Menzies-Gow A N, Flood-Page P T, Robinson D S, Kay A B
Leukocyte Biology Section, National Heart & Lung Institute, Imperial College, London, UK.
Clin Exp Allergy. 2007 Jul;37(7):1023-32. doi: 10.1111/j.1365-2222.2007.02735.x.
Asthma is characterized by increases in mature eosinophils and their progenitors within the bronchus and bone marrow. IL-5 plays a key role in eosinophil development in the bone marrow and at the site of allergic inflammation. We therefore studied the effects of nebulized IL-5 on eosinophils, their progenitors and in situ haemopoiesis within the airway and bone marrow.
Nine atopic asthmatics and 10 non-atopic non-asthmatic control volunteers inhaled 10 microg of IL-5 or placebo via a nebulizer in a double-blind, randomized, cross-over study. Bronchoscopy, bone marrow aspiration and peripheral blood sampling were performed 24 h after nebulization. Four weeks later, volunteers inhaled the alternative solution and underwent a repeat bronchoscopy and bone marrow aspiration.
Inhalation of IL-5 significantly decreased CD34(+)/IL-5Ralpha mRNA(+) cells within the bronchial mucosa and the percentage of CD34(+) cells that were CCR3(+) within the bone marrow of atopic asthmatic, but not control, volunteers. Inhalation of IL-5 also induced a significant increase in bronchial mucosal eosinophils in the non-atopic non-asthmatic control volunteers, but not in the asthmatics. IL-5 had no effect on spirometry or airways hyper-reactivity in either group.
Inhaled IL-5 modulated eosinophil progenitor numbers in both the airways and bone marrow of asthmatics and induced local eosinophilia in non-asthmatics.
哮喘的特征是支气管和骨髓中成熟嗜酸性粒细胞及其祖细胞增多。白细胞介素-5(IL-5)在骨髓嗜酸性粒细胞发育以及过敏性炎症部位发挥关键作用。因此,我们研究了雾化吸入IL-5对嗜酸性粒细胞、其祖细胞以及气道和骨髓原位造血的影响。
在一项双盲、随机、交叉研究中,9名特应性哮喘患者和10名非特应性非哮喘对照志愿者通过雾化器吸入10微克IL-5或安慰剂。雾化24小时后进行支气管镜检查、骨髓穿刺和外周血采样。四周后,志愿者吸入另一种溶液,并再次进行支气管镜检查和骨髓穿刺。
吸入IL-5显著降低了特应性哮喘志愿者支气管黏膜内CD34(+)/IL-5Ralpha mRNA(+)细胞以及骨髓中CCR3(+)的CD34(+)细胞百分比,但对照志愿者未出现此现象。吸入IL-5还使非特应性非哮喘对照志愿者的支气管黏膜嗜酸性粒细胞显著增加,但哮喘患者未出现此现象。IL-5对两组的肺功能或气道高反应性均无影响。
吸入IL-5可调节哮喘患者气道和骨髓中的嗜酸性粒细胞祖细胞数量,并在非哮喘患者中诱导局部嗜酸性粒细胞增多。