Timing-Dependent Cleavage of Interleukin-1 Receptor Antagonist by Alteplase Impairs Neuroprotection in Ischemic Stroke.

Inflammation contributes significantly to neuronal damage in ischemic stroke, with IL (interleukin)-1 being a key mediator. IL-1Ra (IL-1 receptor antagonist) inhibits IL-1 signaling, successfully reducing inflammation in preclinical and clinical stroke studies. However, in the latest phase II trial of IL-1Ra in ischemic stroke (SCIL-STROKE [Subcutaneous Interleukin-1 Receptor Antagonist in Ischemic Stroke]), a secondary mediation analysis uncovered an alternative pathway leading to no overall functional benefit. This was the first IL-1Ra trial where participants (73%) received preceding tPA (tissue-type plasminogen activator), raising the possibility that IL-1Ra and tPA interact negatively in ischemic stroke. We aim to explore this postulated negative interaction.