title: Exogenously administered interleukin-10 decreases pulmonary neutrophil infiltration in a tumor necrosis factor-dependent murine model of acute visceral ischemia.
abstract: BACKGROUND
  Visceral ischemia and reperfusion associated with thoracoabdominal aortic aneurysm (TAAA) repair results in lung injury, which appears to be mediated in part by proinflammatory cytokines. The purpose of this study was to determine the effect of exogenous administration of the antiinflammatory cytokine, recombinant human IL-10 (rhIL-10), on proinflammatory cytokine production (IL-6 and TNF alpha) and pulmonary neutrophil infiltration after acute visceral ischemia-reperfusion.
  
  
  METHODS
  Two hours before 25 minutes of supraceliac aortic occlusion, 80 C57BL/6 mice (20 to 22 g) received an intraperitoneal injection of rhIL-10 (0.2 microgram [n = 20], 2 micrograms [n = 20], 5 micrograms [n = 25], or 20 micrograms [n = 15]), and 16 mice received murine anti-IL-10 IgM 200 micrograms. Twenty-five additional mice underwent visceral ischemia-reperfusion without treatment (controls), and 16 mice underwent laparotomy without aortic occlusion (sham).
  
  
  RESULTS
  Pretreatment with exogenous rhIL-10 resulted in significant reductions in lung neutrophil infiltration with 0.2 microgram, 2 micrograms, and 5 micrograms per mouse of rhIL-10 compared with lung neutrophil levels in control mice that underwent acute visceral ischemia-reperfusion alone (p < 0.05). In addition, serum TNF alpha was detected in 50% of control mice and in 75% of mice that received murine anti-IL-10, but in none of the mice that received rhIL-10 (2 micrograms per mouse) or the mice that underwent sham operative procedures (p < 0.05 by chi 2 analysis).
  
  
  CONCLUSIONS
  Exogenous IL-10 limits pulmonary neutrophil recruitment and the appearance of TNF alpha in this model of visceral ischemia-reperfusion injury. Thus the use of exogenous IL-10 may offer a novel therapeutic approach to decrease the complications that are associated with TAAA repair.
authors.affiliation: Department of Surgery, University of Florida College of Medicine, Gainesville 32610, USA.
authors.forename: P J
authors.initials: PJ
authors.lastname: Hess
authors.forename: J M
authors.initials: JM
authors.lastname: Seeger
authors.forename: T S
authors.initials: TS
authors.lastname: Huber
authors.forename: M B
authors.initials: MB
authors.lastname: Welborn
authors.forename: T D
authors.initials: TD
authors.lastname: Martin
authors.forename: T R
authors.initials: TR
authors.lastname: Harward
authors.forename: S
authors.initials: S
authors.lastname: Duschek
authors.forename: P D
authors.initials: PD
authors.lastname: Edwards
authors.forename: C C
authors.initials: CC
authors.lastname: Solorzano
authors.forename: E M
authors.initials: EM
authors.lastname: Copeland
authors.forename: L L
authors.initials: LL
authors.lastname: Moldawer
mesh_terms: D000208:Acute Disease; D000818:Animals; D001011:Aorta / Q000502:physiology; D002465:Cell Movement; D003250:Constriction; D005260:Female; D007075:Immunoglobulin M / Q000008:administration & dosage; D016753:Interleukin-10 / Q000276:immunology / Q000494:pharmacology*; D015850:Interleukin-6 / Q000097:blood; D008168:Lung / Q000201:enzymology / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000473:pathology* / Q000502:physiology; D009195:Peroxidase / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D014781:Viscera / Q000098:blood supply*
chemical_list: D007075:Immunoglobulin M; D015850:Interleukin-6; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D009195:Peroxidase