title: Upregulation of IL-1β, IL-6, and CCL-2 by a novel mouse model of pancreatic ischemia-reperfusion injury.
abstract: BACKGROUND
  Little is known about the immunologic events surrounding pancreatic ischemia-reperfusion injury (IRI) because of a lack of established experimental models. The purpose of this study was to develop a mouse model for pancreatic IRI to serve as a basis for the immunologic characterization of pancreatic organ damage at transplantation.
  
  
  METHODS
  Reversible ischemia was surgically induced by vascular isolation of the distal pancreas for 0, 10, 20, or 30 min. Mice receiving laparotomy without clamping served as sham-operated controls. After reperfusion, mice were serially assayed for biochemical and histologic evidence of inflammation, proinflammatory cytokine and chemokine production, and inflammatory gene upregulation.
  
  
  RESULTS
  After induction of pancreatic IRI, serum amylase and lactate dehydrogenase peaked at 6 hr and returned to baseline by 120 hr after injury in all groups. Mice undergoing 30 min of IRI demonstrated the greatest biochemical evidence of inflammation. Histologic scoring similarly demonstrated marked inflammation in mice subjected to 30-min IRI compared with controls. Serum cytokine/chemokine analysis demonstrated significant upregulation of granulocyte colony-stimulating factor, interferon γ, tumor necrosis factor α, interleukin (IL)-2, IL-1β, IL-6, chemokine (C-C motif) ligand-2, chemokine (C-C motif) ligand-5, chemokine (C-X-C motif) ligand-1, and macrophage inflammatory protein 2. A similar upregulation of ccl2, il1b, il6, fos, hspa1a, hspd1, and cd14 gene expression was detected by real-time polymerase chain reaction analysis of pancreatic tissue.
  
  
  CONCLUSIONS
  This novel model of distal pancreatic IRI in the mouse demonstrates time-limited pancreatic inflammation and injury by histologic and biochemical indices. Inflammation may be, in part, a result of the immunologic effects of IL-1β, IL-6, and CCL-2. This model provides a method by which immunologic mechanisms of pancreatic IRI can be elucidated.
authors: Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA.
authors: Keri E
authors: KE
authors: Lunsford
authors: Brandon J
authors: BJ
authors: Baird
authors: Gregory D
authors: GD
authors: Sempowski
authors: Diana M
authors: DM
authors: Cardona
authors: Zhiguo
authors: Z
authors: Li
authors: Kent J
authors: KJ
authors: Weinhold
authors: Debra L
authors: DL
authors: Sudan
authors: Todd V
authors: TV
authors: Brennan
mesh_terms: D000818:Animals; D018932:Chemokine CCL2 / Q000097:blood* / Q000235:genetics; D004195:Disease Models, Animal; D018836:Inflammation Mediators / Q000097:blood; D053583:Interleukin-1beta / Q000097:blood* / Q000235:genetics; D015850:Interleukin-6 / Q000097:blood* / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D010179:Pancreas / Q000098:blood supply / Q000276:immunology* / Q000293:injuries* / Q000473:pathology; D016035:Pancreas Transplantation / Q000009:adverse effects / Q000276:immunology / Q000473:pathology; D012313:RNA / Q000235:genetics / Q000378:metabolism; D015427:Reperfusion Injury / Q000097:blood / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D015854:Up-Regulation
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D015850:Interleukin-6; D012313:RNA