Serum Interleukin-1 Receptor Antagonist Research Articles

Increase in Serum Interleukin-1 Receptor Antagonist (IL-1ra) Levels after Wheelchair Half Marathon Race in Male Athletes with Spinal Cord Injury.

Exercise increases the serum level of interleukin-6 (IL-6), which in turn stimulates the production of various inflammatory cytokine antagonists, such as interleukin-1 receptor antagonist (IL-1ra). Individuals with cervical spinal cord injury (CSCI) are at high risk of inflammatory conditions. This study compared the effects of wheelchair half marathon on the immune system of male athletes with CSCI and those with thoracic/lumber spinal cord injury (SCI). Neutrophil count, IL-1ra, IL-6, and various endocrine parameters were measured before, immediately and 1 h after the race in five CSCI and six SCI who completed the wheelchair marathon race. The percentage of neutrophils was significantly higher in CSCI immediately and 1 h after the race, compared with the baseline, and significantly higher in SCI at 1 h after the race. IL-6 was significantly higher immediately and 1 h after the race in SCI, whereas no such changes were noted in IL-6 in CSCI. IL-1ra was significantly higher at 1 h after the race in both SCI and CSCI. The race was associated with an increase in IL-1ra in both CSCI and SCI. These findings suggest wheelchair half marathon race increases IL-1ra even under stable IL-6 status in male CSCI individuals, and that such post-race increase in IL-1ra is probably mediated through circulatory neutrophils.

Apolipoprotein B and interleukin 1 receptor antagonist: reversing the risk of coronary heart disease.

Epidemiological evidence for the link of interleukin 1 (IL-1) and its inhibition with cardiovascular diseases (CVDs) remains controversial. We aim to investigate the cardiovascular effects of IL-1 receptor antagonist (IL-1Ra) and underlying mechanisms. Genetic variants identified from a genome-wide association study involving 30,931 individuals were used as instrumental variables for the serum IL-1Ra concentrations. Genetic associations with CVDs and cardiometabolic risk factors were obtained from international genetic consortia. Inverse-variance weighted method was utilized to derive effect estimates, while supplementary analyses employing various statistical approaches. Genetically determined IL-1Ra level was associated with increased risk of coronary heart disease (CHD; OR, 1.07; 95% CI: 1.03-1.17) and myocardial infarction (OR, 1.13; 95% CI: 1.04-1.21). The main results remained consistent in supplementary analyses. Besides, IL-1Ra was associated with circulating levels of various lipoprotein lipids, apolipoproteins and fasting glucose. Interestingly, observed association pattern with CHD was reversed when adjusting for apolipoprotein B (OR, 0.84; 95%CI: 0.71-0.99) and slightly attenuated on accounting for other cardiometabolic risk factors. Appropriate lifestyle intervention was found to lower IL-1Ra concentration and mitigate the heightened CHD risk it posed. Apolipoprotein B represents the key driver, and a potential target for reversal of the causal link between serum IL-1Ra and increased risk of CHD/MI. The combined therapy involving IL-1 inhibition and lipid-modifying treatment aimed at apolipoprotein B merit further exploration.

Assessment of interleukin 1 receptor antagonist (IL-1RA) levels in children with and without community acquired pneumonia: a hospital based case-control study.

The primary objective was to compare serum interleukin-1 receptor antagonist (IL-1RA) levels in cases of community acquired pneumonia (CAP) and healthy age-gender-matched controls. The secondary objective was to compare serum IL-1RA levels in cases which were positive or negative for Streptococcus pneumoniae in the blood by real-time-polymerase chain reaction (RT-PCR). Hospitalized children with World Health Organization defined CAP, aged 2-59 months, were included as cases. Healthy controls were recruited from the immunization clinic of the hospital. Enzyme-linked immunosorbent assay (ELISA) test was used to detect serum IL-1RA levels. Identification of S.pneumoniae in blood was done by RT-PCR. From October 2019 to October 2021, 330 cases (123, 37.27% female) and 330 controls (151, 45.75% females) were recruited. Mean serum IL-1RA levels (ng/ml) were 1.36 ± 0.95 in cases and 0.25 ± 0.25 in controls (p < 0.001). Within cases, serum IL-1RA levels were significantly higher in those whose RT-PCR was positive for S.pneumoniae. Thus serum IL-1RA levels may be evaluated as a surrogate marker of S.pneumoniae in future studies.

