Intestinal fibrosis in inflammatory bowel disease: progress in basic and clinical science

Abstract

Intestinal fibrosis is a potentially serious complication of inflammatory bowel disease and its pathophysiology is still unclear. This review will discuss recent developments relating to sources of fibroblasts in intestinal inflammation, mediators that modulate fibroblast activation and function, as well as new clinical, laboratory, endoscopic and radiological studies aimed at improving diagnosis and management of intestinal fibrosis in inflammatory bowel disease. The fibroblast remains the central cell responsible for intestinal fibrosis in inflammatory bowel disease and transforming growth factor-beta1 is still the most potent pro-fibrogenic cytokine. Novel mediators, however, are being identified that modulate fibroblast function, such as interleukin-13, interleukin-21, galectin-3, osteopontin, Wnt and toll-like receptor ligands, and anti-tumor necrosis factor-alpha agents. New fibroblast sources are being identified, such as fibrocytes, and new mechanisms of fibroblast generation, like epithelial- and endothelial-to-mesenchymal transition. Animal models of intestinal fibrosis are still few, but new ways to induce gut fibrosis are being explored. Serological markers indicating a clinically complicated course that includes intestinal fibrosis are promising and are being tested in adult and pediatric populations, particularly in Crohn's disease. Video capsule endoscopy, the Given Patency capsule, double balloon enteroscopy, and computed tomographic enteroscopy are some of the new modalities being developed to assess the risk and improve the diagnosis of intestinal fibrosis. Novel therapeutic approaches include endoscopic balloon dilatation with conventional and double balloon enteroscopy, and local injection of glucocorticoids and tumor necrosis factor-alpha blockers, showing partial but encouraging success. More studies are needed to improve knowledge of the pathophysiology of intestinal fibrosis if better preventive, diagnostic and therapeutic measures are to be expected in the near future.