The role of interleukin 6 in the development of cardiovascular pathology

Abstract

According the current concepts, chronic subclinical (low-grade) inflammation, the development of which is associated with uncontrolled activation of innate and adaptive immunity plays a fundamental role at all stages of atherosclerotic progression related to cardiovascular diseases (CVD). The significant contribution of inflammation to the development of atherosclerotic vascular lesions has drawn attention to the similarity between the immunopathogenesis mechanisms of atherosclerosis in CVD and rheumatoid arthritis, and subsequently other systemic immune-mediated rheumatic diseases (IMRDs). Among the numerous inflammatory mediators and “immune” cells involved in the immunopathogenesis of atherosclerosis in both CVD and IMIRDs, central roles are occupied by “pro-inflammatory” cytokines such as interleukin (IL)-1, IL-6, TNFα, as well as IL-17 and interferon type I, which closely interact within the “cytokine network”. As a promising therapeutic target, particular attention is drawn to IL-6, which occupies a central place in the development of many IMIDs and CVDs associated with atherosclerotic vascular lesions: coronary heart disease, acute coronary syndrome, peripheral arterial disease, ischemic stroke, heart failure, and others. Of particular importance is the fact that IL-6 hyperproduction plays a significant role in the development of a wide range of cardiometabolic diseases, including type 2 diabetes mellitus, obesity, chronic kidney disease, and metabolic dysfunction-associated fatty liver disease, associated with the development of atherosclerotic vascular lesions. Data were obtained indicating the important clinical significance of IL-6 determination for predicting the risk of premature mortality and other cardiovascular complications both in the general population of conditionally “healthy” people and in patients with various manifestations and forms of CVD. Currently, several genetically engineered biological agents - monoclonal antibodies specific for both IL-6R and IL-6 itself - have been developed. Several RCTs have recently been initiated to study the efficacy and safety of new anti-IL-6 mAbs: ziltivekimab, clazakizumab, and Pacibekitug (TOUR006) in patients with coronary artery disease, heart failure, and CKD. The article will review new data regarding the pathogenetic and clinical significance of IL-6 and the prospects for IL-6 inhibition as a component of anti-inflammatory therapy for CVD.