A trial of immunotherapy against Leishmania amazonensis infection in vitro and in vivo with Z-100, a polysaccharide obtained from Mycobacterium tuberculosis, alone or combined with meglumine antimoniate
A trial of immunotherapy against Leishmania amazonensis infection in vitro and in vivo with Z-100, a polysaccharide obtained from Mycobacterium tuberculosis, alone or combined with meglumine antimoniate
复制标题
DOI：
10.1093/jac/dkm079
复制
发表时间：
2007-06-01
影响因子：
5.2
通讯作者：
Hashiguchi, Yoshihisa
中科院分区：
文献类型：
--
作者：
Barroso, Paola Andrea;Marco, Jorge Diego;Hashiguchi, Yoshihisa
目的：目的：观察Z-100单用或与锑酸葡胺合用对亚马逊利什曼原虫感染的疗效及免疫调节作用，方法：采用Giemsa染色法观察巨噬细胞内无鞭毛体的数量，用直线回归法测定IC 50。用有限稀释法测定了化合物的抗利什曼原虫作用，用ELISA法测定了化合物的γ-干扰素（IFN-γ）、白细胞介素10（IL-10）、IL-4、IgG 1和IgG 2a的产生。对亚马逊红蜘蛛的IC_（50）为13 mg/L。此外，用Z-100（12 mg/L）处理的感染的巨噬细胞显示出较小的寄生虫空泡，其中寄生虫比对照少。此外，Z-100+葡甲胺锑酸盐[14 mg/L五价锑（Sb-v）]的疗效高于（46%抑制）单独使用Z-100或葡甲胺锑酸盐。然而，未观察到Z-100对纯性前鞭毛体的影响。与对照组相比，单独用Z-100（100 μ g/kg）治疗的感染的BAILB/c小鼠没有显示出任何抗利什曼原虫的作用，并且IFN-γ以及IL-10和IL-4通过治疗被上调。此外，Z-100处理也增加了IgG 1和IgG 2a。虽然Z-100加锑酸葡胺（14或28 mg/kg Sbv）与对照小鼠相比控制了寄生虫负荷和足垫肿胀，但与锑酸葡胺单独使用无显著差异。亚马逊河。然而，在用Z-100处理的感染的BALB/c小鼠中没有观察到效果，这表明通过处理上调IL-10和IL-4产生可能干扰保护性Th 1型应答的发展。为了进一步了解Z-100在体内的作用，未来应测试另一种小鼠品系，如C57 BL/6。
Objectives: To determine the efficacy and the immunomodulatory function of Z-1 00 alone or combined with meglumine antimoniate on Leishmania amazonensis infection.Methods: The effect of the compounds was evaluated by microscopic counting of intracellular amastigotes in macrophages stained with Giemsa, or axenic promastigotes, and IC50 was determined by linear regression. The antileishmanial effect of the compounds was assessed in infected BALB/c mice by a limiting dilution analysis and the production of gamma interferon (IFN-gamma), interleukin 10 (IL-10), IL-4, IgG1 and IgG2a was measured by ELISA.Results: In vitro, Z-100 showed antileishmanial activity against intracellular amastigotes of L. amazonensis with an IC50 of 13 mg/L. Moreover, infected macrophages treated with Z-100 (12 mg/L) showed smaller parasitophorous vacuoles with fewer parasites than the control. In addition, the efficacy of Z-100 plus meglumine antimoniate [14mg/L pentavalent antimony (Sb-v)] was higher (46% inhibition) than either Z-100 or meglumine antimoniate alone. Nevertheless, no effect of Z-100 on axenic promastigotes was observed. Infected BAILB/c mice treated with Z-100 (100 mu g/kg) alone did not show any anti-leishmanial effects in comparison with the control group, and IFN--y, as well as IL-10 and IL-4, was upregulated by the treatment. In addition, both IgG1 and IgG2a were also increased by the Z-100 treatment. Although Z-100 plus meglumine antimoniate (14 or 28 mg/kg Sbv) controlled both the parasite load and the footpad swelling in comparison with control mice, no significant differences were found with meglumine antimoniate alone.Conclusions: In vitro, Z-100 alone or combined with meglumine antimoniate showed an antileishmanial effect on L. amazonensis. However, no effect was observed in infected BALB/c mice treated with Z-100, suggesting that the up-regulation of IL-10 and IL-4 production by the treatment could be interfering with the development of a protective Th1-type response. For further understanding of the effects of Z-100 in vivo, another strain of mice such as C57BL/6 should be tested in future.