Evaluation of serum interleukin-1 receptor antagonist levels in major depressive disorder: A case-control study.

Major depressive disorder (MDD) is characterized by the occurrence of one or more depressive episodes lasting a minimum of 2 weeks and is marked by a persistently low mood and a lack of enjoyment in daily activities. The diagnosis of MDD is not possible by a well-established laboratory test or biomarker. A wide range of potential biomarkers for depression have been proposed by many studies, but none of them has adequately described the correlation between the biomarkers and depression. The purpose of this study was to evaluate serum interleukin-1 receptor antagonist (IL-1RA) levels as an early depression risk factor. The present case-control study included 88 participants. Among them, 44 MDD patients enrolled from the psychiatry department of a public hospital in Dhaka, Bangladesh, and 44 age- and sex-matched healthy controls (HCs) from various sites in Dhaka city. A qualified psychiatrist evaluated the cases and HCs based on the fifth edition of the diagnostic and statistical manual of mental disorders (DSM-5). The Hamilton depression (Ham-D) rating scale was employed to evaluate the intensity of depression. An enzyme-linked immunosorbent assay kit (Boster Bio, USA) was used to determine serum IL-1RA concentrations. We observed no marked alteration in the serum concentration of IL-1RA in MDD patients in comparison to HCs (292.81 ± 24.81 and 288 ± 24.87 pg/mL; p > 0.05). Among MDD patients, we found no noteworthy association between the severity of depression and serum IL-1RA levels. The findings of the present study imply that IL-1RA may not be identified as a promising biomarker for risk assessment of depression. However, its neuroprotective role may be taken into consideration for the understanding of pathophysiology of MDD.

The role of alcohol use and adiposity in serum levels of IL-1RA in depressed patients

BackgroundThe role of Interleukin-1 Receptor antagonist (IL-1Ra), an innate antagonist to pro-inflammatory cytokine IL-1, has attracted increasing attention due to its potential pathogenic and therapeutic implications in depression. However, the role of alcohol and adiposity in modulating IL-1Ra cytokine pathway in depressed patients has remainned unknown. The aim of this study was to follow the changes in IL-1Ra serum levels in depressed patients with or without simultaneous alcohol use disorder (AUD) and different degrees of adiposity during 6 months of follow-up.Materials and methodsA total of 242 patients with depression were followed for 6 months. At baseline 99 patients had simultaneous AUD. Levels of serum IL-1Ra and common mediators of inflammation (IL-6, hs-CRP) were measured. Clinical assessments included Body Mass Index (BMI), Montgomery-Asberg Depression Rating Scale (MADRS) and Alcohol Use Disorders Identification Test (AUDIT) scores.ResultsSignificant reductions in clinical symptoms and IL-1Ra were observed during 6-month follow-up. In hierarchical linear regression analysis, the effect of MADRS score, age, gender, and smoking had a combined effect of 2.4% in the model. The effect of AUDIT score increased the effect to 4.2% of variance (p = 0.08), whereas adding BMI increased the effect to 18.5% (p < 0.001).ConclusionAdiposity may influence the IL-1Ra anti-inflammatory response in depressed patients, whereas the effect of alcohol consumption in these patients seems insignificant. These findings should be considered in studies on the role of IL-1Ra in depression.Trial registrationOstrobothnia Depression Study in ClinicalTrials.gov , Identifier NCT02520271.

