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Psychological Stress, Cytokine Production, and Severity of Upper Respiratory Illness

Cohen, Sheldon PhD; Doyle, William J. PhD; Skoner, David P. MD

Original Articles

Objective The purpose of this study is to assess the role of psychological stress in the expression of illness among infected subjects and to test the plausibility of local proinflammatory cytokine production as a pathway linking stress to illness.

Methods After completing a measure of psychological stress, 55 subjects were experimentally infected with an influenza A virus. Subjects were monitored in quarantine daily for upper respiratory symptoms, mucus production, and nasal lavage levels of interleukin (IL)-6.

Results Higher psychological stress assessed before the viral challenge was associated with greater symptom scores, greater mucus weights, and higher IL-6 lavage concentrations in response to infection. The IL-6 response was temporally related to the two markers of illness severity, and mediation analyses indicated that these data were consistent with IL-6 acting as a major pathway through which stress was associated with increased symptoms of illness. However, this pattern of data is also consistent with increases in IL-6 occurring in response to tissue damage associated with illness symptoms.

Conclusions Psychological stress predicts a greater expression of illness and an increased production of IL-6 in response to an upper respiratory infection.

From the Department of Psychology, Carnegie Mellon University; Department of Otolaryngology, Section of Allergy/Immunology-Department of Pediatrics, Children's Hospital of Pittsburgh and University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.

Address reprint requests to: Sheldon Cohen, Department of Psychology, Carnegie Mellon University, Pittsburgh, PA 15213. E:mail:

Received for publication August 12, 1998; revision received December 3, 1998.

Copyright © 1999 by American Psychosomatic Society
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