title: Active interleukin-1 receptor required for maximal progression of acute pancreatitis.
abstract: OBJECTIVE
  The authors' aim was to determine the requirement for an active interleukin (IL)-1 receptor during the development and progression of acute pancreatitis.
  
  
  BACKGROUND
  Interleukin-1 is a pro- inflammatory cytokine that has been shown to be produced during acute pancreatitis. Earlier animal studies of moderate and severe pancreatitis have shown that blockade of this powerful mediator is associated with attenuated pancreatic destruction and dramatic increases in survival. The exact role played by IL-1 and the requirement for activation of its receptor in the initiation and progression of pancreatitis is unknown.
  
  
  METHODS
  Conventional and IL-1 receptor "knockout" animals were used in parallel experiments of acute pancreatitis induced by intraperitoneal injection of cerulean (50 microg/kg every 1 hour X 4). The conventional mouse strain had the IL-1 receptor blocked prophylactically by means of a recombinant IL-1 receptor antagonist (10 mg/kg injected intraperitoneally every 2 hours). The second mouse strain was genetically engineered by means of gene targeting in murine embryonic stem cells to be devoid of type 1 IL-1 receptor (IL-1 receptor knockout). Animals were killed at 0, 0.5, 1, 2, 4, and 8 hours, with the severity of pancreatitis determined by serum amylase, lipase, and IL-6 levels and blind histologic grading. Strain-specific controls were used for comparison.
  
  
  RESULTS
  The genetic absence of the IL-1 receptor or its pharmacologic blockade resulted in significantly attenuated pancreatic vacuolization, edema, necrosis, inflammation, and enzyme release. Serum IL-6, a marker of inflammation severity, was dramatically decreased in both groups.
  
  
  CONCLUSIONS
  Activation of the IL-1 receptor is not required for the development of pancreatitis but apparently is necessary for the maximal propagation of pancreatic injury and its associated inflammation.
authors.affiliation: Department of Surgery, University of South Florida, Tampa, Florida, USA.
authors.forename: J G
authors.initials: JG
authors.lastname: Norman
authors.forename: G
authors.initials: G
authors.lastname: Fink
authors.forename: M
authors.initials: M
authors.lastname: Franz
authors.forename: J
authors.initials: J
authors.lastname: Guffey
authors.forename: G
authors.initials: G
authors.lastname: Carter
authors.forename: B
authors.initials: B
authors.lastname: Davison
authors.forename: C
authors.initials: C
authors.lastname: Sexton
authors.forename: M
authors.initials: M
authors.lastname: Glaccum
mesh_terms: D000208:Acute Disease; D000818:Animals; D002108:Ceruletide; D004195:Disease Models, Animal; D018450:Disease Progression; D053590:Interleukin 1 Receptor Antagonist Protein; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010195:Pancreatitis / Q000097:blood / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D017472:Receptors, Interleukin-1 / Q000172:deficiency / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D012795:Sialoglycoproteins / Q000494:pharmacology
chemical_list: C507764:Il1rn protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins; D012795:Sialoglycoproteins; D002108:Ceruletide