Role of tumour necrosis factor-alpha in the progression of heart failure: therapeutic implications.

The experimental and clinical evidence that demonstrates the effect of various cytokines, and in particular tumour necrosis factor (TNF)alpha, in patients with heart failure continues to accumulate. It is well established that increased levels of TNFalpha appear in the circulation of patients with heart failure and that the levels may have prognostic significance. Also, increased circulating TNFalpha levels may be responsible for the decreased expression of myocardial TNF receptors observed in failing myocardium. Along with these clinical data, it has been clearly demonstrated that increased levels of TNFalpha lead to cardiomyopathy and eventually death in experimental animals. Therefore, it is reasonable to assume that the increased levels of TNFalpha in patients with heart failure may be detrimental to cardiac function. The hypothesis that TNFalpha contributes to the pathogenesis of heart failure has recently been tested at the clinical level. The results of specific TNFalpha antagonism in patients with symptomatic heart failure demonstrate that anti-TNFalpha therapy is well tolerated and may be effective. This hypothesis is currently being tested in a large randomised, multicentre study that is expected to be complete within the next 2 years. Perhaps the most important aspect of the evolving research into the role of cytokines in heart failure is that the recognition of activation of inflammatory mediators provides new targets for therapeutic intervention.