What question did this study set out to answer?

To evaluate the connection between hematoma cytokine levels and patient outcomes following intracerebral hemorrhage.

May 6, 2026Open Access

Hematoma Interleukin‐1 Receptor Antagonist Concentrations Predict Long‐Term Outcome in Acute Human Intracerebral Hemorrhage

Key Points

To evaluate the connection between hematoma cytokine levels and patient outcomes following intracerebral hemorrhage.
Evaluated cytokine concentrations from hematoma fluid and plasma of participants
Utilized multiple regression models to correlate cytokines with modified Rankin scale scores
Compared cytokine levels by treatment group (surgery vs medical)
Analyzed gene expression in monocyte/macrophages and neutrophils from a subset of participants
High hematoma IL-1 receptor antagonist concentrations predicted good outcomes at one year
Mean hematoma IL-6 levels were also linked to improved outcomes
Hematoma IL-1β was positively correlated with plasma C-reactive protein levels
Cytokine concentrations showed significant associations with the modified Rankin scale scores

Abstract

OBJECTIVES: The interleukin (IL)-1, IL-6, and C-reactive protein (CRP) pathway is central to the immune response after intracerebral hemorrhage (ICH). We tested for associations between hematoma and plasma cytokine concentrations and patient outcomes in Minimally Invasive Surgery Plus Rt-PA for ICH Evacuation Phase III (MISTIE III) participants. METHODS: Inflammation after minimally invasive evacuation of ICH (INFLAME)-ICH was a sub-study nested in MISTIE III. Daily hematoma fluid was collected from surgical patients and peripheral blood for all patients. Multiple regression models compared hematoma cytokine concentrations to the modified Rankin scale (mRS) score at 1 year. Correlations between hematoma and plasma cytokine concentrations were tested. We compared plasma cytokines in patients randomized to surgery (vs medical). Gene expression in monocyte/macrophages and neutrophils were compared in a subset of participants. RESULTS: A total of 89 patients were recruited (47 surgical, 42 medical). Mean hematoma IL-1 receptor antagonist (IL-1Ra) (odds ratio OR: 5.92; 95% confidence interval CI: 1.08-32.54; n = 38) and mean hematoma IL-6 (OR: 3.23; 95% CI: 1.33-7.81; n = 45) were independently associated with good outcome (mRS, 0-3) at 1 year. Higher hematoma IL-1β was associated with higher plasma CRP (β-coefficient: 21.0; 95% CI: 4.4-37.5; n = 117 paired samples). No differences were seen in plasma IL-6, CRP and IL-1Ra in patients by treatment group. IL1B, IL6, and IL1RN transcripts in monocyte/macrophages correlated with respective protein concentrations in hematoma fluid. INTERPRETATION: Hematomal IL-1Ra within a week of ICH is independently associated with a good outcome at 1 year, supporting further investigation of IL-1Ra in ICH. IL-6 is independently associated with a good outcome at 1 year, which might suggest a role in enhancing repair and recovery. ANN NEUROL 2026.

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