Xu Jun, Ma Hsiao-Yen, Liu Xiao, Rosenthal Sara, Baglieri Jacopo, McCubbin Ryan, Sun Mengxi, Koyama Yukinori, Geoffroy Cedric G, Saijo Kaoru, Shang Linshan, Nishio Takahiro, Maricic Igor, Kreifeldt Max, Kusumanchi Praveen, Roberts Amanda, Zheng Binhai, Kumar Vipin, Zengler Karsten, Pizzo Donald P, Hosseini Mojgan, Contet Candice, Glass Christopher K, Liangpunsakul Suthat, Tsukamoto Hidekazu, Gao Bin, Karin Michael, Brenner David A, Koob George F, Kisseleva Tatiana
Department of Medicine.
Department of Surgery, and.
JCI Insight. 2020 Feb 13;5(3):131277. doi: 10.1172/jci.insight.131277.
Chronic alcohol abuse has a detrimental effect on the brain and liver. There is no effective treatment for these patients, and the mechanism underlying alcohol addiction and consequent alcohol-induced damage of the liver/brain axis remains unresolved. We compared experimental models of alcoholic liver disease (ALD) and alcohol dependence in mice and demonstrated that genetic ablation of IL-17 receptor A (IL-17ra-/-) or pharmacological blockade of IL-17 signaling effectively suppressed the increased voluntary alcohol drinking in alcohol-dependent mice and blocked alcohol-induced hepatocellular and neurological damage. The level of circulating IL-17A positively correlated with the alcohol use in excessive drinkers and was further increased in patients with ALD as compared with healthy individuals. Our data suggest that IL-17A is a common mediator of excessive alcohol consumption and alcohol-induced liver/brain injury, and targeting IL-17A may provide a novel strategy for treatment of alcohol-induced pathology.
长期酗酒会对大脑和肝脏产生有害影响。对于这些患者没有有效的治疗方法，并且酒精成瘾以及随之而来的酒精诱导的肝/脑轴损伤的潜在机制仍未得到解决。我们比较了小鼠酒精性肝病（ALD）和酒精依赖的实验模型，并证明IL-17受体A（IL-17ra-/-）的基因敲除或IL-17信号通路的药理学阻断可有效抑制酒精依赖小鼠自愿饮酒量的增加，并阻止酒精诱导的肝细胞和神经损伤。循环中IL-17A的水平与过度饮酒者的酒精使用呈正相关，并且与健康个体相比，ALD患者的该水平进一步升高。我们的数据表明，IL-17A是过度饮酒和酒精诱导的肝/脑损伤的共同介质，靶向IL-17A可能为治疗酒精诱导的病理状况提供一种新策略。
