Last update:
14-Jan-2006

Clinical and laboratory research during the past decade has demonstrated that proinflammatory cytokines play an essential role in the pathogenesis of heart failure; but although numerous studies have focused on this concept, the exact role of these highly potent, pleiotropic substances has not yet been clarified. Investigators have shown that proinflammatory cytokines can be produced by the myocardiocytes of patients with congestive heart failure. It is now believed that overexpression of cytokines in heart failure is not simply an epiphenomenon or a marker of disease severity, but a biological mechanism responsible for the primary progression of the disease. As heart failure progresses, expression of cytokines increases, resulting in a negative inotropic effect, increased oxidative stress, reduced peripheral vasodilation and promotion of myocardiocyte apoptosis. Recent data suggest that treatment of heart failure with β-blockers, angiotensin converting enzyme antagonists and/or calcium channel blockers leads to a decline in circulating plasma levels of proinflammatory cytokines as well as to a reduction of their production in the myocardium. It remains unclear whether this is a drug mediated effect or occurs as a result of general improvement of the disease. Intensive investigation is being directed towards clarification of the hypothesis that inhibition of cytokine production or expression could lead to an improvement of congestive heart failure. Currently, no drug has yet proved effective in treating heart failure by this mechanism.

Key words: Cytokines, Heart failure, Proinflammatory cytokines.