Serum Levels Of Interleukin-1 Receptor Antagonist Research Articles

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.

Serum cytokine, chemokine, and growth factor profiles and their modulation in inflammatory bowel disease

Ulcerative colitis (UC) and Crohn disease (CD) are the most common forms of inflammatory bowel disease (IBD). Because these subtypes of IBD are characterized by periods of activity and remission, an understanding of the modulation of biochemical markers with the clinical features of IBD or its treatment, may be useful for determining the correct treatment protocol.This study aimed to evaluate the serum levels of 27 protein biomarkers to determine their association with IBD, correlation with clinical findings of disease, and modulation according to the pharmacologic therapy.A case–control study was carried out in Zacatecas, Mexico. The 27 protein profiles of serum from 53 participants (23 UC, 11 CD, and 19 controls) were evaluated using the Pro Human Cytokine 27-Plex immunoassay (Bio-Rad).Considering the controls as a reference, the group with IBD endoscopic activity showed higher serum levels of granulocyte colony-stimulating factor (G-CSF), interleukin 1 receptor antagonist (IL-1Ra), and platelet-derived growth factor BB (PDGF-BB) (P < .05). Interferon-induced protein 10 (IP-10) was associated with extraintestinal symptoms of disease (P = .041). Both PDGF-BB and interleukin 6 (IL-6) showed the strongest correlations with clinical features of IBD. Levels of IL-6, IL-7, and monocyte chemoattractant protein 1 were higher with 5-aminosalicylic acid (5-ASA) + Azathioprine therapy than controls (P < .05). Combined therapy with 5-ASA + Adalimumab led to the strongest changes in marker modulation: IL-4, IL-5, IL-15, and PDGF-BB, were upregulated (P < .05).Elevated serum levels of G-CSF, IL-1Ra, and PDGF-BB were associated with IBD endoscopic activity, and of IP-10 with extraintestinal manifestations of IBD. Combined therapy of 5-ASA + Adalimumab produced significant upregulation of IL-4, IL-5, IL-15, and PDGF-BB. This information may be useful for deciding on the course of pharmacologic therapy for patients with IBD and for generating new therapy alternatives to improve the outcome of patients with IBD.

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.

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.

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.

Elevated serum levels of IL-2R, IL-1RA, and CXCL9 are associated with a poor prognosis in follicular lymphoma

AbstractSerum cytokines and chemokines may reflect tumor biology and host response in follicular lymphoma (FL). To determine whether the addition of these biological factors may further refine prognostication, 30 cytokines and chemokines were measured in pretreatment serum specimens from newly diagnosed FL patients (n = 209) and from 400 matched controls. Cytokine levels were correlated with clinical outcome in patients who were observed or received single agent rituximab, or those who received chemotherapy. Correlations with outcome in chemotherapy treated patients were further examined in a separate cohort of 183 South West Oncology Group (SWOG) patients and all patients were then included in a meta-analysis. Si’cytokines were associated with outcome in the Molecular Epidemiology Resource (MER) after adjusting for the FL international prognostic index. In patients who were observed or treated with rituximab alone, increased serum IL-12 and interleukin 1 receptor antagonist (IL-1RA) (P = .005 and .02) were associated with a shorter event-free survival. In patients receiving chemotherapy, hepatocyte growth factor, IL-8, IL-1RA, and CXCL9 (P = .015, .048, .004, and .0005) predicted a shorter EFS. When the MER chemotherapy treated patients and SWOG patients were combined in a meta-analysis, IL-2R, IL-1RA, and CXCL9 (P = .013, .042, and .0012) were associated with a poor EFS.

The relationship between interleukin‐1 receptor antagonist and cognitive function in older adults with bipolar disorder

Cognitive impairments are a feature of bipolar disorder (BD) and could be worsened by inflammatory cytokines. We determined whether (i) serum interleukin-1 receptor antagonist (IL-1RA) was increased in elderly BD subjects; (ii) whether IL-1RA was associated with worse neurocognitive function; and (iii) whether IL-1RA was associated with white matter integrity. Twenty-one euthymic BD patients (65 +/- 9 years) with serum available for IL-1RA measures by enzyme-linked immunoassays were compared with 26 similarly aged control participants. Four factor analysis-derived z-scores and a global z-score were obtained from a battery of 21 neurocognitive tests. Diffusion tensor images were used to obtain fractional anisotropy (FA), and an automated labeling pathway algorithm was used to obtain white matter hyperintensity burden. Interleukin-1 receptor antagonist was elevated in BD subjects compared with controls (439+/-326 pg/mL vs. 269+/-109 pg/mL; p = 0.004). Moreover, IL-1RA was inversely correlated with three cognitive function factors and global cognition (r = -0.37; p = 0.01). IL-1RA continued to correlate with global cognitive function even when covarying for either IL-6 or brain-derived neurotrophic factor. Although FA was lower in BD subjects (0.368 +/- 0.02 vs. 0.381 +/- 0.01; p = 0.02), IL-1RA was not associated with FA or white matter hyperintensity burden. Elevated serum levels of IL-1RA in BD subjects, even during euthymic states, were associated with worse cognitive function. This association was not explained by co-occurring increases in IL-6, by decreased brain-derived neurotrophic factor, nor by measures of white matter integrity. These cross-sectional findings support the possibility that the IL-1 family may contribute to cognitive impairments in BD.

