SPECIFIC CHANGES IN THE PANCREACTIC EXPRESSION OF THE INTERLEUKIN 1 FAMILY OF GENES DURING EXPERIMENTAL ACUTE PANCREATITIS

Interleukin 1β (IL-1β) 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-1β and the remainder of the IL-1 family of genes during sterile acute pancreatitis. Moderate or severe necrotizing pancreatitis was 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-1β, 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-1β. As pancreatitis developed, mRNA for IL-1β, IL-1Ra, and ICE increased in parallel with the degree of pancreatitis severity (allP<0.001 vs baseline) while mRNA for both receptors remained stable (P=NS). Intrapancreatic and systemic IL-1β and IL-1Ra protein also increased as pancreatitis developed (bothP<0.001) with tissue levels being continuously greater than serum. This study demonstrated that sterile, endotoxin-free acute pancreatitis induces the upregulation of specific members of the IL-1 family of genes including production of large amounts of IL-1β and its receptor antagonist within the pancreatic parenchyma. These changes are indicative of pancreatitis severity and are not model dependent.