| Project/Area Number |
06454153
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Environmental physiology (including Physical medicine and Nutritional physiology)
|
|---|
| Research Institution | KYUSHU UNIVERSITY |
|---|
Principal Investigator |
HORI Tetsuro Kyushu University, Dept.of Physiology, Professor, 医学部, 教授 (00022814)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
TAKE Sachiko Kyushu University, Dept.of Physiology, Assistant Professor, 医学部, 助手 (80253425)
TAKAKI Atsushi Kyushu University, Dept.of Physiology, Assistant Professor, 医学部, 助手 (30243934)
KATAFUCHI Toshihiko Kyushu University, Dept.of Physiology, Assistant Professor, 医学部, 講師 (80177401)
AOU Shuji Kyushu University, Dept.of Physiology, Associate Professor, 医学部, 助教授 (40150908)
|
|---|
| Project Period (FY) |
1994 – 1996
|
| Project Status |
Completed (Fiscal Year 1996)
|
| Budget Amount *help |
¥7,200,000 (Direct Cost: ¥7,200,000)
Fiscal Year 1996: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1995: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1994: ¥4,000,000 (Direct Cost: ¥4,000,000)
|
|---|
| Keywords | Neuro-immuno-endocrine networks / Sympathetic nerve / Natural killer cytotoxicity / Corticotropin-releasing factor (CRF) / Prostaglandin E2 (PGE2) / Pain modulation / PGE2 (EP) receptors / Interleukin-1 / プロスタグランディンE2 / EP1レセプター / マイクロダイアリシス法 / TNF / インターロイキン-1β / conrticotropin-releasing factor / マイクロダイアリシス / コルチコトロピン放出因子 / ノルアドレナリン / 迷走神経背側運動核 / インターロイキン-6 / 感覚過敏 / 前頭前野 / 広作動域ニューロン / 第3脳室壁前腹側領域 / 発熱 / プロスタグランディン |
|---|
| Research Abstract |
We have investigated the central and peripheral mechanisms of immunosuppression, pain modulation and fever which are induced by cytokines. (1) Both brain-derived IL-1beta and IFNalpha suppress the natural killer (NK) cytotoxicity in the spleen through an activation of central CRF system and splenic sympathetic mechanisms. While the synthesis of prostanoids is an obligatory step for IL-1beta to activate the CRF system, the action of IFNalpha involves the opioid receptor mechanisms. (2) Non-pyrogenic, small amounts (10-100pg) of IL-1beta, IL-6 and TNFalpha produce hyperalgesia through the production of prostanoids and an alphaMSH-sensitive process in the brain. Moreover, the action of TNFalpha may be mediated, at least in part, by its ability to produce IL-1. The most sensitive site to microinjected IL-1beta for eliciting hyperalgesia is located in the preoptic hypothalamus and the neighboring basal forebrain. By contrast, IL-1beta, when microinjected into the ventromedial hypothalamus,
… More
induces a short-lasting hypoalgesia. (3) Central PGE2 in Large amounts (mug) induces an activation of splenic sympathetic nerve, hypoalgesia and fever through its action on EP1 receptors, whereas small amounts (pg) of PGE2 in the brain elicits hyperalgesia by its action on EP3 receptors. (4) Neurons in the anteroventral wall of the third ventricle (AV3V), which send axons to the preoptic hypothalamus or the paraventricular nucleus, respond to blood-borne IL-1beta in PGs-dependent way, suggesting that the AV3V neurons play a role in the transformation of blood-borne immune signal into brain signal. (5) Immobilization stress induces an enhanced release of noradrenaline (NA) in the medial prefrontal cortex as well as in the spleen in a central CRF-dependent way. This immobilization-induced splenic NA release is found to cause a suppression of NK activity, indicating a cardinal role of splenic sympathetic nerve in the neural modulation of immunity. (6) The vagal nerve innervating the thymus alters the activity in response to intravenous injection of IL-1beta, suggesting another route of central information to the immune system. Less
|
