Συμμετοχή τη εκλυτικής ορμόνης της κορτικοτροπίνης (CRH) στη φλεγμονώδη διαδικασία

Abstract

The term Inflammatory bowel disease (IBD) refers to a chronic inflammatory, relapsing disease represented mainly by ulcerative colitis (U.C.) and Crohn's disease (C.D.). The aetiology of IBD has not yet been elucidated, a fact that contributes to lack of specific effective treatments. The prevailing recent studies, support the role of disruption of the balance of intestinal barrier, which is determined by the interaction between genetic background and the environment. The result of this disorder is the dysfunction of the immune system, mainly the innate immune responses, and the development of chronic active inflammation. In previous studies the proinflammatory effects of corticotrophin releasing hormone / factor (CRH/CRF), a neuropeptide acting as the major mediator of the stress response, in the human and rodent gastrointestinal system have been demonstrated. By means of an experimental model that resembles ulcerative colitis and is linked with innate immunity, the relation between the lack of CRH and the increased susceptibility to disease development was demonstrated. Aiming to investigate the role of CRH in experimental IBD, the course of DSS colitis during the termination of inflammatory response and the repair of tissue injury was observed. Surprisingly, the disease progressed in Crh-/- mice, resulting to their severely compromised survival 5 days after cessation of DSS treatment, while all Crh+/+ mice recovered as expected. This development was characterized by significant continuous body weight loss, active inflammation with evidence of increased angiogenesis, dysfunctional regeneration of the inflamed epithelium and development of fibrosis. This picture was not reversed after normalization of glulcocorticoid levels of the Crh-/- mice, in further support of the hypothesis of direct CRH action in the development of ulcerative colitis. In conclusion, these findings demonstrate the requirement of CRH for the epithelial repair to occur following colitis induction, and the development of adaptive responses in colitis and the resolution of inflammation.