Serum Levels of IL-1 RA Increase with Obesity and Type 2 Diabetes in Relation to Adipose Tissue Dysfunction and are Reduced After Bariatric Surgery in Parallel to Adiposity.

BackgroundExcess adiposity leads to a dysfunctional adipose tissue that contributes to the development of obesity-associated comorbidities such as type 2 diabetes (T2D). Interleukin-1 receptor antagonist (IL-1RA) is a naturally occurring antagonist of the IL-1 receptor with anti-inflammatory properties. The aim of the present study was to compare the circulating concentrations of IL-1RA and its mRNA expression in visceral adipose tissue (VAT) in subjects with normal weight (NW), obesity with normoglycemia (OB-NG), or obesity with impaired glucose tolerance or T2D (OB-IGT&T2D) and to analyze the effect of changes in body fat percentage (BF%) on IL-1RA levels.MethodsSerum concentrations of IL-1RA were measured in 156 volunteers. Expression of IL1RN mRNA in VAT obtained from 36 individuals was determined. In addition, the concentrations of IL-1RA were measured before and after weight gain as well as weight loss following a dietetic program or Roux-en-Y gastric bypass (RYGB).ResultsSerum levels of IL-1RA were significantly increased in individuals with obesity, being further increased in the OB-IGT&T2D group (NW 440 ± 316, OB-NG 899 ± 562, OB-IGT&T2D 1265 ± 739 pg/mL; P<0.001) and associated with markers of inflammation and fatty liver. IL1RN mRNA expression in VAT was significantly increased in the OB-IGT&T2D group and correlated in the global cohort with the mRNA expression of SPP1, CCL2, CD68, and MMP9. Levels of IL-1RA were not modified after modest changes in BF%, but RYGB-induced weight loss significantly decreased IL-1RA concentrations from 1233 ± 1009 to 660 ± 538 pg/mL (P<0.001).ConclusionSerum IL-1RA concentrations are increased in patients with obesity being further elevated in obesity-associated IGT and T2D in association with markers of adipose tissue dysfunction. The mRNA expression of IL1RN is markedly increased in VAT of subjects with obesity and T2D in relation with genes involved in macrophage recruitment, inflammation and matrix remodeling. Serum IL-1RA concentrations are reduced when a notable amount of BF% is loss. Measurement of IL-1RA is an excellent biomarker of adipose tissue dysfunction in obesity-associated metabolic alterations.

TA allele of rs2070673 in the CYP2E1 gene is associated with lobular inflammation and nonalcoholic steatohepatitis in patients with biopsy-proven nonalcoholic fatty liver disease.

Cytochrome P450 2E1 (CYP2E1) plays a role in lipid metabolism, and by increasing hepatic oxidative stress and inflammation, the upregulation of CYP2E1 is involved in development of nonalcoholic steatohepatitis (NASH). We aimed to explore the relationship between CYP2E1-333A>T (rs2070673) and the histological severity of nonalcoholic fatty liver disease (NAFLD). We studied 438 patients with biopsy-proven NAFLD. NASH was defined as NAFLD Activity Score≥5 with existence of steatosis, ballooning, and lobular inflammation. CYP2E1-333A>T (rs2070673) was genotyped by matrix-assisted laser desorption ionization-time of flight mass spectrometry. Serum cytokines related to inflammation were measured by the Bio-plex 200 system to investigate possible mediating factors involved in the process. The TA genotype of rs2070673 had a higher prevalence of moderate/severe lobular inflammation (27.6% vs 20.3% vs 13.3%, P<0.01) and NASH (55.7% vs 42.4% vs 40.5%, P<0.01) compared with the AA and TT genotypes, respectively. In multivariable regression modeling, the heterozygote state TA was associated with moderate/severe lobular inflammation (adjusted odds ratio: 2.31, 95% confidence interval 1.41-3.78, P<0.01) or NASH (adjusted odds ratio: 1.82, 95% confidence interval 1.22-2.69, P<0.01), independently of age, sex, common metabolic risk factors, and presence of liver fibrosis. Compared with no-NASH, NASH patients had significantly higher levels of serum interleukin-1 receptor antagonist, interleukin-18, and interferon-inducible protein-10 (IP-10), whereas only IP-10 was increased with the rs2070673 TA variant (P=0.01). Mediation analysis showed that IP-10 was responsible for ~60% of the association between the rs2070672 and NASH. The TA allele of rs2070673 is strongly associated with lobular inflammation and NASH, and this effect appears to be largely mediated by serum IP-10 levels.

