Brain mechanisms of stress-induced immunomodulation

应激诱导免疫调节的脑机制

• 批准号: 09670072
• 负责人: TAKE Sachiko
• 金额: $ 1.98万
• 依托单位: KYUSHU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09670072/
• 关键词: Stress; Hypothalamus; Cytokines; Cytotoxicity of natural killer cells; c-Fos; Prostaglandin E_2; RNase Protection Assay; Th1; Th2 balance; Thl; NK括牲; 定量化RT-PCR

It is well known that various kinds of stressors modulate immune functions, suggesting the brain control of the immune system. In the present study we attempted to reveal the brain mechanisms of stress-induced modulation of cellular immune functions and have found those findings below :(1)Immobilization stress activated neurons of the hypothalamic nuclei, especially those of the paraventricular nucleus of the hypothalamus (PVN), which regulates both the sympathetic nervous system and the hypothalamic pituitary adrenocortical axis. Prostaglandin E2 induced by immobilization stress in the PVN may play a role in suppressing NK activity with the mediation of the sympathetic nervous system.(2)The PVN and teh ventromedial hypothalamus (VMH) tonically activated and the preoptic hypothalamus (POA) and the lateral hypothalamus (LH) tonically inhibited the activity of the splenic sympathetic nervous system.(3)Non-inflamatory stress such as immobilization stress enhanced the expression of mRNA fo … More r immune cytokines such as IFN-alpha, IL-1beta, TNFalpha, TNFbeta, IL-3, IL-6, and IL-10. Especially IFNalpha and lL-1 beta induce by immobilization stress in the hypothalamus were strongly suggested to be involved immobilization stress-induced modulation of the cellular immunity mediated by the splenic sympathetic nervous system.(4)It is suggested that immobilization stress-induced shift of Thl/Th2 balance from Th1 (cellular immunity) toward Th2 (humoral immunity) may be involved in the immobilization stress-induced modulation of the immunity.(5)Activation of the LH and suppression of the hippocampus are suggested to be involved in stress-induced enhancement of the cellular immunity.Taken all things together, it is suggested that stress-induced cytokines in the hypothalamus modulate the activity of the sympathetic nervous system, which modulates the cellular immunity directly or with the mediation of splenic cytokines induced in the spleen. In addition, the hippocampus and the LH may be involved stress-induced enhancement of the cellular immunity. Less

众所周知，各种应激源调节免疫功能，表明大脑控制免疫系统。在本研究中，我们试图揭示应激诱导细胞免疫功能调节的脑机制，并发现：(1)应激激活了下丘脑核，特别是下丘脑室旁核(PVN)的神经元，它既调节交感神经系统，又调节下丘脑垂体肾上腺皮质轴。(2)室旁核和下丘脑腹内侧核(VmH)张力激活，视前核(POA)和下丘脑外侧核(LH)张力抑制脾交感神经系统的活性。(3)非炎症性应激，如束缚应激，可增强…基因的表达。更多r免疫细胞因子，如干扰素-α、白介素1β、肿瘤坏死因子α、肿瘤坏死因子β、白介素3、白介素6和白介素10。尤其是下丘脑束缚应激诱导的干扰素α和IL-1β参与了束缚应激诱导的脾交感神经系统介导的细胞免疫的调节。(4)束缚应激诱导的Th1/Th2平衡由Th1(细胞免疫)向Th2(体液免疫)的转变可能参与了制动应激诱导的免疫调节。(5)LH值的激活和海马区的抑制可能参与了应激诱导的细胞免疫增强。综上所述，应激诱导的下丘脑细胞因子调节交感神经系统的活动。直接或通过脾内诱导的脾细胞因子调节细胞免疫。此外，海马区和黄体生成素可能参与了应激诱导的细胞免疫增强。较少

项目成果

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李安：《脑与生物防御》日本科学会出版社，248（1999）

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Li,A.: "Brain and Biodefence" Japan Scientific Societies Press, 248 (1998)

李安：《脑与生物防御》日本科学会出版社，248（1998）

Hori, T.: "Neuroimmunomodulatory action of hypothalamic interferon-alpha." Neuroimmunomodulation. 5. 172-177 (1998)

Hori, T.：“下丘脑干扰素-α 的神经免疫调节作用。”

Hori, T.: "Emotions and the immunity." Clinical Neuroscience. (in press.).

Hori, T.：“情绪和免疫力。”