Elevated Circulating Soluble interleukin-2 Receptor in Patients With Chronic Liver Diseases Is Associated With Non-Classical Monocytes

BMC Gastroenterol. 2012 Apr 24;12:38. doi: 10.1186/1471-230X-12-38.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Biomarkers / blood
  • Case-Control Studies
  • Chronic Disease
  • Cytokines / blood
  • Female
  • Humans
  • Interleukin-2 Receptor alpha Subunit / metabolism
  • Lipopolysaccharide Receptors / metabolism
  • Liver Diseases / blood*
  • Liver Diseases / immunology
  • Liver Diseases / pathology
  • Male
  • Middle Aged
  • Monocytes / immunology*
  • Monocytes / pathology*
  • Receptors, IgG / metabolism
  • Receptors, Interleukin-2 / blood*
  • Severity of Illness Index*
  • Young Adult

Substances

  • Biomarkers
  • Cytokines
  • Interleukin-2 Receptor alpha Subunit
  • Lipopolysaccharide Receptors
  • Receptors, IgG
  • Receptors, Interleukin-2