小剂量红霉素对稳定期慢性阻塞性肺疾病患者Th1/Tc1介导气道炎症和运动耐力的影响

目的 探讨长期应用小剂量红霉素对稳定期慢性阻塞性肺疾病（COPD）患者的Th1/Tc1介导气道炎症和运动耐力影响.方法 采用前瞻的、随机分组、自身前后对照的方法,将36例稳定期COPD患者（Ⅱ～Ⅳ级）分为红霉素组（加用红霉素375 mg/d,18例）和对照组（A组,18例）,红霉素组又分为一年组（B组,口服红霉素375 mg/d,12个月,9例）和半年组（C组,口服红霉素375 mg/d,6个月,9例）.分别测定第1天和第6、12个月诱导痰中白细胞总数和分类计数、肺功能和6 min步行距离（6 MWD）;采用酶联免疫吸附实验（ELISA）分别测定诱导痰和外周血中的γ-IFN、TNF-α、IL-8、IL-10、IL-12的浓度.结果 与A组相同时间点比较,B组第6、12个月和C组第6个月的痰白细胞总数、中性粒细胞数、中性粒细胞比例、外周血和诱导痰中的γ-IFN、TNF-α、IL-8浓度减少,深吸气量、6MWD、外周血和诱导痰中IL-10浓度增加（P＜0.05）;B组第6、12个月和C组第6个月的痰白细胞总数、中性粒细胞数、中性粒细胞比例、外周血和诱导痰中的γ-IFN、TNF-α、IL-8、IL-12浓度比治疗前降低,6MWD、外周血和诱导痰中的IL-10浓度上升;B组第12个月痰TNF-α、IL-8、IL-12和血IL-12浓度较治疗前降低（P＜0.05）.结论 长期小剂量红霉素应用可抑制稳定期COPD患者Th1/Tc1介导气道炎症,提高运动耐力,一定程度改善肺功能.与使用红霉素6个月相比,使用至12个月更能持续地抑制气道炎症.

Effect of low-dose erythromycin on the Th1/Tc1-mediated airway inflammation and exercise tolerance in patients with stable chronic obstructive pulmonary disease

Objective To study the effect of low-dose and long-term treatment with erythromycin on the Th1/Tc1-mediated airway inflammation and exercise tolerance in patients with stable chronic obstructive pulmonary disease （COPD）.Methods A total of thirty-six subjects with stable COPD（Ⅱ-Ⅳ）were recruited.They were divided into erythromycin group （n=18） and control group （Group A,n=18） with a prospective randomized,controlled method,the former were subdivided into Group B （n=9,oral erythromycin 375 mg daily for one year） and Group C （n=9,oral erythromycin 375 mg daily for half of a year）.All subjects were maintained their previous treatments.The total and differential leukocyte counts in induced sputum,pulmonary function,six-minute walking distance （6MWD） were measured at day 1,month 6 and month 12 respectively and the concentrations of interferon-gamma,interleukin-8,interleukin-10,interleukin-12,tumor necrosis factor-alpha in the supernatant of sputum and blood were detected by Enzyme-linked immunosorbent assay （ELISA）.Results Compared to those in Group A,total leukocyte counts,neutrophil counts,neutrophil proportion in sputum,the concentrations of γ-IFN,TNF-α,IL-8 in both sputum and blood were decreased while inspiratory capacity,6MWD,the concentrations of IL-10 in both sputum and blood were increased both at month 6 and month 12 in Group B and at month 6 in Group C （P0.05）.Total leukocyte counts,neutrophil counts,neutrophil proportion in sputum,the concentrations of γ-IFN,TNF-α,IL-8,IL-12 in both sputum and blood were reduced while 6MWD,the concentrations of IL-10 in both sputum and blood were upgraded both at month 6 and month 12 in Group B and at month 6 in Group C compared to those at day 1（P0.05）.The concentrations of TNF-α,IL-8,IL-12 in sputum and that of IL-12 in blood also were declined at month 12 in Group B compared to those at day 1（P0.05）.Conclusions The treatment of long-term and low-dose erythromycin can inhibit Th1/Tc1-mediated airway inflammation,increase the exercise tolerance and improve pulmonary function to a certain extent.The 12-month erythromycin can inhibit the airway inflammation better and more continuously than 6-month erythromycin.