Circulating Interleukin-10 Levels Research Articles

Impact of butorphanol versus sufentanil on postoperative cognition and inflammation in elderly: a pilot study.

This randomized controlled trial aimed to compare the effects of butorphanol and sufentanil on early post-operative cognitive dysfunction (POCD) and systemic inflammation in older surgical patients. Patients (aged 65 years or above) undergoing surgeries with general anesthesia were randomized to either the butorphanol group (40 μg/kg during anesthesia induction) or the sufentanil group (0.4 μg/kg). Cognitive function changes during the perioperative period were assessed using the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) scale up to 3 days after surgery. POCD was defined as a Z-score or composite Z-score greater than 1.96 for both MMSE and MoCA scores. Circulating inflammatory factors, including tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL-1β), and interleukin 10 (IL-10), were measured using enzyme-linked immunosorbent assay. The study included 114 patients (median age: 71 years, 57.7% male). Compared to sufentanil, butorphanol significantly reduced the incidence of POCD on the first (11.5% versus 32.7%, p = 0.017) and third day (3.8% versus 15.4%, p = 0.046) after surgery. Additionally, patients receiving butorphanol had significantly lower circulating levels of TNF-α and IL-1β at the time of discharge from the post-anesthesia care unit and on the first and third day after surgery (p < 0.05 for all comparisons). Furthermore, circulating IL-10 levels were significantly higher in patients receiving butorphanol (p < 0.05 for all comparisons). Administration of butorphanol during anesthesia induction, as opposed to sufentanil, was associated with a significant reduction in the early incidence of POCD in older surgical patients, possibly attributed to its impact on systemic inflammation.Clinical trial registration: The present study was registered in the China Clinical Trial Center (ChiCTR2300070805, 24/04/2023).

Peritoneal and Systemic Interleukin-10 as Early Biomarkers for Colorectal Anastomotic Leakage Following Surgery in Colorectal Cancer Patients: A Systematic Review and Meta-Analysis.

&lt;b&gt;&lt;br&gt;Introduction:&lt;/b&gt; Despite advancements in diagnostic methods, the early detection of colorectal anastomotic leakage (CAL) continues to pose challenges. The identification of reliable markers is crucial to reduce patient morbidity and mortality. Cytokines present in drain fluid and systemic cytokine levels have shown promise as predictive markers for CAL; however, additional high-quality evidence is warranted to enhance the reliability and validity of the findings in this field.&lt;/br&gt; &lt;b&gt;&lt;br&gt;Aim:&lt;/b&gt; This systematic review and meta-analysis aimed to assess the significance of peritoneal and serum/plasma interleukin-10 (IL-10) levels in the early detection of CAL in patients undergoing colorectal surgery for colorectal cancer.&lt;/br&gt; &lt;b&gt;&lt;br&gt;Methods:&lt;/b&gt; A comprehensive literature search was conducted in PubMed, Scopus, and Web of Science databases, covering studies published until July 2023. The search aimed to identify relevant studies investigating the levels of plasma/serum and peritoneal IL-10 (or both) in colorectal cancer patients undergoing colorectal surgery, specifically focusing on the presence of CAL. Data on the mean and standard deviation of IL-10 levels in both CAL and non-CAL patients were extracted from the selected studies. Mean differences in IL-10 levels were analyzed for each postoperative day (POD) using the OpenMeta [analyst] software.&lt;/br&gt; &lt;b&gt;&lt;br&gt;Results:&lt;/b&gt; 11 articles were selected for inclusion in this systematic review. Among them, nine articles reported data on peritoneal IL-10 levels, while four articles focused on circulating IL-10 levels. The statistical analysis included four eligible articles that assessed peritoneal IL-10 levels, and the results indicated no significant increase in CAL patients compared to non-CAL patients on any postoperative day (POD). Meta-analysis for circulating IL-10 levels was not feasible.&lt;/br&gt; &lt;b&gt;&lt;br&gt;Conclusions:&lt;/b&gt; Up to now, peritoneal and systemic IL-10 levels cannot be considered as early markers for CAL after colorectal surgery in colorectal cancer patients. More high-quality studies are needed to establish the potential of IL-10 as a reliable marker for detecting anastomotic leakage after colorectal surgery.&lt;/br&gt.

Assessment of interleukin-10 promoter variant (-1082A/G) and cytokine production in patients with hemolytic uremic syndrome.

