ArticleJournal of neuroinflammation2025
Inhibition of IL-6 trans-signaling promotes post-stroke functional recovery in a sex and dose-dependent manner.
Article in Journal of neuroinflammation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Favorable Systemic Immune-Inflammation Status Enhances the Neuroprotective Effects of Butylphthalide in Ischemic Stroke: A Post Hoc Analysis of BAST Trial.CNS neuroscience & therapeutics · 2026Trial
- Effect of IL-6 receptor inhibition on infarct volume after endovascular treatment for ischaemic stroke: a phase 2, randomised, placebo-controlled trial.EBioMedicine · 2026Trial
- Efficacy and Safety of Electroacupuncture Combined with Agomelatine Tablets Therapy in Treating Insomnia After Stroke.Journal of molecular neuroscience : MN · 2025Trial
- Targeting interleukin-6 trans-signaling to improve post-stroke inflammation: A precision immunotherapy perspective.Neural regeneration research · 2026Article
- Taraxerol Alleviates Cerebral Ischemia-Reperfusion Induced Inflammation and Ferroptosis via Regulating AKT/NF-κB Pathway.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Interleukin‑6 and ischemic stroke: From mechanisms to clinical prospects (Review).Molecular medicine reports · 2026Review
- Role of Interleukin-6 in Atherothrombosis and Myocardial Infarction.Current atherosclerosis reports · 2026Review
- Serum interleukin-6 as a neuroinflammatory biomarker across the spectrum of neurological disorders: a large-scale retrospective cohort study of 6,465 individuals.Frontiers in immunology · 2026Observational
- Clinical Use of Interleukin-6 Blockade in Neuroimmunological Disorders.Noro psikiyatri arsivi · 2026Review
- Beyond Reperfusion: Adjunctive Therapies Targeting Inflammation, Edema, and Blood-Brain Barrier Dysfunction in Ischemic Stroke.Cerebrovascular diseases (Basel, Switzerland) · 2026Review
- Soluble gp130 inhibits Th17 polarization in neutrophilic asthma by blocking IL-6Frontiers in immunology · 2026Article
- The synergistic role of viral infection and immune response in the pathogenesis of facial palsy.Journal of neurovirology · 2025Review
- The Role of IL-6 in Ischemic Stroke.Biomolecules · 2025Review
- The role of inflammation in Ischemic stroke: from biomarker to treatment.Frontiers in immunology · 2025Review
- Soluble Glycoprotein 130Fc Reduces Controlled Cortical Impact-Induced Cognitive Deficits in Rats.Neurotrauma reports · 2025Article
- Immune-mediated blood-brain barrier disruption after ischemic stroke: mechanisms and therapeutic targets.Frontiers in immunology · 2025Review
- Peripheral and Central Administration of Soluble Glycoprotein 130 Improves Cognitive Outcomes Following Controlled Cortical Impact in Male Mice.Neurotrauma reportsArticle
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
introductionElevated circulating IL-6 levels are associated with poorer outcomes after stroke, and increased serum IL-6 levels are linked to a higher risk of stroke. IL-6 binds to soluble IL-6 receptors (sIL-6R) and subsequently to ubiquitously expressed gp130, initiating proinflammatory trans-signaling. This study tested the hypothesis that inhibiting IL-6 trans-signaling by administering soluble (s) gp130 improves long-term functional outcomes in young mice after stroke.
methodsRecombinant mouse gp130Fc chimera (sgp130) was administered one hour after middle cerebral artery occlusion (MCAO) followed by twice-weekly administration for 2 weeks in mice (8-15 weeks old). Behavioral assessments were done on days 7 and 28 post-MCAO for chronic studies. Flow cytometry was performed on days 3 (blood) and 7 (spleen and brain) to assess IL-6, mIL-6R, and phosphorylated STAT3 expression.
resultsImproved long-term functional outcomes were observed in male, but not female mice. To investigate the differential response in females, ELISA analyses revealed that plasma IL-6 levels increased in both sexes after MCAO, with a more pronounced induction in females. Additionally, circulating sIL-6R levels were significantly higher in females compared to males (p < 0.05) at 24 h post-MCAO. Administering a higher dose of sgp130 (1 mg/kg) to females improved long-term functional outcomes, suggesting that a higher dose is needed to inhibit IL-6 trans-signaling in females effectively. Mechanistically, sgp130 treatment reduced phosphorylated STAT3 expression in brain F4/80 macrophages and increased the expression of mIL-6R on splenic immune cells at day 7 post-MCAO in both sexes.
conclusionThese findings demonstrate that inhibition of IL-6 trans-signaling with gp130Fc improves long-term functional outcomes in both male and female mice, albeit in a dose-dependent manner. This study provides novel insights into potential therapeutic strategies targeting IL-6 signaling pathways following stroke.
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