The role of IL-6 in atherosclerosis: a narrative review

Atherosclerotic cardiovascular disease (ASCVD) is a chronic inflammatory disease characterized by plaque formation. Inflammatory activity, assessed by high-sensitivity C-reactive protein (hsCRP), is linked to increased ASCVD risk. Recently, there has been much interest in the association between interleukin-6 (IL-6), a cytokine lying upstream of CRP along the inflammatory pathway, and ASCVD. Pre-clinical studies have shown that targeting IL-6 via its mediators may reduce pro-inflammatory effects. In observational studies, IL-6 has been identified as a source of residual risk for ASCVD even after controlling for factors such as male sex, old age and prior ASCVD events. Both genetic predisposition and acquired conditions, such as chronic systemic inflammation and comorbidities, may contribute to modest but persistent elevation in IL-6 levels. While routine IL-6 testing may not currently be feasible in practice, measurements may be informative in selected high-risk patients, as IL-6 may reflect inflammatory activation at an earlier stage than hsCRP. Detecting subtle yet clinically meaningful increases in inflammatory biomarkers in high-risk patients could facilitate earlier identification of ASCVD risk. Additionally, current evidence supports IL-6 as a potential therapeutic target for ASCVD. While trials investigating IL-6 inhibition specifically in ASCVD are limited, studies in patients with autoimmune conditions at increased cardiovascular risk have shown IL-6 inhibition to reduce inflammatory biomarkers without an excess of major adverse cardiovascular events. However, as IL-6 inhibition may raise triglyceride and low-density lipoprotein cholesterol levels, both of which are recognized ASCVD risk factors, further studies are needed to clearly assess the efficacy and safety of IL-6 inhibitors in ASCVD.