Department of Applied Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
Exp Eye Res. 2012 May;98:97-103. doi: 10.1016/j.exer.2012.03.021. Epub 2012 Apr 5.
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.
眼部过敏的瘙痒症状虽可被 H1 组胺受体拮抗剂缓解，但不能完全消除，这表明组胺并非眼部过敏瘙痒的唯一介质。我们研究了速发型过敏反应中是否存在白三烯 B4（LTB4），一种皮肤瘙痒的介质。通过将豚草花粉和明矾反复皮下注射到鼠尾背部，对小鼠进行免疫，并在眼睑下注射豚草花粉提取物以进行过敏挑战。豚草花粉提取物的挑战明显引起了致敏小鼠的眼部搔抓。这种搔抓几乎可被肥大细胞缺乏所消除。H1 拮抗剂特非那定在几乎完全抑制血浆渗出的剂量下部分抑制搔抓。糖皮质激素倍他米松和 5-脂氧合酶抑制剂齐留通在抑制挑战诱导的 LTB4 产生的剂量下抑制搔抓。低于组胺所需剂量的 1/10000 或以下的 LTB4 经结膜下注射可引起未致敏小鼠的眼部搔抓。LTB4 受体拮抗剂 ONO-4057 以抑制 LTB4 诱导的眼部搔抓的剂量抑制了豚草花粉挑战诱导的眼部搔抓。除组胺外，LTB4 还参与花粉过敏的眼部瘙痒。具有抑制 LTB4 作用和/或产生作用的 H1 受体拮抗剂可能比选择性 H1 拮抗剂具有更强的止痒活性。
