Evaluation of Clinical Impact of Interleukin 8 Gene Expression in Patients with Fibromyalgia

Evaluation of Clinical Impact of Interleukin 8 Gene Expression in Patients with Fibromyalgia | 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 Evaluation of Clinical Impact of Interleukin 8 Gene Expression in Patients with Fibromyalgia Carolina Dias da Silva Amorim, Marco Felipe Macêdo Alves, Marcella Dias Teixeira, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5486569/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 5 You are reading this latest preprint version Abstract Background: Fibromyalgia (FM) is a musculoskeletal syndrome characterized by diffuse and chronic pain associated with other symptoms such as fatigue, sleep/cognition disorders, headache, depression and anxiety, resulting from a change in pain processing. Previous research has shown an increase in some interleukins (IL) in patients with FM when compared to controls, however, there is still no uniformity and consensus in the results. There is no study that evaluates IL8 mRNA expression in FM and its association with obesity and other clinical parameters. This study aims to verify the impact of IL8 mRNA expression on the clinical parameters of patients with FM (FMG) in relation to the comparison group (CG). Method: This study evaluated patients diagnosed with FM treated at the rheumatology service of the Hospital das Clínicas of the Federal University of Pernambuco (HC-UFPE). The CG group was composed of individuals without chronic pain (companions of the patients and hospital employees). Clinical and demographic data were collected in both groups, and questionnaires for fatigue (FACIT-F), impact of FM (FIQ-R), depression (BDI), and sleep (NRS) were applied to both groups. Peripheral blood was collected for evaluation of IL8 gene expression through real time polymerase chain reaction (qPCR). Results: Patients with FM show a lower frequency of IL8 gene expression compared to the CG, but FMG presented mainly up regulated in relation to CG. There was no association of IL8 expression and worse FIQ-R indices, sleep disturbance, BMI or fatigue. However, there was an association between IL8 expression and moderate depression ( p = 0.002) and physical activity ( p = 0.039), where patients in FMG who did express IL8 were practicing less physical activity. Conclusion: Patients in FMG did not have a higher frequency of IL8 expression compared to CG, however patients with IL8 expression have a greater association with moderate depression. Fibromyalgia interleukin 8 depression fatigue sleep quality obesity Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Fibromyalgia (FM) is a chronic non-inflammatory pain syndrome characterized by diffuse pain 1 associated with other symptoms such as fatigue, mood and sleep disorders, headache and cognitive impairment, among others 2 . Although some factors are known to predispose an individual to develop FM, such as physical trauma, emotional events, and genetic factors, its exact etiology is still unknown 2 , 3 . To be diagnosed with FM, the patient must present with diffuse pain for more than 3 months and associated symptoms (fatigue, sleep disturbances, cognitive alterations, headache, depression, or abdominal pain) of significant intensity, scoring a specific number in a questionnaire validated for the disease 4 . Among the criteria that define the pathology, there is no characteristic laboratory or imaging data, and the diagnosis is made only with the clinical history and physical examination 2 . Although inflammation and cell destruction are correlated with the pain response, chronic pain is probably not the direct consequence of acute inflammation or cell damage 5 , 6 . One of the main hypotheses investigated in FM refers to changes in nociceptive mechanisms, related to pain modulation, which would result in hyperalgesia and/or allodynia 7 . Some works have evaluated the hypothesis of participation of immunological mechanisms in the genesis and evolution of pain in FM, but the results found are also contradictory and so far, do not allow confirming or excluding this hypothesis 8 . So far, alteration of several markers like cytokines has been demonstrated, but without consensus in research. Some of the interleukins (IL) studied in FM and chronic pain are: IL1β, IL6, IL8, IL10 and IL15 9,10 . More recently, an association of chronic pain with high levels of IL8 has been found, but studies are still not conclusive 11 . In 2019, work was carried out with murine models using the drug Reparixin, an IL8 antagonist, which was able to reduce chronic low back pain 12 . In addition to the relationship with chronic pain, these inflammatory mediators are involved in other pathologies, and it has already been documented that there is an increase in some interleukins such as IL6 and IL8 in obesity 13 . Among prognostic factors of FM, obesity is the most prevalent comorbidity in FM patients compared to healthy population 14 . In addition to prevalence, some studies have shown a relationship between obesity and worse FM indices through the FIQ-R 15 . Several studies have already demonstrated an increase in c-reactive protein (CRP) and other cytokines such as IL8 in patients with obesity, however, only in 2012 this relationship of inflammatory biomarkers and obesity was seen in patients with FM 16 . Since then, other studies have tried to evaluate serum cytokines levels and its association with FM symptoms, but there is no data regarding IL8 gene expression, only serum levels. Considering that cytokines levels are a challenge to be detected because of dynamic secretion processes and short half-lives 9 , our group aimed to examine if the IL8 gene expression is considered to have less changes among circumstances. There is no data evaluating IL8 gene expression in FM and its possible association with obesity and clinical manifestations such as depression, sleep disturbance and fatigue. Methodology Study Design A cross-sectional, observational, analytical study was carried out from August to December of 2021, at the FM outpatient clinic at the rheumatology service of Hospital das Clínicas of the Federal University of Pernambuco (HC-UFPE). The sample was formed by convenience, according to the number of patients treated at the service and cost with material for the evaluation of gene expression. The case group (FMG) was selected from patients undergoing regular clinical follow-up at the specialized FM outpatient clinic, according to the inclusion/exclusion criteria. The comparison group (CG) was composed of individuals without chronic pain and who did not use anti-inflammatory or corticosteroids and were selected from hospital employees and patients' companions. Research variables were the result of IL8 gene expression in FMG and CG, BMI calculation, in addition to the values ​​obtained from different questionnaires for: fatigue (FACIT-F), impact of FM (FIQ-R), depression (BDI), and sleep (NRS). The dependent and independent variables were not defined because there is no definition in the literature regarding IL8 gene expression in the healthy population and in patients with chronic painful disease. The normal values ​​have not been established, as well as the relationship between gene expression and serum values. The FMG were clinically evaluated and answered the study protocol questionnaires: BDI, FIQ-R, FACIT-F and NRS. In the CG, the following questionnaires were applied: BDI, FACIT-F and NRS. Inclusion and exclusion criteria In FMG, the study included women diagnosed with fibromyalgia by 2016 criteria from American College of Rheumatology, being more than 18 years old. For CG was included women with more than 18 years old who do not have chronic pain matched by age. It was excluded participants with overlapping syndromes, current infection, undergoing pregnancy or who had taken anti-inflammatory or corticoid in the last 7 days. Collection Instruments The Functional Assessment of Chronic Illness Therapy (FACIT-F) is an instrument to assess fatigue, initially developed for cancer patients and later adapted for several chronic diseases, such as Lupus, Rheumatoid Arthritis and Anemia. It consists of 13 questions that assess fatigue through the physical and psychological condition of the patient. The questionnaire ranges from 0 to 52 and the higher the result, indicates a lower level of fatigue. It was validated and adapted to the Portuguese language in 2015 by Zumpano 17 . Fibromyalgia Impact Questionnaire Revised (FIQ-R) is a questionnaire that assesses the impact of FM, in addition to the decrease in the patient's functionality and quality of life, through questions about activities of daily living, pain, fatigue, memory, balance, sleep and psychological aspects. It was validated, adapted and translated into Portuguese in 2013 by Paiva 18 . Body mass index (BMI) is an index that assesses nutritional status, which expresses the relationship between body weight and height (kg/m2). A value below 18.5 indicates malnutrition. Other parameters are: 18.5 to 24.9 (normal weight), 25 to 29.9 (overweight), a value greater than or equal to 30 indicates obesity, with a value between 30 and 34.9: grade I obesity, between 35 and 39.9 grade II obesity and above or equal to 40 grade III obesity 19 . The Beck Depression Inventory is a self-reported scale composed of 21 items with a response from zero to three that assesses the degree of depression of the patient. According to the sum of the questions, it can be classified as follows: 0 to 9 (individual without depression), 10 to 18 (mild to moderate depression), 19 to 29 (moderate to severe depression) and 30 to 63 (severe depression). It was validated and adapted to the Portuguese language in 2012 by Gomes-Oliveira 20 . A Numeric Rating Scale of sleep quality (NRS) is an assessment of only one item (sleep quality) defined by choosing a number that best describes the quality of your sleep in the last 24 hours. A score is assigned to the item, ranging from 0 to 10, where 0 is the best possible sleep and 10 the worst possible sleep. Evaluation of IL8 gene expression Blood collection was performed in both groups, by peripheral puncture of the brachial vein, with a syringe of 10 milliliters. The blood sample was stored in an EDTA (Ethylenediaminetetraacetic acid) tube. Total blood RNA extraction was performed using the QIAamp RNA Blood Mini Kit (Qiagen) kit and, afterward, all samples were quantified by the NanoDrop® 2000 Spectrophotometer (Thermo Scientific, Wilmington, DE). The cDNA was obtained from the QuantiTect® Reverse Transcription Kit (Qiagen) following the manufacturer's specification. qPCR analysis was performed on StepOnePlus™ equipment (Applied Biosystems), using the GoTaq® qPCR Master Mix kit (Promega). The cDNA samples were quantified and diluted to 100ng/µL. The b-actin gene was used as a reference gene, and, for the analysis of IL8 expression, specific primers were used at a concentration of 10pM (IDT). The relative expression of IL8 was determined with the comparative cycle threshold (Cq) (2- △△Cq ) method. The samples were evaluated in duplicate and those with a standard deviation of less than 0.5 from the Cqs of the duplicates were considered. Statistical analysis The statistical analysis was performed using the GraphPad Prism Software and the data was correlated with previously obtained clinical information from the patients. In all groups, normality was verified using the Shapiro-Wilk test and the adequate test was performed according to the normality (Student's T-test or Kruskall-Wallis test). To verify the association between quantitative variables, Pearson's chi-square test was applied.The value of p < 0.05 was considered significant for the analysis. Results A total of 91 patients were considered for inclusion in the study, however 2 were excluded for refusing blood collection and another for corticoid use. It was included 89 participants, 44 patients from the FMG and 45 individuals from the CG, all women aged between 18 and 60 years. As described