The sympathetic nervous system tonically inhibits peripheral interleukin-1β and interleukin-6 induction by central lipopolysaccharide

To study the role of the sympathetic nervous system in the induction of inflammatory cytokines elicited by central lipopolysaccharide, sympathetic chemical denervation was performed by intraperitoneal injection of 6-hydroxydopamine. Rats received the neurotoxin according to the following schedule: 50 mg/kg on days 1 and 2, 100 mg/kg on days 3, 4 and 7. On day 8, lipopolysaccharide (2.5 mu g/6 mu l/rat) was injected intracerebroventricularly and rats were killed 2 h later. 6-Hydroxydopamine reduced noradrenaline and dopamine content in the spleen by 88.7% and 88.8%, respectively, without affecting striatal contents indicating that the chemical sympathectomy had been effective and selective. In sympathectomized rats, lipopolysaccharide raised interleukin-1 beta and interleukin-6 serum levels more than in control rats given the vehicle. Tumour necrosis factor-alpha serum levels in sympathectomized rats were no different from those in vehicle-treated rats. Interleukin-1 beta and interleukin-6 messenger RNA expression, measured by northern blot analysis, was clearly detectable in adrenals and spleen of rats given lipopolysaccharide. Sympathectomy increased lipopolysaccharide-induced interleukin-1 beta and interleukin-6 messenger RNA in adrenals and spleen. Corticosterone basal levels were raised by central lipopolysaccharide and not further changed by sympathectomy. The present study shows that sympathetic nervous system denervation enhances the synthesis and production of peripheral interleukin-1 beta and interleukin-6 in rats given central lipopolysaccharide and suggests a tonic inhibitory control of the sympathetic nervous system on these inflammatory cytokines. (C) 1998 IBRO. Published by Elsevier Science Ltd.