Interleukin-1 is a cytokine implicated in the initiation of proinflammatory activities in a number of central nervous system diseases. The activities of IL-1 are regulated, in part, by a specific receptor antagonist, IL-1ra. In this study we assessed the effect of cytokines on IL-1β and IL-1ra mRNA and protein expression by human fetal glia. In microglia, both LPS and IL-1α were potent inducers of IL-1β, but only LPS co-induced IL-Ira. In contrast, IL-4 and IFNβ did not induce IL-1β production, but were potent inducers of IL-1ra and markedly down-regulated both LPS and IL-1α induced IL-1β production. In addition, when given together with LPS, IL-4 and IFNβ enhanced the production of IL-1ra. IL-10, TGFβ and IL-6 did not induce IL-1β, but showed variable induction of IL-1ra. IL-10 and TGFβ inhibited IL-1β expression induced by LPS and IL-1α, respectively. IL-1α/β did not affect the production of IL-1ra by any of the cytokines tested. Interestingly, IFNγ markedly inhibited both LPS and IL-1α induced IL-1β as well as LPS and IFNβ induced IL-1ra. This effect was not due to a generalized inhibition of transcription since LPS induction of TNFα was unaffected by IFNγ. Human fetal astrocytes could not be induced to express either IL-1α or IL-1ra. These results suggest that the production of IL-1ra by IFNβ and IL-4 contribute to the down-regulatory effect of these cytokines on inflammation in the CNS, but that IFNγ may have either pro-or anti-inflammatory activity depending upon the nature of the other cytokines present in the inflammatory microenvironment.
|Original language||English (US)|
|State||Published - Mar 20 1998|
ASJC Scopus subject areas
- Molecular Biology