IL-1RA injected intra-cisterna magna confers extended prophylaxis against lipopolysaccharide-induced neuroinflammatory and sickness responses

J Neuroimmunol. 2012 Nov 15;252(1-2):33-9. doi: 10.1016/j.jneuroim.2012.07.010. Epub 2012 Aug 4.

Abstract

IL-1RA has been used intra-cerebrally to ameliorate neuroinflammatory responses. The present study explored the possibility that the bioactivity of IL-1RA administered intra-cerebrally may be prolonged in the CNS. hIL-1RA was detected in hippocampus from 2h to 14d post-ICM treatment. hIL-1RA ameliorated both the hippocampal cytokine (TNFα and NFκBIα) and sickness response to peripheral LPS administered 4d after hIL-1RA. Four days post treatment, hIL-1RA reduced the basal expression of IL-1R1, Iba-1, MHCII, and TLR4 and blunted the microglial IL-1β and IL-6 response to LPS ex vivo. IL-1RA might be administered prophylactically to prevent the neuroinflammatory effects of trauma.

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Cisterna Magna / drug effects*
  • Cisterna Magna / immunology
  • Cisterna Magna / pathology
  • Encephalitis / immunology
  • Encephalitis / pathology
  • Encephalitis / prevention & control*
  • Enzyme-Linked Immunosorbent Assay
  • Interleukin 1 Receptor Antagonist Protein / administration & dosage*
  • Lipopolysaccharides / immunology
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Interleukin 1 Receptor Antagonist Protein
  • Lipopolysaccharides