Abstracts
1999 Digestive Disease Week

# 2156 TRANSFORMING GROWTH FACTOR b1 INDUCES HEPATOCELLULAR INJURY IN RAT SEVERE ACUTE PANCREATITIS
Yuichi Hori, Yoshifumi Takeyama, Takashi Ueda, Kozo Takase, Masahiro Goshima, Masahiro Yamamoto, Yoshikazu Kuroda, Kobe Univ Sch of Medicine, Kobe Japan

The mechanism of hepatic failure in severe acute pancreatitis is unclear. Cell injury via humoral mediators by activated macrophage have been reported. We have already shown both Kupffer cell and peritoneal macrophage are activated in rat with edematous acute pancreatitis. The purpose of this study is to examine which mediator is responsible for hepatocellular injury in vivo and in vitro. The necrotizing pancreatitis was induced on male Wistar rats by retrograde injection of 20 % sodium deoxycholate into pancreatic duct. The peritoneal exudate was collected aseptically 6 hours after induction of pancreatitis, centrifuged, and then the supernatant was collected as pancreatitis-associated ascitic fluid (PAAF). In vivo studies, the extent of hepatocellular injury was evaluated by the serum level of ALT and immunohistochemical study for tumor necrosis factor-a(TNF-a), inducible nitric oxide synthase (iNOS) and transforming growth factor-b1 (TGF-b1) were examined in the liver and peritoneal macrophages. Moreover, Reverse Transcription-Polymerase Chain Reaction (RT-PCR) was used to quantitate TGF-b1 mRNA in the liver and peritoneal macrophages. Secondly, in vitro study, the cytotoxicity of the PAAF on rat primary-cultured hepatocytes was investigated using MTT cellular proliferation assay. In addition, the effect of neutralizing antibody to TGF-bwas studied in vivo and in vitro studies. In the rats with necrotizing pancreatitis, serum ALT and amylase significantly elevated to 248.2±67.0 IU/L and 37,800±4,800 IU/L, respectively. In the liver and peritoneal macrophages, strong expression of TGF-b1 was detected early in the course of pancreatitis. However, neither TNF-anor iNOS was detected. Moreover, TGF-b1 mRNA was significantly increased quantitatively. The hepatocytocidal activity of PAAF was elevated in a dose-dependent manner. Neutralizing antibody to TGF-bpartly blocked the elevation of serum ALT level (144.2±14.9 IU/L) in vivo and hepatcytocidal activity in vitro. In conclusion, TGF-b1 is possibly involved in hepatocellular injury in severe acute pancreatitis.

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