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

Plasma cytokine levels in SIVmac239-infected rhesus monkeys following HAART treatment and correlation with disease characteristics

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。

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.