Azelastine inhibits stimulated histamine release from human lung tissue in vitro but does not alter cyclic nucleotide content.

To investigate the mechanism by which azelastine may be effective therapeutically in asthma, we studied its ability to inhibit anti-IgE- and calcium ionophore A23187-stimulated histamine release from human lung and to alter lung cyclic nucleotide levels. Significant inhibition of histamine release from both anti-IgE- and A23187-stimulated human tissue was apparent after 30 minutes preincubation of the lung tissue in azelastine. Significant inhibition of anti-IgE-stimulated histamine release was consistently seen in azelastine concentrations greater than or equal to 5 microM, and was dose dependent (r = 0.71, p less than 0.05) with maximal mean inhibition of 53 +/- 11%. For A23187-stimulated lung tissue, consistent inhibition of histamine release was not found until we used 30 microM azelastine, mean 35 +/- 11%. Inhibition in azelastine concentrations below 30 microM was variable and not significant. Lung cyclic AMP and cyclic GMP content was not significantly altered by incubation of lung tissue in 100 microM azelastine. We conclude that azelastine inhibits stimulated histamine release from human lung tissue in vitro but does not alter cyclic nucleotide content.