Thymic Involution Correlates with Severe Ulcerative Colitis Induced by Oral Administration of Dextran Sulphate Sodium in C57BL/6 Mice but not in BALB/c Mice

Abstract

There is accumulating evidence to support the interactions between psychological stress and inflammatory bowel disease (IBD). In order to elucidate the relationship between psycoimmunological stress and IBD, we examined the alteration of immune system during the disease course of experimental Ulcerative colitis(UC)-model induced by dextran sulfate sodium (DSS). When C57BL/6 mice were treated with 4.5% DSS, they developed progressive weight loss. In contrast, the same treatment applied to BALB/c mice led to a small weight loss from which they soon recovered. Surprisingly, we found significant involution of the thymus and a reduction in the number of double positive thymocytes in DSS-treated C57BL/6 mice but not in DSS-treated BALB/c mice. Double negative thymocytes, especially DN1 (CD25-CD44+) and DN2 (CD25+CD44+) thymocytes, were relatively upregulated. The weights of spleens were slightly increased in both C57BL/6 and BALB/c mice following oral administration of DSS. In C57BL/6 spleens, both CD4 and CD8 single positive T cells gradually decreased (day 3), then recovered (day 14) after treatment. Because oral administration causes starvation, we examined the effects of starvation on the thymus and spleen. Although involution of thymus was observed both in starvation and DSS-treatment, the weight of spleen was reduced only in starvation. Also, the population changes in thymocytes in starvation was different from DSS-treatment. The administration of the steroid inhibitor RU486 partially reversed the thymic involution in C57BL/6 mice, thus DSS-treated UC might induce psycoimmunological changes partly through hypothalamic-pituitary-adrenal axis.