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

We show that IL-1Ra is cleaved by plasmin, and its administration during thrombolysis worsens outcomes poststroke. These studies confirm a negative interaction between the 2 drugs, which can be prevented by tPA preceding IL-1Ra treatment. The findings raise broader concerns about how tPA may interfere with other neuroprotective treatments.