Inhibition of kainic acid induced expression of interleukin-1 beta and interleukin-1 receptor antagonist mRNA in the rat brain by NMDA receptor antagonists

Brain Res Mol Brain Res. 2000 Dec 28;85(1-2):103-13. doi: 10.1016/s0169-328x(00)00251-5.


The cytokines interleukin-1 beta (IL-1 beta) and IL-1 receptor antagonist (IL-1ra) are rapidly induced in response to excitotoxic and ischemic brain damage. The aim of the present study was to investigate the influence of a non-competitive (dizocilpine maleate, MK-801) and a competitive ((R)-CPP) NMDA receptor antagonist on the transient cytokine expression in the rat brain induced by systemic kainic acid administration. Peripheral administration of kainic acid (10 mg/kg, i.p.) results in a transient expression of IL-1 beta and IL-1ra mRNA, mainly in microglia, in regions showing neurodegeneration such as the hippocampus, thalamus, amygdala, and certain cortical regions. In addition, a few neurons expressing IL-1ra mRNA were observed in the piriform cortex and amygdala following kainic acid injection. Administration of MK-801 (i.p.) 1 h prior to kainic acid injection reduced cytokine expression in all of these regions. MK-801 at 3.0 mg/kg decreased the IL-1 beta mRNA expression, blocked or decreased the IL-1ra mRNA expression, depending on the brain region. MK-801 at 5.0 mg/kg abolished IL-1ra mRNA expression in all of the regions, whereas the IL-1 beta mRNA expression was decreased or blocked, depending on the brain region, or the time point investigated. Peripheral administration of (R)-CPP (15 mg/kg, i.p.) 15 min prior to the kainic acid injection abolished the IL-1 beta mRNA expression. The IL-1ra mRNA expression was abolished in all regions except for a few neurons in the piriform cortex. The finding that NMDA receptor antagonists inhibit the IL-1 beta and IL-1ra mRNA synthesis induced by kainic acid suggests that NMDA receptor activation may be involved in triggering cytokine synthesis following excitotoxic brain damage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Dizocilpine Maleate / pharmacology
  • Epilepsies, Myoclonic / chemically induced
  • Epilepsies, Myoclonic / drug therapy
  • Epilepsies, Myoclonic / physiopathology
  • Excitatory Amino Acid Agonists / pharmacology*
  • Excitatory Amino Acid Antagonists / pharmacology
  • Gene Expression / drug effects
  • In Situ Hybridization
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1 / genetics*
  • Kainic Acid / pharmacology*
  • Male
  • Microglia / drug effects
  • Microglia / physiology
  • Nerve Degeneration / chemically induced
  • Nerve Degeneration / drug therapy
  • Nerve Degeneration / physiopathology
  • Piperazines / pharmacology
  • RNA, Messenger / analysis
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, N-Methyl-D-Aspartate / agonists
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors*
  • Sialoglycoproteins / genetics*


  • Excitatory Amino Acid Agonists
  • Excitatory Amino Acid Antagonists
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1
  • Piperazines
  • RNA, Messenger
  • Receptors, N-Methyl-D-Aspartate
  • Sialoglycoproteins
  • Dizocilpine Maleate
  • 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid
  • Kainic Acid