Effect of desloratadine and loratadine on rhinovirus-induced intercellularadhesion molecule 1 upregulation and promoter activation in respiratory epithelial cells

Background: Rhinoviruses have been recently associated with the majority of asthma exacerbations for which current therapy is inadequate. Intercellula r adhesion molecule 1 (ICAM-1) has a central role in airway inflammation in asthma, and it is the receptor for 90% of rhinoviruses. Rhinovirus infecti on of airway epithelium induces ICAM-1. Desloratadine and loratadine are co mpounds belonging to the new class of H-1-receptor blockers. Anti-inflammat ory properties of antihistamines have been recently documented, although th e underlying molecular mechanisms are not completely defined. Objective: We have investigated the effects of desloratadine and loratadine on rhinovirus-induced ICAM-1 expression, mRNA upregulation, and promoter a ctivation. Methods: Cultured primary bronchial or transformed (A549) respiratory epith elial cells were pretreated with desloratadine and loratadine for 16 hours and infected with rhinovirus type 16 for 8 hours. ICAM-1 surface expression was evaluated with flow cytometry, and ICAM-1 mRNA was evaluated with spec ific RT-PCR. In A549 cells promoter activation was evaluated with a chloram phenicol acetyltransferase assay, and binding activity of nuclear factor ka ppaB in nuclear extracts was evaluated with an electrophoretic mobility shi ft assay. Results: Desloratadine and loratadine (0.1-10 mu mol/L) inhibited rhinoviru s-induced ICAM-1 upregulation in both primary bronchial or transformed (A54 9) respiratory epithelial cells. In A549 cells the 2 compounds showed a dos e-dependent inhibition with similar efficacy (inhibitory concentration of 5 0%, 1 mu mol/L). Desloratadine and loratadine also inhibited ICAM-1 mRNA in duction caused by rhinovirus infection in a dose-dependent manner, and they completely inhibited rhinovirus-induced ICAM-1 promoter activation. Deslor atadine also inhibited rhinovirus-induced nuclear factor kappaB activation. Desloratadine and loratadine had no direct effect on rhinovirus infectivit y and replication in cultured epithelial cells. Conclusion: These effects are unlikely to be mediated by H-1-receptor antag onism and suggest a novel mechanism of action that may be important for the therapeutic control of virus-induced asthma exacerbations.