IL-1 receptor antagonist prevents apoptosis and caspase-3 activation afterspinal cord injury

One of the consequences of cytokine-orchestrated inflammation after CNS tra uma is apoptosis. Our hypothesis is that cell death in the spinal cord afte r injury results in part from increased synthesis and release of IL-1 beta. Using a ribonuclease protection assay, we demonstrated that there is incre ased transient expression of IL-1 beta mRNA and, by using IL-1 beta protein ELISA assay, that there are increased IL-1 beta protein levels in the cont used rat spinal cord, initially localized to the impact region of the spina l cord (segment T8). Using an ELISA cell death assay, we showed that there is apoptosis in the spinal cord 72 h after injury, a finding that was confi rmed by measuring caspase-3 activity, which also significantly increased at the site of injury 72 h after trauma. Treatment of the contused spinal cor d at the site of injury with the IL-1 receptor antagonist (rmIL-1ra, 750 ng /mL) for 72 h using an osmotic minipump completely abolished the increases in contusion-induced apoptosis and caspase-3 activity.