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Articles in PresS, published online ahead of print December 12, 2001
Am J Physiol Gastrointest Liver Physiol, 10.1152/ajpgi.00314.2001
Submitted on July 18, 2001
Accepted on November 22, 2001
1 Pathology, Amgen Inc, Thousand Oaks, CA, USA
2 Product Development, Amgen Inc, Thousand Oaks, CA, USA
3 Medicine / Digestive Diseases, U of California Los Angeles, Los Angeles, CA, USA; West LA Veterans Affairs Hospital, Greater LA VA Healthcare System, Los Angeles, CA, USA
4 Department of Medicine, Emory University, Atlanta, GA, USA
* To whom correspondence should be addressed. E-mail: fbyrne{at}amgen.com.
There is an acute need for effective therapy for inflammatory bowel disease (IBD), particularly at the level of repair of the damaged epithelium. We evaluated the efficacy of recombinant human keratinocyte growth factor (rHuKGF) in both the dextran sodium sulfate (DSS) and the CD4+CD45RBHi T cell transfer models of IBD. Disease was induced either by the ad libitum administration to normal mice of 4% DSS in the drinking water or by the injection of 4 x 105 CD4+CD45RBHi T cells into immunodeficient scid/scid mice. rHuKGF was administered by sub-cutaneous injection at doses of 1.0 or 3.0 mg/kg in both preventative and therapeutic regimens over the course of both studies. rHuKGF significantly improved survival and body weight (BW) loss in the DSS model, in both preventative and therapeutic dosing regimens. It also improved diarrhea, hematochezia and hematological parameters, as well as large intestine histopathology. In the T cell transfer model, rHuKGF improved BW loss, diarrhea and levels of serum amyloid A as well as large intestine histopathology. In both models of IBD, the colonic levels of intestinal trefoil factor (ITF) were elevated by the disease state and further elevated by treatment with rHuKGF. These data suggest that rHuKGF may prove useful in the clinical management of IBD and its effects are likely mediated by its ability to locally increase the levels of ITF.
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