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.