Lyson K, McCann S M
Department of Physiology, University of Texas Southwestern Medical Center, Dallas 75235-9040.
Ann N Y Acad Sci. 1992 Apr 15;650:182-5. doi: 10.1111/j.1749-6632.1992.tb49118.x.
Recent reports show that cytokines such as interleukin-1 (IL-1), tumor necrosis factor (TNF) and intravenously administered interleukin-6 (IL-6) stimulate adrenocorticotropic hormone (ACTH) release. Both IL-1 and TNF are known to be potent inducers of IL-6, a monokine produced by activated monocytes and folliculo-stellate cells of the pituitary gland and released from the hypothalamus. To determine the site(s) of action of IL-6 in the control of ACTH release, we injected human recombinant IL-6 into the third brain ventricle (3V) of freely moving, conscious male rats and measured ACTH by RIA. Both 0.05 pmole and 0.25 pmole doses of IL-6 were ineffective to change plasma ACTH in comparison to the values in controls. The maximal IL-6 dose tested of 1.25 pmole increased plasma ACTH within 15 min and the response lasted over 180 min. The effects of IL-6 on plasma ACTH were only partially paralleled by increased rectal temperature which suggests that hypothalamic temperature regulating centers were independent of these actions. To evaluate a possible direct effect on the pituitary, IL-6 was incubated in vitro with hemipituitaries under an atmosphere of 95% O2/5% CO2. After 1 hr of incubation IL-6 failed to cause any change in the secretion of ACTH throughout a concentration range of 10(-15) to 10(-9) M. Increased ACTH secretion into the incubation medium was found only with 10(-13) M IL-6 after a 2-hr incubation. The results support a possible role for IL-6 at both hypothalamic and/or pituitary levels to stimulate ACTH release.
最近的报告显示，诸如白细胞介素-1（IL-1）、肿瘤坏死因子（TNF）以及静脉注射的白细胞介素-6（IL-6）等细胞因子可刺激促肾上腺皮质激素（ACTH）的释放。已知IL-1和TNF都是IL-6的强效诱导剂，IL-6是一种由活化的单核细胞和垂体的滤泡-星状细胞产生并从下丘脑释放的单核因子。为了确定IL-6在控制ACTH释放中的作用位点，我们将重组人IL-6注入自由活动、清醒的雄性大鼠的第三脑室（3V），并通过放射免疫分析法（RIA）测量ACTH。与对照组相比，0.05皮摩尔和0.25皮摩尔剂量的IL-6均无法改变血浆ACTH水平。所测试的最大IL-6剂量1.25皮摩尔在15分钟内使血浆ACTH升高，且该反应持续超过180分钟。IL-6对血浆ACTH的影响仅部分与直肠温度升高平行，这表明下丘脑温度调节中枢与这些作用无关。为了评估对垂体的可能直接作用，将IL-6在95% O₂/5% CO₂气氛下与半垂体在体外进行孵育。孵育1小时后，在10⁻¹⁵至10⁻⁹ M的浓度范围内，IL-6未能引起ACTH分泌的任何变化。仅在孵育2小时后，发现10⁻¹³ M的IL-6可使孵育培养基中的ACTH分泌增加。这些结果支持IL-6在下丘脑和/或垂体水平刺激ACTH释放可能发挥的作用。
