Interleukin-1 augments gamma-aminobutyric acidA receptor function in brain.
Interleukin-1 (IL-1), a cytokine involved in the acute phase reaction to injury and infection, has multiple effects in the central nervous system, including induction of fever and sleep and the release of several neuropeptides. We evaluated effects of IL-1 beta on inhibitory postsynaptic function at the gamma-aminobutyric acidA (GABAA) receptor. IL-1 (100 pg/ml to 10 ng/ml) augmented GABAA receptor function in cortical synaptic preparations. This effect of IL-1 was largely prevented by incubation with a specific IL-1 receptor antagonist. The related cytokines interleukin-6 and tumor necrosis factor did not augment GABA-dependent chloride transport. Similar enhancement of GABAA receptor function was observed in tissue prepared from mice previously injected intraperitoneally with IL-1 (1 microgram). Electrophysiological studies in cultured primary cortical neurons demonstrated that IL-1 enhanced the GABA-mediated increase in chloride permeability, whereas IL-1 alone produced no alterations in resting conductance. Behavioral studies indicated that IL-1 is similarly active in vivo; mice treated with IL-1 showed a decrease in open-field activity and an increase in the threshold for pentylenetetrazol-induced seizures. The interaction of IL-1 with GABAA receptors might account for the somnogenic and motor-depressant effects of this cytokine.
Miller
L G
LG
Division of Clinical Pharmacology, Tufts University School of Medicine, Boston, Massachusetts 02111.
Galpern
W R
WR
Dunlap
K
K
Dinarello
C A
CA
Turner
T J
TJ
D000818:Animals; D001921:Brain / Q000502:physiology / Q000648:ultrastructure*; D002712:Chlorides / Q000493:pharmacokinetics; D007375:Interleukin-1 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009118:Muscimol / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology*; D013379:Substrate Specificity; D013569:Synapses / Q000378:metabolism; D013574:Synaptosomes / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D002712:Chlorides; D007375:Interleukin-1; D015850:Interleukin-6; D011963:Receptors, GABA-A; D014409:Tumor Necrosis Factor-alpha; D009118:Muscimol