in the study flowchart, shown in Figure 1, qPCR blood analysis was performed in only 42 from 44 participants in FMG because in 2 samples occurred coagulation of the blood in the tube. The comparison of clinical and demographic characteristics of FMG and CG are present in Table 1. Regarding comorbidities, the FMG had a higher frequency of depression (34.1%), diabetes (25%) and hypertension (36.4%). Dyspareunia was present in 47.7% of FMG, the difference being statistically significant when compared to the CG, where it was only reported in one patient ( p <0.001). The frequency of obesity, assessed by BMI, was higher among patients with FM (52.5%), while in the CG the percentage of obesity was 29.5%. Regarding the practice of physical activity, in the FMG 31 (70.5%) patients did not do any physical activity versus 24 (43.6%) in the CG ( p = 0.038). In the FACIT-F questionnaire, the mean score in the FMG was lower than that observed in the CG ( p < 0.001). The average of NRS and BDI scales were significantly higher in the FMG ( p < 0.001). A difference related to the frequency of depression considered moderate and severe in FMG ( p < 0.001). Regarding FMG, the median time of diagnosis of FM was 10 years, mean time of pain was 13 years and median FIQ-R was 86.7. As for medications, the most frequently used was amitriptyline (24.7%), followed by gabapentin (19.1%), duloxetine (14.6%) and cyclobenzaprine (10.1%). No association was observed between the medians of the BDI, NRS, FACIT-F and FIQ-R scales with BMI stratified into eutrophic, overweight and obese in the FMG and of the BDI, NRS, FACIT-F scales in the CG. Table 1: Comparison of clinical and demographic characteristics of fibromyalgia patients and comparison group. Characteristics FMG (n = 44) CG (n = 45) P-value Age (mean, SD) 42.6 (7.2) 42.5 (7.0) 0.945 Race (n, %) White 11 (25.0%) 18 (40.0%) 0.033 Brown 31 (70.5%) 20 (44.4%) Black 2 (4.5%) 7 (15.6%) Work (n, %) Unemployed 25 (56.8%) 0 (0%) 0.001 Manual work 12 (27.3%) 4 (8.9%) Intellectual work 4 (9.1%) 40 (88.9%) Away on leave 3 (6.8%) 1 (2.2%) Marital Status (n, %) Married 23 (52.3%) 19 (42.2%) 0.157 Single 12 (27.3%) 21 (46.7%) Widow 2 (4.5%) 0 (0%) Divorced 7 (15.9%) 5 (11.1%) Comorbidities (n, %) Depression 15 (34.1%) 3 (6.7%) 0.001 Diabetes 11 (25.0%) 2 (4.4%) 0.007 Hypertension 16 (36.4%) 1 (2.2%) 0.001 Dyspareunia 21 (47.7%) 0 (0%) 0.001 Asthma 0 (0%) 3 (6.7%) 0.242 Dyslipidemia 3 (6.8%) 0 (0%) 0.117 Osteoporosis 1 (2.3%) 1 (2.2%) 0.999 Arthrosis 3 (6.8%) 0 (0%) 0.117 Smoking 1 (2.3%) 2 (4.4%) 0.999 Illicit drugs 0 (0%) 1 (2.2%) 0.999 Boby mass index (n, %) Normal 8 (18.2%) 20 (45.5%) 0.018 Overweight 13 (29.5%) 11 (25.5%) Obesity 23 (52.3%) 13 (29.5%) Does physical activity 0 (0%) 6 (13.3%) 0.012 Aerobic 10 (22.7%) 8(17.8%) 0.561 Resistance 2 (4.5%) 8 (17.8%) 0.090 Ambos 0 (0.0%) 6 (13.3%) 0.026 No activity 31 (70.5%) 24 (43.6%) 0.038 FACIT-F (mean, SD) 14.64 (7.28) 39.84 (9.23) <0.001 NRS (mean, SD) 8.73 (1.82) 2.56 (1.57) <0.001 BDI (mean, SD) 20.23 (10.13) 7.52 (6.07) <0.001 Depression (n,%) Without depression 0 (0%) 32 (72.7%) <0.001 Mild depression 5 (11.4%) 9 (20.4%) Moderate depression 20 (45.4%) 3 (6.8%) Severe depression 19 (43.2%) 0 (0%) FMG: Fibromyalgia group; CG: Comparison group; FACIT-F: Functional Assessment of Chronic Illness Therapy; NRS: Numeric Rating Scale of sleep quality; BDI: Beck depression inventory. SD: Standard Derivation. In the evaluation of IL8 gene expression, 87 of the 89 samples were evaluated, with two being excluded due to blood clotting. Among the 87 samples, 42 were from FMG and 45 from CG. IL8 mRNA expression was detected in 15 individuals from the CG while only 9 patients from the FMG had the gene expression detected. There was no significant difference in △Cq between groups (Figure 2). There was also no significant difference in the relative expression (2 - △△ Cq ) between the groups, and 5 from 9 individual those present the IL8 expression in FGM were up-regulated in relation to individuals from the CG. No association was observed between IL8 gene expression and BMI value (Figure 3), NRS, FIQ-R and FACIT-F. When evaluating IL8 and physical activity, it was observed that FMG patients who did not express IL8 were those who practiced less physical activity ( p = 0.039). Regarding depression, it is observed that among the group with IL8 expression (FMG and CG), worse depression rates were observed ( p = 0.0026) as shown in Figure 4. Regarding the practice of physical activity, 70.5% of the FMG did not practice versus 46.6% on CG. When evaluating exercise with the scales, among patients with FM, there was an association between physical inactivity and worse depression rates ( p = 0.019). There was an association in FMG between worse fatigue rates among sedentary individuals (FMG p = 0.004). Regarding the impact of FM, there was a higher median FIQ-R among cases that did not do physical activity ( p = 0.016) as shown in Table 2. Table 2. Association of physical activity with sleep scale, fatigue and depression in Fibromyalgia and comparison group. Characteristics Does Physical activity No physical activity P-value Fibromyalgia group Sleep scale - Median (IQR) 9 (7.5- 9) 10 (8 - 10) 0.105 BDI - Median (IQR) 23 (14.5 – 29) 29.5 (25 – 36.5) 0.017 Classification - number (%) Mild depression 4 (33.3%) 1 (3.1%) 0.019 Moderate depression 5 (41.7%) 15 (46.9%) Severe depression 3 (25%) 16 (50%) FACIT-F – Median (IQR) 20.5 (13 – 25.5) 11 (7 – 16.5) 0.004 FIQ-R – Median (IQR) 79.3 (61.5 -85.5) 89.2 (81.2 – 95.9) 0.016 Comparison group Sleep scale Median (IQR) 2 (1 – 3) 2 (1 – 5) 0.265 BDI – Median (IQR) 4 (3 – 6) 7 (4 – 10) 0.028 Without depression 14 (82.3%) 18 (66.7%) 0.665 Mild depression 2 (11.8%) 7 (25.9%) Moderate depression 1 (5.9%) 2 (7.4%) FACIT-F – Median (IQR) 44 (40 – 49) 39 (32 – 47) 0.052 IQR : interquartile range; BDI: Beck depression inventory; FACIT-F: Functional Assessment of Chronic Illness Therapy; FIQ-R: Fibromyalgia Impact Questionnaire-Revised. Discussion Searching in the literature, so far, there is no research evaluating IL8 gene expression in peripheral blood samples, only analysis in serum (plasma) and CSF dosage in patients with FM. Therefore, there is a difficulty in comparing our results with those in the literature. Previous studies indicate that IL8 concentration has an important clinical role in FM, mainly associated with pain and sleep disturbances 21 , 22 . However, our study shows that there is a lower frequency in the expression of IL8 in individuals with FM, and IL8 expression was not associated with worsening of the disease, since there was no association with FIQ-R, sleep disturbance, BMI or fatigue. The IL8 expression occurred in a greater number of individuals without FM and IL8 mRNA was mainly upregulated in individuals with FM, but in the present study, no difference was observed between IL8 gene expression in patients with FM compared to healthy individuals. Also, patients with FM were mostly upregulated, although there is no cut off in the literature to IL8 gene expression in patients with FM. This data indicated a greater stimulus to express the IL8 gene in more than half patients with FM, but several post-transcriptional regulation mechanisms can influence the conversion of RNA to protein. Then, a better understanding of post-transcriptional regulation would be important to understand the role of up regulated mRNA IL8 in individuals with FM in our results. Furthermore, there was no difference in obese individuals, where we expected an increase in IL8 given the inflammatory state generated by obesity and other studies using various serum interleukins. We observed that regardless of trophism, there was no increase in IL8 expression, which may represent that obesity, depending on the degree, does not activate gene expression, but has the ability to generate interleukin in large amounts in peripheral blood. These results may show that there must be a different behavior between gene expression and serum level, also because there is more than one stimulus pathway for IL8 production. When comparing our study with previous ones that analyze plasma levels of Interleukin 8 the results are conflicted. The first meta-analysis evaluating IL8 in 2011 showed an increase in IL8 serum levels in FM group 21 . Other studies also found IL8 increased in the cerebrospinal fluid 23 and peripheral blood 24 , 25 , 26 and. More recently, in 2021, a meta-analysis showed increased serum levels of IL8 in patients with FM compared to the group of healthy patients 15 . A Brazilian study in 2016 evaluating IL8 and other cytokines, showed no increase in serum IL8 and no association with disease severity, assessed by FIQ-R, or with depression 25 . Our results are concordant with this one, but we found an association between IL8 gene expression and worse depression scores by the BDI. As in our results, a recent study also did not find a difference in IL8 concentration comparing patients with FM and healthy ones 26 . In addition to contradictory studies, even within the same research group, recent systematic reviews show very small studies (with less than 20 patients) and without rigorous exclusion criteria such as infection, making the serum assessment unreliable. 11 Another important factor that makes it difficult to compare with data from the present study is the way of assessing interleukin (its serum measurement) where there is known to be a lot of interference, large variations during the day, which may change with infection and use of medications. Beyond Fibromyalgia, other chronic pain syndromes may be linked to IL8. A previous study analyzing the CSF of patients with chronic low back pain found elevated IL8 levels compared to pain-free individuals. Moreover, inhibiting IL8 with reparixin in rats led to a reduction in pain-related behaviors 12 . Similarly, patients with chronic pain after laminectomy exhibited higher IL-8 levels in CSF than controls 27 . Lastly, IL-8-reducing polymorphisms (IL-8 rs4073A > T) in patients with endometriosis have been associated with lower levels of chronic pelvic pain 28 . Evaluating gene expression with obesity, sleep disturbance, FIQ-R and physical activity, no association was seen in our study. There are studies in the literature that assess serum levels, with some studies demonstrating an association between better FIQ-R indices and lower plasma IL8 values 8 . There are no reports on gene expression level related to FIQ-R, FACIT or BMI. In the present study, no difference was observed between trophism through BMI and IL8 expression. There is a report in the literature of the relationship between obesity and serum IL8 assessment, showing that patients with FM and high BMI (overweight and obesity) have higher levels of IL8 in the peripheral blood assessment 29 , but there is no data linking obesity with gene expression. In addition, other studies demonstrate high serum levels of IL8 in patients with obesity and a decrease in these indices of physical activity, as demonstrated in 2016, in a study comparing interleukin and degree of physical activity, observing that the more intense the exercise was seen a more significant decrease of IL8 in patients with FM and obesity 29 . In our study, it was seen that in the CG, patients who showed IL8 expression did not practice physical activity. However, the practice of physical activity did not influence the frequency of IL8 expression in the FM group. Regarding the degree of fatigue, assessed by the FACIT, no association was seen between having more fatigue and presenting IL8 expression. There is no similar evaluation in the literature comparing gene expression with fatigue in the population with FM, but there are studies with fatigue and gene expression of IL8 and IL10 in other pathologies such as cancer, showing a significant association in the expression and worsening not only of fatigue, but also of pain and depression 30 , 31 . Also, studies demonstrated an association between better FIQ-R indices and lower plasma IL8 values 30 . However, there is