It is almost generally accepted that an acute-phase ACTH response induced by interleukin (IL)-1 is mediated principally by CRH release from the hypothalamus. However, the precise cellular site of action of IL-1 in activating the CRH neuronal system remains to be determined. Two likely candidates comprise the paraventricular nucleus (PVN) where CRH neuronal cell bodies are located, and the median eminence (ME) where their nerve endings are terminated. Therefore, in this study we performed a comparative perfusion of the ME and the PVN with increasing concentrations of recombinant human IL-1β utilizing the push-pull perfusion technique in freely moving rats. We measured the plasma ACTH and ME and PVN levels of CRH, and also of AVP, because AVP, another secretagogue of ACTH, has its cell body in the PVN and axon terminals partly in the ME. In control groups, the ME or the PVN was perfused with artificial cerebrospinal fluid between 12:00 and 15:00 h, and perfusates and blood samples were collected every 20 min. In the other groups, either the ME or the PVN was perfused with three increasing concentrations (0.1, 1.0, and 10 nM) of recombinant human IL-1β dissolved in artificial cerebrospinal fluid only between 13:00 and 14:00 h with all the other procedures run in the same way as in the controls. In the control perfusions, the hypothalamic release of CRH and AVP and the plasma ACTH did not change significantly during the entire period of observation. In the ME perfusion with IL-1β, 1.0 and 10 nM, but not 0.1 nM, of the cytokine significantly and dose-dependently stimulated CRH and AVP secretions in the ME and the plasma ACTH. ACTH responses during the PVN perfusion with IL-1β were similar to those during the ME perfusion, except that at the PVN the lowest concentration (0.1 nM) of the cytokine was already effective in stimulating ACTH secretion. These in vivo data suggest that IL-1β may act on both the ME and the PVN to stimulate CRH and,’ thereby, ACTH secretions. The secretory response of hypothalamic AVP to IL-1β, which was similar to that of CRH, suggests that not only CRH but also AVP may mediate the IL-1β stimulation of ACTH secretion.

Keywords:
Interleukin-1β, Corticotropin-releasing hormone, Arginine vasopressin, Adrenocorticotropin, Paraventricular nucleus, Median eminence, Push-pull perfusion
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© 1992 S. Karger AG, Basel
1993
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