Altered susceptibility to viral respiratory infection during short-term exposure to nitrogen dioxide

The studies reported here focus on the relation of nitrogen dioxide exposure to susceptibility to viral respiratory infection in a murine model of pneumonia, created by intratracheal inoculation of an endogenous murine pathogen, mouse cytomegalovirus. The purpose of this work is to clarify the potential role of nitrogen dioxide exposure in the pathogenesis of viral infection of the lower respiratory tract. Previous human epidemiologic studies have presented conflicting information about the relationship of nitrogen dioxide to acute, self-limited episodes of respiratory illness, which are characteristic of viral respiratory infection. Some studies have found an association between exposure to elevated ambient levels of nitrogen dioxide and increased occurrence of acute respiratory illness. In one study this association was found to be strongest in children in the first two years of life. However, other epidemiologic studies have failed to observe this relation. To determine if there is scientific evidence for the possible relation of nitrogen dioxide exposure to human respiratory infection, our studies were performed to assess the impact of nitrogen dioxide on respiratory tract susceptibility to initial, or primary, infection, as well as to recurrent infection, or reinfection, with the identical virus. The latter mechanism of viral respiratory infection is of particular interest, since reinfection is a common method for the development of infection of the lower respiratory tract during early childhood. Outbred CD-1 mice were exposed to either air or nitrogen dioxide for six hours a day on two consecutive days prior to inoculation with murine cytomegalovirus, and then were reexposed to the same level of nitrogen dioxide for six hours a day on four consecutive days, beginning the day after viral inoculation. Susceptibility to primary infection was determined by inoculating animals with an amount of virus (10(2) plaque-forming units) that is too small to produce viral infection in the lungs of normal animals. Mice exposed to 5 parts per million (ppm) nitrogen dioxide routinely developed viral replication in the lung and histologic evidence of pneumonitis after inoculation with this amount of virus, whereas air-exposed animals did not. Most importantly, animals exposed to 5 ppm nitrogen dioxide could be infected with a viral inoculum that was 100-fold smaller than that required to consistently produce viral infection in air-exposed mice. Enhanced susceptibility to infection was found after exposure to 5 ppm nitrogen dioxide, but was not observed with exposure to 2.5 or 1 ppm nitrogen dioxide.(ABSTRACT TRUNCATED AT 400 WORDS)