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变应原诱导的气道嗜酸性粒细胞细胞因子产生及气道炎症的动力学

Kinetics of allergen-induced airway eosinophilic cytokine production and airway inflammation.

作者信息

Gauvreau G M, Watson R M, O'Byrne P M

机构信息

Department of Medicine, McMaster University, Hamilton, Ontario, Canada.

出版信息

Am J Respir Crit Care Med. 1999 Aug;160(2):640-7. doi: 10.1164/ajrccm.160.2.9809130.

DOI:10.1164/ajrccm.160.2.9809130
PMID:10430741
Abstract

Airway eosinophilia is the hallmark of asthma exacerbation. Coordination of cytokines such as interleukin (IL)-5, eotaxin and regulated on activation, normal T-cell expressed and secreted (RANTES) seem to be necessary for eosinophil extravasation including adhesion, chemotaxis, and activation. The purpose of this study was to characterize both the kinetics of allergen-induced inflammatory cell recruitment to the airways and cytokines selective for eosinophil chemotaxis, activation, or resolution. Eight atopic asthmatic individuals demonstrating a dual response to inhaled allergen completed a diluent-controlled crossover study. The subjects showed significant allergen-induced early and late airway asthmatic responses (p < 0.001), and an increase in the number of sputum eosinophils and metachromatic cells (p < 0.05). The number of eosinophils immunopositive for IL-5, eotaxin, and RANTES increased 7 h after allergen inhalation (p < 0.05), coincident with the peak number of activated eosinophils. Sputum cells immunopositive for IL-10 decreased significantly following allergen challenge (p = 0. 04), and correlated negatively with sputum eosinophils (r = -0.34, p = 0.02). This study shows that allergen-induced increases in sputum eosinophils are associated with the presence of cytokines specific for the activation and chemotaxis of eosinophils, and suggests that cooperation of eosinophilic cytokines may be important for the accumulation and regulation of activated eosinophils at the site of allergic inflammation.

摘要

气道嗜酸性粒细胞增多是哮喘加重的标志。白细胞介素(IL)-5、嗜酸性粒细胞趋化因子以及正常T细胞激活时表达和分泌的调节因子(RANTES)等细胞因子的协同作用,似乎是嗜酸性粒细胞渗出(包括黏附、趋化和激活)所必需的。本研究的目的是描述变应原诱导的炎症细胞募集至气道的动力学,以及对嗜酸性粒细胞趋化、激活或消退具有选择性的细胞因子。8名对吸入变应原表现出双重反应的特应性哮喘患者完成了一项稀释剂对照交叉研究。受试者表现出显著的变应原诱导的早期和晚期气道哮喘反应(p < 0.001),以及痰嗜酸性粒细胞和异染细胞数量增加(p < 0.05)。吸入变应原7小时后,IL-5、嗜酸性粒细胞趋化因子和RANTES免疫阳性的嗜酸性粒细胞数量增加(p < 0.05),与活化嗜酸性粒细胞的峰值数量一致。变应原激发后,IL-10免疫阳性的痰细胞显著减少(p = 0.04),且与痰嗜酸性粒细胞呈负相关(r = -0.34,p = 0.02)。本研究表明,变应原诱导的痰嗜酸性粒细胞增多与嗜酸性粒细胞激活和趋化特异性细胞因子的存在有关,并提示嗜酸性粒细胞细胞因子的协同作用可能对变应性炎症部位活化嗜酸性粒细胞的聚集和调节很重要。

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