肽SCV-07抗小鼠结核的生物活性研究

Andrey Simbirtsev, Alexander Kolobov, Natalia Zabolotnych, Natalia Pigareva, Valentina Konusova, Alexander Kotov, Elena Variouchina, Vladimir Bokovanov, Tatyana Vinogradova, Svetlana Vasilieva, Cynthia Tuthill
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摘要

SCV-07 (γ -谷氨酰色氨酸)是一种新型的免疫调节化合物,已开发并获得专利,用于组合物和免疫调节用途。研究表明,SCV-07在体内和体外均具有广谱的免疫刺激活性。在本研究中,我们研究了SCV-07在牛分枝杆菌-牛病毒8株诱导的实验性结核(TB)小鼠模型中的生物活性。SCV-07治疗剂量分别为0.01、0.1和1 μ g/kg(每日5次注射),与未治疗的对照组和单独异烟肼治疗的对照组相比,肺损伤指数降低。牛分枝杆菌-牛病毒8在脾脏培养中生长下降。细胞因子研究表明,在用SCV-07治疗后的第24天,IL-2的产生恢复到未感染动物的水平。胸腺和脾脏细胞的增殖反应几乎恢复到未感染动物的反应。胸腺和脾脏细胞产生的ifn - γ及其在血清中的循环水平均因SCV-07治疗而增加。同时,相同细胞类型和血清中IL-4的产生降低。这些变化表明SCV-07刺激T辅助细胞向th1样免疫反应的转变。SCV-07治疗还刺激了巨噬细胞的功能,而巨噬细胞的功能因结核感染和异烟肼治疗而降低,并改善了腹腔巨噬细胞的吞噬活性。结果表明,SCV-07治疗增加了抗结核治疗的疗效和免疫应答的强度。因此,SCV-07是一种有前景的结核病综合治疗免疫调节剂。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Biological Activity of Peptide SCV-07 Against Murine Tuberculosis.

SCV-07 (gamma-glutamyl-tryptophan) is a new immunomodulatory compound that was developed and patented both for composition and immunomodulatory use. SCV-07 was shown to have a broad spectrum of immunostimulatory activities both in vitro and in vivo. In the present study we investigated the biological activity of SCV-07 in a murine model of experimental tuberculosis (TB) induced with M. bovis-bovinus 8 strain. Therapy with SCV-07 at doses of 0.01, 0.1, and 1 &mgr;g/kg (5 daily injections) decreased the lung damage index compared to untreated controls and to those treated with isoniazid alone. The growth of M. bovis-bovinus 8 in spleen culture was decreased. Cytokine studies showed that on the 24th day after the treatment with SCV-07 the production of IL-2 was restored to the level seen in uninfected animals. Proliferative responses for both thymic and spleen cells were nearly restored to the responses observed in uninfected animals. IFN-gamma production by both thymic and spleen cells, as well as its circulating levels in serum, was increased by the SCV-07 treatment. Concurrently, IL-4 production was decreased in the same cell types and the serum. These changes suggest that SCV-07 is stimulating a shift of T helper cells to a Th1-like immune response. SCV-07 treatment also stimulated the macrophage functions, which had been decreased by tuberculosis infection and isoniazid therapy, with an improved phagocytosis activity of peritoneal macrophage. The obtained results suggest that SCV-07 treatment increases the efficacy of anti-tuberculosis therapy as well as the strength of the immune response. Thus, SCV-07 is a prospective immunomodulator for a complex therapy of TB.

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