A high plasma concentration of TNF-α is associated with dementia in centenarians
A high plasma concentration of TNF-α is associated with dementia in centenarians
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DOI：
10.1093/gerona/54.7.m357
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发表时间：
1999-07-01
影响因子：
5.1
通讯作者：
Pedersen, BK
中科院分区：
文献类型：
--
作者：
Bruunsgaard, H;Andersen-Ranberg, K;Pedersen, BK
背景炎症机制和免疫激活被认为在老年性疾病如痴呆和动脉粥样硬化的发病机制中起作用。本研究的目的是评估肿瘤坏死因子（TNF）-α的血浆浓度在一个大型队列的百岁老人，并寻找其与认知功能，动脉粥样硬化和一般健康状况的可能关联。此外，我们还研究了TNF-α浓度是否与白细胞亚群的血液浓度或白细胞介素（IL）-6、可溶性TNF受体II（sTNFR-II）（75 kDa）和C-反应蛋白（CRP）的血浆浓度相关。采用ELISA法测定了126名百岁老人、45名81岁的受试者、23名55-65岁的受试者和38名18-30岁的受试者的血浆TNF-α。动脉粥样硬化通过踝臂血压指数进行评估，一般健康状况通过体重指数和诊断数量进行评估。与年轻的对照组相比，126名百岁老人的TNF-α浓度显着增加，并且高浓度的TNF-α与百岁老人的阿尔茨海默病和全身动脉粥样硬化相关。TNF-α浓度与血浆IL-6、sTNFR-II和CRP浓度呈正相关。未发现与白细胞亚群或体重指数增加相关。这项研究表明，即使在表面上健康的受试者中，由促炎细胞因子水平升高所指示的年龄相关的免疫激活可能反映了数十年来发展的年龄相关的病理过程。
Background Inflammatory mechanisms and immune activation have been hypothesized to play a role in the pathogenesis of age-associated diseases such as dementia and atherosclerosis. The purpose of this study was to evaluate the plasma concentration of tumor necrosis factor (TNF)-alpha in a large cohort of centenarians and to look for its possible associations with cognitive function, atherosclerosis, and general health status. Furthermore, we investigated whether the concentration of TNF-alpha was correlated with the blood concentration of leucocyte subsets or the plasma concentrations of interleukin (IL)-6, soluble TNF receptor II (sTNFR-II) (75 kDa) and C-reactive protein (CRP).Methods. Plasma TNF-alpha was measured by ELISA in 126 centenarians, 45 subjects aged 81 years, 23 subjects aged 55-65 years, and 38 subjects aged 18-30 years. Atherosclerosis was evaluated by the ankle-brachial blood pressure index, and general health status was evaluated by the body mass index and the number of diagnoses presentResults. The concentration of TNF-alpha was significantly increased in 126 centenarians compared to younger control groups, and a high concentration of TNF-alpha was associated with both Alzheimer's disease and generalized atherosclerosis in the centenarians. The concentration of TNF-alpha was positively correlated with the concentrations of plasma IL-6, sTNFR-II, and CRP. No associations were found with increased leucocyte subsets or the body mass index.Conclusion. This study demonstrates that, even in apparently healthy subjects, age-associated immune activation indicated by raised levels of pro-inflammatory cytokines may reflect age-associated pathological processes that develop over decades.