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环孢素A对变应原诱导的迟发性哮喘反应的减轻作用与对支气管嗜酸性粒细胞、白细胞介素-5、粒细胞巨噬细胞集落刺激因子及嗜酸性粒细胞趋化因子的抑制作用相关。

Attenuation of the allergen-induced late asthmatic reaction by cyclosporin A is associated with inhibition of bronchial eosinophils, interleukin-5, granulocyte macrophage colony-stimulating factor, and eotaxin.

作者信息

Khan L N, Kon O M, Macfarlane A J, Meng Q, Ying S, Barnes N C, Kay A B

机构信息

Allergy and Clinical Immunology, Imperial College School of Medicine, National Heart and Lung Institute, London, United Kingdom.

出版信息

Am J Respir Crit Care Med. 2000 Oct;162(4 Pt 1):1377-82. doi: 10.1164/ajrccm.162.4.9911117.

Abstract

The allergen-induced late asthmatic reaction (LAR) is associated with increases in bronchial eosinophils and basophils as well as upregulation of several eosinophil active cytokines and C-C chemokines. Cyclosporin A (CsA) was previously shown to inhibit the LAR, but not the early asthmatic reaction (EAR), and this was associated with a decrease in blood eosinophils. For these reasons, we determined whether CsA inhibited the allergen-induced increases in bronchial eosinophils, basophils, eotaxin, interleukin-5 (IL-5), and granulocyte macrophage colony-stimulating factor (GM-CSF). Subjects with a demonstrable LAR underwent bronchoscopy with biopsy and bronchoalveolar lavage (BAL) at baseline and then were randomly allocated to receive either CsA (n = 13) or placebo (n = 11) before challenge. A second bronchoscopy was performed 24 h later. The LAR, but not the EAR, was significantly attenuated in the CsA group compared with placebo (p < 0.05). CsA significantly inhibited the allergen-induced increases in IL-5 (p = 0.02) and GM-CSF (p = 0. 0028) in mRNA+ cells in BAL, and in a mAB against human activated eosinophils (EG2+) (p = 0.0227). We conclude that inhibition of the LAR by CsA may be related to its inhibitory effects on eosinophil-associated cytokines and chemokines. The beneficial effect of CsA in asthma may also be the result of inhibition of eosinophil accumulation.

摘要

变应原诱导的迟发性哮喘反应(LAR)与支气管嗜酸性粒细胞和嗜碱性粒细胞增多以及多种嗜酸性粒细胞活性细胞因子和C-C趋化因子的上调有关。环孢素A(CsA)先前已被证明可抑制LAR,但不能抑制早发性哮喘反应(EAR),这与血液嗜酸性粒细胞减少有关。基于这些原因,我们确定CsA是否能抑制变应原诱导的支气管嗜酸性粒细胞、嗜碱性粒细胞、嗜酸性粒细胞趋化因子、白细胞介素-5(IL-5)和粒细胞巨噬细胞集落刺激因子(GM-CSF)的增加。有明显LAR的受试者在基线时接受支气管镜检查及活检和支气管肺泡灌洗(BAL),然后在激发前随机分配接受CsA(n = 13)或安慰剂(n = 11)。24小时后进行第二次支气管镜检查。与安慰剂组相比,CsA组的LAR明显减轻,但EAR无明显变化(p < 0.05)。CsA显著抑制变应原诱导的BAL中mRNA+细胞中IL-5(p = 0.02)和GM-CSF(p = 0.0028)以及抗人活化嗜酸性粒细胞单克隆抗体(EG2+)(p = 0.0227)的增加。我们得出结论,CsA对LAR的抑制作用可能与其对嗜酸性粒细胞相关细胞因子和趋化因子的抑制作用有关。CsA在哮喘中的有益作用也可能是抑制嗜酸性粒细胞积聚的结果。

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