Cardiodepression by tumor necrosis factor-alpha

Eur Cytokine Netw. 1998 Dec;9(4):689-91.

Abstract

Cardiodepressant effects of tumor necrosis factor-alpha (TNF-alpha have been documented in numerous experimental settings in vivo and in vitro. In vivo administration of TNF-alpha mimicks the cardiovascular pattern of sepsis including septic cardiomyopathy. Serum levels of TNF-alpha were found to be elevated both in sepsis and in numerous non-septic heart disorders. Although an involvement of TNF-alpha in the pathogenesis of septic cardiomyopathy seems likely, presently no definite conclusion can be drawn with regard to the role of TNF-alpha in chronic heart failure. The origin and trigger mechanisms for the release of TNF-alpha in heart failure are a matter of debate, endotoxin (LPS) from intestinal translocation in venous congestion being one possible player. The negative inotropic impact of TNF-alpha is frequently ascribed to the induction of inducible nitric oxide (NO) synthase (iNOS). Results from in vitro studies rather suggest a complex interaction of TNF-alpha with the heart, with pleiotropic effects on cardiomyocyte performance, including an induction of iNOS at higher TNF-alpha concentrations, but NO-independent cardiodepression at low, pathophysiologically more relevant concentrations. TNF-alpha effects on the heart also vary with regard to the kinetics of the process: rapidly occuring cardiodepressant effects include a release of sphingosine and a suppression of the calcium transient, while chronic administration of TNF-alpha was shown to depress the synthesis of precursors for the phosphoinositide pathway and inhibit pyruvate dehydrogenase activity and mitochondrial function. Whether secondary cytokines induced by TNF-alpha in cardiomyocytes contribute to cardiodepression or whether apoptotic signals activated by TNF-alpha are involved in the cardiodepressive pathways is presently unknown.

Publication types

  • Review

MeSH terms

  • Animals
  • Depression, Chemical
  • Heart / drug effects*
  • Heart / physiopathology
  • Heart Diseases / etiology
  • Heart Diseases / physiopathology
  • Humans
  • In Vitro Techniques
  • Myocardial Contraction / drug effects
  • Myocardial Contraction / physiology
  • Receptors, Tumor Necrosis Factor / physiology
  • Tumor Necrosis Factor-alpha / pharmacology*
  • Tumor Necrosis Factor-alpha / physiology

Substances

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