Sato M, Yamaki J, Hamaya M, Hojo H
Department of Biomolecular Sciences, Fukushima Medical College, Japan.
Int J Immunopharmacol. 1996 Feb;18(2):167-72. doi: 10.1016/0192-0561(95)00118-2.
We investigated the reciprocal effects of interleukin-6 (IL-6), glucocorticoid and zinc (Zn) on metallothionein (MT) synthesis in rats. MT synthesis in the liver, which is a key responsible organ in acute phase responses, was induced by IL-6 or dexamethasone (Dex), and in an additive manner by a combination of IL-6 and Dex 18 h after injection. MT synthesis in the lung and heart was evaluated by immunoassay using a specific antibody to MT-1, because of its low concentration in these tissues. Heart concentrations of MT-1 were significantly increased by IL-6, and were further increased by the combination of IL-6 and Dex, although Dex by itself had no effect. This suggests a synergistic effect of IL-6 and Dex on MT-I synthesis in the heart. A similar synergism was observed in the lung. To study the effect of Zn on the induction of MT and acute phase proteins, Zn, IL-6 and Dex were administered in various concentrations. The increase in liver MT induced by the combination of IL-6 and Dex with Zn (130 micrograms MT/g of liver) was greater than the sum of the increases induced by (IL-6 + Zn) and by (Dex + Zn) (103 micrograms MT/g), suggesting a synergistic increase. The data indicate that the maximal increase in the induction of MT by a combination of IL-6 and Dex depends on an adequate liver Zn content. Thus, the in vivo synergistic induction of acute phase proteins by IL-6, glucocorticoid and Zn may be required for the maximal and rapid response, not only in liver but also in other tissues including heart and lung. This suggests that the synergistic reaction may be important for an enhancement of the radical scavenging ability of tissues in acute phase responses.
我们研究了白细胞介素-6（IL-6）、糖皮质激素和锌（Zn）对大鼠金属硫蛋白（MT）合成的相互作用。肝脏是急性期反应的关键责任器官，IL-6或地塞米松（Dex）可诱导肝脏MT合成，注射18小时后，IL-6和Dex联合使用可产生累加效应。由于肺和心脏组织中MT浓度较低，因此使用针对MT-1的特异性抗体通过免疫测定法评估肺和心脏中的MT合成。IL-6可显著提高心脏中MT-1的浓度，IL-6和Dex联合使用可进一步提高其浓度，尽管Dex单独使用没有效果。这表明IL-6和Dex对心脏中MT-1的合成具有协同作用。在肺中也观察到了类似的协同作用。为了研究锌对MT和急性期蛋白诱导的影响，给予了不同浓度的锌、IL-6和Dex。IL-6和Dex与锌联合诱导的肝脏MT增加量（130微克MT/克肝脏）大于（IL-6 + Zn）和（Dex + Zn）诱导的增加量之和（103微克MT/克），表明存在协同增加。数据表明，IL-6和Dex联合诱导MT的最大增加量取决于肝脏中足够的锌含量。因此，IL-6、糖皮质激素和锌在体内对急性期蛋白的协同诱导可能不仅在肝脏，而且在包括心脏和肺在内的其他组织中都是最大和快速反应所必需的。这表明协同反应可能对增强急性期反应中组织的自由基清除能力很重要。