Hemolytic uremic syndrome (HUS) is a condition that results in acute kidney failure mainly in children, which is caused by Shiga toxin-producing Escherichia coli and inflammatory response. Although anti-inflammatory mechanisms are triggered, studies on the implication in HUS are scarce. Interleukin-10 (IL-10) regulates inflammation in vivo, and the interindividual differences in its expression are related to genetic variants. Notably, the single nucleotide polymorphism (SNP) rs1800896 -1082 (A/G), located in the IL-10 promoter, regulates cytokine expression. Plasma and peripheral blood mononuclear cells (PBMC) were collected from healthy children and HUS patients exhibiting hemolytic anemia, thrombocytopenia, and kidney damage. Monocytes identified as CD14+ cells were analyzed within PBMC by flow cytometry. IL-10 levels were quantified by ELISA, and SNP -1082 (A/G) was analyzed by allele-specific PCR. Circulating IL-10 levels were increased in HUS patients, but PBMC from these patients exhibited a lower capacity to secrete this cytokine compared with those from healthy children. Interestingly, there was a negative association between the circulating levels of IL-10 and inflammatory cytokine IL-8. We observed that circulating IL-10 levels were threefold higher in HUS patients with -1082G allele in comparison to AA genotype. Moreover, there was relative enrichment of GG/AG genotypes in HUS patients with severe kidney failure. Our results suggest a possible contribution of SNP -1082 (A/G) to the severity of kidney failure in HUS patients that should be further evaluated in a larger cohort.

Associations between circulating interleukin-17 levels and Behcet's disease and between IL-17 gene polymorphisms and disease susceptibility: a meta-analysis.

To systematically investigate the relationship between circulating interleukin-17 (IL-17) levels and Behçet's disease (BD) and the associations between polymorphisms in IL17 genes and BD susceptibility. We searched the Medline, Embase, and Cochrane databases for relevant articles. We performed a meta-analysis of serum/plasma IL-17 levels in BD patients and controls and evaluated the associations between IL17A rs4711998, rs8193036, and rs2275913 and IL17F rs763780 and rs2397084 polymorphisms and the risk of BD. Twelve studies, involving 901 patients with BD and 1,131 controls, were included. Our meta-analysis revealed that circulating IL-17 levels were significantly higher in the BD group than in the control group (SMD = 1.422, 95% confidence interval [CI] = 0.689-2.155, p<0.001). Subgroup analysis by data type indicated higher IL-17 levels in the BD group in both the original and calculated data populations. Stratification by publication year revealed significantly lower vitamin D levels in the SSc group in both recent and older publication years. No significant differences in IL-17 levels were observed between the active and inactive disease groups. We found no evidence of associations between BD and IL17A rs2275913, L17F rs763780, or rs2397084 polymorphisms. However, a significant association was found between BD and IL17A rs4711998 and rs8193036 polymorphisms in the pooled cohort of affected individuals compared to that in pooled controls (odds ratio [OR] = 1.347, 95% CI = 1.043-1.741, p<0.001; OR = 0.691, 95% CI = 0.542-0.880, p=0.003). This meta-analysis revealed significantly higher circulating IL-17 levels in BD patients and showed evidence of associations between IL17A rs4711998 and rs8193036 polymorphisms and BD.

Preeclamptic Women Have Decreased Circulating IL-10 (Interleukin-10) Values at the Time of Preeclampsia Diagnosis: Systematic Review and Meta-Analysis.

A key immunomodulatory cytokine, IL-10 (interleukin-10), has been shown to be dysregulated in preeclampsia, a pregnancy-specific hypertensive disorder, further characterized by multi-system involvement. However, studies have reported inconsistent findings about circulating IL-10 levels in preeclamptic versus normotensive pregnancies. The aim of the present systematic review and meta-analysis was to assess circulating IL-10 levels in preeclamptic and normotensive pregnancies at 2 time points: before, and at the time of preeclampsia diagnosis. PubMED, EMBASE, and Web of Science databases were searched to include all published studies examining circulating IL-10 levels in preeclamptic and normotensive pregnancies. Differences in IL-10 levels were evaluated by standardized mean differences. Of 876 abstracts screened, 56 studies were included in the meta-analysis. Circulating IL-10 levels were not different before the time of active disease (standardized mean differences, -0.01 [95% CI, -0.11 to 0.08]; P=0.76). At the time of active disease, women with preeclampsia (n=1599) had significantly lower IL-10 levels compared with normotensive controls (n=1998; standardized mean differences, -0.79 [95% CI, -1.22 to -0.35]; P=0.0004). IL-10 levels were lower in both early/severe and late/mild forms of preeclampsia. Subgroup analysis revealed that IL-10 measurement methodology (ELISA or multiplex bead array) and the sample type (plasma or serum) significantly influenced the observed differences, with the use of sera paired with ELISA technology providing the best distinction in IL-10 levels between preeclamptic and normotensive pregnancies. These findings support the role of decreased IL-10 levels in the pathophysiology of preeclampsia. Future studies should address the therapeutic potential of IL-10 in preeclampsia.

