Simultaneous Targeting of IL-1-Signaling and IL-6-Trans-Signaling Preserves Human Pulmonary Endothelial Barrier Function During a Cytokine Storm-Brief Report

Article Immunology

Identification of IL-6 Signalling Components as Predictors of Severity and Outcome in COVID-19

Maria Angeles Rodriguez-Hernandez et al.

Summary: IL-6 signaling variables serve as useful tools for early identification and stratification of COVID-19 patients, with significant implications for treatment and clinical decision-making.

FRONTIERS IN IMMUNOLOGY (2022)

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Article Medicine, Research & Experimental

Anakinra restores cellular proteostasis by coupling mitochondrial redox balance to autophagy

Frank L. van de Veerdonk et al.

Summary: It has been discovered that anakinra can improve protein stability issues in patients with cystic fibrosis by promoting autophagy driven by oxidative stress. By modulating oxidative stress and autophagy processes, anakinra not only restores defective proteostasis but also has anti-inflammatory properties.

JOURNAL OF CLINICAL INVESTIGATION (2022)

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Article Medicine, General & Internal

Effect of Tocilizumab vs Usual Care in Adults Hospitalized With COVID-19 and Moderate or Severe Pneumonia A Randomized Clinical Trial

Olivier Hermine et al.

Summary: In this clinical trial of COVID-19 patients with pneumonia requiring oxygen support but not in the ICU, tocilizumab did not reduce WHO-CPS scores below 5 by day 4 but may have reduced the risk of needing noninvasive ventilation, mechanical ventilation, or death by day 14. There was no difference in mortality by day 28. Further studies are needed to confirm these preliminary results.

JAMA INTERNAL MEDICINE (2021)

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Article Medicine, General & Internal

Effect of Tocilizumab vs Standard Care on Clinical Worsening in Patients Hospitalized With COVID-19 Pneumonia A Randomized Clinical Trial

Carlo Salvarani et al.

Summary: This study evaluated the use of tocilizumab in hospitalized COVID-19 pneumonia patients and found no significant benefit compared to standard care. Further randomized clinical trials with blinded, placebo-controlled methods are needed to confirm these results and explore potential applications of tocilizumab in different stages of the disease.

JAMA INTERNAL MEDICINE (2021)

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Article Critical Care Medicine

Effect of anakinra versus usual care in adults in hospital with COVID-19 and mild-to-moderate pneumonia (CORIMUNO-ANA-1): a randomised controlled trial

Xavier Mariette et al.

Summary: The study aimed to determine the effectiveness of anakinra in improving outcomes of patients with mild-to-moderate COVID-19 pneumonia, but the results showed that anakinra did not show improvement in patient outcomes. Further studies are needed to assess the efficacy of anakinra in other selected groups of patients with more severe COVID-19.

LANCET RESPIRATORY MEDICINE (2021)

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Article Medicine, General & Internal

Interleukin-6 Receptor Antagonists in Critically Ill Patients with Covid-19

Anthony C. Gordon et al.

Summary: Interleukin-6 receptor antagonists tocilizumab and sarilumab were found to improve outcomes, including survival, in critically ill patients with Covid-19 receiving organ support in ICUs according to an ongoing international trial. The efficacy of these treatments has been confirmed, with patients benefiting from the therapy.

NEW ENGLAND JOURNAL OF MEDICINE (2021)

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Review Biochemistry & Molecular Biology

Role of Interleukin-6 in Vascular Health and Disease

Paulina Villar-Fincheira et al.

Summary: IL-6 is a pleiotropic cytokine involved in regulating immune responses, with dysregulated activity linked to chronic inflammation and autoimmune conditions like atherosclerosis. However, it can also play beneficial roles in situations like exercise, inducing anti-inflammatory effects and metabolic changes. The dual effects of IL-6 may be explained by complex signaling pathways.

FRONTIERS IN MOLECULAR BIOSCIENCES (2021)

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Article Critical Care Medicine

Effect of anti-interleukin drugs in patients with COVID-19 and signs of cytokine release syndrome (COV-AID): a factorial, randomised, controlled trial

Jozefien Declercq et al.

Summary: In this trial evaluating IL-1 and IL-6 blockade treatment in COVID-19 patients, it did not shorten the time to clinical improvement, and there were no significant differences in mortality rate and incidence of serious adverse events between the groups.