Evaluation of alpha defensin, IL-1 receptor antagonist, and IL-18 levels in COVID-19 patients with macrophage activation syndrome and acute respiratory distress syndrome.

BackgroundMany laboratory parameters have been associated with morbidity and mortality in SARS‐CoV‐2 (COVID‐19), which emerged in an animal market in Wuhan, China in December 2019 and has infected over 20 million people. This study investigated the relationship between serum interleukin (IL)‐18, IL‐1 receptor antagonist (IL‐1Ra), and alpha defensin levels and the clinical course and prognosis of COVID‐19.Materials and MethodsThis study included 100 patients who were admitted to the chest diseases department and intensive care unit of our hospital and diagnosed with COVID‐19 by real‐time polymerase chain reaction (PCR) of nasopharyngeal swab samples between March 24 and May 31, 2020. The control group consisted of 50 nonsymptomatic health workers with negative real‐time PCR results in routine COVID‐19 screening in our hospital.ResultsSerum alpha defensin, IL‐1Ra, and IL‐18 levels were significantly higher in patients who developed macrophage activation syndrome (MAS) and acute respiratory distress syndrome (ARDS) compared to patients who did not (p < .001 for all). Alpha defensin, IL‐1Ra, and IL‐18 levels were significantly higher in COVID‐19 patients with and without MAS or ARDS when compared to the control group (p < .001 for all). When the 9 patients who died were compared with the 91 surviving patients, IL‐1Ra and IL‐18 levels were found to be significantly higher in the nonsurvivors (p < .001).ConclusionOur findings of correlations between alpha defensin and levels of IL‐1Ra and IL‐18, which were previously shown to be useful in COVID‐19 treatment and follow‐up, indicates that it may also be promising in treatment.

Activation of Toll-Like Receptor 3 Induces Interleukin-1 Receptor Antagonist Expression by Activating the Interferon Regulatory Factor 3

Toll-like receptor 3 (TLR3) is a sensor of endogenous cell necrosis during the process of acute inflammation. Interleukin (IL)-1 receptor antagonist (IL-1Ra) is an anti-inflammatory cytokine and can negatively regulate the pathogenesis of inflammation. However, whether and how activation of TLR3 can regulate IL-1Ra expression has not been clarified. Here, we show that poly(I:C) induces IL-1Ra expression in primarily cultured human fibroblast-like synoviocytes and other types of cells. Induction of IL-1Ra by poly(I:C) was dependent on TLR3, but was independent of melanoma differentiation-­associated protein 5 or retinoic acid-inducible gene I. Interferon regulatory factor 3 (IRF3) directly binds to the IL-1Ra promoter and promotes IL-1Ra expression in response to poly(I:C) stimulation. Induction of IL-1Ra by poly(I:C) was abolished by the inhibition of the NF-κB signaling, attenuated by the inhibition of the PI3K-Akt signaling, enhanced by inhibition of the ERK1/2 or MSK1/2 activation, but was independent of the p38 MAPK signaling. Treatment with poly(I:C) or Sendai virus elevated the levels of serum IL-1Ra in wild-type, but not in TLR3^–/– or IRF3^–/– mice. Our findings may provide new insights into the intrinsic anti-inflammatory function of TLR3 and double-stranded RNA-induced IL-Ra expression by TLR3 and its regulation.

