The role of interleukin 6 in the development of cardiovascular pathology

Although the role of inflammation in the development of atherosclerotic vascular lesions, as the leading form of organ pathology in the cardiovascular diseases (CVD), has been discussed for more than 100 years, only in the last 30 years has the “inflammatory” theory of atherosclerosis begun to be considered as one of the most important areas of fundamental and clinical research in cardiology and other areas of biology and medicine. According to modern concepts, chronic low-grade inflammation, the development of which is associated with uncontrolled activation of innate and acquired immunity, plays a fundamental role at all stages of the progression of the atherosclerotic process associated with CVD. The fundamental contribution of inflammation to the development of atherosclerotic vascular lesions has drawn attention to the similarity of the mechanisms of immunopathogenesis of atherosclerosis in CVD and rheumatoid arthritis, and subsequently other systemic immune-mediated rheumatic diseases (IMRDs). In the spectrum of numerous inflammatory mediators and “immune” cells involved in the immunopathogenesis of atherosclerosis in both CVD and IMIRD, the central place is occupied by “pro-inflammatory” cytokines such as interleukin (IL) 1, IL-6, tumor necrosis factor α, as well as IL-17 and interferon type I, which closely interact within the “cytokine network”. IL-6, which occupies a central place in the development of many IMIDs, on the one hand, and CVDs associated with atherosclerotic vascular lesions, on the other hand, is attracting special attention as a promising therapeutic “target”: coronary heart disease, acute coronary syndrome, peripheral arterial disease, ischemic stroke, heart failure, and others. Of particular importance is the fact that hyperproduction of IL-6 plays a significant role in the development of a wide range of cardiometabolic diseases, including type 2 diabetes mellitus, obesity, chronic kidney disease, metabolically associated fatty liver disease, associated with the development of atherosclerotic vascular lesions. Data were obtained indicating the important clinical significance of IL-6 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. Several biologics, which are monoclonal antibodies specific for both IL-6R and IL-6 itself, have been developed. Several randomized clinical trials 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 chronic kidney disease. 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.