Associations Between Circulating Interleukin-17 Levels and Systemic Lupus Erythematosus and Between Interleukin-17 Gene Polymorphisms and Disease Susceptibility: A Meta-analysis

Objective. To systematically investigate the relationship between circulating interleukin-17 (IL-17) levels and systemic lupus erythematosus (SLE) and associations between polymorphisms in IL17 genes and SLE susceptibility. Methods. We performed a meta-analysis of serum/plasma IL-17 levels in patients with SLE and controls and evaluated the associations between the IL17A rs2275913, IL17F rs763780, and IL17F rs2397084 polymorphisms and IL17F copy number variations (CNVs) and risk of SLE. Results. Thirteen studies focusing on 2,096 patients with SLE and 2,587 controls were included. Our meta-analysis revealed that IL-17 levels were significantly higher in the SLE group than the control group (standardized mean difference=1.045, 95% confidence interval [95% CI]=0.521∼1.568, p＜0.001). Subgroup analysis using sample size showed increased IL-17 levels in samples from large (n＞100) but not small (n＜90) SLE groups. We found no evidence of associations between SLE and the IL17A rs2275913, IL17F rs763780, and IL17F rs2397084 polymorphisms. However, a significant association was found between SLE and IL17F CNVs in a pooled cohort of affected individuals compared to that in pooled controls (odd ratio=3.663, 95% CI=2.466∼5.221, p＜0.001). Conclusion. This meta-analysis revealed significantly higher circulating IL-17 levels in patients with SLE and showed evidence of associations between IL17F CNVs and SLE. (J Rheum Dis 2020;27:37-44)

Elevated Circulating Interleukin-17 Levels in Patients with Systemic Lupus Erythematosus: A Meta-analysis

ABSTRACT Background Previous studies concerning the circulating interleukin-17 (IL-17) in systemic lupus erythematosus (SLE) were contradictory. Aims To further precisely investigate circulating IL-17 in SLE and evaluate its influential factors by meta-analysis. Methods EMBASE, PubMed and Cochrane Library were comprehensively searched to obtain studies on circulating IL-17 in SLE patients by November 22, 2018. The results were illustrated by pooled standard mean difference (SMD) with corresponding 95% confidence interval (CI) using random-effects model as there was significant heterogeneity, which was estimated using Cochran Q and I2 statistics. Subgroup analyses and sensitivity analyses were also conducted. Results Overall, 1872 articles were reviewed and 20 studies involving 1067 subjects with SLE and 721 healthy controls (HCs) were enrolled in the final analysis according to inclusion criteria. Compared with HCs, circulating IL-17 levels in SLE patients were elevated (SMD: 1.183, 95% CI: 0.763–1.603; P < .001). Moreover, in comparison to HCs, European and Asian SLE patients, age <30 years, disease duration ≥5 years, NOS scores <7 and using ELISA showed increased circulating IL-17 status, whereas no significant change was observed in other subgroups. There was no significant publication bias. Sensitivity analyses demonstrated that the results of our meta-analysis were robust. Conclusions SLE patients have higher circulating IL-17 levels, which is influenced by ethnic, age and disease duration, literature quality and measurements.

Association between IL-17 gene polymorphisms and circulating IL-17 levels in osteoarthritis: ameta-analysis.

