Glucocorticoids and Hypothalamic-Pituitary-Adrenal Interactions in the Modulation of Mucosal Immunity

Since immune responses in Inflammatory Bowel Disease (IBD) may be modulated by the hypothalamic-pituitary-adrenal axis (HPA), we aimed to understand the role of this neuroimmunendocrine interaction in experimental colitis. Therefore, C57BL/6 male mice were subjected to bilateral adrenalectomy and inflammation was induced by oral intake of water containing 3% dextran sulfate sodium (DSS). Colitis led to increased plasma corticosterone levels, which were lowered after adrenalectomy. The absence of endogenous glucocorticoids was associated to elevated disease clinical score and accumulation of CD4 and CD8 T cells in lamina propria together with high local IFN-γ production, despite overall reduced infiltrate and accumulation of tolerogenic dendritic cells in gut mucosa. Furthermore, adrenalectomized mice exposed to DSS presented reduced accumulation of regulatory cells and increased susceptibility to colitis, as observed by the augmented mortality, which was not recued after exogenous glucocorticoid treatment. Finally, we concluded that HPA axis plays important role in the modulation of gut immunity, especially in experimental colitis.

Financial Support: FAPESP under agreement 2010/20162-7.