Judd A M, MacLeod R M
Department of Medicine, University of Virginia Health Sciences Center, Charlottesville 22908.
Endocrinology. 1992 Mar;130(3):1245-54. doi: 10.1210/endo.130.3.1311232.
Interleukin-6 (IL-6) is produced by adrenal zona glomerulosa cells; its release is stimulated by several secretagogues, including IL-1 alpha, IL-1 beta, and angiotensin II. The present study reports that ACTH (0.1-100 nM) increased the release of IL-6 from primary cultures of rat adrenal cells in a concentration-dependent manner. This increase was accompanied by an increase in cAMP content in cell extracts and in the incubation medium. The dynamics of IL-6 release from the adrenal cells also were investigated using a perifusion system; approximately 50 min were required for the effects of IL-1 alpha, IL-1 beta, and ACTH on IL-6 release to become apparent. Following withdrawal of the secretagogues, IL-6 release returned to basal levels within 90-120 min. In some experiments, the adrenal zona glomerulosa was separated from the zona fasciculata/reticularis to determine the origin of secretagogue-stimulated IL-6 release. PGE2 and forskolin increased IL-6 release from both cell types, but maximal release from zona glomerulosa cells was more than 10-fold greater than that from zona fasciculata/reticularis cells. ACTH (0.1-100 nM) increased intracellular cAMP levels in cells from both cell types in a concentration-dependent manner, but increased IL-6 release only from zona glomerulosa cells. Dexamethasone, an inhibitor of IL-6 production in several tissues, had no effect on either basal or stimulated IL-6 production in the adrenal. Because IL-1 beta is produced primarily by tissues of the immune system, whereas ACTH is a classical endocrine hormone, we investigated the effect of interaction of these proteins on IL-6 release from the adrenal. Together, IL-1 beta and ACTH stimulation of IL-6 release was greater than the sum of the effects of each substance separately; however, IL-1 beta did not potentiate the effect of ACTH on cAMP levels. Similarly, IL-1 beta potentiated IL-6 release stimulated by forskolin and (Bu)2cAMP. Thus, the adrenal may be an important convergence point between the immune and endocrine systems, and because IL-6 release is regulated by IL-1 alpha, IL-1 beta, ACTH, and angiotensin II, and this cytokine stimulates corticosterone release, IL-6 may play an important paracrine role in integrating the signals derived from these systems.
白细胞介素-6（IL-6）由肾上腺球状带细胞产生；其释放受到多种促分泌素的刺激，包括IL-1α、IL-1β和血管紧张素II。本研究报告称，促肾上腺皮质激素（ACTH，0.1 - 100 nM）以浓度依赖的方式增加了大鼠肾上腺细胞原代培养物中IL-6的释放。这种增加伴随着细胞提取物和孵育培养基中cAMP含量的增加。还使用灌流系统研究了肾上腺细胞释放IL-6的动力学；IL-1α、IL-1β和ACTH对IL-6释放的影响大约需要50分钟才能显现出来。撤除促分泌素后，IL-6释放在90 - 120分钟内恢复到基础水平。在一些实验中，将肾上腺球状带与束状带/网状带分离，以确定促分泌素刺激的IL-6释放的来源。前列腺素E2（PGE2）和福斯可林增加了两种细胞类型中IL-6的释放，但球状带细胞的最大释放量比束状带/网状带细胞大10倍以上。ACTH（0.1 - 100 nM）以浓度依赖的方式增加了两种细胞类型细胞内的cAMP水平，但仅增加了球状带细胞中IL-6的释放。地塞米松是几种组织中IL-6产生的抑制剂，对肾上腺中基础或刺激的IL-6产生均无影响。由于IL-1β主要由免疫系统的组织产生，而ACTH是一种经典的内分泌激素，我们研究了这些蛋白质相互作用对肾上腺中IL-6释放的影响。IL-1β和ACTH共同刺激IL-6释放大于每种物质单独作用的效果之和；然而，IL-1β并未增强ACTH对cAMP水平的影响。同样，IL-1β增强了福斯可林和（Bu）2cAMP刺激的IL-6释放。因此，肾上腺可能是免疫系统和内分泌系统之间的一个重要交汇点，并且由于IL-6的释放受IL-1α、IL-1β、ACTH和血管紧张素II调节，且这种细胞因子刺激皮质酮释放，IL-6可能在整合来自这些系统的信号中发挥重要的旁分泌作用。
