Efficacy of keratinocyte growth factor-2 in dextran sulfate sodium-inducedmurine colitis

The purpose of this study was to determine the efficacy of a novel human pr otein, keratinocyte growth factor-2 (KGF-2), in a model of murine colitis i nduced by ad libitum exposure to a 4% solution of dextran sulfate sodium (D SS) in the drinking water. Initial evaluation of KGF-2 was based on its abi lity to reduce weight loss, stool score, and histological score in mice exp osed to DSS for 7 days. When KGF-2 (0.1-10.0 mg/kg i.p. or s.c.) was inject ed daily into DSS-treated mice from day 0 to 7, it significantly reduced al l three parameters in a dose-response fashion, with a minimum effective dos e 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, t herapeutic intervention on day 2 or 4 also significantly reduced mortality, weight loss, and stool score at the 1- and 3-mg/kg dose. Therapeutic treat ment 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 bower diseases such as ulcerative colitis and Cro hn's disease.