title: Endogenous interleukin-4 and interleukin-10 regulate experimental lung ischemia reperfusion injury.
abstract: BACKGROUND
  Regulatory cytokines play functional roles in experimental heart, hindlimb, and liver ischemia reperfusion injury. However, little is known about their involvement in direct lung ischemia reperfusion injury (LIRI). These studies were undertaken to investigate the role of two regulatory cytokines, interleukin-4 (IL-4) and IL-10, in an in vivo model of LIRI.
  
  
  METHODS
  Left lungs of Long-Evans rats underwent normothermic ischemia for 90 minutes and reperfusion for up to 4 hours. Treated animals received either recombinant IL-4 or recombinant IL-10, or antibodies to IL-4 or IL-10 immediately before reperfusion. Lung injury was quantitated by permeability indices, lung parenchymal neutrophil sequestration (myeloperoxidase [MPO] content), and alveolar leukocyte content in bronchoalveolar lavage (BAL) effluent. Expression of IL-4 and IL-10 was determined by immunoblotting, and mRNA expression for early response cytokines was evaluated by ribonuclease protection assays.
  
  
  RESULTS
  IL-4 and IL-10 protein expression was significant after 2 hours of reperfusion. Animals receiving anti-IL-4 (p = 0.05) and anti-IL-10 (p = 0.01) antibodies demonstrated increased permeabilities compared with positive controls. Lung tissue neutrophil accumulation (p < 0.004) and BAL leukocyte content (p < 0.04) were also significantly increased in animals receiving anti-IL-10 antibodies. Conversely, animals receiving recombinant IL-4 and recombinant IL-10 demonstrated reduced permeabilities and lung MPO content. Both anti-IL-4 and anti-IL-10 treatment increased mRNA expression for a number of early response cytokines, including TNF-alpha and IL-1beta.
  
  
  CONCLUSIONS
  IL-4 and IL-10 are expressed in response to LIRI and function to decrease injury severity. These effects are partly due to modulated expression of early proinflammatory cytokines.
authors.affiliation: Division of Cardiothoracic Surgery, University of Washington Medical Center, Seattle, Washington 98195, USA. msmmd@u.washington.edu
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Farivar
authors.forename: Baiya
authors.initials: B
authors.lastname: Krishnadasan
authors.forename: Babu V
authors.initials: BV
authors.lastname: Naidu
authors.forename: Steven M
authors.initials: SM
authors.lastname: Woolley
authors.forename: Edward D
authors.initials: ED
authors.lastname: Verrier
authors.forename: Michael S
authors.initials: MS
authors.lastname: Mulligan
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis; D015153:Blotting, Western; D018893:Bronchoalveolar Lavage; D002199:Capillary Permeability / Q000502:physiology; D004195:Disease Models, Animal; D016753:Interleukin-10 / Q000378:metabolism*; D015847:Interleukin-4 / Q000378:metabolism*; D008171:Lung Diseases / Q000378:metabolism / Q000503:physiopathology*; D011336:Probability; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D020318:Rats, Long-Evans; D012016:Reference Values; D015427:Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology*; D012680:Sensitivity and Specificity
chemical_list: D015415:Biomarkers; D012333:RNA, Messenger; D016753:Interleukin-10; D015847:Interleukin-4