Timing-Dependent Cleavage of Interleukin-1 Receptor Antagonist by Alteplase Impairs Neuroprotection in Ischemic Stroke - PubMed
5 hours ago
- #tPA
- #neuroprotection
- #ischemic stroke
- Inflammation significantly contributes to neuronal damage in ischemic stroke, with IL-1 being a key mediator.
- IL-1Ra (IL-1 receptor antagonist) inhibits IL-1 signaling, reducing inflammation in preclinical and clinical stroke studies.
- A phase II trial (SCIL-STROKE) found no overall functional benefit from IL-1Ra, possibly due to interaction with tPA.
- Retrospective analysis showed a 35.8% reduction in plasma IL-1Ra in patients cotreated with tPA, suggesting degradation.
- Biochemical assays confirmed IL-1Ra cleavage by plasmin.
- Preclinical studies showed no negative interactions when IL-1Ra was given after tPA, but worsened outcomes when given during thrombolysis.
- Acute cotreatment of IL-1Ra and tPA reduced tissue perfusion and increased leukocyte infiltration and neutrophil extracellular traps.
- Findings suggest tPA may interfere with other neuroprotective treatments, raising broader concerns.