Effect of nitrogen dioxide on respiratory viral infection in airway epithelial cells.

Nitrogen dioxide (NO(2)) is a common air pollutant outdoors and indoors in homes with unvented combustion sources. It is also a constituent of tobacco smoke. Epidemiological studies suggest that children exposed to NO(2), or living with smoking parents, have an increased incidence of respiratory viral infections. The most common virus causing severe respiratory symptoms in infants and young children is respiratory syncytial virus (RSV). In the present study we investigated whether NO(2) exposure affects RSV infection in airway epithelial cells, the host cells for viral replication and virus-induced cytokine production. Cultures of the bronchial epithelial cell line BEAS-2B exposed to 0.5, 1.0, and 1.5 ppm NO(2) for 60 min were infected with RSV. Viral replication, as well as RSV-induced interleukin (IL)-6 and IL-8, was assessed at various times postinfection. The NO(2) doses used were not toxic to the BEAS-2B cells as measured by release of lactic dehydrogenase (LDH). The internalization of RSV was increased by exposure to 0.5 ppm NO(2) and decreased by exposure to 1.5 ppm NO(2). On the other hand, the release of infectious virus 48 h postexposure was not affected by the two lower doses of NO(2), but was significantly reduced in cells exposed to 1.5 ppm NO(2). Virus-induced cytokine production was also significantly reduced in cells exposed to 1.5 ppm NO(2), and not affected by 0.5 and 1.0 ppm. It is likely that the decrease in cytokine production is related to the decrease in viral burden. These data suggest that possible increases in viral clinical symptoms associated with NO(2) may not be caused by increased susceptibility of the epithelial cells to infection but may result from effects of NO(2) on host defenses that prevent the spread of virus. Copyright 1999 Academic Press.