Central noradrenergic system modulates plasma interleukin-6 production by peripheral interleukin-1.
The role of the central noradrenergic system in systemic interleukin-6 (IL-6) production induced by intravenously administered recombinant human interleukin-1 beta (IL-1 beta) was examined in rats. Pretreatment of rats intracerebroventricularly with 6-hydroxydopamine (6-OHDA, 100 or 200 micrograms/rat) significantly attenuated the increase in plasma IL-6 levels caused by IL-1 beta (2 micrograms/kg i.v.). A modest inhibition of the IL-1 beta-induced plasma IL-6 production was observed following pretreatment with prazosin (20 micrograms/rat i.c.v.) but not after administration of idazoxan or propranolol. There were no significant increases in the IL-6 content in the hypothalamus, medulla oblongata, and cortex of the brain after intravenous IL-1 beta. Adrenalectomy produced an augmented plasma IL-6 response to intravenous IL-1 beta, whereas chemical sympathectomy with intraperitoneal injection of 6-OHDA (50 or 100 mg/kg) decreased the IL-1 beta-induced plasma IL-6 levels. Nor-epinephrine (NE), in the dose range 10(-6)-10(-4) M, significantly increased the IL-6 levels in the rat spleen lymphocyte culture media. At doses of 10(-9)-10(-7) M, NE enhanced the effect of IL-1 beta on the IL-6 release by spleen lymphocytes in a dose-dependent manner. These findings suggest that the plasma IL-6 response to intravenous IL-1 beta is partially mediated through the activation of the central noradrenergic system and a consequent increase in the sympathetic outflow to the peripheral tissues and that the NE released from the sympathetic terminals may function as a mediator and/or modulator to facilitate the synthesis/release of IL-6 in the sympathetic nerve-innervated organs.
Huang
Q H
QH
United States-Japan Biomedical Research Laboratories, Tulane University Hebert Center, Belle Chasse, Louisiana 70037, USA.
Takaki
A
A
Arimura
A
A
D018674:Adrenergic Antagonists / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000378:metabolism*; D006801:Humans; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D007375:Interleukin-1 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000097:blood*; D008099:Liver / Q000378:metabolism; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D009638:Norepinephrine / Q000378:metabolism / Q000502:physiology*; D016627:Oxidopamine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins; D013154:Spleen / Q000166:cytology / Q000378:metabolism
D018674:Adrenergic Antagonists; D007375:Interleukin-1; D015850:Interleukin-6; D011994:Recombinant Proteins; D016627:Oxidopamine; D009638:Norepinephrine