The effects of aerobic exercise combined with resistance training on cardiovascular risk factors in obese adolescent males

Objective To explore the effect of 12 weeks of aerobic exercise combined with resistance training on the cardiovascular risk factors of obese adolescent men. Methods Thirty-six obese male adolescents (the obese group) and 36 age-matched normal-weight adolescent men (the control group) were recruited. Those in both groups maintained their routine eating habits. The obese group participated in a 12-week combined aerobic exercise and resistance training program. Markers of inflammation, blood lipids, insulin sensitivity, vascular endothelium function and body composition were measured before and after the intervention. Results Some in the obese group lost visceral fat mass (VFM) and some gained it. Before the intervention the average levels of serum interleukin-1 receptor antagonist (IL-1Ra), tumor necrosis factor-α, leptin, insulin, insulin resistance index (HOMA-IRI), high-sensitivity C-reactive protein, triglycerides, adiponectin and high-density lipoprotein cholesterol of the obese group were all significantly higher than those of the control group. After the intervention there had been significant decreases in the average levels of IL-1Ra, IFN-γ-inducible protein 10, insulin and HOMA-IRI, but no significant change in average body weight in the obese group as a whole. The group which lost VFM, however, showed greater improvement in triglycerides and insulin resistance than those who gained. Conclusions Twelve weeks of aerobic exercise combined with resistance training can reduce the inflammatory response and insulin resistance of obese adolescent men. The participants who lost more VFM after exercise improved their lipid profile and insulin sensitivity the most. Key words: Exercise; Obesity; Adolescents; Cardiovascular risk factors; Visceral fat

IL-1β predicts IVF outcome: a prospective study.

Retrospective cohort studies have shown a relationship between maternal serum interleukin-1β (IL-1β) and interleukin-1 receptor antagonist (IL-1Ra) levels and in vitro fertilization (IVF) cycle outcome. The objective of this investigation was to explore the correlation between serum IL-1β and/or IL-1Ra levels obtained prospectively and IVF outcomes. Sera from 205 women were collected just prior to initiation of their IVF cycle, at the time of human chorionic gonadotropin administration, day 24 of IVF cycle, day 28, and day 35. Sera were analyzed for IL-1β and IL-1Ra using commercially available ELISA kits. Cycle outcomes were followed prospectively. Data were analyzed using Friedman analysis of variance by ranks and chi-square analysis. Among women with a viable pregnancy, IL-1β serum levels increased over time for those that proceeded to deliver or had an ongoing pregnancy. There was no increase in serum levels for those with subsequent pregnancy loss. Of the women that had an embryo transfer, detectable IL-1β levels at the start of the cycle were associated with successful IVF outcome (p= 0.027). Of women with a positive pregnancy test, undetectable IL-1β at the start of the cycle were associated with subsequent pregnancy loss (p= 0.046). For all IL1-Ra serum analysis, there were no significant results. The increasing levels of IL-1β over time are consistent with the known role of the IL-1 cytokine family in implantation and pregnancy. Additionally, we confirm in a prospective investigation the positive relationship between detectable serum IL-1β at the start of IVF cycle and outcome.

Serum IL-1 Receptor Antagonist Concentrations Associate With Unfavorable Metabolic Features in 12-Year-Old Children.

