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Interleukin-1 beta and interleukin-6 stimulate neurohypophysial hormone release in vitro
S A Yasin1, A Costa, M L Forsling
1Department of Gynaecology, UMDS, London, UK.
Insights
Interleukin-1 beta and Interleukin-6 stimulate vasopressin and oxytocin release via cyclo-oxygenase pathways. These cytokines activate neurohypophysial hormone release, suggesting a role for prostaglandins in this process.
Area of Science:
- Neuroendocrinology
- Cytokine signaling
- Hormone regulation
Background:
- Interleukin-1 (IL-1) and Interleukin-6 (IL-6) are known to stimulate corticotrophin-releasing hormone (CRH) release.
- The effects of these cytokines on vasopressin (AVP) and oxytocin, other key ACTH-releasing hormones, are less understood and data are conflicting.
Purpose of the Study:
- To investigate if IL-1 beta and IL-6 directly activate the AVP and oxytocin neurosecretory system.
- To examine the role of cyclo-oxygenase (CO) and lipoxygenase (LO) pathways in cytokine-mediated AVP and oxytocin release.
Main Methods:
- Utilized a validated rat hypothalamic explant model for in vitro incubation.
- Measured AVP and oxytocin release using radioimmunoassays over consecutive 20-min incubations.
- Administered IL-1 beta, IL-6, and specific CO/LO inhibitors (indomethacin, ibuprofen, BW A4C).
Main Results:
- IL-1 beta dose-dependently increased AVP and oxytocin release.
- IL-6 significantly increased AVP and oxytocin release at a higher dose.
- The stimulatory effects of IL-1 beta and IL-6 were blocked by CO inhibitors but not by the LO inhibitor, indicating prostaglandin involvement.
Conclusions:
- IL-1 beta and IL-6 can directly stimulate the release of AVP and oxytocin from the rat hypothalamus.
- Prostaglandins, mediated by cyclo-oxygenase activity, play a significant role in this cytokine-induced neurohypophysial hormone release.
Abstract:
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-1 beta and IL-6 can directly activate the AVP and oxytocin neurosecretory system. In addition, we have also investigated the effects of inhibition of cyclo-oxygenase (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-1 beta 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-1 beta and IL-6 were blocked by cyclo-oxygenase inhibitors, indomethacin (28 microM) and ibuprofen (100 nM), but not by the lipoxygenase inhibitor, BW A4C (10 micrograms/ml), suggesting that prostaglandins are involved in this process.(ABSTRACT TRUNCATED AT 250 WORDS)