcid":"","institution":"XinHua Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yi-Qian","middleName":"","lastName":"Ren","suffix":""},{"id":362863116,"identity":"5f2950dd-3e4c-49c8-b0e3-b173c835dc17","order_by":2,"name":"Li Zhao","email":"","orcid":"","institution":"XinHua Hospital","correspondingAuthor":false,"prefix":"","firstName":"Li","middleName":"","lastName":"Zhao","suffix":""},{"id":362863117,"identity":"50da9a5b-8171-476f-9609-85f728cfefac","order_by":3,"name":"pengpeng Wang","email":"","orcid":"","institution":"XinHua Hospital","correspondingAuthor":false,"prefix":"","firstName":"pengpeng","middleName":"","lastName":"Wang","suffix":""},{"id":362863119,"identity":"597b00d1-dd69-441b-b173-aae59e98aa64","order_by":4,"name":"xiaodong Zhu","email":"","orcid":"","institution":"XinHua Hospital","correspondingAuthor":false,"prefix":"","firstName":"xiaodong","middleName":"","lastName":"Zhu","suffix":""},{"id":362863122,"identity":"e0c71d1c-5a58-455c-8e92-5e18faf2c484","order_by":5,"name":"Yueniu Zhu","email":"","orcid":"","institution":"XinHua Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yueniu","middleName":"","lastName":"Zhu","suffix":""}],"badges":[],"createdAt":"2024-08-29 11:41:31","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4997373/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4997373/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":67174533,"identity":"036db445-8bdd-41c2-b0ec-714e8156b5a0","added_by":"auto","created_at":"2024-10-22 04:44:02","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":12405,"visible":true,"origin":"","legend":"\u003cp\u003ePatient selection flowchart\u003c/p\u003e","description":"","filename":"Fig11.png","url":"https://assets-eu.researchsquare.com/files/rs-4997373/v1/0fbc678d0925a865c50a4597.png"},{"id":70073542,"identity":"e6f2fce2-a8d2-4b25-81f8-6a206322f508","added_by":"auto","created_at":"2024-11-28 06:02:33","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":643321,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4997373/v1/db7768cb-8707-4f28-9456-478754b39c5a.pdf"},{"id":67174534,"identity":"490ad8b8-013b-4402-88f0-7bddedf4b4b2","added_by":"auto","created_at":"2024-10-22 04:44:02","extension":"docx","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":19694,"visible":true,"origin":"","legend":"","description":"","filename":"Additionalfile1Supptables.docx","url":"https://assets-eu.researchsquare.com/files/rs-4997373/v1/6b4dd3704f2f144e9749463c.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"High IL-6/IL-10 ratios indicate sepsis in children with infectious diseases: A retrospective observational study","fulltext":[{"header":"Background","content":"\u003cp\u003eSepsis, particularly severe sepsis, is a significant contributor to mortality in the pediatric population. In infected children, the early identification of high-risk factors for sepsis and prompt treatment are essential to save their lives, and decrease morbidity.\u003c/p\u003e \u003cp\u003eSepsis is multi-organ dysfunction caused by infection [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. During the pathogenesis of sepsis, immune dysregulation contributes to the deterioration and unfavorable prognosis of sepsis [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Inflammatory mediators are involved in modulating the immune reaction. Both anti-inflammatory and pro-inflammatory cytokines are released to collectively contribute in maintaining the immune homeostasis, and facilitating infection control. However, the excessive release of these inflammatory cytokines can trigger a cytokine storm, and lead to multi-organ dysfunction. Therefore, conducting studies on these cytokine releases can help to better understand the pathogenesis of sepsis, and recognize patients with a high risk to develop severe illnesses [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe cytokine interleukin-6 (IL-6) has pro-inflammatory activities [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Elevated levels of IL-6 are associated to high risk of unfavorable prognosis in sepsis patients [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Although interleukin-10 (IL-10) serves as a crucial anti-inflammatory mediator, high IL-10 level is a risk factor for poor outcomes in sepsis patients [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Several studies have reported the correlation between IL-6/IL-10, and suggested that the IL-6/IL-10 ratio can be used to predict the severity and prognosis of septic patients [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. A recent publication revealed that the IL-6/IL-10 ratio can indicate the disease severity in pediatric sepsis patients with gram-negative infection in the intensive care unit (ICU)[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. However, it remains unknown whether IL-6 and IL-10 can be applied to differentiate sepsis children from non-sepsis children in clinic.\u003c/p\u003e \u003cp\u003eTherefore, the present retrospective study was conducted to investigate the significance of IL-6 and IL-10, and the IL-6/IL-10 ratio in pediatric patients with infections, in order to provide a useful clinical tool to facilitate the early identification and management of pediatric sepsis.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design and participant selection\u003c/h2\u003e \u003cp\u003eThe present retrospective observational study was conducted for children with infectious diseases, who were admitted in Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, China, between January 1, 2018 and December 31, 2022. The study protocol was approved by the hospital ethics committee (Ethics approval number: XHEC-D-2024-136).