title: Peripheral administration of interleukin-1 increases extracellular concentrations of norepinephrine in rat hypothalamus: comparison with plasma corticosterone.
abstract: Peripheral administration of interleukin-1 (IL-1) activates the hypothalamo-pituitary-adrenocortical (HPA) axis and also activates norepinephrine (NE) metabolism in the hypothalamus. Because there is evidence that hypothalamic NE can activate CRF secretion, it has been proposed that changes in hypothalamic noradrenergic activity are instrumental in the IL-1-induced activation of the HPA axis. We have examined this hypothesis by assessing the release of hypothalamic NE using in vivo microdialysis following intravenous (IV) or intraperitoneal (IP) injection of human IL-1 beta and comparing the responses with those in plasma corticosterone. The results indicate that extracellular concentrations of NE in the hypothalamus increased following IV and IP administration of IL-1 beta. The elevation was more rapid following IV IL-1 beta, and reached a peak at 1 h, whereas the slower and smaller increase following IP IL-1 beta did not reach a peak until 2 h. The results were similar in both anesthetized and unanesthetized rats. In unanesthetized rats, plasma corticosterone increased shortly following IV or IP IL-1 beta administration, but the peak concentration following IV IL-1 beta was significantly earlier (around 1 h) than that following IP IL-1 beta (around 2 h). The hypothalamic noradrenergic responses followed a pattern similar to that of plasma corticosterone with either route of IL-1 beta administration, but they were not identical. The results are consistent with the possibility that a central noradrenergic mechanism mediates the activation of the HPA axis by peripherally administered IL-1 beta. However, appreciable differences in the time courses of the responses may indicate the involvement of other factors.
authors.affiliation: Department of Pharmacology and Therapeutics, Louisiana State University Medical Center, Shreveport 71103, USA.
authors.forename: G N
authors.initials: GN
authors.lastname: Smagin
authors.forename: A H
authors.initials: AH
authors.lastname: Swiergiel
authors.forename: A J
authors.initials: AJ
authors.lastname: Dunn
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects*; D003345:Corticosterone / Q000097:blood*; D005110:Extracellular Space / Q000187:drug effects*; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects; D007031:Hypothalamus / Q000187:drug effects*; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D007375:Interleukin-1 / Q000494:pharmacology*; D008297:Male; D017551:Microdialysis; D009638:Norepinephrine / Q000097:blood*; D010913:Pituitary-Adrenal System / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology
chemical_list: D007375:Interleukin-1; D011994:Recombinant Proteins; D003345:Corticosterone; D009638:Norepinephrine