title: Inflammatory mediators and the failing heart: past, present, and the foreseeable future.
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.
authors.affiliation: 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
authors.forename: Douglas L
authors.initials: DL
authors.lastname: Mann
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology; D018450:Disease Progression; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D000068800:Etanercept; D006333:Heart Failure / Q000188:drug therapy / Q000209:etiology* / Q000503:physiopathology*; D006801:Humans; D007074:Immunoglobulin G / Q000009:adverse effects / Q000627:therapeutic use; D007155:Immunologic Factors / Q000009:adverse effects / Q000627:therapeutic use; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D000069285:Infliximab; D010431:Pentoxifylline / Q000009:adverse effects / Q000627:therapeutic use; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D012106:Research / Q000639:trends; D013792:Thalidomide / Q000009:adverse effects / Q000627:therapeutic use; D017211:Treatment Failure; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism; D018487:Ventricular Dysfunction, Left / Q000209:etiology / Q000503:physiopathology; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D016207:Cytokines; D007074:Immunoglobulin G; D007155:Immunologic Factors; D018836:Inflammation Mediators; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D013792:Thalidomide; D000069285:Infliximab; D000068800:Etanercept; D010431:Pentoxifylline