title: Involvement of leukotriene B4 in itching in a mouse model of ocular allergy.
abstract: Itching of ocular allergy is alleviated but not completely relieved by H(1) histamine receptor antagonists, suggesting that histamine is not the sole itch mediator in ocular allergy. We investigated whether leukotriene B(4) (LTB(4)), a mediator of cutaneous itch, is involved in the itch of ocular allergy in mice. Mice were immunized by the repeated subcutaneous injections of ragweed pollen and alum into the caudal back, and given a subconjunctival injection of ragweed pollen extract into the palpebra for allergic challenge. Challenge with ragweed pollen extract markedly elicited ocular scratching in sensitized mice. The scratching was almost abolished by mast cell deficiency. The H(1) antagonist terfenadine partially inhibited scratching at a dose that almost completely suppressed plasma extravasation. Scratching was inhibited by the glucocorticoid betamethasone and the 5-lipoxygenase inhibitor zileuton at doses that inhibited the challenge-induced production of LTB(4). A subconjunctival injection of LTB(4) at doses 1/10,000 or less than that required for histamine elicited ocular scratching in naïve mice. The LTB(4) receptor antagonist ONO-4057 inhibited the ragweed pollen challenge-induced ocular scratching at doses that suppressed LTB(4)-induced ocular scratching. In addition to histamine, LTB(4) is involved in the ocular itching of pollen allergy. H(1) receptor antagonists with an inhibitory effect on the action and/or production of LTB(4) may have more potent anti-pruritic activity than selective H(1) antagonists.
authors.affiliation: Department of Applied Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
authors.forename: Tsugunobu
authors.initials: T
authors.lastname: Andoh
authors.forename: Kazunari
authors.initials: K
authors.lastname: Sakai
authors.forename: Masahisa
authors.initials: M
authors.lastname: Urashima
authors.forename: Kayo
authors.initials: K
authors.lastname: Kitazawa
authors.forename: Azusa
authors.initials: A
authors.lastname: Honma
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kuraishi
mesh_terms: D000485:Allergens / Q000276:immunology; D031164:Ambrosia; D000818:Animals; D003233:Conjunctivitis, Allergic / Q000276:immunology* / Q000517:prevention & control; D004195:Disease Models, Animal; D005938:Glucocorticoids / Q000494:pharmacology; D006632:Histamine / Q000502:physiology; D039563:Histamine H1 Antagonists, Non-Sedating / Q000494:pharmacology; D006918:Hydroxyurea / Q000031:analogs & derivatives / Q000494:pharmacology; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007166:Immunosuppressive Agents / Q000494:pharmacology; D056965:Injections, Intraocular; D007279:Injections, Subcutaneous; D007975:Leukotriene B4 / Q000502:physiology*; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008297:Male; D008407:Mast Cells / Q000276:immunology; D051379:Mice; D008813:Mice, Inbred ICR; D010666:Phenylpropionates; D011058:Pollen / Q000276:immunology; D016593:Terfenadine / Q000494:pharmacology
chemical_list: D000485:Allergens; D005938:Glucocorticoids; D039563:Histamine H1 Antagonists, Non-Sedating; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D016859:Lipoxygenase Inhibitors; D010666:Phenylpropionates; C067523:ONO-LB 457; D007975:Leukotriene B4; D007073:Immunoglobulin E; D016593:Terfenadine; D006632:Histamine; C063449:zileuton; D006918:Hydroxyurea