Cousins R J, Leinart A S
Food Science and Human Nutrition Department, University of Florida, Gainesville 32611.
FASEB J. 1988 Oct;2(13):2884-90. doi: 10.1096/fasebj.2.13.2458983.
Interleukin 1 (IL 1) production is stimulated by infection, cellular injury, and inflammation. This cytokine directs a wide spectrum of host responses. Human interleukin 1 alpha (IL 1 alpha) was used to examine the time course of effects on zinc metabolism as part of the acute phase response. IL 1 produced a transient depression in the serum zinc concentration and increased serum ceruloplasmin. Metallothionein levels were increased in liver 14-fold after IL 1. Increased expression of metallothionein-1 and -2 genes following IL 1 were observed in liver, bone marrow, and thymus. Pulse-labeling experiments with i.v.-administered 65Zn showed that IL 1 drastically altered zinc distribution kinetics among tissues. More 65Zn was taken up (and/or retained) by the liver, bone marrow, and thymus 6 h after IL 1, whereas correspondingly less 65Zn was found in bone, skin, and intestine. Uptake by other tissues was not affected by IL 1. Chromatography of cytosol from tissues with increased 65Zn uptake suggests the IL 1-induced redistribution may be driven by enhanced metallothionein synthesis. Collectively, the results show that IL 1 regulates zinc metabolism and may direct its preferential, tissue-specific distribution via elevated metallothionein-1 and -2 gene expression.
白细胞介素1（IL - 1）的产生受感染、细胞损伤和炎症刺激。这种细胞因子可引发多种宿主反应。作为急性期反应的一部分，使用人白细胞介素1α（IL - 1α）来研究其对锌代谢影响的时间进程。IL - 1使血清锌浓度出现短暂下降，并使血清铜蓝蛋白增加。IL - 1作用后，肝脏中金属硫蛋白水平增加了14倍。在肝脏、骨髓和胸腺中观察到IL - 1作用后金属硫蛋白 - 1和 - 2基因的表达增加。静脉注射65Zn的脉冲标记实验表明，IL - 1显著改变了锌在组织间的分布动力学。IL - 1作用6小时后，肝脏、骨髓和胸腺摄取（和/或保留）了更多的65Zn，而在骨骼、皮肤和肠道中发现的65Zn相应减少。其他组织的摄取不受IL - 1影响。对65Zn摄取增加的组织的胞质溶胶进行色谱分析表明，IL - 1诱导的重新分布可能是由金属硫蛋白合成增强驱动的。总体而言，结果表明IL - 1调节锌代谢，并可能通过提高金属硫蛋白 - 1和 - 2基因的表达来指导其优先的、组织特异性的分布。
