Department of Internal Medicine, Kangwon National University Hospital, School of Medicine,Kangwon National University, Chuncheon, Republic of Korea.
Institute of New frontier Research, Hallym University College of Medicine, Chuncheon, South Korea.
BMC Infect Dis. 2019 Feb 13;19(1):151. doi: 10.1186/s12879-019-3798-5.
Vitamin D levels are associated with the extent of mycobactericidal activity. Interleukin (IL)-15 and IL-32 play roles in the vitamin D-mediated tuberculosis (TB) defense mechanism. Vitamin D induces IL-1β, which plays an important role in terms of resistance to TB. We evaluated whether the levels of vitamin D-related cytokines distinguished between those with active TB and latent TB infection (LTBI).
In total, 50 TB-infected patients (25 with active TB and 25 with LTBI following a TB outbreak in a high school) were enrolled. Plasma 25-hydroxyvitamin D (25[OH]D), IL-15, IL-32, and IL-1β levels were measured via enzyme-linked immunosorbent assays. Mycobacterium tuberculosis-specific antigen-induced and unstimulated cytokine levels were measured in the supernatants of the QuantiFERON TB Gold-In-Tube (QFT-GIT) assay.
Plasma 25(OH)D and plasma IL-15 levels were lower in patients with active TB than in LTBI subjects (25(OH)D: 16.64 ng/mL vs. 21.6 ng/mL, P = 0.031; IL-15: 148.9 pg/mL vs. 189.8 pg/mL, P = 0.013). Plasma 25(OH)D levels correlated with the plasma levels of IL-15 and IL-1β in TB-infected patients. In addition, the plasma 25(OH)D levels correlated positively with the level of unstimulated IL-15 (IL-15) and negatively with that of TB antigen-stimulated IL-32 (IL-32) in QFT-GIT supernatants. Although the IL-15 and IL-15 levels were higher in LTBI subjects than patients with active TB, the IL-32 and IL-32 levels were higher in the latter patients. A combination of the IL-15 and IL-32 levels accurately predicted 91.3% of active TB patients and latent subjects, with an area under the curve of 0.964.
Our preliminary data showed that the levels of the vitamin D-related cytokines IL-15 and IL-32 differed between active TB patients and LTBI subjects. This result might be used as a basic data for developing biomarkers distinguishing between active TB and LTBI.
维生素 D 水平与分枝杆菌杀菌活性的程度有关。白细胞介素（IL）-15 和 IL-32 在维生素 D 介导的结核病（TB）防御机制中发挥作用。维生素 D 诱导 IL-1β，这在抵抗结核病方面起着重要作用。我们评估了维生素 D 相关细胞因子的水平是否可以区分活动性 TB 和潜伏性 TB 感染（LTBI）患者。
共纳入 50 例 TB 感染患者（25 例活动性 TB 和 25 例高中 TB 爆发后的 LTBI）。通过酶联免疫吸附试验测量血浆 25-羟维生素 D（25[OH]D）、IL-15、IL-32 和 IL-1β 水平。在 QuantiFERON TB Gold-In-Tube（QFT-GIT）检测中测量结核分枝杆菌特异性抗原诱导和未刺激的细胞因子水平。
与 LTBI 患者相比，活动性 TB 患者的血浆 25（OH）D 和 IL-15 水平较低（25（OH）D：16.64ng/mL 比 21.6ng/mL，P=0.031；IL-15：148.9pg/mL 比 189.8pg/mL，P=0.013）。TB 感染患者的血浆 25（OH）D 水平与血浆中 IL-15 和 IL-1β 水平相关。此外，血浆 25（OH）D 水平与 QFT-GIT 上清液中未刺激的 IL-15（IL-15）呈正相关，与 TB 抗原刺激的 IL-32（IL-32）呈负相关。虽然 LTBI 患者的 IL-15 和 IL-15 水平高于活动性 TB 患者，但后者患者的 IL-32 和 IL-32 水平更高。IL-15 和 IL-32 水平的组合可以准确预测 91.3%的活动性 TB 患者和潜伏性患者，曲线下面积为 0.964。
我们的初步数据显示，活动性 TB 患者和 LTBI 患者之间维生素 D 相关细胞因子 IL-15 和 IL-32 的水平存在差异。这一结果可作为区分活动性 TB 和 LTBI 的生物标志物的基础数据。