\u003c/p\u003e \u003cp\u003eThe inclusion criteria were, as follows: (1) children\u0026thinsp;\u0026le;\u0026thinsp;18 years old, and (2) children with an infectious disease, as detailed in the following paragraph. The exclusion criteria were, as follows: (1) children with a history of immunodeficiency; (2) children with malignancy; (3) children with autoimmune diseases; (4) children undergoing long-term glucocorticoid or immunosuppressant therapy; (5) children who received immunotherapy in the past three months; (6) children who have incomplete medical records. If the same child was admitted more than once, all admissions were included in the analysis.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eDefinition of infection\u003c/h2\u003e \u003cp\u003eSepsis was defined with reference to the Sepsis-III criteria [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. The Sequential Organ Failure Assessment (SOFA) score of children was based on the standard proposed by Matics \u003cem\u003eet al\u003c/em\u003e [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. The diagnostic criteria for pneumonia, bacterial enteritis, appendiceal abscess, upper urinary tract infection, and cellulitis were established based on the 2005 publication of the ICU infection diagnostic criteria [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe diagnosis of bacterial meningitis required the fulfillment of all the following criteria: (1) fever with rectal temperature of \u0026gt;\u0026thinsp;38.5\u0026deg;C or axillary temperature of \u0026gt;\u0026thinsp;38.0\u0026deg;C; (2) meningeal irritation, headache, or altered mental status; (3) severe leukocytosis of \u0026gt;\u0026thinsp;100\u0026times;10\u003csup\u003e6\u003c/sup\u003e cells/L or moderate leukocytosis of 10\u0026ndash;100\u0026times;10\u003csup\u003e6\u003c/sup\u003e cells/L, but with a decreased glucose level or an elevated protein of \u0026gt;\u0026thinsp;100 mg/dL in the cerebrospinal fluid (CSF) examination [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Viral encephalitis was diagnosed according to the clinical presentation of persistent altered mental status for \u0026gt;\u0026thinsp;24 hours, excluding encephalopathy due to other etiology. The diagnosis required meeting at least three of the following six criteria: (1) fever\u0026thinsp;\u0026gt;\u0026thinsp;38\u0026deg;C within 72 hours before or after hospital admission; (2) seizures not fully explained by pre-existing epilepsy; (3) CSF white blood cell count of \u0026ge;\u0026thinsp;5\u0026times; 10^6/L; (4) new focal neurological signs; (5) new abnormalities in the neurological imaging examination; (6) electroencephalogram suggesting encephalitis [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eCryptococcal meningitis was diagnosed based on the guidelines provided by the Chinese Society of Infection, affiliated with the Chinese Medical Association, with the main criterion being the identification of cryptococcus in the CSF [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eData collection\u003c/h2\u003e \u003cp\u003e The hospital medical records were reviewed to retrieve the following necessary information: demographics, pediatric risk mortality (PRISM) score, SOFA score, etiology, and treatments.\u003c/p\u003e \u003cp\u003eThe IL-6 and IL-10 levels were measured on the first day of admission to the pediatric ICU. Then, the serum concentrations of IL-6 and IL-10 were determined using the MesoScale Discovery method (Meso QuickPlex SQ 120, USA) and human cytokines kit (BD, USA), respectively, according to manufacturer\u0026rsquo;s instructions in the hospital laboratory.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eEligible children were categorized into two groups: sepsis and non-sepsis groups. Continuous data were presented in mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation or median with interquartile range (IQR), and compared by Student \u003cem\u003et\u003c/em\u003e-test or Mann-Whitney test, depending on the normality test results. Categorical data were presented in numbers with percentages, and compared by Chi-square test. Then, multivariate logistic regression analysis was performed to identify the risk factors for sepsis. All statistical analyses were performed using SPSS version 22.0 (SPSS, IBM, NY, USA). A \u003cem\u003ep\u003c/em\u003e-value of \u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eCharacteristics of the study participants\u003c/h2\u003e \u003cp\u003eA total of 412 pediatric patients were admitted during the study period. Among these patients, 185 patients had infections. After excluding 63 pediatric patients, 122 patients were included for the final analysis. These patients had a median age of 32.4 months old (IQR: 16.9 months old, 63.2 months old), and 54.9% (67/122) of these pediatric patients were boys. The participant selection flowchart is presented in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Among these pediatric patients, 18 patients had the following underlying diseases (8 patients from the non-sepsis group and 10 patients from the sepsis group): epilepsy (two cases), congenital esophageal atresia (IIIa) (two cases), cerebral hypoplasia (six cases), methylmalonic acidemia (three cases), asthma (one case), Gaucher disease (one case), bronchopulmonary dysplasia (one case), congenital megacolon (one case), and Reye\u0026rsquo;s syndrome (one case).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThere were no statistically significant differences in gender, age, number of underlying diseases, and length of hospital and ICU stays between the two groups. Sepsis children had higher disease severity (higher SOFA and PRISM scores), when compared to non-sepsis children. Furthermore, compared to non-sepsis children, sepsis children received more frequent mechanical ventilation, hemodialysis/hemofiltration, glucocorticoids, and vasopressors (\u003cem\u003ep\u0026thinsp;\u0026lt;\u003c/em\u003e\u0026thinsp;0.001, Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\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 \u003cp\u003eComparison of baseline characteristics and treatments between the two groups.