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)