Proinflammatory cytokines in heart disease

Proinflammatory cytokines affect nearly all tissues and organ systems, and the vasculature is no exception. Although a considerable amount of research has focused on the role of the two most prominent proinflammatory cytokines, interleukin-1 (IL-1) and tumor necrosis factor (TNF), in the pathogenesis of sepsis and septic shock, the role of these and other cytokines in the pathogenesis of atherosclerotic lesions of the coronary artery, the acute ischemic event associated with myocardial infarction, the progression of myocardiopathies or the loss of myocardial function in congestive heart failure is a relatively recent discovery. Moreover, there has also been significant investigation of the cardioprotective effects of cytokines. Most of the attention has focused on the acute coronary syndromes and the myocardial suppression that takes place as a result of acute ischemia. The potential for anticytokine-based therapies in treating heart disease is great. Parenteral TNF-alpha neutralization and IL-1 receptor blockade are presently used to treat rheumatoid arthritis. Two orally effective agents, the IL-1beta-converting enzyme inhibitor and the mitogen-activating protein kinase p38 inhibitor, are currently being investigated in clinical trials.