Tumour necrosis factor-alpha and the failing heart--pathophysiology and therapeutic implications

Basic Res Cardiol. 2004 Jan;99(1):18-28. doi: 10.1007/s00395-003-0433-8. Epub 2003 Aug 21.


Immune activation plays a significant role in the development and progression of chronic heart failure (CHF). Indeed, pro-inflammatory 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 infliximab, 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 sufficient.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Heart Failure / drug therapy*
  • Heart Failure / metabolism
  • Heart Failure / physiopathology*
  • Humans
  • Receptors, Tumor Necrosis Factor / metabolism
  • Signal Transduction
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Tumor Necrosis Factor-alpha / physiology*


  • Receptors, Tumor Necrosis Factor
  • Tumor Necrosis Factor-alpha