no data linking obesity and IL8 gene expression, sleep disturbance, FIQ-R and physical activity in patients with FM. Evaluating the BDI in our results, there is a difference in the number of individuals with moderate depression and IL8 expression, showing that patients who expressed IL8 were more frequently classified as having moderate depression. These results differ from another study that evaluated IL8 and IL6 in the population with FM, using serum dosage, where no association with mood disorder was seen 24 . In the analysis of BMI with the variables depression, fatigue and sleep, the present study did not show a significant difference, while other studies point to a correlation between depression and fatigue and obesity 32 . However, a more recent study with 239 patients with and without FM, using the same scale (Beck Depression Inventory), did not demonstrate a relationship between depression and obesity, as in the present study, observing, however, a relationship between the practice of physical activity and lower levels of depression 33 . A recent study in 2021 evaluated 2339 patients with FM separated into two groups: underweight and eutrophic versus overweight and obesity, concluding that in the overweight and obese group the FIQ-R values ​​were much higher 19 . With regard to disease control, assessed by FIQ-R, it can be inferred that, if there were a larger sample of patients, a relationship with BMI would probably be found, as there was a tendency of association. Regarding physical activity, an important component for the treatment of obesity and fibromyalgia, more than half of the FM group did not practice any physical activity. There was an association between practicing physical activity and being eutrophic, and also with worsening depression, confirmed by the BDI in addition to worse scores on FACIT and FIQ-R among those who did not do any physical exercise. This data corroborates the result of a randomized clinical trial where patients with FM were divided into groups with an aerobic physical activity program (walking), resisted (weight training) and in the group without follow-up physical activity, showing that those who exercised had a FIQ value -R significantly lower, and the walking group presented even lower values ​​compared to resistance exercise 34 . In 2024, a randomized controlled trial showed higher levels of depression in women with FM compared with women without the disease and evaluated physical activity in the FM group, where after 4 weeks of resistance training, there was a difference in depressive symptoms 35 . In our study, we had only one patient who did resistance exercise, and we were unable to compare whether there was a difference between the modalities. In our study, we had only one patient who did resistance exercise, and we were unable to compare whether there was a difference between the modalities. An umbrella review, published in 2020, which analyzed 37 systematic reviews, showed that aerobic exercise and muscle strength training are the most used non-pharmacological treatments in FM, with strong evidence that adapted physical activity reduces pain perception and improves quality of life of patients with FM 36 . A study involving healthy volunteers who engaged in intense aerobic activity demonstrated a 68% rise in IL-8 levels post-exercise 37 , indicating that exercise can trigger an acute inflammatory response, reflected by elevated IL-8 levels. However, chronic regular exercise appears to exert antiinflammatory effects. In individuals with chronic obstructive pulmonary disease, an eight-week physical training program led to a significant reduction in IL-8 levels in CD4 + T lymphocytes 38 . Regular exercises in patients with rheumatoid arthritis led to lower inflammatory gene expression, including IL8 39 . Therefore, while acute physical activity appears to elevate IL-8 expression, consistent regular exercise seems to reduce it, potentially helping to alleviate chronic pain. Some limitations should be considered in this study, such as the small sample of patients and the possibility of socioeconomic differences between the FMG and CG groups. This difference may reflect nutritional aspects, stress level, access to health and interfere with the IL8 value. In addition to the composition of the sample, it should be noted that the sleep scale is a question that refers to the last day of sleep, which masks the overall sleep assessment because it considers only one day and is a self-report, which may have confounding factors for this note. Some studies use devices to assess sleep quality more objectively. Another limitation was not having evaluated the serum value of IL8 to understand how to improve if there is variation in plasma level between the groups, and to compare with data in the literature. Another important factor that makes it difficult to compare with data from the present study is the way of assessing interleukin (its serum measurement) where there is known to be a lot of interference, large variations during the day, which may change with infection and use of medications. In conclusion, there is no difference in frequency of IL8 gene expression when comparing individuals with FM and healthy. IL8 gene expression was not associated with sleep, fatigue, obesity and FIQ-R among patients with FM, but there was an association between expressing IL8 and having moderate depression. Patients with FM have a higher frequency of obesity, but the BMI value was not associated with worse sleep rate, fatigue, depression, FIQ-R and IL8 expression. Abbreviations BDI Beck depression inventory BMI body mass index CG comparison group CNS Central nervous system CRP C reactive protein CT Threshold cycle EGS Symptom Severity Scale FACIT Functional Assessment of Chronic Illness Therapy FIQ-R fibromyalgia impact questionnaire-revised FM Fibromyalgia GDI Generalized Pain Index IL8 Interleukin 8 NRS numeric rating scale for sleep TNF-α tumor necrosis factor alpha WHO world health organization Declarations Ethical Approval and Consent to participate: This study was approved by the Research Ethics Committee (CEP) with Human Beings of the Hospital das Clínicas - Universidade Federal de Pernambuco, under protocol: 5.004.684 on September 28, 2021. Consent for publication We assure that the data presented here was not published elsewhere and the article has not been submitted to any other journal. We give our consent for the publication of the manuscript Evaluation of Clinical Impact of Interleukin 8 Gene Expression In Patients With Fibromyalgia Availability of data and materials Competing interests Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Acknowledgements Not applicable Author Contribution Marco Felipe - data analysis Aline Ranzolin - data analysis Marcella Dias - data collectionLarissa Queiroz - data collection Danyelle Bruneska - article writing Claudia Marques - article review References Jahan F, Nanji K, Qidwai W, Qasim R. Fibromyalgia syndrome: an overview of pathophysiology, diagnosis and management. Oman Med J. 2012;27(3):192-195. doi:10.5001/omj.2012.44. Galvez-Sánchez CM, Reyes Del Paso GA. Diagnostic Criteria for Fibromyalgia: Critical Review and Future Perspectives. J Clin Med. 2020;9(4):1219. Published 2020 Apr 23. doi:10.3390/jcm9041219. 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Interleukin-8 as a therapeutic target for chronic low back pain: Upregulation in human cerebrospinal fluid and pre-clinical validation with chronic reparixin in the SPARC-null mouse model. EBioMedicine. 2019;43:487-500. doi:10.1016/j.ebiom.2019.04.032. Fain JN. Release of interleukins and other inflammatory cytokines by human adipose tissue is enhanced in obesity and primarily due to the nonfat cells. Vitam Horm. 2006;74:443-77. doi: 10.1016/S0083-6729(06)74018-3. D'Onghia M, Ciaffi J, Lisi L, et al. Fibromyalgia and obesity: A comprehensive systematic review and meta-analysis. Semin Arthritis Rheum. 2021;51(2):409-424. doi:10.1016/j.semarthrit.2021.02.007. Atzeni F, Alciati A, Salaffi F, et al. The association between body mass index and fibromyalgia severity: data from a cross-sectional survey of 2339 patients. Rheumatol Adv Pract. 2021;5(1):rkab015. Published 2021 Mar 1. doi:10.1093/rap/rkab015. Xiao Y, Haynes WL, Michalek JE, Russell IJ. Elevated serum high-sensitivity C-reactive protein levels in fibromyalgia syndrome patients correlate with body mass index, interleukin-6, interleukin-8, erythrocyte sedimentation rate. Rheumatol Int. 2013;33(5):1259-1264. doi:10.1007/s00296-012-2538-6. Zumpano CE, Cross-cultural adaptation and validation of the PROMIS Global Health scale in the Portuguese language. Dissertação [Masters dissertation]. Uberlândia federal university, Uberlândia, 2015. Paiva ES, Heymann RE, Rezende MC, et al. A Brazilian Portuguese version of the Revised Fibromyalgia Impact Questionnaire (FIQR): a validation study. Clin Rheumatol. 2013;32(8):1199-1206. doi:10.1007/s10067-013-2259-6. Antonopoulos AS, Oikonomou EK, Antoniades C, Tousoulis D. From the BMI paradox to the obesity paradox: the obesity-mortality association in coronary heart disease. Obes Rev. 2016;17(10):989-1000. doi:10.1111/obr.12440. Gomes-Oliveira MH, Gorenstein C, Neto FL, Andrade LH, Wang YP. Validation of the Brazilian Portuguese Version of the Beck Depression Inventory-II in a community sample, Revista Brasileira de Psiquiatria. 2012;34(4):389-394. doi: 10.1016/j.rbp.2012.03.005. Uçeyler N, Häuser W, Sommer C. Systematic review with meta-analysis: cytokines in fibromyalgia syndrome. BMC Musculoskelet Disord. 2011;12:245. Published 2011 Oct 28. doi:10.1186/1471-2474-12-245. Rodriguez-Pintó I, Agmon-Levin N, Howard A, Shoenfeld Y. Fibromyalgia and cytokines. Immunol Lett. 2014;161(2):200-203. doi:10.1016/j.imlet.2014.01.009. Kadetoff D, Lampa J, Westman M, Andersson M, Kosek E. Evidence of central inflammation in fibromyalgia-increased cerebrospinal fluid interleukin-8 levels. J Neuroimmunol. 2012;242(1-2):33-38. doi:10.1016/j.jneuroim.2011.10.013. Mendieta D, De la Cruz-Aguilera DL, Barrera-Villalpando MI, et al. IL-8 and IL-6 primarily mediate the inflammatory response in fibromyalgia patients. J Neuroimmunol. 2016;290:22-25. doi:10.1016/j.jneuroim.2015.11.011. Ranzolin A, Duarte AL, Bredemeier M, et al. Evaluation of cytokines, oxidative stress markers and brain-derived neurotrophic factor in patients with fibromyalgia - A controlled cross-sectional study. Cytokine. 2016;84:25-28. doi:10.1016/j.cyto.2016.05.011. Dolcino M, Tinazzi E, Puccetti A, Lunardi C. Gene Expression Profiling in Fibromyalgia Indicates an Autoimmune Origin of the Disease and Opens New Avenues for Targeted Therapy. J Clin Med. 2020;9(6):1814. Published 2020 Jun 10. doi:10.3390/jcm9061814. Giron SE, Bjurstrom MF, Griffis CA, Ferrante FM, Wu II, Nicol AL, Grogan TR, Burkard JF, Irwin MR, Breen EC. Increased Central Nervous System Interleukin-8 in a Majority Postlaminectomy Syndrome Chronic Pain Population. Pain Med. 2018 May 1;19(5):1033-1043. doi: 10.1093/pm/pnx126. PMID: 29016958; PMCID: PMC6659015. Cardoso JV, Machado DE, da Silva MC, de Mello MP, Berardo PT, Medeiros R, Perini JA. Influence of interleukin-8 polymorphism on endometriosis-related pelvic pain. Hum Immunol. 2023 Oct;84(10):561-566. doi: 10.1016/j.humimm.2023.07.004. Epub 2023 Jul 18. PMID: 37468423. Bote ME, García JJ, Hinchado MD, Ortega E. An exploratory study of the effect of regular aquatic exercise on the function of neutrophils from women with fibromyalgia: role of IL-8 and noradrenaline. Brain Behav Immun. 2014;39:107-112. doi:10.1016/j.bbi.2013.11.009. Dorneles GP, Haddad DO, Fagundes VO, et al. High intensity interval exercise decreases IL-8 and enhances the immunomodulatory cytokine interleukin-10 in lean and overweight-obese individuals. Cytokine. 2016;77:1-9. doi:10.1016/j.cyto.2015.10.003 Reyes-Gibby CC, Wang J, Spitz M, Wu X, Yennurajalingam S, Shete S. Genetic variations in interleukin-8 and interleukin-10 are associated with pain, depressed mood, and fatigue in lung cancer patients. J Pain Symptom Manage. 