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      Effect of Continuous Intravenous Injection of lnterleukin-6 and Pretreatment with Cyclooxygenase Inhibitor on Brain c-fos Expression in the Rat

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          Abstract

          The aim of the present study was to assess potential brain sites of stimulation by peripheral interleukin (IL)-6 of the hypothalamo-pituitary-adrenal (HPA) axis in the rat, using c-fos protein as a marker of cellular activation. Involvement of prostaglandins in IL-6-induced ACTH secretion and c-fos expression was also investigated. IL-6 was infused continuously (40 ng/min) for 90 min to conscious male rats. Blood samples were taken before the infusion and at 30 and 90 min for measurement of plasma ACTH. Expression of c-fos in the brain was examined by immunohistochemistry. Administration of IL-6 significantly elevated plasma ACTH levels at 30 min (495 ± 105 vs. 117 ± 17 pg/ml in controls, p < 0.05). Elevated levels were still present at 90 min (596 ± 139 vs. 113 ± 20 pg/ml in controls, p < 0.05). Infusion of IL-6 (3.6 µg/rat) markedly triggered c-fos expression in hypothalamic paraventricular (PVN) and supraoptic nuclei (SON), as well as in the central amygdaloid nucleus (CeA), the nucleus tractus solitarius and the locus coeruleus. Pretreatment with the cyclooxygenase inhibitor indomethacin (10 mg/kg, i.v.) suppressed the ACTH response induced by IL-6. The number of IL-6-induced immunoreactive cells in the PVN was significantly reduced by indomethacin pretreatment (p < 0.01), but the number of IL-6-induced c-fos-positive cells in the SON and CeA remained unchanged. These findings suggest that circulating IL-6 may exert central actions by acting directly or indirectly on brain neurons. In addition, the ability of IL-6 to activate the HPA axis may depend upon the release of prostaglandins, probably in the brain.

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          Author and article information

          Journal
          NEN
          Neuroendocrinology
          10.1159/issn.0028-3835
          Neuroendocrinology
          S. Karger AG
          0028-3835
          1423-0194
          1997
          1997
          09 April 2008
          : 66
          : 1
          : 47-53
          Affiliations
          aDepartment of Clinical Laboratory Medicine and bFirst Department of Internal Medicine, Kagawa Medical University, Miki-Cho, Kita-Gun, Kagawa, Japan
          Article
          127218 Neuroendocrinology 1997;66:47–53
          10.1159/000127218
          9258918
          © 1997 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.

          Page count
          Pages: 7
          Categories
          Neuroimmunology

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