Abstracts
2000 Digestive Disease Week

# 2226 Novel Use of Hepatocyte Growth Factor in the Treatment of Inflammatory Bowel Disease.
Karim Alavi, Marshall Z. Schwartz, Rajeev Prasad, Juan P. Palazzo, Philadelphia, PA, Washington, DC, Wilmington, DE

This study was designed to evaluate the potential therapeutic benefit of Hepatocyte Growth Factor (HGF)in Inflammatory Bowel Disease (IBD). Methods: Five adult F344 and 9 HLA-B27 rats aged 20-24 weeks were used in this study. Five HLA-B27 rats had a 14-day systemic (jugular vein) infusion initiated using subcutaneous osmotic pumps. Rats were divided into 3 groups: F344-no treatment(n=5), HLA-B27-no treatment (n=4),HLA-B27- HGF at 150 µg/kg/d (n=5). Following infusion, all animals were sacrificed, the GI tract harvested, and opened along its antimesenteric border. Total mucosal damage (% surface area) was measured using Image Analysis Software (Sigmascan 2.0). Microscopic analysis was performed and scored as follows: 0-no inflammation, 1-mild inflammation extending into submucosa, 2-moderate inflammation extending into muscularis propria, and 3- severe inflammation. Total RNA was extracted from colonic mucosal samples and assayed for Tumor Necrosis Factor-a (TNF), Interferon-? (INF), and Interleukin-2(IL-2) gene expression by RT/PCR. Glyceraldehyde-3-Phosphate Dehydrogenase (GAPD) was used as the internal standard. Statistical analysis was performed using Student’s t-test and expressed as mean ± SEM. Results: Conclusions: These data demonstrate that HGF significantly reduces gross (90% decrease) and histologic lesions (53% decrease) in a model of IBD. The beneficial effect of HGF is further supported by a significant decrease in gene expression of the inflammatory mediators, TNF(52% decrease) and INF(93% decrease). These results demonstrate a potential therapeutic role for HGF in IBD.