A randomised phase II study of interleukin-1 receptor antagonist in acute stroke patients
Journal of Neurology, Neurosurgery & Psychiatry, 2005•jnnp.bmj.com
Objectives: The cytokine interleukin (IL)-1 mediates ischaemic brain damage in rodents. The
endogenous, highly selective, IL-1 receptor antagonist (IL-1ra) protects against ischaemic
cerebral injury in a range of experimental settings, and IL-1ra causes a marked reduction of
cell death when administered peripherally or at a delay in transient cerebral ischaemia. We
report here the first randomised, double blind, placebo controlled trial of recombinant human
IL-1ra (rhIL-1ra) in patients with acute stroke. Methods: Patients within 6 hours of the onset of …
endogenous, highly selective, IL-1 receptor antagonist (IL-1ra) protects against ischaemic
cerebral injury in a range of experimental settings, and IL-1ra causes a marked reduction of
cell death when administered peripherally or at a delay in transient cerebral ischaemia. We
report here the first randomised, double blind, placebo controlled trial of recombinant human
IL-1ra (rhIL-1ra) in patients with acute stroke. Methods: Patients within 6 hours of the onset of …
Objectives: The cytokine interleukin (IL)-1 mediates ischaemic brain damage in rodents. The endogenous, highly selective, IL-1 receptor antagonist (IL-1ra) protects against ischaemic cerebral injury in a range of experimental settings, and IL-1ra causes a marked reduction of cell death when administered peripherally or at a delay in transient cerebral ischaemia. We report here the first randomised, double blind, placebo controlled trial of recombinant human IL-1ra (rhIL-1ra) in patients with acute stroke.
Methods: Patients within 6 hours of the onset of symptoms of acute stroke were randomised to rhIL-1ra or matching placebo. Test treatment was administered intravenously by a 100 mg loading dose over 60 seconds, followed by a 2 mg/kg/h infusion over 72 h. Adverse events and serious adverse events were recorded for up to 3 months, serial blood samples were collected for biological markers up to 3 months, and 5–7 day brain infarct volume was measured by computed tomography.
Results: No adverse events were attributed to study treatment among 34 patients randomised. Markers of biological activity, including neutrophil and total white cell counts, C reactive protein, and IL-6 concentrations, were lower in rhIL-1ra treated patients. Among patients with cortical infarcts, clinical outcomes at 3 months in the rhIL-1ra treated group were better than in placebo treated.
Conclusions: These data suggest that rhIL-1ra is safe and well tolerated in acute stroke. In addition, rhIL-1ra exhibited biological activity that is relevant to the pathophysiology and clinical outcome of ischaemic stroke. Our findings identify rhIL-1ra as a potential new therapeutic agent for acute stroke.
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