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Molecular mechanisms of the central actions of interleukin-1

IL-1 中枢作用的分子机制

基本信息

批准号：
05454116
负责人：
SAITO Masayuki
金额：
$ 4.29万
依托单位：
Hokkaido University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1994
项目状态：
已结题

项目摘要

It has been established that the central nervous system and the peripheral immune system interact in a biderectional manner. Interleukin-1 (IL-1) is one of the cytokines for the communication between these two systems. In this study, to clarify the cellular and molecular mechanisms for the central action of IL-1, we examined the effects of IL-1 on norepinephrine (NE) turnover (an index of noradrenergic neuronal activity) in the brain and peripheral organs in rats, and obtained the following results :1. When IL-1 was given intraperitoneally, it increased NE turnover in the hypothalamus and also in some peripheral organs such as spleen and lung. These responses were mimicked by an intracerebroventricular (icv) injection of minute amounts of IL-1, suggesting a direct action of IL-1 to the brain.2. The stimulative effects of IL-1 were completely blocked by the pretreatment with either an antibody against corticotropin-releasing hormone (CRH) or indomethacin, an inhibitor of prostaglandin (PG) biosynthesis, suggesting important roles of brain CRH and PGs for the IL-1 action.3. An icv injection of CRH could activate NE turnover in every organs in the same way as the IL-1 injection. In contrast, PGs given intracerebroventricularly were effective for NE turnover in some limited organs : that is , PGE2 for spleen and lung, and PGD2 only for the hypothalamus. Thus, the signal of IL-1 may be converted to the production of PGD2 and PGE2 to activate the noradrenergic neurons projecting to the hypothalamus and peripheral organs, respectively. The molecular mechanisms for such differential regulation of PG production in the brain remain to be further investigated.

已经确定中枢神经系统和外周免疫系统以双向方式相互作用。白细胞介素-1（IL-1）是这两个系统之间通讯的细胞因子之一。本研究旨在探讨IL-1中枢作用的细胞和分子机制，研究IL-1对大鼠脑和外周器官去甲肾上腺素（NE）转换（NE转换是去甲肾上腺素能神经元活动的一个指标）的影响，并获得以下结果：1.当腹腔注射IL-1时，它增加了下丘脑和一些外周器官如脾和肺中的NE周转。这些反应通过侧脑室（icv）注射微量IL-1来模拟，表明IL-1对脑的直接作用。用促肾上腺皮质激素释放激素（CRH）抗体或前列腺素（PG）生物合成抑制剂吲哚美辛预处理可完全阻断IL-1的刺激作用，提示脑CRH和PG在IL-1作用中起重要作用.侧脑室注射CRH可激活各器官NE的更新，其作用与IL-1相同。相比之下，脑室内给予前列腺素对某些有限器官的NE周转有效：即PGE 2对脾和肺有效，而PGD 2仅对下丘脑有效。因此，IL-1的信号可能被转化为PGD 2和PGE 2的产生，以激活分别投射到下丘脑和外周器官的去甲肾上腺素能神经元。这种差异调节大脑中PG产生的分子机制仍有待进一步研究。