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

The Journal of Biological Chemistry
Dov B BallakCharles A Dinarello

Abstract

Obesity and the metabolic syndrome are characterized by chronic, low-grade inflammation mainly originating from expanding adipose tissue and resulting in inhibition of insulin signaling and disruption of glycemic control. Transgenic mice expressing human interleukin 37 (IL-37), an anti-inflammatory cytokine of the IL-1 family, are protected against metabolic syndrome when fed a high-fat diet (HFD) containing 45% fat. Here, we examined whether treatment with recombinant IL-37 ameliorates established insulin resistance and obesity-induced inflammation. WT mice were fed a HFD for 22 weeks and then treated daily with IL-37 (1 μg/mouse) during the last 2 weeks. Compared with vehicle only-treated mice, IL-37-treated mice exhibited reduced insulin in the plasma and had significant improvements in glucose tolerance and in insulin content of the islets. The IL-37 treatment also increased the levels of circulating IL-1 receptor antagonist. Cultured adipose tissues revealed that IL-37 treatment significantly decreases spontaneous secretions of IL-1β, tumor necrosis factor α (TNFα), and CXC motif chemokine ligand 1 (CXCL-1). We also fed mice a 60% fat diet with concomitant daily IL-37 for 2 weeks and observed decreased secretion of IL-1β, ...Continue Reading

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Citations

Aug 4, 2018·International Journal of Molecular Sciences·Eline N KuipersMariëtte R Boon
Feb 23, 2019·Proceedings of the National Academy of Sciences of the United States of America·Suzhao LiCharles A Dinarello
Jun 30, 2019·European Journal of Immunology·Yasmina E Hernandez-SantanaPatrick T Walsh
Sep 11, 2019·Nature Reviews. Immunology·Marc Y DonathThomas Mandrup-Poulsen
Nov 22, 2018·Frontiers in Pharmacology·Giulio Cavalli, Charles A Dinarello
Sep 14, 2019·Nature Reviews. Rheumatology·Charles Anthony Dinarello
Oct 21, 2020·Expert Opinion on Drug Safety·Giulio CavalliLorenzo Dagna
Jan 25, 2021·QJM : Monthly Journal of the Association of Physicians·Sara McCurdyWilliam A Boisvert
Apr 10, 2021·Frontiers in Immunology·Giacomo De LucaMarco Matucci-Cerinic
Apr 8, 2021·Cell Reports·Giulio CavalliCharles A Dinarello
Jun 15, 2021·Frontiers in Cardiovascular Medicine·Hayder M Al-KuraishyGaber El-Saber Batiha
Jul 13, 2021·Frontiers in Immunology·Zhangci Su, Xiaoan Tao
Jul 28, 2021·Advanced Drug Delivery Reviews·Virender KumarRam I Mahato
Aug 10, 2021·Frontiers in Immunology·Danielle M SantarelliMarc A Russo

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