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Vol. 290, Issue 1, 464-471, July 1999

Efficacy of Keratinocyte Growth Factor-2 in Dextran Sulfate Sodium-Induced Murine Colitis

Renée Miceli, Melissa Hubert, Gemma Santiago, Da-Lin Yao, Timothy A. Coleman, Kathleen A. Huddleston and Kevin Connolly

Department of Pharmacology, Human Genome Sciences, Inc., Rockville, Maryland

The purpose of this study was to determine the efficacy of a novel human protein, keratinocyte growth factor-2 (KGF-2), in a model of murine colitis induced by ad libitum exposure to a 4% solution of dextran sulfate sodium (DSS) in the drinking water. Initial evaluation of KGF-2 was based on its ability to reduce weight loss, stool score, and histological score in mice exposed to DSS for 7 days. When KGF-2 (0.1-10.0 mg/kg i.p. or s.c.) was injected daily into DSS-treated mice from day 0 to 7, it significantly reduced all three parameters in a dose-response fashion, with a minimum effective dose of between 1 and 3 mg/kg. When KGF-2 was given therapeutically, starting 4 days after initiation of the 7-day DSS treatment, the 3- but not the 0.5-mg/kg dose significantly enhanced weight recovery after discontinuation of DSS treatment. When DSS treatment was prolonged beyond the normal 7 days, therapeutic intervention on day 2 or 4 also significantly reduced mortality, weight loss, and stool score at the 1- and 3-mg/kg dose. Therapeutic treatment also resulted in reduction of colon myloperoxidase levels by more than 50%. These experiments suggest that KGF-2 may be clinically useful in the treatment of inflammatory bowel diseases such as ulcerative colitis and Crohn's disease.


0022-3565/99/2901-0464$03.00/0
THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Copyright © 1999 by The American Society for Pharmacology and Experimental Therapeutics



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