2013;46(2):161-172. doi:10.1016/j.jpainsymman.2012.07.019 Correa-Rodríguez M, Mansouri-Yachou JE, Casas-Barragán A, Molina F, Rueda-Medina B, Aguilar-Ferrandiz ME. The Association of Body Mass Index and Body Composition with Pain, Disease Activity, Fatigue, Sleep and Anxiety in Women with Fibromyalgia. Nutrients. 2019;11(5):1193. Published 2019 May 27. doi:10.3390/nu11051193 Serpas DG, Zettel-Watson L, Cherry BJ. Fibromyalgia status and depressive symptoms are linked to body mass index and physical performance in mid to late life. Psychol Health Med. 2023;28(5):1230-1243. doi:10.1080/13548506.2021.2002379 Kayo AH, Peccin MS, Sanches CM, Trevisani VF. Effectiveness of physical activity in reducing pain in patients with fibromyalgia: a blinded randomized clinical trial. Rheumatol Int. 2012;32(8):2285-2292. doi:10.1007/s00296-011-1958-z. Vilarino GT, Coimbra DR, Neiva HP, Andrade A. The impact of exercise intensity on depression in fibromyalgia: a randomized controlled trial. Front Psychol. 2024 Sep 27;15:1400590. Masquelier E, D'haeyere J. Physical activity in the treatment of fibromyalgia. Joint Bone Spine. 2021;88(5):105202. Lagzdiņa, R., Rumaka, M., Gersone, G., & Tretjakovs, P. (2023). Circulating Levels of IL-8 and MCP-1 in Healthy Adults: Changes after an Acute Aerobic Exercise and Association with Body Composition and Energy Metabolism. International Journal of Molecular Sciences, 24. https://doi.org/10.3390/ijms241914725. Uzeloto, J., De Toledo-Arruda, A., Silva, B., Braz, A., De Lima, F., Grigoletto, I., Ramos, D., Golim, M., & Ramos, E. (2022). Effect of physical training on cytokine expression in CD4+ T lymphocytes in subjects with stable COPD. Therapeutic Advances in Respiratory Disease, 16. https://doi.org/10.1177/17534666221091179. Patterson, S., Sun, S., Rychkov, D., Katz, P., Tsitsiklis, A., Nakamura, M., Serpa, P., Langelier, C., & Sirota, M. (2022). Physical Activity Associates With Lower Systemic Inflammatory Gene Expression in Rheumatoid Arthritis. The Journal of Rheumatology, 49, 1320 - 1327. https://doi.org/10.3899/jrheum.220050. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 16 Apr, 2025 Reviewers agreed at journal 16 Apr, 2025 Reviewers invited by journal 12 Apr, 2025 Submission checks completed at journal 11 Apr, 2025 First submitted to journal 09 Apr, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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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-5486569","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":442101794,"identity":"f4a18b8d-f7e3-4192-a09d-d35e5a5271d9","order_by":0,"name":"Carolina Dias da Silva Amorim","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA6UlEQVRIiWNgGAWjYLCCBwzMPGwMDIyPwTxm5gbCWhIgWpiNGRgMgBQjcVpAFJs0WAsDAS387WcfPkhgsJbhYz/+rLqg4k80fztQy4+KbTi1SJxJNzZIYEjnYePJMbs944xB7ozDjA2MPWdu49RiwJDGJpHAcBjolxy227xtBrkNQC3MjG14tPA/g2rhf/6sGKRlPkEtEjBbJBLMmEFaNhDSInHjGbNBggHQLxJvjKV5zhjnbgRqOYjPL/z9aYwPPlRY28v3pz/8zFMhlzvv/OGDD35U4NYCCwRUcICA+lEwCkbBKBgFBAAAJT1MQmNpzq8AAAAASUVORK5CYII=","orcid":"","institution":"Programa de pós-graduação em Saúde Translacional","correspondingAuthor":true,"prefix":"","firstName":"Carolina","middleName":"Dias da Silva","lastName":"Amorim","suffix":""},{"id":442101795,"identity":"1ad5a7d9-39be-4efc-94f0-bc285133badc","order_by":1,"name":"Marco Felipe Macêdo Alves","email":"","orcid":"","institution":"Federal University of Pernambuco","correspondingAuthor":false,"prefix":"","firstName":"Marco","middleName":"Felipe Macêdo","lastName":"Alves","suffix":""},{"id":442101796,"identity":"1554c009-ac37-46d7-8c50-8190cb275b07","order_by":2,"name":"Marcella Dias Teixeira","email":"","orcid":"","institution":"Federal University of Pernambuco","correspondingAuthor":false,"prefix":"","firstName":"Marcella","middleName":"Dias","lastName":"Teixeira","suffix":""},{"id":442101801,"identity":"4ae9a189-a892-4be6-bee9-92cbc41e65a0","order_by":3,"name":"Larissa Vasconcelos Queiroz","email":"","orcid":"","institution":"Federal University of Pernambuco","correspondingAuthor":false,"prefix":"","firstName":"Larissa","middleName":"Vasconcelos","lastName":"Queiroz","suffix":""},{"id":442101802,"identity":"a608a926-4bef-4f6c-b84e-02c7ff39dca5","order_by":4,"name":"Thaysa Walleria de Aragão Santos","email":"","orcid":"","institution":"Instituto Keiso Asami (iLIKA), Universidade Federal de Pernambuco","correspondingAuthor":false,"prefix":"","firstName":"Thaysa","middleName":"Walleria de Aragão","lastName":"Santos","suffix":""},{"id":442101803,"identity":"fd34d031-8d77-4e43-a5bc-19007e03bd29","order_by":5,"name":"Aline Ranzolin","email":"","orcid":"","institution":"Hospital das Clínicas da Universidade Federal de Pernambuco","correspondingAuthor":false,"prefix":"","firstName":"Aline","middleName":"","lastName":"Ranzolin","suffix":""},{"id":442101804,"identity":"cf6b5eee-a55c-4bbc-aa84-69fe3c14daab","order_by":6,"name":"Danyelle Bruneska Gondin Martins","email":"","orcid":"","institution":"Instituto Keiso Asami (iLIKA), Universidade Federal de Pernambuco","correspondingAuthor":false,"prefix":"","firstName":"Danyelle","middleName":"Bruneska Gondin","lastName":"Martins","suffix":""},{"id":442101810,"identity":"d3d55abf-8c91-4ea3-8df1-fb840d15e4b8","order_by":7,"name":"Claudia Diniz Lopes Marques","email":"","orcid":"","institution":"Hospital das Clínicas da Universidade Federal de Pernambuco","correspondingAuthor":false,"prefix":"","firstName":"Claudia","middleName":"Diniz Lopes","lastName":"Marques","suffix":""}],"badges":[],"createdAt":"2024-11-20 00:38:09","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5486569/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5486569/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":80783939,"identity":"bc58c7a5-264b-4656-afb6-f0576be45ec1","added_by":"auto","created_at":"2025-04-17 05:32:10","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":58141,"visible":true,"origin":"","legend":"\u003cp\u003eStudy flowchart.\u003c/p\u003e\n\u003cp\u003eFACIT: Functional Assessment of Chronic Illness Therapy; FIQ-R: Fibromyalgia Impact Questionnaire-Revised; BDI: Beck depression inventory; BMI: body mass index.\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5486569/v1/64b0342c8b7f5d9fe8d39295.jpg"},{"id":80785143,"identity":"c334ad4e-3fb1-421d-b2a4-b3882c83a1c9","added_by":"auto","created_at":"2025-04-17 05:40:10","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":42839,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003eIL8\u003c/em\u003emRNA expression in patients with fibromyalgia\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eA:\u003c/strong\u003e\u003cem\u003e IL8\u003c/em\u003e mRNA expression in patients with fibromyalgia in relation to CG. There is no significant (ns) difference between the groups regarding the \u003cem\u003eIL8\u003c/em\u003eexpression. \u003cstrong\u003eB: \u003c/strong\u003eRelative \u003cem\u003eIL8\u003c/em\u003e mRNA expression in FMG. From 9 patients, 5 presented up regulated in relation to CG.\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5486569/v1/ff84345254dedf933e6e872b.jpg"},{"id":80783937,"identity":"b9c82e24-d446-4fa8-968c-425c2d7cea58","added_by":"auto","created_at":"2025-04-17 05:32:10","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":38914,"visible":true,"origin":"","legend":"\u003cp\u003eAssociation between IL8 gene expression (deltaCT) with body mass index in FMG (A) and CG (B)\u003c/p\u003e\n\u003cp\u003eFMG: Fibromyalgia group; CG: comparison group\u003c/p\u003e","description":"","filename":"3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5486569/v1/df2f00289d8f4bf06ccd473e.jpg"},{"id":80783941,"identity":"3be070ab-5a31-4e49-8867-42955c1ba605","added_by":"auto","created_at":"2025-04-17 05:32:10","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":38769,"visible":true,"origin":"","legend":"\u003cp\u003eAssociation of IL8 gene expression (deltaCT) with Beck Depression inventory stratified into normal, mild, moderate and severe.\u003c/p\u003e\n\u003cp\u003eFMG: Fibromyalgia group; CG: comparison group.\u003c/p\u003e","description":"","filename":"4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5486569/v1/66dedd007776f175c28b37e3.jpg"},{"id":80787667,"identity":"5077cb16-9940-4669-95f3-20763dbe7f5a","added_by":"auto","created_at":"2025-04-17 06:08:52","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1106472,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5486569/v1/1e298a22-b8d4-4e7b-a17d-84d1184fcf1e.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eEvaluation of Clinical Impact of Interleukin 8 Gene Expression in Patients with Fibromyalgia\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eFibromyalgia (FM) is a chronic non-inflammatory pain syndrome characterized by diffuse pain\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e associated with other symptoms such as fatigue, mood and sleep disorders, headache and cognitive impairment, among others\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e. Although some factors are known to predispose an individual to develop FM, such as physical trauma, emotional events, and genetic factors, its exact etiology is still unknown\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e,\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e. To be diagnosed with FM, the patient must present with diffuse pain for more than 3 months and associated symptoms (fatigue, sleep disturbances, cognitive alterations, headache, depression, or abdominal pain) of significant intensity, scoring a specific number in a questionnaire validated for the disease\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e. Among the criteria that define the pathology, there is no characteristic laboratory or imaging data, and the diagnosis is made only with the clinical history and physical examination\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eAlthough inflammation and cell destruction are correlated with the pain response, chronic pain is probably not the direct consequence of acute inflammation or cell damage\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e,\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e. One of the main hypotheses investigated in FM refers to changes in nociceptive mechanisms, related to pain modulation, which would result in hyperalgesia and/or allodynia\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e. Some works have evaluated the hypothesis of participation of immunological mechanisms in the genesis and evolution of pain in FM, but the results found are also contradictory and so far, do not allow confirming or excluding this hypothesis\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e. So far, alteration of several markers like cytokines has been demonstrated, but without consensus in research. Some of the interleukins (IL) studied in FM and chronic pain are: IL1β, IL6, IL8, IL10 and IL15\u003csup\u003e9,10\u003c/sup\u003e. More recently, an association of chronic pain with high levels of IL8 has been found, but studies are still not conclusive\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e. In 2019, work was carried out with murine models using the drug Reparixin, an IL8 antagonist, which was able to reduce chronic low back pain\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIn addition to the relationship with chronic pain, these inflammatory mediators are involved in other pathologies, and it has already been documented that there is an increase in some interleukins such as IL6 and IL8 in obesity\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e. Among prognostic factors of FM, obesity is the most prevalent comorbidity in FM patients compared to healthy population\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e. In addition to prevalence, some studies have shown a relationship between obesity and worse FM indices through the FIQ-R\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e. Several studies have already demonstrated an increase in c-reactive protein (CRP) and other cytokines such as IL8 in patients with obesity, however, only in 2012 this relationship of inflammatory biomarkers and obesity was seen in patients with FM\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e. Since then, other studies have tried to evaluate serum cytokines levels and its association with FM symptoms, but there is no data regarding \u003cem\u003eIL8\u003c/em\u003e gene expression, only serum levels. Considering that cytokines levels are a challenge to be detected because of dynamic secretion processes and short half-lives\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e, our group aimed to examine if the \u003cem\u003eIL8\u003c/em\u003e gene expression is considered to have less changes among circumstances. There is no data evaluating \u003cem\u003eIL8\u003c/em\u003e gene expression in FM and its possible association with obesity and clinical manifestations such as depression, sleep disturbance and fatigue.