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This Article Full Text Full Text (PDF) All Versions of this Article: 296/6/E1289    most recent 90489.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Google Scholar Articles by Palin, K. Articles by Moos, F. PubMed PubMed Citation Articles by Palin, K. Articles by Moos, F.

Interleukin-6 activates arginine vasopressin neurons in the supraoptic nucleus during immune challenge in rats

¹Institut National de la Recherche Agronomique, Unité mixte de recherche (UMR) 1286, PsyNuGen, Centre National de la Recherche Scientifique (CNRS), UMR 5226, Université de Bordeaux, IFR8 Neurosciences, F-33076 Bordeaux; ²CNRS UMR 5203, Institut de Génomique Fonctionnelle, Pharmacologie Moléculaire, Institut National de la Santé et de la Recherche Médicale, U661, Université de Montpellier, F-34094, Montpellier, France

Submitted 4 June 2008 ; accepted in final form 25 February 2009

The increase of plasma arginin-vasopressin (AVP) release, which translates hypothalamic AVP neuron activation in response to immune challenge, appears to occur independently of plasma osmolality or blood pressure changes. Many studies have shown that major inflammatory mediators produced in response to peripheral inflammation, such as prostaglandin (PG)-E₂ and interleukin (IL)-1β, excite AVP neurons. However, in vivo electrical activation of AVP neurons was still not assessed in relation to plasma AVP release, osmolality, or blood pressure or to the expression and role of inflammatory molecules like PG-E₂, IL-1β, IL-6, and tumor necrosis factor- (TNF). This study aims at elucidating those factors that underlie the activation of AVP neurons in response to immune stimulation mimicked by an intraperitoneal injection of lipopolysaccharide (LPS) in male Wistar rats. LPS treatment concomittanlty decreased diuresis and increased plasma AVP as well as AVP neuron activity in vivo, and these effects occurred as early as 30 min. Activation was sustained for more than 6 h. Plasma osmolality did not change, whereas blood pressure only transiently increased during the first hour post-LPS. PG-E₂, IL-1β, and TNF mRNA expression were raised 3 h after LPS, whereas IL-6 mRNA level increased 30 min post-LPS. In vivo electrophysiological recordings showed that brain IL-6 injection increased AVP neuron activity similarly to peripheral LPS treatment. In contrast, brain injection of anti-IL-6 antibodies prevented the LPS induced-activation of AVP neurons. Taken together, these results suggest that the early activation of AVP neurons in response to LPS injection is induced by brain IL-6.

lipopolysaccharide induced-hypothalamic vasopressin neuron activation; brain cytokines; diuresis; plasma osmolality; blood pressure

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