Hepatocyte growth factor treatment ameliorates diarrhea and bowel inflammation in a rat model of inflammatory bowel disease

J Pediatr Surg. 2004 Feb;39(2):139-43; discussion 139-43. doi: 10.1016/j.jpedsurg.2003.10.001.

Abstract

Background/purpose: Transfection of the HLA-B27 gene into normal Fischer rats induces phenotypic changes similar to inflammatory bowel disease (IBD). This study investigated the benefits of 2 doses of hepatocyte growth factor (HGF) on the manifestations of IBD in this rat model.

Methods: Fischer rats and HLA-B27 rats were divided into 4 groups: Fischer rats treated with saline, HLA-B27 rats treated with saline, HGF at 150 microg/kg/d, and HGF at 300 microg/kg/d. HGF or saline was infused for 14 days via an osmotic pump attached to a catheter in the internal jugular vein. After treatment, rats were evaluated for diarrhea and reduction in gross and microscopic bowel inflammation. Statistics were determined using analysis of variance (ANOVA). A P value < or =.05 was considered significant.

Results: Administration of HGF at 150 microg/kg/d decreased diarrhea by 40%, gross inflammation by 41%, and microscopic inflammation by 72% (P < or =.05). At 300 microg/kg/d HGF decreased diarrhea by 46%, gross inflammation by 45%, and microscopic inflammation by 54% (P < or =.05).

Conclusions: HGF administration reduces the clinical manifestations of IBD in this rat model. Similar effects were seen at both doses of HGF administration, implying that there is a plateau above which further increases in HGF levels provides no added benefit. HGF administration may be clinically useful in the management of IBD.

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Diarrhea / drug therapy*
  • Diarrhea / etiology
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Drug Evaluation, Preclinical
  • Female
  • HLA-B27 Antigen / genetics*
  • Hepatocyte Growth Factor / administration & dosage
  • Hepatocyte Growth Factor / pharmacology
  • Hepatocyte Growth Factor / therapeutic use*
  • Inflammatory Bowel Diseases / drug therapy*
  • Inflammatory Bowel Diseases / genetics
  • Inflammatory Bowel Diseases / pathology
  • Infusions, Intravenous
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / pathology
  • Rats
  • Rats, Inbred F344
  • Regeneration / drug effects

Substances

  • HLA-B27 Antigen
  • Hepatocyte Growth Factor