title: Elevated circulating soluble interleukin-2 receptor in patients with chronic liver diseases is associated with non-classical monocytes.
abstract: BACKGROUND
  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).
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medicine III, University Hospital, RWTH-Aachen, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Seidler
authors.forename: Henning W
authors.initials: HW
authors.lastname: Zimmermann
authors.forename: Ralf
authors.initials: R
authors.lastname: Weiskirchen
authors.forename: Christian
authors.initials: C
authors.lastname: Trautwein
authors.forename: Frank
authors.initials: F
authors.lastname: Tacke
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002908:Chronic Disease; D016207:Cytokines / Q000097:blood; D005260:Female; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008107:Liver Diseases / Q000097:blood* / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology* / Q000473:pathology*; D017452:Receptors, IgG / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000097:blood*; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D015415:Biomarkers; D016207:Cytokines; D053645:Interleukin-2 Receptor alpha Subunit; D018950:Lipopolysaccharide Receptors; D017452:Receptors, IgG; D015375:Receptors, Interleukin-2