慢性阻塞性肺疾病患者炎症细胞因子与肺通气功能的相关研究

目的　探讨慢性阻塞性肺疾病 (COPD)患者肺通气功能改变与炎症因子变化之间的关系。方法　稳定期COPD和慢性支气管炎 (简称慢支 )患者各 8例 ,,另有 8名健康者作为对照 ,进行肺功能检查 ,并经支气管肺泡灌洗获取肺泡巨噬细胞进行培养 ,采用酶联免疫吸附 (ELISA)方法测定大肠杆菌内毒素 (LPS)刺激后上清液中白细胞介素 8(IL 8)、IL 1β、IL 6和肿瘤坏死因子α(TNF α)的浓度 ,细胞因子之间相关性采用Pearson相关阵分析 ,肺功能值与细胞因子相关性采用多元后退回归法分析。结果　 (1)肺泡巨噬细胞释放IL 8:加入LPS后COPD组为 [(43± 2 7) μg/L和 (5 7± 41) μg/L],与正常对照组 [(13± 10 ) μg/L和 (2 0± 13 ) μg/L) ]比较差异有显著性 (P <0 .0 5 ) ;与慢支组 [(2 9± 2 1)μg/L和 (3 2± 2 3 ) μg/L]比较差异有显著性 (P >0 .0 5 )。 (2 )加入LPS前、后 ,COPD组、慢支组和正常对照组肺泡巨噬细胞释放IL 1β分别为 [(5 0± 41)ng/L、(94± 5 9)ng/L、(3 7± 3 2 )ng/L、(2 2 5± 10 8)ng/L、(15 3± 175 )ng/L、(70± 3 7)ng/L],与IL 8的释放呈正相关 (P <0 .0 5 ) ;三组肺泡巨噬细胞在LPS刺激后释放TNF α分别为 [(12 3 8± 679)ng/L、(3 0 88± 2 879)ng/L、(13 3 2± 1846)ng/L],与IL 1β呈正相

The study of inflammatory mediators and pulmonary ventilatory capacity in patients with chronic obstructive pulmonary disease

OBJECTIVE: To study the correlation between the inflammatory mediators released by alveolar macrophages and the pulmonary ventilatory capacity in patients with chronic obstructive pulmonary disease (COPD). METHODS: Alveolar macrophages were collected by fiberoptic bronchoscopy from 8 patients with chronic bronchitis, 8 with COPD with a forced expiratory volume in one second (FEV(1)) < or = 70%, and 8 healthy nonsmokers. All patients were in the stable stage. The macrophages were cultured and stimulated with lipopolysaccharide (LPS, 10 microg/ml). IL-8, IL-1 beta, TNF-alpha and IL-6 in the supernatants were measured by ELISA. Pulmonary functions were tested in all three groups. The correlation between different cytokines was tested with Pearson's relevant analysis, and the correlation between lung functions and cytokines was tested with multiple reverse regression analysis. RESULTS: (1) The concentrations of IL-8 released from macrophages in the COPD group were (43 +/- 27) microg/L and (57 +/- 41) microg/L (with LPS), higher than those from healthy controls [(13 +/- 10) microg/L and (20 +/- 13) microg/L] (P < 0.05), but not different from those in patients with chronic bronchitis [(29 +/- 21) microg/L and (32 +/- 23) microg/L] (P > 0.05). (2) The concentrations of IL-1 beta released from macrophages in the COPD group, the chronic bronchitis group and the control group were [(50 +/- 41) ng/L, (94 +/- 59) ng/L, (37 +/- 32) ng/L] before LPS, and [(225 +/- 108) ng/L, (153 +/- 175) ng/L, (70 +/- 37) ng/L] after LPS stimulation, which were positively correlated with the concentrations of IL-8 (P < 0.05). The concentrations of TNF-alpha released from macrophages in three groups were [(1,238 +/- 679) ng/L, (3,088 +/- 2,879) ng/L and (1,332 +/- 1,846)ng/L], which were positively correlated with the concentrations of IL-1 beta (P < 0.05). The concentrations of IL-6 released from macrophages in the three groups were [(7,959 +/- 8,458) ng/L, (5,317 +/- 10,112) ng/L and (6,480 +/- 4,982) ng/L, which were positively correlated with the concentrations of IL-8 (P < 0.05). (3) The values of FEV(1)/FVC, V(max50) and V(max25) measured in the COPD group were [(65.1 +/- 5.3)%, (43 +/- 8)% and (37 +/- 11)%, respectively, which were negatively correlated with the concentrations of IL-8 (P < 0.05), but negatively correlated with the concentrations of IL-1 beta only in the presence of LPS (P < 0.05). CONCLUSION: IL-8 released by alveolar macrophages plays an important role in the process from chronic cough to chronic airflow obstruction. TNF-alpha, IL-1 beta and IL-6 released by alveolar macrophages are also involved in the airway inflammation in COPD.