Tumour necrosis factor-alpha and the failing heart--pathophysiology and therapeutic implications.
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.
von Haehling
Stephan
S
Imperial College School of Medicine, National Heart & Lung Institute, Department of Clinical Cardiology, London, UK. stephan.von.haehling@web.de
Jankowska
Ewa A
EA
Anker
Stefan D
SD
D006333:Heart Failure / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*
D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha