Circulation Research. 2002;91:988-998
doi: 10.1161/01.RES.0000043825.01705.1B
doi: 10.1161/01.RES.0000043825.01705.1B
© 2002 American Heart Association, Inc.
Review |
Inflammatory Mediators and the Failing Heart
Past, Present, and the Foreseeable Future
From the 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.
Correspondence to Douglas L. Mann, MD, Winters Center for Heart Failure Research, MS 524, 6565 Fannin, Houston, TX 77030. E-mail dmann{at}bcm.tmc.edu
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.
Key Words: tumor necrosis factor • inflammatory mediators • clinical trial • etanercept • infliximab
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