INTERLEUKIN-1-BETA STIMULATES BOTH CENTRAL AND PERIPHERAL RELEASE OF VASOPRESSIN AND OXYTOCIN IN THE RAT

Simultaneous microdialysis in the brain and blood was used to monitor the release of vasopressin and oxytocin within the hypothalamic supraoptic (SON) and paraventricular (PVN) nuclei and into the systemic circulation of urethane-anaesthetized male rats before and after central administration of interleukin-1 beta (IL-1 beta). Following intracerebroventricular infusion of the cytokine (200 ng/5 mu l), the content of vasopressin (up to 278% compared to vehicle-treated control, P < 0.01 compared to vehicle-treated control and preinfusion baseline) but not oxytocin (up to 148%, not significant) in 30-min blood microdialysates was found to be increased. This peripheral release was accompanied by a transient rise in vasopressin (up to 163%, P < 0.05) and oxytocin (up to 182%, P < 0.05) release within the SON, the peak typically occurring during the first and second 30-min collection intervals after IL-1 beta respectively. In contrast, in the simultaneously microdialysed PVN, both vasopressin and oxytocin failed to respond to intracerebroventricular IL-1 beta. In another series of experiments, IL-1 beta was directly infused (20 ng/0.5 mu l) into either the SON or PVN during microdialysis of the corresponding nucleus, The cytokine caused a significant and immediate rise in intra-SON release of both vasopressin (up to 225%, P < 0.01) and oxytocin (up to 178%, P < 0.05). Again, in the PVN, nonapeptide release, although tending to be stimulated in response to intranuclear IL-1 beta, failed to reach statistical significance. The cytokine-induced central and peripheral release pattern appeared to be independent of the rise in body temperature observed after IL-1 beta administration. In a third series of experiments, bilateral administration of IL-1 beta into the SON (20 ng/0.5 mu l) failed to alter peripheral release of both vasopressin and oxytocin into the systemic circulation. The increase in central nonapeptide release in response to IL-1 beta shown in this paper supports the hypothesis that at least vasopressin might act to oppose central effects of the cytokine, including those on thermoregulation and behaviour, in this way contributing to the neuroendocrine-immune dialogue at brain level.