Arosio Beatrice, Trabattoni Daria, Galimberti Lorenza, Bucciarelli Paolo, Fasano Francesca, Calabresi Carmen, Cazzullo Carlo Lorenzo, Vergani Carlo, Annoni Giorgio, Clerici Mario
Department of Geriatrics, Ospedale Maggiore IRCCS, University of Milano, Milan, Italy.
Neurobiol Aging. 2004 Sep;25(8):1009-15. doi: 10.1016/j.neurobiolaging.2003.10.009.
In the pathogenesis of Alzheimer disease (AD), it has been proposed that the anti-inflammatory interleukins such as IL-10 regulate beta-amyloid-induced microglial inflammatory responses inhibiting the proinflammatory cytokine IL-6. Since the promoters of the IL-10 and IL-6 genes show single nucleotide polymorphisms (SNPs) (IL-10: -1082 G --> A; IL-6: -174 G --> C), we investigated these SNPs and cytokine production by peripheral blood mononuclear cells in 65 AD patients and 65 controls (HC). In AD there was a significant increase of the -1082A IL-10 allele (P=0.009) and a decrease of -1082GG genotype (P=0.019). The frequency of the GG IL-6 genotype in AD was lower and the C allele significantly higher (P <0.005). The co-occurrence of IL-10 A and IL-6 C alleles significantly raised the odds ratio (OR 11.2, confidence interval: CI 1.3-97.3; P <0.05) independently of apolipoprotein E4 (adjusted OR 10.3, CI 1-108; P <0.05). Only amyloid-stimulated IL-10 production differed between the groups (P=0.023). These results raise questions regarding the inflammatory theory in AD, pointing to a pivotal role of IL-10 and IL-6 and a selective alteration in this network.
在阿尔茨海默病（AD）的发病机制中，有人提出抗炎性白细胞介素如IL-10可调节β-淀粉样蛋白诱导的小胶质细胞炎症反应，抑制促炎性细胞因子IL-6。由于IL-10和IL-6基因的启动子存在单核苷酸多态性（SNPs）（IL-10：-1082 G→A；IL-6：-174 G→C），我们研究了65例AD患者和65例对照（HC）外周血单核细胞中的这些SNPs及细胞因子产生情况。在AD患者中，-1082A IL-10等位基因显著增加（P = 0.009），-1082GG基因型减少（P = 0.019）。AD患者中GG IL-6基因型频率较低，C等位基因显著较高（P <0.005）。IL-10 A和IL-6 C等位基因的共出现显著提高了优势比（OR 11.2，置信区间：CI 1.3 - 97.3；P <0.05），且独立于载脂蛋白E4（校正OR 10.3，CI 1 - 108；P <0.05）。仅两组间淀粉样蛋白刺激的IL-10产生存在差异（P = 0.023）。这些结果对AD的炎症理论提出了疑问，指出了IL-10和IL-6的关键作用以及该网络中的选择性改变。