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNon-sepsis group (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;65)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSepsis group (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;57)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGender, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36.00 (55.40%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e31.00 (54.40%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.912\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, months\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36.30 (17.60, 60.60)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e27.00 (15.50, 80.20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.851\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnderlying diseases, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (12.30%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10 (17.50%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.452\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInfectious diseases, \u003cem\u003en\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.767\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePneumonia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\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 \u003cp\u003eViral encephalitis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\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 \u003cp\u003eBacterial meningitis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\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 \u003cp\u003eCryptococcal encephalitis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\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 \u003cp\u003eBacterial enteritis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\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 \u003cp\u003eAppendiceal abscess\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\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 \u003cp\u003eUpper urinary tract infection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\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 \u003cp\u003eCellulitis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDisease severity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSOFA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (0, 1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6 (2, 10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePRISM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0, 2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9 (1, 16)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedical treatments, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInvasive mechanical ventilation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (6.20%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e31 (54.40%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHemodialysis/hemofiltration\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 (21.50%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e31 (54.40%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGlucocorticoids\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24 (36.90%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e41 (71.90%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVasopressors\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0.00%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e41 (71.90%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSurvival, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e65 (100.00%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e40 (17.20%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLength of hospital stay, days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17 (11.00, 25.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e19 (8.50, 30.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.882\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLength of intensive care unit stay, days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (5.00, 12.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9 (5.50, 19.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.112\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003ePneumonia was the most common infection in both groups of children, followed by viral encephalitis and bacterial meningitis (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Furthermore, pathogenic microorganisms were isolated from 58 of 122 children, which included viruses in 15 cases, bacteria in 33 cases, \u003cem\u003eMycoplasma pneumoniae\u003c/em\u003e in seven cases, and fungi in three cases (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\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 \u003cp\u003eDistribution of pathogenic microorganisms in the two groups of children.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003ePathogen identified, \u003cem\u003en\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNon-sepsis group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSepsis group\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVirus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"5\" rowspan=\"6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCytomegalovirus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEpstein-Barr\u0026nbsp;virus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAdenovirus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEnterovirus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eParainfluenza virus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSARS-CoV-2 virus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBacteria\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"6\" rowspan=\"7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eEscherichia coli\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eKlebsiella pneumoniae\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eHaemophilus influenzae\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003ePseudomonas aeruginosa\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eStreptococcus pneumoniae\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eStaphylococcus aureus\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eSalmonella .