Immunopathology and therapy of chronic active hepatitis type B

慢性活动性乙型肝炎的免疫病理学和治疗

基本信息

批准号：
61570345
负责人：
NISHIOKA Mikio
金额：
$ 1.09万
依托单位：
Kagawa Medical School
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1986
资助国家：
日本
起止时间：
1986 至 1988
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-61570345/
关键词：
HBV IL2 Chronic Active Hepatitis Hepatitis B Natural killer細胞 lymphokine avivated killer細胞免疫賦活療法 DNAポリメラーゼトランスアミナーゼ IL-2, Natural Killer細胞 lymphokine activated killer細胞 recombinant interlenkin 2 HBV Natural Killer 細胞 lymphoki

项目摘要

The immunopathologenesis of chronic hepatitis B is still unclear, but one of the approaches to therapy is to enhance the patient's immune response to lyse the infected cells. Interleukin 2(IL2) is a lymphokine which has an important role in the proliferation and differentiation of T lymphocytes. Recent advances in DNA technology now allow production of human recombinant IL2 (rIL2) in quantitis.We have studies the clinical and immunological effects and the antiviral activity of rIL2 in patients with chronic hepatitis B.Ten patients with HBE antigen-positive chronic active hepatitis were treated with rIL2 for 3 to 4 wk. Recombinant IL2 inhibited HBV replication during therapy as judged by decrease of serum DNA polymerase activity. FUrthermore, characteristic increases of serum aminotranserase were observed during rIL2 therapy. This rise might have been mediated by enhanced immune responses to heaptitis B virus and increased rate of lysis of the infected hepatocytes. No consisten changes … More in immmune markers such as OKT4 positive cells or OKT8 positive cells were demonstrated during or after the therapy. THe activities of natural killer cells grandually increased during therapy, although they tended to decrease within 1 wk after the start of rIL2 injections. In two responders who lost HBeAg from serum, the natural killer activity was high before the therapy, compared with nonresponders. Recombinant IL2 therapy over short periods did not result in complete clearance of hepatitis B virus. Further studies with high doses of rIL2 given over longer periods are warranted.Cell-mediated immunity to HBV antigen is considered to play an important tole in HBV infection. We stidued the proliferative response of peripheral blood cells to HBC antigen in patients with HBV infection. A significant T cell proliferative response to HBV antigen was found in patients with acute hepatitis B and some of chronic hepatitis B, suggesting the presence of HBcAg sensitized T cells. Response of CD4 positive cells to HBcAg are stronger than those of CD8 positive cells. Further studies are goinf on whether or not T coll proliferative response to HBcAg reflects cell-mediated immunity to HBv and are able to use as a marker of therapeutic efficacy. Less

慢性乙型肝炎的免疫发病机制尚不清楚，但治疗方法之一是增强患者的免疫反应以裂解受感染的细胞。白细胞介素2（IL2）是一种淋巴因子，在T细胞的增殖和分化中发挥重要作用。 DNA 技术的最新进展现在可以大量生产人重组 IL2 (rIL2)。我们研究了 rIL2 在慢性病患者中的临床和免疫学作用以及抗病毒活性。 10 名 HBE 抗原阳性的慢性活动性肝炎患者接受 rIL2 治疗 3 至 4 周，根据血清 DNA 聚合酶活性的降低判断，重组 IL2 抑制了 HBV 复制。此外，在治疗期间观察到血清转氨酶的特征性升高。 rIL2 治疗。这种升高可能是由于乙型肝炎病毒的免疫反应增强和受感染肝细胞裂解率增加所致。在治疗过程中或治疗后，免疫标记物（例如 OKT4 阳性细胞或 OKT8 阳性细胞）在治疗过程中显着增加，尽管在注射 rIL2 后 1 周内它们趋于下降。与无反应者相比，治疗前血清中的 HBeAg 自然杀伤活性较高，短期重组 IL2 治疗并未导致乙型肝炎病毒完全清除。 rIL2 给予较长时间是必要的。针对 HBV 抗原的细胞介导的免疫被认为在 HBV 感染中发挥重要作用。我们研究了 HBV 感染患者外周血细胞对 HBC 抗原的增殖反应。在急性乙型肝炎和一些慢性乙型肝炎患者中发现了对 HBV 抗原的反应，表明存在 HBcAg 致敏 T 细胞对 CD4 阳性细胞的反应。 HBcAg 比 CD8 阳性细胞更强，T coll 对 HBcAg 的增殖反应是否反映了细胞介导的 HBv 免疫，并可用作治疗效果的标志。