Deficiency of the intestinal growth factor, glucagon-like peptide 2, in the colon of SCID mice with inflammatory bowel disease induced by transplantation of CD4+T cells

Background: Glucagon-like peptide 2 (GLP-2) is produced in endocrine L-cell s of the intestinal mucosa. Recently, GLP-2 was found to stimulate intestin al mucosal growth. Our objective was to study the content of GLP-2 in the l arge intestine in a murine model of T-cell-induced inflammatory bowel disea se. Methods: inflammation was induced by adoptive transfer of CD4+ blast T cells from BALB/c mice to SCID mice. The amount of GLP-2 (1-33) was measure d with a specific, NH2-terminally directed radioimmunoassay in tissue extra cts from the large intestine of transplanted mice developing colitis and fr om BALB/c and SCID control mice. Results: in the middle and descending colo n segments showing the most severe signs of inflammatory lesions in the CD4 + T-cell-transplanted mice, the amount of GLP-2 was significantly lower tha n in similar colon segments in both untransplanted SCID mice and normal BAL B/c mice (P = 0.0013 and 0.0033). In the descending colon the amount of GLP -2 was 6.7 +/- 1.0 pmol/ g protein in the CD4+ transplanted mice compared w ith 68.4 +/- 20.3 and 42.7 +/- 4.3 in the two groups of control mice. Simil ar findings were mode with regard to the contents of the two ether progluca gon-derived intestinal peptides, glicentin and GLP-1. Conclusion: The amoun t of GLP-2 is markedly reduced in the colon of mice with a T-cell-induced i nflammatory bowel disease histopathologically resembling both Crohn disease and ulcerative colitis. This observation may provide a pathophysiologic ra tionale for administration of GLP-2 as a trophic factor in inflammatory bow el disease.