Therapeutic potential of interleukin-6 in preventing obesity- and alcohol-associated fatty liver transplant failure
Therapeutic potential of interleukin-6 in preventing obesity- and alcohol-associated fatty liver transplant failure
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DOI：
10.1016/j.alcohol.2004.07.006
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发表时间：
2004-08-01
期刊：
影响因子：
2.3
通讯作者：
Gao, B
中科院分区：
文献类型：
--
作者：
Gao, B
供体器官短缺严重阻碍了原位肝移植治疗，而肝移植是慢性终末期肝病和急性肝衰竭的唯一有效治疗方法。使情况更为复杂的是，从肥胖和酗酒个体获取的供体肝脏中有13% - 50%存在脂肪变性。这些肝脏在移植后会出现原发性无功能以及功能障碍风险升高的情况。人们正在积极寻求新的治疗方法，以使边缘性脂肪肝适合临床移植。我的研究小组的研究结果表明，白细胞介素 - 6（IL - 6）体外处理可显著降低肥胖 Zucker大鼠脂肪肝同种异体移植物的死亡率、肝损伤以及坏死性凋亡。其他研究结果显示，IL - 6通过防止肝窦内皮细胞损伤，进而改善肝脏微循环，以及防止肝细胞死亡（可能是通过激活信号转导和转录激活因子3/Bcl - X - L介导）来诱导脂肪肝同种异体移植物的肝保护作用。最后，IL - 6体外处理还可防止与酒精性脂肪肝移植相关的死亡。相对于IL - 6对肥胖Zucker大鼠肝脏的保护作用，IL - 6对酒精性脂肪肝的效果较差，这可能是由于乙醇对肝细胞和肝窦内皮细胞中IL - 6激活信号转导和转录激活因子3具有抑制作用。总体而言，这些结果支持这样的观点：对脂肪肝进行IL - 6体外处理可能使同种异体移植物可用于临床移植，从而缩小尸体肝脏同种异体移植物供应短缺与肝脏替代需求高之间的差距。可能需要更高浓度的IL - 6来防止酒精性脂肪肝同种异体移植物损伤，因为酒精会抑制肝脏中IL - 6的信号传导。（C）2005爱思唯尔公司。保留所有权利。
Donor organ shortage significantly hinders orthotopic liver transplantation therapy, the only effective treatment for chronic end-stage liver disease and acute liver failure. Further complicating this matter is the prevalence of steatosis in 13% to 50% of donor livers obtained from obese and alcoholic individuals. When transplanted, these livers are associated with primary nonfunction and an elevated risk of dysfunction. New therapeutic approaches to render marginal fatty livers worthy for clinical transplantation are actively being sought. Study findings obtained from my group show that in vitro treatment with interleukin-6 (IL-6) dramatically reduces mortality, liver injury, and necrapoptosis in steatotic Zucker rat liver isografts. Findings of additional studies indicate that IL-6 induces hepatoprotection of steatotic liver isografts by preventing sinusoidal endothelial cell damage and, consequently, the amelioration of hepatic microcirculation, and by protecting against hepatocyte death, which is likely mediated through activation of signal transducer and activator of transcription 3/Bcl-X-L. Finally, in vitro IL-6 treatment also prevents mortality associated with alcoholic fatty liver transplants. Relative to the protective effect of IL-6 on steatotic Zucker rat liver, EL-6 is less effective in alcoholic fatty livers, which may be due to the inhibitory effects of ethanol on IL-6 activation of signal transducer and activator of transcription 3 in hepatocytes and sinusoidal endothelial cells. Collectively, these results support the assertion that in vitro IL-6 treatment of steatotic livers may render allografts usable for clinical transplantation, thereby decreasing the gap between the short supply of cadaver liver allografts and high demands for replacement livers. Higher concentrations of EL-6 may be required to protect against alcoholic fatty liver isograft injury because alcohol inhibits IL-6 signaling in the liver. (C) 2005 Elsevier Inc. All rights reserved.