Role of Interleukin-6 in Atherothrombosis and Myocardial Infarction

We aimed to summarize the pathogenic role of IL-6 in atherothrombosis and myocardial infarction (MI), with focus on novel pathogenic mechanisms and current IL-6 targeted therapy in clinical cohorts.

IL-6 plays a major role in the pathogenesis of cardiovascular disease interacting with aging- and metabolic-driven inflammation, two conditions with overlapping molecular mechanisms. A novel pathogenic mechanism in cardiovascular disease (CVD) is the interaction between IL-6 and clonal hematopoiesis of indeterminate potential, CHIP, that involve the ten-eleven translocation-2 gene, a molecule with role in epigenetics. Recent studies showed reduced inflammation, a reduction in Lp (a) and inhibitory effects on platelets by anti-IL-6 (ziltivekimab) therapy in patients at risk for CVD. Anti-IL-6 receptor therapy (tocilizumab) showed reduced inflammation and improved myocardial function in MI patients, involving reduced degranulation in neutrophils and modulation of monocytes. Studies with clinical endpoints are still lacking and there also a need for developing therapy that selectively block the harmful IL-6 trans-signaling. IL-6 plays an important and many-faceted role in atherothrombosis including MI and ischemic stroke, and the IL-6 system represent a promising but still evolving therapeutic approach. A comprehensive understanding of the complexity of IL-6 signaling is needed to improve such treatment strategies.