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Psychosomatic Medicine 63:966-972 (2001)
© 2001 American Psychosomatic Society

ORIGINAL ARTICLE

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

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

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: ck{at}uni-duesseldorf.de

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-{alpha}.

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.

Key Words: psychosocial stress, • HPA axis, • sex differences, • salivary cortisol, • Trier Social Stress Test, • inflammatory disease.

Abbreviations: ANCOVA = analysis of covariance;; ANOVA = analysis of variance;; BMI = body mass index;; DEX = dexamethasone;; EDTA = ethylenediaminetetraacetic acid;; ELISA = enzyme-linked immunosorbent assay;; GC = glucocorticoid;; HPA axis = hypothalamus-pituitary-adrenal axis;; HPG axis = hypothalamus-pituitary-gonadal axis;; IC50 = 50% inhibition concentration;; IL = interleukin;; LPS = lipopolysaccharide;; NF-{kappa}B = nuclear factor-{kappa}B;; TSST = Trier Social Stress Test;; TNF-{alpha} = tumor necrosis factor {alpha}.




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