We have established an extracorporeal bowel model system for the analysis of early events in
inflammatory bowel disease (IBD) and therapeutic applications. This model consists of an intestinal segment that is cannulated and perfused in situ, allowing the investigation of cellular responses of apical mucosa cells on
luminal applied substances. Short-term treatment with
iodoacetamide mimicked experimental intestinal
inflammation in IBD, as indicated by histological alterations such as
hemorrhage,
hyperemia and loss of regular crypt architecture, as well as enhanced expression of
cytokines (e.g. IL-6, IL-10 and MCP-1) compared with control segments perfused with media. Perfusion of therapeutic agents (e.g.
dexamethasone or Mutaflor) in the small intestine segment significantly reduced the features of early
inflammation that are induced by
iodoacetamide. Moreover, similar data were obtained for Resormin(®), a
montmorillonite-
illite mixed-layer
mineral (
smectite), indicating that smectites might be a newly identified therapeutic option for IBD. In summary, this model could provide novel insights into epithelial injury as well as genesis of IBD and, therefore, be useful in testing the therapeutic potential of compounds for IBD
therapy.