IL-1 Receptor Antagonist (IL-1Ra) Levels and Management of Metabolic Disorders

Abstract

Low-grade inflammation is a major player in obesity and the metabolic syndrome predicting development of type 2 diabetes (T2DM). The interleukin-1 receptor antagonist (IL-1Ra) is a vital and natural anti-inflammatory factor and mediator in glucose homeostasis disturbances. The predictive role is independent of multiple confounders, and elevated levels appear few years before T2DM. The role of IL-1Ra is important for accumulated risk factors, dysregulated metabolism and glucose homeostasis, and dietary interventions. Longitudinal and cross-sectional population study cohorts have enabled the approximation of IL-1Ra limit values for metabolic dysregulation and guide further analysis as a potential biomarker. The limit value of IL-1Ra is reaching 400 pg/mL with prediabetes and before T2DM. However, subjects with metabolic syndrome are suggested to have lower limit values, especially among men. Future research may evaluate the role of IL-1Ra in actual glucose homeostasis together with routine fasted laboratory tests, such as glucose and C-reactive protein (CRP) instead of the oral glucose tolerance test. The significance of intermediate low IL-1Ra levels in metabolic abnormalities should be further analyzed. It is possible to specify the impact of multiple lifestyle and metabolic parameters together with age and sex. IL-1Ra could be studied in multiple approaches including interventional studies of metabolic diseases.

Rich Oleocanthal and Oleacein Extra Virgin Olive Oil and Inflammatory and Antioxidant Status in people with Obesity and Prediabetes. The APRIL Study: a Randomised, Controlled Crossover Study

“…and IL-1β signalling [35]. While the increase in CXCL1 after olive oil treatments is puzzling given the current lack of studies on the role of this small peptide in obesity and diabetes pathogenesis [33], those of IL-12p40 and IL-1RA fits well with an antiinflammatory effect mediated by blockage of pro-inflammatory signalling through IL-12 and IL-1 receptors, respectively [34,35].…”

“…In addition, IL-12p40 provides a negative feedback loop by competitively binding the pro-inflammatory IL-12 receptor [34]. On the other side, IL-1RA is a natural anti-inflammatory factor and mediator in glucose homeostasis disturbances that blocks IL-1α and IL-1β signalling[35]. While the increase in CXCL1 after olive oil treatments is puzzling given the current lack of studies on the role of this small peptide in obesity and diabetes pathogenesis[33], those of IL-12p40 and IL-1RA fits well with an anti-inflammatory effect mediated by blockage of pro-inflammatory signalling through IL-12 and IL-1 receptors, respectively[34,35].…”

“…On the other side, IL-1RA is a natural anti-inflammatory factor and mediator in glucose homeostasis disturbances that blocks IL-1α and IL-1β signalling[35]. While the increase in CXCL1 after olive oil treatments is puzzling given the current lack of studies on the role of this small peptide in obesity and diabetes pathogenesis[33], those of IL-12p40 and IL-1RA fits well with an anti-inflammatory effect mediated by blockage of pro-inflammatory signalling through IL-12 and IL-1 receptors, respectively[34,35]. Interestingly, IL-12p40 has also been found to suppress IFN-γ secretion [36], a cytokine produced during chronic inflammation and also related to the events initiating obesity-induced adipose tissue inflammation and insulin resistance[37].…”

Changes in novel anti-infalmmatory cytokine concetration in the bood of endurance and race horses at different levels of training

“…However, it was suggested that IL-1ra reduces insulin sensitivity in rats through a muscle-specific decrease in glucose uptake [37] . In obese humans, markedly increased plasma levels of IL-1ra might contribute to the development of insulin resistance [38] . However, IL-1ra correlation with the insulin resistance in obesity is probably connected with high levels of IL-1.…”

Disease Activity Is More Associated with IL-1 Than with IL-6 in Patients with Rheumatoid Arthritis

“…The pooled estimate of IL-6, in the general population, has been described in a recent meta-analysis as 5.186 pg/mL (95%CI: 4.631, 5.740) [ 24 ]. Similarly, IL-1ra has been estimated as 248 (95%CI: 244, 252) pg/mL [ 25 ]. However, we did not aim to compare serum levels of both cytokines between patients and controls, but rather to study the association of these cytokines with disease activity.…”