Okamoto T, Iwata S, Ohnuma K, Dang N H, Morimoto C
Division of Clinical Immunology, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, Japan.
Clin Exp Immunol. 2009 Jul;157(1):27-34. doi: 10.1111/j.1365-2249.2009.03958.x.
Being a first-line treatment for hypersensitivity allergic disease, histamine H1-receptor antagonists possess anti-inflammatory activity in addition to being H1-receptor antagonists. While it is not purely a histamine-related condition, hypersensitivity allergic disease is associated with an increase in the number of T helper type 2 (Th2) cells and Th2 cytokines, and a decrease in the number of Th1 cells and Th1 cytokines. Suppression of Th2-type cytokine production in addition to H1-receptor blockade may therefore represent a successful therapeutic strategy for the treatment of hypersensitivity allergic diseases. H1-receptor antagonists have been reported to modulate immune cascade at various points by acting on T cell-related inflammatory molecules, including adhesion molecules, chemokines and inflammatory cytokines. These effects of H1-receptor antagonists may be optimized for the treatment of allergic diseases. Besides their ability to regulate inflammatory molecules, some H1-receptor antagonists have been reported to down-regulate Th2 cytokine production. In particular, it has been shown that several H1-receptor antagonists specifically inhibit the production of Th2, but not Th1, cytokines. Accumulating evidence indicates a crucial role for Th1/Th2 cytokine imbalance on the development of allergic diseases. Accordingly, the use of H1-receptor antagonist with Th2 cytokine inhibitory activity to modulate Th1/Th2 cytokine imbalance might be a favourable strategy for the treatment of hypersensitivity allergic diseases. Furthermore, the identification of H1-receptor antagonists which possess immunoregulatory activities in addition to their anti-histamine activity will provide an important insight into the development of novel immunoregulatory drugs.
作为过敏性疾病的一线治疗药物，组胺H1受体拮抗剂除了是H1受体拮抗剂外，还具有抗炎活性。虽然超敏反应性过敏性疾病并非纯粹与组胺相关，但它与2型辅助性T细胞（Th2）和Th2细胞因子数量增加以及Th1细胞和Th1细胞因子数量减少有关。因此，除了H1受体阻断外，抑制Th2型细胞因子的产生可能是治疗超敏反应性过敏性疾病的一种成功治疗策略。据报道，H1受体拮抗剂可通过作用于与T细胞相关的炎症分子，包括黏附分子、趋化因子和炎症细胞因子，在多个环节调节免疫级联反应。H1受体拮抗剂的这些作用可能在过敏性疾病治疗中得到优化。除了调节炎症分子的能力外，一些H1受体拮抗剂还被报道可下调Th2细胞因子的产生。特别是，已经表明几种H1受体拮抗剂特异性抑制Th2而非Th1细胞因子的产生。越来越多的证据表明Th1/Th2细胞因子失衡在过敏性疾病发展中起关键作用。因此，使用具有Th2细胞因子抑制活性的H1受体拮抗剂来调节Th1/Th2细胞因子失衡可能是治疗超敏反应性过敏性疾病的有利策略。此外，鉴定除抗组胺活性外还具有免疫调节活性的H1受体拮抗剂将为新型免疫调节药物的开发提供重要见解。
