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      Production of Systemic and Hypothalamic Cytokines during the Early Phase of Endotoxin Fever

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          Abstract

          Changes in concentrations of cytokines in plasma and in hypothalamic push-pull perfusates of guinea pigs were measured within the 1 st hour after intramuscular injections of bacterial Hpopolysaccharide (LPS; Escherichia coli, 20 µg/kg) or solvent (0.9% saline). In control animals injected with solvent, interleukin (IL)-1 and tumor necrosis factor alpha (TNF-α) were not detectable in plasma. Only IL-6 was present in picogram quantities. Within 45 min after injection of LPS, the concentrations of IL-1, TNF-α, and IL-6 increased in the plasma: by several orders of magnitude for TNF-α and about tenfold for IL-G. Picogram amounts of biologically active IL-1 were detected in plasma after injection of LPS. No steady state levels of systemic cytokines were reached during the experimental period. In hypothalamic perfusates of animals injected with the solvent, no IL-1 was detectable. TNF-α could be detected at higher concentrations than IL-6. IL-6 was detectable at tenfold lower concentrations than in the plasma. In animals injected with LPS, the hypothalamic concentration of IL-6 started to increase during the period 15-30 min and the concentrations of TNF-α during the period 30-45 min after LPS injection. The concentrations of IL-6 increased by 300-400% and did not exceed picogram values. No progressive increase of hypothalamic levels of these cytokines was observed during the time course of the experiment. The method used did not detect any changes in the amount of biologically active IL-1 in hypothalamic perfusates of LPS-treated animals. No obvious correlation between concentrations of cytokines in plasma and hypothalamic perfusate was observed, indicating the brain origin of the cytokines. Since the increase in IL-6 goes in parallel with resetting of the body thermostat to the higher level, the data support the hypothesis that the increase in the concentration of IL-6 in the brain, occurring during the early phase of the fever, induces the febrile response.

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          Author and article information

          Journal
          NEN
          Neuroendocrinology
          10.1159/issn.0028-3835
          Neuroendocrinology
          S. Karger AG
          0028-3835
          1423-0194
          1995
          1995
          09 April 2008
          : 62
          : 1
          : 55-61
          Affiliations
          Departments of aComparative Physiology, Faculty of Science, and bImmunology, 2nd Faculty of Medicine, Charles University, Prague, Czech Republic; cPhysiologisches Institut, Klinikum der Justus-Liebig-Universität, Giessen, Germany; dInserm U65, Université de Montpellier II, Montpellier, France
          Article
          126988 Neuroendocrinology 1995;62:55–61
          10.1159/000126988
          7566439
          © 1995 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
          Neuroimmune Interactions

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