Effect of loratadine on nitrogen dioxide-induced changes in electrical resistance and release of inflammatory mediators from cultured human bronchial epithelial cells

Background: Recent studies have demonstrated that some antihistamines can attenuate histamine-induced release of inflammatory mediators from bronchial epithelial cells. Objective: The purpose of study was to test the hypothesis that Loratadine may influence pollution-induced inflammation of the airways by modulating epithelial membrane integrity and the synthesis and/or release of inflammatory mediators from airway epithelial cells. Methods: We have cultured human bronchial epithelial cell (HBEC) cultures from surgical explants and investigated the effect of loratadine on NO2-induced changes in both electrical resistance of HBEC cultures and release of IL-8, RANTES, and soluble intercellular adhesion molecule-1 (sICAM-1) from these cells after exposure for 6 hours to either air or 400 ppb NO2. Results: Exposure for 6 hours to NO2 significantly decreased the electrical resistance of HBEC cultures by 18.1% from baseline (P <.05). Incubation with 0.25 to 25 mu mol/L loratadine did not alter the NO2-induced decrease in the electrical resistance of HBEC cultures. NO2 also significantly increased the release of IL-8 from a control value of 52.5 pg/mu g cellular protein to 81.9 pg/mu g cellular protein (P <.05), RANTES from a control value of 0.023 pg/mu g cellular protein to 0.062 pg/mu g cellular protein (P <.05), and sICAM-1 from a control value of 7.7 pg/mu g cellular protein to 16.3 pg/mu g cellular protein (P <.05), The NO2-induced release of all 3 mediators was significantly attenuated by incubation of HBECs with 25 mu mol/L loratadine. Incubation with 2.5 mu mol/L loratadine also significantly attenuated the NO2-induced release of RANTES and sICAM-1, but not IL-8. Conclusions: These results suggest that loratadine has the potential to reduce airway inflammation by modulating the release of inflammatory cytokines from airway epithelial cells.