IL-1 family members in the pathogenesis and treatment of metabolic disease: Focus on adipose tissue inflammation and insulin resistance

Abstract

Obesity is characterized by a chronic, low-grade inflammation that contributes to the development of insulin resistance and type 2 diabetes. Cytokines and chemokines produced by immunocompetent cells influence local as well as systemic inflammation and are therefore critical contributors to the pathogenesis of type 2 diabetes. Hence, cytokines that modulate inflammatory responses are emerging as potential targets for intervention and treatment of the metabolic consequences of obesity. The interleukin-1 (IL-1) family of cytokines and receptors are key mediators of innate inflammatory responses and exhibit both pro- and anti-inflammatory functions. During the last decades, mechanistic insights into how the IL-1 family affects the initiation and progression of obesity-induced insulin resistance have increased significantly. Here, we review the current knowledge and understanding, with emphasis on the therapeutic potential of individual members of the IL-1 family of cytokines for improving insulin sensitivity in patients with diabetes.

Interleukin-37 treatment of mice with metabolic syndrome improves insulin sensitivity and reduces pro-inflammatory cytokine production in adipose tissue

“…Insulin resistance and glucose intolerance are strongly linked to adipose tissue inflammation (11,28,29). Therefore, we determined whether administration of IL-37 affected adipose tissue secretion of cytokines after 22 weeks of HFD.…”

“…The interleukin-1 family of cytokines plays a critical role in the regulation of metabolic inflammation (11), particularly by pro-inflammatory members IL-1a (12)(13)(14) and IL-1b (15,16). In contrast, the IL-1 Receptor antagonist (IL1Ra), also a member of the IL-1 family, represents an endogenous mechanism to reduce IL-1-driven inflammation (17)(18)(19).…”

Az oxidatív stressz szerepe a diabeteses neuropathia kialakulásában

“…Magasabb IL-1b-, IL-6-és TNF-α-szintek mérhetők T2DM-betegeknél, és össze-függés mutatható ki e gyulladásos markerek és a DN incidenciája között [14,26]. A hyperglykaemia indukálta alternatív anyagcsere-útvonalakon több proinflammatorikus anyag (például NF-κB, TGF-β, TNF-α stb.)…”

MECHANISMS IN ENDOCRINOLOGY: Metabolic and inflammatory pathways on the pathogenesis of type 2 diabetes

“…Several studies have used different approaches to inhibit IL1b as an attempt to modify the course of metabolic disorders. The natural endogenous inhibitor IL1Ra (IL1b receptor antagonist), produced by healthy resting cells, binds to IL1R1 and blocks the interaction and signal transduction of IL1b (125). The use of a recombinant IL1Ra (anakinra) or IL1b antagonists (gevokizumab, canakizumab and LY2189102) improved insulin sensitivity, reduced inflammation markers, corrected glycated haemoglobin levels and improved b-cell function in patients with T2D (126,127).…”