PT  - JOURNAL ARTICLE
AU  - Moore, Beverley A.
AU  - Peffer, Nancy
AU  - Pirone, Allison
AU  - Bassiri, Ashlyn
AU  - Sague, Sarah
AU  - Palmer, Jeffrey M.
AU  - Johnson, Dana L.
AU  - Nesspor, Tom
AU  - Kliwinski, Connie
AU  - Hornby, Pamela J.
TI  - GLP-2 Receptor Agonism Ameliorates Inflammation and Gastrointestinal Stasis in Murine Postoperative Ileus
AID  - 10.1124/jpet.109.161497
DP  - 2010 May 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 574--583
VI  - 333
IP  - 2
4099  - http://jpet.aspetjournals.org/content/333/2/574.short
4100  - http://jpet.aspetjournals.org/content/333/2/574.full
SO  - J Pharmacol Exp Ther2010 May 01; 333
AB  - Glucagon-like peptide 2 (GLP-2) is a pleiotropic intestinotrophic hormone that we hypothesized could lessen gastrointestinal inflammation associated with postoperative ileus (POI). To test this idea, the prophylactic timing and dose of a long-acting variant of human GLP-2 linked to the Fc portion of murine immunoglobulin G (IgG) (GLP-2/IgG) was optimized in a murine model of POI. Surgically treated mice received a single dose of GLP-2/IgG, IgG isotype control, or phosphate-buffered saline 1 to 48 h before small bowel surgical manipulation. The distribution of orally fed fluorescein isothiocyanate-dextran and histological analyses of myeloperoxidase-positive immune cells were determined 24 and 48 h postoperatively. TaqMan quantitative polymerase chain reaction was used to determine early changes in mRNA expression in the muscularis or mucosa. In normal mice, prolonged exposure to GLP-2 increased upper gastrointestinal (GI) transit and mucosal weight. When administered 1 or 3 h before surgery, GLP-2/IgG reduced the leukocyte infiltrate 24 and 48 h postoperatively and improved GI transit 48 h postoperatively. Surgical manipulation rapidly increased gene expression of proinflammatory cytokines and enzymes for kinetically active mediators in the mucosa and muscularis. GLP-2/IgG2a affected the expression of genes associated with mucosal inflammation and barrier function. We conclude that prophylactic treatment with a long-acting GLP-2 agonist ameliorates inflammation and improves intestinal dysmotility associated with surgical manipulation of the bowel. The action of GLP-2 is consistent with a lessening of inflammation, leading to a more rapid recovery. Copyright © 2010 by The American Society for Pharmacology and Experimental Therapeutics