Role of interleukin-7 in acute large vessel occlusion stroke.

Abstract

Emergent large vessel occlusion (ELVO) stroke is a severe ischemic subtype with high morbidity despite mechanical thrombectomy (MT). Current biomarkers inadequately capture the intracranial immune response driving stroke progression. Interleukin-7 (IL-7) is implicated in neuroinflammation but remains understudied in stroke. This study investigates intracranial and systemic IL-7 expression in patients with ELVO stroke, assessing its association with infarct burden and its potential as a prognostic biomarker. Plasma samples were collected from patients with ELVO stroke during MT and from CVD control patients undergoing elective diagnostic cerebral angiography. Systemic and intracranial arterial blood was processed with a proximity extension assay (Olink Proteomics) to quantify IL-7 and other cytokines. Infarct and edema volumes were assessed using MRI or CT at 24 hours post-procedure. Spearman correlation and multivariable linear regression models adjusted for the National Institutes of Health Stroke Scale (NIHSS) score at admission were used to evaluate associations between IL-7 levels (intracranial, systemic, and the difference between compartments) and clinical outcomes. Intracranial IL-7 was independently associated with infarct volume (β=-42 052, P=0.0432; R²=0.232), demonstrating greater overall best fit than systemic IL-7 (P=0.8408) and systemic-intracranial differences (P=0.0857). Intracranial IL-7 was also correlated with infarct volume, edema, and NIHSS score at discharge. Intracranial IL-7 is a significant predictor of infarct burden in ELVO stroke, highlighting its role in localized immune responses. Systemic IL-7 lacked predictive value, suggesting spatially restricted IL-7 signaling within the ischemic environment. IL-7 may serve as a biomarker for stroke severity and a potential therapeutic target.