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Logo of bmcgastBioMed Centralsearchsubmit a manuscriptregisterthis articleBMC Gastroenterology
BMC Gastroenterol. 2012; 12: 38.
Published online Apr 24, 2012. doi:  10.1186/1471-230X-12-38
PMCID: PMC3434055
Elevated circulating soluble interleukin-2 receptor in patients with chronic liver diseases is associated with non-classical monocytes
Sebastian Seidler,1 Henning W Zimmermann,1 Ralf Weiskirchen,2 Christian Trautwein,1 and Frank Tackecorresponding author1
1Department of Medicine III, University Hospital, RWTH-Aachen, Germany
2Institute of Clinical Chemistry and Pathobiochemistry, University Hospital, RWTH-Aachen, Germany
corresponding authorCorresponding author.
Sebastian Seidler: Sebastian.Seidler/at/; Henning W Zimmermann: henningbonn/at/; Ralf Weiskirchen: rweiskirchen/at/; Christian Trautwein: ctrautwein/at/; Frank Tacke: frank.tacke/at/
Received December 28, 2011; Accepted April 24, 2012.
The soluble interleukin-2 receptor (sIL-2R, sIL2R, sTAC, sCD25) is a reliable biomarker for disease activity in inflammatory disorders such as sarcoidosis. Based on the essential pathogenic role of inflammation for progression of liver diseases, we hypothesized that sIL-2R might be an indicator of inflammatory cell activation and disease severity in patients with chronic liver diseases (CLD).
We measured sIL-2R serum levels in 71 patients with different stages and etiologies of CLD in comparison to 41 healthy controls. Serum sIL-2R concentrations were correlated with laboratory markers of liver diseases, cytokine / chemokine levels and circulating immune cell subpopulations as simultaneously assessed by FACS analysis from peripheral leukocytes.
CLD patients showed significantly elevated serum sIL-2R levels compared with controls. sIL-2R was significantly higher in patients with compared to patients without established liver cirrhosis and increased with the Child-Pugh stage of cirrhosis, independent of the underlying etiology. sIL-2R levels correlated inversely with parameters indicating the hepatic biosynthetic capacity, such as albumin or international normalized ratio, and positively with non-invasive markers of liver fibrosis such as hyaluronic acid or procollagen-III-peptide. Circulating immune cells might represent a major source of sIL-2R. In fact, sIL2-R levels correlated closely with circulating monocytes, especially non-classical CD14+ CD16+ monocytes, which were found to express high levels of CD25 by FACS. Pro-inflammatory cytokines, including IL-2, IFNγ or IL-6, and chemokines were also associated with sIL2-R. In addition, renal failure was an important confounder of sIL-2R levels independent of liver dysfunction and inflammation.
sIL-2R is elevated in patients with liver diseases and cirrhosis, is associated with circulating inflammatory cells and is increased in concomitant renal failure. These data indicate that sIL-2R might be a potential marker for immune cell activation in CLD, especially for proinflammatory and profibrogenic non-classical CD14 + CD16+ monocytes.
Keywords: Liver cirrhosis, Liver fibrosis, Interleukin-2, CD25, Monocytes, Macrophages
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