血清细胞因子TNF-α、IL-4、sIL-2R和IFN-γ对预测抗结核治疗效果的价值

doi:10.19982/j.issn.1000-6621.20220167

摘要/Abstract

摘要：

目的:探索肺结核患者血清细胞因子肿瘤坏死因子-α(TNF-α)、白细胞介素4(IL-4)、可溶性白细胞介素受体(sIL-2R)和γ-干扰素(IFN-γ)水平对抗结核治疗效果的预测价值。方法:采用前瞻性队列研究方法,参照入组标准纳入2017年12月至2019年6月首都医科大学附属北京胸科医院收治的67例新诊断活动性肺结核患者作为研究对象。使用酶联免疫吸附试验(ELISA)检测患者治疗前、抗结核治疗1~2个月和治疗6个月时外周血血清TNF-α、IL-4、sIL-2R和IFN-γ水平,对显著差异的指标进行受试者工作特征(ROC)曲线分析以确定其最佳临界值,并以此为界值预测肺结核的活动性和治疗进展。结果:治疗1~2个月的sIL-2R水平[14.1(11.2,19.1)pg/ml]、治疗6个月的TNF-α水平[686.6(226.9,1030.5)pg/ml]和治疗1~2个月的IFN-γ水平[357.0(273.4,431.0)pg/ml]均明显低于治疗前[分别为16.7(12.9,23.9)、848.3(345.2,1201.6)、490.0(303.6,607.9)pg/ml],差异均有统计学意义(χ²=15.276,P=0.036;χ²=33.421,P=0.002;χ²=31.111,P=0.000)。ROC曲线分析显示:当血清TNF-α水平为845.2pg/ml时,治疗有效性的曲线下最大面积(AUC)为0.594(P=0.013);当血清IFN-γ水平为393.3pg/ml时,治疗有效性的AUC为0.651(P=0.017)。以最佳临界值为参照标准,发现治疗前血清IFN-γ和TNF-α水平高于其最佳临界值者(阳性者)分别为43例(64.2%)和34例(50.7%),明显高于治疗1~2个月的IFN-γ[14例(20.9%)]和治疗6个月的TNF-α阳性者[19例(28.4%)],差异均有统计学意义(χ²=34.634,P=0.000;χ²=53.181,P=0.013)。结论:血清TNF-α和IFN-γ水平作为监测抗结核治疗的生物标志物可能具有一定意义。

关键词: 结核, 细胞因子类, 生物学鉴定法, 治疗结果

Abstract:

Objective:To explore the predictive value of serum cytokines TNF-α, IL-4, sIL-2R and IFN-γ for antituberculosis treatment in patients with pulmonary tuberculosis. Methods:By a prospective cohort study method, 67 patients diagnosed active pulmonary tuberculosis admitted to Beijing Chest Hospital Affiliated to Capital Medical University from December 2017 to June 2019 were enrolled according to the enrollment criteria. Serum cytokine levels of TNF-α, IL-4, sIL-2R and IFN-γ were measured by enzyme-linked immunosorbent assay (ELISA) from patients before treatment, 1-2 months and 6 months after treatment. ROC curve analysis was performed to determine the best cut-off value, and treatment progress were predicted with this as the cut-off value. Results:The levels of SIL-2R (14.1 (11.2,19.1) pg/ml) after 1-2 months of treatment, TNF-α (686.6 (226.9,1030.5) pg/ml) after 6 months of treatment, IFN-γ (357.0 (273.4,431.0) pg/ml) after 1-2 months of treatment were significantly lower than that before treatment (16.7 (12.9, 23.9), 848.3 (345.2, 1201.6), 490.0 (303.6,607.9) pg/ml, respectively), with the statistically difference (χ²=15.276, P=0.036; χ²=33.421, P=0.002; χ²=31.111, P=0.000). ROC analysis showed that when serum TNF-α at 845.2 pg/ml and IFN-γ at 393.3 pg/ml,the AUC of therapeutic effectiveness were 0.594 (P=0.013) and 0.651 (P=0.017). With the best cut-off value as the reference standard, serum IFN-γ and TNF-α level above the cut-off value before treatment were 43 cases (64.2%) and 34 cases (50.7%), respectively. In 1-2 months after treatment, 14 cases (20.9%) were positive with the serum IFN-γ significantly lower than that before treatment (χ²=34.634, P=0.000). In 6 months after treatment, 19 cases (28.4%) were positive with the serum TNF-α significantly lower than that before treatment (χ²=53.181, P=0.013). Conclusion:Both serum TNF-α and IFN-γ levels might be useful biomarkers for monitoring treatment progress.

Key words: Tuberculosis, Cytokines, Biological assay, Treatment outcome

中图分类号:

R393.7
R52

聂文娟, 石文卉, 刘佩英, 杨扬, 王隽, 王庆枫, 初乃惠. 血清细胞因子TNF-α、IL-4、sIL-2R和IFN-γ对预测抗结核治疗效果的价值[J]. 中国防痨杂志, 2022, 44(10): 1022-1027. doi: 10.19982/j.issn.1000-6621.20220167

Nie Wenjuan, Shi Wenhui, Liu Peiying, Yang Yang, Wang Jun, Wang Qingfeng, Chu Naihui. Serum cytokine TNF-α, IL-4, sIL-2R and IFN-γ progress in monitoring bacterial load and anti-tuberculosis treatment[J]. Chinese Journal of Antituberculosis, 2022, 44(10): 1022-1027. doi: 10.19982/j.issn.1000-6621.20220167

图/表 3

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