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(Circulation. 1995;92:1379-1382.)
© 1995 American Heart Association, Inc.
Articles |
Is Tumor Necrosis Factor an Important Neurohormonal Mechanism in Chronic Heart Failure?
From the Division of Circulatory Physiology and Center for Heart Failure Research, Columbia University, College of Physicians and Surgeons, New York, NY.
Key Words: Editorials • tumor necrosis factor • heart failure • hormones
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Introduction |
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Although heart failure has traditionally been regarded as a circulatory disorder, physicians have recognized for more than 2500 years that patients with heart failure share many of the clinical features of those afflicted with chronic inflammatory or neoplastic diseases.1 2 As heart failure advances, many patients develop a syndrome known as cardiac cachexia, which is characterized by a profound loss of lean body mass and anorexia and is accompanied by many of the biochemical changes of malnutrition (anemia, hypoalbuminemia, leukopenia, and hypocholesterolemia) and inflammation (increased erythrocyte sedimentation rate, fibrinogen, and acute-phase reactants).3 4 The pathogenesis of cardiac cachexia remained obscure for many years, until it was recognized that patients with cardiac cachexia have high circulating levels of tumor necrosis factor (TNF).5 This pluripotent cytokine causes cachexia, anorexia, and inflammation during long-term administration to experimental animals,6 and high circulating levels of TNF have been reported in patients with a variety of neoplastic, infectious, and collagen vascular disorders characterized by muscle wasting and malnutrition.7 8 9
The first study of elevated circulating levels of tumor necrosis factor
in heart failure used a cytotoxicity assay to measure concentrations of
the cytokine.5 In that study, we noted that
circulating levels of the cytokine were increased primarily in
patients with the most advanced symptoms, peripheral
hypoperfusion and cachexia. Subsequent investigators, using immunologic
assays to measure TNF, confirmed that levels of the cytokine
were increased in patients with heart failure and that there was a
relation between circulating levels of TNF and clinical features of the
disease; furthermore, interventions that
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