The pentavalent antimonial therapy against experimental Leishmania amazonensis infection is more effective under the inhibition of the NF-κB pathway
The pentavalent antimonial therapy against experimental Leishmania amazonensis infection is more effective under the inhibition of the NF-κB pathway
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DOI：
10.1016/j.intimp.2015.07.020
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发表时间：
2015-09-01
影响因子：
5.6
通讯作者：
Nicolete, Roberto
中科院分区：
文献类型：
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作者：
Aragao Macedo, Sharon Rose;de Figueiredo Nicolete, Larissa Deadame;Nicolete, Roberto
在利什曼原虫感染期间，宿主免疫反应对防止细胞内无尾线虫的生长/存活很重要。在本研究中，我们在体外和体内评估了在亚马逊利什曼原虫感染期间，五价锑治疗/治疗是否在tnf - α抑制下更有效。用核因子κ B （nf - κ B）抑制剂和葡聚糖(R) e单独或联合给药治疗亚马逊乳杆菌感染的巨噬细胞（体外模型）和小鼠（体内模型）。在药物作用48 h后，测定体外无尾线虫计数、胞毒素和亚硝酸盐产量。在体内还评估了爪损伤大小和无尾刚体计数。从感染组织中定量IL-1 β。体外结果表明，当感染的巨噬细胞与QNZ +葡聚糖(R)孵育时，观察到对无尾线虫生长的更大清除率，这与仅感染组的亚硝酸盐产量更多有关。体内实验结果显示，接受联合治疗的小鼠足部病变大小和巨噬细胞内的无尾线虫巢明显减少，与IL-1 β水平升高相关。(C) 2015 Elsevier B.V.版权所有
During Leishmania infection, host immune response is important to prevent the growth/survival of intracellular amastigotes. In this study, we evaluated in vitro and in vivo whether or not during Leishmania amazonensis infection, pentavalent antimonial treatment/therapy could be more effective under TNF-alpha inhibition. Both L. amazonensis-infected macrophages (in vitro model) and mice (in vivo model) were treated with a nuclear factor-kappa B (NF-kappa B) inhibitor and with Glucantim (R) e, alone and in combined administrations. The in vitro amastigote counts, cytolcines and nitrites' production were assessed after 48 h incubation with the drugs. Paw lesion sizes and amastigote counts were also evaluated in vivo. Quantification of IL-1 beta from the infected tissue was performed. In vitro results show that when infected macrophages were incubated with QNZ + Glucantime (R), a greater clearance was observed for the amastigotes' growth and this was related to greater nitrite production compared to the group that was only infected. In vivo results show that mice that received the combined treatment had their paw lesion sizes and amastigote nests inside the macrophages greatly diminished, correlating with increased IL-1 beta levels. (C) 2015 Elsevier B.V. All rights reserved.