Anti-inflammatory therapy for atherosclerosis: contribution to and lessons of rheumatology

According to modern views, chronic low-grade inflammation, the development of which is associated with the uncontrolled activation of both innate and acquired immunity, plays a fundamental role at all stages of the atherosclerotic process. The contribution of inflammation to the development of an atherosclerotic vascular lesion drew attention to the similarity of the mechanisms in the immunopathogenesis of atherosclerosis and the classic immunoinflammatory disease (IID) - rheumatoid arthritis (RA). Interleukin 1ß (IL-1ß), which plays an important role in the development of many acute and chronic IIDs, is of particular interest with regard to its implication in the pathogenesis of an atherosclerotic vascular lesion and as a promising therapeutic target. The atherosclerosis development mechanisms related to IL-1ß determine the ability of cholesterol crystals and other proatherogenic factors to induce IL-1 ß synthesis due to NLRP3 inflammasome activation. There is strong evidence that inflammation plays a role in the development of atherosclerosis as a whole and that anti-inflammatory therapy has good prospects particularly in the randomized placebo-controlled trial (RPCT) CANTOS (Canakinumab ANti-inflammatory Thrombosis Outcomes Study) investigating the efficiency of treatment with canakinumab (Novartis International AG), an anti-IL-1ß monoclonal antibodies, in patients with severe atherosclerotic vascular lesions as a new approach to secondary prevention of cardiovascular events. Methotrexate (MTX) has now been convincingly shown to be an effective drug (a gold standard) in not only controlling the inflammatory activity of RA, but also in significantly reducing the risks of cardiovascular catastrophes. This has served as a basis for planning the RPCT CIRT (The Cardiovascular Inflammation Reduction Trial) to evaluate the antiatherogenic effect of MTX in the general population of patients with coronary heart disease. The CANTOS results and the experience gained in rheumatology to determine the cardiovascular effects of innovative anti-inflammatory drugs are of great importance in improving the secondary prevention of atherosclerosis-related cardiovascular events.