Feltis Bryce N, Reid David W, Ward Chris, Walters E Haydn
Respiratory Research Group, Tasmanian School of Medicine, University of Tasmania, Hobart, Tasmania, Australia.
Respirology. 2004 Nov;9(4):507-13. doi: 10.1111/j.1440-1843.2004.00624.x.
In a longitudinal ex vivo placebo-controlled study, asthmatics already treated with inhaled corticosteroid received supplemental long-acting beta-agonist (LABA) or increased doses of their inhaled corticosteroid (ICS). Previously reports have shown significant reductions in biopsy eosinophil numbers after treatment with LABA. Following these findings, eosinophil chemokines eotaxin and IL-5 in the BAL fluid at baseline and after 3 months of study medication have now been measured, and these data with that from new cross-sectional controls have also been compared. It is hypothesised that changes in airway eosinophils would be related to eosinophil cytokines.
BAL cytokines were measured by chemiluminescent enzyme-linked immunosorbent assay, while eosinophils were measured by immunohistochemistry or differential cell counting. For all measures, longitudinal data were compared to that from ICS-free asthmatics (n = 42) and non-asthmatic controls (n = 28).
BAL eotaxin in asthmatics was elevated above non-asthmatic levels regardless of ICS levels. BAL IL-5 was elevated in ICS-free asthmatics, but not in asthmatics on low-dose ICS treatment. Longitudinally, BAL eotaxin was unchanged after 3 months. Unexpectedly, IL-5 increased after 3 months of additional LABA treatment but was not further affected by increasing the dose of ICS. Airway eotaxin seemed to be constitutively raised in asthmatics, whereas, IL-5 levels were more steroid-responsive. No relationship was observed between eosinophils and eosinophilic cytokines in the BAL.
While the elevation of luminal IL-5 with LABA treatment cannot be accounted for, it may have contributed to luminal clearance of airway wall eosinophils. The lack of correlation between airways eosinophils and eosinophilic cytokines in the BAL is particularly important.
在一项纵向离体安慰剂对照研究中,已接受吸入性糖皮质激素治疗的哮喘患者接受补充长效β受体激动剂(LABA)或增加吸入性糖皮质激素(ICS)剂量的治疗。先前的报告显示,LABA治疗后活检嗜酸性粒细胞数量显著减少。基于这些发现,现已测量了基线时和研究药物治疗3个月后支气管肺泡灌洗液(BAL)中的嗜酸性粒细胞趋化因子嗜酸性粒细胞趋化蛋白(eotaxin)和白细胞介素-5(IL-5),并将这些数据与新的横断面对照数据进行了比较。假设气道嗜酸性粒细胞的变化与嗜酸性粒细胞细胞因子有关。
通过化学发光酶联免疫吸附测定法测量BAL细胞因子,而通过免疫组织化学或细胞分类计数法测量嗜酸性粒细胞。对于所有测量指标,将纵向数据与未使用ICS的哮喘患者(n = 42)和非哮喘对照者(n = 28)的数据进行比较。
无论ICS水平如何,哮喘患者的BAL嗜酸性粒细胞趋化蛋白水平均高于非哮喘患者。未使用ICS的哮喘患者BAL中的IL-5水平升高,但低剂量ICS治疗的哮喘患者中未升高。纵向来看,3个月后BAL嗜酸性粒细胞趋化蛋白水平未发生变化。出乎意料的是,额外LABA治疗3个月后IL-5增加,但增加ICS剂量对其没有进一步影响。哮喘患者气道中的嗜酸性粒细胞趋化蛋白似乎是持续升高的,而IL-5水平对类固醇更敏感。在BAL中未观察到嗜酸性粒细胞与嗜酸性粒细胞细胞因子之间的关系。
虽然无法解释LABA治疗导致管腔内IL-5升高的原因,但它可能有助于气道壁嗜酸性粒细胞的管腔清除。BAL中气道嗜酸性粒细胞与嗜酸性粒细胞细胞因子之间缺乏相关性尤为重要。