Interleukin-36: a novel therapeutic target for atherosclerosis

Abstract

Cardiovascular diseases remain the foremost cause of global morbidity and mortality, with atherosclerosis serving as the pathological basis for most related disorders. Despite the clinical benefits of statin therapy, a substantial residual risk persists, underscoring the need to explore novel therapeutic targets. Interleukin-36 (IL-36), a member of the interleukin-1 family, has emerged as a key regulator of immune and inflammatory responses. Beyond its established roles in tissue repair, host defense, and inflammatory signaling, IL-36 has been increasingly implicated in cardiovascular pathology, including myocardial infarction, ischemic injury, and myocarditis. Recent evidence highlights its pro-atherogenic functions mediated through sustained vascular inflammation, abnormal angiogenesis, impaired cholesterol metabolism, excessive neutrophil extracellular trap formation, and disrupted autophagy. These findings collectively suggest that IL-36 not only contributes to the initiation and progression of atherosclerosis but also holds promise as a potential therapeutic target. This review summarizes recent progress on the regulatory roles and signaling mechanisms of IL-36, emphasizing its contribution to atherogenesis.