Effect of Y-24180, an antagonist at platelet-activating factor (PAF) receptors, on IgE-mediated cutaneous reactions in mice

Abstract.

Objective and Design: We examined the effect of Y-24180, a potent platelet-activating factor (PAF) antagonist, on IgE-mediated cutaneous reactions in mice.¶Materials: Female BALB/c mice were used.¶Treatment: Drugs were orally administered 1 h before a dinitrofluorobenzene (DNFB) challenge or 1 h before and 12 h after the challenge.¶Methods: Biphasic increase in ear thickness, with peak responses at 1 h (immediate phase reaction, IPR) and 24 h (late phase reaction, LPR) after the DNFB challenge, were induced in mice which had been passively sensitized with monoclonal anti-dinitrophenyl IgE antibody 24 h before the DNFB challenge. Ear thickness was measured with a dial thickness gauge.¶Results: Y-24180, WEB2086, ketotifen, and suplatast suppressed the IPR. Y-24180 also suppressed the LPR when administered once at 10 mg/kg or twice at 1 to 10 mg/kg. WEB2086 suppressed the LPR only when administered twice. However, ketotifen and suplatast did not suppress the LPR even when administered twice. Single administration of prednisolone significantly suppressed both the IPR and LPR.¶Conclusions: These results indicate that PAF may be involved in the induction of biphasic cutaneous reactions mediated by IgE, and Y-24180 is more effective compared with WEB2086 in this model. It is possible that the difference in the effectiveness between Y-24180 and WEB2086 depends on the persistence of those activities.