Specific changes in the pancreatic expression of the interleukin 1 family of genes during experimental acute pancreatitis.
Interleukin 1beta (IL-1beta) 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-1beta 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-1beta, 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-1beta. As pancreatitis developed, mRNA for IL-1beta, 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-1beta and IL-1Ra protein also increased as pancreatitis developed (both P<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-1beta and its receptor antagonist within the pancreatic parenchyma. These changes are indicative of pancreatitis severity and are not model dependent.
Fink
G W
GW
Department of Surgery and the Pancreas Study Group, University of South Florida, Tampa, FL 33612, USA.
Norman
J G
JG
D000208:Acute Disease; D000818:Animals; D002108:Ceruletide; D017931:DNA Primers; D004195:Disease Models, Animal; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D008297:Male; D051379:Mice; D005810:Multigene Family; D010179:Pancreas / Q000276:immunology*; D010195:Pancreatitis / Q000097:blood / Q000139:chemically induced / Q000235:genetics / Q000276:immunology*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D017472:Receptors, Interleukin-1 / Q000096:biosynthesis* / Q000097:blood; D014158:Transcription, Genetic
D017931:DNA Primers; D007375:Interleukin-1; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1; D002108:Ceruletide