Interleukin-1β and Interleukin-1 receptor antagonist serum levels one week after embryo transfer may predict ectopic pregnancy in IVF cycles

Previous studies have suggested that interleukin1system functions are relevant to IVF success. We investigated whether Interleukin-1β (IL-1B) and Interleukin-1 receptor antagonist (IL-1RA) serum levels in early luteal phase were predictive of IVF cycle outcomes.

Interleukin-6, interleukin-1 beta and interleukin-1 receptor antagonist levels in epileptic seizures

PurposeData are accumulating to support the involvement of inflammatory mechanisms in the pathogenesis and course of epilepsy. MethodsThe aim of this study was to examine seizure-induced changes in plasma concentrations of interleukin-6 (IL-6), interleukin-1 receptor antagonist (IL-1Ra), and interleukin-1 beta (IL-1β) in 23 patients with epilepsy undergoing a video-electroencephalography (EEG) study. Patients were divided into groups based on epilepsy type as follows: temporal lobe epilepsy (TLE) (n=6), extra-temporal lobe epilepsy (XLE) (n=8) and idiopathic generalised epilepsy (IGE) (n=9). Serum levels of IL-1β, IL-1Ra and IL-6 were measured at baseline, immediately after the epileptic seizure, and at 3h, 6h, 12h and 24h after the seizure. ResultsWe demonstrated a significant increase in plasma levels of IL-6 and IL-1Ra that peaked at 12h into the post-ictal period (p<0.05). IL-1β levels did not differ from the baseline levels. We did not observe any differences in post-ictal cytokine release patterns between the TLE, XLE and IGE groups. ConclusionThe present study confirms the findings that epileptic seizures induce the production of IL-6 and IL-1Ra.

In Enterovirus 71 Encephalitis With Cardio-Respiratory Compromise, Elevated Interleukin 1 , Interleukin 1 Receptor Antagonist, and Granulocyte Colony-Stimulating Factor Levels Are Markers of Poor Prognosis

Enterovirus 71 (EV71) causes large outbreaks of hand, foot, and mouth disease (HFMD), with severe neurological complications and cardio-respiratory compromise, but the pathogenesis is poorly understood. We measured levels of 30 chemokines and cytokines in serum and cerebrospinal fluid (CSF) samples from Malaysian children hospitalized with EV71 infection (n = 88), comprising uncomplicated HFMD (n = 47), meningitis (n = 8), acute flaccid paralysis (n = 1), encephalitis (n = 21), and encephalitis with cardiorespiratory compromise (n = 11). Four of the latter patients died. Both pro-inflammatory and anti-inflammatory mediator levels were elevated, with different patterns of mediator abundance in the CSF and vascular compartments. Serum concentrations of interleukin 1β (IL-1β), interleukin 1 receptor antagonist (IL-1Ra), and granulocyte colony-stimulating factor (G-CSF) were raised significantly in patients who developed cardio-respiratory compromise (P = .013, P = .004, and P < .001, respectively). Serum IL-1Ra and G-CSF levels were also significantly elevated in patients who died, with a serum G-CSF to interleukin 5 ratio of >100 at admission being the most accurate prognostic marker for death (P < .001; accuracy, 85.5%; sensitivity, 100%; specificity, 84.7%). Given that IL-1β has a negative inotropic action on the heart, and that both its natural antagonist, IL-1Ra, and G-CSF are being assessed as treatments for acute cardiac impairment, the findings suggest we have identified functional markers of EV71-related cardiac dysfunction and potential treatment options.