\u003c/p\u003e"},{"header":"Methodology","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Design\u003c/h2\u003e \u003cp\u003eA cross-sectional, observational, analytical study was carried out from August to December of 2021, at the FM outpatient clinic at the rheumatology service of Hospital das Cl\u0026iacute;nicas of the Federal University of Pernambuco (HC-UFPE). The sample was formed by convenience, according to the number of patients treated at the service and cost with material for the evaluation of gene expression. The case group (FMG) was selected from patients undergoing regular clinical follow-up at the specialized FM outpatient clinic, according to the inclusion/exclusion criteria. The comparison group (CG) was composed of individuals without chronic pain and who did not use anti-inflammatory or corticosteroids and were selected from hospital employees and patients' companions.\u003c/p\u003e \u003cp\u003eResearch variables were the result of IL8 gene expression in FMG and CG, BMI calculation, in addition to the values ​​obtained from different questionnaires for: fatigue (FACIT-F), impact of FM (FIQ-R), depression (BDI), and sleep (NRS). The dependent and independent variables were not defined because there is no definition in the literature regarding IL8 gene expression in the healthy population and in patients with chronic painful disease. The normal values ​​have not been established, as well as the relationship between gene expression and serum values.\u003c/p\u003e \u003cp\u003eThe FMG were clinically evaluated and answered the study protocol questionnaires: BDI, FIQ-R, FACIT-F and NRS. In the CG, the following questionnaires were applied: BDI, FACIT-F and NRS.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eInclusion and exclusion criteria\u003c/h3\u003e\n\u003cp\u003eIn FMG, the study included women diagnosed with fibromyalgia by 2016 criteria from American College of Rheumatology, being more than 18 years old. For CG was included women with more than 18 years old who do not have chronic pain matched by age. It was excluded participants with overlapping syndromes, current infection, undergoing pregnancy or who had taken anti-inflammatory or corticoid in the last 7 days.\u003c/p\u003e\n\u003ch3\u003eCollection Instruments\u003c/h3\u003e\n\u003cp\u003eThe Functional Assessment of Chronic Illness Therapy (FACIT-F) is an instrument to assess fatigue, initially developed for cancer patients and later adapted for several chronic diseases, such as Lupus, Rheumatoid Arthritis and Anemia. It consists of 13 questions that assess fatigue through the physical and psychological condition of the patient. The questionnaire ranges from 0 to 52 and the higher the result, indicates a lower level of fatigue. It was validated and adapted to the Portuguese language in 2015 by Zumpano\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eFibromyalgia Impact Questionnaire Revised (FIQ-R) is a questionnaire that assesses the impact of FM, in addition to the decrease in the patient's functionality and quality of life, through questions about activities of daily living, pain, fatigue, memory, balance, sleep and psychological aspects. It was validated, adapted and translated into Portuguese in 2013 by Paiva\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eBody mass index (BMI) is an index that assesses nutritional status, which expresses the relationship between body weight and height (kg/m2). A value below 18.5 indicates malnutrition. Other parameters are: 18.5 to 24.9 (normal weight), 25 to 29.9 (overweight), a value greater than or equal to 30 indicates obesity, with a value between 30 and 34.9: grade I obesity, between 35 and 39.9 grade II obesity and above or equal to 40 grade III obesity\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe Beck Depression Inventory is a self-reported scale composed of 21 items with a response from zero to three that assesses the degree of depression of the patient. According to the sum of the questions, it can be classified as follows: 0 to 9 (individual without depression), 10 to 18 (mild to moderate depression), 19 to 29 (moderate to severe depression) and 30 to 63 (severe depression). It was validated and adapted to the Portuguese language in 2012 by Gomes-Oliveira\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eA Numeric Rating Scale of sleep quality (NRS) is an assessment of only one item (sleep quality) defined by choosing a number that best describes the quality of your sleep in the last 24 hours. A score is assigned to the item, ranging from 0 to 10, where 0 is the best possible sleep and 10 the worst possible sleep.\u003c/p\u003e \u003cp\u003e \u003cb\u003eEvaluation of\u003c/b\u003e \u003cb\u003eIL8\u003c/b\u003e \u003cb\u003egene expression\u003c/b\u003e\u003c/p\u003e \u003cp\u003eBlood collection was performed in both groups, by peripheral puncture of the brachial vein, with a syringe of 10 milliliters. The blood sample was stored in an EDTA (Ethylenediaminetetraacetic acid) tube. Total blood RNA extraction was performed using the QIAamp RNA Blood Mini Kit (Qiagen) kit and, afterward, all samples were quantified by the NanoDrop\u0026reg; 2000 Spectrophotometer (Thermo Scientific, Wilmington, DE). The cDNA was obtained from the QuantiTect\u0026reg; Reverse Transcription Kit (Qiagen) following the manufacturer's specification. qPCR analysis was performed on StepOnePlus\u0026trade; equipment (Applied Biosystems), using the GoTaq\u0026reg; qPCR Master Mix kit (Promega). The cDNA samples were quantified and diluted to 100ng/\u0026micro;L. The b-actin gene was used as a reference gene, and, for the analysis of IL8 expression, specific primers were used at a concentration of 10pM (IDT). The relative expression of \u003cem\u003eIL8\u003c/em\u003e was determined with the comparative cycle threshold (Cq) (2-\u003csup\u003e△△Cq\u003c/sup\u003e) method. The samples were evaluated in duplicate and those with a standard deviation of less than 0.5 from the Cqs of the duplicates were considered.\u003c/p\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eThe statistical analysis was performed using the GraphPad Prism Software and the data was correlated with previously obtained clinical information from the patients. In all groups, normality was verified using the Shapiro-Wilk test and the adequate test was performed according to the normality (Student's T-test or Kruskall-Wallis test). To verify the association between quantitative variables, Pearson's chi-square test was applied.The value of \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered significant for the analysis.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 91 patients were considered for inclusion in the study, however 2 were excluded for refusing blood collection and another for corticoid use. It was included 89 participants, 44 patients from the FMG and 45 individuals from the CG, all women aged between 18 and 60 years. As described in the study flowchart, shown in Figure 1, qPCR blood analysis was performed in only 42 from 44 participants in FMG because in 2 samples occurred coagulation of the blood in the tube.\u003c/p\u003e\n\u003cp\u003eThe comparison of clinical and demographic characteristics of FMG and CG are present in Table 1.\u0026nbsp;Regarding comorbidities, the FMG had a higher frequency of depression (34.1%), diabetes (25%) and hypertension (36.4%). Dyspareunia was present in 47.7% of FMG, the difference being statistically significant when compared to the CG, where it was only reported in one patient (\u003cem\u003ep\u003c/em\u003e\u0026lt;0.001). The frequency of obesity, assessed by BMI, was higher among patients with FM (52.5%), while in the CG the percentage of obesity was 29.5%. Regarding the practice of physical activity, in the FMG 31 (70.5%) patients did not do any physical activity versus 24 (43.6%) in the CG (\u003cem\u003ep\u003c/em\u003e= 0.038). In the FACIT-F questionnaire, the mean score in the FMG was lower than that observed in the CG (\u003cem\u003ep\u003c/em\u003e\u0026lt; 0.001). The average of NRS and BDI scales were significantly higher in the FMG (\u003cem\u003ep\u003c/em\u003e\u0026lt; 0.001). A difference related to the frequency of depression considered moderate and severe in FMG (\u003cem\u003ep\u003c/em\u003e\u0026lt; 0.001). Regarding FMG, the median time of diagnosis of FM was 10 years, mean time of pain was 13 years and median FIQ-R was 86.7. As for medications, the most frequently used was amitriptyline (24.7%), followed by gabapentin (19.1%), duloxetine (14.6%) and cyclobenzaprine (10.1%). No association was observed between the medians of the BDI, NRS, FACIT-F and FIQ-R scales with BMI stratified into eutrophic, overweight and obese in the FMG and of the BDI, NRS, FACIT-F scales in the CG.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1:\u0026nbsp;\u003c/strong\u003eComparison of clinical and demographic characteristics of fibromyalgia patients and comparison group.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"567\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCharacteristics\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFMG\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n = 44)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCG\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n = 45)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge (mean, SD)\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003e42.6 (7.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e42.5 (7.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0.945\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRace (n, %)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003eWhite\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003e11 (25.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e18 (40.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.033\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003eBrown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003e31 (70.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e20 (44.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003eBlack\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003e2 (4.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e7 (15.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eWork (n, %)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003eUnemployed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003e25 (56.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"4\" valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003eManual work\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003e12 (27.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e4 (8.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003eIntellectual work\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003e4 (9.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e40 (88.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003eAway on leave\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003e3 (6.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e1 (2.