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


METHODS
Male BALB/c and BALB/c-nu/nu mice were used.


METHODS
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.


METHODS
Mice actively sensitized with OA were challenged by intradermally injecting OA into both ears. Ear thickness was measured with a dial thickness gauge.


RESULTS
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.


CONCLUSIONS
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.
Yamaguchi
S
S
Pharmacology, Drug Development Laboratories, Welfide Corporation, Fukuoka, Japan. yamaguchi_shuji@welfide.co.jp
Tomomatsu
N
N
Komatsu
H
H
D000284:Administration, Oral; D000287:Administration, Topical; D000485:Allergens / Q000276:immunology; D000818:Animals; D018926:Anti-Allergic Agents / Q000008:administration & dosage / Q000494:pharmacology; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001190:Arylsulfonates / Q000008:administration & dosage / Q000494:pharmacology; D001381:Azepines / Q000008:administration & dosage / Q000494:pharmacology*; D017449:Dermatitis, Allergic Contact / Q000276:immunology* / Q000473:pathology; D004423:Ear / Q000473:pathology; D004804:Eosinophils / Q000276:immunology; D006634:Histamine H1 Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D006854:Hydrocortisone; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007665:Ketotifen / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010047:Ovalbumin / Q000276:immunology; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors*; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D013452:Sulfonium Compounds / Q000008:administration & dosage / Q000494:pharmacology; D013997:Time Factors; D014230:Triazoles / Q000008:administration & dosage / Q000494:pharmacology*
D000485:Allergens; D018926:Anti-Allergic Agents; D000893:Anti-Inflammatory Agents; D001190:Arylsulfonates; D001381:Azepines; D006634:Histamine H1 Antagonists; D007074:Immunoglobulin G; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D013452:Sulfonium Compounds; D014230:Triazoles; C039351:platelet activating factor receptor; C068035:4-(2-chlorophenyl)-2-(2-(4-isobutylphenyl)ethyl)-6,9-dimethyl-6H-thieno(3,2-f)(1,2,4)triazolo(4,3-a)(1,4)diazepine; D007073:Immunoglobulin E; D010047:Ovalbumin; C073028:suplatast tosilate; D006854:Hydrocortisone; D007665:Ketotifen