The peritoneal macrophage inflammatory profile in cirrhosis depends on the alcoholic or hepatitis C viral etiology and is related to ERK phosphorylation

BMC Immunology

Pilar García-Peñarrubia³  Rubén Francés¹  José Such¹  Manuel Miras-López²  Cristina Martínez-Pascual²  Trinidad Hernández-Caselles³  Antonio J Ruiz-Alcaraz³  María Martínez-Esparza³  Ana Tapia-Abellán³ 

[1] CIBERehd, Instituto de Salud Carlos III, Madrid, Spain;Unidad de Trasplante Hepático, Servicio de Aparato Digestivo, Hospital Universitario Virgen de la Arrixaca, Murcia, Spain;Departamento de Bioquímica, Biología Molecular (B) e Inmunología Facultad de Medicina, Universidad de Murcia, Murcia, 30100, Spain

关键词: Alcohol;    HCV;    MAP kinases;    Etiology;    Cytokines;    Cirrhosis;    Ascites;   

Others  :  1077890
DOI  :  10.1186/1471-2172-13-42

 received in 2012-04-02, accepted in 2012-07-24,  发布年份 2012

【 摘 要 】

Background

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.

Results

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.

Conclusions

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.

【 授权许可】

   
2012 Tapia-Abellán et al.; licensee BioMed Central Ltd.

【 图 表 】

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