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      Catecholamine, Indoleamine and Corticosteroid Responses in Mice Bearing Tumors

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          Abstract

          The neurochemical and endocrine responses to inoculation of mice with the murine lymphoma cell line AW5E was studied. This cell line was chosen because it is NK cell lysis resistant and thus does not induce a normal immune response. Immune activation has long been known to be a potent stimulator of the hypothalamo-pituitary-adrenocortical (HPA) axis as well as brain catecholamine and indoleamine metabolism, involving increases in the brain concentrations of catabolites of norepinephrine (NE) and serotonin (5-HT), as well as free tryptophan. Mice injected intravenously with AW5E tumor cells exhibited small increases in plasma corticosterone and hypothalamic NE and 5-HT catabolites one day after injection. There were no significant changes after 6 or 8 days, but a sustained increase in hypothalamic NE and 5-HT metabolism appeared 10 days after injection. There were similar, but more limited changes in the brain stem and prefrontal cortex. On the last day tested (day 14), plasma corticosterone was slightly elevated, as were hypothalamic dopamine, NE and 5-HT catabolites and tryptophan. These results indicate that inoculation with AW5E tumor cells increases brain catecholamine and serotonin metabolism, the hypothalamus being the most sensitive region. The most marked increases occurred in the few days preceding death, and thus may be associated with the pathology of the tumor growth.

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          The role of cytokines in cancer cachexia

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            Systematic interleukin-1 administration stimulates hypothalamic norepinephrine metabolism parallelling the increased plasma corticosterone

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              Virus infection as a stressor: influenza virus elevates plasma concentrations of corticosterone, and brain concentrations of MHPG and tryptophan.

              Balb/c mice were infected with influenza virus PR8 (H1N1) by the intranasal route. At various subsequent times, brain samples were examined for their content of catecholamine and indoleamine metabolites, and plasma corticosterone was measured. Virus infection was associated with a progressive loss of body and thymus weights, and an increase in plasma corticosterone. Spleen weight initially increased then decreased. There were also increases in the cerebral content of free tryptophan throughout the brain, and of MHPG, a major catabolite of norepinephrine, especially prominent in the hypothalamus. Thus influenza virus can be regarded as a stressor because, like behavioral stressors, it activates the hypothalamic-pituitary-adrenal axis, and increases cerebral concentrations of tryptophan and norepinephrine catabolites. These changes resemble those observed following administration of sheep red blood cells and Newcastle disease virus, noninfectious activators of the immune system, suggesting that noradrenergic and HPA activation are common concomitants of antigenic stimulation. The mediator of these effects may be interleukin-1 released by activated macrophages. It should be noted that animals infected with viruses can be expected to exhibit stress-like endocrine and neurochemical changes.
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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
                : 107-113
                Affiliations
                aDepartment of Pharmacology and Therapeutics and bDepartment of Microbiology and Immunology, Louisiana State University Medical Center, Shreveport, La., USA
                Article
                54269 Neuroimmunomodulation 2000;8:107–113
                10.1159/000054269
                11124575
                2d4acc56-8bc2-4ece-8fb3-88401e5fa163
                © 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.

                History
                Page count
                Figures: 5, Tables: 1, References: 48, Pages: 7
                Categories
                Original Paper

                Endocrinology & Diabetes,Neurology,Nutrition & Dietetics,Sexual medicine,Internal medicine,Pharmacology & Pharmaceutical medicine
                Tryptophan,Serotonin,Tumor,Norepinephrine,Cancer,Dopamine,Corticosterone

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