ArticleThe Journal of clinical investigation2023
IL-6 in the infarcted heart is preferentially formed by fibroblasts and modulated by purinergic signaling.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
41 citing papers in PubMed, 55 citations in OpenAlex.
- The role of hypoxia-inducible factors in myocardial ischaemia-reperfusion injury and cardioprotection.Nature reviews. Cardiology · 2026Review
- The inflammatory/fibrotic axis across organs: myelofibrosis as a model of reversibility.JCI insight · 2026Review
- Cardiac fibroblasts in myocardial injury and heart failure.European heart journal · 2026Review
- Research on Therapeutic Strategy of Inhalable Cell Membrane-Coated Nanodelivery Complexes Mediating Nrf2 Pathway for Ameliorating Pulmonary Fibrosis.ACS applied materials & interfaces · 2026Article
- Admission C-Reactive Protein and Mortality After STEMI: A Retrospective Cohort Study Identifying Subgroup-Specific Risk Thresholds.Journal of clinical medicine · 2026Article
- Microproteins in Human Physiology and Pathology.Biochemistry · 2026Review
- Grape Seed Oil Attenuates Myocardial Fibrosis by Inhibiting the PI3K/AKT Signaling Pathway.Foods (Basel, Switzerland) · 2026Article
- Role of Interleukin-6 in Atherothrombosis and Myocardial Infarction.Current atherosclerosis reports · 2026Review
- Interleukin-6 blockade modulates monocyte recruitment to protect against diastolic dysfunction associated with inflammatory arthritis.Arthritis research & therapy · 2026Article
- Severity and 28-day in-hospital mortality of interleukin-6, neutrophil to lymphocyte ratio, and APACHE II score in patients with sepsis.Frontiers in cellular and infection microbiology · 2026Article
- T cell-derived adenosine regulates fibroblast IL-6 formation via APurinergic signalling · 2025Article
- Interferon gamma signaling drives cardiac metabolic rewiring.bioRxiv : the preprint server for biology · 2025Article
- Differences in inflammation biomarkers between patients with paroxysmal and persistent atrial fibrillation in the femoral vein and coronary sinus blood samples; a cohort study.European heart journal open · 2025Article
- Artesunate Nanoplatform Targets the Serine-MAPK Axis in Cancer-Associated Fibroblasts to Reverse Photothermal Resistance in Triple-Negative Breast Cancer.Advanced materials (Deerfield Beach, Fla.) · 2025Article
- The Role of C-Reactive Protein in Acute Myocardial Infarction: Unmasking Diagnostic, Prognostic, and Therapeutic Insights.Journal of clinical medicine · 2025Review
- A cardiac fibroblast-enriched micropeptide regulates inflammation in ischemia/reperfusion injury.JCI insight · 2025Article
- A novel L-shaped ortho-quinone analog targeting adenosine A2b receptor to inhibit epithelial-mesenchymal transition in colorectal cancer cells.Medical oncology (Northwood, London, England) · 2025Article
- Macrophage-mediated IL-6 signaling drives ryanodine receptor-2 calcium leak in postoperative atrial fibrillation.The Journal of clinical investigation · 2025Article
- A secretome atlas of cardiac fibroblasts from healthy and infarcted mouse hearts.Communications biology · 2025Article
- Interleukin-6: Molecular Mechanisms and Therapeutic Perspectives in Atrial Fibrillation.Current medical science · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Plasma IL-6 is elevated after myocardial infarction (MI) and is associated with increased morbidity and mortality. Which cardiac cell type preferentially contributes to IL-6 expression and how its production is regulated are largely unknown. Here, we studied the cellular source and purinergic regulation of IL-6 formation in a murine MI model. We found that IL-6, measured in various cell types in post-MI hearts at the protein level and by quantitative PCR and RNAscope, was preferentially formed by cardiac fibroblasts (CFs). Single-cell RNA-Seq (scRNA-Seq) in infarcted mouse and human hearts confirmed this finding. We found that adenosine stimulated fibroblast IL-6 formation via the adenosine receptor A2bR in a Gq-dependent manner. CFs highly expressed Adora2b and rapidly degraded extracellular ATP to AMP but lacked CD73. In mice and humans, scRNA-Seq revealed that Adora2B was also mainly expressed by fibroblasts. We assessed global IL-6 production in isolated hearts from mice lacking CD73 on T cells (CD4-CD73-/-), a condition known to be associated with adverse cardiac remodeling. The ischemia-induced release of IL-6 was strongly attenuated in CD4-CD73-/- mice, suggesting adenosine-mediated modulation. Together, these findings demonstrate that post-MI IL-6 was mainly derived from activated CFs and was controlled by T cell-derived adenosine. We show that purinergic metabolic cooperation between CFs and T cells is a mechanism that modulates IL-6 formation by the heart and has therapeutic potential.
Indexed as
Identifiers
What OpenQuestion holds
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.