Cited by 119Frailty in Older AdultsNutrition and Health in AgingGenetics, Aging, and Longevity in Model Organisms

Upregulated monocytic expression of CXC chemokine ligand 10 (CXCL-10) and its relationship with serum interleukin-6 levels in the syndrome of frailty

Open access
Qu, Tao, Yang, Huanle, Walston, Jeremy D., Fedarko, Neal S., Leng, Sean X.·2009·Cytokine

Abstract

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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Crossref · 10.1016/j.cyto.2009.02.015

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  • Inflammation appears central to frailty via an abnormal low-grade state that overreacts to stimuli and remains active long after the trigger is gone.

    “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]

  • Several inflammatory markers-IL-6, CRP, TNFα and CXCL-10 among them-have each been independently linked to frailty.

    “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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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)
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
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 › 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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