Effect of exposure to diesel exhaust particles on the susceptibility of the lung to infection

There are at least three mechanisms by which alveolar macrophages play a cr itical role in protecting the lung from bacterial or viral infections: prod uction of inflammatory cytokines that recruit and activate lung phagocytes, production of antimicrobial reactive oxidant species, and production of in terferon (an antiviral agent). In this article we summarize data concerning the effect of exposure to diesel exhaust particles on these alveolar macro phage functions and the role of adsorbed organic chemicals compared to the carbonaceous core in the toxicity of diesel particles. In vitro exposure of rat alveolar macrophages to diesel exhaust particles decreased the ability of lipopolysaccharide (LPS), a bacterial product] to stimulate the product ion of inflammatory cytokines interleukin-1 (IL-1) and tumor necrosis facto r-alpha (TNF-alpha). Methanol extract exhibited this potential but methanol -washed diesel particles did not. Exposure of rats to diesel exhaust partic les by intratracheal instillation also decreased LPS-induced TNF-alpha and IL-1 production from alveolar macrophages. In contrast, carbon black did no t exhibit this inhibitory effect. Exposure of rats to diesel exhaust partic les by inhalation decreased the ability of alveolar macrophages to produce antimicrobial reactive oxidant species in response to zymosan (a fungal com ponent). In contrast, exposure to coal dust increased zymosan-stimulated ox idant production. In vivo exposure to diesel exhaust particles but not to c arbon black decreased the ability of the lungs to clear bacteria. Inhalatio n exposure of mice to diesel exhaust particles but not to coal dust depress ed the ability of the lung to produce the antiviral agent interferon and in creased viral multiplication in the lung. These results support the hypothe sis that exposure to diesel exhaust particles increases the susceptibility of the lung to infection by depressing the antimicrobial potential of alveo lar macrophages. This inhibitory effect appears to be due to adsorbed organ ic chemicals rather than the carbonaceous core of the diesel particles.