INTERLEUKIN-1 RECEPTOR ANTAGONIST INHIBITS NEURONAL DAMAGE CAUSED BY FLUID PERCUSSION INJURY IN THE RAT

Increased expression of the cytokine interleukin-1 (IL-1) has been obs erved in rodent and human brain after injury, and IL-1 has been implic ated in ischaemic and excitotoxic brain damage in the rat. These data suggest that neurodegeneration caused by brain injury may be mediated by local IL-1 production and action. This hypothesis was tested by stu dying the effects of central injection of recombinant human interleuki n-1 receptor antagonist (rhIL-1ra) on brain damage (assessed histologi cally, H and E stain) induced by fluid percussion trauma in the rat. I njection of rhIL-1ra (10 mu g, i.c.v.) 15 min and 2, 4, 6, 8, 24 and 4 8 h after injury significantly reduced, by 44%, the extent of damage m easured 3 days later. Similar protection was observed in animals kille d 7 days after injury. Delayed administration of rhIL-1ra (4, 6, 8, 24 and 48 h) after injury also significantly reduced (by 28%) neuronal d amage. These data indicate that endogenous IL-1 mediates damage caused by traumatic brain injury and that rhIL-1ra offers significant protec tion even when treatment is-delayed.