| Co-Investigator(Kenkyū-buntansha) |
MORI Toshinori Kyushu University Fac. of Med. ; Instructor., 医学部, 助手 (40200373)
AOU Shuji Kyushu University Fac. of Med. ; Associate Professor., 医学部, 助教授 (40150908)
KAIZUKA Yasuo Kyushu University Fac. of Med. ; Instructor., 医学部, 助手 (00224329)
SHIMIZU Nobuaki Kyushu University Fac. of Med. ; Assistant Professor., 医学部, 講師 (50019634)
KATAFUCHI Toshihiko Kyushu University Fac. of Med. ; Instructor., 医学部, 助手 (80177401)
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| Research Abstract |
We investigathed how the hypothalamus is involved in the reciprocal communication between the brain and the immune system thereby producing alterations in immunity, thermoregulation and feeding.
(1) Effects of interleukin-1 (IL-1) and interferona (IFN alpha) on the hypothalamic neurons : . (a) Direct application of IL-1 beta (2.8-l2OpM) and IFNa (500-200OU/ml) altered the activities of thermosensitive and glucoseresponsive neurons in the hypothalamus of rats in such a way to produce fever and anorexia, respectively. While the actions of IL-1, 8 on hypothalamic neurons required the local production of PGE2, those of IFN a were mediated by the opioid receptors. The effects of IL-1, 8 on the neurons, like those on lymphocytes, were antagonized by a MSH. (b) Neurons in the organum vasculosum lamina terminalis (OVLT) were found to be more sensitive to PGE2 than those in the preoptic hypothalamus. Most OVLT warmsensitive neurons were inhibited by PGE2. The results provide further evidence for
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the critical involvement ofthe OVLT in mediating fever to blood-borne cytokines through the local release of PGE2.
(2) Effects of temperatures, on the splenic NK cytotoxicity : Both the hyperthermic (39-49pﾟC) and hypothermic (34-36ﾟC) rats which were subjected to either environmental heat and cold stresses or hypothalamic cooling and warming exhibited the reduced NK activity. Preincubation at higher temperatures (39-40ﾟC) in vitro also decreased the NK activity. Thus, NK activity, unlike T cell functions, is depressed by febrile temperatures in vivo and in vitro.
(3) Involvement of brain opioids and sympathetic nerves in the stress-induced immunosuppression : Intracerebral injections of IFN and 8 endorphin in the rat suppressed the splenic NK activity by activation of brain opioid receptors. This immunosuppression was found to be mediated predominantly by the splenic sympathetic nerve from the results of the experiments with recording of its electrical activity, its electrical stimulation, splenic denervation and splenic noradrenaline release as determined by in vivo microdialysis. Less
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