Laboratório de Pesquisas Clínicas, Programa de Pós-Graduação em Ciências Farmacêuticas (CiPHARMA), Escola de Farmácia, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brazil.
Laboratório de Imunopatologia, Núcleo de Pesquisas em Ciências Biológicas, Instituto de Ciências Exatas e Biológicas, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brazil.
Antimicrob Agents Chemother. 2017 Oct 24;61(11). doi: 10.1128/AAC.00962-17. Print 2017 Nov.
Pentavalent antimonial has been the first choice treatment for visceral leishmaniasis; however, it has several side effects that leads to low adherence to treatment. Liposome-encapsulated meglumine antimoniate (MA) arises as an important strategy for chemotherapy enhancement. We evaluated the immunopathological changes using the mixture of conventional and pegylated liposomes with MA. The mice were infected with and a single-dose treatment regimen. Comparison was made with groups treated with saline, empty liposomes, free MA, and a liposomal formulation of MA (Lipo MA). Histopathological analyses demonstrated that animals treated with Lipo MA showed a significant decrease in the inflammatory process and the absence of granulomas. The stimulation of splenocytes showed a significant increase of gamma interferon (IFN-γ) produced by CD8 T cells and a decrease in interleukin-10 (IL-10) produced by CD4 and CD8 T cells in the Lipo MA. Furthermore, the Lipo MA group showed an increase in the IFN-γ/IL-10 ratio in both CD4 and CD8 T cell subsets. According to the parasite load evaluation using quantitative PCR, the Lipo MA group showed no DNA in the spleen (0.0%) and 41.4% in the liver. In addition, we detected a low positive correlation between parasitism and histopathology findings (inflammatory process and granuloma formation). Thus, our results confirmed that Lipo MA is a promising antileishmanial formulation able to reduce the inflammatory response and induce a type 1 immune response, accompanied by a significant reduction of the parasite burden into hepatic and splenic compartments in treated animals.
五价锑一直是治疗内脏利什曼病的首选药物；然而，它有几个副作用，导致治疗依从性低。脂质体包裹的葡甲胺锑（MA）作为化疗增强的重要策略出现。我们使用常规和聚乙二醇化脂质体与 MA 的混合物来评估免疫病理变化。用感染了的小鼠进行单次剂量治疗方案。与用生理盐水、空脂质体、游离 MA 和 MA 的脂质体制剂（Lipo MA）治疗的组进行比较。组织病理学分析表明，用 Lipo MA 治疗的动物炎症过程明显减少，没有肉芽肿。脾细胞刺激显示 CD8 T 细胞产生的伽马干扰素（IFN-γ）显著增加，CD4 和 CD8 T 细胞产生的白细胞介素-10（IL-10）减少，Lipo MA 中。此外，Lipo MA 组中 CD4 和 CD8 T 细胞亚群的 IFN-γ/IL-10 比值均增加。根据使用定量 PCR 评估寄生虫负荷，Lipo MA 组脾脏中无（0.0%）和肝脏中（41.4%）的 DNA。此外，我们检测到寄生虫病与组织病理学发现（炎症过程和肉芽肿形成）之间存在低度正相关。因此，我们的结果证实，Lipo MA 是一种有前途的抗利什曼原虫制剂，能够减少炎症反应，并诱导 1 型免疫反应，同时显著减少治疗动物肝脾部位的寄生虫负荷。
