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-1β (IL-1β) was examined in rats. Pretreatment of rats intracerebroventricularly with 6-hydroxydopamine (6-OHDA, 100 or 200 μg/rat) significantly attenuated the increase in plasma IL-6 levels caused by IL-1β (2 μg/kg iv). A modest inhibition of the IL-1β-induced plasma IL-6 production was observed following pretreatment with prazosin (20 μg/rat icv) 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-1β. Adrenalectomy produced an augmented plasma IL-6 response to intravenous IL-1β, whereas chemical sympathectomy with intraperitoneal injection of 6-OHDA (50 or 100 mg/kg) decreased the IL-1β-induced plasma IL-6 levels. Norepinephrine (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-1β 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-1β 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.