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