The scientific literature suggests that ambient levels of
nitrogen dioxide increase susceptibility to
respiratory infections. However, this association has not been conclusively demonstrated. The epidemiologic data regarding this relationship are inconclusive because these studies have used parameters of "acute respiratory illness" that are not necessarily related to infectious episodes. Previous animal studies have used either mortality after
bacterial infection with virulent bacteria or decreased rate of intrapulmonary killing of bacteria with low virulence. Studies using appropriate bacterial and viral challenge organisms, with morbidity as an endpoint, provide a better basis for extrapolation to humans. The investigations in animals suggest a relationship between
nitrogen dioxide and increased susceptibility to respiratory
infection, but studies in which functional parameters of host resistance to such
infections have been used are few. The aim of this work was to determine the threshold level of acute
nitrogen dioxide exposure that would induce increased susceptibility to, and increased severity of, viral and
bacterial infections. Physiologic parameters of host resistance to
respiratory infections were used as endpoints. A composite picture was developed of dose-response relationships between
nitrogen dioxide and the impairment of a spectrum of defense parameters in the murine respiratory tract against viral and bacterial challenges. The salient findings of this study are as follows: (1) the intrapulmonary killing of Staphylococcus aureus was impaired at 5 ppm of
nitrogen dioxide; (2) this effect was found at 2.5 ppm or less when
nitrogen dioxide exposure was superimposed on lungs predisposed to lowered resistance through immunosuppression with
corticosteroids; (3) the adverse effect of
nitrogen dioxide occurred at lower concentrations when exposure followed bacterial challenge; and (4) during the course of murine Sendai virus
infection, exposure to
nitrogen dioxide for four hours per day did not alter the
infection in the lungs, but rather it enhanced lung pathology. The implications of these findings are that the antibacterial defenses of the lungs are susceptible to the inhibiting effects of short acute exposures of lower concentrations of
nitrogen dioxide when the lungs are predisposed by bacteria present or, even more so, by immunosuppression. The alveolar macrophage phagocytic system is the defense component of the lungs that is most susceptible to the adverse effects of
nitrogen dioxide. The finding that
nitrogen dioxide increases virus-associated lung damage suggests that the increased severity of the disease process results from the proliferation of the virus to high titers, rather than from alterations of the infective process.