ArticleNature cardiovascular research2025
IL6 genetic perturbation mimicking IL-6 inhibition is associated with lower cardiometabolic risk.
Article in Nature cardiovascular research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 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
13 citing papers in PubMed.
- Interleukin-6 as an Oral-Vascular Inflammatory Bridge: Integrating CXCL10 and Haptoglobin 2-2 into a Potential Model of Periodontitis-Associated Cardiovascular Risk.International journal of molecular sciences · 2026Review
- Recombinant shingles vaccination and the risk of cardiovascular events.Nature medicine · 2026Article
- Proteogenomics in human populations.Nature reviews. Genetics · 2026Review
- Mendelian Randomization Reveals Interleukin-6 Receptor-Lipoprotein(a) Interplay With Independent Cardiovascular Risk Reductions.JACC. Basic to translational science · 2026Article
- Interplay Between Interleukin-6 Receptor and Lipoprotein(a) in the Causal Association With Cardiovascular Disease.JACC. Basic to translational science · 2026Article
- The Immediate Impact of Infarct Size on the Systemic Inflammatory Response: IL-6 as Central Mediator Identified through Biomarker and Proteomic Profiling.Journal of cardiovascular translational research · 2026Article
- Clonal Hematopoiesis and Risk of Stroke: Evidence From Over 800 000 Individuals Across 3 Cohorts.Stroke · 2026Article
- Cytokines as Key Drivers of Pathological Root Resorption: Integrating Molecular Mechanisms, Genetic Determinants, and Biomarker-Based Insights.Biomedicines · 2026Review
- Anti-Inflammatory Therapies in Acute Coronary Syndromes-A Review of Immunological, Genetic, and Clinical Challenges for Precision Medicine.Journal of clinical medicine · 2026Review
- Integrating genetic data with biological insight: A practical guide to cis-Mendelian randomization.American journal of human genetics · 2026Review
- Interleukin‑6 and ischemic stroke: From mechanisms to clinical prospects (Review).Molecular medicine reports · 2026Review
- Targeting GPR68 Alleviates Inflammation and Lipid Accumulation in Metabolic Dysfunction-Associated Steatohepatitis.Biology · 2026Article
- Operationalizing Chronic Inflammation: An Endotype-to-Care Framework for Precision and Equity.Clinics and practice · 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
6 authors.
Funding
Abstract
Human genetics supports a causal involvement of IL-6 signaling in atherosclerotic cardiovascular disease, prompting the clinical development of anti-IL-6 therapies. Genetic evidence has historically focused on IL6R missense variants, but emerging cardiovascular treatments target IL-6, not its receptor, questioning the translatability of genetic findings. Here we develop a genetic instrument for IL-6 signaling downregulation comprising IL6 locus variants that mimic the effects of the anti-IL-6 antibody ziltivekimab and use it to predict the effects of IL-6 inhibition on cardiometabolic and safety endpoints. Similar to IL6R, we found that genetically downregulated IL-6 signaling via IL6 perturbation is associated with lower lifetime risks of coronary artery disease, peripheral artery disease and ischemic atherosclerotic stroke in individuals of European and East Asian ancestry. Unlike IL6R missense variants linked to bacterial infections, the IL6 instrument was associated with lower risk of pneumonia hospitalization. Our data suggest that IL-6 inhibition can reduce cardiovascular risk without major unexpected safety concerns.
Indexed as
Identifiers
What Socratic 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 Socratic graph.