BACKGROUND & AIMS : Bacterial infections commonly occur in
decompensated cirrhosis resulting from bacterial translocation
from the intestine. We studied the role of intestinal macrophages
and the epithelial barrier in cirrhosis.
METHODS : Forty-four patients with NASH/ASH cirrhosis (decompensated
n = 29, compensated n = 15) and nineteen controls
undergoing endoscopy were recruited. Serum was obtained and
LPS and LBP levels determined. Intestinal macrophages were
characterized by flow cytometry, immunohistochemistry, and
nitric oxide (NO) production measured in supernatant of cultured
duodenal samples. Quantitative RT-PCR was performed on duodenal
biopsies assessing 84 inflammatory genes. Protein levels
of cytokines/chemokines were assessed in serum and supernatant.
The duodenal wall was assessed by electron microscopy,
tight junction protein expression determined by RT-PCR, immunohistochemistry,
and Western blot and, functional analysis
performed by transepithelial resistance measurement and permeability
studies.RESULTS : Increased plasma LPS, LBP levels and higher numbers of
duodenal CD33+/CD14+/Trem-1+ macrophages, synthesizing iNOS
and secreting NO were present in decompensated cirrhosis.
Upregulation of IL-8, CCL2, CCL13 at the transcriptional level,
and increased IL-8, and IL-6 were detected in supernatant and
serum in cirrhosis. IL-6 and IL-8 co-localised with iNOS+ and
CD68+, but not with CD11c+ cells. Electron microscopy demonstrated
an intact epithelial barrier. Increased Claudin-2 was
detected by Western blot and immunohistochemistry, while
decreased transepithelial resistance and increased duodenal permeability
were detected in decompensated cirrhosis.
CONCLUSIONS : Our study shows the presence of activated CD14+-
Trem-1+iNOS+ intestinal macrophages, releasing IL-6, NO, and
increased intestinal permeability in patients with cirrhosis, suggesting
that these cells may produce factors capable of enhancing
permeability to bacterial products.