The sympathetic nervous system tonically inhibits peripheral interleukin-1beta 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 microg/6 microl/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-1beta 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-1beta 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-1beta 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-1beta and interleukin-6 in rats given central lipopolysaccharide and suggests a tonic inhibitory control of the sympathetic nervous system on these inflammatory cytokines.
De Luigi
A
A
Istituto di Ricerche Farmacologiche, Mario Negri, Milano, Italia.
Terreni
L
L
Sironi
M
M
De Simoni
M G
MG
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D003345:Corticosterone / Q000097:blood; D004298:Dopamine / Q000378:metabolism; D004926:Escherichia coli; D005786:Gene Expression Regulation / Q000187:drug effects; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000097:blood; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000097:blood; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D016627:Oxidopamine; D051381:Rats; D013154:Spleen / Q000187:drug effects / Q000378:metabolism; D013563:Sympathectomy, Chemical; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D016627:Oxidopamine; D004298:Dopamine; D003345:Corticosterone; D009638:Norepinephrine