LANCET RESPIRATORY MEDICINE (2021)

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Article Critical Care Medicine

Longitudinal respiratory subphenotypes in patients with COVID-19-related acute respiratory distress syndrome: results from three observational cohorts

Lieuwe D. J. Bos et al.

Summary: This study aimed to identify respiratory subphenotypes of COVID-19-related ARDS using data-driven approaches. While no consistent subphenotypes were identified at baseline, two distinct subphenotypes were found during the first 4 days of invasive mechanical ventilation. These subphenotypes demonstrated differences in patient outcomes, indicating the importance of subtyping in the progression and outcomes of ARDS patients.

LANCET RESPIRATORY MEDICINE (2021)

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Review Medicine, General & Internal

The Effect of Anakinra in Hospitalized Patients with COVID-19: An Updated Systematic Review and Meta-Analysis

Konstantinos G. Kyriakoulis et al.

Summary: Immunomodulatory agent anakinra has shown significant clinical benefits in treating hospitalized patients with COVID-19 and hyperinflammation. A recent systematic review and meta-analysis found that anakinra may have a beneficial role in the treatment of selected COVID-19 patients, although the evidence is mainly based on observational studies.

JOURNAL OF CLINICAL MEDICINE (2021)

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Article Medicine, General & Internal

Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Obbina Abani et al.

LANCET (2021)

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Review Respiratory System

Acute respiratory distress syndrome in COVID-19: possible mechanisms and therapeutic management

Anolin Aslan et al.

Summary: The COVID-19 pandemic is a serious issue in the new era, with a focus on controlling lung diseases such as ARDS and lung failure. Ongoing research is crucial, with current emphasis on managing COVID-19 patients and evaluating treatment strategies for ARDS induced by COVID-19.

PNEUMONIA (2021)

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Review Pharmacology & Pharmacy

COVID-19 and the cardiovascular system: insights into effects and treatments

Joey Chammas et al.

Summary: COVID-19, an acute and highly transmissible infectious disease, poses a global challenge to healthcare systems. The complex pathogenesis of the disease can lead to severe cardiovascular manifestations and mortality, highlighting the importance of effective treatment strategies and a better understanding of the mechanisms involved.

CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY (2021)

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Review Biochemistry & Molecular Biology

Interplay between interleukin-6 signaling and the vascular endothelium in cytokine storms

Sujin Kang et al.

Summary: Interleukin-6 (IL-6) plays a key role in inflammation, and blocking its signaling can help in the treatment of various chronic inflammatory diseases. Tocilizumab, an antibody to the IL-6 receptor, has shown therapeutic potential in conditions like rheumatoid arthritis and juvenile systemic idiopathic arthritis.

EXPERIMENTAL AND MOLECULAR MEDICINE (2021)

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Article Medicine, General & Internal

Association Between Administration of IL-6 Antagonists and Mortality Among Patients Hospitalized for COVID-19 AMeta-analysis

Manu Shankar-Hari et al.

Summary: This study identified 27 clinical trials and found that the use of IL-6 antagonists was associated with lower 28-day all-cause mortality in patients hospitalized for COVID-19 compared to usual care or placebo. Different risk effects were observed between tocilizumab and sarilumab, increasing understanding of the treatment with these drugs.

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION (2021)

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Review Medicine, General & Internal

Acute respiratory distress syndrome

Nuala J. Meyer et al.

Summary: This article summarizes the epidemiology, diagnosis, and treatment of acute respiratory distress syndrome (ARDS), while also discussing the similarities and differences between ARDS caused by COVID-19 and ARDS caused by other factors.

LANCET (2021)

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Article Biochemistry & Molecular Biology

Early treatment of COVID-19 with anakinra guided by soluble urokinase plasminogen receptor plasma levels: a double-blind, randomized controlled phase 3 trial

Evdoxia Kyriazopoulou et al.

Summary: The SAVE-MORE phase 3 study demonstrated the efficacy of anakinra, an IL-1 alpha/beta inhibitor, in patients with COVID-19 and high serum levels of soluble plasminogen activator receptor, showing significant reduction in clinical deterioration and decreased 28-day mortality.

NATURE MEDICINE (2021)

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Editorial Material Biochemistry & Molecular Biology

Calming the cytokine storm in COVID-19

Randy Q. Cron et al.

