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      Endotoxin-Stimulated Release of Cytokines by Cultured Cells from the Murine Neurohypophysis: Role of Dexamethasone and Indomethacin

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          Abstract

          It is well established that many cell types produce inflammatory cytokines and we were interested to see whether cells in the neurohypophysis had this ability. This study examines the effect of lipopolysaccharide (LPS) on cytokine production in cultured murine neural lobe (NL) cells. Cells were cultured from the neurohypophysis of mice not older than 5 days and the experiments were performed after 12 days in culture. The majority of cells in culture were immunoreactive for glial fibrillary acidic protein, indicating that the cells were pituicytes. Cytokines were measured in 24-hour samples using commercial ELISA kits. Cells growing in a medium free of endotoxin released 94.3 ± 6.6 pg IL-6/NL/24 h (mean ± SEM, n = 21). The release of interleukin-6 (IL-6) was reversible and increased concentration dependently with LPS in the concentration range of 0.1–1 ng/ml. The addition of 1 ng/ml LPS increased the IL-6 release 12-fold to a maximum value of 1,134 ± 85.5 pg IL-6/NL/24 h (mean ± SEM, n = 6). No trace of interleukin-1β (IL-1β) (<3 pg/NL/24 h) or tumor necrosis factor-α (<10 pg/NL/24 h) was detected after LPS stimulation. We examined the effect of dexamethasone (10<sup>–6</sup> M) and indomethacin (10<sup>–4</sup> M) on the release of IL-6 in submaximally stimulated cells. Dexamethasone inhibited the unstimulated and the LPS-stimulated release of IL-6 by 70 and 81%, respectively. Indomethacin had no influence on the release, and it is concluded that cyclooxygenase is not involved in the response. A close association exists between the membrane of the neurosecretory endings and the pituicytes in the neurohypophysis. This naturally raises the question as to whether IL-6 might reflect a physiological connection between the two cell types.

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          Most cited references 5

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          Induction of tumor necrosis factor-alpha mRNA in the brain after peripheral endotoxin treatment: comparison with interleukin-1 family and interleukin-6.

           S Gatti,  T Bartfai (1993)
          The constitutive expression of tumor necrosis factor-alpha (TNF alpha) mRNA and its induction (60 min later) by peripheral injection of Escherichia coli lipopolysaccharide (2 mg/kg i.p.) was demonstrated by polymerase chain reaction (PCR), in the pituitary and hypothalamus but not in the striatum or hippocampus of the rat. The pattern of TNF alpha mRNA induction is different from that observed for mRNAs of IL-1 alpha and IL-1 beta, IL-1ra and IL-6 respectively. This demonstration of the induction of TNF alpha in the brain may contribute to our understanding of the central effects of TNF alpha in fever and anorexia.
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            Immunoreactive interleukin-1β localization in the rat forebrain

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              The role of interleukin-1 and tumor necrosis factor α in the neurochemical and neuroendocrine responses to endotoxin

               Adrian Dunn (1992)
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                Author and article information

                Journal
                NIM
                Neuroimmunomodulation
                10.1159/issn.1021-7401
                Neuroimmunomodulation
                S. Karger AG
                1021-7401
                1423-0216
                1999
                August 1999
                01 September 1999
                : 6
                : 5
                : 330-335
                Affiliations
                Department of Pharmacology, The Royal Danish School of Pharmacy, Copenhagen, Denmark
                Article
                26392 Neuroimmunomodulation 1999;6:330–335
                10.1159/000026392
                10474051
                © 1999 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: 5, References: 16, Pages: 6
                Categories
                Original Paper

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