白细胞介素-32，在慢性阻塞性肺疾病吸烟者中不会被沙美特罗/丙酸氟替卡松降低。

Interleukin-32, not reduced by salmeterol/fluticasone propionate in smokers with chronic obstructive pulmonary disease.

作者信息

Du Yipeng, Wang Wei, Yang Wei, He Bei

机构信息

Department of Respiratory Medicine, Peking University Third Hospital, Beijing 100191, China.

Department of Respiratory Medicine, Peking University Third Hospital, Beijing 100191, China. Email:

出版信息

Chin Med J (Engl). 2014;127(9):1613-8.

PMID:24791863

Abstract

BACKGROUND

The interleukin (IL)-32/tumor necrosis factor (TNF) a pathway is supposed to play a key role in the amplification of the immune response in chronic obstructive pulmonary disease (COPD) inflammation. Inhaled corticosteroids (ICS) in combination with long-acting β2-agonists (LABA) have shown airway anti-inflammatory effects in recent studies, but the mechanism is still uncertain.

METHODS

Patients were treated in a randomized, open-labeled, parallel group clinical trial with either a combination of salmeterol xinafoate/fluticasone propionate (SF; Seretide, GlaxoSmithKline) Diskus (50/500 µg twice daily) or ipratropium bromide/salbutamol (IS; Combivent, Boehringer Ingelheim) MDI (42 µg/240 µg quartic daily) for 12 weeks. At the start and the end of treatment, induced sputum was collected and the concentration of IL-32 and TNF-α, the number of neutrophils and eosinophils were measured.

RESULTS

Following 12 weeks of treatment, a statistically significant fall from baseline in the concentration of TNF-α in sputum (P = 0.004) was seen after treatment with SF but not with IS. However, neither treatment had significant effects on the concentration of IL-32 in sputum. There was a decrease from baseline in the number of sputum neutrophils with SF that approached statistical significance (P = 0.028) but not with IS, while the number of sputum eosinophils did not change significantly from baseline in either treatment group. There was a statistically significant decline from baseline in the quality of life as assessed by the St George's respiratory questionnaire in both the SF (P = 0.004) and IS (P = 0.030) treatment groups, but no evidence of improvement in lung function was observed in either group.

CONCLUSION

The sputum TNF-α and neutrophils, but not IL-32 and macrophages, could be reduced by ICS/LABA treatment, suggesting that IL-32 could be involved in the corticosteroid resistance of COPD inflammation.

摘要

背景

白细胞介素（IL）-32/肿瘤坏死因子（TNF）α通路被认为在慢性阻塞性肺疾病（COPD）炎症中免疫反应的放大过程中起关键作用。近期研究表明，吸入性糖皮质激素（ICS）联合长效β2受体激动剂（LABA）具有气道抗炎作用，但其机制仍不明确。

方法

患者在一项随机、开放标签、平行组临床试验中接受治疗，分别使用沙美特罗昔萘酸盐/丙酸氟替卡松（SF；舒利迭，葛兰素史克）准纳器（50/500μg，每日两次）或异丙托溴铵/沙丁胺醇（IS；可必特，勃林格殷格翰）定量吸入器（42μg/240μg，每日四次），为期12周。在治疗开始和结束时，收集诱导痰，检测IL-32和TNF-α的浓度、中性粒细胞和嗜酸性粒细胞的数量。

结果

治疗12周后，SF治疗后痰中TNF-α浓度较基线有统计学意义的下降（P = 0.004），而IS治疗后未出现下降。然而，两种治疗对痰中IL-32浓度均无显著影响。SF治疗后痰中中性粒细胞数量较基线有所减少，接近统计学意义（P = 0.028），而IS治疗后未出现此情况，且两个治疗组痰中嗜酸性粒细胞数量较基线均无显著变化。圣乔治呼吸问卷评估显示，SF（P = 0.004）和IS（P = 0.030）治疗组的生活质量较基线均有统计学意义的下降，但两组均未观察到肺功能改善的证据。