Glucagonlike peptide-2 analogue: A possible new approach in the management of inflammatory bowel disease

Background/Purpose: Glucagonlike peptide-2alpha (GLP-2alpha) has been shown to be a growth factor for the small intestine. This study investigated the benefits of intravenous and intraluminal administration of GLP-2alpha using a rat model of inflammatory bowel disease (IBD). Methods: Normal Fisher rats and HLA-B27 (IBD) rats were treated for 14 days as follows: Fisher, intravenous saline (n = 6); HLA-B27, intravenous saline (n = 6); HLA-B27, intravenous GLP-2alpha (50 mug/kg/d; n = 5); Fisher, intraluminal saline (n = 5); HLA-B27, intraluminal saline (n = 5); or intraluminal GLP-2alpha (50 mug/kg/d; n = 5). Rats were evaluated for frequency of diarrhea, and the bowel was analyzed for gross and microscopic lesions. Statistical evaluations were determined using analysis of variance (ANOVA). A P value of .05 was significant. Results: Intravenous GLP-2alpha decreased diarrhea and the number of bowel lesions (P < .05). Microscopic inflammation was reduced by 24% but was not statistically significant. Intraluminal GLP-2α decreased the number of small intestine lesions (P < .05) and the microscopic inflammation (P < .05) but did not significantly reduce diarrhea or the overall number of bowel lesions. Conclusions: GLP-2α ameliorates the signs of IBD in HLA-B27 rats. Intravenous GLP-2α reduces diarrhea more effectively than intraluminal administration, and both routes are equally effective in ameliorating inflammation. GLP-2α potentially provides a new modality for the treatment of IBD.