ContextElevated IL-1 receptor antagonist (IL-1Ra) concentrations are associated with obesity, insulin resistance, and cardiovascular disease (CVD) risk in adults.ObjectiveTo determine if serum IL-1Ra and high-sensitivity C-reactive protein (hs-CRP) levels are associated with markers of reduced insulin sensitivity (IS) and serum lipids in 12-year-old children.Design and ParticipantsOf 191 children (n = 109 girls), 78 were categorized as having had birth weight and length appropriate for gestational age (AGA), 69 were small for gestational age, and 44 were AGA and from preeclamptic pregnancies. Serum markers of low-grade inflammation, IS, and lipids were measured. Quantitative Insulin Sensitivity Check Index (QUICKI) was calculated.ResultsMean serum IL-1Ra levels did not differ between the sexes or among the gestational categories. Children in the highest IL-1Ra tertile had lower QUICKI, IGF-binding protein-1, SHBG, and high-density lipoprotein cholesterol values; and higher body mass index (BMI), waist circumference to height ratio (WHtR), and serum insulin, hs-CRP, leptin, and triglyceride concentrations than those in the lowest IL-1Ra tertile. Logistic regression analysis showed higher serum hs-CRP and leptin levels, and WHtR were associated with high serum IL-1Ra levels. IL-1Ra concentration could be used to discriminate the children with lowest IS (area under the curve, 0.68; P < 0.001); hs-CRP level could not.ConclusionChildren with the highest IL-1Ra levels had lower IS, higher hs-CRP levels and BMI, and a less favorable lipid profile than those with the lowest IL-1Ra levels, suggesting that high IL-1Ra concentrations may be associated with increased CVD risk in 12-year-old children.

Interleukin 1 receptor antagonist (IL1RA) gene polymorphism and levels associated with adverse outcome in severe community-acquired pneumonia in children: A hospital-based study in India.

High morbidity and mortality due to community-acquired pneumonia (CAP) is seen in children under 5 years of age in India. Besides identified risk factors for CAP, there may be a phenotype-genotype association with cytokines, resulting in enhanced inflammatory response resulting in the adverse outcome (AO), namely complications and death. To assess the association of IL1RA gene polymorphism on serum levels of IL1RA and with AO in children under 5 years of age hospitalized with WHO-defined severe CAP. A prospective cohort study with nested case-control design conducted in a tertiary care teaching hospital after obtaining institutional ethical approval. Included were children between 2 and 59 months of age hospitalized with WHO-defined severe CAP with consistent radiological abnormalities. Excluded were those with suspected or proven cystic fibrosis, pulmonary tuberculosis, malignancy, immunodeficiency, and congenital heart disease. Polymerase chain reaction (PCR) was used to analyze the Variable Number of Tandem Repeats (VNTRs) of IL1RA gene polymorphism and ELISA test to detect serum levels of IL1RA. From 2014 to 2016, of 420 screened cases, 350 were eligible and included, of which 132 (37.7%) had no complication and 218 (62.3%) had AO, which included complications like empyema, pyopneumothorax, acute respiratory distress syndrome (ARDS), and septic shock of these 24 (6.9%) expired. Higher risk of AO was seen in A2A2 genotype (OR 11.18, p 0.0001) and lower in A1A1 genotype (OR 0.18, P < 0.0001). Serum IL1RA (ng/mL) was statistically significantly elevated in CAP with AO (2.55 ± 1.44) versus uncomplicated (0.87 ± 0.52) (P < 0.0001). In IL1RA gene, A1A1 genotype was associated with lower risk and A2A2 genotype with increased the risk of AO. Higher serum levels of IL1RA were found in A2A2 genotype indicating possibly enhanced inflammatory response resulting in AO of CAP.

Influence of exercise and dietary omega-3 oil supplementation on interleukin 1-Ra serum concentrations in Standardbred horses

In this study, the influence of fish oil eicosapentaenoic acid and docosahexaenoic acid supplementation on serum interleukin-1 receptor antagonist (IL-1Ra) concentrations was evaluated in horses subjected to a regular racing program. IL-1Ra is an anti-inflammatory protein. It binds to IL-1 receptors blocking the attachment of pro-inflammatory cytokines. Ten regularly trained Standardbred horses (6 geldings and 4 mares, 4–5 years old, mean bodyweight 500 ± 25 kg) were used. They were randomly divided in two equal groups. The experimental group received a supplementation of 70 mL of fish oil (Omega Horse; NBF Lanes, Milan, Italy) every day for 30 days. The control group did not receive any food supplement. Every 10 days (T0, T10, T20 and T30), the horses took part in a 1600-m harness race, and blood samples were collected from each horse before the race and after the race for the measurement of IL-1Ra serum concentration. The application of general linear model-multivariate analysis of variance (ANOVA) showed an effect of race and dietary supplementation. The effect of race on serum IL-1Ra concentrations was observed starting from T20. In particular, serum IL-1Ra showed higher values after the race in both groups at T20; whereas at T30, serum IL-1Ra values increased in the control group and decreased in the experimental group. The results obtained in the present study suggest that submaximal exercise induces an increase of IL-1Ra serum concentration after 20 days of a racing program. Fish oil supplementation had a positive effect on post-exercise response of serum IL-1Ra concentration compared with the unsupplemented control group, suggesting dietary fish oil reduces the response to inflammatory processes induced by physical activity.

