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 H1 histamine receptor antagonists, suggesting that histamine is not the sole itch mediator in ocular allergy. We investigated whether leukotriene B4 (LTB4), 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 H1 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 LTB4. A subconjunctival injection of LTB4 at doses 1/10,000 or less than that required for histamine elicited ocular scratching in naïve mice. The LTB4 receptor antagonist ONO-4057 inhibited the ragweed pollen challenge-induced ocular scratching at doses that suppressed LTB4-induced ocular scratching. In addition to histamine, LTB4 is involved in the ocular itching of pollen allergy. H1 receptor antagonists with an inhibitory effect on the action and/or production of LTB4 may have more potent anti-pruritic activity than selective H1 antagonists.