Mechanism of interleukin-6 induction by intraperitoneal administration of carbon tetrachloride and its effect on hepatic injury

四氯化碳已被用作肝毒性研究的模型化合物。我们之前证明，在四氯化碳给药后的早期，大鼠通过腹腔或皮下注射而不是口服注射诱导了高水平的白细胞介素(IL)-6，并且至少部分是由腹膜浆膜中的腹膜细胞通过各种炎症因子产生的。在本研究中，我们探讨了内源性诱导IL-6产生和上调保护蛋白的机制。腹腔注射四氯化碳后，炎症因子IL-la、IL-1B、肿瘤坏死因子-a、pmstaglandin E_2水平升高，腹膜细胞数量减少，随着四氯化碳载体的增加，炎症因子的增加和细胞数量均减少。认为四氯化碳溶解在小剂量的载体中，容易与膜脂组分发生反应，使腹膜细胞活化或溶解，释放炎症因子。从IL-1a在腹膜渗出液中诱导IL-6的高效力和浓度来看，IL-1a似乎是炎症因子中促进IL-6产生最有效的因子。四氯化碳腹腔注射大鼠血红素加氧酶-1 （HO-1）的诱导率高于口服；热休克蛋白（HSP） 72和HSP90的表达均有相似程度的升高。抗大鼠IL-6抗体预处理可部分降低HO-1的表达，表明肝脏HO-1。是由内源性诱导上调的。IL-6，除了已经报道的由细胞色素P450衍生的血红素上调外。由于已知HO-1可以减少组织损伤，因此在使用四氯化碳诱导的肝损伤模型分析数据时应考虑到目前的发现。少

Carbon tetrachloride has been used as a model compound for studying hepatotoxicity. We previously demonstrated that a high level of interleukin (IL)-6 was induced in the early period after carbon tetrachloride administration via the intraperitoneal or subcutaneous mute, but not via the oral mute, in rats and it was produced at least partially by peritoneal cells in the serous membrane of the peritoneum through various inflammatory factors. In the present study we examined the mechanisms of IL-6 production and up-regulation of protective proteins by endogenously induced IL-6. Levels of inflammatory factors such as IL-la, IL-1B, tumor necrosis factor-a and pmstaglandin E_2 were increased and number of peritoneal cells was decreased in the peritoneum immediately after intraperitoneal carbon tetrachloride administration, and both increase in inflammatory factors and lass of cells were reduced as the vehicle-to-carbon tetrachloride was increased. It was considered that carbon tetrachloride … More dissolved in a small dose of vehicle easily reacted with membrane lipid components and caused activation or lysis of peritoneal cells to release inflammatory factors. IL-1a seems to contribute to IL-6 production most effectively among the inflammatory factors, judging from its high IL-6-inducing potency and concentration in the peritoneal exudate. Heme oxygenase-1 (HO-1) was induced more in rats administered carbon tetrachloride intraperitoneally compared with orally ; while, expression of heat shock protein (HSP) 72 and HSP90 were increased to similar extents in both experimental groups. The fact that the HO-1 expression was partially reduced by pretreatment with anti-rat IL-6 antibody shows that hepatic HO-1. is up-regulated by endogenously induced by .IL-6, in addition to its up-regulation by heme derived from cytochrome P450 which has already been reported. Since HO-1 is known to reduce tissue injuries, the present findings should be taken into consideration during the analysis of data using the carbon tetrachloride-induced liver injury model. Less