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Interleukin-6 and Tumor Necrosis Factor-α Production After Acute Psychological Stress, Exercise, and Infused Isoproterenol: Differential Effects and Pathways

Goebel, Marion U. MSc; Mills, Paul J. PhD; Irwin, Michael R. MD; Ziegler, Michael G. MD


Objective The aim of the study was to assess the effects of three different methods of acute activation of the sympathetic nervous system on lipopolysaccharide-induced in vitro production of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α).

Methods Thirty-two healthy volunteers performed speech and exercise tasks and underwent a 30-minute infusion of isoproterenol.

Results As expected, acute activation of the sympathetic nervous system led to leukocytosis, including increases in lymphocyte, monocyte, and granulocyte populations (p values < .05). Lipopolysaccharide-induced IL-6 production was increased after both the speaking and exercise tasks (p values < .001), whereas TNF-α production was elevated only after exercise (p < .05). In contrast, infusion of isoproterenol inhibited TNF-α production (p < .001) and caused no change in IL-6 production.

Conclusions In response to the challenges, IL-6 and TNF-α production showed different profiles. Purely β-agonist stimulation led to downregulation of TNF-α production, providing evidence of the antiinflammatory effect of in vivo β-receptor activation. The enhanced production of both cytokines after exercise, and of IL-6 after the speech task, can be best explained by a simultaneous upregulation of proinflammatory and inflammation-responding mediators. These effects may have an important role in controlling the immune response to acute psychological and physical stress.

From the Departments of Psychiatry (M.U.G., P.J.M., M.R.I.) and Medicine (M.G.Z.), University of California, San Diego, La Jolla, CA; Department of Medical Psychology (M.U.G.), University of Essen, Essen, Germany; and Veterans Affairs Medical Center (M.R.I.), La Jolla, CA.

Received for publication June 21, 1999;

revision received January 14, 2000.

Address reprint requests to: Marion Goebel, Department of Medical Psychology, Medical Faculty, University of Essen, Hufelandstr. 55, D-45122 Essen, Germany. Email:

Copyright © 2000 by American Psychosomatic Society
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