CENTRAL LIPOPOLYSACCHARIDE ELEVATES PLASMA IL-6 CONCENTRATION BY AN ALPHA-ADRENOCEPTOR-MEDIATED MECHANISM

High circulating levels of interleukin-6 (IL-6) are evident after intr acerebroventricular injection of lipopolysaccharide (LPS). To investig ate the pathway of centrally induced IL-6 production, in the present s tudy we evaluated the effects of specific alpha-adrenergic receptor an tagonists administered peripherally on IL-6 production and hypertrigly ceridemia induced by LPS administered centrally. In the first study, a dult male Wistar-Furth rats were injected intracerebroventricularly wi th LPS. Centrally injected LPS increased plasma IL-6 and triglycerides (TG) in a dose-dependent fashion. To determine if LPS increased plasm a IL-6 and TG through an alpha-adrenoreceptor mechanism, rats were pre treated intraperitoneally with either vehicle, phentolamine (alpha(1)- and alpha(2)-receptor antagonist), prazosin (alpha(1)-receptor antago nist), or yohimbine (alpha(2)-receptor antagonist). Thirty minutes lat er, rats were injected intracerebroventricularly with LPS. Whereas pra zosin 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 subse quent activation of alpha(1)- and alpha(2)-adrenergic receptors are im portant for controlling peripheral metabolic and endocrine systems whe n inflammatory stimuli are present in the brain.