Synergism between rhinovirus infection and oxidant pollutant exposure enhances airway epithelial cell cytokine production.
Of the several factors believed to exacerbate asthmatic symptoms, air pollution and viral infections are considered to be particularly important. Although evidence indicates that each of these respiratory insults individually can increase asthma severity in susceptible individuals, we know little about the extent to which exposure to environmental oxidant pollutants can influence the course of respiratory viral infection and its associated inflammation. To investigate the interaction of these two stimuli within their common epithelial cell targets in the upper and lower respiratory tracks, we infected primary human nasal epithelial cells and cells of the BEAS-2B line grown at the air-liquid interface with human rhinovirus type 16 (RV16) and exposed them to NO2 (2.0 ppm) or O3 (0.2 ppm) for 3 hr. Independently, RV16, NO2, and O3 rapidly increased release of the inflammatory cytokine interleukin-8 through oxidant-dependent mechanisms. The combined effect of RV16 and oxidant ranged from 42% to 250% greater than additive for NO2 and from 41% to 67% for O3. We abrogated these effects by treating the cells with the antioxidant N-acetylcysteine. Surface expression of intercellular adhesion molecule 1 (ICAM-1) underwent additive enhancement in response to combined stimulation. These data indicate that oxidant pollutants can amplify the generation of proinflammatory cytokines by RV16-infected cells and suggest that virus-induced inflammation in upper and lower airways may be exacerbated by concurrent exposure to ambient levels of oxidants commonly encountered the indoor and outdoor environments.
Department of Environmental Health Sciences, The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21205, USA. espannha@jhsph.edu
E William
EW
Spannhake
Sekhar P M
SP
Reddy
David B
DB
Jacoby
Xiao-Ying
XY
Yu
Bahman
B
Saatian
Jingyan
J
Tian
D018929:Cell Culture Techniques; D016207:Cytokines / Q000096:biosynthesis*; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007249:Inflammation; D009585:Nitrogen Dioxide; D009666:Nose / Q000166:cytology; D010083:Oxidants, Photochemical / Q000009:adverse effects*; D010126:Ozone / Q000009:adverse effects*; D010850:Picornaviridae Infections / Q000276:immunology* / Q000503:physiopathology; D012229:Rhinovirus / Q000472:pathogenicity
D016207:Cytokines; D010083:Oxidants, Photochemical; D010126:Ozone; D009585:Nitrogen Dioxide