Specific changes in the pancreatic expression of the interleukin 1 family of genes during experimental acute pancreatitis

Interleukin 1 beta (IL-1 beta) is produced in large amounts during acute pancreatitis and is believed to play a primary role in determining pancreatitis severity and the degree of pancreatic tissue destruction, This study was undertaken to characterize intrapancreatic production of IL-1 beta and the remainder of the IL-1 family of genes during sterile acute pancreatitis, Moderate or severe necrotizing pancreatitis wits induced by the intraperitoneal injection of a cholecystokinin analogue or the feeding of a choline deficient diet, respectively, Animals were killed during the progression of pancreatitis with severity scored by histological grading and serum amylase concentration, The expression of IL-1 beta, IL-1 Receptor 1 (IL-1R1), IL-1R2, IL-1R antagonist (IL-1Ra), and ICE mRNA within the pancreas was examined by quantitative differential RT-PCR, Corresponding intrapancreatic and serum proteins were measured by enzyme-linked immunosorbent assay (ELISA). There was constitutive expression of pancreatic IL-1R1, IL-1R2, IL-1Ra, and ICE but not IL-1 beta, As pancreatitis developed, mRNA for IL-1 beta, IL-1Ra, and ICE increased in parallel with the degree of pancreatitis severity (all P < 0.001 vs baseline) while mRNA for both receptors remained stable (P = NS), Intrapancreatic and systemic IL-1 beta and IL-1Ra protein also increased as pancreatitis developed (both P < 0.001) with tissue levels being continuously greater than serum, This study demonstrates that sterile, endotoxin-free acute pancreatitis induces the upregulation of specific members of the IL-I family of genes including production of large amounts of IL-1 beta and its receptor antagonist within the pancreatic parenchyma, These changes are indicative of pancreatitis severity are not model dependent, (C) 1997 Academic Press Limited.