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

IF 7.7 1区医学 Q1 CLINICAL NEUROLOGY

Annals of Neurology Pub Date : 2026-05-03 DOI:10.1002/ana.78237

Adrian R Parry-Jones, Blessing Nyakutsikwa, Michael H Askenase, Matthew Gittins, Mary Newland, Siobhan Crilly, Paul R Kasher, Yvonne Davidson, Federico Roncaroli, Stuart M Allan, Lauren H Sansing, Wendy Ziai, Daniel F Hanley

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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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血肿白细胞介素-1受体拮抗剂浓度预测急性人脑出血的长期预后。

目的：白细胞介素(IL)-1、IL-6和c反应蛋白（CRP）途径是脑出血（ICH）后免疫反应的核心。我们测试了血肿和血浆细胞因子浓度与微创手术加Rt-PA治疗ICH疏散III期（MISTIE III）患者预后之间的关系。方法：脑出血微创引流后的炎症(INFLAME)-ICH是MISTIE III的一项亚研究。每天采集手术患者的血肿液和所有患者的外周血。多元回归模型比较血肿细胞因子浓度与1年修正Rankin量表（mRS）评分。检测血肿与血浆细胞因子浓度的相关性。我们比较了随机手术组（与内科组）患者的血浆细胞因子。在一部分参与者中比较了单核细胞/巨噬细胞和中性粒细胞的基因表达。结果：共纳入89例患者（47例外科，42例内科）。平均血肿IL-1受体拮抗剂（IL-1Ra）（比值比[OR]: 5.92； 95%可信区间[CI]: 1.08-32.54; n = 38）和平均血肿IL-6 （OR: 3.23; 95% CI: 1.33-7.81; n = 45）与1年的良好预后（mRS, 0-3）独立相关。血肿IL-1β升高与血浆CRP升高相关（β系数：21.0;95% CI: 4.4-37.5; n = 117对样本）。两组患者血浆IL-6、CRP、IL-1Ra均无显著差异。单核细胞/巨噬细胞中的IL1B、IL6和IL1RN转录物与血肿液中各自的蛋白浓度相关。结论：脑出血1周内的血液IL-1Ra与1年的良好预后独立相关，支持进一步研究IL-1Ra在脑出血中的作用。IL-6与1年的良好预后独立相关，这可能提示在增强修复和恢复中起作用。Ann neurol 2026。

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来源期刊

Annals of Neurology 医学-临床神经学

CiteScore

18.00

自引率

1.80%

发文量

270

审稿时长

3-8 weeks

期刊介绍： Annals of Neurology publishes original articles with potential for high impact in understanding the pathogenesis, clinical and laboratory features, diagnosis, treatment, outcomes and science underlying diseases of the human nervous system. Articles should ideally be of broad interest to the academic neurological community rather than solely to subspecialists in a particular field. Studies involving experimental model system, including those in cell and organ cultures and animals, of direct translational relevance to the understanding of neurological disease are also encouraged.