Summary: Cytokine blockade can improve the survival rate of COVID-19 patients at risk of respiratory failure, with timing and patient selection being crucial factors.

NATURE MEDICINE (2021)

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Letter Medicine, General & Internal

Effectiveness of Tocilizumab in Patients Hospitalized With COVID-19 A Follow-up of the CORIMUNO-TOCI-1 Randomized Clinical Trial

Xavier Mariette et al.

Summary: This follow-up study explores the relationship between survival and C-reactive protein levels in patients hospitalized with COVID-19 who were treated with tocilizumab.

JAMA INTERNAL MEDICINE (2021)

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Review Infectious Diseases

The Safety and Efficacy of Anakinra, an Interleukin-1 Antagonist in Severe Cases of COVID-19: A Systematic Review and Meta-Analysis

Manoj Kumar Reddy Somagutta et al.

Summary: The study found that anakinra is beneficial in reducing mortality in COVID-19 patients and demonstrates a significant effect in reducing the need for mechanical ventilation. However, the evaluation of safety suggests that the differences in thromboembolism risk and liver transaminases elevation between the anakinra group and the control group were not statistically significant.

INFECTION AND CHEMOTHERAPY (2021)

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Article Biochemistry & Molecular Biology

Compensatory increase of VE-cadherin expression through ETS1 regulates endothelial barrier function in response to TNFα

Natalia Colas-Algora et al.

CELLULAR AND MOLECULAR LIFE SCIENCES (2020)

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Article Biochemistry & Molecular Biology

Single-Cell Transcriptome Atlas of Murine Endothelial Cells

Joanna Kalucka et al.

CELL (2020)

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Article Critical Care Medicine

Sepsis-associated acute respiratory distress syndrome in individuals of European ancestry: a genome-wide association study

Beatriz Guillen-Guio et al.

LANCET RESPIRATORY MEDICINE (2020)

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Article Medicine, General & Internal

Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid-19

Maximilian Ackermann et al.

NEW ENGLAND JOURNAL OF MEDICINE (2020)

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Article Medicine, Research & Experimental

Cytokine profile in plasma of severe COVID-19 does not differ from ARDS and sepsis

Jennifer G. Wilson et al.

JCI INSIGHT (2020)

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Letter Medicine, General & Internal

Steroids for sepsis and ARDS: this eternal controversy remains with COVID-19

Jean Carlet et al.

LANCET (2020)

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Article Biochemistry & Molecular Biology

An inflammatory cytokine signature predicts COVID-19 severity and survival

Diane Marie Del Valle et al.

NATURE MEDICINE (2020)

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Letter Biochemistry & Molecular Biology

Scoring cytokine storm by the levels of MCP-3 and IL-8 accurately distinguished COVID-19 patients with high mortality

Liting Chen et al.

SIGNAL TRANSDUCTION AND TARGETED THERAPY (2020)

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Review Biochemistry & Molecular Biology

How many cadherins do human endothelial cells express?

Natalia Colas-Algora et al.

CELLULAR AND MOLECULAR LIFE SCIENCES (2019)

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Article Oncology

CCL2 Is a Vascular Permeability Factor Inducing CCR2-Dependent Endothelial Retraction during Lung Metastasis

Marko Roblek et al.

MOLECULAR CANCER RESEARCH (2019)

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Article Biochemistry & Molecular Biology

Time-Variant SRC Kinase Activation Determines Endothelial Permeability Response

Jennifer E. Klomp et al.

CELL CHEMICAL BIOLOGY (2019)

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Article Cell Biology

Interleukin-6 promotes a sustained loss of endothelial barrier function via Janus kinase-mediated STAT3 phosphorylation and de novo protein synthesis

Hiba Alsaffar et al.

AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY (2018)

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Review Multidisciplinary Sciences

Organotypic vasculature: From descriptive heterogeneity to functional pathophysiology

Hellmut G. Augustin et al.

SCIENCE (2017)

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Article Critical Care Medicine

Interleukin-1 Receptor Blockade Is Associated With Reduced Mortality in Sepsis Patients With Features of Macrophage Activation Syndrome: Reanalysis of a Prior Phase III Trial

Bita Shakoory et al.

CRITICAL CARE MEDICINE (2016)

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Article Medicine, General & Internal

The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)

Mervyn Singer et al.

