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[干扰素(IFN)治疗B型和C型慢性肝炎患者的作用机制]

[Mechanisms of the effect of interferon (IFN) therapy in patients with type B and C chronic hepatitis].

作者信息

Karino Y

机构信息

Third Department of Internal Medicine, Hokkaido University School of Medicine, Sapporo, Japan.

出版信息

Hokkaido Igaku Zasshi. 1993 May;68(3):297-309.

PMID:7686526
Abstract

The relationship between 2', 5'-oligoadenylate synthetase (2-5AS) and HLA class I antigen in the hepatocyte of patients with type B or type C chronic hepatitis with and without interferon (IFN) therapy was investigated. The expression of HLA class I antigen of hepatocytes of biopsied specimen and PBL HLA class I antigen expression showed relevancy. Then, the HLA antigen expression of peripheral blood lymphocyte (PBL) and the 2-5AS activity of peripheral blood mononuclear cell (PBMC) were analyzed. In patients with type B or type C hepatitis, the mean activity of PBMC 2-5AS was significantly higher than that of healthy controls. Also the HLA class I antigen expression of PBL was significantly intense in patients with type B or type C hepatitis compared with healthy controls. In the acute exacerbated phase of type B chronic hepatitis, the HLA class I antigen expression of PBL and 2-5AS activity of PBMC increased along with elevation of serum GPT and then decreased with the remission of serum GPT. These results suggest that endogenously produced IFN leads the lysis of hepatocyte infected with hepatitis B virus (HBV) by cytotoxic T cells, and the restriction of HBV replication by activation of the 2-5A system simultaneously, and then leads the elimination of HBV. The activity of PBMC 2-5AS and the expression of PBL HLA class I antigen increased significantly during IFN therapy. In type B chronic hepatitis, the effective cases showed relatively high activity of serum 2-5AS compared with the non-effective cases. On the other hand, there were no significant differences in PBL HLA class I antigen expression between effective cases and non-effective cases. In type C chronic hepatitis, most patients with type III and type IV HCV genotype showed disappearance of HCV-RNA regardless of serum 2-5AS activity. In patients with type II HCV genotype, the serum 2-5AS activity was related to the anti-viral effect of IFN therapy.

摘要

研究了B型或C型慢性肝炎患者肝细胞中2',5'-寡腺苷酸合成酶(2-5AS)与HLA I类抗原之间的关系,这些患者接受或未接受干扰素(IFN)治疗。活检标本中肝细胞HLA I类抗原的表达与外周血淋巴细胞(PBL)HLA I类抗原表达具有相关性。然后,分析了外周血淋巴细胞(PBL)的HLA抗原表达和外周血单个核细胞(PBMC)的2-5AS活性。在B型或C型肝炎患者中,PBMC 2-5AS的平均活性显著高于健康对照组。与健康对照组相比,B型或C型肝炎患者PBL的HLA I类抗原表达也明显增强。在B型慢性肝炎急性加重期,PBL的HLA I类抗原表达和PBMC的2-5AS活性随着血清谷丙转氨酶(GPT)升高而增加,随后随着血清GPT缓解而降低。这些结果表明,内源性产生的干扰素通过细胞毒性T细胞导致感染乙型肝炎病毒(HBV)的肝细胞溶解,同时通过激活2-5A系统限制HBV复制,进而导致HBV的清除。在IFN治疗期间,PBMC 2-5AS的活性和PBL HLA I类抗原的表达显著增加。在B型慢性肝炎中,有效病例的血清2-5AS活性相对高于无效病例。另一方面,有效病例和无效病例之间PBL HLA I类抗原表达没有显著差异。在C型慢性肝炎中,大多数III型和IV型丙型肝炎病毒(HCV)基因型患者的HCV-RNA消失,与血清2-5AS活性无关。在II型HCV基因型患者中,血清2-5AS活性与IFN治疗的抗病毒效果有关。

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