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Upregulated monocytic expression of CXC chemokine ligand 10 (CXCL-10) and its relationship with serum interleukin-6 levels in the syndrome of frailty
Open accessAbstract
Frailty is an important geriatric syndrome that predicts disability and mortality. Substantial evidence suggests inflammation marked by elevated IL-6 levels as a key pathophysiologic factor that contributes to frailty. CXCL-10, a potent pro-inflammatory chemokine, has increased levels with age and is implicated in several inflammatory conditions. To better understand molecular mechanisms of inflammation activation in frailty, we evaluated monocytic expression of CXCL-10 and other inflammatory pathway genes by pathway-specific gene array analysis and quantitative RT-PCR. Frailty status was determined by the validated criteria. Sixteen pairs of community-dwelling frail and age-, race-, and sex-matched non-frail participants (mean age 83 years, range 72-94) completed the study. Here we report that frail participants had higher CXCL-10 expression levels than matched non-frail controls (1.05+/-0.88 versus 0.53+/-0.39, p=0.04). CXCL-10 expression correlated with IL-6 levels only in frail participants (Spearman correlation coefficient r=0.52, p=0.03). Furthermore, frailty-associated CXCL-10 upregulation was highly correlated with IL-6 elevation, both measured by frail-over-non-frail ratios (r=0.93, p<0.0001). These findings suggest upregulated monocytic expression of CXCL-10 as an important molecular mechanism that contributes to inflammation activation in frail older adults. Therapeutic implications include potential development of CXCL-10-based interventional strategies for the prevention and treatment of frailty in older adults.
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“There is evidence that inflammation has a key role in the pathophysiology of frailty through an abnormal, low-grade inflammatory response that is hyper-responsive to stimuli and that persists for a prolonged period following removal of the initial inflammatory stimulus (19, 52-57).”
From Frailty in elderly people (2013) · cites this paper as [57]
In the citing paper
“A range of inflammatory cytokines have been independently associated with frailty including interleukin-6 (IL-6), C-reactive protein (CRP), tumour necrosis factor-α (TNFα) and CXC chemokine ligand-10 (CXCL-10), a potent pro-inflammatory mediator (52, 54-58).”
From Frailty in elderly people (2013) · cites this paper as [57]
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Metadata
- Authors
- Qu, T., Yang, H., Walston, J. D., Fedarko, N. S., & Leng, S. X.
- Affiliations
- Johns Hopkins University (US)
- Corresponding author
- Leng, Sean X.
- Venue
- Cytokine
- Publisher
- Elsevier BV
- Published
- 2009-06
- Volume
- 46
- Issue
- 3
- Pages
- 319-324
- ISSN
- 1043-4666 (ISSN-L)
- PMC
- PMC3159181
- OpenAlex
- W2016068403
- Cited by
- 117
- References
- 33
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 9 · 2023: 5 · 2022: 20 · 2021: 7 · 2020: 11 · 2019: 8 · 2018: 3 · 2017: 13 · 2016: 5 · 2015: 5 · 2014: 4 · 2013: 8 · 2012: 1
- FWCI
- 3.56
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Cytokine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (R21AG024235, K23AG028963)
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Frailty in Older Adults
- Health Sciences › Medicine › Physiology (medical) › Nutrition and Health in Aging
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- frailty, CXCL10, interleukin-6, inflammation, older adults, geriatric syndromes, chemokines, frailty biomarkers
- MeSH terms
- Adult, Aged, Aged, 80 and over, Female, Humans, Monocytes, Syndrome, Interleukin-6, Up-Regulation, Frail Elderly, Gene Expression Profiling, Microarray Analysis, Chemokine CXCL10
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