Abstract
SUMMARYWe 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.
Highlights
Crohn’s disease (CD) and ulcerative colitis (UC), collectively termed inflammatory bowel diseases (IBD), represent chronic relapsing and remitting disorders of the gastrointestinal tract
The authors generated an extracorporeal bowel system based on a single-pass intestinal in situ perfusion method, using iodoacetamide (IA), an alkylating agent that induces irreversible mucosal cell damage
IA treatment significantly enhanced mRNA transcript levels of pro-inflammatory cytokines and reduced the mRNA expression of the mucosal defense factor intestinal alkaline phosphatase. These data indicate that IA treatment mimicked the experimental intestinal inflammation characteristics of IBD
Summary
Crohn’s disease (CD) and ulcerative colitis (UC), collectively termed inflammatory bowel diseases (IBD), represent chronic relapsing and remitting disorders of the gastrointestinal tract. Crohn’s disease and ulcerative colitis are types of inflammatory bowel disease (IBD). Both are chronic, non-infectious inflammatory diseases of the human gastrointestinal tract. There is currently no cure for IBD, and affected individuals usually have to undergo lifelong drug therapy and/or surgical treatment. Several animal models have been established, allowing the analysis of the pathology of IBD.
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