This study systemically reviewed the evidence regarding associations between polymorphisms in interleukin-17 (IL-17) genes and osteoarthritis (OA) susceptibility, and the relationship between circulating IL-17 levels and OA. We performed ameta-analysis of the associations between the IL-17A rs2275913 and IL-17F rs763780 polymorphisms and risk for OA and serum/plasma IL-17 levels in OA patients and controls. Eight studies including 2214 OA patients and 2474 controls were included. Our meta-analysis identified asignificant association between OA and the AA genotype of the IL-17A rs2275913 polymorphism in apooled cohort of affected individuals, compared to the case in apooled cohort of control participants (OR = 1.516, 95% CI = 1.260-1.825, P < 0.001), and asignificant association between OA and the CC genotype of the IL-17F rs763780 polymorphism (OR = 2.257, 95% CI = 1.376-3.704, p = 0.001). OA site-based stratification identified an association between the AA genotype of the IL-17A rs2275913 polymorphism and the CC genotype of the IL-17F rs763780 polymorphism and knee OA, but not hip OA. Furthermore, the same patterns of significant associations between OA and the IL-17A rs2275913 and IL-17F rs763780 polymorphisms were identified based on homozygote contrasts. The OA patients showed significantly higher IL-17 levels than the control subjects (SMD = 1.830, 95% CI = 1.184-2.477, P < 0.001). Our meta-analysis revealed associations between the IL-17A rs2275913 and IL-17F rs763780 polymorphisms and OA susceptibility, and the presence of significantly higher circulating IL-17 levels in OA patients.

Prevention of lipopolysaccharide-induced CD11b+ immune cell infiltration in the kidney: role of AT2 receptors.

Immune cell infiltration plays a central role in mediating endotoxemic acute kidney injury (AKI). Recently, we have reported the anti-inflammatory and reno-protective role of angiotensin-II type-2 receptor (AT2R) activation under chronic low-grade inflammatory condition in the obese Zucker rat model. However, the role of AT2R activation in preventing lipopolysaccharide (LPS)-induced early infiltration of immune cells, inflammation and AKI is not known. Mice were treated with AT2R agonist C21 (0.3 mg/kg), with and without AT2R antagonist PD123319 (5 mg/kg) prior to or concurrently with LPS (5 mg/kg) challenge. Prior-treatment with C21, but not concurrent treatment, significantly prevented the LPS-induced renal infiltration of CD11b+ immune cells, increase in the levels of circulating and/or renal chemotactic cytokines, particularly interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) and markers of renal dysfunction (blood urea nitrogen and albuminuria), while preserving anti-inflammatory interleukin-10 (IL-10) production. Moreover, C21 treatment in the absence of LPS increased renal and circulating IL-10 levels. To investigate the role of IL-10 in a cross-talk between epithelial cells and monocytes, we performed in vitro conditioned media (CM) studies in human kidney proximal tubular epithelial (HK-2) cells and macrophages (differentiated human monocytes, THP-1 cells). These studies revealed that the conditioned-media derived from the C21-treated HK-2 cells reduced LPS-induced THP-1 tumor necrosis factor-α (TNF-α) production via IL-10 originating from HK-2 cells. Our findings suggest that prior activation of AT2R is prophylactic in preventing LPS-induced renal immune cell infiltration and dysfunction, possibly via IL-10 pathway.

Associations between circulating IL-17 levels and rheumatoid arthritis and between IL-17 gene polymorphisms and disease susceptibility: a meta-analysis

ObjectivesTo systematically review evidence regarding the relationship between circulating interleukin-17 (IL-17) levels and rheumatoid arthritis (RA), and associations between polymorphisms in IL-17 genes and RA susceptibility.MethodWe performed a meta-analysis of...

Circulating interleukin-10 levels and human papilloma virus and Epstein-Barr virus-associated cancers: evidence from a Mendelian randomization meta-analysis based on 11,170 subjects.

Recent studies have showed interleukin 10 (IL-10) is a critical cytokine that determines antiviral immune response and is related to virus-associated cancers. However, whether genetically elevated circulating IL-10 levels are associated with the risk of human papilloma virus and Epstein–Barr virus-associated cancers (HEACs) is still unclear. Mendelian randomization method was implemented to meta-analyze available observational studies by employing IL-10 three variants (−592C>A, −819C>T, and −1082A>G) as instruments. A total of 24 articles encompassing 11,170 subjects were ultimately eligible for the meta-analysis. Overall, there was a significant association between IL-10 promoter variant −1082A>G and HEACs under allelic and dominant models (both P<0.01). Subgroup analysis by cancer type indicated that the risk estimate of −1082A>G was significant for nasopharyngeal cancer under allelic, homozygous genotypic and dominant models (all P<0.001). Moreover by ethnicity, carriers of −1082G allele had a 74% increased risk for nasopharyngeal cancer in Asians under dominant model (odds ratio [OR] =1.737; 95% confidence interval [CI]: 1.280–2.358; P<0.001). In further Mendelian randomization analysis, the predicted OR for 10 pg/mL increment in IL-10 levels was 1.14 (95% CI: 1.01–16.99) in HEACs. Our findings provided strong evidence for a critical role of genetically elevated circulating IL-10 levels in the development of HEACs, especially in Asian population and for nasopharyngeal cancer.

