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Circ Res. 2002 Nov 29;91(11):988-98.

Inflammatory mediators and the failing heart: past, present, and the foreseeable future.

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1
Winters Center for Heart Failure Research, the Cardiology Section, Department of Medicine, Veterans Administration Medical Center, Methodist Hospital, and Baylor College of Medicine, Houston, Tex 77030, USA. dmann@bcm.tmc.edu

Abstract

Recent studies have identified the importance of proinflammatory mediators in the development and progression of heart failure. The growing appreciation of the pathophysiological consequences of sustained expression of proinflammatory mediators in preclinical and clinical heart failure models culminated in a series of multicenter clinical trials that used "targeted" approaches to neutralize tumor necrosis factor in patients with moderate to advanced heart failure. However, these targeted approaches have resulted in worsening heart failure, thereby raising a number of important questions about what role, if any, proinflammatory cytokines play in the pathogenesis of heart failure. This review will summarize the tremendous growth of knowledge that has taken place in this field, with a focus on what we have learned from the negative clinical trials, as well as the potential direction of future research in this area.

[Indexed for MEDLINE]

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