IL-6 was independently associated with unfavorable outcomes in patients undergoing endovascular therapy for acute ischemic stroke, with postoperative infarct volume growth partially mediating the effect of IL-6 on clinical outcomes.
Key Findings
Results
Elevated IL-6 levels measured on postoperative day 1 were independently associated with unfavorable 90-day functional outcomes after endovascular therapy.
Unfavorable outcome was defined as a modified Rankin Scale score of 3-5 at the 90-day follow-up.
On multivariate analysis, IL-6 had an odds ratio of 1.02 (95% confidence interval 1.01-1.03) for unfavorable outcome.
Of 105 patients included, 51 (approximately 49%) experienced unfavorable outcomes.
IL-6 was measured on postoperative day 1 following endovascular therapy.
Results
Infarct volume growth partially mediated the relationship between elevated IL-6 levels and unfavorable clinical outcomes.
Mediation analysis was employed to assess the indirect pathway from IL-6 through infarct growth to clinical outcome.
The mediation was partial, meaning IL-6 also had a direct effect on outcomes independent of infarct volume growth.
Infarct volume was evaluated using head CT on postoperative day 7.
Infarct growth was independently associated with unfavorable outcomes on both univariate and multivariate analyses.
Results
Higher baseline NIHSS scores, elevated fasting blood glucose, and infarct growth were all independently associated with unfavorable outcomes in addition to IL-6.
Univariate analysis identified elevated IL-6, higher baseline National Institutes of Health Stroke Scale (NIHSS) scores at admission, increased fasting blood glucose levels, and infarct growth as significantly associated with unfavorable outcomes.
All four factors remained independently associated with unfavorable outcomes after multivariate adjustment.
The study population consisted of 105 patients from the EVTRNA (Circulating Non-coding RNA in Acute Ischemic Stroke with Endovascular Treatment) trial.
All patients underwent pre-endovascular therapy multimodal MRI prior to treatment.
Methods
The study utilized a retrospective analysis of the EVTRNA trial, including patients with acute large vessel occlusion stroke who underwent endovascular therapy with specific imaging and laboratory criteria.
Inclusion required pre-endovascular therapy multimodal MRI, postoperative day 1 inflammatory factor testing, and postoperative day 7 head CT for infarct volume evaluation.
A total of 105 patients met inclusion criteria.
The study examined peripheral inflammatory factors as potential mediators between endovascular therapy and clinical outcomes.
Regression analysis and mediation analysis were the primary statistical approaches used.
What This Means
This research suggests that a protein involved in inflammation, called interleukin-6 (IL-6), measured in the blood the day after a stroke procedure called endovascular therapy (a treatment that removes blood clots from brain arteries), is linked to worse recovery three months later. The study looked at 105 stroke patients and found that those with higher IL-6 levels were more likely to have significant disability at 90 days. Higher blood sugar, more severe stroke symptoms at admission, and larger growth of the damaged brain area over the first week were also associated with worse outcomes.
Importantly, the study found that IL-6 does not only directly worsen outcomes — part of its harmful effect appears to work through causing the area of brain damage (the infarct) to expand in the days following the procedure. This 'mediation' relationship means that inflammation may contribute to ongoing brain injury even after the blocked artery has been reopened. However, since the mediation was only partial, IL-6 also appears to harm recovery through other mechanisms not captured by infarct growth alone.
This research suggests that monitoring inflammatory markers like IL-6 after endovascular stroke treatment could help identify patients at higher risk of poor recovery. It also raises the possibility that targeting inflammation after stroke treatment might help limit brain damage and improve outcomes, though further research would be needed to test whether reducing IL-6 activity actually benefits patients.
Li S, Zhang S, Ji L, Qu Y, Huang Z, Gao J, et al.. (2026). Serum IL-6 and functional outcome after endovascular therapy: the mediating role of infarct volume growth in acute ischemic stroke.. Frontiers in immunology. https://doi.org/10.3389/fimmu.2026.1800891