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

Palin K, Moreau ML, Sauvant J, Orcel H, Nadjar A, Duvoid-Guillou A, Dudit J, Rabie A, Moos F. Interleukin-6 activates arginine vasopressin neurons in the supraoptic nucleus during immune challenge in rats. Am J Physiol Endocrinol Metab 296: E1289-E1299, 2009. First published March 3, 2009; doi:10.1152/ajpendo.90489.2008.-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)-E-2 and interleukin (IL)-1 beta, 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-E-2, IL-1 beta, IL-6, and tumor necrosis factor-alpha (TNF alpha). 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-E-2, IL-1 beta, and TNF alpha 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.