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支气管哮喘患者外周血单个核细胞体外对鼻病毒的固有免疫反应受损。

Peripheral blood mononuclear cells from patients with bronchial asthma show impaired innate immune responses to rhinovirus in vitro.

机构信息

Department of Pediatrics, Jikei University School of Medicine, Tokyo, Japan.

出版信息

Int Arch Allergy Immunol. 2011;155 Suppl 1:27-33. doi: 10.1159/000327262. Epub 2011 Jun 1.

DOI:10.1159/000327262
PMID:21646792
Abstract

BACKGROUND

Asthmatic patients have a higher susceptibility to rhinovirus (RV) infection, and impaired IFN-β and IFN-λ production has been demonstrated in bronchial epithelial cells from asthmatic adults upon exposure to RV. However, the mechanisms underlying the increased susceptibility of asthmatic patients to RV infection remain poorly understood. The present study aimed to elucidate the characteristics of the immune responses of asthmatic patients' peripheral blood mononuclear cells (PBMCs) to RV exposure.

METHODS

PBMCs obtained from 3 different age groups (2-6 years: young-children group; 7-19 years: youth group; ≥20 years: adult group) of asthmatic patients and nonasthmatic control subjects were stimulated with RV-14 for 72 h. Healthy adults with a history of childhood asthma were also enrolled. The concentrations of IFN-α, IL-6, TNF-α, IL-10, and soluble Fas ligand (sFasL) in the culture supernatants were measured by ELISA.

RESULTS

When compared with age-matched control subjects, IFN-α production was significantly lower in the asthmatic youth group. IL-6, TNF-α, IL-10, and sFasL productions were significantly lower in both the asthmatic youth group and the adult group. Such impaired responses were not found in healthy adults with a history of childhood asthma. No significantly different responses were found between the asthmatics and controls in the young-children group, whereas young asthmatic children with persistent wheeze during a 2-year follow-up showed significantly lower IL-10 production than those without wheeze.

CONCLUSIONS

These results imply the involvement of impaired production of both IFN-α and inflammatory cytokines seen in asthmatic patients' PBMCs upon exposure to RV in the higher susceptibility of those patients to RV infection.

摘要

背景

哮喘患者对鼻病毒(RV)感染的易感性更高,并且已经在哮喘成人的支气管上皮细胞中证明,暴露于 RV 后 IFN-β 和 IFN-λ 的产生受损。然而,哮喘患者对 RV 感染易感性增加的机制仍知之甚少。本研究旨在阐明哮喘患者外周血单核细胞(PBMC)对 RV 暴露的免疫反应特征。

方法

从 3 个不同年龄组(2-6 岁:幼儿组;7-19 岁:青年组;≥20 岁:成年组)的哮喘患者和非哮喘对照者获得 PBMC,并将其用 RV-14 刺激 72 小时。还招募了有儿童期哮喘病史的健康成年人。通过 ELISA 测量培养上清液中 IFN-α、IL-6、TNF-α、IL-10 和可溶性 Fas 配体(sFasL)的浓度。

结果

与年龄匹配的对照组相比,哮喘青年组 IFN-α 的产生明显较低。哮喘青年组和成年组的 IL-6、TNF-α、IL-10 和 sFasL 的产生均明显较低。在有儿童期哮喘病史的健康成年人中,未发现这种受损的反应。在幼儿组中,哮喘患者和对照组之间没有发现明显不同的反应,而在为期 2 年的随访中持续喘息的年轻哮喘儿童的 IL-10 产生明显低于无喘息的儿童。

结论

这些结果表明,哮喘患者 PBMC 暴露于 RV 后 IFN-α 和炎症细胞因子产生受损可能参与了这些患者对 RV 感染的易感性增加。

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