Circulating Levels of Interleukin 1-Receptor Antagonist and Risk of Cardiovascular Disease: Meta-Analysis of Six Population-Based Cohorts.

Interleukin (IL)-1β represents a key cytokine in the development of cardiovascular disease (CVD). IL-1β is counter-regulated by IL-1 receptor antagonist (IL-1RA), an endogenous inhibitor. This study aimed to identify population-based studies on circulating IL-1RA and incident CVD in a systematic review, estimate the association between IL-1RA and incident CVD in a meta-analysis, and to test whether the association between IL-1RA and incident CVD is explained by other inflammation-related biomarkers in the MONICA/KORA Augsburg case-cohort study (Multinational Monitoring of Trends and Determinants in Cardiovascular Disease/Cooperative Health Research in the Region of Augsburg). We performed a systematic literature search and identified 5 cohort studies on IL-1RA and incident CVD in addition to the MONICA/KORA Augsburg case-cohort study for a meta-analysis based on a total of 1855 CVD cases and 18 745 noncases with follow-up times between 5 and 16 years. The pooled standardized hazard ratio (95% confidence interval) for incident CVD was 1.11 (1.06-1.17) after adjustment for age, sex, anthropometric, metabolic, and lifestyle factors (P<0.0001). There was no heterogeneity in effect sizes (I2=0%; P=0.88). More detailed analyses in the MONICA/KORA study showed that the excess risk for CVD was attenuated by ≥10% after additional separate adjustment for serum levels of high-sensitivity C-reactive protein, IL-6, myeloperoxidase, soluble E-selectin, or soluble intercellular adhesion molecule-1. Serum IL-1RA levels were positively associated with risk of CVD after adjustment for multiple confounders in a meta-analysis of 6 population-based cohorts. This association may at least partially reflect a response to triggers inducing subclinical inflammation, oxidative stress, and endothelial activation.

Assessment of serum interleukin-1receptor antagonist (IL-1RN) levels in overweight-obese women and its relation to the cardiovascular risk using Framingham score

Assessment of serum interleukin-1receptor antagonist (IL-1RN) levels in overweight-obese women and its relation to the cardiovascular risk using Framingham score

Effect of serum interleukin-1 receptor antagonist level on survival of patients with non-small cell lung cancer.

Due to poor prognosis in advanced non-small cell lung cancer (NSCLC), new effective markers are required in the monitoring of the disease. The present study aimed to investigate the association between the serum IL-1 receptor antagonist (IL-1Ra) level, overall survival (OS), and treatment response in NSCLC, and to evaluate the usefulness of the serum IL-1Ra level as a prognostic marker for NSCLC. Eighty patients (72 men and 8 women) and 40 healthy volunteers (13 men and 27 women) were included in the present study. The median progression-free survival was 16 weeks for patients with high serum IL-1Ra levels, and 35 weeks for patients with low serum IL-1Ra levels (P=0.027). The median OS was 38 weeks in patients with a high serum IL-1Ra level, and 62 weeks in patients with a low serum IL-1Ra level (P=0.065). The results of the present study have demonstrated that there was a significant correlation between IL-1Ra levels and NSCLC progression and survival, although the correlation between IL-1Ra levels and the response to treatment was not statistically significant. Therefore, the pre-treatment IL-1Ra level has been identified as a putative prognostic factor for NSCLC.

