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Role of Tumour Necrosis Factor-α in the Progression of Heart Failure

Therapeutic Implications

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Abstract

The experimental and clinical evidence that demonstrates the effect of various cytokines, and in particular tumour necrosis factor (TNF)α, in patients with heart failure continues to accumulate. It is well established that increased levels of TNFα appear in the circulation of patients with heart failure and that the levels may have prognostic significance. Also, increased circulating TNFα levels may be responsible for the decreased expression of myocardial TNF receptors observed in failing myocardium. Along with these clinical data, it has been clearly demonstrated that increased levels of TNFα lead to cardiomyopathy and eventually death in experimental animals. Therefore, it is reasonable to assume that the increased levels of TNFα in patients with heart failure may be detrimental to cardiac function.

The hypothesis that TNFα contributes to the pathogenesis of heart failure has recently been tested at the clinical level. The results of specific TNFα antagonism in patients with symptomatic heart failure demonstrate that anti-TNFα therapy is well tolerated and may be effective. This hypothesis is currently being tested in a large randomised, multicentre study that is expected to be complete within the next 2 years. Perhaps the most important aspect of the evolving research into the role of cytokines in heart failure is that the recognition of activation of inflammatory mediators provides new targets for therapeutic intervention.

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Acknowledgements

This work was partially supported by an unrestricted grant from SmithKline Beecham Pharmaceuticals and The Methodist Hospital Foundation. We are grateful to Douglas L. Mann for scientific support and to Ms Anna Zamora for editorial assistance.

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Authors and Affiliations

  1. The Winters Center for Heart Failure Research and the ‘Eugene and Judith Campbell’ Laboratory for Cardiac Transplantation Research, Section of Cardiology, Baylor College of Medicine, 6550 Fannin, MS: SM 1901, Houston, Texas, 77030, USA

    Guillermo Torre-Amione, Mary T. Vooletich & John A. Farmer

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  1. Guillermo Torre-Amione
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  2. Mary T. Vooletich
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  3. John A. Farmer
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Correspondence to Guillermo Torre-Amione.

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Torre-Amione, G., Vooletich, M.T. & Farmer, J.A. Role of Tumour Necrosis Factor-α in the Progression of Heart Failure. Drugs 59, 745–751 (2000). https://doi.org/10.2165/00003495-200059040-00002

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  • DOI: https://doi.org/10.2165/00003495-200059040-00002

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