Epidermal growth factor protects against pancreatic damage in cerulein-induced pancreatitis

Epidermal growth factor (EGF) exhibits gastroprotective and ulcer-healing a ction. These observations prompted us to determine the influence of EGF on cerulein-induced pancreatitis (CIP) in the rat. Acute pancreatitis was indu ced by subcutaneous infusion of cerulein (10 mu g/kg/h) for 5 h, Initially EGF was administrated twice at doses of 1, 5, 10 or 100 mu g/kg s.c. (first injection 30 min prior to cerulein infusion, and the second injection 2.5 h after the start of cerulein infusion) and from this part of study 10 mu g /kg was chosen for the next experiments. CIP led to a significant decrease in DNA synthesis and a reduction in pancreatic blood flow (PBF) by 42 and 3 0%, respectively, as well as a significant increase in pancreatic weight, p lasma amylase concentration, plasma interleukin-1 beta (IL-1 beta) level an d the development of the histological signs of pancreatic damage with marke d edema, leukocyte infiltration and vacuolization of acinar cells. Treatmen t with EGF attenuated the pancreatic tissue damage in CIP as manifested by partial reversal of the drop in DNA synthesis and improvement of pancreatic histology. Moreover, EGF administration attenuated the fall in PBF and sig nificantly reduced the cerulein-evoked increase in pancreatic weight. Also plasma amylase and IL-1 beta were decreased in rats treated with EGF. We co nclude that: (1) EGF exerts a protective effect against CIP, and (2) the be neficial activity of EGF in CIP seems to depend on the increase in pancreat ic cell proliferation, the reduction in cytokine generation and the attenua tion of the fall in PBF.