Th1/Th2免疫应答系统在结核性胸膜炎患者中的表达

目的分析结核性胸膜炎患者辅助T细胞(Th)亚型Th1样细胞因子γ干扰素(IFN-γ)、白细胞介素(IL)-2和Th2样细胞因子IL-4、IL-10在血清与胸腔积液中的分布特点,探讨系统及局部的Th1/Th2免疫应答在人类结核性胸膜炎病理生理过程中的可能作用.方法应用夹心酶联免疫吸附测定(ELISA)法检测51例结核性胸膜炎患者(胸膜炎组)血清及胸液标本中IFN-γ、IL-2、IL-4、IL-10的浓度,并与肺结核患者(肺结核组,36例)和健康人(健康人组,24名)比较.结果(1)3组受试者血清IFN-γ、IL-2、IL-4、IL-10浓度中位数分别为胸膜炎组为118.60 ng/L、0.00 ng/L、1.49 ng/L、0.00 ng/L;肺结核组为265.75 ng/L、18.03 ng/L、16.00 ng/L、0.00 ng/L;健康人组为221.70 ng/L、18.52 ng/L、16.00 ng/L、0.00 ng/L.3组受试者血清IFN-γ、IL-2浓度差异无显著性(K-W检验χ2值分别是1.15、4.68,P> 0.05).肺结核组和健康人组受试者血清IL-4、IL-10浓度差异无显著性 (Mann-Whitney 检验Z值分别为-0.27、-1.93, P>0.05),结核性胸膜炎患者血清IL-4浓度明显低于肺结核组(Mann-Whitney检验Z值-2.84,P<0.01).(2)3组受试者血清IFN-γ与IL-4浓度之比依次为胸膜炎组27.93,肺结核组21.72,健康人组10.82,经检验差异无显著性(K-W检验χ2值为4.18,P>0.05).(3)结核性胸腔积液细胞因子浓度(中位数)IFN-γ为832.70 ng/L,IL-2为43.76 ng/L, IL-4为26.00 ng/L, IL-10为38.69 ng/L, 与血清浓度相比较差异有显著性(Wilcoxon Signed Rank检验,Z值分别为-4.34、-2.82、-3.29、-5.15,P<0.05 ).结论免疫功能健全的肺结核和结核性胸膜炎患者其系统的Th1应答相似;而结核性胸膜炎患者系统Th2应答降低,系统Th1/Th2平衡有所上调.结核性胸膜炎患者胸膜局部的Th1/Th2应答较系统明显增强,这可能是结核性胸膜炎病理生理的特征.Th1/Th2免疫应答在结核性胸膜炎病理生理过程中起重要作用,但这种作用的因果关系尚待进一步研究.

A study on the Th1/Th2 cytokines in the pathogenesis of human tuberculous pleuritis

OBJECTIVE: To evaluate the distribution characteristics of Th1-type cytokines (IFN-gamma and IL-2) and Th2-type cytokines (IL-4 and IL-10) in the serum and the pleural effusion in patients with pleural tuberculosis, therefore to gain insight into the possible role of the local and the systemic Th1/Th2 cell-mediated immune response in the pathogenesis of human pleural tuberculosis. METHODS: The concentrations of IFN-gamma, IL-2, IL-4, and IL-10 in the serum and the pleural effusion of patients with pleural tuberculosis (Group pleuritis) were measured with enzyme linked immuno-sorbent assay (ELISA). The serum levels of the four cytokines were compared with those of patients with pulmonary tuberculosis (Group tuberculosis) and of healthy controls with positive reaction to PPD skin test (Group healthy). RESULTS: (1) The median concentrations of IFN-gamma, IL-2, IL-4, and IL-10 in serum were 118.60 ng/L, 0.00 ng/L, 1.49 ng/L, and 0.00 ng/L respectively in Group pleuritis, 265.75 ng/L, 18.03 ng/L, 16.00 ng/L, and 0.00 ng/L respectively in Group tuberculosis; and 221.70 ng/L, 18.52 ng/L, 16.00 ng/L, and 0.00 ng/L respectively in Group healthy. (2) For IFN-gamma and IL-2, there existed no statistical differences among the three groups (K-W chi(2) value was 1.15 and 4.68, P > 0.05); For IL-4 and IL-10, there existed no statistical differences between Group tuberculosis and Group healthy (Mann-Whitney Z value was -0.27 and -1.93, P > 0.05), but the level of IL-4 in Group pleuritis was lower than that in Group tuberculosis (Mann-Whitney Z value was -2.84, P < 0.01). (3) The ratio of the median of IFN-gamma to IL-4 in serum was 27.93 in Group pleuritis, 21.72 in Group tuberculosis, and 10.82 in Group healthy respectively. There existed no statistical difference among the three groups (K-W chi(2) value was 4.18, P > 0.05). (4) The median concentrations of IFN-gamma, IL-2, IL-4, and IL-10 in pleural effusion of Group pleuritis were 823.37 ng/L, 43.76 ng/L, 26 ng/L and 38.69 ng/L respectively, each being statistically higher than that in the serum (Wilcoxon Signed Rank test Z value was -4.34, -2.82, -3.29 and -5.15, P < 0.05). CONCLUSIONS: Immunocompetent persons including patients with pleural tuberculosis, with pulmonary tuberculosis or the healthy with positive results to PPD test, showed similar systemic Th1 response to Mycobacterium bacilli. Due to the relatively lower level of systemic Th2 response, patients with pleural tuberculosis had higher systemic Th1/Th2 level and the enhancement of local Th1 and Th2 responses in the pleural cavity was a pathophysiologic characteristic of human pleural tuberculosis. Both Th1 and Th2 responses might play an important role in the pathogenesis of human pleural tuberculosis.