Interleukin-1 modulates GABAergic and glutamatergic function in brain.
Interleukin-1 is a polypeptide cytokine involved in the acute-phase response. We examined the effects of IL-1 on the major inhibitory and excitatory neurotransmitter systems in brain mediated by GABA and glutamate, respectively. IL-1 enhanced the effects of GABA as determined by GABA-dependent chloride uptake at 1 and 10 ng/ml in cortical synaptoneurosomes. This effect was attenuated by pretreatment with the IL-1 receptor antagonist. Neither IL-6 nor TNF was effective in this system. IL-1 decreased the effect of NMDA and glycine on intracellular calcium concentrations in cultured chick cortical neurons in both the presence and absence of the endogenous polyamine spermine. This effect was attenuated by pretreatment with the AMPA/kainate antagonist CNQX. These data indicate that IL-1 modulates both inhibitory and excitatory neurotransmitter function in brain.
Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, Massachusetts 02111.
L G
LG
Miller
J M
JM
Fahey
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002642:Chick Embryo; D018698:Glutamic Acid / Q000502:physiology*; D005998:Glycine / Q000494:pharmacology; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D013096:Spermine / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology / Q000502:physiology*
D007375:Interleukin-1; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D013096:Spermine; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D016202:N-Methylaspartate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D002118:Calcium; D005998:Glycine