title: Protective effects of isoflurane pretreatment in endotoxin-induced lung injury.
abstract: BACKGROUND
  The concept of antiinflammatory effects of volatile anesthetics is well established in vitro and in some organ systems. Their protective role in lung injury, however, remains to be elucidated. The authors hypothesized that in the lung, isoflurane pretreatment may attenuate neutrophil infiltration and reduce endotoxin-induced injury.
  
  
  METHODS
  Male C57Bl/6 mice were exposed to aerosolized lipopolysaccharide. Neutrophil recruitment into the pulmonary vasculature and migration into the different lung compartments (interstitium and alveolar air space) were determined by flow cytometry. Capillary protein leakage, formation of lung edema, and concentration of the chemokines keratinocyte-derived chemokine (CXCL1) and macrophage inflammatory protein 2 (CXCL2/3) in bronchoalveolar lavage were compared in mice with or without isoflurane treatment (1.4% inspired for 30 min) at different times before and after endotoxin exposure.
  
  
  RESULTS
  Endotoxin inhalation induced significant neutrophil migration into all lung compartments. Isoflurane pretreatment attenuated both neutrophil recruitment into lung interstitium and alveolar space when given 1 or 12 h before or 1 h after lipopolysaccharide but not at 4, 6, or 24 h before endotoxin exposure. Isoflurane pretreatment 1 or 12 h before lipopolysaccharide also reduced protein leakage and pulmonary edema. Production of CXCL1 and CXCL2/3 in the bronchoalveolar lavage was reduced when isoflurane was given 1 h but not 12 h before lipopolysaccharide, suggesting different mechanisms for early and late protection.
  
  
  CONCLUSIONS
  Isoflurane pretreatment reduces acute lung injury when given 1 or 12 h before an endotoxin challenge or within the first hour of an already established inflammation.
authors.affiliation: Robert M. Berne Cardiovascular Research Center, University of Virginia Health System, USA. joerg.reutershan@med.uni-tuebingen.de
authors.forename: Jörg
authors.initials: J
authors.lastname: Reutershan
authors.forename: Daniel
authors.initials: D
authors.lastname: Chang
authors.forename: John K
authors.initials: JK
authors.lastname: Hayes
authors.forename: Klaus
authors.initials: K
authors.lastname: Ley
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D018925:Chemokines / Q000378:metabolism; D004731:Endotoxins / Q000633:toxicity*; D007530:Isoflurane / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000502:physiology; D052247:Nitric Oxide Synthase Type II / Q000502:physiology; D011654:Pulmonary Edema / Q000517:prevention & control; D012128:Respiratory Distress Syndrome / Q000517:prevention & control*
chemical_list: D018685:Anesthetics, Inhalation; D018925:Chemokines; D004731:Endotoxins; D007530:Isoflurane; D052247:Nitric Oxide Synthase Type II