Effects of Sleep Deprivation on Nocturnal Cytokine Concentrations in Depressed Patients and Healthy Control Subjects

Previous studies have reported alterations of cytokine and cytokine-receptor concentrations in psychiatric patient populations, including patients with major depressive disorder (MDD). However, study results are conflicting, and possible causes for these abnormalities are unknown. Since sleep deprivation may induce a rapid improvement of mood in depressed patients, the authors investigated the impact of total sleep deprivation (TSD) for one night, and subsequent recovery sleep, on nocturnal concentrations of interleukin-6 (IL-6), interleukin-1-receptor antagonist (IL-1RA), and soluble IL-2 receptor (sIL-2R) in 15 unmedicated patients with MDD and 16 healthy volunteers. Whereas IL-6 levels normalized again during the recovery night in depressed patients, they were still elevated in control subjects. Serum levels of IL-1RA were higher in depressed patients than in controls, but were not affected by TSD. During recovery sleep, IL-1RA levels increased as compared with the preceding TSD night only in controls. Responders (N=8) differed from nonresponders (N=7) to TSD with regard to IL-1RA, which increased significantly during TSD in responders only. Sleep deprivation therefore seems to significantly affect cytokine levels in both depressed patients and healthy subjects, but does so in different ways. Sleep disturbances in depressed patients could account for the increased levels of cytokines found in these patients in several previous studies. The interaction between antidepressant effects of TSD and alterations of cytokines warrants further investigation.

Serum interleukin 1 receptor antagonist as an independent marker of non-alcoholic steatohepatitis in humans

Mechanisms leading to non-alcoholic steatohepatitis (NASH) have remained unclear, and non-invasive diagnosis of NASH is challenging. In this study, we investigated the benefits of measuring serum interleukin 1 receptor antagonist (IL-1RA) levels. Liver biopsies from 119 morbidly obese individuals (47.5 ± 9.0 years, BMI 44.9 ± 5.9 kg/m(2)) were used for histological and gene expression assessment. In a cross-sectional population-based cohort of 6447 men (58 ± 7 years, BMI 27.0 ± 3.9 kg/m(2)) the association of serum IL1-RA with serum alanine aminotransferase (ALT) levels was investigated. Serum levels of IL-1RA, and liver mRNA expression of IL1RN are associated with NASH and the degree of lobular inflammation in liver (p<0.05). The decrease in serum IL-1RA level and expression of IL1RN after obesity surgery correlated with the improvement of lobular inflammation (p<0.05). We developed a novel NAFLD Liver Inflammation Score, including serum Il-1RA concentration, which performed better to diagnose NASH than did previously published scores. Results from the population study confirmed the potential of measuring serum IL-1RA level. The strongest determinants of the ALT concentration at the population level were Matsuda insulin sensitivity index (r(2)=0.130, p=7 × 10(-197)) and serum IL-1RA concentration (r(2)=0.074, p=1 × 10(-110)). IL-1RA concentrations associated significantly with ALT levels even after adjusting for BMI, alcohol consumption and insulin sensitivity (p=2 × 10(-21)). IL-1RA serum levels associate with liver inflammation and serum ALT independently of obesity, alcohol consumption and insulin resistance, suggesting a potential use of IL-1RA as a non-invasive inflammatory marker for NASH.

Measurement of interleukin-1 receptor antagonist in patients with systemic lupus erythematosus could predict renal manifestation of the disease

Interleukin-1 receptor antagonist (IL-1Ra) is a good indicator of disease activity in patients with systemic lupus erythematosus (SLE). Glucocorticosteroids are the most frequently used drugs in SLE. Our goal was to compare IL-1Ra activity in SLE patients with and without renal involvement and to determine the effect of different dosage of glucocorticosteroids used in 17 patients with active SLE without nephritis, 7 patients with inactive lupus nephritis (LN), and 8 patients with active LN, along with 10 healthy controls. IL-1Ra levels were measured in the serum of SLE patients by Human Luminex [100] analyzer. Both in patients with active SLE without nephritis and in patients with LN, serum levels of IL-1Ra ( p<0.001) were significantly higher compared with those in the controls. IL-1Ra was significantly higher in patients with active LN than in patients with inactive LN ( p = 0.028). The use of methylprednisolone was significantly higher in the active LN group compared with the inactive LN group ( p = 0.013). SLE patients with higher IL-1Ra are at lower risk for developing nephritis. The higher doses of glucocorticosteroids needed in active LN could be due to steroid resistance and IL-1Ra polymorphism. Measurement of IL-1Ra levels in SLE patients could help to predict future renal involvement.

Accelerated Increase in Serum Interleukin-1 Receptor Antagonist Starts 6 Years Before Diagnosis of Type 2 Diabetes

