The emerging role of interleukin-37 in cardiovascular diseases

Immun Inflamm Dis. 2017 Sep;5(3):373-379. doi: 10.1002/iid3.159. Epub 2017 May 26.

Abstract

Introduction: Interleukin (IL)-37 is a newly identified member of the IL-1 family, and shows a growing role in a variety of diseases. This review aims at summarizing and discussing the role of IL-37 in cardiovascular diseases.

Methods: Data for this review were identified by searches of MEDLINE, Embase, and PubMed using appropriate search terms.

Results: IL-37 is a newly identified cytokine belonging to the IL-1 family and is expressed in inflammatory immune cells and several parenchymal cells. It has potent anti-inflammatory and immunosuppressive properties, with two mechanisms underlying this function. IL-37 is produced as a precursor and then cleaved into mature form in the cytoplasm by caspase-1, translocating to nucleus and suppressing the transcription of several pro-inflammatory genes by binding SMAD-3. Besides, IL-37 can be secreted extracellularly, and binds to IL-18Ra chain and recruits Toll/IL-1R (TIR)-8 for transducing anti-inflammatory signaling. IL-37 is upregulated in an inducible manner and negatively regulates signaling mediated by TLR agonists and pro-inflammatory cytokines. The cytokine has been shown to inhibit both innate and adaptive immunological responses, exert antitumor effects, and act as a prognostic marker in a variety of autoimmune diseases.

Conclusions: Recent studies have suggested that IL-37 plays a role in cardiovascular diseases. In this review, we provide an overview of the cytokine biology, discuss recent advances made in unraveling its cardio-protective effects, and suggest guidelines for future research.

Keywords: IL-37; cardiovascular diseases; inflammatory immunity response.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptive Immunity*
  • Animals
  • Cardiovascular Diseases / immunology*
  • Cardiovascular Diseases / pathology
  • Humans
  • Immunity, Innate*
  • Interleukin-1 / immunology*
  • Smad3 Protein / immunology
  • Up-Regulation / immunology*

Substances

  • IL37 protein, human
  • Interleukin-1
  • SMAD3 protein, human
  • Smad3 Protein