肺功能正常吸烟者和慢性阻塞性肺疾病患者肺组织中白细胞介素17的表达及意义

Interleukin-17 expression and significance in normal lung function smokers and chronic obstructive pulmonary disease patients

目的 探讨白细胞介素17（IL-17）在肺功能正常吸烟者和慢性阻塞性肺疾病（COPD）患者肺部炎症反应发生机制中的作用.方法 将需手术治疗的周围型肺癌患者分为肺功能正常非吸烟组（NS组,10例）、肺功能正常吸烟组（S组,13例）和吸烟COPD稳定期组（COPD组,10例）.于手术切除标本选取距肺癌病灶5 cm以上的新鲜正常肺组织,酶联免疫吸附试验检测各组肺组织匀浆IL-17含量,HE和维多利亚蓝＋范吉逊染色检测各组平均肺泡面积、小气道病理总积分和肺腺泡肌型动脉（MA）管壁厚度,免疫组织化学方法检测IL-17＋及CD4＋、CD8＋T细胞在肺泡壁、小气道壁及MA管壁的表达,分析IL-17表达与CD4＋、CD8＋T细胞以及与肺实质病理改变和肺功能指标的相关关系.结果 NS组、S组和COPD组肺组织匀浆IL-17含量分别为6.1（3.7～12.4）、9.7（3.5～69.7）和22.7（7.0～114.4）pg/mg,S组和COPD组明显高于明显NS组（P〈0.05,P〈0.01）,COPD组明显高于S组（P〈0.05）;平均肺泡面积分别为（50 708±4 125）、（106 517±13 851）和（152 344±43 783）μm^2,小气道病理总积分分别为（49±10）、（101±34）和（163±36）分,MA管壁厚度分别为（119±11）、（139±25）和（172±28）μm,S组和COPD组均明显高于NS组（P〈0.05,P〈0.01）,COPD组明显高于S组（P〈0.05,P〈0.01）.IL-17主要表达于肺实质浸润的炎症细胞,S组和COPD组肺泡壁、小气道壁及MA管壁IL-17＋T细胞均明显多于NS组（均P〈0.01）,COPD组明显多于S组（均P〈0.05）.IL-17表达与平均肺泡面积（r=0.561）、小气道病理总积分（r=0.425）、MA管壁厚度（r=0.682）呈显著正相关（均P〈0.05）.肺泡壁、小气道壁和MA管壁中IL-17表达与CIM＋、CD8＋细胞呈显著正相关（P〈0.05,P〈0.01）.肺组织匀浆IL-17含量与第1秒用力呼气容积占预计值百分比呈显著负相关（r=-0.471,P〈0.01）.结论 IL-17在肺功能正常吸烟者和COPD患者肺组织中表达增高,与肺CIM＋、CD8＋T细胞及肺组织破坏、气道炎症、肺动脉重构和气流受限密切相关,提示IL-17在吸烟者和COPD患者肺部炎症反应发生机制中有促炎作用.

Objective To study the effect of interleukin 17 （IL-17） with mechanism of pulmonary inflammatory in smokers with normal lung junction and chronic obstructive pulmonary disease （ COPD） patients. Methods The peripheral lung cancer patients in need of a surgical therapy were divided into normal lung function and non-smoking group （NS group,n=10）, normal lung function and smoking group （S group,n=13） and smoking with stable COPD group （COPD group,n=10）. The fresh normal lung tissue was harvested from the surgical specimens with a margin of 5 cm away from resection foci. Then the lung tissue levels of IL-17 were detected with enzyme-linked immunosorbent assay. The average alveolar area, the total small airway pathology score and the pulmonary muscular artery （MA） wall thickness were measured by HE and Victoria blue-Van Gieson＇s stains. The IL-17＋cells and CD4＋, CD8＋lymphocytes in alveolar walls, small airways and lung MA were analyzed by immunohistochemistry. The investigators also explored the relationships between IL-17 level, pathological morphology of pulmonary parenchyma, small airway, pulmonary artery reconstruction and pulmonary functions. Results The IL-17 levels in lung tissue of NS, S and COPD groups were 6. 1 （3.7-12.4）, 9.7 （3.5-69.7） and 22.7 （7.0-114.4） pg/mg respectively. The S and COPD groups were significantly higher than the NS group （P 〈 0. 05, P 〈 0.01）. The S group was significantly higher than the NS group （P〈0. 05 ） . The average alveolar area were （50 708 ± 14 125）, （106 517 ± 13 851） and （152 344 ± 43 783 ）μm2 , the total small airway pathology score （49 ± 10） , （101 ±34） and （163 ±36）, and the MA wall thickness （119 ± 11）, （139 ± 25） and （172 ± 28） μm respectively. The S and COPD groups were significantly higher than the NS group （ P 〈 0. 05, P 〈 0. 01）. And the COPD group was significantly higher than the S group （P 〈 0. 05, P 〈 0. 01）. IL-17 was predominantly expressed in lung infiltration of inflammatory cells. IL-17 of alveolar walls, small airway wall and MA wall in the S and COPD groups were significantly higher than the NS group. And the COPD group was significantly higher than NS group （P 〈 0. 05）. IL-17 ＋ cells were positively correlated with the average alveolar area in pulmonary parenchyma （r = 0. 561, P 〈 0. 01）, the pulmonary artery wall thickness in M A （ r =0. 682, P 〈 0. 01） and the pathological score in small airways （r =0. 425, P 〈 0. 05）. IL-17 ＋ cells of pulmonary parenchyma, small airways and MA were positively correlated with CD4 ＋ and CD8 ＋ lymphocytes in lung （P 〈 0. 05, P 〈 0.01）. The levels of IL-17 in lung homogenate tissue showed a negative correlation with the FEV1 percentage of predicted value （ r = - 0. 471, P 〈 0. 01）. Conclusions IL-17 is up-regulated in lung tissues of normal lung function smokers and COPD patients. And it has a close correlation with CD4 ＋ and CD8 ＋ lymphocytes in lung, lung parenchyma destruction, pulmonary inflammation, pulmonary artery reconstruction and airflow limitation. All of these suggest that IL-17 plays an important pro-inflammatory role in COPD.