Interleukin-1 receptor antagonist inhibits neuronal damage caused by fluid percussion injury in the rat

Brain Res. 1995 Feb 13;671(2):261-6. doi: 10.1016/0006-8993(94)01343-g.


Increased expression of the cytokine interleukin-1 (IL-1) has been observed in rodent and human brain after injury, and IL-1 has been implicated 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 studying the effects of central injection of recombinant human interleukin-1 receptor antagonist (rhIL-1ra) on brain damage (assessed histologically, H and E stain) induced by fluid percussion trauma in the rat. Injection of rhIL-1ra (10 micrograms, i.c.v.) 15 min and 2, 4, 6, 8, 24 and 48 h after injury significantly reduced, by 44%, the extent of damage measured 3 days later. Similar protection was observed in animals killed 7 days after injury. Delayed administration of rhIL-1ra (4, 6, 8, 24 and 48 h) after injury also significantly reduced (by 28%) neuronal damage. These data indicate that endogenous IL-1 mediates damage caused by traumatic brain injury and that rhIL-1ra offers significant protection even when treatment is delayed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Injuries / pathology*
  • Cerebral Cortex / pathology
  • Injections, Intraventricular
  • Interleukin-1 / administration & dosage
  • Interleukin-1 / pharmacology
  • Male
  • Nerve Degeneration / drug effects
  • Neurons / drug effects*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Interleukin-1 / antagonists & inhibitors*
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / pharmacology


  • Interleukin-1
  • Receptors, Interleukin-1
  • Recombinant Proteins