Interleukin-18 induces expression and release of cytokines from murine glial cells: Interactions with interleukin-1β

Rachel D. Wheeler, David Brough, Rosalind A. Le Feuvre, Kiyoshi Takeda, Yoichiro Iwakura, Giamal N. Luheshi, Nancy J. Rothwell

Research output: Contribution to journalArticlepeer-review


Interleukin (IL)-18, a member of the IL-1 cytokine family, is an important mediator of peripheral inflammation and host defence responses. IL-1 is a key proinflammatory cytokine in the brain, but the role of IL-18 in the CNS is not yet clear. The objective of this study was to investigate the actions of IL-18 on mouse glial cells. IL-18 induced intracellular expression of IL-1α and proIL-1β, and release of IL-6 from mixed glia. Treatment of lipopolysaccharide-primed microglia with adenosine triphosphate (ATP), an endogenous secondary stimulus, induced IL-1β and IL-18 release. Although deletion of the IL-18 gene did not affect IL-1β expression or release in this experimental paradigm, IL-1β knockout microglia released significantly less IL-18 compared to wild-type microglia. In addition, ATP induced release of mature IL-1β from IL-18-primed microglia. These data suggest that IL-18 may contribute to inflammatory responses in the brain, and demonstrate that, in spite of several common features, IL-18 and IL-1β differ in their regulation and actions.
Original languageEnglish
Pages (from-to)1412-1420
Number of pages8
JournalJournal of neurochemistry
Issue number6
Publication statusPublished - Jun 2003


  • ATP
  • Caspase-1
  • Glia
  • IL-1β
  • IL-18

Research Beacons, Institutes and Platforms

  • Dementia@Manchester
  • Manchester Institute of Biotechnology


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