Dynamic changes in serum IL-6, IL-8, and IL-10 predict the outcome of ICU patients with severe COVID-19

Li, Jia; Liu, Rong; Cui, Rongqiang; Feng, Jiaqi; Jin, Yuebo; Chen, Xiaoxiang; Xu, Renying

doi:10.21037/apm-20-2134

Cited by 53 publications

(64 citation statements)

References 29 publications

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“…Several reports show in particular that high serum levels of not only of the pro-inflammatory IL-6, IL-1b and TNFa but also anti-inflammatory cytokine IL-10 are associated with the severity of the disease and a higher comorbidity index among adults with COVID-19 (38,39,(41)(42)(43)(44)(45)(46)57). Changes in serum IL-6 and IL-10 levels act as a predictive biomarker to determining severe patient COVID-19 (44).…”

Section: Discussionmentioning

confidence: 99%

“…IL-6 and IL-10 are found to predict disease severity ( 38 ). Elevated serum levels of IL-6, IL-10, and tumor necrosis factor alpha (TNFα) in non-survivors have been detected, compared to those in the survivors ( 44 ). Also, a fatal outcome has been observed in patients with severe COVID-19 with kinetic variations in IL-6, IL-8, and IL-10, independently of sex, age, absolute lymphocyte count, direct bilirubin, hypertension, and chronic obstructive pulmonary disease ( 44 ).…”

Section: Introductionmentioning

confidence: 99%

“…Elevated serum levels of IL-6, IL-10, and tumor necrosis factor alpha (TNFα) in non-survivors have been detected, compared to those in the survivors ( 44 ). Also, a fatal outcome has been observed in patients with severe COVID-19 with kinetic variations in IL-6, IL-8, and IL-10, independently of sex, age, absolute lymphocyte count, direct bilirubin, hypertension, and chronic obstructive pulmonary disease ( 44 ). Two meta-analyses on IL-6 and IL-10 circulating levels found a correlation between the disease severity and mortality in COVID-19 patients ( 45 , 46 ).…”

Section: Introductionmentioning

confidence: 99%

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Preliminary Evidence for IL-10-Induced ACE2 mRNA Expression in Lung-Derived and Endothelial Cells: Implications for SARS-Cov-2 ARDS Pathogenesis

et al. 2021

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Angiotensin-converting enzyme 2 (ACE2) is a receptor for the spike protein of SARS-COV-2 that allows viral binding and entry and is expressed on the surface of several pulmonary and non-pulmonary cell types, with induction of a “cytokine storm” upon binding. Other cell types present the receptor and can be infected, including cardiac, renal, intestinal, and endothelial cells. High ACE2 levels protect from inflammation. Despite the relevance of ACE2 levels in COVID-19 pathogenesis, experimental studies to comprehensively address the question of ACE2 regulations are still limited. A relevant observation from the clinic is that, besides the pro-inflammatory cytokines, such as IL-6 and IL-1β, the anti-inflammatory cytokine IL-10 is also elevated in worse prognosis patients. This could represent somehow a “danger signal”, an alarmin from the host organism, given the immuno-regulatory properties of the cytokine. Here, we investigated whether IL-10 could increase ACE2 expression in the lung-derived Calu-3 cell line. We provided preliminary evidence of ACE2 mRNA increase in cells of lung origin in vitro, following IL-10 treatment. Endothelial cell infection by SARS-COV-2 is associated with vasculitis, thromboembolism, and disseminated intravascular coagulation. We confirmed ACE2 expression enhancement by IL-10 treatment also on endothelial cells. The sartans (olmesartan and losartan) showed non-statistically significant ACE2 modulation in Calu-3 and endothelial cells, as compared to untreated control cells. We observed that the antidiabetic biguanide metformin, a putative anti-inflammatory agent, also upregulates ACE2 expression in Calu-3 and endothelial cells. We hypothesized that IL-10 could be a danger signal, and its elevation could possibly represent a feedback mechanism fighting inflammation. Although further confirmatory studies are required, inducing IL-10 upregulation could be clinically relevant in COVID-19-associated acute respiratory distress syndrome (ARDS) and vasculitis, by reinforcing ACE2 levels.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Preliminary Evidence for IL-10-Induced ACE2 mRNA Expression in Lung-Derived and Endothelial Cells: Implications for SARS-Cov-2 ARDS Pathogenesis

et al. 2021

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“…The patients who were admitted to the ICU were also found to have higher plasma levels of IL-2, IL-7, IL-10, GCSF, IP-10, MCP-1, MIP-1α, and TNF-α than non-ICU patients [113]. Interestingly, while many of these cytokines and chemokines were also elevated in SARS and MERS patients, several studies have reported an increase in Th2-related anti-inflammatory cytokines IL-4 and IL-10 [115] in COVID-19 patients [113,[116][117][118][119][120], ascribing a seemingly unique cytokine profile to COVID-19. Even more interesting is that IL-10 levels were increased in severe COVID-19 patients, compared to the mild patients [113,[116][117][118][119][120].…”

