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结核治疗过程中免疫变化及其与 HIV-1 合并结核分枝杆菌感染患者肾上腺激素变化的关系。

Immune variations throughout the course of tuberculosis treatment and its relationship with adrenal hormone changes in HIV-1 patients co-infected with Mycobacterium tuberculosis.

机构信息

Universidad de Buenos Aires. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones Biomédicas en Retrovirus y Sida (INBIRS). Facultad de Medicina, Ciudad Autónoma de Buenos Aires, Argentina.

Hospital Juan A. Fernández. Buenos Aires, Argentina.

出版信息

Tuberculosis (Edinb). 2021 Mar;127:102045. doi: 10.1016/j.tube.2020.102045. Epub 2021 Jan 2.

Abstract

HIV infection is a major risk factor predisposing for Mycobacterium tuberculosis infection and progression to active tuberculosis (TB). As host immune response defines the course of infection, we aimed to identify immuno-endocrine changes over six-months of anti-TB chemotherapy in HIV+ people. Plasma levels of cortisol, DHEA and DHEA-S, percentages of CD4 regulatory T cell subsets and number of IFN-γ-secreting cells were determined. Several cytokines, chemokines and C-reactive protein levels were measured. Results were correlated with clinical parameters as predictors of infection resolution and compared to similar data from HIV+ individuals, HIV-infected persons with latent TB infection and healthy donors. Throughout the course of anti-TB/HIV treatment, DHEA and DHEA-S plasma levels raised while cortisol diminished, which correlated to predictive factors of infection resolution. Furthermore, the balance between cortisol and DHEA, together with clinical assessment, may be considered as an indicator of clinical outcome after anti-TB treatment in HIV+ individuals. Clinical improvement was associated with reduced frequency of unconventional Tregs, increment in IFN-γ-secreting cells, diminution of systemic inflammation and changes of circulating cytokines and chemokines. This study suggests that the combined anti-HIV/TB therapies result in partial restoration of both, immune function and adrenal hormone plasma levels.

摘要

HIV 感染是导致结核分枝杆菌感染和发展为活动性肺结核(TB)的主要危险因素。由于宿主免疫反应决定了感染的过程,我们旨在确定 HIV+人群在抗结核化疗的六个月内免疫内分泌的变化。测定了皮质醇、DHEA 和 DHEA-S 的血浆水平、CD4 调节性 T 细胞亚群的百分比以及 IFN-γ 分泌细胞的数量。测量了几种细胞因子、趋化因子和 C 反应蛋白的水平。将结果与感染消退的临床参数相关联,并与 HIV+个体、HIV 感染潜伏性结核感染个体和健康供体的类似数据进行比较。在整个抗结核/抗 HIV 治疗过程中,DHEA 和 DHEA-S 的血浆水平升高,而皮质醇降低,这与感染消退的预测因素相关。此外,皮质醇与 DHEA 的平衡以及临床评估可被视为 HIV+个体抗结核治疗后临床结果的指标。临床改善与非常规 Tregs 的频率降低、IFN-γ 分泌细胞的增加、全身炎症的减少以及循环细胞因子和趋化因子的变化有关。这项研究表明,联合抗 HIV/TB 治疗可部分恢复免疫功能和肾上腺激素的血浆水平。

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