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 (IL-1 beta) is particularly important in this regard and is known to stimulate a myriad of illness-related outcomes such as fever, sickness behavior, aphagia, adipsia, hypothalamic-pituitary-adrenal activation, and changes in pain reactivity. Thus peripherally released IL-1 beta has potent neural effects and is a critical mediator of the impact of immune processes on brain. There is, however, uncertainty concerning the communication pathways involved. We provide evidence that a primary route of peripheral cytokine signalling is through stimulation of peripheral vagal afferents rather than or in addition to direct cytokine access to brain. Subdiaphragmatic, but not hepatic vagotomy, blocked rhIL-1 beta-induced hypothalamic norepinephrine depletion and attenuated rhIL-1 beta-induced increases in serum corticosterone. These data suggest 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.
Fleshner
M
M
Department of Psychology, University of Colorado at Boulder 80309, USA.
Goehler
L E
LE
Hermann
J
J
Relton
J K
JK
Maier
S F
SF
Watkins
L R
LR
D000818:Animals; D003345:Corticosterone / Q000097:blood*; D003964:Diaphragm / Q000294:innervation; D004305:Dose-Response Relationship, Drug; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D007375:Interleukin-1 / Q000494:pharmacology*; D008099:Liver / Q000294:innervation; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D014628:Vagotomy; D014630:Vagus Nerve / Q000502:physiology*
D007375:Interleukin-1; D011994:Recombinant Proteins; D003345:Corticosterone; D009638:Norepinephrine