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Published on: September 22, 2012
Hematoma Interleukin-1 Receptor Antagonist Concentrations Predict Long-Term Outcome in Acute Human Intracerebral
Adrian R Parry-Jones1,2, Blessing Nyakutsikwa3, Michael H Askenase4
1Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
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;100:345-360.
