EFFECTS OF OZONE ON THE EPITHELIAL AND INFLAMMATORY RESPONSES IN THE AIRWAYS - ROLE OF TUMOR-NECROSIS-FACTOR

We have investigated the possibility that tumor necrosis factor alpha (TNF) plays a role in the increased airway permeability and an inflamm atory response following an acute ozone (O-3) exposure. Male Sprague-D awley rats were injected, intraperitoneally, with either rabbit anti-m ouse antibody to TNF (anti-TNF) or preimmune rabbit serum, 2 h before a 3-h exposure to O-3 or purified air. Permeability, as determined by [Tc-99m] diethylenetriamine pentaacetate (DTPA) transport, total prote in and albumin concentrations in the bronchoalveolar lavage (BAL), and the inflammatory cell response in the BAL were assessed 10 h after th e exposure was completed. The O-3-exposed group that was injected with anti-TNF showed a significant decrease in permeability to DTPA in com parison to the O-3-exposed group injected with preimmune rabbit serum. There was no difference between tile anti-TNF group and the purified air group. In contrast the total protein and albumin levels in the BAL were significantly greater in both of the O-3-exposed groups than in the purified air group. The concentrations of protein and albumin in t he anti-TNF group did, however, show an attenuating trend when compare d to the preimmune O-3-exposed group. The polymorphonuclear leukocytes (PMNs) in BAL of the anti-TNF group also showed an attenuating trend when compared to the preimmune O-3-exposed group, but both of these O- 3-exposed groups were significantly greater than the purified air grou p. Lung sections stained with naphthol AS-D chloroacetate esterase slo wed an increase in the number of stained PMNs in the anti-TNF group in comparison to the preimmune O-3- and air-exposed groups. These data s uggest that TNF plays a role in the increase in tracheal permeability as determined by DTPA transport, while the contributing role that TNF plays in bronchoalveolar permeability and the inflammatory response se en following an acute exposure to 0.8 ppm O-3 is less evident.