Effects Of Acute Exposure To Phosgene On Pulmonary Host Defenses And Resistance To Infection

Abstract

Phosgene is a toxic gas widely used in industrial processes. The most sensitive endpoint for phosgene toxicity in mice is decreased resistance to challenge with bacterial infection or tumor cells. These effects were attributed to impaired alveolar macrophage (AM) and pulmonary natural killer cell (NK) function. The purpose of this study was to investigate whether similar effects occurred in Fischer 344 rats. Intrapulmonary killing of bacteria was impaired and the inflammatory response enhanced in rats infected by aerosol with Streptococcus zooepidemicus immediately after a 6-/1 exposure to 0.1 or 0.2 ppm phosgene as compared to air controls. Also, ingestion of latex beads in vitro by AM obtained from bronchoalveolar lavage (BAD fluid of rats exposed to 0.2 ppm phosgene was significantly less than controls. If infection or BAL were delayed until 18 h after exposure, there was no difference between phosgene and air exposed rats. In uninfected rats polymorphonuclear leukocytes were increased in BAL fluid 18 h after exposure to 0.5 ppm but not lower concentrations of phosgene. Pulmonary NK activity was suppressed immediately and 18 h after exposure to 0.5 ppm but not 0.1 ppm. The data indicate that, as in the mouse, intrapulmonary killing of bacteria is the most sensitive endpoint for phosgene toxicity in the rat, although recovery from acute phosgene exposure is rapid. Consequences of repeated chronic exposure remain to be elucidated.