The role of tumor necrosis factor-α in the pathogenesis of aspiration pneumonitis in rats

Bruce A. Davidson*, Paul R. Knight, Jadwiga D. Helinski, Nader D. Nader, Thomas P. Shanley, Kent J. Johnson

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

79 Scopus citations


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-α (TNF-α), 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-α concentration of bronchoalveolar lavage fluid was determined using a bioassay, upregulation of lung TNF-α mRNA was also measured. The effect of intratracheal anti-rat TNF- α 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-α peak 1-2 h after injury in the lavage fluid. Both particulate and acidic particulate groups produced a much more robust TNF-α signal that reached a plateau at 2-4 h after injury and declined at 8 h. Upregulation of TNF-α 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-α 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-α is differentially manifested according to the components that make up the aspirate but the levels of TNF-α expression do not correlate with the severity of the resultant injury. However, the reduction in acid-induced lung injury by anti-TNF-α treatment indicates that TNF-α plays a role in the pathogenesis of aspiration pneumonitis.

Original languageEnglish (US)
Pages (from-to)486-499
Number of pages14
Issue number2
StatePublished - Aug 1999


  • ARDS
  • Acid aspiration
  • Particulate aspiration
  • Pulmonary injury

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine


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