Hepatocyte growth factor attenuates pancreatic damage in caerulein-inducedpancreatitis in rats

Hepatocyte growth factor (HGF) overexpression was reported in experimental and clinical acute pancreatitis. These observations prompted us to determin e the effect of HGF administration on the development of caerulein-induced pancreatitis in rats, Acute pancreatitis was induced by s.c. infusion of ca erulein (10 mug/kg/h) for 5 h. HGF was administrated twice (30 min before c aerulein or saline infusion and 3 h later) at the doses: 0.4, 2, 10 or 50 m ug/kg s.c. Immediately after cessation of caerulein or saline infusion, the pancreatic blood flow, plasma amylase and lipase activity, plasma cytokine s concentration, cell proliferation, and morphological signs of pancreatiti s were examined. Caerulein administration induced acute edematous pancreati tis manifested by 41% decrease in DNA synthesis, 53% inhibition of pancreat ic blood flow, a significant increase in plasma amylase and lipase activity , plasma interleukin-1 beta and interleukin-6 concentration, as well as, th e development of the histological signs of pancreatic damage (edema, leukoc yte infiltration, and vacuolization). Administration of HGF without inducti on of pancreatitis increased plasma interleukin-10. Treatment with HGF, dur ing induction of pancreatitis, increased plasma interleukin-10 and attenuat ed the pancreatic damage, what was manifested by histological improvement o f pancreatic integrity, the partial reversion of the drop in DNA synthesis and pancreatic blood flow, and the reduction in pancreatitis evoked increas e in plasma amylase, lipase, and interleukin-ID and interleukin-6 levels. H GF administrated at the dose 2 mug/kg exhibited a similar beneficial effect as administration of HGF at the doses 10 or 50 mug/kg. Treatment with HGF at the dose 0.4 mug/kg was less effective. We conclude that: (1) administra tion of HGF attenuates pancreatic damage in caerulein-induced pancreatitis; (2) this effect seems to be related to the increase in production of inter leukin-10, the reduction in release of interleukin-lp and interleukin-6, an d the improvement of pancreatic blood flow. (C) 2001 Elsevier Science B.V. All rights reserved.