Department of Internal Medicine I, Gastroenterology, Endocrinology & Metabolism, Medical University Innsbruck, Innsbruck, Austria.
Department of Interdisciplinary Medicine, University of Bari, Bari, Italy.
Liver Int. 2018 Jun;38(6):1095-1101. doi: 10.1111/liv.13642. Epub 2017 Dec 16.
BACKGROUND & AIMS: Chronic alcohol consumption and alcoholic liver disease (ALD) afflicts individuals with substantial morbidity and mortality with limited treatment options available. Hepatic inflammation, triggered by activated Kupffer cells, is a driving force in alcoholic liver disease. Interleukin 37 (IL-37) exerts anti-inflammatory effects in hepatic diseases, however, the impact of Interleukin 37 on alcoholic liver disease is unknown. In this study, we addressed the role of Interleukin 37 in alcoholic liver disease.
We utilized Interleukin 37 expressing transgenic mice and human recombinant Interleukin 37 in models of alcoholic liver disease. Interleukin 37 expression was measured in liver samples of 20 alcoholic steatohepatitis and 36 non-alcoholic fatty liver disease patients.
Interleukin 37 transgenic mice are not protected against hepatic injury and inflammation in alcoholic liver disease. Ethanol suppressed Interleukin 37 expression in transgenic mice. Alcoholic steatohepatitis (ASH) patients similarly exhibited reduced Interleukin 37 expression when compared to non-alcoholic fatty liver disease (NAFLD) patients. Human recombinant Interleukin 37 ameliorated hepatic inflammation in a binge drinking model of alcoholic liver disease.
We provide evidence for an exogenous noxae that suppresses Interleukin 37 expression which limits its anti-inflammatory effects in alcoholic liver disease.
慢性酒精摄入和酒精性肝病（ALD）会导致个体出现严重的发病率和死亡率，而目前的治疗选择有限。由激活的库普弗细胞引发的肝脏炎症是酒精性肝病的主要驱动因素。白细胞介素 37（IL-37）在肝脏疾病中具有抗炎作用，然而，白细胞介素 37 对酒精性肝病的影响尚不清楚。在这项研究中，我们研究了白细胞介素 37 在酒精性肝病中的作用。
我们利用表达白细胞介素 37 的转基因小鼠和人重组白细胞介素 37 建立了酒精性肝病模型。在 20 名酒精性脂肪性肝炎和 36 名非酒精性脂肪性肝病患者的肝组织样本中检测了白细胞介素 37 的表达。
白细胞介素 37 转基因小鼠不能预防酒精性肝病中的肝损伤和炎症。乙醇抑制了转基因小鼠中白细胞介素 37 的表达。与非酒精性脂肪性肝病患者相比，酒精性脂肪性肝炎（ASH）患者的白细胞介素 37 表达也降低。人重组白细胞介素 37 改善了酒精性肝病 binge 饮酒模型中的肝脏炎症。
我们提供了证据表明，外源性有害物质抑制了白细胞介素 37 的表达，限制了其在酒精性肝病中的抗炎作用。
