Effects of Intravenous Administration of Interleukin-1-Beta on the Release of Prostaglandin E₂, Corticotropin-Releasing Factor, and Arginine Vasopressin in Several Hypothalamic Areas of Freely Moving Rats: Estimation by Push-Pull Perfusion

Abstract

Utilizing the push-pull perfusion technique, we examined the effect of an intravenous bolus injection of recombinant human interleukin (IL)-1β on the release of prostaglandin E₂ (PGE2), CRF, and AVP in several hypothalamic areas of freely moving rats, simultaneously monitoring plasma ACTH levels. Perfused hypothalamic areas were the median eminence (ME), the paraventricular nucleus (PVN), and the medial preoptic area (MPOA). During the period 12:00-15:00 h, perfusates and blood samples were collected every 10 min (between 13:00 and 13:40 h) or 20 min (between 12:00 and 13:00 h, and between 13:40 and 15:00 h). IL-1β (1.0 µg/rat) or vehicle only (in control groups) was injected at 13:00 h. In both the ME and the PVN but not in the MPOA, the outputs of CRF and AVP were significantly stimulated by IL-1β, prior to the rise in plasma ACTH. A significant stimulation of PGE2 by IL-1β was observed only in the PVN, and its temporal profile was very similar to those of CRF and AVP in the PVN. These results suggest that PGE₂ may be a trigger in the PVN for the activation of CRF and AVP neurons, and thereby ACTH secretion, which follows IL-1β injection.

Effect of Acute Systemic Inflammatory Response and Cytokines on the Transcription of the Genes Encoding Cyclooxygenase Enzymes (COX‐1 and COX‐2) in the Rat Brain

“…Systemic IL-i injection provokes sharp increases in the levels of PGE2 in the PVN (Watanobe and Takebe, 1994), whereas PGE2-immunoreactive neurons were detected in the PVN of LPS-treated rats (Van Dam et al, 1993). Moreover, the endocrine hypothalamus exhibits positive hybridization signal for the mRNA encoding EP1 PGE2 receptor subtype (Batshake et al, 1995).…”

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.…”

“…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.…”

NFκB Activatesin vivothe Synthesis of Inducible Cox-2 in the Brain

“…Induction of Cox-2 in vascular endothelial cells participates to the cerebral vasodilatation effect of IL-1b (Osuka et al, 1997) through accumulation of cyclic nucleotides and increase of NO production (Bonmann et al, 1997). Interleukin-1b is also a potent activator of the hypothalamo-pituitaryadrenal (HPA) axis (Schobitz et al, 1994;Besedovsky et al, 1991) through PGs and this is consistent with the strong hybridization signal for Cox-2 mRNA (Watanobe and Takebe, 1994) and Cox-2 immunoreactivity observed along the microvessels of the parvocellular PVN in the present study. The use of the selective Cox-2 inhibitor (NS 398) totally abolished the effect of IL-1 on plasma ACTH and POMC transcripts at the pituitary level although the effect on corticosterone secretion was mitigated (Parsadaniantz et al, 2000).…”