rHuKGF ameliorates symptoms in DSS and CD4(+)CD45RB(Hi) T cell transfer mouse models of inflammatory bowel disease.

Published

Journal Article

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(+)CD45RB(Hi) 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 10(5) CD4(+)CD45RB(Hi) 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.

Full Text

Duke Authors

Cited Authors

  • Byrne, FR; Farrell, CL; Aranda, R; Rex, KL; Scully, S; Brown, HL; Flores, SA; Gu, LH; Danilenko, DM; Lacey, DL; Ziegler, TR; Senaldi, G

Published Date

  • April 2002

Published In

Volume / Issue

  • 282 / 4

Start / End Page

  • G690 - G701

PubMed ID

  • 11897629

Pubmed Central ID

  • 11897629

International Standard Serial Number (ISSN)

  • 0193-1857

Digital Object Identifier (DOI)

  • 10.1152/ajpgi.00314.2001

Language

  • eng

Conference Location

  • United States