Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Shanghai Medical College, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, 12 Wulumuqi Zhong Road, Shanghai, 200040, People's Republic of China.
Department of Respiratory Medicine, No. 905 Hospital of PLA Navy, Shanghai, People's Republic of China.
BMC Immunol. 2024 Oct 9;25(1):66. doi: 10.1186/s12865-024-00652-w.
There is substantial evidence indicating that cytokines play a role in the immune defense against tuberculosis. This study aims to evaluate the levels of various cytokines in pleural effusion to ditinguish between tuberculosis pleurisy and malignant pleurisy.
A total of 82 participants with pleural effusion were included in the training cohort, and 76 participants were included in the validation cohort. The individuals were divided into tuberculosis and malignant pleurisy groups. The concentrations of interleukin-1β (IL-1β), IL-4, IL-6, IL-10, IL-17 A, IL-17 F, IL-21, IL-22, IL-25, IL-31, IL-33, interferon-γ (IFN-γ), soluble CD40 ligand (sCD40L) and tumor necrosis factor-α (TNF-α) in pleural effusion were measured using a multiplex cytokine assay. The threshold values were calculated according to the receiver operating characteristic (ROC) curve analysis to aid in diagnosing tuberculosis pleurisy. Furthermore, the combined measure was validated in the validation cohort.
The levels of all 14 cytokines in pleural effusion were significantly higher in participants with tuberculosis compared to those with malignant pleurisy (all P < 0.05). The area under the curve (AUC) was ≥ 0.920 for the IL-22, sCD40L, IFN-γ, TNF-α and IL-31, which were significantly increased in tuberculous pleural effusion (TPE) compared to MPE in the training cohort. Threshold values of 95.80 pg/mL for IFN-γ, 41.80 pg/mL for IL-31, and 18.87 pg/mL for IL-22 provided ≥ 90% sensitivity and specificity in distinguishing between tuberculosis pleurisy and malignant pleurisy in the training cohort. Among these, IL-22 combined with sCD40L showed the best sensitivity and specificity (94.0% and 96.9%) for diagnosing tuberculosis pleurisy, and this finding was validated in the validation cohort.
We demonstrated that the levels of IL-1β, IL-4, IL-6, IL-10, IL-17 A, IL-17 F, IL-21, IL-22, IL-25, IL-31, IL-33, IFN-γ, sCD40L and TNF-α in pleural effusion had significant difference between tuberculosis pleurisy and malignant pleurisy. Specifically, IL-22 ≥ 18.87 pg/mL and sCD40L ≥ 53.08 pg/mL can be clinically utilized as an efficient diagnostic strategy for distinguishing tuberculosis pleurisy from malignant pleurisy.
有大量证据表明细胞因子在抗结核免疫防御中发挥作用。本研究旨在评估胸腔积液中各种细胞因子的水平，以区分结核性胸膜炎和恶性胸腔积液。
纳入了 82 例胸腔积液患者作为训练队列，76 例患者作为验证队列。将这些患者分为结核性胸膜炎和恶性胸腔积液组。采用多因子细胞因子检测法检测胸腔积液中白细胞介素-1β（IL-1β）、IL-4、IL-6、IL-10、IL-17A、IL-17F、IL-21、IL-22、IL-25、IL-31、IL-33、干扰素-γ（IFN-γ）、可溶性 CD40 配体（sCD40L）和肿瘤坏死因子-α（TNF-α）的浓度。根据受试者工作特征（ROC）曲线分析计算出阈值，以辅助诊断结核性胸膜炎。此外，还在验证队列中对联合指标进行了验证。
与恶性胸腔积液患者相比，结核性胸膜炎患者胸腔积液中所有 14 种细胞因子的水平均显著升高（均 P<0.05）。在训练队列中，与恶性胸腔积液相比，结核性胸腔积液中 IL-22、sCD40L、IFN-γ、TNF-α 和 IL-31 的曲线下面积（AUC）均≥0.920。IFN-γ 的阈值为 95.80 pg/mL，IL-31 的阈值为 41.80 pg/mL，IL-22 的阈值为 18.87 pg/mL，在训练队列中，这些指标对结核性胸膜炎和恶性胸腔积液的鉴别具有≥90%的灵敏度和特异性。在这些指标中，IL-22 联合 sCD40L 对诊断结核性胸膜炎的灵敏度和特异性（94.0%和 96.9%）最高，这一发现也在验证队列中得到了验证。
本研究表明，胸腔积液中 IL-1β、IL-4、IL-6、IL-10、IL-17A、IL-17F、IL-21、IL-22、IL-25、IL-31、IL-33、IFN-γ、sCD40L 和 TNF-α 的水平在结核性胸膜炎和恶性胸腔积液之间有显著差异。具体而言，IL-22≥18.87 pg/mL 和 sCD40L≥53.08 pg/mL 可作为临床上区分结核性胸膜炎和恶性胸腔积液的有效诊断策略。
