在 BALB/c 小鼠急性利什曼原虫感染的致病性过程中，地芬诺酯可减少 CD8+ 淋巴细胞和 IL-4，并提高 IgG2a/IgG1 比率。

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cytokine Pub Date : 2024-11-02 DOI:10.1016/j.cyto.2024.156792

Pourandokht Mousavian , Vahid Mashayekhi Goyonlo , Mohammad Javanbakht , Mahmoud Reza Jafari , Hamidreza Moosavian , Monovar Afzal Aghaei , Mohammadreza Malekzadeh

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引用次数: 0

摘要

背景：不同的免疫细胞和细胞因子在控制或促进利什曼原虫细胞内生长中的确切作用仍是一个有争议的话题。本研究的目的是研究二苯基丙酮（DCP）对 BALB/c 小鼠急性利什曼原虫感染致病性的细胞变化和细胞介导免疫中相关细胞因子的影响。将小鼠随机分为三组，每组 15 只：（1）对照组，不做任何处理。(2）丙酮组：每周将丙酮局部涂抹在皮肤病变处；(3) DCP 组：在小鼠皮损处局部涂抹二氯丙醇，浓度不断增加，以诱发局部过敏。第八周结束时对小鼠进行随访，然后测定小鼠的宏观变化、组织病理学、免疫学研究和器官寄生虫负荷：结果：与其他组相比，DCP 组的溃疡面积和溃疡部位及脾脏的寄生虫量明显增加。溃疡部位有深层淋巴组织细胞浸润。总 IgG、IgG1 和 IgG2a 水平以及 IgG2a/IgG1 比率和 CD8+ 淋巴细胞内的 IFN-gamma 均明显升高。DCP组的IL4和T CD8+淋巴细胞明显降低。所有组的 IgG2a/IgG1 比值均大于 1：我们的研究结果表明，DCP 减少了 CD8+ 淋巴细胞和 IL-4 的产生。结论：我们的研究结果表明，DCP 减少了 CD8+ 淋巴细胞和 IL-4 的产生，尽管 IgG2a/IgG1 比率增加，但感染小鼠的寄生虫负荷和炎症严重程度却增加了。这些结果表明，CD8+淋巴细胞与 Th1 淋巴细胞一起在控制小鼠急性利什曼病感染中发挥着关键作用。

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Diphencyprone reduces the CD8+ lymphocytes and IL-4 and enhences IgG2a/IgG1 ratio in pathogenicity of acute leishmania major infection in BALB/c mice

Background

The exact role of different immune cells and cytokines in control or promotion of intracellular growth of leishmania has still remained a controversial topic. The aim of the present study was to study effects of cellular changes and relevant cytokines in cell mediated immunity by diphencyprone (DCP) in pathogenicity of acute L.major infection in BALB/c mice.

Methods

45 healthy female BALB/c mice were injected with L. major promastigotes under the base of tail. The mice were randomly divided to three groups of 15 mice: (1) control group without any treatment. (2) acetone group: Acetone was applied topically on the cutaneous lesions weekly and (3) DCP group: DCP was applied topically on the cutaneous lesions with increasing concentrations to induce local allergy. The mice were followed by the end of eighth week, and then macroscopic changes, histopathology, immunology studies, and organ parasite burden were determined.

Results

In DCP group, in comparison to other groups the ulcer size and parasite burden in ulcer site and spleen increased, significantly. There was a deep lymphohistiocytic infiltration in the ulcer site. Total IgG, IgG1, and IgG2a levels as well as IgG2a/IgG1 ratio and intracellular IFN-gamma in CD8⁺ lymphocytes were significantly higher. IL4 and T CD8⁺ lymphocytes were significantly lower in DCP group. The IgG2a/IgG1 ratio was more than 1 in all groups.

Conclusion

Our findings demonstrated that DCP reduced the CD8⁺ lymphocytes and IL-4 production. In spite of increased IgG2a/IgG1 ratio, the parasite burden and inflammation severity increased in infected mice. The results can show the pivotal role of CD8⁺ lymphocytes in conjunction with Th1 lymphocytes in the control of acute leishmania infection in mice.

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来源期刊

Cytokine 医学-免疫学

CiteScore

7.60

自引率

2.60%

发文量

262

审稿时长

48 days

期刊介绍： The journal Cytokine has an open access mirror journal Cytokine: X, sharing the same aims and scope, editorial team, submission system and rigorous peer review. * Devoted exclusively to the study of the molecular biology, genetics, biochemistry, immunology, genome-wide association studies, pathobiology, diagnostic and clinical applications of all known interleukins, hematopoietic factors, growth factors, cytotoxins, interferons, new cytokines, and chemokines, Cytokine provides comprehensive coverage of cytokines and their mechanisms of actions, 12 times a year by publishing original high quality refereed scientific papers from prominent investigators in both the academic and industrial sectors. We will publish 3 major types of manuscripts: 1) Original manuscripts describing research results. 2) Basic and clinical reviews describing cytokine actions and regulation. 3) Short commentaries/perspectives on recently published aspects of cytokines, pathogenesis and clinical results.