Mann Douglas L
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.
Circ Res. 2002 Nov 29;91(11):988-98. doi: 10.1161/01.res.0000043825.01705.1b.
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.
最近的研究已经确定了促炎介质在心力衰竭发生和发展中的重要性。在临床前和临床心力衰竭模型中，人们越来越认识到促炎介质持续表达所带来的病理生理后果，这最终促成了一系列多中心临床试验，这些试验采用“靶向”方法来中和中重度心力衰竭患者体内的肿瘤坏死因子。然而，这些靶向方法却导致心力衰竭恶化，从而引发了一些重要问题，即促炎细胞因子在心力衰竭发病机制中究竟扮演何种角色（如果有任何角色的话）。本综述将总结该领域已取得的巨大知识进展，重点关注我们从阴性临床试验中学到的内容，以及该领域未来研究的潜在方向。
