EFFECTS OF ACUTE EXPOSURE TO PHOSGENE ON PULMONARY HOST DEFENSES AND RESISTANCE TO INFECTION

Phosgene is a toxic gas widely used in industrial processes. The most sensitive endpoint for phosgene toxicity in mice is decreased resistan ce to challenge with bacterial infection or tumor cells. These effects were attributed to impaired alveolar macrophage (AM) and pulmonary na tural killer cell (NK) function. The purpose of this study was to inve stigate whether similar effects occurred in Fischer 344 rats. Intrapul monary killing of bacteria was impaired and the inflammatory response enhanced in rats infected by aerosol with Streptococcus zooepidemicus immediately after a 6-h exposure to 0.1 or 0.2 ppm phosgene as compare d to air controls. Also, ingestion of latex beads in vitro by AM obtai ned from bronchoalveolar lavage (BAL) fluid of rats exposed to 0.2 ppm phosgene was significantly less than controls. If infection or BAL we re delayed until 18 h after exposure, there was no difference between phosgene and air exposed rats. In uninfected rats polymorphonuclear le ukocytes were increased in BAL fluid 18 h after exposure to 0.5 ppm bu t not lower concentrations of phosgene. Pulmonary NK activity was supp ressed 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 ba cteria is the most sensitive endpoint for phosgene toxicity in the rat , although recovery from acute phosgene exposure is rapid. Consequence s of repeated chronic exposure remain to be elucidated.