Ulcerative colitis: immune function, tissue fibrosis and current therapeutic considerations.

BACKGROUND: Ulcerative colitis (UC) is a complex disease in which the interaction of genetic, environmental and microbial factors drives chronic intestinal inflammation that finally leads to extensive tissue fibrosis. DISCUSSION: The present review discusses the current knowledge on genetic susceptibility, especially of the IL-12/IL-23 pathway, the pathophysiologic role of the involved cytokines (e.g. IL-13, IL-23, TGFβ1) and immune cells (e.g. T cells, epithelial cells, fibroblasts) in UC followed by an overview on actual therapeutic considerations. These future therapies will target selectively the involved cell types by blocking their activation and its downstream signalling, by inhibiting their migration to the inflamed site and by anti-cytokine strategies. This may avoid-when initiated in time-the perpetuation of the inflammatory mechanisms thus preventing fibrosis. With respect to animal models that have guided the most productive efforts for understanding human inflammatory bowel disease, these will be shortly discussed in the respective context.