me Role of Tumor Necrosis Factor - a in the Pathogenesis of Aspiration Pneumonitis in Rats

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 cytokhe, tumor necrosis factor-a (TNFa), 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-a concentration of bronchoalveolar lavage fluid was determined using a bioassay. upregulation of lung TNF-a mRNA was also measured. The effect of intratracheal anti-rat TNF-a treatment was assessed by lung protein permeabdity, blood gases, and lung myeloperoxidase activity. Results: Injury vehicle alone and acid injury resulted in a small TNF-a peak 1-2 h after injury in the lavage fluid. Both particulate and acidic particulate groups produced a much more robust TNF-a signal that reached a plateau at 2-4 h after injury and declined at 8 h. Upregulation of TNF-a mRNA was only detected in the particulate-containing groups. Acidic par-