Abstract Number: Esoc2026lb125 Interleukin-6 Receptor Blockade Reduces Neutrophil Extracellular Traps and Protects the Blood-brain Barrier in Ischemic Stroke
Year: 2026
Type: conference-abstract
Abstract: Background and aims Although the Stroke Preclinical Assessment Network (SPAN) reported neutral effects of tocilizumab in rodent stroke models, this does not fully exclude the translational potential of IL-6R inhibition, as tocilizumab is a humanized antibody that does not bind the murine IL-6 receptor. We aim to use a species-matched anti-mouse IL-6R antibody (15A7) to evaluate the efficacy, optimal dose, and underlying mechanisms of IL-6R blockade in ischemic stroke. Methods Transient middle cerebral artery occlusion was induced in mice, followed by intravenous administration of 15A7 (25, 50, or 75 mg/kg) 30 min after ischemia. Infarct volume and neurological deficits were evaluated to determine the lowest effective dose. BBB disruption was assessed by Evans blue extravasation, brain water content, tight-junction protein expression (ZO-1, occludin, claudin-5), and MMP-9 levels. Neutrophil infiltration and NETs formation were examined by immunofluorescence and western blotting. Clinically, serum citH3, MPO-DNA, and occludin were measured using serum samples from 108 stroke patients receiving tocilizumab or placebo. Results 15A7 at 50 and 75 mg/kg comparably reduced infarct volume and improved neurological outcomes; therefore, 50 mg/kg was selected for subsequent experiments. At this dose, 15A7 reduced BBB leakage and cerebral edema, restored tight-junction proteins, decreased MMP-9 expression, and suppressed neutrophil infiltration and NETs formation. Clinically, tocilizumab-treated patients exhibited lower serum citH3, MPO-DNA, and occludin levels. NETs markers correlated with occludin and largely mediated the treatment effect. Conclusions IL-6R blockade could reduce infarct volume and improve neurological function, by preserving BBB integrity and reducing NETs. Conflict of interest
Source: European Stroke Journal
Authors: Mingde Fang, Xuehong Chu, Mingtong Fang, Xunming Ji, Jing Lan, Chuanjie Wu
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,400
OpenAlex ID: W7160447168
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