Murine microglial cells produce and respond to interleukin-18

J Neurochem. 1999 May;72(5):2215-8. doi: 10.1046/j.1471-4159.1999.0722215.x.


Interleukin (IL)-18 (interferon-gamma-inducing factor or IL-1gamma) belongs structurally to the IL-1 cytokine family and shares biological properties with IL-12. Expression, intracellular signaling, and functional relevance of IL-18 within the CNS are mostly unknown. We show that IL-18 protein is synthesized within mouse brain, preferentially during early postnatal stages, and that microglial cells but not astrocytes are a potential source. IL-18 is produced by cultured microglia on exposure to lipopolysaccharide (LPS). Microglia also express major components of the IL-1/IL-18 receptor system. On IL-18 stimulation, microglial IL-1 receptor-associated kinase (IRAK) can be coprecipitated with tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) but not with IL-1 receptor type I, indicating that IRAK recruits TRAF6 during IL-18 signaling. IL-18 inhibits the LPS-induced release of IL-12 and attenuates that of TNF-alpha, whereas the production of IL-6 and macrophage inflammatory protein-1alpha is only marginally affected. IL-18 may play a role during CNS development and can be produced by activated microglia, thus probably contributing to immune and inflammatory processes in the brain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / metabolism
  • Animals
  • Brain / cytology
  • Brain / metabolism
  • Cells, Cultured
  • Cytokines / metabolism
  • Interleukin-1 Receptor-Associated Kinases
  • Interleukin-18 / metabolism*
  • Interleukin-18 / pharmacology*
  • Lipopolysaccharides / pharmacology
  • Mice
  • Microglia / drug effects*
  • Microglia / metabolism*
  • Protein Kinases / metabolism
  • Proteins / metabolism
  • Recombinant Proteins
  • TNF Receptor-Associated Factor 6


  • Cytokines
  • Interleukin-18
  • Lipopolysaccharides
  • Proteins
  • Recombinant Proteins
  • TNF Receptor-Associated Factor 6
  • Protein Kinases
  • Interleukin-1 Receptor-Associated Kinases