小剂量茶碱短期治疗对慢性阻塞性肺疾病患者痰中炎症细胞及炎症介质的影响

Effects of low-dose of oral thephylline on sputum inflammatory cells and inflammatory mediators in patients with COPD

目的 探讨小剂量茶碱短期治疗稳定期慢性阻塞性肺疾病（COPD）患者的抗炎疗效及其作用机制.方法 稳定期COPD患者34例,按随机数字表法分为茶碱组（18例）和安慰剂组（16例）,另12例健康非吸烟者为正常对照组.COPD患者在雾化吸入硫酸沙丁胺醇的基础上,早餐和晚睡前各口服缓释茶碱或安慰剂100 mg,疗程为12周.分别计数治疗前后各组痰液中性粒细胞百分比、巨噬细胞百分比,采用ELISA法测定痰上清液中IL-17、IL-8和TNF-α的含量.结果 （1）茶碱组治疗前痰液中性粒细胞比值[（89±4.14）％]高于治疗后[（83.4±6.98）％,P ＜0.05],巨噬细胞比值[（6.4±4.11）％]低于治疗后[（12.3±6.96）％,P ＜0.05].安慰剂组治疗前痰液中中性粒细胞和巨噬细胞比值与治疗后比较差异均无统计学意义（均P ＞0.05）.茶碱组与安慰剂组治疗前后中性粒细胞比值、巨噬细胞比值与正常对照组[（67.3±12.92）％、（30.8±13.47）％]比较差异有统计学意义（均P ＜0.01）.（2）茶碱组和安慰剂组治疗前、后痰上清中TNF-α、IL-8和IL-17水平均明显高于正常对照组;茶碱组治疗后痰上清TNF-α、IL-8和IL-17水平均较治疗前明显降低,亦较安慰剂组治疗后明显降低（P均＜0.05）;安慰剂组治疗后痰上清IL-17和IL-8水平高于治疗前（P＜0.01）,但TNF-α较治疗前差异无统计学意义（P＞0.05）.（3）痰上清中IL-17、TNF-α及IL-8与痰液中中性粒细胞数呈正相关（r =0.471、0.652、0.466,均P＜0.01）,与第一秒用力呼气容积占预计值百分比（FEV1％）呈负相关（r=-0.516、-0.652、-0.496,均P＜0.01）.结论 COPD患者痰中的中性粒细胞和炎症介质IL-17、TNF-α和IL-8水平升高,茶碱可能通过降低气道的炎症细胞和炎症介质等抗炎作用以治疗COPD.

Objective To investigate the anti-inflammatory effects of low-dose and sustained release oral theophylline on the chronic obstructive pulmonary disease （COPD） patients.Methods Thirty four patients with stable COPD were randomly divided into two groups：theophylline group （n =18） was treated with slow-release theophylline （100 mg,twice daily）,and placebo group （n =16） was given with placebo.Healthy non-smokers （n =12） were taken as control.The course of treatment was 12 weeks both of theophylline group and placebo group.The percentages of Neu/Leu and Mφ/Leu in sputum were detected before and after treatment and the concentrations of interleukin （IL）-17,IL-8,and tumor necrosis factor-α （TNF-α） were detected with enzyme linked immunosobent assay （ELISA）.Results （1） Compared to pretreatment with theophylline group,the Neu/Leu was increased [（89 ±4.14）% vs （83.4 ±6.98）%,P 〈0.05] and the Mφ/Leu was decreased [（6.4 ± 4.11） % vs （12.3 ± 6.96） %,P 〈 0.05] in the post-treated theophylline group.No significant changes in both Neu/Leu and Mφ/Leu were observed before and after placebo-treatment （P 〉 0.05）.（2） Compared to the control group,the concentrations of TNF-α,IL-8,and IL-17 in the sputum supernatant were significantly increased in both pretreatment and posttreatment with the theophylline or the placebo.Sputum TNF-α,IL-8,and IL-17 levels were significantly decreased in COPD patients who were given theophylline.Compared to pre-treatment with placebo group,the IL-8 and IL-17 levels were significantly increased in the post-treated placebo group （P 〈0.01）.There was no significant change in TNF- level between before and after treatment with the placebo.（3） The concentrations of IL-17,IL-8,and TNF-α in the sputum supernatant were positively correlated with the Neu/Leu counts （r =0.471,0.652,0.466,respectively,all P 〈0.01）,negatively correlated with the forced expiratory volume in one second （FEV1 %） （r =-0.516,-0.652,-0.496,respectively,all P 〈 0.01）.Conclusions Low-dose and sustained-release oral theophylline was efficient in improving airway inflammatory cells and inflammatory mediators,which plays an anti-inflammatory effect.