Department of Medicine III, University Hospital, RWTH-Aachen, Germany.
BMC Gastroenterol. 2012 Apr 24;12:38. doi: 10.1186/1471-230X-12-38.
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.
可溶性白细胞介素-2 受体 (sIL-2R，sIL2R，sTAC，sCD25) 是一种可靠的生物标志物，可用于监测如结节病等炎症性疾病的疾病活动度。基于炎症在肝脏疾病进展中的重要致病作用，我们假设 sIL-2R 可能是慢性肝脏疾病 (CLD) 患者炎症细胞激活和疾病严重程度的指标。
我们比较了 71 名不同阶段和病因的 CLD 患者与 41 名健康对照者的血清 sIL-2R 水平。通过 FACS 分析同时评估外周白细胞中的细胞因子/趋化因子水平和循环免疫细胞亚群，将血清 sIL-2R 浓度与肝脏疾病的实验室标志物进行相关性分析。
CLD 患者的血清 sIL-2R 水平明显高于对照组。与无肝硬化患者相比，有肝硬化的患者 sIL-2R 水平显著升高，且随着肝硬化 Child-Pugh 分期的增加而升高，与潜在病因无关。sIL-2R 水平与反映肝脏生物合成能力的参数呈负相关，如白蛋白或国际标准化比值，与肝纤维化的非侵入性标志物如透明质酸或 III 型前胶原肽呈正相关。循环免疫细胞可能是 sIL-2R 的主要来源。事实上，sIL2-R 水平与循环单核细胞密切相关，尤其是非经典 CD14+CD16+单核细胞，通过 FACS 发现其表达高水平的 CD25。促炎细胞因子，包括 IL-2、IFNγ或 IL-6，以及趋化因子也与 sIL2-R 相关。此外，肾功能衰竭是独立于肝功能障碍和炎症的 sIL-2R 水平的重要混杂因素。
sIL-2R 在肝脏疾病和肝硬化患者中升高，与循环炎症细胞相关，并在合并肾功能衰竭时增加。这些数据表明，sIL-2R 可能是 CLD 中免疫细胞激活的潜在标志物，特别是促炎和促纤维化的非经典 CD14+CD16+单核细胞。
