The cytokine network in heart failure: pathogenetic importance and potential therapeutic targets

Abstract

Accumulating evidence indicates that inflammatory mediators are important in the pathogenesis of chronic heart failure. Several studies have shown raised levels of inflammatory cytokines in patients with congestive heart failure (CHF), in both plasma and circulating leukocytes, as well as in the failing myocardium itself. Importantly, many of the inflammatory cytokines (e.g. tumor necrosis factor-a and interleukin-6) have the potential to negatively influence heart contractility, induce hypertrophy, and promote apoptosis or fibrosis, thereby contributing to the continuous remodeling process in CHF. Traditional cardiovascular drugs seem to have little influence on the cytokine network in CHF patients, and immunomodulatory therapy, in addition to 'optimal' cardiovascular treatment regimens, has emerged as an option. Thus, several small studies with therapy targeted against inflammatory mediators have shown promising effects on functional capacity and myocardial performance. These studies suggest a potential for immunomodulating therapy, in addition to optimal conventional cardiovascular-treatment regimens in CHF patients. However, the results in these small studies will have to be confirmed in larger placebo-controlled mortality studies. More importantly, further research in this area will have to precisely identify the most important components in the immunopathogenesis of chronic heart failure, in order to develop more specific immunomodulating agents in this disorder.