Interleukin-1β and interleukin-6 stimulate neurohypophysial hormone release in vitro

Interleukin-1 (IL-1) and interleukin-6 (IL-6) have been reported to stimulate the release of corticotrophin-releasing hormone (CRH) in vitro, the response being antagonized by the cyclo-oxygenase inhibitor, indomethacin. The effects of cytokines on the other major ACTH-releasing hormone, vasopressin (AVP), and the other neurohypophysial hormone, oxytocin, have been little studied, and the published data are conflicting. We have therefore used a previously validated rat hypothalamic explant model to evaluate whether IL-1β and IL-6 can directly activate the AVP and oxytocin neurosecretory system. In addition, we have also investigated the effects of inhibition of cyclooxygenase (CO) and lipoxygenase (LO) activities on the stimulated release of AVP and oxytocin by means of a series of antagonists, including a specific LO pathway inhibitor. The static rat hypothalamic incubation system used involves fresh hypothalamic explants with consecutive 20-min incubations, and estimation of AVP and oxytocin concentrations in the medium by specific and sensitive radioimmunoassays. It was found that IL-1β produced a dose-dependent increase in the release of AVP and oxytocin at doses of 10 and 100 U/ml (P <0.005). Only at the higher dose of 100 U/ml was IL-6 able to increase significantly AVP and oxytocin release (P <0.05). These stimulatory effects of IL-1β and IL-6 were blocked by cyclo-oxygenase inhibitors, indomethacin (28 μM) and ibuprofen (100 nM), but not by the lipooxygenase inhibitor, BW A4C (10 μg/ml), suggesting that prostaglandins are involved in this process. Thus, cytokines are clearly able to modulate the neurohypophysial system in vitro, the effects probably being mediated by cyclo-oxygenase products.