Cytokine effects on glutamate uptake by human astrocytes

Glutamate uptake by astrocytes has been postulated to play a neuroprotective role during brain inflammation. Using primary human fetal astrocyte cultures, we investigated the influence of selected cytokines on glutamate uptake activity. Interleukin (IL)-1 beta and tumor necrosis factor-tr dose-dependently inhibited astrocyte glutamate uptake, whereas interferon (IFN)-gamma alone stimulated this activity. The nitric oxide synthase inhibiter, N-G-monomethyl-L-arginine, blocked IL-1 beta-mediated inhibition of glutamate uptake, suggesting involvement of nitric oxide in the effect of IL-1 beta. IL-1 receptor antagonist protein totally reversed the inhibitory effect of cytokines, suggesting a critical role of IL-1 beta. The anti-inflammatory cytokine IFN-beta blocked cytokine (IL-1 beta plus IFN-gamma)-induced inhibition of glutamate uptake with a corresponding reduction in nitric oxide generation. Taken together, these findings suggest that proinflammatory cytokines inhibit astrocyte glutamate uptake by a mechanism involving nitric oxide, and that IFN-beta may exert a therapeutically beneficial effect by blocking cytokine-induced nitric oxide production in inflammatory diseases of the brain. Copyright (C) 2000 S. Karger AG, Basel.