Evaluation of Th1/Th2 ratio and cytokine production profile during acute exacerbation and convalescence in asthmatic children
Evaluation of Th1/Th2 ratio and cytokine production profile during acute exacerbation and convalescence in asthmatic children
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DOI：
10.1016/s1081-1206(10)63297-8
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发表时间：
2001-03-01
影响因子：
5.9
通讯作者：
Hsieh, KH
中科院分区：
文献类型：
--
作者：
Kuo, ML;Huang, JL;Hsieh, KH
背景：Th 2型细胞因子IL-4、IL-5在过敏性哮喘的发病中起重要作用。相反，Th 1型细胞因子，特别是干扰素（IFN）-γ，被认为对Th 2免疫应答细胞具有下调作用。因此，Th 1和Th 2细胞的失衡可能是与疾病严重程度相关的关键因素。目的：本研究的目的是观察哮喘儿童急性发作期和恢复期Th 1/Th 2比例和细胞因子产生谱的变化。方法：本研究包括12例哮喘患者。IFN-γ或IL-4产生细胞的百分比用细胞内蛋白检测的流式细胞术方法测定。从正常对照和两个阶段的患者获得的新鲜全血用布雷菲德菌素A、佛波醇肉豆蔻酸酯乙酸酯和离子霉素刺激4小时。将细胞固定，并用异硫氰酸荧光素或藻蓝蛋白缀合的抗体与抗CD 4组合对每种细胞因子进行细胞内染色。采用ELISA法检测经佛波酯和离子霉素激活的外周血单个核细胞（PBMC）培养上清中细胞因子的浓度。IL-4（+）细胞百分比从急性发作期的8.18 ± 4.77%显著下降到恢复期的4.18 ± 1.26%（P <0.020）。IFN-（+）细胞的百分比也从13.49 +/- 4.21%下降到9.03 +/- 5.42%（P <0.052）。两期患者Th 1/Th 2比值相似，均低于正常对照组。结论：哮喘急性发作后单个细胞水平上IFN-γ（+）和IL-4（+）细胞的减少可能是哮喘急性发作后恢复期的一个潜在机制。正常对照PBMC的高Th 1/Th 2比值和低IL-5产生支持哮喘患者的偏向性Th 2免疫应答的想法。
Background: Th2-type cytokines, such as IL-4 and IL-5, are generally believed to play an important role in the pathogenesis of allergic asthma. In contrast, Th1-type cytokine, especially interferon (IFN)-gamma, is thought to have a downregulatory effect on Th2 immune response cells. Thus, the imbalance of Th1 and Th2 cells may be a key factor in relation to disease severity.Objective: The aim of this study is to examine the changes in the Th1/Th2 ratios and cytokine production profiles of asthmatic children at acute attacks and convalescent stages.Methods: Twelve asthmatic patients were included in this study. The percentages of IFN-gamma- or IL-4-producing cells were determined with a flow-cytometric method of intracellular protein detection. Fresh whole blood obtained from normal controls and patients at two stages was stimulated with brefeldin A, phorbol myristate acetate, and ionomycin for 4 hours. Cells were fixed and stained intracellularly with fluorescein isothiocyanate- or phycoerythrin-conjugated antibody specific to each cytokine in combination with anti-CD4. ELISA assays were applied to measure cytokine concentrations of supernatant from peripheral blood mononuclear cells (PBMC) activated with phorbol myristate acetate and ionomycin for 24 hours.Results: Among CD4(+) cells. the percentage of IL-4(+) cells decreased significantly from 8.18 +/- 4.77% at acute attacks to 4.18 +/- 1.26% (P < .020) at convalescence. The percentage of IFN-(+) cells also decreased from 13.49 +/- 4.21% to 9.03 +/- 5.42% (P < .052). The Th1/Th2 ratios of patients at the two stages were similar, and both were lower than the normal controls. Significantly higher IL-5 and lower IFN- production were detected from activated PBMC of asthmatic patients than normal controls.Conclusions: The decrease of IFN-gamma (+) and IL-4(+) cells detected at the single-cell level may explain the potential mechanism of convalescence from acute asthma attacks. High Th1/Th2 ratio and low IL-5 production from the PBMC of normal controls support the idea of a biased Th2 immune response in asthmatic patients.