title: The role of tumor necrosis factor-alpha in the pathogenesis of aspiration pneumonitis in rats.
abstract: BACKGROUND
  Aspiration pneumonitis is characterized by proteinaceous pulmonary edema and acute infiltration of neutrophils into the alveolar space. This study examined the role of the proinflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha), on the pathogenesis of the injury produced by the different components that may be present in the aspirate, acid, or gastric particles.
  
  
  METHODS
  Rats were injured by intratracheal instillation of a vehicle containing acid or gastric particles. TNF-alpha concentration of bronchoalveolar lavage fluid was determined using a bioassay. upregulation of lung TNF-alpha mRNA was also measured. The effect of intratracheal anti-rat TNF-alpha treatment was assessed by lung protein permeability, blood gases, and lung myeloperoxidase activity.
  
  
  RESULTS
  Injury vehicle alone and acid injury resulted in a small TNF-alpha peak 1-2 h after injury in the lavage fluid. Both particulate and acidic particulate groups produced a much more robust TNF-alpha signal that reached a plateau at 2-4 h after injury and declined at 8 h. Upregulation of TNF-alpha mRNA was only detected in the particulate-containing groups. Acidic particulate exposure yielded a synergistic increase in protein permeability and decrease in blood oxygenation. Anti-TNF-alpha treatment reduced protein permeability and myeloperoxidase activity and increased blood oxygenation in the groups exposed to only acid. Such treatment had no effect on either of the particulate containing injuries.
  
  
  CONCLUSIONS
  TNF-alpha is differentially manifested according to the components that make up the aspirate but the levels of TNF-alpha expression do not correlate with the severity of the resultant injury. However, the reduction in acid-induced lung injury by anti-TNF-alpha treatment indicates that TNF-alpha plays a role in the pathogenesis of aspiration pneumonitis.
authors.affiliation: Department of Anesthesiology, State University of New York at Buffalo, 14214-3013, USA. bdavidso@buffalo.edu
authors.forename: B A
authors.initials: BA
authors.lastname: Davidson
authors.forename: P R
authors.initials: PR
authors.lastname: Knight
authors.forename: J D
authors.initials: JD
authors.lastname: Helinski
authors.forename: N D
authors.initials: ND
authors.lastname: Nader
authors.forename: T P
authors.initials: TP
authors.lastname: Shanley
authors.forename: K J
authors.initials: KJ
authors.lastname: Johnson
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology; D015152:Blotting, Northern; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D018496:Hyperoxia / Q000150:complications; D008168:Lung / Q000378:metabolism; D008297:Male; D009504:Neutrophils / Q000502:physiology; D011015:Pneumonia, Aspiration / Q000209:etiology*; D011506:Proteins / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000502:physiology*
chemical_list: D000906:Antibodies; D011506:Proteins; D014409:Tumor Necrosis Factor-alpha