Immunopathology and therapy of chronic active hepatitis type B

慢性乙型肝炎的免疫发病机制尚不清楚，但治疗的方法之一是增强患者的免疫反应，溶解感染的细胞。白介素2(IL2)是一种淋巴因子，在T淋巴细胞的增殖和分化中起重要作用。近年来，DNA技术的进步使得重组人白细胞介素2(RIL2)的大量生产成为可能。我们研究了重组人白细胞介素2(RIL2)对慢性乙型病毒性肝炎患者的临床、免疫学作用和抗病毒活性。根据血清DNA聚合酶活性的降低判断，重组IL2在治疗期间抑制了乙肝病毒的复制。此外，在rIL2治疗过程中还观察到血清氨基转移酶的特征性升高。这种升高可能是通过增强对乙型肝炎病毒的免疫反应和增加感染肝细胞的裂解率来实现的。无一致性更改…免疫标志物如OKT4阳性细胞或OKT8阳性细胞在治疗过程中或治疗后出现较多。自然杀伤细胞的活性在治疗过程中逐渐增加，但在开始注射rIL2后1周内趋于下降。在两名从血清中失去HBeAg的应答者中，与无应答者相比，治疗前的自然杀伤活性较高。短期重组IL2治疗并不能使乙肝病毒完全清除。在更长的时间内给予大剂量rIL2的进一步研究是有保证的。细胞介导的对乙肝病毒抗原的免疫被认为在乙肝病毒感染中起重要作用。我们抑制了乙肝病毒感染者外周血细胞对HBc抗原的增殖反应。急性乙肝和部分慢性乙肝患者T细胞对HBV抗原有明显的增殖反应，提示存在HBcAg致敏的T细胞。CD4阳性细胞对HBcAg的反应性强于CD8阳性细胞。关于T细胞对HBcAg的增殖反应是否反映了细胞对乙肝病毒的免疫反应并能够作为疗效的标志，进一步的研究还在进行中。较少

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