Chronic Low-grade Inflammatory Phenotype (CLIP) and Senescent Immune Dysregulation

Chen, Yiyin; Liu, Sally; Leng, Sean X.

doi:10.1016/j.clinthera.2019.02.001

Cited by 81 publications

(71 citation statements)

References 63 publications

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“…The use of quantitative and phenotypic alterations of T lymphocytes may be helpful as early biomarkers for dementia, but this needs to be further investigated. Earlier studies have reported conflicting results, compounded by the fact that immune changes accompanying normal aging can be confounding factors [31][32][33]. Studies with a larger sample size and validation cohorts are still required for assessing whether CD4+ and CD8+ T-cell subset distributions can be used as robust and early diagnostic markers of AD or other dementia forms.…”

Section: Discussionmentioning

confidence: 99%

Exploratory study on immune phenotypes in Alzheimer’s disease and vascular dementia

D’Angelo

Goldeck

Pawelec

et al. 2020

Euro J of Neurology

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Background and purpose The differentiation of Alzheimer’s disease (AD) dementia from vascular dementia (VaD) and mixed‐type dementia (mixed dementia) requires stepwise analysis and usually occurs late in the disease process. Early diagnosis and therapy monitoring would benefit greatly from the identification of biomarkers of neurodegeneration, especially blood biomarkers. To this end, the aim of the present pilot study was to investigate differences in the distribution of peripheral T‐cell populations in patients with AD compared to VaD and mixed dementia. Methods Flow cytometry was performed on blood samples from 11 patients with AD, six with VaD and six with mixed dementia, as well as 17 healthy control subjects (HCs). CD4+ and CD8+ T cells were typed for expression of CD45, CD27, CD28, CD25, FoxP3, CCR4 and CCR6; the other leukocytes were also assessed. Functionally, immune cell uptake of the β‐amyloid (Aβ) toxic fragment (Aβ1–42) was also evaluated. Results A higher proportion of CD4+CD28− memory T cells and a reciprocal reduction of CD4+CD28+CD27+ naïve T lymphocytes was detected in all patient groups relative to controls. Significantly fewer CD4+CD25+FoxP3 regulatory T cells were present in patients with VaD, and significantly more CCR6+ and CCR4+ CD4+ T cells in those with AD. Higher CCR6+ T‐cell frequencies were also present in patients with mixed dementia, potentially due to the inflammation and immune cell chemoattraction triggered by Aβ. Conclusions The present study was a comprehensive investigation comparing different kinds of dementia, revealing differentially expressed peripheral markers that are potentially useful for early AD, VaD and mixed dementia diagnoses, and that would assist in proper treatments for these disparate diseases. Validation is now required.

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Section: Discussionmentioning

confidence: 99%

Exploratory study on immune phenotypes in Alzheimer’s disease and vascular dementia

D’Angelo

Goldeck

Pawelec

et al. 2020

Euro J of Neurology

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“…The role of systemic inflammation as a key element of functional decline during aging is based on the hypothesis that the aging process is related to a systemic increase in pro-inflammatory mediators from various sources [ 24 , 25 ]. The increase in circulating pro-inflammatory cytokines (IL-6, TNF-alpha, IL-beta) and other inflammatory markers (PCR and white blood cell counts) concentrations have been also associated with frailty syndrome in several studies [ 26 , 27 , 28 , 29 , 30 , 31 ]. Cytokines overproduction such as IL-6, TNF-alpha, IL-8 have been also involved in the PCa pathophysiology [ 32 , 33 , 34 , 35 , 36 , 37 ] and thus inflammation could be common pathophysiological framework for frailty syndrome and ADT treatment in PCa patients.…”

Section: Introductionmentioning

confidence: 99%

Interleukin-6 and Lymphocyte Count Associated and Predicted the Progression of Frailty Syndrome in Prostate Cancer Patients Undergoing Antiandrogen Therapy

