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      Interleukin-1β and Interleukin-6 Specifically Increase the Release of Prostaglandin E 2 from Rat Hypothalamic Explants in vitro

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          Abstract

          It has previously been shown that the cytokines interleukin-1β and interleukin-6 (IL-1β and IL-6) stimulate directly the release of corticotrophin-releasing-hormone-41 from the rat hypothalamus in vitro, while IL-1β can also stimulate the release of somatostatin. These effects can be antagonized by drugs which block prostaglandin (PG) synthesis. PGs are also involved in the control of hypothalamic neuropeptides by other neuron transmitters. In the present study, we have characterized the production of PGs from the rat hypothalamus in vitro, and investigated the effects of IL-1β and IL-6, as well as the neurotransmitters norepinephrine, acetylcholine and 5-hydroxytryptamine, on the acute release of PGs, using a well-validated acute hypothalamic incubation system. The rate of release of PGs [PGE<sub>2</sub>, PGF<sub>2α</sub> 6-keto-PGF<sub>1α </sub>(6KPGF<sub>1α</sub>) and thromboxane B<sub>2</sub> (TXB<sub>2</sub>) in the medium was found to stabilize after 60 min of preincubation and thereafter remain constant, with TXB<sub>2</sub> being the predominant species. Twenty-minute incubation in the presence of human recombinant IL-1β or IL-6, in the dose range 1-100 U/ml, had no effect on the release of PGF<sub>2α</sub>, 6KPGF<sub>1α</sub> or TXB<sub>2</sub>; however, the release of PGE2 was significantly increased by both IL-1β and IL-6. The effect of IL-1β was antagonized by both indomethacin and dexamethasone. None of the other neurotransmitters tested had any effect on the release of any of the PGs. It is concluded that the regulation of hypothalamic PG release may be investigated by means of acute rat hypothalamic explants, as has previously been shown for hypothalamic peptides and amines. Furthermore, IL-1β and IL-6 specifically stimulate PGE2 release, possibly implicating this PG in certain of the hypothalamic effects of IL-1β and IL-6.

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          Author and article information

          Journal
          NEN
          Neuroendocrinology
          10.1159/issn.0028-3835
          Neuroendocrinology
          S. Karger AG
          0028-3835
          1423-0194
          1992
          1992
          07 April 2008
          : 56
          : 1
          : 61-68
          Affiliations
          aDepartment of Pharmacology, Catholic University Medical School, Rome, Italy; bDepartment of Endocrinology, St. Bartholomew’s Hospital, London, UK
          Article
          126209 Neuroendocrinology 1992;56:61–68
          10.1159/000126209
          1641074
          © 1992 S. Karger AG, Basel

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          Page count
          Pages: 8
          Categories
          Original Paper

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