IL-37-a putative therapeutic agent in cardiovascular diseases

Abstract

Although it is a member of the Interleukin (IL)-1 family, IL-37 is unique in that it has wide-ranging anti-inflammatory characteristics. It was originally thought to prevent IL-18-mediated inflammation by binding to the IL-18-binding protein. However, upon discovery that it binds to the orphan receptor, IL-1R8, further studies have revealed an expanded role of IL-37 to include several intracellular and extracellular pathways that affect various aspects of inflammation. Its potential role specifically in cardiovascular diseases (CVD) stemmed initially from the discovery of elevated plasma IL-37 levels in human patients with acute coronary syndrome and atrial fibrillation. Other studies using mouse models of ischemia/reperfusion injury, vascular calcification and myocardial infarction have revealed that IL-37 can have a beneficial role in these conditions. This review will explore recent research on the effects of IL-37 on the pathogenesis of CVD.

Figure 1.

Summary of the inhibitors and promoters (left) of IL-37 and its effects discussed. Data originated from in vivo studies performed with patients (blue) or mice (red), or in vitro studies (green). Abbreviations: AIS, acute ischemic stroke; CHF, chronic heart failure; CAC, coronary artery calcification; CAD, coronary artery disease; DC, dendritic cell; EC, endothelial cell; ICAM-1, intracellular adhesion molecule 1; MCP-1, monocyte chemoattractant protein 1; OPG, osteoprotergerin; PBMCs, peripheral blood mononuclear cells.