Efficacy of keratinocyte growth factor-2 in dextran sulfate sodium-induced murine colitis.
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.
Miceli
R
R
Department of Pharmacology, Human Genome Sciences, Inc., Rockville, Maryland, USA.
Hubert
M
M
Santiago
G
G
Yao
D L
DL
Coleman
T A
TA
Huddleston
K A
KA
Connolly
K
K
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D003106:Colon / Q000201:enzymology; D016264:Dextran Sulfate; D005243:Feces; D005260:Female; D051526:Fibroblast Growth Factor 10; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism*; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism
C496463:FGF10 protein, human; C496453:FGF7 protein, human; C496464:Fgf10 protein, mouse; C496454:Fgf7 protein, mouse; D051526:Fibroblast Growth Factor 10; D006133:Growth Substances; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D016264:Dextran Sulfate; D009195:Peroxidase