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

Published on Oct 1, 2015in Cytokine3.078
· DOI :10.1016/j.cyto.2015.05.005
Dov B. Ballak6
Estimated H-index: 6
(Radboud University Nijmegen),
Rinke Stienstra31
Estimated H-index: 31
(Radboud University Nijmegen)
+ 2 AuthorsJ.A. van Diepen2
Estimated H-index: 2
(Radboud University Nijmegen)
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.
  • References (174)
  • Citations (66)
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References174
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#1M.G. NeteaH-Index: 6
Last. Lieke JoostenH-Index: 20
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Induction, production, and release of proinflammatory cytokines are essential steps to establish an effective host defense. Cytokines of the interleukin-1 (IL-1) family induce inflammation and regulate T lymphocyte responses while also displaying homeostatic and metabolic activities. With the exception of the IL-1 receptor antagonist, all IL-1 family cytokines lack a signal peptide and require proteolytic processing into an active molecule. One such unique protease is caspase-1, which is activat...
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#1Suzhao Li (University of Colorado Denver)H-Index: 9
#2C. Preston Neff (University of Colorado Denver)H-Index: 14
Last. Charles A. Dinarello (Radboud University Nijmegen)H-Index: 179
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Interleukin-1 family members are highly inflammatory but IL-37 member broadly suppresses inflammation and specific immunity. Initially, the mechanism of this suppression was shown to be via translocation to the nucleus following cleavage of the precursor by intracellular caspase-1. We now show that recombinant forms of IL-37 limit inflammation by extracellular binding to surface receptors but require the IL-1 family decoy receptor IL-1R8. Unexpectedly, picomolar concentrations of the IL-37 precu...
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#2Justin I. Odegaard (UCSF: University of California, San Francisco)H-Index: 28
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