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苯硝唑:慢性恰加斯病患者细胞免疫反应的英雄还是恶棍?

Benznidazole: Hero or villain of cellular immune response in chronic Chagas disease patients?

机构信息

Instituto Aggeu Magalhães - IAM/Fiocruz, Recife, PE, Brazil; Fundação Altino Ventura - FAV, Recife, PE, Brazil.

Instituto Aggeu Magalhães - IAM/Fiocruz, Recife, PE, Brazil; Hospital das Clínicas - HC/UFPE, Recife, PE, Brazil.

出版信息

Immunobiology. 2021 Jan;226(1):152046. doi: 10.1016/j.imbio.2020.152046. Epub 2020 Dec 4.

Abstract

Although the treatment of chronic Chagas disease (CCD) patients with Benznidazole (Bz) is still controversial, its use may prevent or delay the progression of the disease to the most severe forms. One of the main factors that can influence the effectiveness of the treatment is the possible cooperation between drug effect and the host immune response. Herein, we evaluated the immune response of peripheral blood mononuclear cells (PBMCs) infected with Trypanosoma cruzi and submitted to Bz treatment. Blood samples of CCD patients (n = 7) and non-infected individuals (n = 6) were drawn to obtain PBMCs. After cell culture, the supernatants were harvested and stored, and the cell analyzed by flow cytometer. The results showed that Bz positively regulated the molecular process of cell activation (CD80) and antigen presentation (HLA-DR), increased phagocytosis receptor and macrophage activation (CD64), and did not induce an exacerbated immune response. In conclusion, these results highlight the relevance of using Bz that, despite not being a true hero, it is also not a villain, as it presents a wide range of pharmacological/immunological response interactions, important for the immune balance in the clinical progression of CCD.

摘要

虽然用 Benznidazole(Bz)治疗慢性恰加斯病(CCD)患者仍存在争议,但它的使用可能预防或延缓疾病向最严重形式的进展。影响治疗效果的主要因素之一可能是药物作用与宿主免疫反应之间的协同作用。在此,我们评估了感染 Trypanosoma cruzi 的外周血单核细胞(PBMC)的免疫反应,并对其进行了 Bz 治疗。从 CCD 患者(n=7)和未感染者(n=6)中抽取血液样本以获得 PBMC。细胞培养后,收集上清液并储存,通过流式细胞仪分析细胞。结果表明,Bz 可正向调节细胞激活(CD80)和抗原呈递(HLA-DR)的分子过程,增加吞噬受体和巨噬细胞激活(CD64),且不会引起免疫反应加剧。总之,这些结果强调了使用 Bz 的相关性,尽管它不是真正的治疗药物,但也不是恶棍,因为它具有广泛的药理学/免疫学反应相互作用,这对于 CCD 的临床进展中的免疫平衡很重要。

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