title: Modulation of pulmonary defense mechanisms against viral and bacterial infections by acute exposures to nitrogen dioxide.
abstract: 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.
authors.affiliation: Department of Environmental Health Sciences, Johns Hopkins School of Hygiene and Public Health, Baltimore, MD.
authors.forename: G J
authors.initials: GJ
authors.lastname: Jakab
mesh_terms: D000818:Animals; D005260:Female; D007165:Immunosuppression Therapy; D008168:Lung / Q000187:drug effects / Q000276:immunology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D051379:Mice; D009585:Nitrogen Dioxide / Q000009:adverse effects*; D010222:Parainfluenza Virus 1, Human; D018184:Paramyxoviridae Infections / Q000276:immunology*; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000276:immunology; D012141:Respiratory Tract Infections / Q000276:immunology*; D013203:Staphylococcal Infections / Q000276:immunology*
chemical_list: D009585:Nitrogen Dioxide