Department of Paediatrics, The University of Melbourne and Murdoch Children's Research Institute, Royal Children's Hospital Melbourne, Parkville, VIC, Australia.
Victorian Infectious Diseases Reference Laboratory, Parkville, VIC, Australia.
Tuberculosis (Edinb). 2015 May;95(3):343-9. doi: 10.1016/j.tube.2015.02.039. Epub 2015 Feb 14.
The ability to monitor and confirm adequate treatment of latent TB infection (LTBI) would be a major advance. The potential immunomodulatory effects of anti-tuberculous drugs and steroids need to be considered in assessing the utility of cytokine-based assays for this purpose.
We determined whether anti-tuberculous antibiotics or dexamethasone affect the production of IFN-γ and other potential cytokine biomarkers (TNF-α, IL-1ra, IL-2, IL-10, IL-13, IP-10, MIP-1β) in the QuantiFERON-TB Gold In-Tube (QFT-IT) assay. Blood from ten adults with LTBI was added to one standard set of QFT-IT tubes and five further sets containing therapeutic concentrations of either isoniazid, rifampicin, isoniazid and rifampicin, ciprofloxacin or dexamethasone. Resulting supernatants were analysed by ELISA (QFT-IT assay IFN-γ) and xMAP-Luminex assays (all cytokines).
Anti-tuberculous antibiotics had only a limited effect on categorical QFT-IT assay results and the production of cytokines. In contrast, dexamethasone resulted in a change in categorical results from positive to negative in four of ten patients, and caused a marked reduction in IL-13 and IL-1ra responses.
Substantial changes in TB-antigen-induced IFN-γ and other cytokine responses during treatment likely primarily reflect host immunological changes rather than immunomodulatory effects of anti-tuberculous antibiotics. Results from cytokine-based assays in patients on corticosteroids should be interpreted with caution.
能够监测和确认潜伏性结核感染（LTBI）的充分治疗将是一个重大进展。在评估基于细胞因子的检测方法的用途时，需要考虑抗结核药物和类固醇的潜在免疫调节作用。
我们确定抗结核抗生素或地塞米松是否会影响 IFN-γ和其他潜在细胞因子生物标志物（TNF-α、IL-1ra、IL-2、IL-10、IL-13、IP-10、MIP-1β）在 QuantiFERON-TB Gold In-Tube（QFT-IT）检测中的产生。将来自 10 名 LTBI 成人的血液添加到一个标准的 QFT-IT 管组和另外 5 个管组中，其中包含异烟肼、利福平、异烟肼和利福平、环丙沙星或地塞米松的治疗浓度。通过 ELISA（QFT-IT 检测 IFN-γ）和 xMAP-Luminex 检测（所有细胞因子）分析产生的上清液。
抗结核抗生素对分类 QFT-IT 检测结果和细胞因子的产生只有有限的影响。相比之下，地塞米松导致十个患者中的四个从阳性到阴性的分类结果发生变化，并导致 IL-13 和 IL-1ra 反应明显减少。
治疗期间结核抗原诱导的 IFN-γ和其他细胞因子反应的显著变化可能主要反映宿主免疫变化，而不是抗结核抗生素的免疫调节作用。应谨慎解释接受皮质类固醇治疗的患者的细胞因子检测结果。
