Project/Area Number |
04454144
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Research Category |
Grant-in-Aid for General Scientific Research (B)
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Allocation Type | Single-year Grants |
Research Field |
環境生理学(含体力医学・栄養生理学)
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Research Institution | KYUSHU UNIVERSITY |
Principal Investigator |
HORI Tetsuo Kyushu Univ., Fac. of Medicine, Professor, 医学部, 教授 (00022814)
|
Co-Investigator(Kenkyū-buntansha) |
TAKAKI Atsushi Kyushu Univ., Fac. of Medicine, Associate Professor, 医学部, 助手 (30243934)
KAIZUKA Yasuo Kyushu Univ., Fac. of Medicine, Associate Professor, 医学部, 助手 (00224329)
KATAFUCHI Toshihiko Kyushu Univ., Fac. of Medicine, Associate Professor, 医学部, 講師 (80177401)
SHIMIZU Nobuaki Kyushu Univ., Fac. of Engineering, Associate Professor, 工学部, 助教授 (50019634)
粟生 修司 九州大学, 医学部, 助教授 (40150908)
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Project Period (FY) |
1992 – 1993
|
Keywords | Interleukin-1beta / Prostaglandine / alpha-MSH / CRF / Splenic noradrenaline / Interferon palpha / Preoptic hypothalamus / Circumventricular organs |
Research Abstract |
The aim of this project was to investigagte mechanisms of the environmental stress- induced immunosuppressionl Our findings are as follows. 1. The environmental stress and the hypothatmo-autonomic-immune system : (1) The cytotoxic activity of the splenic natural killer cells (NK activity) of rats was highest at the normal temperature (37-38゚C), while it was suppressed both at hyperthemia and hypothermia. This is obviously different from temperature sensitivity of T cells which are known to be most active at 39-40゚C.(2) Immobilization stress suppressed the splinic NK activity which was abolished by the surgical denervation of the spleen. An in vivo microdialysis of the spleen revealed that the release of the noradrenaline (NA) from the sympathetic nerve terminals markedly increased by the immobilizatin stress. (3) Central and peripheral injection of interleukin-1beta (IL-1 beta) increased the activity of the splenic nerve and the release of NA in the spleen, resulting in the suppression
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of the cellular immunity. The effects of IL-1 beta was found to be IL-1 receptor-mediated and alpha-MSH sensitive process, which was dependent on the prostaglandins (PGs) and the CRF system. 2. The mechanisms of the environmental stress-induced immunomodulation : We examined the effects of central interferon- alpha (IFN- plpha) on the splenic NK cell activity as an experimental model of opioid dependent stress-induced suppression of the cellular immunity. When recombinant human IFN- alpha, which is known to bind central opiod receptors in rats and mice, was microinjected into the preoptic/anterior hypothalamus (POA), the splenic sympathetic nerve activity increased through an activation the central CRF system. The enhancement of the nerve activity resulted in the suppression of the splenic NK activity through a beta -adrenetgic action. 3. Blood-borne immunocytokines and the hypothalamic neuronal activity : All neurons in the anteroventral region of the third ventricle (AV3V), which h The results suggested that AV3V is important in the transduction mechanisms of blood-borne cytokines into brain signals. Less
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