EFFECTS OF INHALED SULFURIC-ACID AEROSOLS ON PULMONARY IMMUNOCOMPETENCE - A COMPARATIVE-STUDY IN HUMANS AND ANIMALS

There is increasing concern regarding the potential health effects ass ociated with the inhalation of ambient acid aerosols. Laboratory studi es with animals have demonstrated that inhalation exposure to sulfuric acid (H2SO4) can alter airway responsiveness, cause cell damage leadi ng to alveolitis and edema, produce hypertrophy/hyperplasia of epithel ial secretory cells in the tracheobronchial tree, and alter nonspecifi c and specific immune defense mechanisms. While the adverse effects of inhaled H2SO4 upon pulmonary immunocompetence in animals appear relat ively clear, data concerning effects on host defense in exposed humans are inconclusive and appear to contrast with those observed in animal models. Despite the fact that extrapolation between different species is of major importance in inhalation toxicology, baseline comparative data between species are lacking, which often results in the question able validity of extrapolation modeling. This interlaboratory study wa s designed to compare the effects produced by a single inhalation expo sure (3 h) of H2SO4 at 1 mg/m(3) in human subjects with those in a sim ilarly exposed animal model in order to provide a basis for extrapolat ion to human health effects. Bronchoalveolar lavage of rabbits and hum an volunteers was performed after exposure and the recovered macrophag es (M phi) used to assess effects upon macrophage attachment uptake an d intracellular killing of Staphylococcus aureus; modulation of F-c re ceptor (FcR) expression; phagocytosis of opsonized latex particles; an d resting and stimulated production of superoxide (. O-2(-)) and hydro gen peroxide (H2O2). Effects upon bronchopulmonary lavage fluid and la vaged cell profiles were also evaluated in this study. Similarities wi th respect to effects upon cell attachment, lavaged cell numbers and M phi viability, total lavageable protein, polymorphonuclear cell infil tration, . O-2(-) and H2O2 production, FcR expression, and the percent age of phagocytically active cells were observed between rabbits and h umans in response to H2SO4 exposure. Alternatively, while the capacity to phagocytose latex particles was significantly increased in rabbit cells, phagocytic capacity was reduced by 28% in human M phi. Acid exp osure significantly reduced the ex vivo uptake and killing of ingested S. aureus by rabbit cells, but the data were inconclusive for humans. This investigation represents the first attempt to directly compare, using similar assay protocols and experimental methods, the immunotoxi c effects of inhaled H2SO4 in an animal model with those in exposed hu man volunteers. Although making interspecies comparisons between human s and rabbits is complicated and needs to be approached with caution d ue to differences in such things as breathing rates, metabolism, and d eposition, results of this study provide a database for future immunot oxicological studies and support the applicability of rabbits as a mod el to predict H2SO4-induced alterations in human pulmonary immunocompe tence.