\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOthers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eMycoplasma pneumoniae\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eCryptococcus\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eCandida albicans\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003ePathogen not detected\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e18\u003c/p\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=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eDifferences in inflammatory cytokine levels between groups\u003c/h2\u003e \u003cp\u003eThe concentrations of IL-6 and IL-10 in both groups of children are presented in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. The median levels of IL-6 and IL-10 were significantly higher in the sepsis group, when compared to the non-sepsis group. Similarly, the median IL-6/IL-10 ratio was significantly higher in the sepsis group, when compared to the non-sepsis group. Next, a multivariate logistic regression analysis was further performed, with sepsis as the dependent variable, and demographics, underlying diseases, disease severity, IL-6, IL-10, and the IL-6/IL-10 ratio as independent variables. The association among IL-6, IL-10, and the occurrence of sepsis had no statistical significance in the multiple regression analysis (Tables S1 and S2), while the high IL-6/IL-10 ratio was associated to sepsis occurrence in children with infectious diseases (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\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 \u003cp\u003eComparison of cytokine levels between the two groups.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eCytokines\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eNon-sepsis group (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;65)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eSepsis group (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;57)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIQR\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eP\u003csub\u003e50\u003c/sub\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eIQR\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP\u003csub\u003e50\u003c/sub\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIL-6 (pg/ml)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12.00, 116.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e44.60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13.00, 66.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e89.90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.020\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIL-10 (pg/ml)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.80, 39.90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10.80, 227.50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e58.90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIL-6/IL-10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.70, 5.20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.90, 8.20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.020\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\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 \u003cp\u003eResults for the multivariate logistic regression analysis.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"9\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eβ\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eS.E.\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eWald\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003edf\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eExp(β)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e \u003cp\u003e95% EXP(β)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eLower\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eUpper\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGender (male)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.888\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.580\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.427\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.232\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e6.604\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.298\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e146.248\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHave underlying diseases\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.428\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.014\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.549\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.033\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e619.013\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1.683\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e227,614.702\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (months)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0.007\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.020\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.137\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.711\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.993\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.954\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1.032\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSOFA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.822\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.642\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8.062\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.005\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e6.182\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1.758\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e21.736\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIL-6/IL-10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.441\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.232\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.605\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.040\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.147\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1.214\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e2.450\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eConstant\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-11.361\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.312\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.941\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.008\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"9\"\u003e\u003cb\u003eNotes\u003c/b\u003e: