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      Interleukin-1α and Interleukin-1β Stimulate Adrenocorticotropin Secretion in the Rat through a Similar Hypothalamic Receptor(s): Effects of Interleukin-1 Receptor Antagonist Protein

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      , ,
      Neuroendocrinology
      S. Karger AG
      Median eminence, intracerebral

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          Abstract

          Numerous reports have demonstrated that interleukin-1 β (IL-1β) is a potent secretagogue for adrenocorticotropin (ACTH) and that IL-1α appears to be considerably less efficacious. To clarify apparent differences in the potency of IL- 1α vs. -β on ACTH secretion from a functional perspective, the IL-1 receptor antagonist protein, IRAP, was utilized. Following administration to rats either intravenously (i.v.) or adjacent to the median eminence (intra-ME), IL-1β was approximately 8-fold more potent than IL-1α. IRAP, delivered i.v. or intra-ME, inhibited ACTH secretion due to the administration of IL-1α or -β by the corresponding route. Similar amounts of IRAP were required to attenuate ACTH responses to approximately equieffective i.v. doses of IL-1α (200 ng) or -β (25 ng): IC50 for IRAP inhibition of IL-1α vs. -β was approximately 2.5 or 5.5 µg, respectively. At these IC50 doses, the ratios of IRAP/IL-1 were 12.5 and 220 for IL-1α vs. -β, respectively. These ratios are compatible with mediation by a type I-like IL-1 receptor. To compare these properties of the central IL-1 receptor to a peripheral type I IL-1 receptor in the same species, the IL-1 -enhanced rat thymocyte comitogenesis assay was utilized. Thymocyte proliferation in response to equieffective doses of IL-1α or -β was similarly inhibited by IRAP: approximate IC50 for inhibition of IL-1α vs. -β was 12.5 or 25 ng/ml, respectively. Relative to the dose of IL-1α and -β (5 ng/ml), these amounts of IRAP are within the range required to inhibit (1) the ACTH response to IL-1 in rats, reported herein, and (2) type I IL-1 receptor-mediated responses in peripheral tissues from other species. Thus, the ACTH responses to both IL-1α and IL-1β may be mediated through a central type I-like IL-1 receptor(s), which appears to be similar to the peripheral rat type I receptor. IRAP was effective at inhibiting ACTH secretion stimulated by IL-l when these agents were administered i.v. or into the hypothalamic median eminence, suggesting that type I-like IL-l receptors are present in the median eminence where they are readily accessible to modulation by circulating IL-l.

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          Author and article information

          Journal
          NEN
          Neuroendocrinology
          10.1159/issn.0028-3835
          Neuroendocrinology
          S. Karger AG
          0028-3835
          1423-0194
          1993
          1993
          08 April 2008
          : 57
          : 1
          : 14-22
          Affiliations
          Endocrine Neuroscience Laboratories, Minneapolis Medical Research Foundation and the Departments of Medicine, Hennepin County Medical Center and University of Minnesota, Minneapolis, Minn., USA
          Article
          126336 Neuroendocrinology 1993;57:14–22
          10.1159/000126336
          8386818
          87da9fce-a4d5-4d11-881e-8b8f80a30d97
          © 1992 S. Karger AG, Basel

          Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

          History
          : 28 February 1992
          : 11 May 1992
          Page count
          Pages: 9
          Categories
          Original Paper

          Endocrinology & Diabetes,Neurology,Nutrition & Dietetics,Sexual medicine,Internal medicine,Pharmacology & Pharmaceutical medicine
          Median eminence, intracerebral

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