Get access

Peritoneal macrophage priming in cirrhosis is related to ERK phosphorylation and IL-6 secretion

Authors

Errata

This article is corrected by:

  1. Errata: Corrigendum Volume 41, Issue 4, 464, Article first published online: 9 March 2011

Rubén Francés, PhD, Unidad Hepática – CIBERehd, Hospital General Universitario de Alicante, Avda. Pintor Baeza 12, 03010 Alicante, Spain. Tel.: +34 965 937 951; fax: +34 965 938 355; e-mail: frances_rub@gva.es

Abstract

Eur J Clin Invest 2010; 41 (1): 8–15

Abstract

Background  Bacterial infections are common complications arising in patients with cirrhosis and ascites. Translocation of bacterial DNA is a dynamic process that is associated with an increased inflammatory response and a poor prognosis in this setting. The aim of this study was to study whether peritoneal macrophages remain in a chronic primed status to allow a rapid response to subsequent events of bacterial translocation.

Patients and methods  Peritoneal monocyte-derived macrophages were isolated from 25 patients with cirrhosis and non-infected ascites and compared with donor’s blood monocytes. Activation cell-surface markers were screened using flow-cytometry, and the phosphorylation state of ERK 1/2, p38 MAP Kinase, PKB/Akt and transcription factors c-Jun and p65 NFκB were evaluated using Western blot. Synthesis of tumour necrosis factor alpha, interleukin 6 (IL-6) and interleukin-10 (IL-10) at baseline and in response to bacterial stimuli was evaluated using ELISA.

Results  A high expression of CD54, CD86 and HLA-DR at baseline was displayed by peritoneal macrophages. Increased phosphorylated levels of ERK1/2, protein kinase B (PKB) and c-Jun, together with IL-6 production, were observed in peritoneal macrophages at baseline compared with donors’ blood monocytes. A positive correlation was established between basal IL-6 levels and extracellular signal-regulated kinase (ERK) phosphorylation in peritoneal macrophages from patients with cirrhosis (r = 0·9; P = 0·005). Addition of lipopolysaccharide induced higher phosphorylation levels of all studied signalling intermediates than synthetic-oligodeoxydinucleotides, but similar end-stage p65 NFκB.

Conclusions  A sustained immune response is present in ascitic fluid of cirrhotic patients, even in the temporal absence of bacterial antigens. This would facilitate a fast response, probably controlled by IL-6, against repeated bacterial-DNA translocation or in liver chronic inflammation.

Get access to the full text of this article

Ancillary