Interleukin-10 and soil-transmitted helminth infections in Honduran children.

BackgroundSoil-transmitted helminths (STH) establish chronic infections in the human intestine. The host reacts to these infections with a dominant T-helper type 2 cell (Th2) response that while attempting to control the worm population, can also provide an anti-inflammatory environment favourable for parasite survival. Regulatory cytokine interleukin 10 (IL-10) has been proposed as a key molecule involved in the attenuation of chronic inflammation and the ensuing tolerance for these helminth parasites. The objective of this study was to determine whether STH-infected children from an endemic community had increased circulating IL-10 levels when compared to non-infected children.ResultsA total of 39 children (25 boys and 14 girls, 7–15 years of age) were enrolled in study. Utilizing the Kato-Katz method to detect intestinal helminthiases, 10 children were non-infected and 29 were harbouring STH infections by Ascaris lumbricoides, Trichuris trichiura and/or hookworms. Of the 29 infected children, 11 had single-species infections and 18 were polyparasitized with two or three STH species. Serum samples from all 39 children were tested for IL-10 serum concentrations, out of which 12 had undetectable levels while 27 had levels ranging from 0.4-105 pg/mL. Excluding extreme outlying values, 25 samples had IL-10 concentration values ranging from 0.4 -7.2 pg/mL. Differences in IL-10 levels among non-parasitized, monoparasitized, and polyparasitized groups were not statistically significant. However, children infected with any of the three STH species investigated had higher IL-10 levels than non-parasitized children (geometric means: 0.89 pg/mL vs. 0.74 pg/mL, p = 0.428). Similarly, polyparasitized children had higher IL-10 levels than both monoparasitized and non-parasitized children (1.04 pg/mL, 0.69 pg/mL, and 0.74 pg/mL, respectively, p = 0.481). A significant moderate negative correlation between IL-10 levels and children’s age was found, but no correlations were observed between IL-10 levels and intensity of infection by any of the parasite species investigated.ConclusionsWe found no strong evidence for an association between STH infection and serum IL-10 concentration levels. However, the trends identified here warrant further investigation. Additional research is needed to expand the current understanding of the immune response elicited by STH infections in children living in endemic communities.

Elevated Interleukin-10 and “Disappearing HDL Syndrome” in Lymphoproliferative Disorders

BACKGROUND: Acquired severe HDL deficiency is relatively uncommon. It may occur with use of high doses of anabolic steroids or in severe liver diseases, which can lead to low LCAT activity and decreased apoA-I production. “Disappearing HDL Syndrome”*, a term first used by Goldberg and Mendez, refers to cases of severe HDL deficiency in patients that are not critically ill, sometimes long before the clinical or biochemical features of the underlying primary disease become evident. Disappearing HDL Syndrome can also result from an idiosyncratic reaction to medications, such as peroxisome proliferation-activated receptor (PPAR) agonists. Additionally, autoantibodies against LCAT in non-Hodgkin lymphoma have been described as a possible cause. Low high-density lipoprotein-cholesterol (HDL-C) is a risk factor for coronary artery disease.OBJECTIVE: To determine the cause of low HDL-C in patients with severe acquired HDL deficiency noted as an incidental finding associated with lymphoma and autoimmune lymphoproliferative syndrome (ALPS)** as well as following recombinant human IL10 therapy in psoriatric arthritis patients. Investigating mechanisms underlying acquired severe HDL deficiency in non-critically ill patients (“Disappearing HDL Syndrome”) could provide new insights into HDL metabolism and its role in lymphomagenesis.PATIENTS AND RESULTS: Patients with intravascular large B-cell lymphoma (IVLBCL, n=2), diffuse large B-cell lymphoma (DLBCL, n=1), and ALPS-FAS (n=1) presenting with markedly decreased HDL-C, low LDL-C and elevated triglycerides were identified. The abnormal lipoprotein profile returned to normal following therapy in all four cases (Figure). All of them were found to have markedly elevated serum interleukin-10 (IL-10) levels at presentation that also normalized following therapy. Besides accumulation of abnormal lymphocytes in lymph nodes and spleen, ALPS patients have elevated serum IL-10. In a cohort of ALPS patients with genetic mutations in FAS (n=93), IL-10 showed a strong inverse correlation with HDL-C (R2=0á3720, P<0á0001). A direct causal role for increased serum IL-10 in inducing the observed changes in lipoproteins was established in a randomized, placebo-controlled clinical trial of recombinant human IL-10 (rhIL-10) in psoriatic arthritis patients (n=18). Within a week of initiating subcutaneous rhIL-10 injections, HDL-C precipitously decreased to near-undetectable levels. LDL-C also decreased by over 50% (P<0.0001) and triglycerides increased by approximately 2-fold (P<0.005). All values returned to baseline after stopping IL-10 therapy.CONCLUSION: Increased IL-10 causes severe HDL-C deficiency, low LDL-C and elevated triglycerides. IL-10 is thus a potent modulator of lipoprotein levels, a potential new biomarker for B-cell disorders, and a novel cause of Disappearing HDL Syndrome. Elevated IL-10 plays a key role in linking inflammation and lipoprotein metabolism. As evidence for its causality, rhIL-10 treatment in a clinical trial of psoriasitic arthritis patients precipitously lowered HDL-C. Finding elevated IL-10 as a cause of “Disappearing HDL Syndrome” in patients with 3 different types of B-cell disorders suggests that IL-10 and low HDL-C could be useful biomarkers of disease activity in these conditions. Finally, future research focusing on strategies to alter lipoprotein levels by modulating circulating IL-10 levels or its signaling pathways may be useful for developing novel targeted therapies.*Ref: Severe acquired (secondary) high-density lipoprotein deficiency. Goldberg RB, Mendez AJ. J Clin Lipidol. 2007;1:41-56**Ref: Natural history of autoimmune lymphoproliferative syndrome associated with FAS gene mutations. Price S, Shaw PA, Seitz A et al. Blood. 2014 Mar 27;123(13):1989-99. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Environmental and Genetic Factors Influence the Relationship Between Circulating IL‐10 and Obesity Phenotypes

