Nitrogen dioxide exposure in vivo and human alveolar macrophage inactivation of influenza virus in vitro

Environ Res. 1989 Apr;48(2):179-92. doi: 10.1016/s0013-9351(89)80033-7.


Epidemiologic studies have reported an increased incidence of respiratory infections and illness in association with elevated indoor levels of nitrogen dioxide (NO2). Animal exposure studies have found that brief exposures to peak levels of NO2 produce greater morbidity than continuous lower level exposure. In order to examine the effect of NO2 inhalation on human alveolar macrophages, normal volunteers were exposed sequentially to air or NO2, by double-blind randomization, in an environmental chamber. Two exposure protocols with comparable concentration x time products were used: (a) continuous 0.60 ppm NO2 (n = 9), and (b) background 0.05 ppm NO2 with three 15-min peaks of 2.0 ppm (n = 15). Inhalation of NO2 caused no significant changes in pulmonary function or airway reactivity in either exposure protocol. Alveolar macrophages obtained by bronchoalveolar lavage 3 1/2 hr after exposure to continuous 0.60 ppm NO2 tended to inactivate influenza virus in vitro less effectively than cells collected after air exposure (1.96 vs 1.25 log10 plaque-forming units on Day 2 of incubation, P less than 0.07). Four of nine subjects accounted for the observed impairment in virus inactivation; cells from these four subjects demonstrated an increase in interleukin-1 (IL-1) production after NO2 vs air, whereas the five remaining subjects decreased IL-1 production after NO2. In contrast, intermittent peak exposure did not alter the rate of viral inactivation or IL-1 production. This methodology has the potential to identify pollutant effects on mechanisms of respiratory defense in humans.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Air Pollutants*
  • Atmosphere Exposure Chambers
  • Bronchoalveolar Lavage Fluid / analysis
  • Bronchoalveolar Lavage Fluid / cytology
  • Bronchoalveolar Lavage Fluid / immunology
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Influenza A virus / immunology*
  • Interleukin-1 / analysis
  • Macrophages / drug effects*
  • Macrophages / immunology
  • Male
  • Nitrogen Dioxide / adverse effects*
  • Pulmonary Alveoli / drug effects*
  • Pulmonary Alveoli / immunology
  • Time Factors


  • Air Pollutants
  • Interleukin-1
  • Nitrogen Dioxide