Carvalho Lívia Mendes, Ferreira Francielle Carvalho, Gusmão Miriã Rodrigues, Costa Ana Flávia Pereira, de Brito Rory Cristiane Fortes, Aguiar-Soares Rodrigo Dian de Oliveira, Reis Alexandre Barbosa, Cardoso Jamille Mirelle de Oliveira, Carneiro Cláudia Martins, Roatt Bruno Mendes
Laboratório de Imunopatologia, Núcleo de Pesquisas em Ciências Biológicas/NUPEB, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brazil.
Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais, INCT-DT, Brazil.
Curr Res Immunol. 2021 Nov 5;2:194-201. doi: 10.1016/j.crimmu.2021.10.003. eCollection 2021.
Visceral leishmaniasis (VL) is a serious and neglected disease present worldwide. Chemotherapy using pentavalent antimony (Sb) is the most practical and inexpensive strategy available for the VL treatment today, however, it has high toxicity. Alternatively, other drugs are used as viable leishmanicidal therapeutic options. Miltefosine is the only anti-leishmanial agent administered orally, however, it has been reducing its effectiveness. In this sense, there is no ideal therapy for VL since the drugs currently used trigger severe side effects causing discontinuation of treatment, which carries an imminent risk for the emergence of parasite resistance. With that, other therapeutic strategies are gaining prominence. Among them, immunotherapy and/or immunochemotherapy, which the activation/modulation of the immune system can redirect the host's immune response to an effective therapeutic result. Therefore, this work was designed to assess an immunochemotherapy protocol composed of half course of Miltefosine associated with LBSap vaccine (Milt+LBSap) using the hamster as an experimental model for VL treatment. When evaluating the main hematobiochemical, immunological and therapeutic efficacy parameters, it was demonstrated that the treatment with Milt+LBSap showed restoration of hematobiochemical condition and reduced serum levels of IgG-anti- compared to animals infected non treated (INT). Beyond that, an increase in the number of CD4 lymphocytes producers of IFN-γ in relation to INT or to animals treated with miltefosine during 28 days, and TNF-α increased compared to INT were observed. Also, it was found a reduction of IL-10-production in relation to INT, or animals that received LBSap vaccine only, or miltefosine, following by a reduction in the splenic parasitic burden. These results demonstrate that the immunochemotherapy protocol used can stimulate the immune response, inducing an expressive cellular response sufficient to control spleen parasitism, standing out as a promising proposal for the VL treatment.
内脏利什曼病（VL）是一种在全球范围内存在的严重且被忽视的疾病。使用五价锑（Sb）进行化疗是目前VL治疗中最实用且成本最低的策略，然而，它具有高毒性。另外，其他药物也被用作可行的杀利什曼原虫治疗选择。米替福新是唯一一种口服的抗利什曼原虫药物，然而，它的有效性一直在降低。从这个意义上说，目前还没有针对VL的理想疗法，因为目前使用的药物会引发严重的副作用，导致治疗中断，这带来了寄生虫耐药性出现的紧迫风险。因此，其他治疗策略正变得越来越重要。其中，免疫疗法和/或免疫化学疗法，即免疫系统的激活/调节可以将宿主的免疫反应导向有效的治疗结果。因此，本研究旨在评估一种免疫化学疗法方案，该方案由半疗程的米替福新与LBSap疫苗联合组成（Milt+LBSap），以仓鼠作为VL治疗的实验模型。在评估主要血液生化、免疫学和治疗效果参数时，结果表明，与未治疗的感染动物（INT）相比，Milt+LBSap治疗显示出血液生化状况的恢复以及血清IgG抗体水平的降低。除此之外，与INT相比，或与接受28天米替福新治疗的动物相比，产生IFN-γ的CD4淋巴细胞数量增加，且TNF-α水平相对于INT有所升高。此外，与INT、仅接受LBSap疫苗或米替福新治疗的动物相比，IL-10的产生减少，随后脾脏寄生虫负荷降低。这些结果表明，所使用的免疫化学疗法方案可以刺激免疫反应，诱导足以控制脾脏寄生虫感染的显著细胞反应，是VL治疗的一个有前景的方案。
