Interleukin-1 beta 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-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)
Yasin
S A
SA
Department of Gynaecology, UMDS, London, UK.
Costa
A
A
Forsling
M L
ML
Grossman
A
A
D000818:Animals; D001127:Arginine Vasopressin / Q000378:metabolism; D044482:Benzeneacetamides; D006877:Hydroxamic Acids / Q000494:pharmacology; D007052:Ibuprofen / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology*; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008297:Male; D010121:Oxytocin / Q000378:metabolism; D010904:Pituitary Gland, Posterior / Q000187:drug effects / Q000378:metabolism*; D010909:Pituitary Hormones, Posterior / Q000096:biosynthesis*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013268:Stimulation, Chemical
D044482:Benzeneacetamides; D006877:Hydroxamic Acids; D007375:Interleukin-1; D015850:Interleukin-6; D016859:Lipoxygenase Inhibitors; D010909:Pituitary Hormones, Posterior; C056614:N-(3-phenoxycinnamyl)acetohydroxamic acid; D001127:Arginine Vasopressin; D010121:Oxytocin; D011189:Potassium Chloride; D007052:Ibuprofen; D007213:Indomethacin