Buigues

Navarro-Martínez

Sánchez-Martínez

et al. 2020

Cancers

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Frailty syndrome is a functional state that includes a loss of ability to react to stressors, and is associated with poor outcomes, morbidity and premature mortality. The first line treatment in many men with prostate cancer (PCa) consists of an androgen-deprivation therapy (ADT) which can promote or favor frailty syndrome and ADT may therefore favor the progression of frailty over time. Among the pathophysiological bases of frailty, the presence of chronic low-grade inflammation has been associated with its adverse outcomes, but longitudinal studies are needed to validate these biomarkers. In this study, we prospectively evaluate frailty syndrome and blood inflammatory markers (IL1-beta, IL-6, IL-8, TNF alpha, C reactive protein) and leukocytes were measured at baseline and an average of 1 year later in PCa under ADT. Frailty was defined as having three or more of the following components: low lean mass, weakness, self-reported exhaustion, low activity level, and slow walking speed; prefrailty was defined as having one or two of those components. Multinomial regression analysis showed that among the inflammatory biomarkers, those significantly and repeatedly (baseline and follow-up time points) (p < 0.05) associated with frailty syndrome were high IL-6 levels and low lymphocyte counts in blood. Other biomarkers such as IL-8, monocyte counts and C reactive protein were significantly associated with frailty syndrome (p < 0.05) in cross-sectional analyses, but they do not predict frailty progression at 1 year-follow-up. Receiver operating characteristic curve analysis showed that both lymphocyte counts and IL-6 concentration significantly (p < 0.05) (although moderately) discriminate PCa patients that progressed in the severity of frailty syndrome. IL-6 and lymphocytes count are possible biomarkers, useful for identifying frail patients and predicting the progression of frailty in PCa under ADT. Our study suggests the use of these biomarkers to guide clinical decisions on prostate cancer treatment based on a multidisciplinary approach.

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“…Immune modulation on chronic inflammation, i.e., aforementioned age-related CLIP or inflammaging, has also been proposed as an attractive underlying mechanism. This is because age-related CLIP or inflammaging is known to play an important role in the development of atherosclerosis, coronary artery disease, and stroke ( Chen et al, 2019 ; Elkind, 2009 ; Ferrucci and Fabbri, 2018 ). Acutely, influenza infection can cause local and systemic inflammatory response ( Madjid et al, 2007 ) that can adversely impact plaque stability, leading to plaque rupture and acute cardiovascular events ( Barnett, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

“…This is likely because of the multifaceted immune system remodeling during aging, leading to immune functional decline in older adults, or immunosenescence ( Nikolich-Žugich, 2018 ). The aging immune system also manifests a chronic low-grade inflammatory phenotype (CLIP) or inflammaging that has been implicated in the pathogenesis of almost all age-related chronic conditions including those in the cardiovascular and respiratory systems ( Chen et al, 2019 ; Franceschi et al, 2000 ). This increased vulnerability to respiratory infections is further demonstrated by the ongoing coronavirus disease 2019 (COVID-19) pandemic as older adults suffer disproportionately high rate of severe COVID-19 disease and deaths ( Salje and Tran Kiem, 2020 ; Zhou et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Effects of influenza vaccination on the risk of cardiovascular and respiratory diseases and all-cause mortality

Cheng

Cao

et al. 2020

Ageing Research Reviews

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Highlights Compared to unvaccinated people, influenza-vaccinated people had the risk reduction of 26% for cardiovascular diseases (63 studies), 18% for respiratory diseases (29 studies), and 43% for all-cause mortality (43 studies). Influenza vaccination was associated with reduced risk of stroke, myocardial infarction, acute coronary syndrome (ACS), heart failure, ischemic heart disease (IHD), major adverse cardiovascular events (MACEs), and cardiovascular mortality. There was a statistically significant reduction in pneumonia and respiratory mortality in those who received the influenza vaccination, with relative risks of 0.79 (95% CI = 0.65-0.95) and 0.79 (95% CI = 0.67-0.92), respectively. The protective effects of vaccination were evident in the general adult population and particularly robust in older adults and in those with pre-existing specific diseases.

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Chronic Low-grade Inflammatory Phenotype (CLIP) and Senescent Immune Dysregulation

Cited by 81 publications

References 63 publications

Exploratory study on immune phenotypes in Alzheimer’s disease and vascular dementia

Exploratory study on immune phenotypes in Alzheimer’s disease and vascular dementia

Interleukin-6 and Lymphocyte Count Associated and Predicted the Progression of Frailty Syndrome in Prostate Cancer Patients Undergoing Antiandrogen Therapy

Effects of influenza vaccination on the risk of cardiovascular and respiratory diseases and all-cause mortality

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