目的研究难治性肺结核患者外周血单个核细胞(PBMCs)经结核分枝杆菌特异性抗原肽(ESAT-6,CFP.10)刺激后代表性Thl细胞因子IFN一叫、IL-2和TNF.d的表达特点及意义。方法纳入67例初治肺结核患者、28例难治性肺结核患者和25位结核分枝杆菌潜伏感染者,分离外周血单个核细胞(PBMCs),用ESAT-6,CFP-10肽库刺激PBMCs,采用FlowCytomix流式技术检测细胞培养液上清中细胞因子IFN-γ、IL-2和TNF-α的浓度。结果PBMCs经结核分枝杆菌特异性抗原肽刺激后,IFN-γ、IL-2和TNF-α均因刺激而升高,初治组的三个因子的水平均显著高于难治组和潜伏感染组(与难治组比较,Mann-WhitneyU值=119.0,282.5、339.5,P均〈0.01;与潜伏感染组比较,Mann-WhitneyU值=387.0,477.0、374.5,P=0.0002,0.0033、0.0001),难治组IFN-γ和IL-2的水平显著低于潜伏感染组(Mann-WhitneyU值=105.5、162.5,P〈0.01),TNF-α的水平在难治组和潜伏感染组间的差异无统计学意义(Mann-WhitneyU值=265.0,P=0.2695)。结论难治性肺结核患者结核分枝杆菌特异性Thl细胞因子反应低下,针对结核病的免疫治疗可能对难治性肺结核发挥更大的作用。
Objective To investigate the feature of Thl cytokines induced by Mtb-specific antigen in patients with refractory pulmonary tuberculosis. Methods 28 patients with refractory pulmonary tubercu- losis, 67 patients with first-treated pulmonary tuberculosis, and 25 healthy controls with positive T. spot (LTBI group) were enrolled. IFN-γ, IL-2 and TNF-α in supernatants from PBMCs stimulated with ESAT-6 and CFP-10 were analyzed with Bender Flowcytomix on flow cytometry. Results The levels of the three cytokines were utmost high in patients with first-treated pulmonary tuberculosis. The lowest level of IFN-γand IL-2 were induced in patients with refractory pulmonary tuberculosis, and were significantly lower than the LTBI group( Mann-Whitney U = 105.5,162. 5, P 〈 0.01 ). Conclusions The immunotherapy with IFN-γ and IL-2 may play a role in treatment for refractory pulmonary tuberculosis but not for most of first-treated pulmonary tuberculosis.