INVOLVEMENT OF INTERLEUKIN-1 IN IMMOBILIZATION STRESS-INDUCED INCREASE IN PLASMA ADRENOCORTICOTROPIC HORMONE AND IN RELEASE OF HYPOTHALAMIC MONOAMINES IN THE RAT
INVOLVEMENT OF INTERLEUKIN-1 IN IMMOBILIZATION STRESS-INDUCED INCREASE IN PLASMA ADRENOCORTICOTROPIC HORMONE AND IN RELEASE OF HYPOTHALAMIC MONOAMINES IN THE RAT
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DOI：
10.1523/jneurosci.15-03-01961.1995
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发表时间：
1995-03-01
影响因子：
5.3
通讯作者：
ASAI, M
中科院分区：
文献类型：
--
作者：
SHINTANI, F;NAKAKI, T;ASAI, M
我们研究了制动应激（IS）是否增加了大鼠下丘脑中白细胞介素-1（IL-1）的活性，以及用白细胞介素-1受体拮抗剂（IL-1 Ra）预处理是否能够抑制IS诱导的下丘脑去甲肾上腺素（NE）、多巴胺（DA）和5-羟色胺（5-HT）及其代谢产物以及血浆促肾上腺皮质激素（ACTH）水平的升高。使用伴刀豆球蛋白A存在下小鼠胸腺细胞增殖的生物测定法估计IL-1活性。IL-1 Ra直接给药到下丘脑前部，单胺测定使用微透析技术和HPLC系统。首先，我们发现大鼠下丘脑中的IL-1活性水平在开始IS后60分钟达到最大值。第二，IL-1 Ra（2 μ g）显著抑制IS诱导的下丘脑NE、DA和5-HT水平及其代谢产物水平的升高。此外，IL-1 Ra（2 μ g）也抑制IS诱导的血浆ACTH水平升高。第三，检查IL-1 Ra给药对IS诱导的单胺或ACTH反应的时间效应。在IS开始前5或60分钟给予IL-1 Ra（2 μ g），但在IS开始后5或60分钟不给予，对这些反应产生抑制作用，表明IL-1的作用发生在IS开始后5分钟内。总之，这些结果表明，IS增强下丘脑中的生物活性IL-1，并且下丘脑IL-1在IS诱导的反应的调节中起作用，包括下丘脑中单胺释放升高和下丘脑-垂体-肾上腺轴的激活。此外，由于5分钟对于IS诱导IL-1的产生来说是太短的时间，IS可以增强下丘脑中预先存在的IL-1的作用。
We investigated whether interleukin-1 (IL-1) activity in the rat hypothalamus was increased by immobilization stress (IS), and whether pretreatment with an interleukin-1 receptor antagonist (IL-1Ra) is capable of inhibiting IS-induced elevations of hypothalamic norepinephrine (NE), dopamine (DA), and serotonin (5-HT) and the levels of their metabolites as well as of plasma adrenocorticotropic hormone (ACTH). IL-1 activity was estimated with a bioassay using mouse thymocyte proliferation in the presence of concanavalin A. IL-1Ra was administered directly into the anterior hypothalamus, and monoamines were determined using a microdialysis technique and an HPLC system. First, we found that levels of IL-1 activity in the rat hypothalamus reached a maximum at 60 min after starting IS. Second, IL-1Ra (2 mu g) significantly inhibited IS-induced increases in hypothalamic NE, DA, and 5-HT levels as well as the levels of their metabolites. In addition, IL-1Ra (2 mu g) also inhibited the IS-induced elevation of plasma ACTH levels. Third, timing effects of IL-1Ra administration on the IS-induced monoamines or ACTH responses were examined. IL-1Ra (2 mu g) administered at 5 or 60 min before the start of IS, but not at 5 or 60 min after IS had been started, exerted inhibitory effects on these responses, indicating that the effects of IL-1 occurred within 5 min after the initiation of IS. In summary, these results suggest that IS enhances biologically active IL-1 in the hypothalamus, and that hypothalamic IL-1 plays a role in the regulation of IS-induced responses including elevated monoamine release in the hypothalamus and activation of the hypothalamo-pituitary-adrenal axis. Moreover, since 5 min is too short a time for IS to induce production of IL-1, IS may augment the effects of preexisting IL-1 in the hypothalamus.