PULMONARY HOST DEFENSES AND RESISTANCE TO INFECTION FOLLOWING SUBCHRONIC EXPOSURE TO PHOSGENE

Acute exposure to phosgene, a toxic gas widely used in industrial proc esses, decreases resistance to bacteria in mice and rats and enhances susceptibility to B16 tumor cell challenge in mice. These effects appe ar to De due to impaired alveolar macrophage and natural killer (NK) c ell activity, respectively. In this study effects of repeated phosgene exposures on bacterial infection and NK activity were determined. Rat s were exposed for 4 or 12 wk, 6 h/day, 5 days/wk, to 0.1 or 0.2 ppm p hosgene or 2 days/wk to 0.5 ppm and infected by aerosol with Streptoco ccus zooepidemicus immediately after the last exposure. An additional group was also infected after 4 wk of recovery following the 12-wk exp osure regimens. Bronchoalveolar lavage (BAL) fluid was assessed 0, 6, and 24 h postinfection for bacteria and inflammatory cells. Differenti al cell counts in BAL and pulmonary NK activity were also determined i n uninfected rats 18 h after the last exposure. All phosgene exposures impaired clearance of bacteria from the lungs and caused an increase in polymorphonuclear leukocytes (PMNs) in BAL of infected rats. Effect s in the 0.5 ppm exposure group were greatest, and were significantly different from those in the 0.2 ppm exposure group, although the produ ct of concentration x time was the same. BAL cell counts and bacterial clearance were normal in rats assessed 4 wk after the 12-wk phosgene exposures. Bacterial clearance and the PMN response to infection follo wing repeated exposure were similar to those observed after a single e xposure; that is, for these endpoints, effects due to repetitive expos ure were neither additive nor attenuated. In contrast, NK activity was suppressed only at the 0.5 ppm level, and the magnitude of suppressio n was much less than that following acute exposure, suggesting that at tenuation of this effect did occur with repeated exposure. The data in dicate that susceptibility to streptococcal infection is a sensitive e ndpoint for phosgene toxicity following subchronic exposure.