| Roles of sympathetic nervous system in the suppression of cytotoxicity of splenic natural killer cells in the rat. | |
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MedLine Citation:
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PMID: 8229839 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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1. We previously demonstrated that a central injection of interferon-alpha in rats induced a suppression of cytotoxicity of splenic natural killer cells which depended upon intact splenic sympathetic innervation, suggesting the important role of the splenic nerve in immunosuppression. To further study the mechanisms of this phenomenon, we investigated: (1) the effects of a central injection of recombinant human interferon-alpha on the electrical activity of the splenic nerve, and (2) the responses of splenic natural killer cytotoxicity on the electrical stimulation of the splenic nerve in urethane with alpha-chloralose anaesthetized rats. 2. An injection of recombinant human interferon-alpha (1.5 x 10(3) and 6.0 x 10(3) units (u) per rat) into the third cerebral ventricle produced a sustained and long lasting (at least for more than 60 min) increase in the electrical activity of splenic sympathetic nerve filaments in a dose-dependent manner. Following an intra-third-ventricular injection of recombinant human interferon-alpha at a dose of 6.0 x 10(3) u, the efferent discharges were elevated 2-6 times that of the pre-injection level with a mean onset latency of 12 min (8-16 min). No changes in the arterial blood pressure and body temperature were observed after injections of recombinant human interferon-alpha. 3. The excitation of the nerve activity induced by intra-ventricular recombinant human interferon-alpha was reversibly suppressed by an intravenous injection of an opioid antagonist, naloxone (1 mg/kg in 0.1 ml saline), whereas the injection of naloxone alone did not affect either the baseline level of the nerve activity or the systemic blood pressure. 4. The cytotoxicity of natural killer cells in the spleen measured by a standard chromium release assay was reduced 20 min after the laparotomy alone in anaesthetized rats. The reduced natural killer activity then recovered significantly when the splenic nerve was cut immediately after the laparotomy. When the peripheral cut end of the splenic nerve was subsequently stimulated (0.5 mA, 0.5 ms, 20 Hz for 20 min), a further suppression of natural killer cytotoxicity was observed. 5. The reduction of natural killer cytotoxicity produced by the stimulation of the splenic nerve was completely blocked by an intravenous injection of nadolol (a peripherally acting beta-adrenergic receptor antagonist), but not by that of prazosin (an alpha-antagonist). 6. These results indicate that a central injection of recombinant human interferon-alpha activates the splenic sympathetic nerve through brain opioid receptors and thereby suppresses the natural killer cytotoxicity by beta-adrenergic mechanisms.(ABSTRACT TRUNCATED AT 400 WORDS) |
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Authors:
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T Katafuchi; S Take; T Hori |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: The Journal of physiology Volume: 465 ISSN: 0022-3751 ISO Abbreviation: J. Physiol. (Lond.) Publication Date: 1993 Jun |
Date Detail:
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Created Date: 1993-11-29 Completed Date: 1993-11-29 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 0266262 Medline TA: J Physiol Country: ENGLAND |
Other Details:
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Languages: eng Pagination: 343-57 Citation Subset: IM |
Affiliation:
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Department of Physiology, Faculty of Medicine, Kyushu University, Fukuoka, Japan. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Blood Pressure / drug effects Cell Survival / drug effects Denervation Electric Stimulation Injections, Intraventricular Interferon Type I, Recombinant / administration & dosage, pharmacology* Killer Cells, Natural / physiology* Male Nadolol / pharmacology Naloxone / administration & dosage, pharmacology Neurons, Efferent / physiology Prazosin / pharmacology Rats Rats, Wistar Spleen / cytology*, innervation Sympathetic Nervous System / physiology* Tumor Cells, Cultured |
| Chemical | |
Reg. No./Substance:
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0/Interferon Type I, Recombinant; 19216-56-9/Prazosin; 42200-33-9/Nadolol; 465-65-6/Naloxone |
| Comments/Corrections | |
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