Dependent variable: sepsis occurrence or no sepsis occurrence. Exp(β)\u0026thinsp;=\u0026thinsp;1.147, 95% confidence interval\u0026thinsp;=\u0026thinsp;1.214\u0026ndash;2.450. SOFA, Sequential Organ Failure Assessment.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eChildren with sepsis carry a high mortality rate. In the present study, it was found that children with sepsis had higher levels of IL-6 and IL-10, when compared to children without sepsis. In addition, the ratio of IL-6 to IL-10 was notably higher in sepsis children, when compared to non-sepsis children. These results show that the increase in IL-6/IL-10 ratio can indicate the presence of sepsis in children with infectious diseases.\u003c/p\u003e \u003cp\u003eIn the present study participants, the most common infection sites included pneumonia, and the central nervous system, which is consistent with the findings of a previous study [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe present study revealed that in children with infectious diseases, both IL-6 and IL-10 were associated to sepsis, which is consistent to the reports of previous studies [\u003cspan additionalcitationids=\"CR4\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. As an important proinflammatory factor, the high level of IL-6 was found to be a risk factor for poor outcomes in sepsis patients. Thus, IL-6 can be used as a valuable biomarker for sepsis diagnosis [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Compared to non-sepsis patients, the level of IL-6 can be significantly higher in sepsis patients at disease onset [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. In addition, it was reported that IL-6 can be applied to indicate the severity of sepsis, and predict the sepsis prognosis. Among sepsis patients, patients with septic shock presented with significantly higher IL-6 levels, when compared to patients without septic shock[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Furthermore, among sepsis patients, patients with elevated levels of IL-6 presented with a significant increase in mortality within 28 days [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. The presence of a\u0026thinsp;\u0026ge;\u0026thinsp;86% reduction in IL-6 levels within the initial 24 hours of ICU admission would indicate a favorable prognosis [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. The level of IL-6 upon discharge can be applied to predicate the all-cause mortality in sepsis patients [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAs an anti-inflammatory cytokine, IL-10 is a risk factor for severe sepsis and unfavorable prognosis in sepsis patients [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. It was reported that IL-10 is a valuable biomarker to diagnose neonatal sepsis at its early stage [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. A higher level of IL-10 can predict the severity of infection in patients with febrile neutropenia [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. The persistent elevated levels of IL-10 in septic shock patients might inhibit the release of pro-inflammatory factors, and induce immunosuppression [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e], finally contributing to the pathogenesis of multiple organ failure (MOF) [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe findings of the present study suggest that elevated IL-6/IL-10 ratios might contribute to sepsis development in pediatric patients with infectious diseases, which is consistent with the reports of previous studies [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan additionalcitationids=\"CR25\" citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Loisa \u003cem\u003eet al.\u003c/em\u003e reported that a high IL-6/IL-10 ratio might be involved in MOF development in patients with severe sepsis [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. In patients with \u003cem\u003ePneumocystis\u003c/em\u003e pneumonia, the severe and non-survival groups presented with high IL-6/IL-10 ratios [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. In the present study, it was found that the IL-6/IL-10 ratio can indicate the presence of sepsis in children with infectious diseases. The IL-6/IL-10 ratio can be used to assess the relationship between pro-inflammatory and anti-inflammatory states, with alterations in this relationship closely associated to patient outcomes and disease severity. The early mortality of sepsis patients primarily stems from the exaggerated pro-inflammatory response, resulting in organ dysfunction. During this stage, the body exhibits a hyper-inflammatory state [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. An elevated IL-6/IL-10 ratio suggests that the body is experiencing a strong inflammatory reaction, which might contribute to MOF and death.\u003c/p\u003e \u003cp\u003eThe present study investigated the correlation between IL-6/IL-10 and disease severity, primarily during the stages of the disease. The dynamic balance between anti-inflammatory and pro-inflammatory responses may vary over time. Therefore, the clinical implications of IL-6/IL-10 during the course of sepsis might change with its management. Further studies to monitor the dynamic changes of IL-6/IL-10 are required.