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孕期母体细胞因子的产生与三岁后代儿童喘息及过敏性疾病的发展

Maternal cytokine production during pregnancy and the development of childhood wheezing and allergic disease in offspring three years of age.

作者信息

Kim Jeong Ho, Kim Kye-Hyun, Woo Hee Yeon, Shim Jung Yeon

机构信息

Department of Pediatrics, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.

出版信息

J Asthma. 2008 Dec;45(10):948-52. doi: 10.1080/02770900802419676.

DOI:10.1080/02770900802419676
PMID:19085588
Abstract

Allergic diseases are multifactorial; they develop from complex interactions between genes and the environment. The immunological bias toward atopy and asthma might be established during in utero development of the fetal immune system. We prospectively investigated the association between maternal cytokine changes during pregnancy and the development of childhood wheezing and atopy at three years of age. Blood samples from 90 pregnant women were assayed for TNF-alpha, TGF-beta, IFN-gamma, IL-4, IL-6, and IL-2 at 18 weeks of gestation and at 6 weeks after delivery. Telephone interviews were performed and a questionnaire administered to assess wheezing and allergic disease in the children. The serum total IgE and specific IgE to eggs, milk and dust mites were measured. Maternal IFN-gamma, TNF-alpha and TGF-beta levels significantly decreased during pregnancy compared to the levels after delivery. However, the IL-4 levels did not change. Maternal TNF-alpha and IFN-gamma levels were decreased both before and after delivery in children with reported wheezing. Individual maternal IL-4 levels, before delivery, were higher than after delivery in the children that developed wheezing. There were no significant differences in maternal cytokine levels between children with and without asthma. In children with atopy, the maternal IFN-gamma /IL-4 ratio, during the first trimester, had a tendency to decrease compared to the children without atopy, whereas the maternal IL-2 levels at 6 weeks after delivery were increased. A first pregnancy showed higher concentrations of IL-4 before and after delivery than did women with multiple pregnancies. Maternal cytokine levels begin to change toward a Th2 immunity starting in the first trimester. A stronger Th2 immune response during the first trimester of pregnancy is associated with childhood wheezing and atopy at three years of age, and a first pregnancy.

摘要

过敏性疾病是多因素导致的;它们由基因与环境之间的复杂相互作用引发。对特应性和哮喘的免疫倾向可能在胎儿免疫系统的子宫内发育过程中就已确立。我们前瞻性地研究了孕期母亲细胞因子变化与儿童三岁时喘息和特应性疾病发生之间的关联。在妊娠18周和分娩后6周,对90名孕妇的血样进行肿瘤坏死因子-α(TNF-α)、转化生长因子-β(TGF-β)、干扰素-γ(IFN-γ)、白细胞介素-4(IL-4)、白细胞介素-6(IL-6)和白细胞介素-2(IL-2)检测。进行电话访谈并发放问卷以评估儿童的喘息和过敏性疾病情况。检测血清总IgE以及针对鸡蛋、牛奶和尘螨的特异性IgE。与分娩后水平相比,孕期母亲的IFN-γ、TNF-α和TGF-β水平显著下降。然而,IL-4水平未发生变化。报告有喘息症状的儿童,其母亲分娩前后的TNF-α和IFN-γ水平均降低。出现喘息症状的儿童,其母亲分娩前的个体IL-4水平高于分娩后。有哮喘和无哮喘儿童的母亲细胞因子水平无显著差异。在患有特应性疾病的儿童中,孕早期母亲的IFN-γ/IL-4比值相较于无特应性疾病的儿童有下降趋势,而分娩后6周母亲的IL-2水平升高。初产妇分娩前后的IL-4浓度高于经产妇。从孕早期开始,母亲细胞因子水平就开始向Th2免疫方向转变。妊娠早期较强的Th2免疫反应与儿童三岁时的喘息和特应性疾病以及初产有关。

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