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细胞因子作为生物标志物,监测麻风病患者免疫反应中多药治疗的影响。

Cytokines as biomarkers to monitoring the impact of multidrug therapy in immune response of leprosy patients.

机构信息

Programa de Pós-graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.

Imunologia Celular e Molecular, Centro de Pesquisa René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, MG, Brazil; Laboratório de Biologia das Interações Celulares, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.

出版信息

Cytokine. 2017 Sep;97:42-48. doi: 10.1016/j.cyto.2017.05.020. Epub 2017 May 29.

Abstract

Leprosy or Hansen's disease is a chronic infectious disease of the skin and nerves, caused by the intracellular bacilli Mycobacterium leprae. It is characterized by a spectrum of clinical forms depending on the host's immune response to M. leprae. Patients with tuberculoid (TT) leprosy have strong cell-mediated immunity (CMI) with elimination of the bacilli, whereas patients with lepromatous (LL) leprosy exhibit defective CMI to M. leprae. Despite advances in the understanding of the pathogenesis of leprosy and the development of new therapeutic strategies, there is a need for the identification of biomarkers which be used for early diagnosis and to discrimination between different forms of the disease, as prognostic markers. Here, we analyzed the serum levels of IL-1β, IL-6, IL-8, IL-10, IL-12p70, IL-13, IL-17A, IFN-γ and TNF in order to address the contribution of these cytokines in late phase of M. leprae infection, and the impact of multidrug therapy (MDT). Our results demonstrated that patients of LL group presented higher expression of serum levels of inflammatory cytokines before MDT, while TT patients presented a balance between inflammatory and regulatory cytokines. MDT changes the profile of serum cytokines in M. leprae infected patients, as evidenced by the cytokine network, especially in TT patients. LL patients displayed a multifaceted cytokine system characterized by strong connecting axes involving inflammatory/regulatory molecules, while TT patients showed low involvement of regulatory cytokines in network overall. Cytokines can be identified as good biomarkers of the impact of MDT on the immune system and the effectiveness of treatment.

摘要

麻风病,又称汉森氏病,是一种由麻风分枝杆菌引起的慢性传染病,主要侵犯皮肤和外周神经。其临床表现多样,取决于宿主对麻风分枝杆菌的免疫反应。结核样型麻风(TT)患者具有较强的细胞免疫(CMI),能够清除麻风分枝杆菌;而界限类偏结核样型麻风(BT)患者则表现出对麻风分枝杆菌的细胞免疫缺陷。尽管人们对麻风病的发病机制和新治疗策略的发展有了更深入的了解,但仍需要识别生物标志物,用于早期诊断和区分不同形式的疾病,以及作为预后标志物。在这里,我们分析了 IL-1β、IL-6、IL-8、IL-10、IL-12p70、IL-13、IL-17A、IFN-γ 和 TNF 等细胞因子在麻风分枝杆菌感染晚期的作用,以及多药联合化疗(MDT)的影响。结果表明,LL 组患者在 MDT 前血清炎症细胞因子水平较高,而 TT 患者表现出炎症和调节细胞因子之间的平衡。MDT 改变了麻风分枝杆菌感染患者的血清细胞因子谱,这可以从细胞因子网络中得到证明,尤其是 TT 患者。LL 患者表现出多方面的细胞因子系统,涉及炎症/调节分子的强连接轴,而 TT 患者的网络整体上调节细胞因子的参与度较低。细胞因子可以作为 MDT 对免疫系统影响和治疗效果的良好生物标志物。

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