实用医学杂志 ›› 2022, Vol. 38 ›› Issue (17): 2203-2208.doi: 10.3969/j.issn.1006⁃5725.2022.17.016

• 临床研究 • 上一篇    下一篇

血清中相关细胞因子表达水平变化对 肺结核治疗效果的评估

李华1 许婉华2 龚兰1 谢贝1 杨瑜1 刘志辉1 吴玲1 孟繁荣1 王楠1 王琪1 张言斌3   

  1. 1 广州市胸科医院肺部疾病研究所(广州 510095);2 广州市结核病防治所二分所(广州 510095); 3 广州市红十字会医院(广州 510220)

  • 出版日期:2022-09-10 发布日期:2022-09-10
  • 通讯作者: 张言斌 E⁃mail:zh⁃yb2002@163.com
  • 基金资助:
    广州市科技计划项目(编号:202102020910);广州市科技计划项目(编号:202002030152);广州市科技计划项目(编号:
    202206010134);广州市高水平临床重点专科和培育专科建设项目(编号:穗卫函[2019]1555号);广州市医学重点学科(结核病学)建设项目

Efficacy in cytokine expression levels in serums in evaluating treatment effect of pulmonary tuberculosis

LI Hua*,XU WanHua,GONG Lan,XIE Bei,YANG Yu,LIU Zhihui,WU Ling,MENG Fanrong,WANG Nan, WANG Qi,ZHANG Yanbing.   

  1. Institute of Pulmonary Diseases,Guangzhou Chest Hospital,Guangzhou 510095 China 

  • Online:2022-09-10 Published:2022-09-10
  • Contact: ZHANG Yanbing E⁃mail:zh⁃yb2002@163.com

摘要:

目的 分析血清中相关细胞因子表达水平变化在肺结核治疗效果评估中的检验效能。 方法 分别收集肺结核患者治疗前和治疗 2 月时血清,通过流式细胞术测量其中白细胞介素(IL)⁃1β IL⁃2、IL⁃4、IL⁃5、IL⁃6、IL⁃8、IL⁃10、IL⁃12P70、IL⁃17、肿瘤坏死因子(TNF)⁃α、干扰素(IFN)⁃γ IFN⁃α 的表 达水平。同时影像学监测病灶变化情况,较治疗前,治疗 2 月时病灶无变化及增大为无效组,病灶吸收 为有效组。受试者工作曲线分析血清中各细胞因子治疗 2 月与治疗前浓度的比值(Ratio 值)区分肺结 核治疗无效和有效的界值和检验效能。进一步将不同细胞因子串联或并联后,分析其组合后的检验效 能。结果 (1)无效组和有效组患者的年龄和性别差异无统计学意义。总体而言,肺结核患者治疗两 月后血清中 IL⁃6、IFN⁃γ 表达水平较治疗前降低,差异具有统计学意义(P = 0.020、0.023),IL⁃10 表达水 平较治疗前升高,差异具有统计学意义(P = 0.011)。有效组治疗两月后肺结核患者血清中 IL⁃6 表达水 平较治疗前降低,差异具有统计学意义(P = 0.033)。(2)TNF、IL⁃17、IL⁃1β、IL⁃4、IL⁃6、IFN⁃γ、IL⁃12P70 IFN⁃α IL⁃8 Ratio 值在判断肺结核治疗无效时的敏感度> 80%,但特异度较低;IL⁃5 IL⁃10 Ratio 值在判断肺结核治疗无效时的特异度> 80%,但敏感度较低。(3)IFN⁃γ、IL⁃17 IFN⁃α 三种细胞因子串 联组合后,在判断肺结核治疗无效时的灵敏度 84.00%,特异度 70.97%,准确度 76.79%;IL⁃6 IFN⁃α 种细胞因子串联组合后,在判断肺结核治疗无效时的灵敏度 80.00%,特异度 67.74%,准确度 73.21% 结论 对比治疗前,肺结核患者治疗 2 月后血清中部分细胞因子表达水平的变化有用于抗结核治疗效 果监测的潜力。

关键词:

肺结核, 细胞因子, 表达水平变化, 治疗效果

Abstract:

Objective To analyze the efficacy of changes in serum cytokine expression levels in the evalu⁃ ation of pulmonary tuberculosis treatment effects. Methods The serums of pulmonary tuberculosis patients were collected before treatment and after 2⁃month treatment. The expression levels of interleukin(IL)⁃1β,IL⁃2,IL⁃4 IL⁃5,IL⁃6,IL⁃8,IL⁃10,IL⁃12P70,IL⁃17,tumor necrosis factor(TNF)⁃α,interferon(IFN)⁃γ and IFN⁃α were measured by flow cytometry. At the same time,the changes of the lesions were monitored by imaging. The treat⁃ ment was considered as ineffective if the lesions did not change or increased after 2⁃month treatment when com⁃ pared with before treatment,and as effective when the lesions disappeared. Receiver operating curve analysis was done to analyze the cut⁃off value of ratio(ratio of the concentration of each cytokine in serum after 2⁃month treat⁃ ment to that before treatment)and identify the boundary value and test power between the ineffective and effective treatment of pulmonary tuberculosis. After further connecting different cytokines in series or in parallel,the com⁃ bined test performance was analyzed. Results (1)There was no significant difference in age and gender betweenthe ineffective group and the effective group. Overall,the expression levels of IL⁃6 and IFN⁃ γ in the serums of tuberculosis patients after two⁃month treatment were significantly lower than those before treatment(P = 0.020,P = 0.023,respectively). The expression level of IL⁃10 in the serums after two⁃month treatment was significantly higher than that before treatment(P = 0.011). After two⁃month treatment,the expression level of IL⁃6 in the serums in the effective group was significantly lower than that before treatment(P = 0.033).(2)The sensitivity of the ratio of TNF,IL⁃17,IL⁃1β,IL⁃4,IL⁃6,IFN⁃γ,IL⁃12P70,IFN⁃α and IL⁃8 in judging the ineffectiveness of pulmonary tuberculosis treatment was >80%,but the specificity was low. The specificity of the ratio of IL⁃5 and IL⁃10 in judging the ineffectiveness of treatment was >80%,but the sensitivity was low.(3)After combination of IFN⁃ γ,IL⁃17 and IFN⁃ α in series,the sensitivity of judging the ineffectiveness of treatment was 84.00%,the specificity was 70.97%,and the accuracy was 76.79%. After combining the IL⁃6 and IFN⁃α in series,the sensitivi⁃ ty,specificity,and accuracy of judging the ineffectiveness were 80.00% ,67.74% ,and 73.21% ,respectively. Conclusion Compared with before treatment ,the changes in the expression levels of some cytokines in the serums of pulmonary tuberculosis patients after 2⁃month treatment have the potential for monitoring the effect of anti⁃ tuberculosis treatment. 

Key words:

tuberculosis, cytokines, changes in expression level, therapeutic effect