title: Systemic Interleukin-1beta stimulates the simultaneous release of norepinephrine in the paraventricular nucleus and the median eminence.
abstract: Interleukin-1beta (IL-1beta), a cytokine with pronounced central effects such as fever, anorexia, analgesia, etc., is also known to activate the hypothalamo-pituitary-adrenal (HPA) axis. Corticotropin releasing hormone (CRH) neurons located in the hypothalamus are important for HPA activation. The cell bodies of CRH neurons are located in the paraventricular nucleus (PVN) and their terminals are present in the median eminence (ME). Although the catecholamines, norepinephrine (NE) and dopamine (DA) are believed to be crucial factors in the stimulation of CRH neurons, it is not clear if they affect the cell bodies or terminals of these neurons to cause HPA activation. This study was done to determine if IL-1beta affects NE and DA release at the level of CRH cell bodies or their terminals. Adult male Sprague-Dawley rats were implanted with two push-pull cannulae, one in the PVN and another in the ME, and were subjected to push-pull perfusion. They were treated either with 0, 1 or 5 microg of IL-1beta. Perfusates were collected for 2 h after treatment and analyzed for NE concentrations using HPLC-EC. NE levels in the control and low dose groups did not change significantly during the entire period of observation both in the PVN and ME. In contrast, treatment with 5 microg of IL-1beta produced a marked increase in NE release in the PVN at 20 and 40 min post-treatment. NE release in the ME increased from 10 to 140 min post-treatment. There were no significant changes in the release of DA from both these areas. These results indicate that IL-1beta increases NE levels both in the PVN and in the ME and this could be a possible mechanism by which it stimulates the HPA axis.
authors.affiliation: Neuroendocrine Research Laboratory, Department of Pathobiology and Diagnostic Investigation, Veterinary Medical Center, A-20, Michigan State University, East Lansing, MI 48824, USA. mohankumrs@cvm.msu.edu
authors.forename: Sheba M J
authors.initials: SM
authors.lastname: MohanKumar
authors.forename: P S
authors.initials: PS
authors.lastname: MohanKumar
mesh_terms: D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004563:Electrochemistry / Q000379:methods; D007375:Interleukin-1 / Q000494:pharmacology*; D008297:Male; D008473:Median Eminence / Q000187:drug effects* / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D007375:Interleukin-1; D004298:Dopamine; D009638:Norepinephrine