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Background: Graft-versus-host disease (GVHD) is associated with high mortality. Early diagnosis is essential to start treatment and to improve outcomes. Because of the inflammatory nature, we hypothesis that cytokine profile of patients with GVHD may serve as diagnostic markers. The present study was to evaluate the role of cytokine profile in the diagnosis of GVHD., Methods: An immunoassay was used to detect 29 cytokines simultaneously in the serum; the measuring sensitivity of all cytokines was pg/mL. Healthy subjects undergoing annual routine physical examinations served as negative controls; 23 patients with hepatocellular carcinoma (HCC) who had undergone liver transplantation (the LT group) comprised the test subjects. A total of 22 kidney recipients with biopsy-confirmed GVHD (the RT group) were included for comparison. HCC patients with radical surgery (the HCC group, n=22) served as positive control. The liver contents of the three cytokines, IL-2, IL-18, and IFN-gamma, were detected with immunohistochemistry. Serum granzyme B and perforin were measured by flow cytometry., Results: Of the 29 cytokines, the levels of IL-2 and IL-18 were increased significantly in liver recipients with GVHD compared with healthy controls (P<0.05). The serum levels of these three cytokines in the healthy, HCC, LT, and RT groups were IL-2: 0.90+/-0.02, 4.14+/-0.61, 5.10+/-0.89, and 1.48+/-0.09 pg/mL; IL-18: 80.61+/-9.35, 109.51+/-10.93, 230.11+/-12.92, and 61.98+/-7.88 pg/mL; IFN-gamma: 24.06+/-3.88, 24.84+/-3.21, 40.37+/-5.88, and 15.33+/-4.72 pg/mL, respectively. Immunohistochemistry showed that these 3 cytokines expressions in the liver were parallel to the serum cytokine. After standard anti-GVHD treatment, the expressions of IL-2, IL-18, and IFN-gamma were decreased in the liver (P<0.05). Serum granzyme B and perforin were significantly increased in GVHD patients (P<0.05)., Conclusions: IL-2, IL-18 and IFN-gamma were from liver and might serve as biomarkers for monitoring GVHD development and the effects of anti-GVHD treatment. Granzyme B and perforin may play a role in increasing IL-2, IL-18, and IFN-gamma levels in GVHD patients.

Background: Mesenchymal stem cells (MSCs) and fibroblasts have intimate relationships, and the phenotypic homology between fibroblasts and MSCs has been recently described. The aim of this study was to investigate the hepatic differentiating potential of human fibroblasts in cirrhotic liver., Methods: The phenotypes of fibroblasts in cirrhotic liver were labeled by biological methods. After that, the differentiation potential of these fibroblasts in vitro was characterized in terms of liver-specific gene and protein expression. Finally, an animal model of hepatocyte regeneration in severe combined immunodeficient (SCID) mice was created by retrorsine injection and partial hepatectomy, and the expression of human hepatocyte proteins in SCID mouse livers was checked by immunohistochemical analysis after fibroblast administration., Results: Surface immunophenotyping revealed that a minority of fibroblasts expressed markers of MSCs and hepatic epithelial cytokeratins as well as alpha-smooth muscle actin, but homogeneously expressed vimentin, desmin, prolyl 4-hydroxylase and fibronectin. These fibroblasts presented the characteristics of hepatocytes in vitro and differentiated directly into functional hepatocytes in the liver of hepatectomized SCID mice., Conclusions: This study demonstrated that fibroblasts in cirrhotic liver have the potential to differentiate into hepatocyte-like cells in vitro and in vivo. Our findings infer that hepatic differentiation of fibroblasts may serve as a new target for reversion of liver fibrosis and a cell source for tissue engineering.