HAART 治疗 SIVmac239 感染恒河猴血浆细胞因子与疾病指征的相关性分析
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中国医学科学院医学实验动物研究所,北京协和医学院比较医学中心,卫健委人类疾病比较医学重点实验室,国家中医药管理局人类疾病动物模型三级实验室,新发再发传染病动物模型研究北京市重点实验室,北京 100021

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R-33

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Plasma cytokine levels in SIVmac239-infected rhesus monkeys following HAART treatment and correlation with disease characteristics
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Comparative Medicine Center, Peking Union Medical College(PUMC)&Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS);Key Laboratory of Human Diseases Comparative Medicine, Ministry of Health; Key Laboratory of Human Diseases Animal Models, State administration of Traditional Chinese medicine, Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Beijing 100021, China

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    摘要:

    检测 SIVmac239(猴免疫缺陷病毒)感染恒河猴血浆细胞因子的浓度并分析其与疾病特征的相关性。 方法 SIVmac239 慢性感染的中国恒河猴,给予为期 147 d 的 HAART (高效抗逆转录病毒治疗)。测定血浆病毒载量及细胞因子浓度,检测外周血 T 淋巴细胞亚群变化,并分析血浆细胞因子和疾病特征的相关性。 结果 HAART 治疗期间 SIVmac239 感染的恒河猴血浆病毒载量降低到检测限以下。大部分细胞因子的浓度在感染后增高并在 HAART 治疗期间持续升高。在停止 HAART 治疗后,IL-1β、IL-6、IL-10、TGF-β1 和 IL-2 浓度稍有下降,但仍明显高于感染前。 TNF-α、IFN-α、IFN-γ 则持续增高。只有 IP-10 在 HAART 治疗期间浓度出现了下降 IL-6、IL-1β 和 TGF-β1 与血浆病毒载量呈负相关,IP-10 与血浆病毒载量呈正相关。结论 建立感染和 HAART 治疗中多数细胞因子均升高,停药以后多数细胞因子浓度降低但仍高于正常水平。 IL-6、TGF-β1、IP-10 这三种细胞因子无论变 化趋势还是与疾病特征的相关性都与临床相符合。

    Abstract:

    Objective We examined the expression level of plasma cytokines in SIVmac239-infected rhesus monkeys before and during antiviral treatment and assessed correlations with disease characteristics. Methods The SIVmac239 virus was administered intravenously to healthy Chinese rhesus monkeys, which were then treated with HAART (Highly active antiretroviral therapy) as an AIDS treatment model. Flow cytometry was used to detect CD4+T cell counts in peripheral blood, and Luminex was used to detect plasma cytokines. Results After HAART treatment, the plasma viral load of SIVmac239-infected rhesus monkeys decreased below the detection limit, and the CD4+ T cell count and CD4+ / CD8+ ratio recovered to pre-infection levels. Expression of all cytokines detected after infection, except IL-8, was elevated. After HAART treatment, except for a decrease in IP-10 expression levels, IL-8 remained unchanged and other cytokine levels continued to rise. After stopping drug treatment, levels of pro-inflammatory factors TNF-α, antiviral factors IFN-γ and IFN-α, and the expression of chemokine MCP-1 decreased. The pro-inflammatory factor IL-6 and the anti-inflammatory factor TGF-siowere most strongly correlated with plasma viral load. Conclusions Most cytokines were elevated after infection and HAART treatment, and expression of most cytokines decreased after stopping the drug, although they remained higher than normal. Levels of IL-6, TGF-β1, and IP-10 cytokines are consistent with clinical manifestations regardless of changing trends or correlations with disease characteristics.

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田 龙,童 玲,丛 喆,陈 霆,薛 婧,魏 强. HAART 治疗 SIVmac239 感染恒河猴血浆细胞因子与疾病指征的相关性分析[J].中国比较医学杂志,2020,30(5):21~26.

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  • 收稿日期:2019-11-29
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  • 在线发布日期: 2020-06-19
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