Ulcerative colitis is a multi-factorial disease, with immunological, genetic and environmental factors playing an important role in its pathogenesis. Here we investigated the consequences of exposure to chronic psycho-social 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 to 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 while plasma ACTH concentrations and hypothalamic CRH mRNA expression did not differ between stressed and non-stressed groups. Additionally, adrenal cells from SD/OC mice showed a decreased in vitro response to ACTH stimulation. Subsequent treatment with 1% DSS for 7 days resulted in a more severe intestinal inflammation in SD/OC mice, as reflected by an increase in body weight loss, in histological damage scores and in secretion of IL-6, TNF- and IFN- 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 exposure to a psycho-social stressor before the induction of acute DSS-colitis results in adrenal insufficiency and increases the severity of the acute inflammation and impairs the healing phase.