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

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-1alpha and proIL-1beta, and release of IL-6 from mixed glia. Treatment of lipopolysaccharide-primed microglia with adenosine triphosphate (ATP), an endogenous secondary stimulus, induced IL-1beta and IL-18 release. Although deletion of the IL-18 gene did not affect IL-1beta expression or release in this experimental paradigm, IL-1beta knockout microglia released significantly less IL-18 compared to wild-type microglia. In addition, ATP induced release of mature IL-1beta 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-1beta differ in their regulation and actions.