Tilg Herbert, Kaser Arthur, Moschen Alexander R
Department of Medicine, Division of Gastroenterology and Hepatology, Innsbruck Medical University, Austria.
Liver Int. 2006 Nov;26(9):1029-39. doi: 10.1111/j.1478-3231.2006.01339.x.
Most acute and chronic liver diseases are characterized by inflammatory processes with enhanced expression of various pro- and anti-inflammatory cytokines in the liver. These cytokines are the driving force of many inflammatory liver disorders often resulting in fibrosis and cirrhosis. Severe alcoholic hepatitis is a prototypic tumor necrosis factor-alpha (TNF-alpha)-associated disease. This knowledge has recently led to pilot studies with promising results investigating specific anti-TNF drugs such as infliximab or etanercept in the treatment of this disease, although a recently performed controlled French study did show a potential detrimental effect of this approach. Anti-TNF treatment strategies might also improve chronic hepatitis C infection as shown by one controlled trial using etanercept administered subcutaneously for 24 weeks. Furthermore, several case reports suggest that TNF-alpha neutralization is not harmful to patients chronically infected with this virus. In contrast, neutralization of TNF-alpha worsens and might even be associated with fatalities in chronic hepatitis B infection. Anti-inflammatory cytokines such as interleukin-10 (IL-10) have also been tried in patients with chronic liver diseases. Whereas IL-10 administered to patients with chronic hepatitis C virus infection shows indeed anti-inflammatory effects in the liver, it seems to act as a proviral agent thereby limiting its clinical utility. Another cytokine with major anti-inflammatory potential is the adipokine adiponectin, as its administration is beneficial in many experimental models of liver injury. Interference with cytokine pathways and/or administration of anti-inflammatory cytokines will be of major interest in the future therapy of many liver diseases.
大多数急性和慢性肝病的特征是肝脏中各种促炎和抗炎细胞因子表达增强的炎症过程。这些细胞因子是许多炎症性肝病的驱动力，常导致肝纤维化和肝硬化。严重酒精性肝炎是一种典型的与肿瘤坏死因子-α（TNF-α）相关的疾病。这一认识最近促使开展了一些初步研究，研究诸如英夫利昔单抗或依那西普等特异性抗TNF药物治疗该疾病，结果令人鼓舞，尽管最近一项法国对照研究确实显示了这种方法可能存在有害影响。如一项使用皮下注射依那西普24周的对照试验所示，抗TNF治疗策略也可能改善慢性丙型肝炎感染。此外，一些病例报告表明，TNF-α中和对慢性感染该病毒的患者无害。相反，TNF-α中和会使慢性乙型肝炎感染恶化，甚至可能导致死亡。抗炎细胞因子如白细胞介素-10（IL-10）也已在慢性肝病患者中进行试验。虽然给慢性丙型肝炎病毒感染患者施用IL-10确实在肝脏中显示出抗炎作用，但它似乎充当一种前病毒因子，从而限制了其临床应用。另一种具有主要抗炎潜力的细胞因子是脂肪因子脂联素，因为其施用在许多肝损伤实验模型中是有益的。干扰细胞因子途径和/或施用抗炎细胞因子在未来许多肝病的治疗中将备受关注。
