ArticlePloS one2018
Interleukin-6 inhibition of hERG underlies risk for acquired long QT in cardiac and systemic inflammation.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers, 3 of them syntheses that pooled it.
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Who cites it
105 citing papers in PubMed, 3 syntheses or guidelines pooled it, 138 citations in OpenAlex.
- Considerations for drug interactions on QTc interval in exploratory COVID-19 treatment.Heart rhythm · 2020Guideline
- Considerations for Drug Interactions on QTc Interval in Exploratory COVID-19 Treatment.Journal of the American College of Cardiology · 2020Guideline
- Factors affecting the electrocardiographic QT interval in malaria: A systematic review and meta-analysis of individual patient data.PLoS medicine · 2020Pooled it
- Oxidative Stress and Inflammatory Cytokines as Drivers of Cardiac Remodeling in COPD Patients.Antioxidants (Basel, Switzerland) · 2026Article
- Ventricular arrhythmogenesis in pulmonary hypertension: From right ventricular remodeling to clinical implications.Physiological reports · 2026Review
- The Immune System as a Proarrhythmic Mediator: A Novel Paradigm for the Development of New Antiarrhythmic Therapy.The Canadian journal of cardiology · 2026Review
- Subchronic PAH Exposure Impacts Cardiac Electrophysiology of the Polar Fish, Navaga Cod (Toxics · 2026Article
- Inflammation-Mediated Mechanisms of Arrhythmias After Acute Myocardial Infarction.Reviews in cardiovascular medicine · 2026Review
- Inflammatory Biomarkers and Their Associations with Arrhythmic Burden Following SGLT2-I Treatment in Chronic Heart Failure-A Subanalysis of the ERASe Trial.Journal of clinical medicine · 2026Article
- Systemic Inflammation Is Associated with Resting Premature Atrial and Ventricular Contractions in American Older Adults.The Journal of innovations in cardiac rhythm management · 2026Article
- hERG epitope mimic-decoy peptide corrects autoimmune-long QT syndrome in guinea pigs.Communications medicine · 2026Article
- QT interval prolongation and mortality in sepsis: a retrospective cohort study from the MIMIC-IV database.BMC cardiovascular disorders · 2026Article
- Exploring the link between atherosclerosis indicators and QT interval in type 2 diabetes: a retrospective cross-sectional analysis.Therapeutic advances in endocrinology and metabolism · 2026Article
- Phenotypes in Brugada syndrome with different genotypes triggered by fever or inflammation using gene-edited iPSCs.Stem cell research & therapy · 2025Article
- Sex Hormone Profiles in Patients With Torsades de Pointes Ventricular Tachycardia: A Clinical-Electrophysiological Translational Study.JACC. Clinical electrophysiology · 2025Article
- Systemic Inflammation and Myocardial Repolarization Heterogeneity in Heart Failure and Obstructive Sleep Apnea: Impact on Arrhythmic Risk.Medicina (Kaunas, Lithuania) · 2025Article
- Arrhythmias in Rheumatoid Arthritis: A Call for a Multidisciplinary Team.Life (Basel, Switzerland) · 2025Review
- The Impact of Basal Inflammatory Status on Post-CABG Atrial and Ventricular Ectopy and Remodeling Pathways.Medicina (Kaunas, Lithuania) · 2025Article
- Cardiac alterations induced by Trypanosoma cruzi extracellular vesicles and immune complexes.PLoS neglected tropical diseases · 2025Article
- Proarrhythmic Lipid Inflammatory Mediators: Mechanisms in Obesity Arrhythmias.Journal of cellular physiology · 2025Review
45 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
Abstract
Increased proinflammatory interleukin-6 (IL-6) levels are associated with acquired long QT-syndrome (LQTS) in patients with systemic inflammation, leading to higher risks for life-threatening polymorphic ventricular tachycardia such as Torsades de Pointes. However, the functional and molecular mechanisms of this association are not known. In most cases of acquired LQTS, the target ion channel is the human ether-á-go-go-related gene (hERG) encoding the rapid component of the delayed rectifier K current, IKr, which plays a critical role in cardiac repolarization. Here, we tested the hypothesis that IL-6 may cause QT prolongation by suppressing IKr. Electrophysiological and biochemical assays were used to assess the impact of IL-6 on the functional expression of IKr in HEK293 cells and adult guinea-pig ventricular myocytes (AGPVM). In HEK293 cells, IL-6 alone or in combination with the soluble IL-6 receptor (IL-6R), produced a significant depression of IKr peak and tail current densities. Block of IL-6R or Janus kinase (JAK) reversed the inhibitory effects of IL-6 on IKr. In AGPVM, IL-6 prolonged action potential duration (APD) which was further prolonged in the presence of IL-6R. Similar to heterologous cells, IL-6 reduced endogenous guinea pig ERG channel mRNA and protein expression. The data are first to demonstrate that IL-6 inhibition of IKr and the resulting prolongation of APD is mediated via IL-6R and JAK pathway activation and forms the basis for the observed clinical QT interval prolongation. These novel findings may guide the development of targeted anti-arrhythmic therapeutic interventions in patients with LQTS and inflammatory disorders.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.