BackgroundAspiration 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.MethodsRats 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.ResultsInjury 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.ConclusionsTNF‐[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.