Effect of interleukin-6 and tumor necrosis factor-alpha on GABA release from mediobasal hypothalamus and posterior pituitary.
The release of cytokines during infection, inflammation and stress induces brain-mediated responses, including alterations of neuroendocrine functions. We examined the effect of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) on release of gamma-aminobutyric acid (GABA) from mediobasal hypothalamic (MBH) explants and posterior pituitaries (PP) of male rats. IL-6 (10 ng/ml) did not modify basal GABA release from MBH and PP, but significantly increased GABA release under depolarizing conditions (40 mM K(+)). This effect was abolished by incubation of the tissue with indomethacin, an inhibitor of cyclooxygenase activity, indicating that prostaglandins could mediate the stimulation of GABA release induced by IL-6. On the contrary, TNF-alpha (50 ng/ml) significantly decreased K(+)-evoked GABA release from both MBH and PP. This inhibitory effect was not modified by indomethacin. Neither IL-6 nor TNF-alpha affected nitric oxide synthesis, as measured by [(14)C]citrulline production. The current results indicate that IL-6 stimulates GABA release from both hypothalamus and posterior pituitary by a mechanism mediated by prostaglandins. On the contrary, TNF-alpha inhibits GABA release from both tissues. These results suggest the possibility that GABAergic activity in the hypothalamic-pituitary axis could be involved in neuroendocrine responses to cytokines.
De Laurentiis
A
A
Centro de Investigaciones en Reproducción, Facultad de Medicina, Universidad de Buenos Aires, Argentina.
Pisera
D
D
Lasaga
M
M
Díaz
M
M
Theas
S
S
Duvilanski
B
B
Seilicovich
A
A
D000818:Animals; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D007033:Hypothalamus, Middle / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010904:Pituitary Gland, Posterior / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D011188:Potassium / Q000819:agonists / Q000037:antagonists & inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*; D000093242:Interleukin-6 Inhibitors
D016861:Cyclooxygenase Inhibitors; D007213:Indomethacin; D015850:Interleukin-6; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D011188:Potassium; D014409:Tumor Necrosis Factor-alpha; D005680:gamma-Aminobutyric Acid; D000093242:Interleukin-6 Inhibitors