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Sex Differences in Glucocorticoid Sensitivity of Proinflammatory Cytokine Production After Psychosocial Stress

Rohleder, Nicolas Dipl-Psych; Schommer, Nicole C. Dipl-Psych; Hellhammer, Dirk H. PhD; Engel, Renate MTA, and; Kirschbaum, Clemens PhD

Special Issue: Outerspace Research: Original Articles

Objective Men and women show marked differences in susceptibility to disorders related to the immune system. These gender differences have been proposed to be mediated by functional interactions of the hypothalamus-pituitary-adrenal (HPA) and hypothalamus-pituitary-gonadal (HPG) axes. A potential mechanism involved in this interaction is the glucocorticoid (GC) sensitivity of relevant target tissues for GC. Therefore, the aim of the study reported here was to investigate the impact of psychosocial stress and HPA axis activation on the GC sensitivity of proinflammatory cytokine production in men and women.

Methods A total of 45 healthy subjects were investigated. Eighteen women in the luteal phase of their menstrual cycle and 27 men were exposed to a psychosocial stress test (Trier Social Stress Test). Salivary free cortisol levels were measured repeatedly after exposure to the stressor. GC sensitivity was assessed in vitro by dexamethasone inhibition of lipopolysaccharide-stimulated production of interleukin-6 and tumor necrosis factor-α.

Results The stress test induced significant increases in salivary free cortisol with no significant differences between men and women. In contrast, GC sensitivity and lipopolysaccharide-stimulated cytokine production showed large gender differences. In men GC sensitivity was markedly increased 1 hour after stress, whereas GC sensitivity decreased significantly in women. Similarly, lipopolysaccharide-induced cytokine production decreased in response to stress in men but increased in women.

Conclusions These results demonstrate that despite similar free cortisol responses of men and women (studied in the luteal phase) to psychosocial stress, gender may exert differential effects on the immune system by modulating GC sensitivity of proinflammatory cytokine production.

From the Center for Psychobiological and Psychosomatic Research (N.C.S., D.H.H., R.E., C.K.), University of Trier, Trier, Germany; and Institute of Physiological Psychology II (N.R., C.K.), University of Düsseldorf, Düsseldorf, Germany.

Address reprint requests to: Clemens Kirschbaum, PhD, Institute of Physiological Psychology II, University of Düsseldorf, Universitätsstrasse 1, D-40225 Düsseldorf, Germany. Email:

Received for publication July 5, 2000; revision received February 28, 2001.

Copyright © 2001 by American Psychosomatic Society
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