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION (2016)

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Article Cell Biology

RhoB controls endothelial barrier recovery by inhibiting Rac1 trafficking to the cell border

Beatriz Marcos-Ramiro et al.

JOURNAL OF CELL BIOLOGY (2016)

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Review Respiratory System

The pulmonary endothelium in acute respiratory distress syndrome: insights and therapeutic opportunities

Fraser R. Millar et al.

THORAX (2016)

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Review Hematology

New paradigms in sepsis: from prevention to protection of failing microcirculation

J. Hawiger et al.

JOURNAL OF THROMBOSIS AND HAEMOSTASIS (2015)

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Review Hematology

TNF-induced endothelial barrier disruption: beyond actin and Rho

Beatriz Marcos-Ramiro et al.

THROMBOSIS AND HAEMOSTASIS (2014)

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Article Multidisciplinary Sciences

Electric Cell-substrate Impedance Sensing for the Quantification of Endothelial Proliferation, Barrier Function, and Motility

Robert Szulcek et al.

JOVE-JOURNAL OF VISUALIZED EXPERIMENTS (2014)

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Review Cell Biology

VE-Cadherin and Endothelial Adherens Junctions: Active Guardians of Vascular Integrity

Monica Giannotta et al.

DEVELOPMENTAL CELL (2013)

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Article Hematology

Crosstalk Between Reticular Adherens Junctions and Platelet Endothelial Cell Adhesion Molecule-1 Regulates Endothelial Barrier Function

Laura Fernandez-Martin et al.

ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY (2012)

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Article Biochemistry & Molecular Biology

Endothelial-Derived Angiocrine Signals Induce and Sustain Regenerative Lung Alveolarization

Bi-Sen Ding et al.

CELL (2011)

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Article Critical Care Medicine

Selective blockade of interleukin-6 trans-signaling improves survival in a murine polymicrobial sepsis model

Tanja Barkhausen et al.

CRITICAL CARE MEDICINE (2011)

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Article Cell Biology

Protein 4.1R regulates cell migration and IQGAP1 recruitment to the leading edge

Ana Ruiz-Saenz et al.

JOURNAL OF CELL SCIENCE (2011)

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Article Cell Biology

Broken Barriers: A New Take on Sepsis Pathogenesis

Neil M. Goldenberg et al.

SCIENCE TRANSLATIONAL MEDICINE (2011)

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Article Physiology

Role of protein tyrosine phosphatase SHP2 in barrier function of pulmonary endothelium

K. L. Grinnell et al.

AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY (2010)

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Article Cell Biology

The PI3K p110α isoform regulates endothelial adherens junctions via Pyk2 and Rac1

Robert J. Cain et al.

JOURNAL OF CELL BIOLOGY (2010)

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Article Cell Biology

Transactivation of vascular endothelial growth factor receptor-2 by interleukin-8 (IL-8/CXCL8) is required for IL-8/CXCL8-induced endothelial permeability

Melissa L. Petreaca et al.

MOLECULAR BIOLOGY OF THE CELL (2007)

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Review Pharmacology & Pharmacy

Anakinra: Review of recombinant human interieukin-1 receptor antagonist in the treatment of rheumatoid arthritis

DE Furst

CLINICAL THERAPEUTICS (2004)

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Article Multidisciplinary Sciences

Targeted recycling of PECAM from endothelial surface-connected compartments during diapedesis

Z Mamdouh et al.

NATURE (2003)

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Article Pathology

Regulatory effects of NOS on acute lung inflammatory responses in mice

CL Speyer et al.

AMERICAN JOURNAL OF PATHOLOGY (2003)

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Review Pharmacology & Pharmacy

Cytokine therapeutics for the treatment of sepsis: Why has nothing worked?

DG Remick

CURRENT PHARMACEUTICAL DESIGN (2003)

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Article Biochemistry & Molecular Biology

Characterization of binding sites for chemokines MCP-1 and MIP-1α on human brain microvessels

AV Andjelkovic et al.

JOURNAL OF NEUROCHEMISTRY (2000)

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Review Medicine, General & Internal

Medical progress - The acute respiratory distress syndrome.

LB Ware et al.

NEW ENGLAND JOURNAL OF MEDICINE (2000)

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Simultaneous Targeting of IL-1-Signaling and IL-6-Trans-Signaling Preserves Human Pulmonary Endothelial Barrier Function During a Cytokine Storm-Brief Report

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