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eFor children with infectious diseases, high IL-6 and IL-10 levels, and IL-6/IL-10 ratio can indicate the presence of sepsis, requiring prompt management. These present study findings offer novel insights for assessing the severity of infectious diseases in pediatric patients.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eIL-6：interleukin-6；IL-10：interleukin-10；ICU：intensive care unit;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSOFA: Sequential Organ Failure Assessment; CSF: cerebrospinal fluid; PRISM: pediatric risk mortality; IQR：interquartile range; MOF: multiple organ failure\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEthical approval was provided by the Xinhua Hospital Affiliate, Shanghai Jiao Tong University School of Medicine (XHEC-D-2024-136)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to participate:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent for publication of their clinical details and/or clinical\u003c/p\u003e\n\u003cp\u003eimages were obtained from the guardian of the patient. A copy of the consent form is available for review by the Editor of this journal.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication:\u0026nbsp;\u003c/strong\u003eNOT applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated during and analyzed during the current study are not publicly available now because the follow-up observation test is still in progress; but are available from the corresponding author or first author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding source: \u0026nbsp;\u003c/strong\u003eNo Funding.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eLL C, program design, implementation, data collection and analysis, writing manuscript; YQ R, specimen detection and analysis; L Z, specimen collection, storage and sample preprocessing; PP W, case admission, specimen collection, data collection; XD Z: case admission, data collection; YN Z: quality control, review and editing the manuscript. All authors have read and agreed to the published version of the manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements:\u0026nbsp;\u003c/strong\u003eWe sincerely thank the children and their parents who participated in this study.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eSinger M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016;315(8):801\u0026ndash;10.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMithal LB, Arshad M, Swigart LR, Khanolkar A, Ahmed A, Coates BM. Mechanisms and modulation of sepsis-induced immune dysfunction in children. Pediatr Res. 2022;91(2):447\u0026ndash;53.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFajgenbaum DC, June CH. Cytokine Storm. N Engl J Med. 2020;383(23):2255\u0026ndash;73.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCicchese JM, Evans S, Hult C, Joslyn LR, Wessler T, Millar JA, Marino S, Cilfone NA, Mattila JT, Linderman JJ, et al. Dynamic balance of pro- and anti-inflammatory signals controls disease and limits pathology. Immunol Rev. 2018;285(1):147\u0026ndash;67.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMisra AK, Levy MM, Ward NS. Biomarkers of Immunosuppression. Crit Care Clin. 2020;36(1):167\u0026ndash;76.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eXiao L, Ran X, Zhong Y, Le Y, Li S. A combined ratio change of inflammatory biomarkers at 72 h could predict the severity and prognosis of sepsis from pulmonary infections. Immunobiology. 2022;227(6):152290.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ede Brito RC, Lucena-Silva N, Torres LC, Luna CF, Correia JB, da Silva GA. The balance between the serum levels of IL-6 and IL-10 cytokines discriminates mild and severe acute pneumonia. BMC Pulm Med. 2016;16(1):170.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhang Y, Li B, Ning B. Evaluating IL-6 and IL-10 as rapid diagnostic tools for Gram-negative bacteria and as disease severity predictors in pediatric sepsis patients in the intensive care unit. Front Immunol. 2022;13:1043968.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMatics TJ, Sanchez-Pinto LN. Adaptation and Validation of a Pediatric Sequential Organ Failure Assessment Score and Evaluation of the Sepsis-3 Definitions in Critically Ill Children. JAMA Pediatr. 2017;171(10):e172352.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCalandra T, Cohen J. The international sepsis forum consensus conference on definitions of infection in the intensive care unit. \u003cem\u003eCritical care medicine\u003c/em\u003e 2005, 33(7):1538\u0026ndash;1548.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003evan de Beek D, Cabellos C, Dzupova O, Esposito S, Klein M, Kloek AT, Leib SL, Mourvillier B, Ostergaard C, Pagliano P, et al. ESCMID guideline: diagnosis and treatment of acute bacterial meningitis. Clin Microbiol infection: official publication Eur Soc Clin Microbiol Infect Dis. 2016;22(Suppl 3):S37\u0026ndash;62.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVenkatesan A, Tunkel AR, Bloch KC, Lauring AS, Sejvar J, Bitnun A, Stahl JP, Mailles A, Drebot M, Rupprecht CE, et al. Case definitions, diagnostic algorithms, and priorities in encephalitis: consensus statement of the international encephalitis consortium. Clin Infect diseases: official publication Infect Dis Soc Am. 2013;57(8):1114\u0026ndash;28.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChinese Medical Association Infectious Diseases Division. Consensus on Diagnosis and Treatment of Cryptococcal Meningitis. Chin J Infect Dis. 2018;36:193\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCecconi M, Evans L, Levy M, Rhodes A. Sepsis and septic shock. Lancet (London England). 2018;392(10141):75\u0026ndash;87.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMa L, Zhang H, Yin YL, Guo WZ, Ma YQ, Wang YB, Shu C, Dong LQ. Role of interleukin-6 to differentiate sepsis from non-infectious systemic inflammatory response syndrome. Cytokine. 