Interleukin-8 is activated in patients with chronic liver diseases and associated with hepatic macrophage accumulation in human liver fibrosis

PLoS One. 2011;6(6):e21381. doi: 10.1371/journal.pone.0021381. Epub 2011 Jun 22.


Background: Interleukin-8 (IL-8, CXCL8) is a potent chemoattractant for neutrophils and contributes to acute liver inflammation. Much less is known about IL-8 in chronic liver diseases (CLD), but elevated levels were reported from alcoholic and hepatitis C-related CLD. We investigated the regulation of IL-8, its receptors CXCR1 and CXCR2 and possible IL-8 responding cells in CLD patients.

Methodology: Serum IL-8 levels were measured in CLD patients (n = 200) and healthy controls (n = 141). Intrahepatic IL-8, CXCR1 and CXCR2 gene expression was quantified from liver samples (n = 41), alongside immunohistochemical neutrophil (MPO) and macrophage (CD68) stainings. CXCR1 and CXCR2 expression was analyzed on purified monocytes from patients (n = 111) and controls (n = 31). In vitro analyses explored IL-8 secretion by different leukocyte subsets.

Principal findings: IL-8 serum levels were significantly increased in CLD patients, especially in end-stage cirrhosis. Interestingly, patients with cholestatic diseases exhibited highest IL-8 serum concentrations. IL-8 correlated with liver function, inflammatory cytokines and non-invasive fibrosis markers. Intrahepatically, IL-8 and CXCR1 expression were strongly up-regulated. However, intrahepatic IL-8 could only be associated to neutrophil infiltration in patients with primary biliary cirrhosis (PBC). In non-cholestatic cirrhosis, increased IL-8 and CXCR1 levels were associated with hepatic macrophage accumulation. In line, CXCR1, but not CXCR2 or CXCR3, expression was increased on circulating monocytes from cirrhotic patients. Moreover, monocyte-derived macrophages from CLD patients, especially the non-classical CD16⁺ subtype, displayed enhanced IL-8 secretion in vitro.

Conclusions: IL-8 is strongly activated in CLD, thus likely contributing to hepatic inflammation. Our study suggests a novel role of IL-8 for recruitment and activation of hepatic macrophages via CXCR1 in human liver cirrhosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Case-Control Studies
  • Chronic Disease
  • Female
  • Humans
  • Inflammation Mediators / metabolism
  • Interleukin-8 / blood*
  • Interleukin-8 / genetics*
  • Liver / metabolism*
  • Liver Cirrhosis / blood*
  • Liver Cirrhosis / etiology
  • Liver Cirrhosis / genetics*
  • Liver Cirrhosis / pathology
  • Macrophages / metabolism*
  • Male
  • Middle Aged
  • Monocytes / metabolism
  • Neutrophils / metabolism
  • Receptors, Interleukin-8A / genetics
  • Receptors, Interleukin-8A / metabolism
  • Severity of Illness Index
  • Up-Regulation / genetics
  • Young Adult


  • CXCL8 protein, human
  • Inflammation Mediators
  • Interleukin-8
  • Receptors, Interleukin-8A