Effects of HC 20-511 (ketotifen) on chemiluminescence of human neutrophils

Abstract

The effects of ketotifen on the chemiluminescence (CL) and chemotaxis of human neutrophils were studied in vitro. Stimulations of neutrophils by concanavalin A (Con A), calcium ionophore A23187 (CI) and formyl-methionyl-leucyl-phenylalanine (FMLP) were strongly suppressed in contrast with that by zymosan, which was only slightly inhibited in CL assay; the inhibitory effect of ketotifen was dose dependent. The addition of ketotifen even after stimulations of CI' and FMLP also inhibited CL response. The neutrophils which were activated by incubation with FMLP (10(-7)M) at 37 degrees C for 60 min emitted much greater light in CI-induced CL assay than those without the pretreatment with FMLP. Such enhanced CL of activated cells was also markedly suppressed by ketotifen. On the other hand, ketotifen did not show any inhibitory effect on the direct movement of neutrophils by FMLP (10(-7)M) at the concentrations which inhibited CL responses. These unique pharmacological activities of ketotifen are encouraging for its potential clinical usage as an antiinflammatory agent in some disorders associated with neutrophils as well as for its experimental usefulness for the analysis of various functions of neutrophils.