ArticleProceedings of the National Academy of Sciences of the United States of America2024
Gp130-HIF1α axis-induced vascular damage is prevented by the short-term inhibition of IL-6 receptor signaling.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 11 citations in OpenAlex.
- Effects of moxibustion therapies on immune function in cancer animal models: a systematic review and meta-analysis.Frontiers in immunology · 2026Pooled it
- Adenosine receptor signaling in vascular diseases: from molecular mechanisms to targeted therapeutics.Acta pharmacologica Sinica · 2026Review
- Intravenous placenta-derived mesenchymal stem cells enhance early survival as an adjunct to supportive care in severe burn: a preclinical study.Stem cell research & therapy · 2026Article
- Diabetes Mellitus with Influenza Virus and Subsequent Bacterial Infection: Triple Pathological Interactions and Challenges.International journal of molecular sciences · 2026Review
- Multiple organ dysfunction syndrome: molecular mechanisms and therapeutic strategies.Signal transduction and targeted therapy · 2026Review
- Peripheral inhibition of IL-6 signaling with tocilizumab improves stroke outcomes in aged mice but requires sex-specific dosing.bioRxiv : the preprint server for biology · 2026Article
- Angiogenesis, Angiogenic Factors, and Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS).International journal of urology : official journal of the Japanese Urological Association · 2026Review
- Molecular Interplay between hypertension and dyslipidemia in cardiovascular pathogenesis: toward precision-based therapeutic strategies.Frontiers in cardiovascular medicine · 2026Review
- RIPK3 Protects Against Endothelial Activation and Vascular Permeability in a Mouse Model of Ischemia-Reperfusion Injury.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- Challenges and strategies in clinical applications of CAR-T therapy for autoimmune diseases.Journal of hematology & oncology · 2025Review
- Analysis of serum levels of HIF-1α and IL-6 in patients with acute stanford type a aortic dissection.Journal of cardiothoracic surgery · 2025Article
- Deep insight into cytokine storm: from pathogenesis to treatment.Signal transduction and targeted therapy · 2025Review
- Cardiovascular disease and depression: a bidirectional relationship and its clinical implications.Frontiers in psychiatry · 2025Review
- Natural hydrogen gas and engineered microalgae prevent acute lung injury in sepsis.Materials today. Bio · 2024Article
- Interleukin-6 drives endothelial glycocalyx damage in COVID-19 and bacterial sepsis.Angiogenesis · 2024Observational
- Nonspecific Inhibition of IL6 Family Cytokine Signalling by Soluble gp130.International journal of molecular sciences · 2024Article
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
Protection against endothelial damage is recognized as a frontline approach to preventing the progression of cytokine release syndrome (CRS). Accumulating evidence has demonstrated that interleukin-6 (IL-6) promotes vascular endothelial damage during CRS, although the molecular mechanisms remain to be fully elucidated. Targeting IL-6 receptor signaling delays CRS progression; however, current options are limited by persistent inhibition of the immune system. Here, we show that endothelial IL-6 trans-signaling promoted vascular damage and inflammatory responses via hypoxia-inducible factor-1α (HIF1α)-induced glycolysis. Using pharmacological inhibitors targeting HIF1α activity or mice with the genetic ablation of gp130 in the endothelium, we found that inhibition of IL-6R (IL-6 receptor)-HIF1α signaling in endothelial cells protected against vascular injury caused by septic damage and provided survival benefit in a mouse model of sepsis. In addition, we developed a short half-life anti-IL-6R antibody (silent anti-IL-6R antibody) and found that it was highly effective at augmenting survival for sepsis and severe burn by strengthening the endothelial glycocalyx and reducing cytokine storm, and vascular leakage. Together, our data advance the role of endothelial IL-6 trans-signaling in the progression of CRS and indicate a potential therapeutic approach for burns and sepsis.
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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.