Abstract 2679: Recombinant Human Interleukin-1 Receptor Antagonist- Anakinra Attenuates The Deterioration Of Motor Function Induced By Spinal Cord Ischemia In Rabbits
Objective: In certain patients, thoracic and thoracoabdominal aortic surgery is complicated by subacute or delayed paraplegia. Pro-inflammatory cytokine interleukin-1β(IL-1β) has been implicated in extensive inflammation and progressive neurodegeneration after ischemia. We investigated the neuroprotective effects of recombinant human IL-1 receptor antagonist (rhIL-1ra)- Anakinra, in a temporal fashion.
Methods: Spinal cord ischemia was induced by aortic cross-clamping in New Zealand White rabbits. The animals were assigned to three groups. Group C (n=17) received saline (0.2ml) and group I (n=17) received rhIL-1ra (200μg/0.2ml) intrathecally just after reperfusion. Group S (n=3) underwent sham operation without aortic occlusion. We assessed the neuroprotective effects of rhIL-1ra by evaluating neurological function, histopathological changes, and in-situ terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL staining). Each evaluation was performed sequentially within 120 hours after reperfusion.
Results: Neurological function was scaled by modified Tarlov score. Group C showed progressive deterioration of motor function which became statistically significant from 48 hours after the onset of reperfusion. In histopathological examination, group C had progressive neurodegeneration, whereas there were fewer evidences of neuronal damages with a higher number of viable neurons (group C vs I; p=0.008, 0.032 and 0.026 at 24, 72, 120 hours, respectively) and low histological injury score (group C vs. group I; p=0.016 and 0.038 at 24, 120 hours, respectively) in group I. TUNEL-positive neurons were also significantly reduced by the administration of rhIL-1ra (group C vs I; p=0.047, p=0.018 at 72, 120 hours, respectively).
Conclusion: Administration of rhIL-1ra attenuates the severity of the motor function after ischemia by reducing both neuronal necrosis and apoptosis. This study suggests that IL-1-targetted anti-cytokine therapy possesses therapeutic potential with regard to neurological injury after thoracic and thoracoabdominal aortic surgery.