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外周炎性细胞因子作为阿尔茨海默病和轻度认知障碍的生物标志物

Peripheral inflammatory cytokines as biomarkers in Alzheimer's disease and mild cognitive impairment.

作者信息

Guerreiro Rita João, Santana Isabel, Brás José Miguel, Santiago Beatriz, Paiva Artur, Oliveira Catarina

机构信息

Center for Neuroscience and Cell Biology, Faculty of Medicine, Coimbra University, Coimbra, Portugal.

出版信息

Neurodegener Dis. 2007;4(6):406-12. doi: 10.1159/000107700. Epub 2007 Oct 9.

Abstract

BACKGROUND

Several lines of evidence in the literature have shown that inflammation is involved in the pathogenesis of Alzheimer's disease (AD). However, the results from the evaluation of serum inflammatory markers in AD patients have been controversial.

OBJECTIVE

To determine if any differences exist in the monocytic secretion pattern of IL-1beta, IL-6, IL-12 and TNF-alpha from mild cognitive impairment (MCI) and AD patients, when compared with healthy age-matched controls.

METHODS

To evaluate the percentage of peripheral monocytes secreting IL-1beta, IL-6, IL-12 and TNF-alpha along with the relative levels of these proteins, a cytofluorimetric analysis was conducted under basal conditions and after lipopolysaccharide-induced cell activation.

RESULTS

We found, in AD and MCI patients, a significant raise in the percentage of monocytes producing the studied cytokines (under basal conditions and after the exposure to an inflammatory stimulus), as well as a decreased competence of these cells to respond to inflammatory challenges, when compared with controls.

CONCLUSIONS

These results agree with a persistent inflammatory status in AD, reinforcing the hypothesis of a progressive impairment of the immune response in this disorder and suggesting that monocytes may be good targets to study the progression from MCI to AD.

摘要

背景

文献中的多条证据表明,炎症参与了阿尔茨海默病(AD)的发病机制。然而,对AD患者血清炎症标志物评估的结果一直存在争议。

目的

确定与年龄匹配的健康对照相比,轻度认知障碍(MCI)和AD患者单核细胞分泌白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、白细胞介素-12(IL-12)和肿瘤坏死因子-α(TNF-α)的模式是否存在差异。

方法

为了评估分泌IL-1β、IL-6、IL-12和TNF-α的外周单核细胞百分比以及这些蛋白质的相对水平,在基础条件下和脂多糖诱导的细胞活化后进行细胞荧光分析。

结果

我们发现,与对照组相比,AD和MCI患者中产生所研究细胞因子的单核细胞百分比显著升高(在基础条件下和暴露于炎症刺激后),并且这些细胞对炎症刺激的反应能力下降。

结论

这些结果与AD中持续的炎症状态一致,强化了该疾病免疫反应进行性受损的假设,并表明单核细胞可能是研究从MCI进展到AD的良好靶点。

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