Circulation, Vol 90, 694-699, Copyright © 1994 by American Heart Association
K Vaddi, FA Nicolini, P Mehta and JL Mehta
BACKGROUND: There is growing evidence for a pathogenic role for cytokines
in atherogenesis. The presence of certain cytokines has been documented in
human atherosclerotic vessels. This study was designed to investigate
cytokine production by mononuclear leukocytes from patients with ischemic
heart disease. METHODS AND RESULTS: We measured kinetics of secretion of
tumor necrosis factor-alpha (TNF-alpha) and interferon- gamma (IFN-gamma)
by mononuclear leukocytes from 8 control subjects, 10 patients with stable
angina pectoris, and 10 patients with unstable angina pectoris. Mononuclear
leukocytes were isolated and incubated with or without the plant lectin
mitogen concanavalin A for 48 hours. TNF-alpha and IFN-gamma secretion were
measured by ELISA. The effect of TNF-alpha and IFN-gamma on superoxide
radical generation by neutrophils was also examined. Secretion of both
TNF-alpha and IFN-gamma by mononuclear leukocytes increased progressively
over 48 hours, and it was consistently higher (P < .02) in patients
compared with control subjects. A similar increase in cytokine secretion
was observed in patients with stable or unstable angina pectoris. In
addition, there was no relation between the severity of coronary artery
disease by angiography and cytokine secretion. Basal neutrophil superoxide
radical generation was increased in patients with ischemic heart disease,
and incubation with cytokines failed to further stimulate superoxide
generation in these patients. CONCLUSIONS: Similar increases in cytokine
secretion by mononuclear leukocytes in stable or unstable angina pectoris
indicate that the increased cytokine release is not a nonspecific
inflammatory response in acute myocardial ischemia. Increased cytokine
secretion in ischemic heart disease may play a role in superoxide radical
generation, endothelial injury, deposition and activation of cellular
elements on the vessel wall, and possibly in the progression of
atherosclerosis.
ARTICLES
Increased secretion of tumor necrosis factor-alpha and interferon-gamma by mononuclear leukocytes in patients with ischemic heart disease. Relevance in superoxide anion generation
Department of Medicine, University of Florida, College of Medicine, Gainesville 32610.
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