Interleukin-10 (IL-10) is a centrally operating anti-inflammatory cytokine that plays a crucial role in the regulation of the innate immune system. It has strong inactivating properties on the inflammatory host response and has been related with viral persistence. We aimed to evaluate the association among circulating IL-10, obesity phenotypes, IL-10 and IL-10R1 gene polymorphisms, and the environmental exposure to viral infection. IL-10 -819C/T gene promoter and IL-10 receptor-1 -243A/G gene polymorphisms were studied in 760 subjects, whereas the former was also investigated in a replication study of 676 subjects. The association of circulating IL-10 levels (enzyme-linked immunosorbent assay) with the serum IgG against adenoviruses and enteroviruses was evaluated in a subset of 189 subjects. Circulating levels of IL-10 were increased in obese people and were positively associated with weight, BMI, waist, waist-to-hip ratio, fat mass, systolic pressure, and, interestingly, the titer of adenoviruses and enteroviruses. Obese subjects with adenovirus titer over the median had the highest circulating IL-10 concentration. Both obesity and adenovirus titer were independently associated with IL-10 variance. Nonmorbid obese T carriers for the -819CT IL-10 gene polymorphism had significantly higher BMI and waist circumference, and those with normal fasting glucose had increased fasting triglycerides. G carriers for the -536AG IL-10R1 gene polymorphism had higher systolic and diastolic pressures, and IL-10 levels; and obese G carriers had an increased waist-to-hip ratio. In summary, circulating IL-10 levels were associated not only with obesity status but also with genetic factors and with the exposure to environmental pathogens.

Apolipoprotein E Genotype and Circulating Interleukin-10 Levels in Patients With Stable and Unstable Coronary Artery Disease

This study was designed to assess the relation between apolipoprotein E (apoE) genotype and serum interleukin (IL)-10 levels in patients with acute coronary syndrome (ACS) and chronic stable angina (CSA). Genetic variations in the apoE gene affect the risk for coronary artery disease (i.e., carriers of the e4 allele have an increased risk). Increased levels of C-reactive protein (CRP), an inflammatory marker, correlate with an increased risk of acute coronary events, whereas increased IL-10 concentrations have an atheroprotective role. Studies have reported a negative association between the apoE e4 allele and CRP levels. Apolipoprotein E genotypes were assessed in 166 consecutive ACS patients (119 men, mean age 68 years, interquartile range [IQR] 60 to 74 years) and 70 CSA patients (54 men, mean age 65 years, IQR 62 to 68 years). Serum IL-10 and CRP were assessed at study entry. Analysis of covariance showed that genetic variation in the apoE gene locus significantly influences serum IL-10 levels in both ACS (p = 0.009) and CSA patients (p = 0.013). Among ACS patients, IL-10 levels were lower in E3/E4 carriers compared with E3/E3 carriers (p = 0.01) and marginally lower compared with E2/E3 carriers (p = 0.065). Among CSA patients, IL-10 levels were lower in E3/E4 carriers compared with E2/E3 carriers (p = 0.004) and marginally lower compared with E3/E3 carriers (p = 0.086). The IL-10 concentrations differ in ACS and in CSA patients with different apoE genotypes. The e4 allele was associated with a trend toward lower IL-10 serum levels. Our results may provide an explanation of findings in previous studies that cardiovascular risk is higher in e4 carriers despite the presence of low CRP levels.

