Effect of azelastine on airway hyperresponsiveness mediated by stimulated macrophages

Abstract

The effect of the anti-allergic drug azelastine, 4-( p-chlorobenzyl)-2-(hexahydro-1-methyl-1 H-azepine-4-yl)-1-(2H)-phthalazione), on airway hyperresponsiveness induced by immunologically stimulated pulmonary alveolar macrophages was investigated in canine bronchial segments under isometric conditions in vitro. Macrophages stimulated with anti-dinitrophenyl immunoglobulin E (IgE) antibody and dinitrophenyl-human serum albumin potentiated the contractile responses to electrical field stimulation at all frequencies, an effect that was abolished by azelastine (3 × 10 −5 M). In contrast, azelastine had no effect on the potentiation of the contractile responses to electrical stimulation by U46619, a thromboxane A 2 mimetic. The IgE-mediated release of thromboxane A 2 from macrophages was inhibited by azelastine in a concentration-dependent fashion, the maximal decrease and the concentration required to produce a half-maximal effect being 84 ± 6% ( P < 0.001) and 16 μM, respectively. These results suggest that azelastine may attenuate macrophage-induced parasympathetic airway hyperresponsiveness through an inhibition of the release of thromboxane A 2.