IL-5单抗在轻度哮喘中可改变鼻病毒诱导的巨噬细胞、B细胞及中性粒细胞反应(MATERIAL研究): 一项安慰剂对照、双
2018/11/13
IL-5单抗在轻度哮喘中可改变鼻病毒诱导的巨噬细胞、B细胞及中性粒细胞反应(MATERIAL研究): 一项安慰剂对照、双盲研究
摘要基本原理：嗜酸性粒细胞介导了嗜酸性粒细胞哮喘的稳定和加重的病理生理过程，因此治疗的重点在于减少嗜酸性粒细胞的数量。美泊利单抗是一种能中和白细胞介素(IL)-5并有效降低嗜酸性粒细胞的人源化单克隆抗体，在严重嗜酸性粒细胞性哮喘中被证实有效，但在轻度哮喘中无效。
目的：研究在轻度哮喘中美泊利单抗对病毒诱导免疫应答的影响。
方法：在安慰剂对照双盲试验中，未使用激素治疗且嗜酸性粒细胞数量随机的轻度哮喘患者接受750毫克美泊利单抗静脉注射治疗，两周后患者感染鼻病毒(RV)16。评估美泊利单抗治疗和RV16感染前后患者的FEV1、FVC、FeNO、症状评分(ACQ)、嗜酸性粒细胞计数以及血液、支气管肺泡灌洗液（BALF）和痰液中病毒载量(PCR)、体液(luminex、ELISA)和细胞(流式细胞术)中的免疫参数。
步骤和主要结果：美泊利单抗降低了基线血嗜酸性粒细胞数量及其其活化，减少了痰中嗜酸性粒细胞的数量，并增加了循环血中NK细胞的数目。无论是在基线水平还是在RV16感染后，美泊利单抗对FEV1、FVC和FeNO均无影响。在感染RV16后，美泊利单抗并不能阻止嗜酸性粒细胞活化，提高局部B淋巴细胞和巨噬细胞数目并降低中性粒细胞的数目及其活性。美泊利单抗还能增加BALF中的分泌型IgA并降低类胰蛋白酶的数量。最后，美泊利单抗可显著影响BALF中RV16诱导的MIP-3a、VEGF-A和IL-1RA的产生。
结论：美泊利单抗未能阻止轻度哮喘患者剩余嗜酸性粒细胞的活化，并改变了轻度哮喘中RV16诱导的免疫反应。虽然后一种影响可能是嗜酸性粒细胞数量减少造成的，但我们不能排除嗜碱性粒细胞的作用。
（复旦大学附属中山医院呼吸与危重症医学科 魏婷婷 摘译 毕晶 审校）
（Am J Respir Crit Care Med. 2018 Sep 7.）
（Am J Respir Crit Care Med. 2018 Sep 7.）
Anti-IL5 in Mild Asthma Alters Rhinovirus-Induced Macrophage, B Cell and Neutrophil Responses (MATERIAL): A Placebo-Controlled, Double-Blind Study.
Sabogal Piñeros YS et al. Am J Respir Crit Care Med. 2018 Sep 7.
Abstract
RATIONALE:Eosinophils drive pathophysiology in stable and exacerbating eosinophilic asthma and therefore treatment is focused on the reduction of eosinophil numbers. Mepolizumab, a humanized monoclonal antibody that neutralizes interleukin (IL)-5 and efficiently attenuates eosinophils, proved clinically effective in severe eosinophilic asthma but not in mild asthma.
OBJECTIVES:Study the effect of Mepolizumab on virus-induced immune responses in mild asthma.
METHODS:Mild asthma patients, steroid-naïve and randomized for eosinophil numbers, received 750 mg Mepolizumab iv in a placebo-controlled double-blind trial, 2 weeks after which patients were challenged with rhinovirus(RV)16. FEV1, FVC, FeNO, symptom scores (ACQ), viral load (PCR), eosinophil numbers, humoral (luminex, ELISA) and cellular (flow cytometry) immune parameters in blood, BALF and sputum, before and after Mepolizumab and RV16, were assessed.
MEASUREMENTS AND MAIN RESULTS:Mepolizumab attenuated baseline blood eosinophils and their activation, attenuated trend wise sputum eosinophils and enhanced circulating NK cells. Mepolizumab did not affect FEV1, FVC and FeNO, neither at baseline nor after RV16. Upon RV16 challenge Mepolizumab did not prevent eosinophil activation, enhanced local B-lymphocytes and macrophages and reduced neutrophils and their activation. Mepolizumab also enhanced sIgA and reduced tryptase in BALF. Finally, Mepolizumab affected particularly RV16-induced MIP-3a, VEGF-A and IL-1RA production in BALF.
CONCLUSION:Mepolizumab failed to prevent activation of remaining eosinophils and changed RV16-induced immune responses in mild asthma. Although these latter effects likely are due to attenuated eosinophil numbers, we cannot exclude a role for basophils.
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长期口服糖皮质激素(OCS)治疗成人重症哮喘的作用及其相关副作用
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规律使用口服糖皮质激素治疗的哮喘患者的医疗资源利用与成本 – 一项瑞典观察性队列研究（PACEHR）
