微卡与维生素D联合应用对初治涂阳肺结核CD4^(+)T细胞亚群平衡的影响

Effect of microcard combined with vitamin D on the balance of CD4^(+)T cell subsets in initially treated patients with smear positive pulmonary tuberculosis

目的:探讨微卡(母牛分枝杆菌菌苗)联合维生素D辅助治疗对初治涂阳肺结核(pulmonary tuberculosis,PTB)CD4^(+)T细胞亚群平衡的影响,并分析其临床疗效。方法:采用前瞻性研究方法,于2019年6月至2022年6月,参照入组标准及患者意愿将河南省胸科医院收治的初治涂阳PTB患者分别纳入常规抗结核治疗组(对照组)、常规抗结核+微卡治疗组(微卡组)和常规抗结核+微卡+维生素D辅助治疗组(联合组)。排除中途因各种原因退出或脱落而不能完成6个月治疗方案者,最终以74例为3组不同组别的纳入患者数(共计222例)。检测不同组别PTB患者治疗前及治疗后6个月的外周血辅助性T细胞1(Th1)、Th2、Th17、调节性T细胞(Treg细胞)比例及血清γ-干扰素(IFN-γ)、白细胞介素-4(IL-4)、IL-17、IL-10水平,记录不同组别PTB患者治疗6个月的痰菌阴转率、肺部病灶和空洞改善率及综合疗效情况,并进行数据的统计分析。结果:治疗6个月后,联合组Th1/Th2、Treg/Th17比值和IFN-γ水平[2.32±0.39、0.45±0.03和(16.13±2.67)pg/ml]均明显高于微卡组[2.19±0.25、0.34±0.03和(14.16±3.45)pg/ml;t=2.414,P=0.017;t=22.303,P=0.000;t=3.885,P=0.000]和对照组[2.08±0.37、0.26±0.02和(12.34±1.73)pg/ml;t=3.840,P=0.000;t=45.331,P=0.000;t=10.248,P=0.000],IL-4、IL-17和IL-10水平[(36.54±2.01)pg/ml、(27.10±3.58)pg/ml和(35.46±3.84)pg/ml]均明显低于微卡组[(37.23±1.78)pg/ml、(28.43±2.16)pg/ml和(43.58±4.06)pg/ml;t=2.211,P=0.029;t=2.736,P=0.007;t=12.499,P=0.000]和对照组[(38.89±2.16)pg/ml、(29.40±3.27)pg/ml和(50.24±4.22)pg/ml;t=6.851,P=0.000;t=4.732,P=0.000;t=22.284,P=0.000];痰涂片阴转率[97.30%(72/74)]和总有效率[91.89%(68/74)]均明显优于微卡组[83.78%(62/74)和79.73%(59/74);χ^(2)=7.889,P=0.005;χ^(2)=4.495,P=0.034]和对照组[78.38%(58/74)和77.03%(57/74);χ^(2)=12.397,P=0.000;χ^(2)=6.229,P=0.013]。结论:常规抗结核联合微卡和维生素D辅助治疗可明显促进患者T细胞亚群Th1/Th2、Th17/Treg平衡恢复,有效改善IFN-γ、IL-4、IL-17和IL-10细胞因子水平,临床疗效显著。

Objective:To evaluate the effect of the combination of microcard(Mycobacterium vaccae vaccine)and vitamin D adjuvant therapy on the balance of CD4^(+)T cell subsets in initially treated patients with smear positive pulmonary tuberculosis(PTB),and to analyze its clinical efficacy.Methods:A prospective study was designed.According to the inclusion criteria and patient’s willing,the initially treated patients with smear positive PTB(PTB group)admitted to Henan Chest Hospital from June 2019 to June 2022 were enrolled into conventional anti-tuberculosis treatment group(control group),conventional anti-tuberculosis with microcard treatment group(microcard group)and conventional anti-tuberculosis combined with microcard and vitamin D adjuvant therapy group(combined group).Excluding those who could not complete the 6-month treatment course due to various reasons,74 cases in each group were included(222 patients).The proportion of Th1,Th2,Th17,Treg cells and the levels of IFN-γ,IL-4,IL-17,IL-10 in peripheral blood of patients/healthy subjects were detected in each group before treatment and after 6-month treatment,and the sputum negative conversion rate,lesion and pulmonary cavities and comprehensive efficacy were evaluated by the end of 6-month treatment.Results:After six months treatment,the Th1/Th2,Treg/Th17 ratios and IFN-γlevels in the combined group(2.32±0.39,0.45±0.03 and(16.13±2.67)pg/ml)were significantly higher than those in the microcard group(2.19±0.25,0.34±0.03 and(14.16±3.45)pg/ml;t=2.414,P=0.017;t=22.303,P=0.000;t=3.885,P=0.000)and control group(2.08±0.37,0.26±0.02 and(12.34±1.73)pg/ml;t=3.840,P=0.000;t=45.331,P=0.000;t=10.248,P=0.000).The levels of IL-4,IL-17 and IL-10((36.54±2.01)pg/ml,(27.10±3.58)pg/ml and(35.46±3.84)pg/ml)in the combined group were significantly lower than those in the microcard group((37.23±1.78)pg/ml,(28.43±2.16)pg/ml and(43.58±4.06)pg/ml;t=2.211,P=0.029;t=2.736,P=0.007;t=12.499,P=0.000)and control group((38.89±2.16)pg/ml,(29.40±3.27)pg/ml and(50.24±4.22)pg/ml;t=6.851,P=0.000;t=4.732,P=0.000;t=22.284,P=0.000);the negative conversion rate of sputum smear(97.30%(72/74))and the total effective rate(91.89%(68/74))were significantly higher than those in the microgram group(83.78%(62/74)and 79.73%(59/74);χ^(2)=7.889,P=0.005;χ^(2)=4.495,P=0.034)and control group(78.38%(58/74)and 77.03%(57/74);χ^(2)=12.397,P=0.000;χ^(2)=6.229,P=0.013).Conclusion:Conventional anti-tuberculosis combined with microcard and vitamin D adjuvant therapy can significantly promote the balance restoration of T lymphocyte subsets Th1/Th2 and Th17/Treg,and effectively improve cytokines levels of IFN-γ,IL-4,IL-17 and IL-10,and it has a significant clinical benefit.