Tumor Necrosis Factor-α Production by Alveolar Macrophages During the Early Development of Phosgene-Induced Lung Injury

Abstract

Several lines of circumstantial evidence suggest that an elevated production of tumor necrosis factor-α (TNF-α) by lung macrophages may play a role in the development of phosgene-induced pulmonary edema. The present study was undertaken to investigate this possibility. Fischer 344 rats were exposed to 23.2 ppm phosgene or air for 10 min, and bronchoalveolar lavage was performed during the early development of the pulmonary edematous response to phosgene, that is, 1 and 3 h after exposure. Lavage fluids were analyzed for the presence of TNF-α, and the constitutive and lipopolysaccharide (LPS)-stimulated productions of TNF-α by lavaged alveolar macrophages (AM) were assessed in vitro. No increases in TNF-α in the lavage fluids were observed at either of the two time points after phosgene exposure. The numbers and viabilities of AM lavaged 1 h after exposure to phosgene and air were closely similar. By 3 h after exposure to phosgene, fewer AM were harvested by lavage and their viabilities were reduced below air control values. The unstimulated or LPS-stimulated production of TNF-α by the AM from the air- and phosgene-exposed lungs was not significantly different from one another when assessed by an enzyme-linked immunosorbent assay for murine TNF-α, whereas TNF-α production measured by an L929 cell cytotoxicity assay indicated that the production of this pro-inflammatory cytokine by LPS-stimulated AM was abnormally decreased at both the 1-and 3-h postexposure times. The results of this study suggest that TNF-α production by AM does not play an important role in mediating the early phase of development of phosgene-induced pulmonary edema.