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      A Potential Mechanism of Local Anti-Inflammatory Action of Alpha-Melanocyte-Stimulating Hormone within the Brain: Modulation of Tumor Necrosis Factor-Alpha Production by Human Astrocytic Cells

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          Abstract

          The proinflammatory cytokine tumor necrosis factor-α(TNF-α) occurs in CNS tissue in neurological disorders, infection, and injury. Its excessive production is believed to contribute to local pathology, in which case modulation of TNF-αproduction should promote survival of neural tissue. The neuropeptideα-melanocyte stimulating hormone [α-MSH (1-13)] inhibits TNF-αproduction in vivo and in vitro, and in this research we tested the capacity of the peptide, and of an anti-inflammatory COOH-terminal tripeptide fragment of it, to inhibit TNF-αproduction induced by bacterial endotoxin in cells of a human glioma line (A-172, anaplastic astrocytoma cells). Both peptides were effective, although theα-MSH (1–13) sequence was more potent. Preincubation of the cells withα-MSH (1–13) markedly increased its effectiveness. The anticytokine effect ofα-MSH in glioma cells may be mediated by human melanocortin-1 receptors; mRNA for this receptor subtype was isolated from resting A-l 72 cells. These results, combined with prior evidence of effectiveness ofα-MSH molecules in modulating inflammatory processes and of their low toxicity, suggest that the molecules may be useful in the treatment of CNS disorders that have an inflammatory component.

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          Author and article information

          Journal
          NIM
          Neuroimmunomodulation
          10.1159/issn.1021-7401
          Neuroimmunomodulation
          S. Karger AG
          1021-7401
          1423-0216
          1997
          1997
          12 September 1997
          : 4
          : 1
          : 37-41
          Affiliations
          Departments of aPhysiology and bAnesthesiology and Pain Management, University of Texas Southwestern Medical Center at Dallas, Tex., USA; cClinica Medica 3, Ospedale Maggiore, Milan, Italy
          Article
          97313 Neuroimmunomodulation 1997;4:37–41
          10.1159/000097313
          9326743
          © 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: 5
          Categories
          Original Paper

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