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人可透析白细胞提取物(IMMODIN)作为阿苯达唑佐剂在幼虫期绦虫感染小鼠模型中的应用:免疫调节和肝保护作用。

The utilisation of human dialyzable leukocyte extract (IMMODIN) as adjuvant in albendazole therapy on mouse model of larval cestode infection: Immunomodulatory and hepatoprotective effects.

机构信息

Institute of Parasitology of the Slovak Academy of Sciences, Hlinkova 3, 04001 Košice, Slovak Republic.

The University of Veterinary Medicine and Pharmacy in Košice, 041 81 Košice, Slovak Republic.

出版信息

Int Immunopharmacol. 2018 Dec;65:148-158. doi: 10.1016/j.intimp.2018.09.045. Epub 2018 Oct 10.

Abstract

Metacestode (larval) stages of zoonotic cestodes of medical and veterinary importance cause chronic infections associated with immunosuppression. During mouse model of cestode infection induced by larvae of Mesocestoides (M.) vogae, we investigated the effects of dialyzable leukocyte extract (DLE) containing low-molecular weight substances (under 10 kDa) prepared from peripheral blood leukocytes of healthy human donors (available under commercial name IMMODIN). In the experiment, the effects of DLE as adjuvant to anthelmintic albendazole (ABZ) as well ABZ mono-therapy were also investigated. We showed that DLE enhanced therapeutic effect of ABZ by significant reduction of parasites number in both biased sites. Furthermore, administration of DLE reduced fibrosis and concentrations of lipid peroxides in the liver and thereby showed cytoprotective effect. In contrast, higher hydroxyproline level and numbers of larvae enclosed in fibrous capsules were found in ABZ-treated group. In order to investigate whether DLE could affect parasite-induced immunosuppression, we evaluated selected immune parameters. The results showed that DLE administration to mice increased proliferation of concanavalin A stimulated splenic cells ex vivo. Similarly, in vitro study confirmed that DLE ameliorated hypo-responsiveness of T lymphocytes and partially reverted suppressive effect of parasites excretory-secretory products. In addition, flow cytometric analysis revealed higher numbers of T helper and NK cells in the spleen and peritoneal cavity of infected mice after DLE + ABZ therapy. We also found strongly reduced serum levels of TGF-β1 and IL-17 as well as modulation of cytokines associated with Th1/Th2 immunity. These results suggest that IMMODIN could serve as a suitable adjuvant to the primary anthelmintic therapy.

摘要

医学生物学和兽医学中具有重要意义的后生动物绦虫的类囊蚴(幼虫)阶段会引起与免疫抑制相关的慢性感染。在由Mesocestoides(M.)vogae 幼虫引起的小鼠绦虫感染模型中,我们研究了低分子量物质(小于 10 kDa)的可透析白细胞提取物(DLE)对角质层的影响,这些物质是从健康供体的外周血白细胞中制备的(以商业名称 IMMODIN 提供)。在实验中,还研究了 DLE 作为驱虫药阿苯达唑(ABZ)佐剂以及 ABZ 单药治疗的效果。我们表明,DLE 通过显著减少寄生虫数量,增强了 ABZ 的治疗效果,这在两个偏向部位均有体现。此外,DLE 的给药减少了肝脏中的纤维化和脂质过氧化物浓度,从而显示出细胞保护作用。相比之下,在 ABZ 治疗组中发现羟脯氨酸水平升高和幼虫数量增加,这些幼虫被包裹在纤维囊中。为了研究 DLE 是否会影响寄生虫引起的免疫抑制,我们评估了所选免疫参数。结果表明,DLE 给药可增加 ConA 刺激的脾细胞的体外增殖。同样,体外研究证实 DLE 改善了 T 淋巴细胞的低反应性,并部分逆转了寄生虫排泄-分泌产物的抑制作用。此外,流式细胞术分析显示,在接受 DLE+ABZ 治疗的感染小鼠的脾脏和腹腔中,T 辅助和 NK 细胞数量增加。我们还发现,TGF-β1 和 IL-17 的血清水平以及与 Th1/Th2 免疫相关的细胞因子发生了强烈下调。这些结果表明,IMMODIN 可作为原发性驱虫治疗的合适佐剂。

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