Effect of Y-24180, a receptor antagonist to platelet-activating factor (PAF), on allergic cutaneous reactions in actively sensitized mice.

Abstract

We examined the effect of Y-24180, a potent antagonist to platelet-activating factor (PAF), on allergic cutaneous reactions in actively sensitized mice. Male BALB/c and BALB/c-nu/nu mice were used. Y-24180, ketotifen fumarate (ketotifen), and suplatast tosilate (suplatast) were orally administered twice a day for 3 days beginning 2 days before an ovalbumin (OA) challenge. Hydrocortisone 17-butyrate (hydrocortisone) was applied topically to ear surface once a day for 3 days, beginning 2 days before the OA challenge. Mice actively sensitized with OA were challenged by intradermally injecting OA into both ears. Ear thickness was measured with a dial thickness gauge. Increase in ear thickness, with peak responses at 1 h (immediate phase reaction, IPR) and 24 h (late phase reaction, LPR) after the challenge, were induced in actively sensitized BALB/c mice. The reactions were not induced in T cell-deficient BALB/c-nu/nu mice. Y-24180 suppressed both the IPR and LPR of BALB/c mice. Although suplatast suppressed the LPR, the IPR was not affected. Ketotifen suppressed the IPR, but not the LPR. Hydrocortisone suppressed both the IPR and LPR of BALB/c mice. Furthermore, Y-24180 in combination with hydrocortisone significantly enhanced the effect of hydrocortisone on both the reactions. Y-24180 was demonstrated not only to suppress the IPR and LPR, but also to show strong suppressive effects in combination with topical hydrocortisone. Therefore, Y-24180 is expected to contribute to the treatment of inflammatory skin diseases including atopic dermatitis.