Synergism between interleukin-6 and interleukin-1beta in hypothalamic serotonin release: a reverse in vivo microdialysis study in F344 rats.
The effects of interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) perfused locally into the anterior hypothalamus (AHY) on serotonin (5-hydroxytryptamine, 5-HT) release were investigated in the same region using in vivo microdialysis in conscious, freely moving F344 rats. IL-1beta (1 ng/rat) or IL-6 (50 ng/rat) injected directly into the AHY elicited a rapid and transient statistically significant increase in extracellular 5-HT levels (to 161% and 145% of the respective AUC (area under the curve) basal value, 100%). Intra-hypothalamic infusion of IL-1-receptor antagonist IL-1Ra (2 mug/rat) prevented this effect of IL-1beta, but not that of IL-6, suggesting an IL-1beta-independent mechanism for hypothalamic 5-HT release by this latter cytokine. Furthermore, intra-hypothalamic co-perfusion of IL-6 with IL-1beta at sub-optimal doses (10 ng/rat and 0.5 ng/rat, respectively) synergized in releasing hypothalamic 5-HT, thus providing in vivo evidence that both cytokines, IL-6 and IL-1beta are able to modulate the neuronal 5-HT response in the rat AHY.
Wu
Y
Y
Institut de Signalisation et d'Innovation Thérapeutique (IFR-ISIT), Chatenay-Malabry, France.
Shaghaghi
E K
EK
Jacquot
C
C
Pallardy
M
M
Gardier
A M
AM
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D007032:Hypothalamus, Anterior / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D007263:Infusions, Parenteral; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000008:administration & dosage / Q000494:pharmacology*; D015850:Interleukin-6 / Q000008:administration & dosage / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D017551:Microdialysis; D051381:Rats; D011916:Rats, Inbred F344; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D012701:Serotonin / Q000378:metabolism*; D012795:Sialoglycoproteins / Q000008:administration & dosage / Q000494:pharmacology
D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D015850:Interleukin-6; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins; D012701:Serotonin