Cytokine effects on glutamate uptake by human astrocytes

Neuroimmunomodulation. 2000;7(3):153-9. doi: 10.1159/000026433.


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)-1beta and tumor necrosis factor-alpha dose-dependently inhibited astrocyte glutamate uptake, whereas interferon (IFN)-gamma alone stimulated this activity. The nitric oxide synthase inhibitor, N(G)-monomethyl-L-arginine, blocked IL-1beta-mediated inhibition of glutamate uptake, suggesting involvement of nitric oxide in the effect of IL-1beta. IL-1 receptor antagonist protein totally reversed the inhibitory effect of cytokines, suggesting a critical role of IL-1beta. The anti-inflammatory cytokine IFN-beta blocked cytokine (IL-1beta 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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Astrocytes / metabolism*
  • Biological Transport / drug effects
  • Cells, Cultured
  • Drug Synergism
  • Fetus
  • Glutamic Acid / metabolism*
  • Humans
  • Inflammation
  • Interferon-beta / pharmacology*
  • Interferon-gamma / pharmacology*
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1 / pharmacology*
  • Nitric Oxide / physiology
  • Recombinant Proteins / pharmacology
  • Sialoglycoproteins / pharmacology*
  • Tumor Necrosis Factor-alpha / pharmacology*
  • omega-N-Methylarginine / pharmacology


  • IL1RN protein, human
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1
  • Recombinant Proteins
  • Sialoglycoproteins
  • Tumor Necrosis Factor-alpha
  • omega-N-Methylarginine
  • Nitric Oxide
  • Glutamic Acid
  • Interferon-beta
  • Interferon-gamma