title: Mechanical ventilation exacerbates alveolar macrophage dysfunction in the lungs of ethanol-fed rats.
abstract: BACKGROUND
  Patients with alcohol abuse have a two- to three-fold increased risk of acute lung injury and respiratory failure after sepsis or trauma but are also at increased risk of nosocomial pneumonia. Mechanical ventilation exacerbates lung injury during critical illnesses. In this study we tested whether mechanical ventilation of the alcoholic lung promotes on balance a proinflammatory phenotype favoring ventilator-induced lung injury or an immunosuppressive phenotype favoring ventilator-associated pneumonia.
  
  
  METHODS
  Lungs from rats fed an isocaloric diet with or without ethanol (six weeks) were isolated and ventilated ex vivo with a low-volume (protective) or high-volume (injurious) strategy for two hours with or without prior endotoxemia (two hours). In other experiments, rats were subjected to high-volume ventilation in vivo. Airway levels of the proinflammatory cytokines tumor necrosis factor-alpha, macrophage inflammatory protein-2, and interleukin-1beta were determined after mechanical ventilation ex vivo and compared with edematous lung injury after high-volume ventilation in vivo. In parallel, alveolar macrophage phagocytosis of bacteria and secretion of interleukin-12 during ventilation ex vivo and endotoxin-stimulated alveolar macrophage phagocytosis and tumor necrosis factor-alpha secretion in vitro were determined.
  
  
  RESULTS
  Ethanol ingestion suppressed the proinflammatory response to injurious mechanical ventilation and did not increase experimental ventilator-induced lung injury. In parallel, ethanol ingestion blunted the innate immune response of alveolar macrophages during injurious ventilation ex vivo and after endotoxin stimulation in vitro.
  
  
  CONCLUSIONS
  Ethanol ingestion dampens ventilator-induced inflammation but exacerbates macrophage immune dysfunction. These findings could explain at least in part why alcoholic patients are at increased risk of ventilator-associated pneumonia.
authors.affiliation: Atlanta Veterans Administration Medical Center and the Department of Pediatrics, Emory University, Atlanta, Georgia, USA.
authors.forename: Pradip P
authors.initials: PP
authors.lastname: Kamat
authors.forename: Arthur
authors.initials: A
authors.lastname: Slutsky
authors.forename: Haibo
authors.initials: H
authors.lastname: Zhang
authors.forename: Rabih I
authors.initials: RI
authors.lastname: Bechara
authors.forename: Lou Ann S
authors.initials: LA
authors.lastname: Brown
authors.forename: Raena C
authors.initials: RC
authors.lastname: Garcia
authors.forename: Pratibha C
authors.initials: PC
authors.lastname: Joshi
authors.forename: Corey D
authors.initials: CD
authors.lastname: Kershaw
authors.forename: David M
authors.initials: DM
authors.lastname: Guidot
mesh_terms: D000437:Alcoholism / Q000276:immunology*; D000818:Animals; D019446:Endotoxemia / Q000276:immunology; D000431:Ethanol / Q000633:toxicity*; D018836:Inflammation Mediators / Q000097:blood; D008168:Lung / Q000276:immunology*; D055370:Lung Injury; D016676:Macrophages, Alveolar / Q000276:immunology*; D008297:Male; D009894:Opportunistic Infections / Q000276:immunology; D011175:Positive-Pressure Respiration; D051381:Rats; D017207:Rats, Sprague-Dawley; D012486:Salmonella typhimurium / Q000276:immunology; D013990:Tidal Volume / Q000502:physiology
chemical_list: D018836:Inflammation Mediators; D000431:Ethanol