Interleukin-1 Directly Stimulates the Release of Corticotrophin Releasing Factor from Rat Hypothalamus

While interleukin-1 (IL-1), a monocyte-derived polypeptide, clearly stimulates the hypothalamo-pituitary-adrenal (HPA) axis, its precise site of action is controversial. In these studies, the possibility of a hypothalamic and/or a pituitary site of action was investigated in vitro, using incubated rat hypothalami and perifused dispersed pituitary cells. Both forms of IL-1, IL-1 alpha and IL-1 beta, produced a dose-dependent stimulation of CRF-41 release from incubated rat hypothalami in the dose range of 1-100 U/ml (p less than 0.01). However, concentrations of both interleukins of 1-1,000 U/ml given as 10-min infusions had no effect on ACTH release from dispersed pituitary cells. Moreover, IL-1 beta, used in the concentration range of 1-100 U/ml, was unable to potentiate CRF-41-induced ACTH release. These data therefore provide evidence that at least the acute stimulatory effects of IL-1 on the HPA axis are predominantly mediated via a direct stimulation of hypothalamic CRF-41, suggesting that the hypothalamus may provide an interface between the neuroendocrine and immune axes.