OBJECTIVEAlthough interleukin-1 receptor antagonist (IL-1Ra) treatment is associated with improved β-cell function and glycemic control in patients with type 2 diabetes, its role in the development of type 2 diabetes remains unclear. We used repeated measurements to characterize IL-1Ra trajectories in individuals who developed type 2 diabetes.RESEARCH DESIGN AND METHODSThis case-cohort study, nested within the Whitehall II cohort, was based on 335 incident type 2 diabetes cases and 2,475 noncases. We measured serum IL-1Ra levels at up to three time points per individual and estimated retrospective trajectories of IL-1Ra before diabetes diagnosis (case subjects) or end of follow-up (control subjects) using multilevel analysis. Models were adjusted for age, sex, and ethnicity.RESULTSIL-1Ra levels were already higher in the case than control subjects 13 years before diabetes diagnosis/end of follow-up (mean [95% CI] 302 [290–314] vs. 244 [238–249] pg/ml). In control subjects, IL-1Ra levels showed a modest linear increase throughout the study period. In case subjects, IL-1Ra trajectories were parallel to those in control subjects until 6 years (95% CI 7.5–4.5) before diagnosis and then rose steeply to 399 (379–420) pg/ml at the time of diagnosis (P < 0.0001 for slope difference). Adjustment for BMI and waist circumference as time-varying covariates had little impact on these trajectories.CONCLUSIONSWe show elevated IL-1Ra levels for 13 years and an accelerated increase during the last 6 years before type 2 diabetes diagnosis, indicating the presence of an anti-inflammatory response that may act to counterbalance the metabolic and immunologic disturbances that precede type 2 diabetes.

Sustained Effects of Interleukin-1 Receptor Antagonist Treatment in Type 2 Diabetes

OBJECTIVEInterleukin (IL)-1 impairs insulin secretion and induces β-cell apoptosis. Pancreatic β-cell IL-1 expression is increased and interleukin-1 receptor antagonist (IL-1Ra) expression reduced in patients with type 2 diabetes. Treatment with recombinant IL-1Ra improves glycemia and β-cell function and reduces inflammatory markers in patients with type 2 diabetes. Here we investigated the durability of these responses.RESEARCH DESIGN AND METHODSAmong 70 ambulatory patients who had type 2 diabetes, A1C >7.5%, and BMI >27 kg/m2 and were randomly assigned to receive 13 weeks of anakinra, a recombinant human IL-1Ra, or placebo, 67 completed treatment and were included in this double-blind 39-week follow-up study. Primary outcome was change in β-cell function after anakinra withdrawal. Analysis was done by intention to treat.RESULTSThirty-nine weeks after anakinra withdrawal, the proinsulin-to-insulin (PI/I) ratio but not stimulated C-peptide remained improved (by −0.07 [95% CI −0.14 to −0.02], P = 0.011) compared with values in placebo-treated patients. Interestingly, a subgroup characterized by genetically determined low baseline IL-1Ra serum levels maintained the improved stimulated C-peptide obtained by 13 weeks of IL-1Ra treatment. Reductions in C-reactive protein (−3.2 mg/l [−6.2 to −1.1], P = 0.014) and in IL-6 (−1.4 ng/l [−2.6 to −0.3], P = 0.036) were maintained until the end of study.CONCLUSIONSIL-1 blockade with anakinra induces improvement of the PI/I ratio and markers of systemic inflammation lasting 39 weeks after treatment withdrawal.

Clinical utility of serum Interleukin-1 receptor antagonist levels as a diagnostic and prognostic assay in surgical patients

Clinical utility of serum Interleukin-1 receptor antagonist levels as a diagnostic and prognostic assay in surgical patients

Gender-based dimorphic pattern for interleukin-1 receptor antagonist in type 2 diabetes mellitus

Adipose tissue secretes a variety of cytokines, some of which are increased in the serum of obese patients. The anti-inflammatory interleukin-1 receptor antagonist (IL-1Ra) is the most highly elevated known cytokine in human obesity, and its serum levels are strongly associated with the degree of insulin resistance in non-diabetic patients. Aim The present study examined serum levels of IL-1Ra in type 2 diabetic patients (T2DM) and their relationships with three other adipokines (leptin, interleukin-6 [IL-6], adiponectin). Their correlation with anthropometric and biochemical variables was examined, as well as their intraindividual fluctuations. Methods Fifty T2DM patients, aged 58 ± 13 years, were consecutively recruited among those electively hospitalized for a one-week intensive training course with our Diabetes Education Service. Anthropometric measurements and blood samples were taken after an overnight fast on admission (baseline) and after four days. Results Mean serum levels of IL-1Ra and leptin, but not of IL-6 and adiponectin, were significantly higher in women than in men ( P < 0.0006), and this difference persisted after correction for body mass index (BMI) ( P < 0.0004). In addition, IL-1Ra and leptin were strongly correlated with the BMI ( P < 0.0004). By contrast, no significant correlations were observed between IL-1Ra and glucose-control parameters. Finally, all four adipokines exhibited wide interindividual variability, but with limited intraindividual fluctuations over the short time period. Conclusion IL-1Ra, leptin and adiponectin serum levels exhibit marked interindividual variation with high intraindividual consistency. A gender-based dimorphic pattern for IL-1Ra, independent of the degree of adiposity and glucose control, was also found.