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      Interleukin-2: Structural and Biological Relatedness to Opioid Peptides

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          Abstract

          Interleukin (IL)-2 is not only an immunoregulatory factor, but also an analgesic molecule. There are distinct domains of immune and analgesic functions in the IL-2 molecule. The analgesic domain is located around the 45th Tyr residue of human IL-2 in tertiary structure. Antiopioid (β-endorphin, Leu-enkephalin, Met-enkephalin and dynorphin A1–13) sera partially neutralized the analgesic activity of IL-2. Monoclonal antibody against the IL-2 receptor α subunit (Tac) could not block the analgesic activity of IL-2. There existed cross-reactivity between IL-2 and antiopioid sera by indirect ELISA. These studies show strong structural and biological similarities between IL-2 and opioid peptides. The tertiary structure around the 45th residue of IL-2 composes the analgesic domain that is similar to that of endogenous opioids. These results are consistent with the hypothesis that multiple domains of cytokines serve as the structural bases for the immunoregulatory and neuroregulatory effects of cytokines.

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          Most cited references 4

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          Interleukin-2 as a neuroregulatory cytokine

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            Immunoautoradiographic localization of interleukin 2-like immunoreactivity and interleukin 2 receptors (Tac antigen-like immunoreactivity) in the rat brain

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              Behavioural and ECoG spectrum changes induced by intracerebral infusion of interferons and interleukin 2 in rats are antagonized by naloxone.

              Rat interferon, alpha-interferon, interleukin 2 and recombinant interleukin-2 injected into the third cerebral ventricle produced typical behavioural sedation and/or sleep and ECoG synchronization in rats while beta-interferon produced no behavioural sleep or ECoG synchronization. A slight sedation was observed after the largest dose of beta-interferon only. During sleep induced by lymphokines, a dose-dependent increase in total voltage power as well as in the 0.5-3, 4-7 and 12-16 Hz frequent bands was observed. Much smaller doses were required to produce similar behavioural and ECoG spectrum effects after infusion of interferons and interleukin-2 into the locus coeruleus. No significant behavioural and ECoG changes were obtained after infusion of the same doses of interferons and interleukin-2 into other areas of the brain (caudate nucleus, dorsal hippocampus, substantia nigra pars compacta, ventromedial hypothalamus). The behavioural and ECoG effects of alpha-interferon, rat interferon and interleukin-2 were blocked in animals pretreated with naloxone. These results are consistent with the hypothesis that the behavioural and ECoG effects of these lymphokines are mediated at locus coeruleus level by stimulation of opiate receptors.
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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
                June 2000
                08 June 2000
                : 8
                : 1
                : 20-24
                Affiliations
                aDepartment of Neurobiology, Second Military Medical University, bShanghai Institute of Biochemistry, Chinese Academy of Science, Shanghai, People’s Republic of China
                Article
                26448 Neuroimmunomodulation 2000;8:20–24
                10.1159/000026448
                10859484
                © 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.

                Page count
                Figures: 2, References: 18, Pages: 5
                Categories
                Original Paper

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