The role of IL-1 in the pathogenesis of heart disease

Abstract

Interleukin (IL)-1 consists of two distinct ligands, IL-1α and IL-1β, with indistinguishable biological activities that signal through the IL-1 type I receptor (IL-1RI). A naturally occurring IL-1 receptor antagonist (IL-1Ra) binds to IL-1RI without initiating signal transduction and prevents IL-1 signaling, competitively inhibiting IL-1-mediated responses. Emerging evidence suggests that the balance between IL-1 agonists and antagonists plays an essential role in a variety of cardiovascular conditions. IL-1 may play a role in atherothrombotic disease by promoting the formation of atheromatous lesions, enhancing vascular inflammation, and triggering plaque destabilization. Following myocardial infarction, IL-1 critically regulates the inflammatory response and is involved in the development of adverse remodeling by enhancing expression of matrix metalloproteinases. IL-1 signaling may also be an essential mediator in the pathogenesis of heart failure by suppressing cardiac contractility, promoting myocardial hypertrophy, and inducing cardiomyocyte apoptosis. The present review summarizes current available data showing the significant role of IL-1 signaling in heart disease and raising the possibility that IL-1 inhibitors (such as anakinra, a nonglycosylated recombinant human IL-1Ra) may be clinically useful agents in patients with certain cardiovascular conditions.