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Research ArticleArticle

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
Journal of Pharmacology and Experimental Therapeutics July 1999, 290 (1) 464-471;
Renée Miceli
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Melissa Hubert
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Gemma Santiago
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Da-Lin Yao
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Timothy A. Coleman
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Kathleen A. Huddleston
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Kevin Connolly
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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

  • 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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Journal of Pharmacology and Experimental Therapeutics: 290 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 290, Issue 1
1 Jul 1999
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Research ArticleArticle

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
Journal of Pharmacology and Experimental Therapeutics July 1, 1999, 290 (1) 464-471;

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Research ArticleArticle

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
Journal of Pharmacology and Experimental Therapeutics July 1, 1999, 290 (1) 464-471;
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