Feng Dechun, Wang Ying, Xu Yan, Luo Qingqiong, Lan Bin, Xu Lingyun
Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Biochem Pharmacol. 2009 Jan 15;77(2):277-84. doi: 10.1016/j.bcp.2008.09.028. Epub 2008 Oct 1.
The prediction and prevention of drug-induced liver injury (DILI) have been hindered by limited knowledge of the underlying mechanisms, in part the result of a lack of animal models. Using a newly established DILI model induced by halothane, we found increased liver damage susceptibility in interleukin 10 (IL-10) knockout (KO) mice. Extensive neutrophil infiltration and chemoattractant factor interleukin 8 (IL-8) expression in IL-10 KO mice were observed after halothane administration. The elevation of IL-8 expression was NF-kappaB- and P38 MAPK-dependent. In addition, increased signal transducer and activator of transcription factors (STAT) 1 and STAT3 were observed in halothane treated IL-10 KO mice. Exogenous IL-10 treatment protected susceptible mice from halothane induced liver injury (HILI). In conclusion, IL-10 deficiency increases susceptibility to HILI and increased IL-8 expression as well as neutrophil infiltration may be responsible for this phenomenon.
药物性肝损伤（DILI）的预测和预防因对其潜在机制的了解有限而受到阻碍，部分原因是缺乏动物模型。使用新建立的氟烷诱导的DILI模型，我们发现白细胞介素10（IL-10）基因敲除（KO）小鼠的肝损伤易感性增加。氟烷给药后，在IL-10 KO小鼠中观察到广泛的中性粒细胞浸润和趋化因子白细胞介素8（IL-8）表达。IL-8表达的升高依赖于NF-κB和P38丝裂原活化蛋白激酶（MAPK）。此外，在氟烷处理的IL-10 KO小鼠中观察到信号转导子和转录激活因子（STAT）1和STAT3增加。外源性IL-10治疗可保护易感小鼠免受氟烷诱导的肝损伤（HILI）。总之，IL-10缺乏增加了对HILI的易感性，IL-8表达增加以及中性粒细胞浸润可能是导致这种现象的原因。
