ArticleThe European respiratory journal2020
Cellular sources of interleukin-6 and associations with clinical phenotypes and outcomes in pulmonary arterial hypertension.
Article in The European respiratory journal, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 75 citations in OpenAlex.
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- Endothelial USP2a-METTL16 loop potentiates IL-6 signaling via mCell death and differentiation · 2026Article
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- The Potential Role of Calcium Channels in Pulmonary Hypertension.BioMed research international · 2026Review
- Research advances in connective tissue disease-associated pulmonary arterial hypertension with an emphasis on the Chinese population.Frontiers in medicine · 2026Review
- Advances in Novel Therapeutic Strategies for Pulmonary Arterial Hypertension.Canadian respiratory journal · 2026Review
- Transpulmonary Proteome Gradients Identify Pathways Involved in Pulmonary Vascular Disease Due To Heart Failure.Circulation. Heart failure · 2025Observational
- Current landscape for connective tissue disease associated-pulmonary arterial hypertension: a focus on right ventricular adaptation and failure.Future cardiology · 2025Review
- CTRP7 as a molecular biomarker associating with responsiveness to pulmonary vasodilators: insights from human and animal studies in pulmonary arterial hypertension.Cardiovascular research · 2025Article
- New insights into pulmonary arterial hypertension: interaction between PANoptosis and perivascular inflammatory responses.Apoptosis : an international journal on programmed cell death · 2025Review
- Cellular Communication Network Protein 2 in the Right Ventricle of Pulmonary Arterial Hypertension.Pulmonary circulation · 2025Article
- Molecular and pathophysiological intersections between arterial hypertension, pulmonary inflammation and diabetes mellitus.Frontiers in pharmacology · 2025Review
- Equivalency of Multiple Biomarkers to Clinical Pulmonary Arterial Hypertension Survival Risk Models.Chest · 2024Article
- Research Progress on Using Nanoparticles to Enhance the Efficacy of Drug Therapy for Chronic Mountain Sickness.Pharmaceutics · 2024Review
- Immunotherapy for Pulmonary Arterial Hypertension: From the Pathogenesis to Clinical Management.International journal of molecular sciences · 2024Review
- Emerging connectivity of programmed cell death pathways and pulmonary vascular remodelling during pulmonary hypertension.Journal of cellular and molecular medicine · 2024Review
- Urolithin A Protects against Hypoxia-Induced Pulmonary Hypertension by Inhibiting Pulmonary Arterial Smooth Muscle Cell Pyroptosis via AMPK/NF-κB/NLRP3 Signaling.International journal of molecular sciences · 2024Article
- Causal effect of interleukin (IL)-6 on blood pressure and hypertension: A mendelian randomization study.Immunogenetics · 2024Article
- AFrontiers in cardiovascular medicine · 2024Article
Corrections and comments
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- Erratum issued
Authors and funding
17 authors at 5 institutions in 1 country.
Funding
Abstract
The pro-inflammatory cytokine interleukin (IL)-6 has been associated with outcomes in small pulmonary arterial hypertension (PAH) cohorts composed largely of patients with severe idiopathic PAH (IPAH). It is unclear whether IL-6 is a marker of critical illness or a mechanistic biomarker of pulmonary vascular remodelling. We hypothesised that IL-6 is produced by pulmonary vascular cells and sought to explore IL-6 associations with phenotypes and outcomes across diverse subtypes in a large PAH cohort.IL-6 protein and gene expression levels were measured in cultured pulmonary artery smooth muscle cells (PASMCs) and endothelial cells (PAECs) from PAH patients and healthy controls. Serum IL-6 was measured in 2017 well-characterised PAH subjects representing each PAH subgroup. Relationships between IL-6 levels, clinical variables, and mortality were analysed using regression models.Significantly higher IL-6 protein and gene expression levels were produced by PASMCs than by PAECs in PAH (p<0.001), while there was no difference in IL-6 between cell types in controls. Serum IL-6 was highest in PAH related to portal hypertension and connective tissue diseases (CTD-PAH). In multivariable modelling, serum IL-6 was associated with survival in the overall cohort (hazard ratio 1.22, 95% CI 1.08-1.38; p<0.01) and in IPAH, but not in CTD-PAH. IL-6 remained associated with survival in low-risk subgroups of subjects with mild disease.IL-6 is released from PASMCs, and circulating IL-6 is associated with specific clinical phenotypes and outcomes in various PAH subgroups, including subjects with less severe disease. IL-6 is a mechanistic biomarker, and thus a potential therapeutic target, in certain PAH subgroups.
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