Analysis of determinants responsible for preferential development of Th2 cells in allergic diseases

在过敏性疾病中，变应原特异性Th2细胞优先分化，并在IgE反应性、器官高反应性和过敏性炎症的形成中发挥核心作用。在这项研究中，哪些决定因素可能导致Th2的分化，并检测了可能导致Th2优先分化的细胞因子的表达和候选基因的多态性。对变态反应性疾病患者和对照组5“IL-4调控区、IL-4受体(R)和b2-肾上腺素能受体(ADR)基因的多态性分析表明，IL-4R-50Val/Ile与变态反应性疾病显著相关(优势比2.3)。此外，IL-4R-50和b2-ADR-16Arg/Gly等位基因多态的组合分析显示，OR值为5.8。IL-18是最近发现的一种具有Th2诱导活性的细胞因子，它直接作用于激活的嗜酸性粒细胞，从而促进IL-8的产生。在患有…的患者中都是如此更多的主题皮炎(AD)，在AD模型小鼠，NC/NGA，血清IL-18水平升高。然而，持续注射抗IL-18抗体加剧了皮肤损伤。需要进一步的研究来评估IL-18在特应性皮炎中的作用。人类IL-18外显子基因105A/C存在一种多态性，其意义目前尚不清楚。临床研究测试了一种民间药物对AD患者的疗效，促使我们对该药物中的抗过敏物质进行了检测。柿叶提取物及其主要成分黄芪甲素可抑制嗜碱性粒细胞释放组胺，灌胃给药可显著抑制NC/NGA小鼠皮炎的发生、IgE升高和皮肤水分丢失。此外，某些黄酮类化合物对活化的嗜碱性粒细胞表达Th2细胞因子(IL-4、IL-5、IL-13)具有抑制作用。这些研究提出了一种可能性，即这些抗过敏物质可能是替代药物或补充药物。较少

In allergic diseases, allergen specific Th2 cells are preferentially differentiated and play central roles on the formation of IgE responsiveness, organ hyper-reactivity and allergic inflammation. In this study what determinants might be responsible for such Th2 differentiation was asked.The expression of cytokine and polymorphisms of candidate genes, which might cause preferential Th2 differentiation were examined. Analyses of gene polymorphisms including 5"IL-4 regulatory region, IL-4 receptor (R) and b2-adrenoceptor (ADR) genes in the patients with allergic diseases and controls showed that IL-4R-50Val/Ile was significantly associated with allergic diseases (odds ratio 2.3). In addition, combinational analysis of polymorphisms (IL-4R-50 and b2-ADR-16Arg/Gly) revealed that the odds ratio was 5.8. IL-18, a cytokine, recently found to possess an activity of Th2 induction, directly functioned activated eosinophils, resulting in enhancement of IL-8 production. Both in the patients with a … More topic dermatitis (AD) and in the AD model mouse, NC/Nga, serum levels of IL-18 were elevated. Continuous injection of anti-IL-18 Ab exacerbated skin lesions, however. Further studies were required to evaluate roles of IL-18 on atopic dermatitis. One polymorphism in human IL-18 exon gene (105A/C) was found and its significance remained unknown at the present time.The clinical study testing efficacy of one folk remedy on the patients with AD prompted us to examine anti-allergic substances in the remedy. Persimmon leaf extract and its major ingredient, astragalin, a flavonol inhibit histamine release from basophils and oral administration of these substances strikingly inhibit development of dermatitis, IgE elevation and transepidermal water loss in NC/Nga mice. In addition, some kinds of flavonoids showed an inhibitory activity of expression of Th2 cytokines (IL-4, IL-5, IL-13) by activated basophils. These studies raised a possibility that these anti-allergic substances might to be alternative or complementary medicine. Less