| Co-Investigator(Kenkyū-buntansha) |
ARIMURA Akira US-Japan Biomedical Research Laboratories, Tulane University, ヘベルトセンター・米日生物医学研究所(アメリカ合衆国), 所長教授
WALTER Riede マックス, プランク生理学臨床研究所・生理学部I(ドイツ国), 教授
ECKHART Simo マックス, プランク生理学臨床研究所・生理学部I(ドイツ国), 教授
SHIMIZU Nobuaki Faculty of Engineering, Kanazawa University, 工学部, 助教授 (50019634)
KATAFUCHI Toshihiko Faculty of Medicine, Kyushu University, 医学部, 講師 (80177401)
AOU Shuji Faculty of Medicine, Kyushu University, 医学部, 助教授 (40150908)
SIMON Eckhart Max-Planck-Institut
RIEDEL Walter Max-Planck-Institut
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| Research Abstract |
The aim of this project was to elucidate roles of hypothalamus-endocrine and autonomic axis in neuroimmunomodulation. We investigated mechanisms of central interferon-alpha-induced immunosuppression and a part of the results was presented by a member of this project, Dr.T.Katafuch, at 2nd international congress of neuroimmunomodulation at Paestum, Italy (September, 1993).
After the congress, he visited Max-Planck-Institute, and discussed with Drs.Simon and Riedel. In September 1993, Dr.Riedel visited our laboratory to present his results and to discuss with us. The details of the results of this project are as follows.
1)Microinjection of interferon-alpha (IFN-alpha) into the preoptic/anterior hypothalamic area (POA), but not into other hypothalamic nuclei, resulted in a marked decrease in the splenic natural killer (NK) cell activity. The suppression was completely blocked by splenic denervation.
2)Microinjection of IFN-alpha into the POA, but not into the paraventricular nucleus (PVN),
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produced an increase in the splenic nerve activity for more than 1 hour. However, CRF was effective in increasing the nerve activity when injected into both POA and PVN.
3)Intraventricular injection of interleukin-1beta(IL-1beta) induced a prolonged increase in the splenic nerve activity, which was blocked by pretreatment with alpha-MSH. In addition, pretreatment with salicylate completely blocked the IL-1beta induced activation of the nerve activity.
4)All neurons which antidromically responded to stimulation of POA or PVN altered their firing rates following intravenous injection of IL-1beta. These responses to IL-1beta were attenuated by iontophoretic application of salicylate, suggesting a local synthesis of prostadrandins following systemic IL-1beta which would change the firing rates of the neurons.
5)Application of PACAP to the magnocellular neurons in the PVN resulted in an increase in firing rate in a dose-dependent manner. This finding may explain a possible mechanism for PACAP-induced secretion of vasopressin. Less
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