Brain interleukin-1 as a mediator of stress responses

脑白细胞介素 1 作为应激反应的调节剂

• 批准号: 09460132
• 负责人: SAITO Masayuki
• 金额: $ 1.98万
• 依托单位: HOKKAIDO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 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-09460132/
• 关键词: interleukin-1; interleukin-6; stress; brain; immunomodulation; インターロイキン1; 交感神経; リンパ球

Peripheral immune functions are modified by various stressors, but the mechanisms of the stress-induced immunomodulation are poorly understood. There have been reports that brain interleukin (IL)-1 is involved in the stress-induced adrenocortical activation, In this study, I have investigated about possible roles of brain IL-1 in the stress-induced immunomodulation using rats and mice as experimental animals. When mice and/or rats were subjected to immobilization stress, the serum IL-6 level rose in 1 hr, following increased expression of IL-6 mRNA in both the liver and the spleen. Immunohistochemical examinations of liver tissue revealed that the stress induced IL-6 mainly in hepatic parenchymal cells. The serum IL-6 response to the stress was much attenuated when an antibody against IL-1 was injected into the cerebral ventricle, but mimicked by an intracerebroventricular injection of minute amounts of IL-1. It was also found that the brain IL-1 mRNA level rose immediately after the stress. From these results, I conclude that the peripheral IL-6 response to immobilization stress is mediated by brain IL-1.

外周免疫功能受到各种应激因素的影响，但应激诱导的免疫调节机制尚不清楚。脑白细胞介素-1（IL-1）参与了应激诱导的肾上腺皮质激活。本研究以大鼠和小鼠为实验动物，探讨了脑IL-1在应激诱导的免疫调节中的可能作用。当小鼠和/或大鼠受到制动应激时，随着肝脏和脾脏中IL-6 mRNA的表达增加，血清IL-6水平在1小时内升高。肝组织免疫组织化学检查显示，应激主要在肝实质细胞中诱导IL-6。当将抗IL-1的抗体注入脑室时，血清IL-6对应激的反应大大减弱，但通过侧脑室注射微量IL-1来模拟。应激后即刻脑IL-1mRNA水平升高。从这些结果中，我得出结论，外周IL-6响应制动应力介导的脑IL-1。

项目成果

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A.Terao 等人：“肿瘤坏死因子-a 对慢波睡眠的增强是由环加氧酶-2 介导的。”

H.Kitamura et al.: "Immobilization stress increases hepatic IL-6 expression in mic" Biochem.Biophys.Res.Commun. 238. 707-711 (1997)

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A.Terao 等人：“Interleukin-1 会在大鼠大脑中前列腺素 D2 敏感的促进睡眠区诱导慢波睡眠。”

A.Terao et al.: "Enhancement of slow-wave sleep by tumor necrosis factor-a is mediated by cyclooxyqenase-2 in rats." NeuroReport. 9. 3791-3796 (1998)

A.Terao 等人：“肿瘤坏死因子-a 对慢波睡眠的增强是由环氧化酶-2 介导的。”

S.Okamoto et al.: "Potent suppressive effects of urocortin on splenic lymphocyte activity in rats." NeuroReport. 9. 4035-4039 (1998)

S.Okamoto 等人：“尿皮质素对大鼠脾淋巴细胞活性的有效抑制作用。”