Changes in circulating levels of an anti-inflammatory cytokine interleukin 10 in burned patients

In order to understand the role of an anti-inflammatory cytokine interleukin 10 (IL-10) in the pathophysiology of burn injury, IL-10 levels in serial serum samples of 22 burned patients were analyzed. The total body surface areas (TBSA) of the burn injury ranged from 30 to 90%. Among these 22 patients, 14 recovered and the other eight, who were septic, expired. A significant difference in serum IL-10 values on admission (5–20 h postburn) was found ( P<0.05) between patients who survived or died from burn injury as analyzed by the Student’s t test. In addition, a significant difference in serum IL-10 on admission was also found ( P<0.05) between patients with TBSA of greater or less than 50%. An initial peak serum IL-10 response was detected within 2.5 days postburn. Significant differences in the peak serum IL-10 levels were not found between patients with TBSA of greater or less than 50% and patients who survived or expired from burn injury. Afterwards, serum IL-10 remained low in the survivors, while an increase in serum IL-10 could be detected in the non-survivors with proven sepsis. Levels of circulating IL-6 in these non-surviving patients showed a tendency to increase starting from about 1–2 weeks postburn which coincided temporally with the detection of infections. However, marked increases in circulating IL-10 levels were observed just before death in four of the eight non-survivors. The serum samples of these four patients were collected at 31 h (404.8 pg/ml), 2 h (773.9 pg/ml), 5 days (150.7 pg/ml) and 12 h (177.1 pg/ml) before the expiration of these patients, respectively. IL-10 levels of 28.6, 27.5 and 13.5 pg/ml were detected in sera of three of the remaining four non-survivors that were collected at 2.5 h, 36 h and 30 h before the expiration of these patients, respectively. There was one non-surviving patient who suffered an 80% burn (patient D4 in Table 1 and Fig. 4) and his IL-10 level at 20 days postburn was 13.4 pg/ml. The serum sample of this patient was collected 22 days before death and he was not suffering from sepsis at this stage. In conclusion, an initial increase in serum levels of IL-10 was detected postburn. A marked increase in serum levels of IL-10 was detected in four of the eight septic patients just before their death. It was considered that a lack and/or a delay in the increase of circulating IL-10 may play a significant role in the pathophysiology of sepsis in burned patients.

Circulating interleukin 6 and interleukin 10 in community acquired pneumonia.

Inflammatory cytokine concentrations correlate with severity of sepsis. We hypothesised that patients with community acquired pneumonia (CAP) associated with systemic inflammatory response syndrome (SIRS) would have greater interleukin 6 (IL-6) production due to activation of the inflammatory cytokine cascade, matched by a significant anti-inflammatory cytokine response. Interleukin 10 (IL-10) was evaluated as a potential surrogate marker of severity of sepsis in CAP and age related impairment of the cytokine response was studied in elderly patients with CAP. Circulating immunoreactive IL-6 and IL-10 levels were measured in 38 patients with CAP subdivided into a group fulfilling the criteria for SIRS (n = 28) and a non-SIRS group (n = 10) in a variety of age groups and correlated with APACHE II scores. 80% had circulating IL-6 levels (median 46.7 pg/ml, range 4.6-27,000) and 60% had circulating IL-10 levels (median 15.5 pg/ml, range 2.5-765). Concentrations of both were significantly increased in patients with SIRS compared with non-SIRS patients. Those with activation of the inflammatory cytokine cascade (IL-6 positive) produced more IL-10 than IL-6 negative patients. Older patients had a similar cytokine response. Both cytokines correlated positively with APACHE II scores. This is the first demonstration of circulating IL-10 in CAP. A greater counter-inflammatory response in patients with SIRS and in IL-6 positive patients suggests a potential immunomodulatory role for IL-10 in controlling the inflammatory cytokine response in CAP. IL-10 concentrations correlate with severity of illness in CAP and may be of prognostic importance. There is no age related impairment in the cytokine response.

