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      Radiodetoxified Lipopolysaccharide Fails to Activate the Hypophyseal- Pituitary-Adrenal Axis in the Rat

      a , b , c , a

      Neuroimmunomodulation

      S. Karger AG

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          Abstract

          Lipopolysaccharide (LPS) is known to raise the concentration of the circulating stress hormones such as ACTH, corticosterone and β-endorphin. This effect of endotoxin is mediated by different immune system-released hormone-like factors (e.g. interleukins, tumor necrosis factor etc.). Gamma-ray irradiation of LPS alters its biological properties and results in a radiodetoxified LPS preparation with numerous beneficial effects and decreased toxicity. In this study we compared the neuroendocrine effects of a commercial LPS and our native and radiodetoxified LPS preparations in rats. Plasma ACTH, corticosterone and β-endorphin levels were measured by specific radioimmunoassays 120 min after intraperitoneal LPS administration. Control animals were injected with saline. Results show a dramatic increase in all hormones after administration of commercial and our native LPS preparation. Hormone levels in saline-injected controls and radiodetoxified LPS-treated rats did not rise significantly. These results suggest that radio-detoxification disintegrated that part of the LPS molecule complex which is responsible for toxicity including an enhanced production of cytokines, which trigger the hypothalamo-pituitary-adrenal axis.

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          Regulation of the HPA axis by cytokines.

          Cytokines are a group of polypeptide mediators, classically associated with the regulation of immunity and inflammation. However, these peptides regulate not only local immune/inflammatory responses, but also elicit many CNS-mediated responses which accompany such immune/inflammatory reactions. This article reviews the evidence that interleukin (IL)-1, IL-6, and tumor necrosis factor alpha (TNFalpha) produce hypothalamo-pituitary-adrenal (HPA) axis activation in response to various threats to homeostasis. To aid such an examination, and to gain insights into the potential mechanisms by which these cytokines influence the HPA axis, experimental findings are discussed within a framework of criteria. If a particular cytokine plays a significant role in the regulation of the HPA axis in response to a particular pathophysiology, then necessarily: (1) receptors for that cytokine should be present within tissues associated with the HPA axis; (2) administration of that cytokine should elicit HPA activation; (3) the HPA axis should be exposed to that cytokine; and (4) inhibition of the action of that cytokine should prevent HPA activation. The evidence discussed indicates that some, if not all, of these criteria are met for each of IL-1, IL-6, and TNFalpha. However, the extensive interactions between different cytokines, the broad spectrum of pathophysiologies associated with increased cytokine production (including inflammatory and non-inflammatory stresses), and the number of tissues/cells capable of either synthesizing or responding to cytokines, suggest that multiple mechanisms mediate the influence of cytokines on the HPA axis.
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            Effects of mediobasal hypothalamic lesion on immunoreactive ACTH/β-endorphin levels in cerebrospinal fluid, in discrete brain regions, in plasma, and in pituitary of the rat

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              Author and article information

              Journal
              NIM
              Neuroimmunomodulation
              10.1159/issn.1021-7401
              Neuroimmunomodulation
              S. Karger AG
              1021-7401
              1423-0216
              2000
              December 2000
              15 December 2000
              : 8
              : 3
              : 128-131
              Affiliations
              aInstitute of Experimental Medicine, Hungarian Academy of Sciences, and b‘Fodor József’ National Center of Public Health, Frédéric Joliot-Curie Research Institute for Radiobiology and Radiohygiene, Budapest, Hungary; cMaryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, Md., USA
              Article
              54272 Neuroimmunomodulation 2000;8:128–131
              10.1159/000054272
              11124578
              © 2000 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
              Figures: 3, References: 27, Pages: 4
              Categories
              Original Paper

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