Tumor necrosis factor alpha (TNF alpha) is cardiodepressant in pathophysiologically relevant concentrations without

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Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo
08:19

Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo

Published on: July 20, 2019

U Müller-Werdan1, H Schumann, R Fuchs

  • 1Department of Medicine III, Klinikum Kröllwitz, University of Halle-Wittenberg, Ernst-Grube-Strasse 40, Halle, D-06097, Germany.

Journal of Molecular and Cellular Cardiology
|February 28, 1998
PubMed

Insights

Tumor necrosis factor alpha (TNF alpha) depresses heart cell contractility independently of nitric oxide (NO) in low, non-toxic concentrations. This finding challenges the established role of NO in TNF alpha-induced cardiac dysfunction, suggesting alternative mechanisms in heart failure.

Area of Science:

  • Cardiology
  • Molecular Biology
  • Cell Biology

Background:

  • Elevated tumor necrosis factor alpha (TNF alpha) is linked to cardiac hypertrophy and heart failure, but its role is debated.
  • TNF alpha's negative inotropic effect in septic cardiomyopathy is often attributed to inducible nitric oxide synthase (iNOS) and nitric oxide (NO) production.

Purpose of the Study:

  • To investigate whether TNF alpha affects cardiomyocyte contractility independently of NO production.
  • To determine the concentration-dependent effects of TNF alpha on cardiomyocyte function and iNOS expression.

Main Methods:

  • Primary neonatal rat cardiomyocytes were treated with varying concentrations of TNF alpha.
  • Contractile performance was assessed by measuring beating amplitude and response to adrenergic stimulation.
  • iNOS induction was evaluated using reverse transcriptase polymerase chain reaction (RT-PCR).
  • Nitrite levels in cell culture supernatants were measured as an indicator of NO production.

Main Results:

  • Low TNF alpha concentrations (10 U/ml) impaired adrenergic-stimulated contractility and calcium responsiveness without altering basal contractility.
  • These low concentrations did not induce iNOS mRNA or increase nitrite production, even with dexamethasone.
  • High TNF alpha concentrations (1000 U/ml) weakly induced iNOS mRNA and moderately increased nitrite production, accompanied by increased interleukin-6 release.

Conclusions:

  • TNF alpha depresses cardiomyocyte contractility at pathophysiologically relevant concentrations independent of NO.
  • The findings suggest that NO-independent mechanisms contribute to TNF alpha-induced cardiac dysfunction.
  • This study provides novel insights into the non-inotropic effects of TNF alpha on the heart.

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