急性肝衰竭（ALF）发病机制复杂，以Kupffer细胞（KCs）为主的先天性免疫系统紊乱至为关键。然而在我们建立的药物性猴ALF模型中，病程启动24h内KCs活化轻微，而血清中重要的促炎急性期反应蛋白IL-6骤升近百倍，远早于其他数十种因子；KCs大量浸润后IL-6却急剧下降，提示IL-6并非单纯来源于KCs。经外周血输入人脐带间充质干细胞（hUC-MSCs）能显著改善ALF猴肝功能和组织学，强烈抑制KCs活化及IL-6等多种炎症介质。KCs主要来自循环单核细胞，后者迁移并分化为KCs后才被激活，但我们推测其在入肝前已活化，是IL-6的主要来源和系统性炎症的重要参与者，也极可能是hUC-MSCs调控的靶细胞。本研究将探讨ALF时循环单核细胞活化规律，证实hUC-MSCs抑制循环单核细胞活化的作用及其机制，以期阐明ALF发生发展及转归规律，为将hUC-MSCs用于临床ALF治疗奠定基础。

Acute liver failure (ALF) can occur as a result of various etiologies with sophisticated pathogenesis that has not been fully elucidated. It is well known that the disorder of the innate immune cells including Kupffer cells (KCs) plays a dominant role in the initiation, progression and prognosis of ALF. We previously established a drug-induced non-human primate ALF model and unexpectedly observed that during the first 24 h, KCs were only slightly activated. However, serum IL-6, the crucial pro-inflammatory cytokine and acute phase reactive protein that mainly produced by macrophages, was robustly increased and was much earlier than dozens of other cytokines. Most intriguing, IL-6 was rapidly decreased accompanied with the extensive KCs infiltration and activation, suggesting that IL-6 is not uniquely produced by KCs. When the monkeys were treated with peripheral infusion of human umbilical cord mesenchymal stem cells (hUC-MSCs), their liver function, hepatic histopathology and survival were significantly improved and the activation of KCs, serum levels of IL-6 as well as other inflammatory cytokines were tremendously reduced. Circulating monocytes can migrate into liver and different into KCs when they are chemo-attracted by local damage and are regarded as the major source of KCs. It was reported that circulating monocytes could not be activated until they different into KCs, however, our findings demonstrated that circulating monocytes are likely extensively activated before they migrate into liver, and act as IL-6 producers and play a critical role in the exacerbation of systemic inflammation. Furthermore, we speculate that circulating monocytes are the target cells of hUC-MSCs. In this study, we aim to elucidate the activation of circulating monocytes during the full course of ALF and investigate whether and how hUC-MSCs inhibit the function of the circulating monocytes.