BACKGROUND As the widely used biomarker of whole-blood stimulation assays for tuberculosis diagnosis, the release of IFN-γ might be affected by multiple factors, such as immunosuppression and some infectious agents. Here, we evaluated additional cytokines as diagnostic biomarkers. METHODS Forty-three cytokines were measured by Luminex xMAP technologies in 30 healthy and 10 naturally Mycobacterium tuberculosis (MTB)-infected rhesus monkeys pre- and post-stimulation by purified protein derivative (PPD). RESULTS After stimulation, production of 23 and 38 cytokines was markedly increased in healthy and MTB-infected macaques, respectively. A comparison of the stimulation index (SI) between MTB infections and healthy macaques showed that the SIs of 32 cytokines in MTB-infected macaques were significantly higher than those in healthy macaques. Pooling the results, eight cytokines were suggested as ideal biomarkers for a whole-blood stimulation assay for MTB diagnosis. CONCLUSION PPD could induce multiple cytokine responses in either healthy or MTB-infected monkeys, and eight cytokines had reliable predictive capacity as diagnostic biomarkers of MTB infection.

中文翻译：

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健康和天然感染结核分枝杆菌的恒河猴（Macaca mulatta）中多种细胞因子对纯化蛋白衍生物的体外反应。

背景技术作为用于结核病诊断的全血刺激测定法广泛使用的生物标志物，IFN-γ的释放可能受到多种因素的影响，例如免疫抑制和某些感染因子。在这里，我们评估了其他细胞因子作为诊断生物标志物。方法用Luminex xMAP技术在纯化的蛋白衍生物（PPD）刺激前后，对30只健康的和10只天然结核分枝杆菌（MTB）感染的恒河猴测量了43种细胞因子。结果刺激后，健康和MTB感染的猕猴分别显着增加了23种和38种细胞因子的产生。比较MTB感染和健康猕猴的刺激指数（SI），发现MTB感染猕猴中32种细胞因子的SI显着高于健康猕猴。综合这些结果，八种细胞因子被建议作为用于MTB诊断的全血刺激测定的理想生物标志物。结论PPD可在健康或MTB感染的猴子中诱导多种细胞因子反应，并且八种细胞因子具有可靠的预测能力，可作为MTB感染的诊断生物标志物。