Th17和 Treg 细胞及其相关细胞因子在结核性胸膜炎患者中的变化及意义

Changes of Th17 cells, Treg cells and Th17/Treg cell-associated cytokines in patients with tubercu-lous pleurisy and significance of the changes

目的检测健康人和结核性胸膜炎患者外周血Th17细胞和调节性T细胞（ Treg细胞）（ CD4＋CD25＋Foxp3＋）在CD4＋T细胞中的表达率以及IL-17、IL-23、IL-6、TGF-β血清水平和患者胸水中的IL-17、IL-23、IL-6、TGF-β水平，研究Th17细胞和调节性T细胞以及IL-17、IL-23、IL-6、TGF-β在结核性胸膜炎发病机制中的作用。方法使用流式细胞术检测患者以及健康对照人群外周血Th17细胞和调节性T细胞表达率，ELSIA方法定量检测血清以及胸水中IL-17、IL-23、IL-6、TGF-β水平，使用SPSS17．0统计学软件，分析健康人和结核性胸膜炎患者上述指标之间的差异以及各指标间的相关性。结果结核性胸膜炎患者外周血Th17细胞表达率（1．02％±0．20％）明显高于健康人外周血Th17细胞表达率（0．89％±0．13％，P＝0．002＜0．05）；结核性胸膜炎患者外周血调节性T细胞表达率（4．64％±0．77％）明显低于健康人外周血调节性T细胞表达率（5．10％±0．90％，P＝0．000＜0．05）；结核性胸膜炎患者Th17/Treg细胞的比率（0．25±0．07）明显高于健康人（0．17±0．05，P＝0．000＜0．05）；结核性胸膜炎患者外周血IL-17（17．49 ng/L±3．94 ng/L）和IL-23（90．42 ng/L±23．06 ng/L）水平和胸水中IL-17（26．13 ng/L±5．98 ng/L）和IL-23（122．26 ng/L±31．71 ng/L）水平显著高于对照组外周血IL-17（14．45 ng/L±3．81 ng/L）和IL-23（77．55 ng/L±20．26 ng/L）的水平，P值分别为0．022、0．039、0．000、0．000；患者胸水中IL-17和IL-23浓度也显著高于本人血液中的IL-17和IL-23浓度，P值为0．000和0．000；患者胸水中IL-6的浓度（5．31 ng/L±0．74 ng/L）显著高于患者血液中IL-6的浓度（4．54 ng/L±1．02 ng/L）和对照组血液中IL-6的浓度（4．26 ng/L±0．91 ng/L），P值分别为0．003和0．000，患者血液与对照组血液中IL-6的浓度没有显著差别（P＝0．274）；对照组外周血液TGF-β浓度（3．95 ng/L±0．79 ng/L）显著高于患者外周血液TGF-β浓度（3．32 ng/L±0．80 ng/L）及胸水中TGF-β浓度（3．12±0．77），P值分别为0．005和0．000，患者血液及胸水中TGF-β水平之间没有显著差别（P＝0．365）；结核性胸膜炎患者外周血Th17细胞的表达率与其Treg细胞在外周血的表达率呈显著负相关（r＝-0．684， P＝0．000＜0．05），结核性胸膜炎患者外周血Th17细胞的表达率与其外周血中的IL-17、IL-23、IL-6水平呈明显的正相关（r＝0．479，0．441，0．326，P＝0．013，0．015，0．017）；患者血液中TGF-β水平与Treg细胞在外周血的表达率呈明显的正相关（r＝0．297，P＝0．024），与Th17细胞表达率没有明显相关性（r＝0．091，P＝0．659）。结论 Th17和Treg细胞可能参与了结核性胸膜炎的免疫病理机制，有关细胞因子的变化可能参与了Th17和Treg细胞变化的调控以及炎症反应， Th17和Treg细胞以及有关细胞因子的变化可能是结核性胸膜炎重要的免疫病理机制。

Objective To investigate the significance of Th 17 cells, Treg cells and Th17/Treg cell-associated cytokines in the development of tuberculous pleurisy through detecting the expressions of Th 17 cells and Treg cells （CD4＋CD25＋Foxp3＋） in CD4＋T cells, analyzing concentrations of IL-17, IL-23, IL-6＆nbsp;and TGF-βin serum of patients with tuberculous pleurisy and healthy controls and measuring levels of IL -17, IL-23, IL-6 and TGF-βin hydrothorax of patients with tuberculous pleurisy .Methods Flow cytometry was used to detect expressions of Th 17 and Treg cells in peripheral blood of patients with tuberculous pleurisy and healthy controls.ELISA method was performed for quantitative detection of concentrations of IL -17, IL-23, IL-6 and TGF-βin serum and hydrothorax .Differences and correlations between the above measured data were analyzed by the statistical software SPSS 17.0.Results Compared with the healthy control group , the expressions of Th17 cells in peripheral blood of the patients were significantly increased （1.02%±0.20%vs.0.89%±0.13%, P=0.002〈0.05）, while the expressions of Treg cells were significantly decreased （4.64%±0.77%vs.5.10%±0.90%, P=0.000〈0.05）.Correspondingly, the ratio of Th17/Treg cells （0.25±0.07） in the patients were significantly higher than that in the healthy controls （0.17±0.05, P=0.000〈0.05）.Concentrations of IL-17, IL-23 and IL-6 in peripheral blood and in hydrothorax of the pa-tients were （17.49±3.94） ng/L, （90.42±23.06） ng/L, （4.54±1.02） ng/L and （26.13±5.98） ng/L, （122.26±31.71） ng/L, （5.31±0.74） ng/L respectively, which were remarkably higher than the levels of IL-17 （14.45±3.81） ng/L, IL-23 （77.55±20.26） ng/L and IL-6 （4.26±0.91） ng/L in control group. In tuberculous pleurisy group , concentrations of IL-17, IL-23 and IL-6 in hydrothorax were significantly higher than those in peripheral blood with P values of 0.000, 0.000 and 0.003.There was no difference be-tween IL-6 levels in peripheral blood from patients and IL-6 levels in peripheral blood from the healthy con-trols, P=0.274.In comparison with the control group , TGF-βlevels in peripheral blood and in hydrothorax of the patients were significantly decreased （3.95 ng/L±0.79 ng/L, 3.12 ng/L±0.77 ng/L vs.3.32 ng/L ±0.80 ng/L） .In tuberculous pleurisy patients , the expression of Th17 cells in peripheral blood was nega-tively correlated with Treg cells in peripheral blood （r=-0.684, P=0.000〈0.05）, but was positively relat-ed to the levels of IL-17, IL-23 and IL-6 （r=0.479, 0.441, 0.326, P=0.013, 0.015, 0.017）.TGF-βlevel had significantly positive correlations with Treg cells in the peripheral blood of the patients （r=0.297, P=0.024）, but no significant correlation with Th17 cells was found （r=0.091, P=0.659）.Conclusion Th17/Treg cell-associated cytokines might regulate the expressions of Th 17 and Treg cells and inflammatory reaction.Changes of Th17 cells, Treg cells and related cytokines might be important immunopathological mechanisms for tuberculous pleurisy .