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      lnterleukin-10 Inhibits Lipopolysaccharide-Induced Tumor Necrosis Factor and Interleukin-1β Production in the Brain without Affecting the Activation of the Hypothalamus-Pituitary-Adrenal Axis

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          Abstract

          Interleukin (IL) 10 inhibits endotoxin (lipopolysaccharide; LPS) induced tumor necrosis factor (TNF) production in vivo and in vitro. In turn, IL-10 is induced by LPS and acts as a negative feedback to limit TNF production. We investigated the effects of IL-10 on brain TNF and IL-1β production induced by a central LPS administration in mice. Because central LPS also induces peripheral TNF, we also measured the serum TNF levels. A single intracere-broventricular injection of murine recombinant IL-10 (75 ng/mouse) simultaneously with LPS (2.5 µg/mouse) almost completely inhibited brain TNF production. The brain IL-1β production was also inhibited, as was the serum concentration of the acute-phase protein serum amyloid A. On the other hand, intracerebroventricular administration of an anti-IL-10 monoclonal antibody (JES5-2A5; 60 µg/mouse) potentiated brain TNF and IL-1β production. Identical results were obtained when the serum TNF levels were measured. IL-10 did not affect the LPS-induced increase of serum corticosterone, the main endogenous inhibitor of TNF production, or the induction of IL-6. These results indicate that LPS-induced IL-10 can act as an important endogenous inhibitor of brain TNF production and suggest an anti-inflammatory role for IL-10 in the central nervous system.

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          Author and article information

          Journal
          NIM
          Neuroimmunomodulation
          10.1159/issn.1021-7401
          Neuroimmunomodulation
          S. Karger AG
          1021-7401
          1423-0216
          1995
          1995
          20 November 1995
          : 2
          : 3
          : 149-154
          Affiliations
          a Istituto di Ricerche Farmacologiche ‘Mario Negri’ Milano; b Department of Immunology, Pharmacia, Nerviano (Milan), Italy; c Department of Medical Genetics-1RIBHN and d Service d'Immunologie, Hopital Erasme, Université Libre de Bruxelles, Belgium
          Article
          96885 Neuroimmunomodulation 1995;2:149–154
          10.1159/000096885
          8646564
          6d46f9de-9fc0-418c-9c9b-358e96ed05fd
          © 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.

          History
          Page count
          Pages: 6
          Categories
          Original Paper

          Endocrinology & Diabetes,Neurology,Nutrition & Dietetics,Sexual medicine,Internal medicine,Pharmacology & Pharmaceutical medicine
          Hypothalamus-pituitary-adrenal axis,Interleukin 1,Interleukin 10,Tumor necrosis factor,Endotoxin,Serum amyloid A

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