INTERLEUKIN-1-BETA INDUCED CORTICOSTERONE ELEVATION AND HYPOTHALAMIC NE DEPLETION IS VAGALLY MEDIATED

Processes occurring within the immune system can alter neural function . Cytokines released by cells of the immune system during illness are key messengers in immune-to-brain communication. Interleukin-1 beta (I L-1 beta) is particularly important in this regard and is known to sti mulate a myriad of illness-related outcomes such as fever, sickness be havior, aphagia, adipsia, hypathalamic-pituitary-adrenal activation, a nd changes in pain reactivity. Thus peripherally released IL-1 beta ha s potent neural effects and is a critical mediator of the impact of im mune processes on brain. There is, however, uncertainty concerning the communication pathways involved. We provide evidence that a primary r oute of peripheral cytokine signalling is through stimulation of perip heral vagal afferents rather than or in addition to direct cytokine ac cess to brain. Subdiaphragmatic, but not hepatic vagotomy, blocked rhI L-1 beta-induced hypothalamic norepinephrine depletion and attenuated rhIL-1 beta-induced increases in serum corticosterone. These data sugg est that rhIL-1 beta activates the hypothalamic-pituitary-adrenal axis via stimulation of peripheral vagal afferents and further support the hypothesis that peripheral cytokine signalling to the CNS is mediated primarily by stimulation of peripheral afferents.