Serum levels of interleukin-22, cardiometabolic risk factors and incident type 2 diabetes: KORA F4/FF4 study

AimsInterleukin-22 (IL-22) has beneficial effects on body weight, insulin resistance and inflammation in different mouse models, but its relevance for the development of type 2 diabetes in humans is unknown. We aimed to identify correlates of serum IL-22 levels and to test the hypothesis that higher IL-22 levels are associated with lower diabetes incidence.MethodsCross-sectional associations between serum IL-22, cardiometabolic risk factors and glucose tolerance status were investigated in 1107 persons of the population-based KORA F4 study. The prospective association between serum IL-22 and incident type 2 diabetes was assessed in 504 initially non-diabetic study participants in both the KORA F4 study and its 7-year follow-up examination KORA FF4, 76 of whom developed diabetes.ResultsMale sex, current smoking, lower HDL cholesterol, lower estimated glomerular filtration rate and higher serum interleukin-1 receptor antagonist were associated with higher IL-22 levels after adjustment for confounders (all P < 0.05). Serum IL-22 showed no associations with glucose tolerance status, prediabetes or type 2 diabetes. Baseline serum IL-22 levels (median, 25th/75th percentiles) for incident type 2 diabetes cases and non-cases were 6.28 (1.95; 12.35) and 6.45 (1.95; 11.80) pg/ml, respectively (age and sex-adjusted P = 0.744). The age and sex-adjusted OR (95% CI) per doubling of IL-22 for incident type 2 diabetes of 1.02 (0.85; 1.23) was almost unchanged after consideration of further confounders.ConclusionsHigh serum levels of IL-22 were positively rather than inversely associated with several cardiometabolic risk factors. However, these associations did not translate into an increased risk for type 2 diabetes. Thus, our data argue against the utility of IL-22 as biomarker for prevalent or incident type 2 diabetes in humans, but identify potential determinants of IL-22 levels which merits further research in the context of cardiovascular diseases.

Correlation between serum interleukin-1 receptor antagonist and disease severity in patients with HBV-related liver failure

Correlation between serum interleukin-1 receptor antagonist and disease severity in patients with HBV-related liver failure

IL-1 receptor antagonist levels are associated with glucose tolerance in polycystic ovary syndrome.

To investigate serum interleukin-1 receptor antagonist (IL-1Ra) levels in women with polycystic ovary syndrome (PCOS). Serum IL-1Ra levels were measured at baseline in 73 women with PCOS and 45 control subjects (18-47 years), and in 27 women with PCOS who underwent oral and intravenous glucose tolerance tests (OGTTs and IVGTTs). IL-1Ra concentrations predicted OGTT 2-h glucose levels independently of BMI and insulin resistance (P ≤ 0·001) in women with PCOS. Serum IL-1Ra concentration was elevated in women with PCOS compared with controls [mean (SD): 309·5 (208·8) vs 199·1 (81·4) ng/l, P < 0·001], but the difference disappeared after adjusting for BMI. An increment of five BMI units raised IL-1Ra levels by 108·5 ng/l [95% confidence interval (CI): 85·5-131·5, r(2) = 0·603] in women with PCOS and only by 77·0 ng/l (95% CI: 50·5-103·5, r(2) = 0·512) in controls when adjusted for BMI and age. Levels of IL-1Ra in obese women with PCOS reflected decreasing OGTT-derived insulinogenic index (P = 0·032) and disposition index (P = 0·046) independently of BMI. Increased levels of IL-1Ra correlated with indices showing increasing insulin resistance and AUC insulin (P ≤ 0·002). Increased IL-1Ra levels in women with PCOS were largely explained by increasing adiposity. However, serum IL-1Ra concentrations predicted 2-h glucose levels independently of BMI suggesting that increased IL-1Ra may be associated with disturbed glucose metabolism.