2016;88:126\u0026ndash;35.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSong J, Park DW, Moon S, Cho HJ, Park JH, Seok H, Choi WS. Diagnostic and prognostic value of interleukin-6, pentraxin 3, and procalcitonin levels among sepsis and septic shock patients: a prospective controlled study according to the Sepsis-3 definitions. BMC Infect Dis. 2019;19(1):968.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYu B, Chen M, Zhang Y, Cao Y, Yang J, Wei B, Wang J. Diagnostic and Prognostic Value of Interleukin-6 in Emergency Department Sepsis Patients. Infect Drug Resist. 2022;15:5557\u0026ndash;66.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eThao PTN, Tra TT, Son NT, Wada K. Reduction in the IL-6 level at 24 h after admission to the intensive care unit is a survival predictor for Vietnamese patients with sepsis and septic shock: a prospective study. BMC Emerg Med. 2018;18(1):39.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNaffaa M, Makhoul BF, Tobia A, Kaplan M, Aronson D, Saliba W, Azzam ZS. Interleukin-6 at discharge predicts all-cause mortality in patients with sepsis. Am J Emerg Med. 2013;31(9):1361\u0026ndash;4.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang Q, Peng G, Gan L, Deng Z, Zeng L, Deng J. The Value of Interleukin-10 in the Early Diagnosis of Neonatal Sepsis: A Meta-Analysis. Pediatr Crit care medicine: J Soc Crit Care Med World Federation Pediatr Intensive Crit Care Soc. 2021;22(9):e492\u0026ndash;501.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDoerflinger M, Haeusler GM, Li-Wai-Suen CSN, Clark JE, Slavin M, Babl FE, Allaway Z, Mechinaud F, Smyth GK, De Abreu Lourenco R, et al. Procalcitonin and Interleukin-10 May Assist in Early Prediction of Bacteraemia in Children With Cancer and Febrile Neutropenia. Front Immunol. 2021;12:641879.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSfeir T, Saha DC, Astiz M, Rackow EC. Role of interleukin-10 in monocyte hyporesponsiveness associated with septic shock. Crit Care Med. 2001;29(1):129\u0026ndash;33.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFabri A, Kandara K, Coudereau R, Gossez M, Abraham P, Monard C, Cour M, Rimmel\u0026eacute; T, Argaud L, Monneret G, et al. Characterization of Circulating IL-10-Producing Cells in Septic Shock Patients: A Proof of Concept Study. Front Immunol. 2020;11:615009.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLoisa P, Rinne T, Laine S, Hurme M, Kaukinen S. Anti-inflammatory cytokine response and the development of multiple organ failure in severe sepsis. Acta Anaesthesiol Scand. 2003;47(3):319\u0026ndash;25.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSun J, Su J, Xie Y, Yin MT, Huang Y, Xu L, Zhou Q, Zhu B. Plasma IL-6/IL-10 Ratio and IL-8, LDH, and HBDH Level Predict the Severity and the Risk of Death in AIDS Patients with Pneumocystis Pneumonia. \u003cem\u003eJournal of immunology research\u003c/em\u003e 2016, 2016:1583951.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMcElvaney OJ, Hobbs BD, Qiao D, McElvaney OF, Moll M, McEvoy NL, Clarke J, O'Connor E, Walsh S, Cho MH et al. A linear prognostic score based on the ratio of interleukin-6 to interleukin-10 predicts outcomes in COVID-19. \u003cem\u003eEBioMedicine\u003c/em\u003e 2020, 61:103026.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBiron BM, Ayala A, Lomas-Neira JL. Biomarkers for Sepsis: What Is and What Might Be? Biomark insights. 2015;10(Suppl 4):7\u0026ndash;17.\u003c/span\u003e\u003c/li\u003e\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":"sepsis, interleukin-6, interleukin-10, pediatrics","lastPublishedDoi":"10.21203/rs.3.rs-4997373/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4997373/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eThe present study aims to investigate the levels of IL-6 and IL-10, and the ratio of IL-6 to IL-10 in children with or without sepsis, in order to explore the roles of these cytokines in pediatric sepsis.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eA retrospective observational study was performed between January 1, 2018, and December 31, 2022. Children with infectious diseases were reviewed and assigned to the sepsis and non-sepsis groups, respectively. Information on the demographics, clinical characteristics, laboratory results on IL-6 and IL-10, and treatments were retrieved from the medical records, and compared between the two groups.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eA total of 122 children were analyzed, with 57 and 65 children in the sepsis and non-sepsis groups, respectively. Compared to children in the non-sepsis group, children in the sepsis group had higher IL-6 and IL-10 levels, and IL-6/IL-10 ratios on the first day of hospital admission (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). The further multivariate logistic regression analysis confirmed the statistically significant association between the IL-6/IL-10 ratio, and the presence of sepsis.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eSepsis children present with higher IL-6 and IL-10 levels, and IL-6/IL-10 ratios, when compared to non-sepsis children. This can be used to evaluate the disease severity in this children population.\u003c/p\u003e","manuscriptTitle":"High IL-6/IL-10 ratios indicate sepsis in children with infectious diseases: A retrospective observational study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-10-22 04:43:56","doi":"10.21203/rs.3.rs-4997373/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":"5a31d980-12c9-4c20-ab5c-021f6383eb75","owner":[],"postedDate":"October 22nd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-11-28T05:53:23+00:00","versionOfRecord":[],"versionCreatedAt":"2024-10-22 04:43:56","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4997373","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4997373","identity":"rs-4997373","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}