Circulating Muramyl Dipeptide Is Negatively Associated with Interleukin-10 in the Frail Elderly
Circulating Muramyl Dipeptide Is Negatively Associated with Interleukin-10 in the Frail Elderly
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DOI：
10.1007/s10753-014-0030-z
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发表时间：
2015-02-01
期刊：
影响因子：
5.1
通讯作者：
Bowdish, Dawn M. E.
中科院分区：
文献类型：
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作者：
Verschoor, Chris P.;Naidoo, Avee;Bowdish, Dawn M. E.
血清细胞因子（免疫激活和慢性炎症的标志）水平升高通常与年龄有关，是老年人全因死亡率的一个重要危险因素。这种现象与患有炎症性疾病和慢性病毒感染（如人类免疫缺陷病毒（HIV））的个体所表现出的情况非常相似。虽然细胞因子随年龄增长而慢性升高的原因尚不清楚，但对于慢性疾病和病毒感染，循环细菌产物和其他模式识别受体（PRR）配体的作用已被提出。鉴于此，我们试图研究135名高龄、体弱老年人的循环细胞因子(肿瘤坏死因子（TNF）、干扰素- γ （ifn - γ)、白细胞介素(IL)-1 β、IL-6、IL-8、IL-10、IL-12）水平是否与血浆脂多糖（LPS）、muramyl二肽（MDP）、16S核糖体DNA、总游离DNA和宿主来源的线粒体DNA水平相关。经过多次测试调整后，未观察到流通产品与供者年龄、性别或合并症之间的关联。然而，MDP与IL-10呈显著负相关。考虑到IL-10的抗炎特性，与强效炎症激动剂（如MDP）的负相关关系并不令人惊讶，这表明循环MDP在年龄相关免疫激活的传播中可能起作用。
Elevated levels of serum cytokines, a marker of immune activation and chronic inflammation, are commonly associated with age and are a significant risk factor for all-cause mortality in the elderly. This phenomenon is very similar to that exhibited by individuals with diseases of inflammatory etiology and chronic viral infections such as human immunodeficiency virus (HIV). Although the origin of chronically elevated cytokines with age is unknown, for chronic diseases and viral infections, a role for circulating bacterial products and other pattern recognition receptor (PRR) ligands has been suggested. Given this, we sought to examine whether the levels of circulating cytokines (tumour necrosis factor (TNF), interferon-gamma (IFN-gamma), interleukin (IL)-1 beta, IL-6, IL-8, IL-10, IL-12) in the advanced-age, frail elderly (n = 135) correlated with plasma levels of lipopolysaccharide (LPS), muramyl dipeptide (MDP), 16S ribosomal DNA, total cell-free DNA and host-derived mitochondrial DNA. After adjusting for multiple testing, no associations between circulating products and donor age, sex or comorbidities were observed. However, a significant negative correlation between MDP and IL-10 was identified. Given the anti-inflammatory nature of IL-10, a negative relationship with a potent inflammatory agonist such as MDP is not surprising and suggests a potential role for circulating MDP in the propagation of age-related immune activation.