Th1／Th2细胞因子在暴露粉尘工人血清中的表达及在煤工尘肺监测中的价值

Expression of type 1 and type 2 cytokines from serum of coal miners and the evaluation insurveillance of coal workers＇ pneumoconiosis at earlier stage

目的探讨Thl／Th2细胞因子在暴露粉尘工人血清中的表达及其在煤工尘肺病（CWP）早期监测中的价值。方法在2013年1月至2015年12月采用单纯随机法，从某煤业集团职业病防治院选取CWP壹期患者90例及新确诊的19例CWP患者作为病例组，同时采用单纯随机法从某煤业集团下属9个煤矿的粉尘作业工人中，选取180例诊断为“尘肺观察对象”的工人作为观察组；以1：1的比例匹配年龄相近、胸片结果正常的暴露粉尘工人180名作为接尘组；以就业前体检结果正常且未从事过粉尘作业的工人161名为对照组；观察组、接尘组、对照组总称为非尘肺组。调查研究对象的基本信息及职业史，并检测血清中IL-1B、IL-8、IFN-γ IL-6、IL．10的表达水平，并以其表达水平对CWP进行筛检。绘制受试者工作特征（ROC）曲线并确定最佳截断值，并进行筛检实验的真实性及可靠性评价。结果对照组、接尘组、观察组及病例组的年龄分别为（27．4＋5．0）、（43．4±10．7）、（48．2±6．2）、（64．7±7.0）岁，病例组IL-1B、IL-8、IFN-γ、IL-6的表达水平M（1638．30、2099．49、815．18、140．32pg／m1）高于非尘肺组M（1445．57、1402．26、736．38、95．73pg／m1）（P〈O．05）；观察组IL-8（1503．99pg／m1）高于对照组（1295．67pg／m1）和接尘组（1376．94pg／m1），而IL-10（654．08pg／m1）低于对照组（596．64pg／m1）。IFN-γ／IL-6的比值介于5-8之间，病例组（5．87）低于非尘肺组（7．61）。接尘组不同工龄调查对象的IL．6、IL-8的差异有统计学意义（P〈0．05）。根据ROC曲线，IL-1β、IL-6、IL-8、IL-10和INF-1的界值分别为1582．65、116．53、1791．54、581．08和792．69pg／ml，曲线下面积分别为0．668、0．895、0．859、0．716、0．637。研究结果显示，IL-6和IL．8可用作筛检CWP的指标，曲线下面积分别为0．895和0．859、灵敏度分别为82．6％和78．0％、特异度分别为84．6％和84．8％、约登指数分别为0．674和0．628，符合率分别为84．3％和83．7％，Kappa值分别为0．55和0．52。结论CWP患者存在Thl／Th2平衡紊乱，IL-6和IL-8有望作为监测和有效预测早期肺组织损伤的效应标志物。

Objectives To explore the expression regulation of type 1 and type 2 （Thl and Th2） cytokines from serum of coal miners and the evaluation in surveillance of coal workers＇ pneumoconiosis, 630 coal miners were studied. Methods A total of 90 male patients diagnosed as coal wmkers＇ pneumoconiosis （CWP） in a institute for occupational health and 19 male workers newly diagnosed as CWP patients was chosen as CWP group with simple random sampling method from a coal mine group from January 2013 to December in 2015. 180 male coal miners with abnormal but not diagnosed as CWP were selected as CWPsuspected group with simple random sampling methods, meanwhile 180 male coal miners with normal chest X-ray photograph was as dust-exposed group by 1 ： 1 matched as age. And 161 healthy males accepted pre- employed examination were selected as control group, CWP suspected group, dust-exposed group and control group called as non-CWP group. According to screening test and diagnosis test, the basic information and occupational history of all subjects were collected, and cytokines including IL-113, IL-8, IFN-γ, IL-6 and IL-10 of serum were detected. Receiver operator characteristic （ROC） curve was used to determine the optimal cutoff value of each cytokine. Area under curve （AUC）, the validity and reliability were calculated and judged. Results The average age of control group, dust-exposed group, CWP suspected group and CWP group were （27.4±5.0）, （43.4±10.7）, （48.2±6.2）, （64.7±7.0） years old, respectively. The median level of IL-1β, IL-8, IFN-γ/and IL-6 in eases group （1 638.30, 2 099.49, 815.18,140.32 pg/ml） were higher than that of non-cases group （1 445.57, 1 402.26, 736.38, 95.73 pg/ml）（P〈0.05）. The level of IL-8（1 503.99 pg/ml） in CWP suspected group was higher than that of control group （ 1 295.67 pg/ml） and dust-exposed group （ 1 376.94 pg/ml）, but the level of IL- 10 （654.08 pg/ml） was lower than that of control group （596.64 pg/ml）. The ratio of IFN-γ/IL-6 ranged from 5 to 8, and the ratio in CWP group（5.87）was lower than that of non- CWP group （7.61）. The IL-6 and IL-8 among the subjects of dust-exposed group in terms of the age distribution of among had reached statistical significance. According to ROC, the cutoff value of IL-1β, IL-6, IL-8, IL-10 and INF-＇y reached 1 582.65, 116.53, 1 791.54, 581.08 and 792.69 pg/ml, respectively. The AUC was 0.668, 0.895, 0.859, 0.716 and 0.637, respectively. It was found that IL-6 and IL-8 could be used as biomarkers in detecting CWP, the sensitivity and specificity was 82.6% and 84.6%, 78.0% and 84.8%, respectively; Youden＇s index was 0.674 and 0.628 and the consistency rate was 84.3% and 83.7%, while Kappa value was 0.55 and 0.52. Conclusion There was Type 1 and type 2 cytokine dysregulation in CWP patients. IL-6 and IL-8 can be used as effective biomarkers to forecast lung injury before X-ray changes.