Tumor necrosis factor-alpha in the failing human heart: Does it play a role in disease progression?

An increasing body of clinical and experimental evidence suggesting that TN Falpha may play a pathogenetic role in failing hearts continues to accumula te. Perhaps the most direct evidence for the role of TNFalpha in heart fail ure will come from the analysis of the phase I study in which a soluble rec ombinant human TNF receptor: Fc fusion protein was utilized in patients wit h moderate to severe heart failure. Enrollment in that trial was recently c ompleted; the results will soon be available for analysis. But perhaps more importantly, the knowledge gained from studying the role of TNFalpha in ca rdiac function draws attention to a series of molecules previously unrecogn ized as potential mediators in the pathogenesis of heart failure. Various c ytokines and TNFalpha, in particular, represent new targets for therapeutic intervention in patients with heart failure.