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