Tumour necrosis factor-α and the failing heart -: Pathophysiology and therapeutic implications

Immune activation plays a signicant role in the development and progression of chronic heart failure (CHF). Indeed, pro-inammatory cytokines, especially tumour necrosis factor-alpha (TNFalpha) are activated in this condition and exert direct detrimental actions on the myocardium. Physiological dampeners of TNFalpha production, such as interleukin-10, catecholamines, cortisol, and others fail in the course of the disease. However, the outcomes of two large-scale clinical trials with etanercept and iniximab, which directly antagonise TNFalpha have been rather disappointing. Nevertheless, TNFalpha antagonism remains a major target of CHF therapy, although counterbalancing this cytokine alone may not be sufcient.