The emerging role of interleukin‐37 in cardiovascular diseases

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.