INTERLEUKINS-1 AND INTERLEUKINS-6 STIMULATE THE RELEASE OF CORTICOTROPIN-RELEASING HORMONE-41 FROM RAT HYPOTHALAMUS INVITRO VIA THE EICOSANOID CYCLOOXYGENASE PATHWAY
INTERLEUKINS-1 AND INTERLEUKINS-6 STIMULATE THE RELEASE OF CORTICOTROPIN-RELEASING HORMONE-41 FROM RAT HYPOTHALAMUS INVITRO VIA THE EICOSANOID CYCLOOXYGENASE PATHWAY
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DOI：
10.1210/endo-128-1-37
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发表时间：
1991-01-01
期刊：
影响因子：
4.8
通讯作者：
GROSSMAN, AB
中科院分区：
文献类型：
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作者：
NAVARRA, P;TSAGARAKIS, S;GROSSMAN, AB
此前已有研究表明，白细胞介素-1（IL-1）在体外直接刺激大鼠下丘脑释放CRH-41，这表明细胞因子可能介导免疫状态变化对下丘脑-垂体肾上腺轴（HPA）的影响。 然而，很可能有几种细胞因子可以引起神经内分泌功能的变化，我们现在已经研究了一系列其他细胞因子对 HPA 的中枢活性：IL-2、IL-6、IL-8、肿瘤坏死因子（恶病素）、干扰素-α-2 和干扰素-γ。 使用的静态大鼠下丘脑培养系统包括连续培养 20 分钟的新鲜下丘脑外植体，并通过特定的 RIA 估计培养基中的 CRH-41 浓度；还测量了细胞因子对大鼠分散的垂体细胞释放促肾上腺皮质激素的急性影响。 IL-6 增加下丘脑 CRH-41 分泌，范围为 10-100 U/ml，但对在相同条件下体外培养的孤立正中隆起没有影响。 当以 10 分钟脉冲给药时，IL-6 (1-1000 U/ml) 对新鲜分散的大鼠垂体前叶细胞的 ACTH 分泌也没有影响。 IL-1 和 IL-6 的作用均被类二十烷酸环加氧酶途径的阻断所拮抗，但脂加氧酶的阻断则不能拮抗。 IL-2 (1-10000 U/ml)、IL-8 (0.1-10 nM)、肿瘤坏死因子 (10-1000 U/ml)、干扰素-α-2 (10-1000 U/ml) 或干扰素-γ (10-1000 U/ml) 对下丘脑 CRH-41 释放或垂体 ACTH 释放没有任何影响。 因此得出的结论是，IL-6 与 IL-1 一样，可以通过在人血浆和脑脊液中已知的浓度，急性刺激下丘脑在正中隆起水平以上的位置分泌 CRH-41，对 HPA 产生有效的增强作用。 这些作用可能是由环氧合酶产物介导的。 研究的其他细胞因子对 HPA 的急性刺激作用不太可能直接通过 CRH-41 或 ACTH 的变化来发挥。
It has previously been shown that interleukin-1 (IL-1) directly stimulates the release of CRH-41 from rat hypothalamus in vitro, suggesting that cytokines may mediate the effects of changes in immune state on the hypothalamo-pituitary adrenal axis (HPA). However, it is likely that several cytokines can cause changes in neuroendocrine function, and we have now investigated a series of others for central activity on the HPA: IL-2, IL-6, IL-8, tumor necrosis factor (cachectin), interferon-alpha-2, and interferon-gamma. The static rat hypothalamic incubation system used involves fresh hypothalamic explants with consecutive 20-min incubation, and estimation of CRH-41 concentrations in the medium by a specific RIA; the acute effects of cytokines on ACTH release from rat dispersed pituitary cells were also measured. IL-6 increased hypothalamic CRH-41 secretion in the range 10-100 U/ml, but had no effect on isolated median eminences incubated in vitro under the same conditions. IL-6 (1-1000 U/ml) also had no effect on the secretion of ACTH from freshly dispersed rat anterior pituitary cells when administered in 10-min pulses. The effects of both IL-1 and IL-6 were antagonized by blockade of the eicosanoid cyclooxygenase pathway, but not by lipooxygenase blockade. Neither IL-2 (1-10000 U/ml), IL-8 (0.1-10 nM), tumor necrosis factor (10-1000 U/ml), interferon-alpha-2 (10-1000 U/ml) nor interferon-gamma (10-1000 U/ml) had any effect on hypothalamic CRH-41 release or pituitary ACTH release. It is therefore concluded that IL-6, like IL-1, can exert a potent enhancing effect on the HPA by acutely stimulating the secretion of CRH-41 from the hypothalamus at a site above the level of the median eminence, at concentrations known to occur in human plasma and cerebrospinal fluid. These effects are probably mediated by cyclooxygenase products. Acute stimulatory effects of the other cytokines investigated on the HPA are unlikely to be exerted through changes in either CRH-41 or ACTH directly.