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMarital Status (n, %)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003eMarried\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003e23 (52.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e19 (42.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"4\" valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0.157\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003eSingle\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003e12 (27.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e21 (46.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003eWidow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003e2 (4.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003eDivorced\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003e7 (15.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e5 (11.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eComorbidities (n, %)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003eDepression\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003e15 (34.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e3 (6.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003eDiabetes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003e11 (25.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e2 (4.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.007\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003eHypertension\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003e16 (36.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e1 (2.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003eDyspareunia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003e21 (47.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003eAsthma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e3 (6.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0.242\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003eDyslipidemia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003e3 (6.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0.117\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003eOsteoporosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003e1 (2.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e1 (2.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0.999\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003eArthrosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003e3 (6.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0.117\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003eSmoking\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003e1 (2.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e2 (4.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0.999\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003eIllicit drugs\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e1 (2.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0.999\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBoby mass index (n, %)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003eNormal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003e8 (18.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e20 (45.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.018\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003eOverweight\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003e13 (29.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e11 (25.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003eObesity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003e23 (52.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e13 (29.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDoes physical activity\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e6 (13.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.012\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003eAerobic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003e10 (22.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e8(17.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026nbsp;0.561\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003eResistance\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003e2 (4.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e8 (17.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0.090\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003eAmbos\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e6 (13.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.026\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003eNo activity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003e31 (70.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e24 (43.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.038\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFACIT-F (mean, SD)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003e14.64 (7.28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e39.84 (9.23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNRS (mean, SD)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003e8.73 (1.82)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e2.56 (1.57)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBDI (mean, SD)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003e20.23 (10.13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e7.52 (6.07)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDepression (n,%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003eWithout depression\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e32 (72.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"4\" valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003eMild depression\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003e5 (11.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e9 (20.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003eModerate depression\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003e20 (45.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e3 (6.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 218px;\"\u003e\n \u003cp\u003eSevere depression\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003e19 (43.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 141px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eFMG: Fibromyalgia group; CG: Comparison group; FACIT-F: Functional Assessment of Chronic Illness Therapy; NRS: Numeric Rating Scale of sleep quality; BDI: Beck depression inventory. SD: Standard Derivation.\u003c/p\u003e\n\u003cp\u003eIn the evaluation of \u003cem\u003eIL8\u003c/em\u003e gene expression, 87 of the 89 samples were evaluated, with two being excluded due to blood clotting. Among the 87 samples, 42 were from FMG and 45 from CG. \u003cem\u003eIL8\u003c/em\u003e mRNA expression was detected in 15 individuals from the CG while only 9 patients from the FMG had the gene expression detected. There was no significant difference in △Cq between groups (Figure 2). There was also no significant difference in the relative expression (2\u003csup\u003e-\u003c/sup\u003e\u003csup\u003e△△\u003c/sup\u003e\u003csup\u003eCq\u003c/sup\u003e) between the groups, and 5 from 9 individual those present the \u003cem\u003eIL8\u0026nbsp;\u003c/em\u003eexpression in FGM were up-regulated in relation to individuals from the CG.\u003c/p\u003e\n\u003cp\u003eNo association was observed between \u003cem\u003eIL8\u003c/em\u003e gene expression and BMI value (Figure 3), NRS, FIQ-R and FACIT-F. When evaluating \u003cem\u003eIL8\u003c/em\u003e and physical activity, it was observed that FMG patients who did not express IL8 were those who practiced less physical activity (\u003cem\u003ep\u003c/em\u003e= 0.039).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eRegarding depression, it is observed that among the group with \u003cem\u003eIL8\u003c/em\u003e expression (FMG and CG), worse depression rates were observed (\u003cem\u003ep\u003c/em\u003e= 0.0026) as shown in Figure 4.\u003c/p\u003e\n\u003cp\u003eRegarding the practice of physical activity, 70.5% of the FMG did not practice versus 46.6% on CG. When evaluating exercise with the scales, among patients with FM, there was an association between physical inactivity and worse depression rates (\u003cem\u003ep\u003c/em\u003e= 0.019). There was an association in FMG between worse fatigue rates among sedentary individuals (FMG \u003cem\u003ep\u003c/em\u003e= 0.004).\u0026nbsp;Regarding the impact of FM, there was a higher median FIQ-R among cases that did not do physical activity (\u003cem\u003ep\u003c/em\u003e= 0.016) as shown in Table 2.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2.\u0026nbsp;\u003c/strong\u003eAssociation of physical activity with sleep scale, fatigue and depression in Fibromyalgia and comparison group.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"567\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 215px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCharacteristics\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDoes Physical activity\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo physical activity\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 215px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFibromyalgia group\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 215px;\"\u003e\n \u003cp\u003eSleep scale - Median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp\u003e9 (7.5- 9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp\u003e10 (8 - 10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e0.105\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 215px;\"\u003e\n \u003cp\u003eBDI - Median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp\u003e23 (14.5 \u0026ndash; 29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp\u003e29.5 (25 \u0026ndash; 36.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.017\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 215px;\"\u003e\n \u003cp\u003eClassification - number (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 215px;\"\u003e\n \u003cp\u003eMild depression\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp\u003e4 (33.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp\u003e1 (3.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.019\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 215px;\"\u003e\n \u003cp\u003eModerate depression\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp\u003e5 (41.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp\u003e15 (46.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 215px;\"\u003e\n \u003cp\u003eSevere depression\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp\u003e3 (25%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp\u003e16 (50%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 215px;\"\u003e\n \u003cp\u003eFACIT-F \u0026ndash; Median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp\u003e20.5 (13 \u0026ndash; 25.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp\u003e11 (7 \u0026ndash; 16.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.004\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 215px;\"\u003e\n \u003cp\u003eFIQ-R \u0026ndash; Median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp\u003e79.3 (61.5 -85.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp\u003e89.2 (81.2 \u0026ndash; 95.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.016\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 215px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eComparison group\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 215px;\"\u003e\n \u003cp\u003eSleep scale Median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp\u003e2 (1 \u0026ndash; 3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp\u003e2 (1 \u0026ndash; 5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e0.265\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 215px;\"\u003e\n \u003cp\u003eBDI \u0026ndash; Median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp\u003e4 (3 \u0026ndash; 6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp\u003e7 (4 \u0026ndash; 10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.028\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 215px;\"\u003e\n \u003cp\u003eWithout depression\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp\u003e14 (82.