Abstract
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.
Footnotes
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Send reprint requests to: Kevin Connolly, Ph.D., Department of Pharmacology, Human Genome Sciences, Inc., 9410 Key West Ave., Rockville, MD 20850. E-mail: kevin_connolly{at}hgsi.com
- Abbreviations:
- DSS
- dextran sulfate sodium
- FGF
- fibroblast growth factor
- IBD
- inflammatory bowel disease
- KGF
- keratinocyte growth factor
- MPO
- myloperoxidase
- TNF
- tumor necrosis factor
- Received October 30, 1998.
- Accepted March 17, 1999.
- The American Society for Pharmacology and Experimental Therapeutics
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