title: Mitochondrial antioxidant function is a potential mechanism for organ differences in interleukin-1-mediated tolerance to oxidative injury.
abstract: BACKGROUND
  Pretreatment with interleukin-1 (IL-1) induces resistance to lung injury from hyperoxia exposure and to cardiac dysfunction after ischemia-reperfusion in animal models. In contrast, IL-1 pretreatment did not produce tolerance to ischemia-reperfusion injury and did not seem to alter antioxidant enzyme activities in the kidney. Recently, we determined that mitochondria scavenge superoxide anion via a nonenzymatic mechanism and that this newly identified intracellular antioxidant function was inducible in the lung. Based on these observations, we hypothesized that organ differences after IL-1 pretreatment between the lung and the heart, which become tolerant, and the kidney, which does not become tolerant, were a consequence of differential responses in mitochondrial superoxide scavenging.
  
  
  METHODS
  Rats were given IL-1alpha (50 ng intratracheally, 36 hrs before assay) and lung and kidney mitochondria were isolated. Mitochondrial scavenging of superoxide anion was then determined by using an assay that we developed and published previously. We then tested the effects of IL-1 pretreatment on lung mitochondrial scavenging of superoxide after hyperoxia exposure.
  
  
  RESULTS
  We found that intratracheal administration of IL-1 did not affect lung mitochondrial superoxide scavenging but decreased kidney mitochondrial superoxide scavenging by 75%. In addition, IL-1 pretreatment preserved lung mitochondrial superoxide scavenging in rats exposed to hyperoxia (95% O2 for 24 hours) compared with untreated rats exposed to hyperoxia in which lung mitochondrial superoxide scavenging was decreased by more than 50%.
  
  
  CONCLUSIONS
  We conclude that IL-1 pretreatment has divergent effects on mitochondrial antioxidant function in the lung and the kidney and speculate that this may reflect previously unidentified tissue-specific differences in mitochondrial function during systemic inflammation. This study offers new insights into why the lung, but not the kidney, acquires tolerance to subsequent oxidative injury after IL-1 pretreatment.
authors.affiliation: Webb-Waring Antioxidant Research Institute, University of Colorado Health Sciences Center, Denver, USA. dguidot@emory.edu
authors.forename: D M
authors.initials: DM
authors.lastname: Guidot
authors.forename: A D
authors.initials: AD
authors.lastname: Kitlowski
authors.forename: B M
authors.initials: BM
authors.lastname: Hybertson
authors.forename: J E
authors.initials: JE
authors.lastname: Repine
mesh_terms: D000818:Animals; D018496:Hyperoxia / Q000378:metabolism; D007375:Interleukin-1 / Q000008:administration & dosage / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D008168:Lung / Q000378:metabolism*; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D013481:Superoxides / Q000378:metabolism*
chemical_list: D007375:Interleukin-1; D013481:Superoxides