Effects of anti-allergy drugs on fMet-Leu-Phe-stimulated superoxide generation in human neutrophils.

Abstract

We examined effects of six oral anti-allergy drugs used to treat bronchial asthma on fMet-Leu-Phe (N-formyl-methionyl-leucyl-phenylalanine)-induced superoxide (O2-) generation and mobilization of intracellular free calcium ([Ca2+]i) in human neutrophils. We also evaluated the direct action of these drugs on NADPH (reduced nicotinamide-adenine dinucleotide phosphate)-oxidase activity in cell lysate (cell-free system). Ketotifen (25 approximately 200 microM) enhanced fMet-Leu-Phe-stimulated O2- generation and [Ca2+]i mobilization, although it directly inhibited NADPH oxidase in the cell-free study. Low concentrations of oxatomide (5-20 microM) enhanced O2- generation, but concentrations > 25 microM inhibited O2- generation. In concentrations below 20 microM, oxatomide had no effects on fMet-Leu-Phe-stimulated [Ca2+]i mobilization, but at concentrations above 25 microM, it inhibited [Ca2+]i mobilization. Oxatomide inhibited NADPH oxidase activity at all concentrations examined. Azelastine, pemirolast, tranilast, and repirinast inhibited O2- generation and [Ca2+]i mobilization. Azelastine and pemirolast directly inhibited NADPH oxidase, but tranilast and repirinast did not. Our results indicated that except for ketotifen and low concentration of oxatomide, oral anti-allergy drugs used to treat bronchial asthma inhibited fMet-Leu-Phe-induced O2- generation in human neutrophils. Based on IC50 values, potency of drugs was as follows: oxatomide > azelastine > tranilast > pemirolast > repirinast.