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Am J Physiol Gastrointest Liver Physiol 282: G690-G701, 2002. First published December 12, 2001; doi:10.1152/ajpgi.00314.2001
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Vol. 282, Issue 4, G690-G701, April 2002

rHuKGF ameliorates symptoms in DSS and CD4+CD45RBHi T cell transfer mouse models of inflammatory bowel disease

Fergus R. Byrne1, Catherine L. Farrell2, Richard Aranda3, Karen L. Rex1, Sheila Scully1, Heather L. Brown1, Silvia A. Flores1, Li H. Gu4, Dimitry M. Danilenko1, David L. Lacey1, Thomas R. Ziegler4, and Giorgio Senaldi1

1 Departments of Pharmacology and Pathology and 2 Product Development, Amgen, Thousand Oaks, 91320, 3 Division of Digestive Diseases, UCLA School of Medicine and Greater Los Angeles Veterans Affairs Hospital System, Los Angeles, California 90095 and 4 Department of Medicine, Emory University, Atlanta, Georgia 30322

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 × 105 CD4+CD45RBHi T cells into immunodeficient scid/scid mice. rHuKGF was administered by subcutaneous injection at doses of 1.0 or 3.0 mg/kg in both preventative and therapeutic regimens during both studies. rHuKGF significantly improved survival and body weight 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 body weight 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.

colitis; growth factor; epithelial repair; intestinal trefoil factor


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