Elevated circulating soluble interleukin-2 receptor in patients with chronic liver diseases is associated with non-classical monocytes

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.