Cytokines are being increasingly recognised as important factors in the pathogenesis and pathophysiology of
heart failure. Elevated levels of circulating
cytokines have been reported in patients with
heart failure, and various
cytokines have been shown to depress myocardial contractility in vitro and in vivo. In our murine model of
congestive heart failure resulting from encephalomyocarditis virus
infection, survival and myocardial damage were markedly improved by treatment with
vesnarinone.
Vesnarinone inhibited the increase in natural killer cell activity and production of tumour
necrosis factor-alpha (
TNFalpha) in this animal model.
Vesnarinone also inhibited the production of various
cytokines by peripheral blood and by endothelial cells. These findings provide evidence that
vesnarinone plays an important role in the regulation of
cytokine production, and suggest that the reduction of
cytokine release may contribute to the beneficial effects of the
drug for the treatment of
heart failure. As we learn more about the pathophysiological and pathogenetic role of
cytokines in
heart failure, it should be possible to design better and more targeted pharmacological agents. Furthermore, the investigation of inotropic agents that are effective against the production of
cytokines may help in the classification of these agents.