EFFECTS OF ANTIASTHMA DRUGS ON SUPEROXIDE ANION GENERATION FROM HUMAN POLYMORPHONUCLEAR LEUKOCYTES OR HYPOXANTHINE-XANTHINE OXIDASE SYSTEM

Airway inflammation with human polymorphonuclear leukocytes (PMNs) may play an important role in the pathophysiology of bronchial asthma. Superoxide anion (O2-) and other active oxygen species derived from PMNs cause tissue damage. To evaluate the effects of antiasthma drugs on airway inflammation or antioxidative actions due to the inhibition of O2- generation, we investigated the effects of antiallergic drugs. beta-adrenergic agonists, theophylline and corticosteroids, on the in vitro generation of O2- by human PMNs, using a chemiluminescence (CL) method dependent on a Cypridina luciferin analog (MCLA), a highly sensitive and specific CL probe for O2-. We found that azelastine, one of the antiallergic drugs, and isoproterenol inhibited FMLP-induced O2- generation in a dose-dependent fashion, whereas the other drugs exhibited no such inhibitory action except at very high concentrations. Furthermore, we found that isoproterenol inhibited O2- generation from the hypoxanthine-xanthine oxidase system (an O2--generating system) in a dose-dependent fashion, unlike azelastine and the other drugs. These results suggest that azelastine and isoproterenol inhibit the process of O2- generation from PMNs, while isoproterenol also scavenges O2-. These drugs may be beneficial in the treatment of airway inflammation due to O2- generation in bronchial asthma.