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Chronic Intermittent Psychosocial Stress (Social Defeat/Overcrowding) in Mice Increases the Severity of an Acute DSS-Induced Colitis and Impairs Regeneration

Institute of Zoology (S.O.R., I.D.N.) and Department of Internal Medicine 1 (F.O., H.R.S., W.F.), University of Regensburg, 93053 Regensburg, Germany

Address all correspondence and requests for reprints to: Dr. Inga D. Neumann, Department of Zoology, University of Regensburg, 93040 Regensburg, Germany. E-mail: inga.neumann{at}biologie.uni-regensburg.de.

Ulcerative colitis is a multifactorial disease, with immunological, genetic, and environmental factors playing an important role in its pathogenesis. Here we investigated the consequences of exposure to chronic psychosocial stress on the severity of a dextran sulfate sodium (DSS)-induced colitis in male C57BL/6 mice. Chronic stress was induced by repeated exposure to social defeat (SD, 2 h) and overcrowding (OC, 24 h) during 19 consecutive days. SD/OC mice showed a diminished body weight gain, thymus-atrophy, and adrenal hypertrophy, but similar light-phase plasma corticosterone concentrations, compared with unstressed mice. In contrast, the rise in dark-phase corticosterone concentration was significantly attenuated in SD/OC mice, whereas plasma ACTH concentrations and hypothalamic CRH mRNA expression did not differ between stressed and nonstressed groups. Additionally, adrenal cells from SD/OC mice showed a decreased in vitro response to ACTH stimulation. Subsequent treatment with 1% DSS for 7 d resulted in a more severe intestinal inflammation in SD/OC mice, as reflected by an increase in body weight loss, histological damage scores, and secretion of IL-6, TNF, and interferon- from mesenteric lymph node cells and by decreased colon length. The impaired health status of stressed mice was also reflected by a significantly lower survival rate after termination of the DSS treatment. In conclusion, the present findings demonstrate that chronic intermittent exposure to a psychosocial stressor before the induction of acute DSS-colitis results in adrenal insufficiency, increases in the severity of the acute inflammation, and impairs the healing phase.

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