Possible Role of Interleukin-10 (IL-10) and CD40 Ligand Expression in the Pathogenesis of Hypergammaglobulinemia in Human Immunodeficiency Virus Infection: Modulation of IL-10 and Ig Production After Intravenous Ig Infusion

The mechanisms leading to polyclonal hypergammaglobulinemia in patients with human immunodeficiency virus (HIV) infection are not well understood. In light of the important role of interleukin-10 (IL-10) and the interaction between CD40 and CD40 ligand in the normal regulation of B-lymphocyte function and Ig production, we examined these parameters in 24 HIV-infected patients. Both plasma IL-10 levels and the percentage of CD4(+) and CD8(+) lymphocytes expressing CD40 ligand were significantly higher in the patients than in the 10 blood donor controls. Serum IgG correlated positively with circulating IL-10 levels and the percentage of CD4(+) lymphocytes expressing CD40 ligand. Furthermore, a single bolus infusion of intravenous Ig (0.4 g/kg) in 8 HIV-infected patients caused a further increase in IL-10 levels in plasma and an increase in both IL-10 and IgG production in peripheral blood mononuclear cell cultures. In another patient group (Wegener's granulomatosis) receiving a single bolus infusion of intravenous Ig, a similar increase in plasma IL-10 levels was found, suggesting that this may be a general effect of intravenous Ig. In patients with HIV infection, our data suggest that a vicious cycle may be operative where high endogenous Ig levels may enhance IL-10 production that, in turn, leads to higher Ig production.

Possible Role of Interleukin-10 (IL-10) and CD40 Ligand Expression in the Pathogenesis of Hypergammaglobulinemia in Human Immunodeficiency Virus Infection: Modulation of IL-10 and Ig Production After Intravenous Ig Infusion

AbstractThe mechanisms leading to polyclonal hypergammaglobulinemia in patients with human immunodeficiency virus (HIV) infection are not well understood. In light of the important role of interleukin-10 (IL-10) and the interaction between CD40 and CD40 ligand in the normal regulation of B-lymphocyte function and Ig production, we examined these parameters in 24 HIV-infected patients. Both plasma IL-10 levels and the percentage of CD4+ and CD8+lymphocytes expressing CD40 ligand were significantly higher in the patients than in the 10 blood donor controls. Serum IgG correlated positively with circulating IL-10 levels and the percentage of CD4+ lymphocytes expressing CD40 ligand. Furthermore, a single bolus infusion of intravenous Ig (0.4 g/kg) in 8 HIV-infected patients caused a further increase in IL-10 levels in plasma and an increase in both IL-10 and IgG production in peripheral blood mononuclear cell cultures. In another patient group (Wegener’s granulomatosis) receiving a single bolus infusion of intravenous Ig, a similar increase in plasma IL-10 levels was found, suggesting that this may be a general effect of intravenous Ig. In patients with HIV infection, our data suggest that a vicious cycle may be operative where high endogenous Ig levels may enhance IL-10 production that, in turn, leads to higher Ig production.

Stability of serum interleukin-10 levels during the menstrual cycle.

Menstrual cycle-associated variability in the circulating levels of several cytokines can be a confounding factor in measurements of in vivo cytokine levels in clinical studies. Since pregnancy-associated increases in interleukin-10 (IL-10) levels are well documented, we have investigated the variability in serum levels of IL-10 in healthy women at different stages of the menstrual cycle to ascertain whether this is a problem in comparative studies of circulating IL-10 levels. We obtained fifty-four successive serum samples at points in the menstrual cycles of 12 healthy fertile women, precisely timed by measurement of the luteinizing hormone surge, and measured the interleukin-10 levels. Levels of IL-10 in successive serum samples from each woman taken on days LH - 7 (that is seven days prior to LH surge), LH - 4, LH + 1, LH + 7, and LH + 10 showed that IL-10 does not vary in a systematic way during the menstrual cycle. These results validate the sampling of women in studies of IL-10 levels in various clinical situations and establish that these levels are not dependent on menstrual cycle dates. They also suggest that menstrual cycle-related changes in IL-1 are not mediated by IL-10. The rise in progesterone in the luteal phase of the menstrual cycle is not mirrored by a rise in the circulating IL-10 level, which implies either that the pregnancy-associated rise is not related to progesterone or that it is only observed at the higher progesterone levels in pregnancy.