Increased sensitivity of IL-6-deficient mice to carbon tetrachloride hepatotoxicity and protection with an IL-6 receptor-IL-6 chimera.
Increased sensitivity of IL-6-deficient mice to carbon tetrachloride hepatotoxicity and protection with an IL-6 receptor-IL-6 chimera.
复制标题
IL-6 缺陷小鼠对四氯化碳肝毒性的敏感性增加以及 IL-6 受体-IL-6 嵌合体的保护。
DOI：
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发表时间：
1998
期刊：
影响因子：
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通讯作者：
M. Revel
中科院分区：
文献类型：
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作者：
A. Katz;J. Chebath;J. Friedman;M. Revel
研究发现，白细胞介素 6 (IL-6) 缺陷型小鼠比具有完整 IL-6 系统的小鼠对四氯化碳 (CCl4) 造成的肝损伤更加敏感。在 CCl4 剂量范围为 2 至 3.5 ml/kg 体重时，IL-6 基因敲除 (IL-6-/-) 小鼠的 24 小时平均死亡率为 71%，而正常 IL-6+/+ 小鼠的平均死亡率为 12%。在亚致死剂量下，IL-6缺陷小鼠的肝脏中出现广泛的实质坏死，而在对照动物中未观察到这种情况。 IL-6-/- 小鼠中，CCl4 诱导的脂质过氧化程度高出 10 倍。注射含有与可溶性受体融合的 IL-6 的嵌合蛋白（IL-6R-IL-6 嵌合体），可诱导 IL-6-/- 和 IL-6+/+ 小鼠的肝细胞免受 CCl4 损伤。用IL-6R-IL-6治疗使IL-6-/-小鼠的存活率恢复至IL-6+/+动物的水平。游离 IL-6 不能有效减少 CCl4 诱导的肝毒性，但在减少小鼠黑色素瘤模型中转移死亡方面与 IL-6R-IL-6 一样有效。因此，IL-6R-IL-6嵌合体似乎对化学性肝毒性损伤特别有效。
Interleukin-6 (IL-6)-deficient mice were found to be much more sensitive to liver injury by carbon tetrachloride (CCl4) than mice with an intact IL-6 system. At doses of CCl4 ranging from 2 to 3.5 ml/kg body weight, mean mortality in the IL-6 gene knockout (IL-6-/-) mice was 71% at 24 hours versus 12% in normal IL-6+/+ mice. At sublethal doses, there was extensive parenchymal necrosis in the livers of IL-6-deficient mice, which was not seen in the control animals. Lipid peroxidation induced by CCl4 was up to 10-fold higher in the IL-6-/- mice. Injections of a chimeric protein containing IL-6 fused to its soluble receptor (IL-6R-IL-6 chimera) induced hepatocyte protection against CCl4 damage in both IL-6-/- and IL-6+/+ mice. Treatment with IL-6R-IL-6 restored the survival of the IL-6-/- mice to the level of IL-6+/+ animals. Free IL-6 was not effective in reducing CCl4-induced liver toxicity, but was as effective as IL-6R-IL-6 in reducing death from metastases in a murine melanoma model. Hence the IL-6R-IL-6 chimera appears to be particularly effective against chemical hepatotoxic injury.