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Tumour Necrosis Factor in Chronic Heart Failure

A Peripheral View on Pathogenesis, Clinical Manifestations and Therapeutic Implications

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Abstract

The development of chronic heart failure (CHF) includes phenotypic changes in a host of homeostatic systems so that, as the disease advances, CHF may be seen as a multi-system disorder with its origins in the heart but embracing many extra-cardiac manifestations. Immunological abnormalities are recognised in this context, in particular, changes in the expression of mediators of the innate immune response. Higher levels of the pro-inflammatory cytokine tumor necrosis factor (TNF) are found in the circulation and in the myocardium of patients with CHF than in controls, and TNF has been implicated in a number of pathophysiological processes that are thought important to the progression of CHF. Therapies directed against this cytokine therefore represent a novel approach to heart failure management.

Anti-TNF strategies in CHF may target the mechanisms of immune activation, the intracellular pathways regulating TNF production, or the fate of TNF once it has been released into the circulation. Circulating endotoxin may be an important stimulus to TNF production by circulating monocytes, tissue macrophages and cardiac myocytes in CHF and efforts to limit this phenomenon are of interest. Several established pharmacological therapies for patients with CHF, including angiotensin converting enyzme inhibitors, β-blockers, and phosphodiesterase inhibitors may modify cellular TNF production by their action on intracellular mechanisms, whereas TNF receptor fusion proteins have been developed that target circulating TNF itself. Patients with New York Heart Association class IV symptoms, those with cardiac cachexia and those with oedematous decompensation of their disease have the highest serum TNF levels and are most likely to benefit most from such a therapeutic approach.

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Acknowledgements

Dr Aidan Bolger is supported by the British Heart Foundation Montagne-Barlow Junior Research Fellowship. Dr Stefan Anker is supported with a postgraduate fellowship of the Max Delbrück Centrum for Molecular Medicine, Berlin, Germany.

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Authors and Affiliations

  1. Cardiac Medicine, National Heart and Lung Institute, Imperial College School of Medicine, London, England

    Aidan P. Bolger &  Stefan D. Anker

  2. Franz Volhard Klinik (Charité, Campus Berlin-Buch) at Max Delbrück Centrum for Molecular Medicine, Berlin, Germany

    Stefan D. Anker

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  1. Aidan P. Bolger
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  2. Stefan D. Anker
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Correspondence to Stefan D. Anker.

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Bolger, A.P., Anker, S.D. Tumour Necrosis Factor in Chronic Heart Failure. Drugs 60, 1245–1257 (2000). https://doi.org/10.2165/00003495-200060060-00002

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