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp\u003e18 (66.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e0.665\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 215px;\"\u003e\n \u003cp\u003eMild depression\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp\u003e2 (11.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp\u003e7 (25.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 215px;\"\u003e\n \u003cp\u003eModerate depression\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp\u003e1 (5.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp\u003e2 (7.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 215px;\"\u003e\n \u003cp\u003eFACIT-F \u0026ndash; Median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp\u003e44 (40 \u0026ndash; 49)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp\u003e39 (32 \u0026ndash; 47)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e0.052\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;IQR\u003csub\u003e:\u0026nbsp;\u003c/sub\u003einterquartile range; BDI: Beck depression inventory; FACIT-F: Functional Assessment of Chronic Illness Therapy; FIQ-R: Fibromyalgia Impact Questionnaire-Revised.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eSearching in the literature, so far, there is no research evaluating \u003cem\u003eIL8\u003c/em\u003e gene expression in peripheral blood samples, only analysis in serum (plasma) and CSF dosage in patients with FM. Therefore, there is a difficulty in comparing our results with those in the literature. Previous studies indicate that IL8 concentration has an important clinical role in FM, mainly associated with pain and sleep disturbances\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e,\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e. However, our study shows that there is a lower frequency in the expression of \u003cem\u003eIL8\u003c/em\u003e in individuals with FM, and \u003cem\u003eIL8\u003c/em\u003e expression was not associated with worsening of the disease, since there was no association with FIQ-R, sleep disturbance, BMI or fatigue.\u003c/p\u003e \u003cp\u003eThe \u003cem\u003eIL8\u003c/em\u003e expression occurred in a greater number of individuals without FM and \u003cem\u003eIL8\u003c/em\u003e mRNA was mainly upregulated in individuals with FM, but in the present study, no difference was observed between \u003cem\u003eIL8\u003c/em\u003e gene expression in patients with FM compared to healthy individuals. Also, patients with FM were mostly upregulated, although there is no cut off in the literature to \u003cem\u003eIL8\u003c/em\u003e gene expression in patients with FM. This data indicated a greater stimulus to express the \u003cem\u003eIL8\u003c/em\u003e gene in more than half patients with FM, but several post-transcriptional regulation mechanisms can influence the conversion of RNA to protein. Then, a better understanding of post-transcriptional regulation would be important to understand the role of up regulated mRNA \u003cem\u003eIL8\u003c/em\u003e in individuals with FM in our results.\u003c/p\u003e \u003cp\u003eFurthermore, there was no difference in obese individuals, where we expected an increase in IL8 given the inflammatory state generated by obesity and other studies using various serum interleukins. We observed that regardless of trophism, there was no increase in IL8 expression, which may represent that obesity, depending on the degree, does not activate gene expression, but has the ability to generate interleukin in large amounts in peripheral blood. These results may show that there must be a different behavior between gene expression and serum level, also because there is more than one stimulus pathway for IL8 production.\u003c/p\u003e \u003cp\u003eWhen comparing our study with previous ones that analyze plasma levels of Interleukin 8 the results are conflicted. The first meta-analysis evaluating IL8 in 2011 showed an increase in IL8 serum levels in FM group\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e. Other studies also found IL8 increased in the cerebrospinal fluid\u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e and peripheral blood \u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e,\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e,\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e and. More recently, in 2021, a meta-analysis showed increased serum levels of IL8 in patients with FM compared to the group of healthy patients\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e. A Brazilian study in 2016 evaluating IL8 and other cytokines, showed no increase in serum IL8 and no association with disease severity, assessed by FIQ-R, or with depression\u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e. Our results are concordant with this one, but we found an association between \u003cem\u003eIL8\u003c/em\u003e gene expression and worse depression scores by the BDI. As in our results, a recent study also did not find a difference in IL8 concentration comparing patients with FM and healthy ones\u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIn addition to contradictory studies, even within the same research group, recent systematic reviews show very small studies (with less than 20 patients) and without rigorous exclusion criteria such as infection, making the serum assessment unreliable.\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e Another important factor that makes it difficult to compare with data from the present study is the way of assessing interleukin (its serum measurement) where there is known to be a lot of interference, large variations during the day, which may change with infection and use of medications.\u003c/p\u003e \u003cp\u003eBeyond Fibromyalgia, other chronic pain syndromes may be linked to IL8. A previous study analyzing the CSF of patients with chronic low back pain found elevated IL8 levels compared to pain-free individuals. Moreover, inhibiting IL8 with reparixin in rats led to a reduction in pain-related behaviors\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e. Similarly, patients with chronic pain after laminectomy exhibited higher IL-8 levels in CSF than controls\u003csup\u003e\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e. Lastly, IL-8-reducing polymorphisms (IL-8 rs4073A\u0026thinsp;\u0026gt;\u0026thinsp;T) in patients with endometriosis have been associated with lower levels of chronic pelvic pain\u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eEvaluating gene expression with obesity, sleep disturbance, FIQ-R and physical activity, no association was seen in our study. There are studies in the literature that assess serum levels, with some studies demonstrating an association between better FIQ-R indices and lower plasma IL8 values\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e. There are no reports on gene expression level related to FIQ-R, FACIT or BMI.\u003c/p\u003e \u003cp\u003eIn the present study, no difference was observed between trophism through BMI and IL8 expression. There is a report in the literature of the relationship between obesity and serum IL8 assessment, showing that patients with FM and high BMI (overweight and obesity) have higher levels of IL8 in the peripheral blood assessment\u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e, but there is no data linking obesity with gene expression.\u003c/p\u003e \u003cp\u003eIn addition, other studies demonstrate high serum levels of IL8 in patients with obesity and a decrease in these indices of physical activity, as demonstrated in 2016, in a study comparing interleukin and degree of physical activity, observing that the more intense the exercise was seen a more significant decrease of IL8 in patients with FM and obesity\u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e. In our study, it was seen that in the CG, patients who showed \u003cem\u003eIL8\u003c/em\u003e expression did not practice physical activity. However, the practice of physical activity did not influence the frequency of \u003cem\u003eIL8\u003c/em\u003e expression in the FM group.\u003c/p\u003e \u003cp\u003eRegarding the degree of fatigue, assessed by the FACIT, no association was seen between having more fatigue and presenting IL8 expression. There is no similar evaluation in the literature comparing gene expression with fatigue in the population with FM, but there are studies with fatigue and gene expression of \u003cem\u003eIL8\u003c/em\u003eand \u003cem\u003eIL10\u003c/em\u003e in other pathologies such as cancer, showing a significant association in the expression and worsening not only of fatigue, but also of pain and depression\u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e,\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u003c/sup\u003e. Also, studies demonstrated an association between better FIQ-R indices and lower plasma IL8 values\u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e. However, there is no data linking obesity and \u003cem\u003eIL8\u003c/em\u003e gene expression, sleep disturbance, FIQ-R and physical activity in patients with FM.\u003c/p\u003e \u003cp\u003eEvaluating the BDI in our results, there is a difference in the number of individuals with moderate depression and \u003cem\u003eIL8\u003c/em\u003e expression, showing that patients who expressed \u003cem\u003eIL8\u003c/em\u003e were more frequently classified as having moderate depression. These results differ from another study that evaluated IL8 and IL6 in the population with FM, using serum dosage, where no association with mood disorder was seen\u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIn the analysis of BMI with the variables depression, fatigue and sleep, the present study did not show a significant difference, while other studies point to a correlation between depression and fatigue and obesity\u003csup\u003e\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u003c/sup\u003e. However, a more recent study with 239 patients with and without FM, using the same scale (Beck Depression Inventory), did not demonstrate a relationship between depression and obesity, as in the present study, observing, however, a relationship between the practice of physical activity and lower levels of depression\u003csup\u003e\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eA recent study in 2021 evaluated 2339 patients with FM separated into two groups: underweight and eutrophic versus overweight and obesity, concluding that in the overweight and obese group the FIQ-R values ​​were much higher\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e. With regard to disease control, assessed by FIQ-R, it can be inferred that, if there were a larger sample of patients, a relationship with BMI would probably be found, as there was a tendency of association.