Departamento de Bioquímica, Biología Molecular (B) e Inmunología Facultad de Medicina, Universidad de Murcia, and Unidadde Trasplante Hepático, Servicio de Aparato Digestivo, Hospital Universitario Virgen de la Arrixaca, Murcia, 30100, Spain.
BMC Immunol. 2012 Aug 6;13:42. doi: 10.1186/1471-2172-13-42.
The development of ascites in cirrhotic patients generally heralds a deterioration in their clinical status. A differential gene expression profile between alcohol- and hepatitis C virus (HCV)-related cirrhosis has been described from liver biopsies, especially those associated with innate immune responses. The aim of this work was to identify functional differences in the inflammatory profile of monocyte-derived macrophages from ascites in cirrhotic patients of different etiologies in an attempt to extrapolate studies from liver biopsies to immune cells in ascites. To this end 45 patients with cirrhosis and non-infected ascites, distributed according to disease etiology, HCV (n=15) or alcohol (n=30) were studied. Cytokines and the cell content in ascites were assessed by ELISA and flow cytometry, respectively. Cytokines and ERK phosphorylation in peritoneal monocyte-derived macrophages isolated and stimulated in vitro were also determined.
A different pattern of leukocyte migration to the peritoneal cavity and differences in the primed status of macrophages in cirrhosis were observed depending on the viral or alcoholic etiology. Whereas no differences in peripheral blood cell subpopulations could be observed, T lymphocyte, monocyte and polymorphonuclear cell populations in ascites were more abundant in the HCV than the alcohol etiology. HCV-related cirrhosis etiology was associated with a decreased inflammatory profile in ascites compared with the alcoholic etiology. Higher levels of IL-10 and lower levels of IL-6 and IL-12 were observed in ascitic fluid from the HCV group. Isolated peritoneal monocyte-derived macrophages maintained their primed status in vitro throughout the 24 h culture period. The level of ERK1/2 phosphorylation was higher in ALC peritoneal macrophages at baseline than in HCV patients, although the addition of LPS induced a greater increase in ERK1/2 phosphorylation in HCV than in ALC patients.
The macrophage inflammatory status is higher in ascites of alcohol-related cirrhotic patients than in HCV-related patients, which could be related with differences in bacterial translocation episodes or regulatory T cell populations. These findings should contribute to identifying potential prognostic and/or therapeutic targets for chronic liver diseases of different etiology.
肝硬化患者腹水的发展通常预示着其临床状况恶化。已经从肝活检中描述了酒精和丙型肝炎病毒（HCV）相关肝硬化之间的差异基因表达谱，特别是那些与先天免疫反应相关的基因表达谱。本研究的目的是鉴定不同病因肝硬化患者腹水单核细胞来源巨噬细胞炎症谱的功能差异，试图从肝活检推断免疫细胞在腹水的研究。为此，根据疾病病因，将 45 例非感染性肝硬化腹水患者（HCV 组，n=15；酒精组，n=30）分为 HCV 相关肝硬化和酒精性肝硬化两组。通过 ELISA 和流式细胞术分别评估腹水细胞因子和细胞含量。还测定了分离和体外刺激的腹腔单核细胞来源巨噬细胞中的细胞因子和 ERK 磷酸化。
根据病毒或酒精病因，观察到白细胞向腹腔迁移的模式不同，以及巨噬细胞在肝硬化中的初始状态不同。尽管在外周血细胞亚群中未观察到差异，但 HCV 组腹水 T 淋巴细胞、单核细胞和多形核细胞数量多于酒精组。与酒精性肝硬化相比，HCV 相关肝硬化的腹水炎症谱较低。与酒精组相比，HCV 组腹水的 IL-10 水平较高，而 IL-6 和 IL-12 水平较低。从 HCV 组腹水分离的腹腔单核细胞来源巨噬细胞在体外整个 24 小时培养期间保持其初始状态。与 HCV 患者相比，ALC 患者的腹腔巨噬细胞中 ERK1/2 磷酸化的基线水平较高，尽管 LPS 可诱导 HCV 患者中 ERK1/2 磷酸化的增加大于 ALC 患者。
酒精性肝硬化患者腹水的巨噬细胞炎症状态高于 HCV 相关患者，这可能与细菌易位发作或调节性 T 细胞群体的差异有关。这些发现有助于确定不同病因慢性肝病的潜在预后和/或治疗靶点。
