Can we influence fibrosis in Crohn's disease?

Despite recent advances in the therapy of active Crohn's disease (CD) fibrostenosis remains a challenging complication of the disease. Transmural inflammation of CD is associated with phenotypic switch of the mesenchymal cells resulting in proliferation and collagen deposition. Both resident myofibroblasts and smooth muscle are candidate progenitor cells of the fibrogenic cells in CD stenoses. The principal growth factors involved in intestinal fibrosis have not been identified although TGF-beta1 and 2, PDGF and IL-1 may be involved. Research aimed at elucidating the basic mechanisms underlying fibrosis in the gut has been hindered by the lack of an adequate animal model. Recently, however, new rodent models of chronic inflammation with distinct fibrosis have been described. Cell culture research has provided more information about possible pathways that may limit uncontrolled mesenchymal proliferation in the inflamed intestinal wall. The modulator role of neurotransmitters such as VIP, nitric oxide and prostaglandines is an important target for therapeutic intervention. Interfering with the phenotypic switch of mesenchymal cells may offer new therapeutic perspectives in the prevention of fibrostenosis. Further in vitro and animal studies as well as restenosis prevention studies are needed to develop pharmacological tools in the prevention of Crohn's disease fibrostenosis.