INTERLEUKIN-6, THE 3RD MEDIATOR OF ACUTE-PHASE REACTION, MODULATES HEPATIC PROTEIN-SYNTHESIS IN HUMAN AND MOUSE - COMPARISON WITH INTERLEUKIN-1-BETA AND TUMOR NECROSIS FACTOR-ALPHA
INTERLEUKIN-6, THE 3RD MEDIATOR OF ACUTE-PHASE REACTION, MODULATES HEPATIC PROTEIN-SYNTHESIS IN HUMAN AND MOUSE - COMPARISON WITH INTERLEUKIN-1-BETA AND TUMOR NECROSIS FACTOR-ALPHA
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DOI：
10.1002/eji.1830180817
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发表时间：
1988-08-01
影响因子：
5.4
通讯作者：
BUSCHENFELDE, KHMZ
中科院分区：
文献类型：
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作者：
RAMADORI, G;VANDAMME, J;BUSCHENFELDE, KHMZ
白细胞介素6（IL 6）是先前根据其生物活性命名的一组细胞因子的新定义，例如B细胞刺激因子2（BSF-2）、杂交瘤浆细胞瘤生长因子（HGF）、干扰素-β 2（IFN-β 2）、肝细胞刺激因子（HSF）。最近提出，IL 6可能代表急性期蛋白质应答的主要介质，而IL 1 β可能代表急性期蛋白质应答的主要介质。和TNF-α可以扮演一个小角色。我们通过体外和体内实验比较了三种细胞因子对肝脏蛋白质合成的影响。将人肝癌细胞（PLC/PRF 5）分别暴露于每种细胞因子20 h，然后在蛋白质和RNA水平上研究效果。所有三种细胞因子减少白蛋白和增加C3和铜蓝蛋白的生物合成。细胞因子在RNA水平诱导相同的效应，表明调节是翻译前的。细胞因子的作用是特异性的，因为肌动蛋白基因表达没有改变;此外，该作用被针对细胞因子的特异性抗体阻断。单一细胞因子的作用是剂量和时间依赖性的，并且在数量上是相当的。没有一种细胞因子能够改变α 1-抗胰蛋白酶合成。用小鼠进行的体内实验显示IL 1 β。和TNF-α均诱导小鼠肝脏中的血清淀粉样蛋白A（SAA）mRNA并增加因子B（Bf）基因表达。人重组IL 6诱导SAA基因表达，腹腔注射后对Bf基因表达也有弱的正效应。这些数据表明，研究的三种细胞因子在定量和定性上是相当的，并且所有三种细胞因子都可能参与急性期蛋白反应。
Interleukin 6 (IL 6) is the new definition of a group of cytokines previously named according to their biological activity, e.g. B cell stimulatatory factor 2 (BSF-2), hybridoma plasmocytoma-growth factor (HGF), interferon-.beta.2 (IFN-.beta.2), hepatocyte stimulating factor (HSF). It has recently been suggested that IL6 may represent the major mediator of acute-phase protein response whereas IL1.beta. and TNF-.alpha. could play a minor role. We compared the effect of the three cytokines on hepatic protein synthesis by performing in vitro as well as in vivo experiments. Human hepatoma cells (PLC/PRF5) were exposed to each cytokine separately for 20 h, and the effect was then studied at the protein and RNA level. All three cytokines reduced albumin and increased C3 and ceruloplasmin biosynthesis. The cytokines induced the same effect at the RNA level indicating that the modulation was pretranslational. The effect of the cytokines was specific since actin gene expression was not changed; furthermore the effect was blocked by specific antibodies against the cytokines. The effect of the single cytokines was dose and time dependent, and quantitatively comparable. None of the cytokines was able to alter .alpha.1-anti-trypsin synthesis. In vivo experiments with mice showed that IL1.beta. and TNF-.alpha. both induce serum amyloid A (SAA) mRNA in the mouse liver and increase factor B (Bf) gene expression. Human recombinant IL6 induced SAA gene expression and it also had a weak positive effect on Bf gene expression after i.p. injection. These data demonstrate that the three cytokines studied are quantitatively and qualitatively comparable, and that all three are probably involved in acute-phase protein response.