Intrahypothalamic Perfusion with lnterleukin-1-Beta Stimulates the Local Release of Corticotropin-Releasing Hormone and Arginine Vasopressin and the Plasma Adrenocorticotropin in Freely Moving Rats: A Comparative Perfusion of the Paraventricular Nucleus and the Median Eminence

Abstract

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.

Temporal Profiles of Interleukin-1.BETA., Interleukin-6, and Tumor Necrosis Factor-.ALPHA. in the Plasma and Hypothalamic Paraventricular Nucleus after Intravenous or Intraperitoneal Administration of Lipopolysaccharide in the Rat. Estimation by Push-Pull Perfusion.

“…Temporal changes in plasma ACTH and CRH levels in the PVN were also monitored. To accomplish this, we employed the push-pull perfusion (PPP) technique of the rat brain as in our previous reports [24][25][26][27][28][29]. Second, we compared the effects of iv versus ip injections of LPS to determine if the route of administration causes any fundamental differences in response of the three cytokines in either the peripheral circulation or the PVN.…”

“…Second, we compared the effects of iv versus ip injections of LPS to determine if the route of administration causes any fundamental differences in response of the three cytokines in either the peripheral circulation or the PVN. We chose the PVN as the site to determine cytokine levels, because that nucleus is where the CRH neuronal cell bodies are located, and we [27] and other investigators [30,31] have previously reported that the PVN may be a potential site within the hypothalamus where brainderived IL-1 activates the HPA axis. Adult male rats (350-400 g) of the WistarImamichi strain were used.…”

“…As described in our previous reports [27][28][29], PPP cannulae (outer diameter, 0.7 mm) were constructed in our laboratory according to a design similar to that described by Levine and Ramirez [32]. The guide cannulae with a removable inner stylette were stereotaxically implanted towards the PVN.…”

“…At about 07 : 00 h on the day of PPP, the inner stylette was removed and replaced with the inner cannula perfusion assembly. Immediately thereafter, we started infusing artificial cerebrospinal fluid, of which constituents were the same as in our previous studies [24][25][26][27][28][29], through the push cannula, and collected perfusates from the pull cannula at a flow rate of 15 p1/mm. Subsequently, the jugular vein catheter was exteriorized to allow for sequential blood sampling.…”

Central interleukin‐1 beta stimulation of vasopressin release into the rat brain: activation of an antipyretic pathway.

“…The minimally effective dose of IL-/I for AVP release into the VSA was between 125 and 500 pg (2 /sl)-' (approximately 10 nM). This is similar to that necessary to evoke AVP release from the median eminence in vivo (Watanobe & Takebe, 1993) but at least 100-fold less than that required to induce hypothalamic release of serotonin metabolites in vivo (Mohankumar, Thyagarajan & Quadri, 1993).…”