Central lipopolysaccharide elevates plasma IL-6 concentration by an alpha-adrenoreceptor-mediated mechanism.
High circulating levels of interleukin-6 (IL-6) are evident after intracerebroventricular injection of lipopolysaccharide (LPS). To investigate the pathway of centrally induced IL-6 production, in the present study we evaluated the effects of specific alpha-adrenergic receptor antagonists administered peripherally on IL-6 production and hypertriglyceridemia induced by LPS administered centrally. In the first study, adult male Wistar-Furth rats were injected intracerebroventricularly with LPS. Centrally injected LPS increased plasma IL-6 and triglycerides (TG) in a dose-dependent fashion. To determine if LPS increased plasma IL-6 and TG through an alpha-adrenoreceptor mechanism, rats were pretreated intraperitoneally with either vehicle, phentolamine (alpha 1- and alpha 2-receptor antagonist), prazosin (alpha 1-receptor antagonist), or yohimbine (alpha 2-receptor antagonist). Thirty minutes later, rats were injected intracerebroventricularly with LPS. Whereas prazosin and yohimbine attenuated the increases in plasma IL-6 caused by LPS, phentolamine completely blocked the peripheral effects of central LPS. These data suggest that increased sympathetic activity and subsequent activation of alpha 1- and alpha 2-adrenergic receptors are important for controlling peripheral metabolic and endocrine systems when inflammatory stimuli are present in the brain.
Finck
B N
BN
Department of Animal Sciences, University of Illinois, Urbana 61801, USA.
Dantzer
R
R
Kelley
K W
KW
Woods
J A
JA
Johnson
R W
RW
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000378:metabolism*; D007276:Injections, Intraventricular; D015850:Interleukin-6 / Q000097:blood*; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D009994:Osmolar Concentration; D051381:Rats; D011920:Rats, Inbred WF; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*
D000317:Adrenergic alpha-Antagonists; D015850:Interleukin-6; D008070:Lipopolysaccharides; D011942:Receptors, Adrenergic, alpha