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Vol. 5, No. 3-4, 1998
Issue release date: May–August 1998
Section title: Paper
Neuroimmunomodulation 1998;5:172–177
(DOI:10.1159/000026334)

Neuroimmunomodulatory Actions of Hypothalamic Interferon-α

Hori T. · Katafuchi T. · Take S. · Shimizu N.
Department of Physiology, Kyushu University Faculty of Medicine, Fukuoka, Japan

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Article / Publication Details

First-Page Preview
Abstract of Paper

Published online: 9/4/1998

Number of Print Pages: 6
Number of Figures: 0
Number of Tables: 0

ISSN: 1021-7401 (Print)
eISSN: 1423-0216 (Online)

For additional information: http://www.karger.com/NIM

Abstract

Recent studies have revealed that the brain produces interferon-α (IFN-α) in response to noninflammatory as well as inflammatory stress and that it might have a role in normal physiology. When administered intracerebrally, IFN-α causes diverse effects including fever, anorexia, analgesia and changes in the central neuronal activities. These responses are inhibited by the opioid receptor antagonist naloxone. This is consistent with the reports suggesting that recombinant human (rh) IFN-α binds to opioid receptors in rodent brain membrane. We revealed that rhIFN-α altered the activity of thermosensitive neurons in the medial preoptic area (MPO) and glucose-responsive neurons in the ventromedial hypothalamus in an opioid-receptor-dependent way. As a stress which produces opioid-dependent analgesia is known to suppress the cytotoxicity of splenic natural killer cells, we investigated whether the administration of β-endorphin and rhIFN-α may induce a similar immunosuppression. We found that central, but not peripheral, injection of both compounds inhibited natural killer (NK) cytotoxicity. Further studies revealed that rhIFN-α decreased the activity of MPO neurons via opioid receptors and the altered activity of MPO neurons in turn resulted in the activation of corticotropin-releasing factor neurons, thereby suppressing NK cytotoxicity predominantly through activation of the splenic sympathetic nerve and β-receptor mechanisms in splenocytes. Thus, IFN-α may alter the brain activity to exert a feedback effect on the immune system. Further detailed whole-cell clamping analyses on neuronal mechanisms in rat brain tissue slices showed that the inhibitory effect of rhIFN-α on N-methyl-D-aspartate-induced membrane current responses of MPO neurons was mediated not only by opioid receptors but also by the local production of reactive oxygen intermediates, nitric oxide and prostanoids, possibly due to neuron-glial cell interaction.


  

Author Contacts

Dr. Tetsuro Hori, Department of Physiology
Kyushu University Faculty of Medicine
Fukuoka 812-8582 (Japan)
Tel. +81 92 642 6085, Fax +81 92 642 6093
E-Mail thori@physiol.med.kyushu-u.ac.jp

  

Article Information

Number of Print Pages : 6
Number of Figures : 0, Number of Tables : 0, Number of References : 63

  

Publication Details

NeuroImmunoModulation
Official Journal of the International Society for Neuroimmunomodulation

Vol. 5, No. 3-4, Year 1998 (Cover Date: May-August 1998)

Journal Editor: S.M. McCann, Dallas, Tex.; J.M. Lipton, Dallas, Tex.
ISSN: 1021–7401 (print), 1423–0216 (Online)

For additional information: http://www.karger.ch/journals/nim


Article / Publication Details

First-Page Preview
Abstract of Paper

Published online: 9/4/1998

Number of Print Pages: 6
Number of Figures: 0
Number of Tables: 0

ISSN: 1021-7401 (Print)
eISSN: 1423-0216 (Online)

For additional information: http://www.karger.com/NIM


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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 goverment 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.
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