Involvement of interleukin-1 in glial responses to lipopolysaccharide: Endogenous versus exogenous interleukin-1 actions

Interleukin-1β (IL-1β) participates in neuroinflammation and neurodegeneration. Its mechanisms of action are not fully understood, but appear to involve complex interactions between neurons and glia. The objective of this study was to determine the involvement of endogenous IL-1β in inflammatory responses to LPS in cultured mouse glial cells, and compare this to the effects of exogenous IL-1β. Activation of primary mixed glial cultures by incubation with LPS (1 μg/ml, 24 h), caused marked (approximately ten-fold) increases in release of NO, twenty-fold increases in PGE2 and ninety-fold increases of IL-6 release. Incubation with human recombinant IL-1β (100 ng/ml) also stimulated NO and IL-6 release to a similar extent to LPS, but IL-1β (1 or 100 ng/ml) caused only modest increases (approximately seven-fold) in PGE2 release. Co-incubation with IL-1ra inhibited the effects of LPS on NO release (-65%) and IL-6 production (-30%), but failed to reduce PGE2 release. These results indicate that exogenous IL-1β induces release of NO, PGE2 and IL-6 in mixed glial cultures, and that endogenous IL-1β mediates inflammatory actions of LPS on NO and to a lesser extent IL-6, but not on PGE2 release in mixed glial cultures. Indeed endogenous IL-1β appears to inhibit LPS-induced PGE2 release. Copyright (C) 2000 Elsevier Science B.V.