Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland 20892, USA.
J Gastroenterol Hepatol. 2012 Mar;27 Suppl 2(Suppl 2):89-93. doi: 10.1111/j.1440-1746.2011.07003.x.
The activation of innate immunity by various factors (e.g. lipopolysaccharide and complements) plays an important role in initiating and promoting alcoholic liver injury via the stimulation of Kupffer cells to induce oxidative stress and to produce pro-inflammatory cytokines (e.g. tumor necrosis factor [TNF]-α) that cause hepatocellular damage. Accumulating evidence suggests that the activation of innate immunity also stimulates Kupffer cells to produce the hepatoprotective cytokine interleukin-6 (IL-6) and the anti-inflammatory cytokine IL-10 during alcoholic liver injury. IL-6 protects against alcoholic liver injury via the activation of signal transducer and activator of transcription 3 (STAT3) and the subsequent induction of a variety of hepatoprotective genes in hepatocytes. IL-10 inhibits alcoholic liver inflammation via the activation of STAT3 in Kupffer cells/macrophages and the subsequent inhibition of liver inflammation. Recent studies have suggested that IL-10 may play a dual role in controlling ethanol-induced steatosis and liver injury via the inhibition of the pro-inflammatory cytokine TNF-α, thereby ameliorating alcoholic liver injury, or via the inhibition of the hepatoprotective cytokine IL-6, thereby potentiating alcoholic liver injury. IL-22 is another important hepatoprotective cytokine that protects against acute and chronic alcoholic liver injury by binding to a receptor complex composed of IL-10R2 and IL-22R chains on the surfaces of hepatocytes. Finally, IL-22 treatment is a potential therapeutic option for treating severe forms of alcoholic liver disease because of its antioxidant, antiapoptotic, antisteatotic, proliferative, and antimicrobial effects, as well as the potential added benefit of few side effects.
各种因素（例如脂多糖和补体）激活先天免疫在通过刺激枯否细胞诱导氧化应激和产生促炎细胞因子（例如肿瘤坏死因子 [TNF]-α）导致肝细胞损伤方面在启动和促进酒精性肝损伤中起重要作用。越来越多的证据表明，先天免疫的激活也会刺激枯否细胞在酒精性肝损伤期间产生具有肝保护作用的细胞因子白细胞介素-6（IL-6）和抗炎细胞因子白细胞介素-10（IL-10）。IL-6 通过激活信号转导和转录激活因子 3（STAT3）并随后诱导肝细胞中各种肝保护基因的表达来保护肝脏免受酒精性肝损伤。IL-10 通过在枯否细胞/巨噬细胞中激活 STAT3 并随后抑制肝脏炎症来抑制酒精性肝炎症。最近的研究表明，IL-10 可能通过抑制促炎细胞因子 TNF-α来控制乙醇诱导的脂肪变性和肝损伤，从而改善酒精性肝损伤，或者通过抑制具有肝保护作用的细胞因子 IL-6 来增强酒精性肝损伤，从而在控制乙醇诱导的脂肪变性和肝损伤方面发挥双重作用。IL-22 是另一种重要的肝保护细胞因子，通过与 IL-10R2 和 IL-22R 链组成的受体复合物结合，在肝细胞表面发挥作用，从而防止急性和慢性酒精性肝损伤。最后，由于其抗氧化、抗凋亡、抗脂肪变性、增殖和抗菌作用，以及潜在的副作用较少的额外益处，IL-22 治疗可能成为治疗严重形式的酒精性肝病的一种潜在治疗选择。