Section: Cytokine and Chemokine Response To Sars-cov-2 Infectionmentioning

confidence: 99%

“…Interestingly, while many of these cytokines and chemokines were also elevated in SARS and MERS patients, several studies have reported an increase in Th2-related anti-inflammatory cytokines IL-4 and IL-10 [115] in COVID-19 patients [113,[116][117][118][119][120], ascribing a seemingly unique cytokine profile to COVID-19. Even more interesting is that IL-10 levels were increased in severe COVID-19 patients, compared to the mild patients [113,[116][117][118][119][120]. The induction of overlapping cytokines in SARS-CoV, MERS-CoV, and SARS-CoV-2 infections suggests a possible common immunopathogenic pathway induced by these highly pathogenic hCoVs.…”

Section: Cytokine and Chemokine Response To Sars-cov-2 Infectionmentioning

confidence: 99%

Human Coronaviruses: Counteracting the Damage by Storm

Schoeman

Fielding

2021

Viruses

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Over the past 18 years, three highly pathogenic human (h) coronaviruses (CoVs) have caused severe outbreaks, the most recent causative agent, SARS-CoV-2, being the first to cause a pandemic. Although much progress has been made since the COVID-19 pandemic started, much about SARS-CoV-2 and its disease, COVID-19, is still poorly understood. The highly pathogenic hCoVs differ in some respects, but also share some similarities in clinical presentation, the risk factors associated with severe disease, and the characteristic immunopathology associated with the progression to severe disease. This review aims to highlight these overlapping aspects of the highly pathogenic hCoVs—SARS-CoV, MERS-CoV, and SARS-CoV-2—briefly discussing the importance of an appropriately regulated immune response; how the immune response to these highly pathogenic hCoVs might be dysregulated through interferon (IFN) inhibition, antibody-dependent enhancement (ADE), and long non-coding RNA (lncRNA); and how these could link to the ensuing cytokine storm. The treatment approaches to highly pathogenic hCoV infections are discussed and it is suggested that a greater focus be placed on T-cell vaccines that elicit a cell-mediated immune response, using rapamycin as a potential agent to improve vaccine responses in the elderly and obese, and the potential of stapled peptides as antiviral agents.

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Alzheimer's disease and inflammatory biomarkers positively correlate in plasma in the UK‐ADRC cohort

Foley,

Winder,

Sudduth

et al. 2023

Alzheimer's & Dementia

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INTRODUCTIONProtein‐based plasma assays provide hope for improving accessibility and specificity of molecular diagnostics to diagnose dementia.METHODSPlasma was obtained from participants (N = 837) in our community‐based University of Kentucky Alzheimer's Disease Research Center cohort. We evaluated six Alzheimer's disease (AD)‐ and neurodegeneration‐related (Aβ40, Aβ42, Aβ42/40, p‐tau181, total tau, and NfLight) and five inflammatory biomarkers (TNF𝛼, IL6, IL8, IL10, and GFAP) using the SIMOA‐based protein assay platform. Statistics were performed to assess correlations.RESULTSOur large cohort reflects previous plasma biomarker findings. Relationships between biomarkers to understand AD–inflammatory biomarker correlations showed significant associations between AD and inflammatory biomarkers suggesting peripheral inflammatory interactions with increasing AD pathology. Biomarker associations parsed out by clinical diagnosis (normal, MCI, and dementia) reveal changes in strength of the correlations across the cognitive continuum.DISCUSSIONUnique AD–inflammatory biomarker correlations in a community‐based cohort reveal a new avenue for utilizing plasma‐based biomarkers in the assessment of AD and related dementias.Highlights Large community cohorts studying sex, age, and APOE genotype effects on biomarkers are few. It is unknown how biomarker–biomarker associations vary through aging and dementia. Six AD (Aβ40, Aβ42, Aβ42/40, p‐tau181, total tau, and NfLight) and five inflammatory biomarkers (TNFα, IL6, IL8, IL10, and GFAP) were used to examine associations between biomarkers. Plasma biomarkers suggesting increasing cerebral AD pathology corresponded to increases in peripheral inflammatory markers, both pro‐inflammatory and anti‐inflammatory. Strength of correlations, between pairs of classic AD and inflammatory plasma biomarker, changes throughout cognitive progression to dementia.

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Dynamic changes in serum IL-6, IL-8, and IL-10 predict the outcome of ICU patients with severe COVID-19

Cited by 53 publications

References 29 publications

Preliminary Evidence for IL-10-Induced ACE2 mRNA Expression in Lung-Derived and Endothelial Cells: Implications for SARS-Cov-2 ARDS Pathogenesis

Preliminary Evidence for IL-10-Induced ACE2 mRNA Expression in Lung-Derived and Endothelial Cells: Implications for SARS-Cov-2 ARDS Pathogenesis

Human Coronaviruses: Counteracting the Damage by Storm

Alzheimer's disease and inflammatory biomarkers positively correlate in plasma in the UK‐ADRC cohort

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