Department of Laboratory Medicine, The Second Hospital of Shandong University, 247#, Beiyuan Dajie, Jinan, 250033, China,
Inflammation. 2013 Dec;36(6):1374-82. doi: 10.1007/s10753-013-9677-0.
The aim of this study is to investigate the optimal dose, treatment time, and possible immunologic mechanisms of interferon alpha (IFN-α) in the treatment of liver fibrosis. Mice were injected intraperitoneally with 10 % carbon tetrachloride to induce liver fibrosis, except in the normal control group. The experimental mice were randomly divided into four groups: physiological saline group, 20 U/gb wt IFN-α group, 40 U/gb wt IFN-α group, and 60 U/gb wt IFN-α group. After 3 and 6 weeks, type I collagen was detected in liver by hematoxylin and eosin (HE) stain, Masson's trichrome stain, and immunohistochemical staining. The number of CD8(+) T cells, the number of CD4(+)CD25(+)Foxp3(+) Tregs and the activation of CD4(+) T cells were detected in liver and spleen. Beneficial effects were observed in the 40 U/gb wt IFN-α group by pathological analysis. The number of CD8(+) T cells in the liver was significantly lower in mice receiving middle-dose IFN-α therapy as compared to mice receiving physiological saline (P < 0.05), while CD4(+)CD25(+)Foxp3(+) Tregs and activation of CD4(+) T cells in the liver were significantly higher in the therapeutic group than in the physiological saline group (P < 0.05). CD8(+) T cells (r = 0.3796) and activated CD4(+) T cells (r = 0.2437) were found to be positively correlated with the degree of liver fibrosis. CD4(+)CD25(+)Foxp3(+) Tregs (r = -0.7932) was found to be negatively correlated with the degree of liver fibrosis. IFN-α can inhibit liver fibrosis following 6 weeks of middle-dose IFN-α therapy by upregulating CD4(+)CD25(+)Foxp3(+) Tregs and suppressing CD8(+) T cells.
本研究旨在探讨干扰素 α（IFN-α）治疗肝纤维化的最佳剂量、治疗时间和可能的免疫机制。除正常对照组外，其余小鼠均经腹腔注射 10%四氯化碳诱导肝纤维化。将实验小鼠随机分为生理盐水组、20U/gbwt IFN-α 组、40U/gbwt IFN-α 组和 60U/gbwt IFN-α 组。3 周和 6 周后，采用苏木精-伊红（HE）染色、Masson 三色染色和免疫组织化学染色检测肝组织 I 型胶原，检测肝、脾中 CD8(+)T 细胞、CD4(+)CD25(+)Foxp3(+)Tregs 数量及 CD4(+)T 细胞活化。病理分析显示，中剂量 IFN-α 组疗效较好。与生理盐水组相比，中剂量 IFN-α 治疗组小鼠肝内 CD8(+)T 细胞数量明显减少（P<0.05），而肝内 CD4(+)CD25(+)Foxp3(+)Tregs 和 CD4(+)T 细胞活化明显升高（P<0.05）。肝内 CD8(+)T 细胞（r=0.3796）和活化的 CD4(+)T 细胞（r=0.2437）与肝纤维化程度呈正相关，而 CD4(+)CD25(+)Foxp3(+)Tregs（r=-0.7932）与肝纤维化程度呈负相关。中剂量 IFN-α 治疗 6 周可通过上调 CD4(+)CD25(+)Foxp3(+)Tregs、抑制 CD8(+)T 细胞抑制肝纤维化。
