ArticleNature immunology2022
IL-1 and IL-1ra are key regulators of the inflammatory response to RNA vaccines.
Article in Nature immunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 323 papers.
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Who cites it
323 citing papers in PubMed, 481 citations in OpenAlex.
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- Interleukin-1 receptor antagonist polymorphisms in women receiving epidural analgesia who develop maternal intrapartum fever: a prospective, multicentre Mendelian randomised study.British journal of anaesthesia · 2025Trial
- Shared clinical and immunologic features of mRNA vaccines: preliminary results from a comparative clinical study.Frontiers in immunology · 2025Trial
- Novel lipid nanoparticle in a mRNA cancer vaccine drives tumor control via type I IFNs and effector CD8Molecular therapy. Nucleic acids · 2026Article
- Human trilayer engineered blood vessel reveals influence of fibroblasts on disease progression in model of Hutchinson-Gilford progeria.Science advances · 2026Article
- Elucidate the structural role of helper lipids in modulating hepatic expression following repeated intravenous administration of mRNA-LNPs.Materials today. Bio · 2026Article
- Charge-switching ionizable lipids lower the toxicity of lipid nanoparticles.Nature nanotechnology · 2026Article
- Comparative analysis of clinically approved lipid nanoparticles for intranasal siRNA delivery against SARS-CoV-2.Drug delivery and translational research · 2026Article
- RNA therapeutics: current status and future directions.Signal transduction and targeted therapy · 2026Review
- Spatiotemporal control of STING activation and saRNA delivery decouples humoral and cellular immunity.bioRxiv : the preprint server for biology · 2026Article
- New approach methodologies (NAMs) for preclinical and translational evaluation of mRNA-lipid nanoparticle (LNP) therapeutics.Journal of controlled release : official journal of the Controlled Release Society · 2026Review
- β-Lactam antibiotics trigger mouse TLR2/4- and human TLR2/5-dependent Jarisch-Herxheimer reaction in leptospirosis.bioRxiv : the preprint server for biology · 2026Article
- Systemically delivered mRNA-LNPs transfect primary and secondary liver tumors.Molecular therapy. Nucleic acids · 2026Article
- Advancements of mRNA-lipid nanoparticle links to gene editing and immune responses.Journal, genetic engineering & biotechnology · 2026Review
- mRNA-based tuberculosis vaccines BNT164a1 and BNT164b1 are immunogenic, well tolerated and efficacious in rodent models.Nature immunology · 2026Article
- Self-Cooperative RNA Vaccine Mitigates Dendritic Cell-Mediated Acquired Immune Resistance to Potentiate Cell Therapy for Solid Tumors.Advanced materials (Deerfield Beach, Fla.) · 2026Article
- Defining Composition-Cytokine Relationships Enables the Design of Lipid Nanoparticles with Programmed Immunogenicity.Small (Weinheim an der Bergstrasse, Germany) · 2026Article
- Dual Blockade of LILRB1 and LILRB2 Enhances Antiviral Immune Responses in SIV Infection.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Lipid nanoparticle formulations including stereochemically defined glycomacromolecules for delivery of saRNA.Chemical science · 2026Article
- Next-Generation Nanocarrier Platforms for RNA Vaccines: Advances in Formulation, Stability Engineering, and Translational Manufacturing Challenges.Pharmaceutics · 2026Review
263 more citing papers are in PubMed but not listed here.
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Authors and funding
20 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The use of lipid-formulated RNA vaccines for cancer or COVID-19 is associated with dose-limiting systemic inflammatory responses in humans that were not predicted from preclinical studies. Here, we show that the 'interleukin 1 (IL-1)-interleukin 1 receptor antagonist (IL-1ra)' axis regulates vaccine-mediated systemic inflammation in a host-specific manner. In human immune cells, RNA vaccines induce production of IL-1 cytokines, predominantly IL-1β, which is dependent on both the RNA and lipid formulation. IL-1 in turn triggers the induction of the broad spectrum of pro-inflammatory cytokines (including IL-6). Unlike humans, murine leukocytes respond to RNA vaccines by upregulating anti-inflammatory IL-1ra relative to IL-1 (predominantly IL-1α), protecting mice from cytokine-mediated toxicities at >1,000-fold higher vaccine doses. Thus, the IL-1 pathway plays a key role in triggering RNA vaccine-associated innate signaling, an effect that was unexpectedly amplified by certain lipids used in vaccine formulations incorporating N1-methyl-pseudouridine-modified RNA to reduce activation of Toll-like receptor signaling.
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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.