VAGAL PARAGANGLIA BIND BIOTINYLATED INTERLEUKIN-1 RECEPTOR ANTAGONIST- A POSSIBLE MECHANISM FOR IMMUNE-TO-BRAIN COMMUNICATION

Interleukin-1 beta is a proinflammatory cytokine released by activated immune cells. In addition to orchestrating immune responses to infect ion, interleukin-1 beta is a key mediator of immune-to-brain communica tion. Interleukin-1 beta and endotoxin (which releases IL1 beta from i mmune cells) cause centrally mediated illness responses such as fever, aphagia, etc. These effects are blocked by intraperitoneal IL1 recept or antagonist (IL1ra), suggesting critical involvement of peripheral I L1 receptors. Centrally mediated illness responses are also blocked by vagotomy, suggesting that IL1 beta directly or indirectly activates v agal afferents, To test for IL1 beta binding, whole vagus (abdominal, laryngeal, and thoracic) and sections of hepatic vagus and liver hilus were incubated with biotinylated IL1ra and processed for avidin-bioti n complex (ABC) or avidin-FITC histochemistry, Glomus cells of vagal p araganglia were labeled in all regions of the vagus. Biotinylated IL1r a also labeled smooth muscle and endothelial cells of blood vessels an d lymphoid tissues. No label was present in omission or competition co ntrols, These data suggest that centrally mediated illness responses r esult from IL1 activation of vagal paraganglia. (C) 1997 Elsevier Scie nce Inc.