\u003c/p\u003e \u003cp\u003eRegarding physical activity, an important component for the treatment of obesity and fibromyalgia, more than half of the FM group did not practice any physical activity. There was an association between practicing physical activity and being eutrophic, and also with worsening depression, confirmed by the BDI in addition to worse scores on FACIT and FIQ-R among those who did not do any physical exercise. This data corroborates the result of a randomized clinical trial where patients with FM were divided into groups with an aerobic physical activity program (walking), resisted (weight training) and in the group without follow-up physical activity, showing that those who exercised had a FIQ value -R significantly lower, and the walking group presented even lower values ​​compared to resistance exercise\u003csup\u003e\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e\u003c/sup\u003e. In 2024, a randomized controlled trial showed higher levels of depression in women with FM compared with women without the disease and evaluated physical activity in the FM group, where after 4 weeks of resistance training, there was a difference in depressive symptoms\u003csup\u003e\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e\u003c/sup\u003e. In our study, we had only one patient who did resistance exercise, and we were unable to compare whether there was a difference between the modalities. In our study, we had only one patient who did resistance exercise, and we were unable to compare whether there was a difference between the modalities. An umbrella review, published in 2020, which analyzed 37 systematic reviews, showed that aerobic exercise and muscle strength training are the most used non-pharmacological treatments in FM, with strong evidence that adapted physical activity reduces pain perception and improves quality of life of patients with FM\u003csup\u003e\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eA study involving healthy volunteers who engaged in intense aerobic activity demonstrated a 68% rise in IL-8 levels post-exercise\u003csup\u003e\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e\u003c/sup\u003e, indicating that exercise can trigger an acute inflammatory response, reflected by elevated IL-8 levels. However, chronic regular exercise appears to exert antiinflammatory effects. In individuals with chronic obstructive pulmonary disease, an eight-week physical training program led to a significant reduction in IL-8 levels in CD4\u0026thinsp;+\u0026thinsp;T lymphocytes\u003csup\u003e\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e\u003c/sup\u003e. Regular exercises in patients with rheumatoid arthritis led to lower inflammatory gene expression, including IL8\u003csup\u003e39\u003c/sup\u003e. Therefore, while acute physical activity appears to elevate IL-8 expression, consistent regular exercise seems to reduce it, potentially helping to alleviate chronic pain.\u003c/p\u003e \u003cp\u003eSome limitations should be considered in this study, such as the small sample of patients and the possibility of socioeconomic differences between the FMG and CG groups. This difference may reflect nutritional aspects, stress level, access to health and interfere with the \u003cem\u003eIL8\u003c/em\u003e value. In addition to the composition of the sample, it should be noted that the sleep scale is a question that refers to the last day of sleep, which masks the overall sleep assessment because it considers only one day and is a self-report, which may have confounding factors for this note. Some studies use devices to assess sleep quality more objectively. Another limitation was not having evaluated the serum value of IL8 to understand how to improve if there is variation in plasma level between the groups, and to compare with data in the literature. Another important factor that makes it difficult to compare with data from the present study is the way of assessing interleukin (its serum measurement) where there is known to be a lot of interference, large variations during the day, which may change with infection and use of medications.\u003c/p\u003e \u003cp\u003eIn conclusion, there is no difference in frequency of \u003cem\u003eIL8\u003c/em\u003e gene expression when comparing individuals with FM and healthy. \u003cem\u003eIL8\u003c/em\u003e gene expression was not associated with sleep, fatigue, obesity and FIQ-R among patients with FM, but there was an association between expressing \u003cem\u003eIL8\u003c/em\u003e and having moderate depression. Patients with FM have a higher frequency of obesity, but the BMI value was not associated with worse sleep rate, fatigue, depression, FIQ-R and \u003cem\u003eIL8\u003c/em\u003e expression.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eBDI Beck depression inventory\u003c/p\u003e\n\u003cp\u003eBMI body mass index\u003c/p\u003e\n\u003cp\u003eCG comparison group\u003c/p\u003e\n\u003cp\u003eCNS Central nervous system\u003c/p\u003e\n\u003cp\u003eCRP C reactive protein\u003c/p\u003e\n\u003cp\u003eCT Threshold cycle\u003c/p\u003e\n\u003cp\u003eEGS Symptom Severity Scale\u003c/p\u003e\n\u003cp\u003eFACIT Functional Assessment of Chronic Illness Therapy\u003c/p\u003e\n\u003cp\u003eFIQ-R fibromyalgia impact questionnaire-revised\u003c/p\u003e\n\u003cp\u003eFM Fibromyalgia\u003c/p\u003e\n\u003cp\u003eGDI Generalized Pain Index\u003c/p\u003e\n\u003cp\u003eIL8 Interleukin 8\u003c/p\u003e\n\u003cp\u003eNRS numeric rating scale for sleep\u003c/p\u003e\n\u003cp\u003eTNF-\u0026alpha; tumor necrosis factor alpha\u003c/p\u003e\n\u003cp\u003eWHO world health organization\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthical Approval and Consent to participate:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Research Ethics Committee (CEP) with Human Beings of the Hospital das Clínicas - Universidade Federal de Pernambuco, under protocol: 5.004.684 on September 28, 2021.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe assure that the data presented here was not published elsewhere and the article has not been submitted to any other journal. We give our consent for the publication of the manuscript Evaluation of Clinical Impact of Interleukin 8 Gene Expression In Patients With Fibromyalgia\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCompeting interests\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eMarco Felipe - data analysis Aline Ranzolin - data analysis Marcella Dias - data collectionLarissa Queiroz - data collection Danyelle Bruneska - article writing Claudia Marques - article review\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eJahan F, Nanji K, Qidwai W, Qasim R. 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Psychol Health Med. 2023;28(5):1230-1243. doi:10.1080/13548506.2021.2002379\u003c/li\u003e\n\u003cli\u003eKayo AH, Peccin MS, Sanches CM, Trevisani VF. Effectiveness of physical activity in reducing pain in patients with fibromyalgia: a blinded randomized clinical trial. Rheumatol Int. 2012;32(8):2285-2292. doi:10.1007/s00296-011-1958-z.\u003c/li\u003e\n\u003cli\u003eVilarino GT, Coimbra DR, Neiva HP, Andrade A. The impact of exercise intensity on depression in fibromyalgia: a randomized controlled trial. Front Psychol. 2024 Sep 27;15:1400590.\u003c/li\u003e\n\u003cli\u003eMasquelier E, D\u0026apos;haeyere J. Physical activity in the treatment of fibromyalgia. Joint Bone Spine. 2021;88(5):105202.\u003c/li\u003e\n\u003cli\u003eLagzdiņa, R., Rumaka, M., Gersone, G., \u0026amp; Tretjakovs, P. (2023). Circulating Levels of IL-8 and MCP-1 in Healthy Adults: Changes after an Acute Aerobic Exercise and Association with Body Composition and Energy Metabolism. International Journal of Molecular Sciences, 24. https://doi.org/10.3390/ijms241914725.\u003c/li\u003e\n\u003cli\u003eUzeloto, J., De Toledo-Arruda, A., Silva, B., Braz, A., De Lima, F., Grigoletto, I., Ramos, D., Golim, M., \u0026amp; Ramos, E. (2022). Effect of physical training on cytokine expression in CD4+ T lymphocytes in subjects with stable COPD. Therapeutic Advances in Respiratory Disease, 16. https://doi.org/10.1177/17534666221091179.\u003c/li\u003e\n\u003cli\u003ePatterson, S., Sun, S., Rychkov, D., Katz, P., Tsitsiklis, A., Nakamura, M., Serpa, P., Langelier, C., \u0026amp; Sirota, M. (2022). Physical Activity Associates With Lower Systemic Inflammatory Gene Expression in Rheumatoid Arthritis. The Journal of Rheumatology, 49, 1320 - 1327. https://doi.org/10.3899/jrheum.220050.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"advances-in-rheumatology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"adrh","sideBox":"Learn more about [Advances in Rheumatology](https://advancesinrheumatology.biomedcentral.com/)","snPcode":"42358","submissionUrl":"https://submission.springernature.com/new-submission/42358/3","title":"Advances in Rheumatology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Fibromyalgia, interleukin 8, depression, fatigue, sleep quality, obesity","lastPublishedDoi":"10.21203/rs.3.rs-5486569/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5486569/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eFibromyalgia (FM) is a musculoskeletal syndrome characterized by diffuse and chronic pain associated with other symptoms such as fatigue, sleep/cognition disorders, headache, depression and anxiety, resulting from a change in pain processing. Previous research has shown an increase in some interleukins (IL) in patients with FM when compared to controls, however, there is still no uniformity and consensus in the results. There is no study that evaluates \u003cem\u003eIL8\u003c/em\u003e \u0026nbsp;mRNA expression in FM and its association with obesity and other clinical parameters. This study aims to verify the impact of \u003cem\u003eIL8 \u003c/em\u003emRNA expression on the clinical parameters of patients with FM (FMG) in relation to the comparison group (CG).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethod:\u003c/strong\u003e This study evaluated patients diagnosed with FM treated at the rheumatology service of the Hospital das Clínicas of the Federal University of Pernambuco (HC-UFPE). The CG group was composed of individuals without chronic pain (companions of the patients and hospital employees). Clinical and demographic data were collected in both groups, and questionnaires for fatigue (FACIT-F), impact of FM (FIQ-R), depression (BDI), and sleep (NRS) were applied to both groups. Peripheral blood was collected for evaluation of \u003cem\u003eIL8 \u003c/em\u003egene expression through real time polymerase chain reaction (qPCR).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e Patients with FM show a lower frequency of \u003cem\u003eIL8\u003c/em\u003e gene expression compared to the CG, but FMG presented mainly up regulated in relation to CG. There was no association of \u003cem\u003eIL8\u003c/em\u003e expression and worse FIQ-R indices, sleep disturbance, BMI or fatigue. However, there was an association between \u003cem\u003eIL8\u003c/em\u003e expression and moderate depression (\u003cem\u003ep\u003c/em\u003e= 0.002) and physical activity (\u003cem\u003ep\u003c/em\u003e= 0.039), where patients in FMG who did express \u003cem\u003eIL8\u003c/em\u003e were practicing less physical activity.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e Patients in FMG did not have a higher frequency of \u003cem\u003eIL8 \u003c/em\u003eexpression compared to CG, however patients with \u003cem\u003eIL8\u003c/em\u003e expression have a greater association with moderate depression.\u003c/p\u003e","manuscriptTitle":"Evaluation of Clinical Impact of Interleukin 8 Gene Expression in Patients with Fibromyalgia","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-04-17 05:32:05","doi":"10.21203/rs.3.rs-5486569/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2025-04-16T13:00:04+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"16438145674788660248349804178247253271","date":"2025-04-16T12:51:54+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-04-12T16:49:10+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-04-11T05:20:20+00:00","index":"","fulltext":""},{"type":"submitted","content":"Advances in Rheumatology","date":"2025-04-09T23:06:12+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"advances-in-rheumatology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"adrh","sideBox":"Learn more about [Advances in Rheumatology](https://advancesinrheumatology.biomedcentral.com/)","snPcode":"42358","submissionUrl":"https://submission.springernature.com/new-submission/42358/3","title":"Advances in Rheumatology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"40450bb2-56fc-4d84-bc17-a5e98b085216","owner":[],"postedDate":"April 17th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-04-17T05:32:05+00:00","versionOfRecord":[],"versionCreatedAt":"2025-04-17 05:32:05","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5486569","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5486569","identity":"rs-5486569","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}