CENTRAL INTERLEUKIN-1-BETA ENHANCES SPLENIC SYMPATHETIC-NERVE ACTIVITY IN RATS

The central administration of immune cytokines such as interleukin-1 ( IL-1) and interferon-alpha (IFN-alpha) results in the suppression of p eripheral cellular immunity, which depends, at least partly, on the sy mpathetic nervous activity. An intrathird cerebroventricular (I3V) inf usion of recombinant human IL-1 beta (rhIL-1 beta) (1-5 ng/rat) elicit ed a dose dependent increase in the electrical activity of the splenic sympathetic nerve in urethane and cu-chloralose anesthetized rats. Th e effect of rhIL-1 beta (1 ng/rat) was completely blocked by pretreatm ent with an IL-1 receptor antagonist (1 mu g/rat, I3V 10 min before rh IL-1 beta), sodium salicylate (1 mu g/rat), or cu-melanocyte stimulati ng hormone (cu-MSH) (400 ng/rat). Furthermore, an antagonist of cortic otropin-releasing factor (CRF), alpha-helical CRF(9-41) (2 mu g/rat), completely abolished the rhIL-1 beta-induced increase in the splenic n erve activity, although an I3V infusion of CRF(1 mu g/rat) excited it. These results suggest that IL-1 beta in the brain activates splenic s ympathetic activity by its receptor-mediated and prostaglandin-depende nt action that is sensitive to a-MSH, depending on CRF system. Our fin dings, together with the previous results, suggest that the splenic sy mpathetic nerve represents one of the communication channels from the brain to the immune system.