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 peripheral cellular immunity, which depends, at least partly, on the sympathetic nervous activity. An intrathird cerebroventricular (I3V) infusion of recombinant human IL-1 beta (rhIL-1 beta) (1-5 ng/rat) elicited a dose dependent increase in the electrical activity of the splenic sympathetic nerve in urethane and cu-chloralose anesthetized rats. The effect of rhIL-1 beta (1 ng/rat) was completely blocked by pretreatment with an IL-1 receptor antagonist (1 mu g/rat, I3V 10 min before rhIL-1 beta), sodium salicylate (1 mu g/rat), or cu-melanocyte stimulating hormone (cu-MSH) (400 ng/rat). Furthermore, an antagonist of corticotropin-releasing factor (CRF), alpha-helical CRF(9-41) (2 mu g/rat), completely abolished the rhIL-1 beta-induced increase in the splenic nerve 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 sympathetic activity by its receptor-mediated and prostaglandin-dependent action that is sensitive to a-MSH, depending on CRF system. Our findings, together with the previous results, suggest that the splenic sympathetic nerve represents one of the communication channels from the brain to the immune system.