title: Inhibition of xanthine oxidase does not influence immunosuppression after hemorrhagic shock.
abstract: BACKGROUND
  Resuscitated hemorrhagic shock causes global ischemia reperfusion with generation of toxic oxygen metabolites. We hypothesized that the immunosuppression that follows hemorrhagic shock may be linked to this process.
  
  
  METHODS
  Forty-five male Sprague-Dawley rats (weight, 250-300 g) were bled to a mean arterial pressure of 30 mm Hg for 60 minutes, then were resuscitated with three times the maximum blood loss of lactated Ringer's solution. Immune response was assessed by splenocyte proliferation and interleukin-2 (IL-2) production 72 hours after hemorrhage. Allopurinol (50 mg/kg) was given after hemorrhage and immediately before resuscitation.
  
  
  RESULTS
  Hemorrhagic shock caused significant decreases in splenocyte proliferation (cpm: (157,880 +/- 22,068 (mean +/- SD) vs. 37,787 +/- 15,849) and IL-2 production (1/2 max U/ml: 79.6 +/- 7.9 vs. 48.0 +/- 7.7) (both p < 0.05). Hepatic xanthine oxidase was significantly increased with hemorrhage and resuscitation. Hepatic xanthine oxidase activity after hemorrhage and resuscitation was significantly decreased after treatment with allopurinol (74.2 +/- 41.7 vs. 9.2 +/- 9.40). Allopurinol did not affect splenocyte proliferation (cpm: 21,875 +/- 9,316) or IL-2 production (1/2 max U/ml: 45.0 +/- 7.1).
  
  
  CONCLUSIONS
  These results demonstrate that inhibition of xanthine oxidase by allopurinol after hemorrhagic shock did not affect splenocyte proliferation or IL-2 production. We conclude that the immunosuppression after hemorrhagic shock is not dependent on xanthine oxidase-induced production of toxic oxygen metabolites.
authors.affiliation: Department of Surgery, Case Western Reserve University School of Medicine, MetroHealth Medical Center, Cleveland, Ohio 44109-1998, USA.
authors.forename: G C
authors.initials: GC
authors.lastname: Pinault
authors.forename: A J
authors.initials: AJ
authors.lastname: Sanson
authors.forename: M A
authors.initials: MA
authors.lastname: Malangoni
mesh_terms: D000493:Allopurinol / Q000627:therapeutic use*; D000818:Animals; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D007108:Immune Tolerance / Q000187:drug effects*; D007376:Interleukin-2 / Q000276:immunology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology* / Q000378:metabolism; D012151:Resuscitation / Q000009:adverse effects*; D012771:Shock, Hemorrhagic / Q000628:therapy*; D013154:Spleen / Q000276:immunology; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors*
chemical_list: D004791:Enzyme Inhibitors; D007376:Interleukin-2; D017382:Reactive Oxygen Species; D000493:Allopurinol; D014969:Xanthine Oxidase