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-γ), interleukin (IL)-1β, 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.
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Funding for this study was supported by the Canadian Institutes of Health Research (CIHR) and a Pfizer-Ontario Lung Association award. Work in the Bowdish lab is supported in part by the M.G. DeGroote Institute for Infectious Disease Research (IIDR) and the McMaster Immunology Research Centre (MIRC). Chris Verschoor is funded by the 2013 Canadian Lung Association (Canadian Thoracic Society) postdoctoral fellowship, and Jennie Johnstone is supported by a CIHR fellowship.
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Verschoor, C.P., Naidoo, A., Wallace, J.G. et al. Circulating Muramyl Dipeptide Is Negatively Associated with Interleukin-10 in the Frail Elderly. Inflammation 38, 272–277 (2015). https://doi.org/10.1007/s10753-014-0030-z
- chronic immune activation
- cell-free DNA
- mitochondrial DNA