结核性与肿瘤性胸腔积液中多种细胞因子的表达及其对鉴别诊断的作用

Expressions and diagnostic value of the cytokines in tuberculous and malignant pleural effusion

目的探讨液态芯片技术检测结核性和肿瘤性胸腔积液中细胞因子的表达及其在结核性胸腔积液中的诊断价值。方法共纳入结核性胸腔积液患者53例，肿瘤性胸腔积液患者28例。应用液态芯片技术检测患者胸腔积液中的促炎性细胞因子IL-1β、IL-6、IL-12、γ干扰素（TNF-γ）和TNF-α，抗炎性细胞因子IL-1受体拮抗剂（IL-1ra）、IL-4和IL-10，趋化因子γ干扰素诱导蛋白（IP）-10、巨噬细胞炎症蛋白（macrophage inflammatory protein，MIP）-1α、MIP-1β和单核细胞趋化蛋白（MCP）-1等。统计学处理采用Mann-Whitney检验。结果结核性胸腔积液组TNF-γ（1 064.33 pg/mL比294.78 pg/mL, U＝130.5, P〈0.01）和IP-10（39 179.86 pg/mL比9 411.73 pg/mL, U＝98.0, P〈0.01）的表达水平明显高于肿瘤性胸腔积液组，IL-10的表达水平则显著低于肿瘤性胸腔积液组（11.52 pg/mL比17.77 pg/mL, U＝565.5, P＝0.017）。进一步分析发现，IFN-γ/IL-10（100.07比16.19, U＝116.0, P〈0.01）和IP-10/IL-10（2 930.91比591.18, U＝75.0, P〈0.01）在结核性胸腔积液中显著高于在肿瘤性胸腔积液中。TNF-γ、IP-10、IFN-γ/IL-10和IP-10/IL-10的受试者工作特征曲线下面积（AUC）分别为0.91、0.93、0.92和0.95，最佳阈值分别为483.5 pg/mL、20 340 pg/mL、41.11和1 614。TNF-γ≥483.5 pg/mL、IP-10≥20 340 pg/mL、IFN-γ/IL-10≥41.11和IP-10/IL-10≥1 614诊断结核性胸腔积液的敏感度分别为0.830（95%CI：0.702～0.920）、0.906（95%CI：0.793～0.969）、0.811（95%CI：0.680～0.906）和0.868（95%CI：0.747～0.945）；特异度分别为0.962（95%CI：0.804～0.999）、0.923（95%CI：0.749～0.991）、0.962（95%CI：0.80.4～0.999）和0.923（95%CI：0.749～0.991）。结论利用液态芯片技术检测胸腔积液中TNF-γ、IP-10和IL-10表达水平有助于诊断结核性胸腔积液，具有操作方便、快速、创伤小的优点且敏感度和特异度较高。

Objective To analyze the levels of pro-inflammatory cytokines, anti-inflammatory cytokines and chemokines in tuberculous and malignant pleural effusion using Luminex method, and to evaluate their diagnostic value in tuberculous pleural effusion. Methods Fifty-three patients with tuberculous pleural effusion and 28 patient with malignant pleural effusion were included in this study. Luminex method was applied to detect the levels of pro-inflammatory cytokines （interleukin IL-1β、IL-6、IL-12、 interferon [IFN]-γand tumor necrosis factor [TNF]-a）, anti-inflammatory cytokines （IL-1 receptor antagonist [IL-lra], IL-4, and IL-10）, and chemokines （IFN-7 inducible protein [IP]-10, macrophage inflammatory protein [MIP]-la, MIP-1β, and monocyte chemo-attractant protein [MCP]-I） in all patients. The levels of cytokines were compared using Mann-Whitney test. Results The levels ofIFN-7 （1 064. 33 pg/mL vs 294. 78 pg/mL, U= 130. 5, P〈0. 01） and IPl0 （39 179. 86 pg/mL vs 9 411.73 pg/mL, U=98.0, P〈0.01） in tuberculous pleural effusion were significantly higher than those in malignant pleura[ effusion, while the IL-10 level （11.52 pg/mL vs 17. 77 pg/mL, U= 565. 5, P〈 0. 017） was significantly lower than that in malignant pleural effusion. Furthermore, IFN-7/IL-10 （100.07 vs 16. 19, U=116.0, P〈0.01） and IP-10/IL-10 （2 930.91 vs 591.18, U=75.0, P〈0.01） in tuberculous pleural effusion were significantly higher than those in malignant pleural effusion. Area under the curve of receiver operating characteristic of IFN-7, IP-10, IFN-y/IL-10, and IP-10/IL 10 were 0.91, 0.93, 0.92 and 0.95, respectively, with the cut-off value of 483.5 pg/mL, 20 340 pg/mL, 41.11 and 1 614. For the diagnosis of tuberculous pleural effusion, the sensitivities and specific[ties of IFN-Y〉483.5 pg/mL, IP- 10-20 340 pg/mL, IFN-7/IL-10%41.11, and IP-10/IL-10%I 614 were 0. 830（95%CI：0. 702--0. 920） and 0. 962（95%CI： 0. 804--0. 999）, 0. 906（95%CI： 0. 793--0. 969） and 0. 923（95%CI： 0. 749--0. 991）, 0.811 （95%CI： 0.680--0.906） and 0. 923（95%CI： 0. 749--0. 991）, 0. 868（95%CI： 0. 747--0. 945） and 0. 923 （95%CI： 0. 749--0. 991）, respectively. Conclusions The expression levels of IFN-Y, IP 10 and IL 10 in pleural effusion detected by Luminex method is convenient, rapid, noninvasive, sensitive and specific, which is helpful for the diagnosis of tuberculous pleural effusion.