Effect of ozone and nitrogen dioxide on the release of proinflammatory mediators from bronchial epithelial cells of nonatopic nonasthmatic subjects and atopic asthmatic patients in vitro

Background: Although studies have suggested that ozone (O-3) and nitrogen d ioxide (NO2) may play a role in the pathogenesis of asthma, the underlying mechanisms are not clear. Objective: We aimed to investigate the effects of O-3 and NO2 on the releas e of IL-8, GM-CSF, RANTES, and soluble intercellular adhesion molecule 1 (s ICAM-1) from human bronchial epithelial cells (HBF,Cs) of nonatopic nonasth matic subjects (nonasthmatic subjects) and atopic subjects with mild asthma (asthmatic subjects) in vitro. Methods: We cultured HBECs from bronchial biopsy specimens of nonasthmatic and asthmatic subjects; exposed these for 6 hours to air, 10 to 100 ppb O-3 , or 100 to 400 ppb NO2; and analyzed the release of IL-8, GM-CSF, RANTES, and sICAM-1 after 24 hours' incubation. Results: There was no significant difference between the constitutive relea se of IL-8, GM-CSF; and sICAM-1 from HBECs of asthmatic and nonasthmatic su bjects, RANTES was detected only in HBECs derived from asthmatic subjects. Exposure of HBECs of asthmatic subjects to both 50 to 100 ppb O-3 and 200 t o 400 ppb NO2 significantly increased the release of IL-8, GM-CSF, RANTES, and sICAM-1 from these cells after 24 hours of incubation. However, 50 to 1 00 ppb O-3 and 200 to 400 ppb NO2 led to a significant increase in release of only IL-8 and sICAM-1 from HBECs of nonasthmatic subjects after 24 hours ' incubation. A comparison between the pollutant-induced release of mediato rs demonstrated that 100 ppb O-3. induced release of GM-CSF and sICAM-1 was significantly greater in HBECs of asthmatic subjects (medians, 0.59 and 27 .4 pg/mug cellular protein, respectively) than in HBECs of nonasthmatic sub jects (medians, 0.27 and 14.4 pg/mug cellular protein, respectively; P<.02) . Conclusion: These results suggest that O-3 and NO2 may modulate airway dise ases, such as asthma, by increasing the release of inflammatory mediators f rom bronchial epithelial cells and that the cells of asthmatic subjects may be more susceptible to the adverse effects of these pollutants.