PERIPHERAL ADMINISTRATION OF INTERLEUKIN-1 INCREASES EXTRACELLULAR CONCENTRATIONS OF NOREPINEPHRINE IN RAT HYPOTHALAMUS - COMPARISON WITH PLASMA-CORTICOSTERONE

Peripheral administration of interleukin-1 (IL-1) activates the hypoth alamo-pituitary-adrenocortical (HPA) axis and also activates norepinep hrine (NE) metabolism in the hypothalamus. Because there is evidence t hat hypothalamic NE can activate CRF secretion, it has been proposed t hat changes in hypothalamic noradrenergic activity are instrumental in the IL-1-induced activation of the HPA axis. We have examined this hy pothesis by assessing the release of hypothalamic NE using in vivo mic rodialysis following intravenous (IV) or intraperitoneal (IP) injectio n 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 TV and IP administratio n of IL-1 beta. The elevation was more rapid following IV IL-1 beta, a nd reached a peak at 1 h, whereas the slower and smaller increase foll owing IP IL-1 beta did not reach a peak until 2 h. The results were si milar 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 be ta (around 2 h). The hypothalamic noradrenergic responses followed a p attern similar to that of plasma corticosterone with either route of I L-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.