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

在过敏性疾病中，过敏原特异性Th 2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。本研究探讨了影响Th 2细胞优先分化的因素，并对可能导致Th 2细胞优先分化的细胞因子表达和候选基因多态性进行了研究。对变应性疾病患者和对照组的IL-4 5 '调控区、IL-4受体（R）和β 2肾上腺素受体（ADR）基因多态性分析表明，IL-4 R-50 Val/Ile与变应性疾病有显著相关性（OR = 2.3）。此外，多态性（IL-4 R-50和b2-ADR-16 Arg/Gly）的组合分析显示，比值比为5.8。IL-18是一种细胞因子，最近发现具有Th 2诱导活性，直接作用于活化的嗜酸性粒细胞，导致IL-8产生的增强。无论是在患有 ...更多信息 在AD模型小鼠NC/Nga中，血清IL-18水平升高。然而，持续注射抗IL-18 Ab加重了皮肤病变。IL-18在特应性皮炎中的作用有待进一步研究。在人类IL-18外显子基因（105 A/C）上发现了一个多态性位点，其意义目前尚不清楚。Percedonia叶提取物及其主要成分，甘草素，一种黄酮醇抑制组胺从嗜碱性粒细胞释放，口服这些物质显着抑制NC/Nga小鼠皮炎的发展，IgE升高和经表皮水分流失。此外，部分黄酮类化合物对活化的嗜碱性粒细胞表达Th 2型细胞因子（IL-4、IL-5、IL-13）有抑制作用。这些研究提出了这些抗过敏物质可能成为替代或补充药物的可能性。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