Glucagon-like peptide-2 and common therapeutics in a murine model of ulcerative colitis.
The intestinal hormone glucagon-like peptide-2 (GLP-2) enhances bowel growth and reduces the severity of colonic injury in dextran sulfate sodium (DSS)-induced colitis in mice. In humans, ulcerative colitis is normally treated with aminosalicylates (ASAs) and corticosteroids (CSs) to reduce inflammation. However, whether the intestinotropic effects of GLP-2 are altered when combined with ASAs and/or CSs has not previously been explored. Thus, each agent [vehicle, ASA (sulfasalazine), CS (methylprednisolone), and ASA + CS] was administered alone or with GLP-2 to normal mice or mice with 3.5% DSS in the drinking water, for 10 consecutive days. GLP-2 treatment of DSS-mice increased survival and small intestinal weight (p < 0.05), and decreased body weight loss and colonic damage (p < 0.05). Furthermore, GLP-2 increased the number of proliferating cells in the colonic crypts of DSS-mice (p < 0.05). Administration of ASA, CS, or ASA + CS alone did not affect growth of the intestine in DSS-mice. However, administration of GLP-2 in combination with ASA was permissive for the beneficial effects of GLP-2 on survival and colonic damage, whereas CS treatment prevented these effects of GLP-2. Concomitant administration of GLP-2 with ASA + CS resulted in intermediate effects. No differences between colonic myeloperoxidase activity or IkappaB levels (an inhibitor of the nuclear factor-kappaB pro-inflammatory pathway) were found for any of these therapeutic agents. When taken together, the ability of GLP-2 to protect colonic mucosal architecture in DSS-colitis, and its effectiveness when given in combination with ASA, but not with CS, suggests a novel approach for the treatment of patients with colitis.
L'Heureux
Marie-Claude
MC
Department of Physiology, University of Toronto, Medical Sciences Building, Room 3366, 1 King's College Circle, Toronto, Ontario, M5S 1A8, Canada.
Brubaker
Patricia L
PL
D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D000636:Aminosalicylic Acids / Q000627:therapeutic use*; D000818:Animals; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000473:pathology; D003106:Colon / Q000187:drug effects; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005260:Female; D053767:Glucagon-Like Peptide 2; D004763:Glucagon-Like Peptides; D006801:Humans; D007421:Intestine, Small / Q000187:drug effects; D051379:Mice; D010446:Peptide Fragments / Q000627:therapeutic use; D010455:Peptides / Q000627:therapeutic use*
D000305:Adrenal Cortex Hormones; D000636:Aminosalicylic Acids; D053767:Glucagon-Like Peptide 2; D010446:Peptide Fragments; D010455:Peptides; D004763:Glucagon-Like Peptides