Recent advances in the understanding of the biochemistry and clinical pharmacology of interleukin-2.
Recent advances in the understanding of the biochemistry and clinical pharmacology of interleukin-2.
复制标题
IL-2 的生物化学和临床药理学的最新进展。
DOI：
--
复制
发表时间：
1987
期刊：
影响因子：
--
通讯作者：
A. L. Goldstein
中科院分区：
文献类型：
--
作者：
M. Fletcher;A. L. Goldstein
本文综述了1984年至1986年9月期间对白介素2(IL-2)的生物化学和临床药理学方面的重要研究进展。其中包括IL-2及其受体的分子生物学研究进展。人IL-2由Taniguchi等人克隆并测序。1983年。人IL-2基因位于4号染色体的长臂上，其二级结构以α螺旋为主。成熟的基因产物是一个133个氨基酸的糖蛋白，分子量为15,420道尔顿。IL-2受体是一个由272个氨基酸组成的糖蛋白。成熟的受体分子量为55,000道尔顿。对IL-2的作用机制，特别是其在诱导IL-2受体中的作用，以及对IL-2产生的控制方面也有了更准确的理解。代谢和形态研究表明，T细胞抗原受体的激活使细胞对IL-2产生反应，但不能使它们通过细胞周期。相反，似乎是IL-2刺激G1期细胞进入S期。猛烈的转变。在这个过程中，细胞原癌基因c-myb被瞬时诱导到基础水平的6到7倍。IL-2作为几个T细胞亚群的生长因子的作用已经被证实，并被定义为B细胞的一个新的生长因子。最重要的是，IL-2被证明是外周血细胞的直接有丝分裂细胞和扩增亚群，称为淋巴因子激活的杀伤细胞(LAK)和肿瘤浸润性淋巴细胞(TIL)。IL-2的产生或活性有多种病理机制，包括霍奇金氏病、移植物抗宿主病、系统性红斑狼疮、麻风、获得性免疫缺陷综合征和成人T细胞白血病。在此综述的小鼠和人类体内研究揭示了这种生长因子的治疗潜力和毒性的重要参数。最后，胸腺肽组分5和胸腺肽α1对人PBL上IL-2受体的调节表明，在某些疾病状态下，可能上调IL-2受体的表达，从而提高IL-2的疗效。
This review covers significant developments in the understanding of the biochemistry and clinical pharmacology of Interleukin-2 (IL-2) that were achieved from 1984 through September 1986. These include developments in the molecular biology of IL-2 and its receptors. Human IL-2 was cloned and sequenced by Taniguchi et al. in 1983. The gene for human IL-2 is located on the long arm of chromosome 4. The secondary structure of the gene is predominantly alpha helix. The mature gene product is a 133 amino acid glycoprotein with a molecular weight of 15,420 Daltons. The IL-2 receptor was revealed to be a glycoprotein of 272 amino acids. The mature receptor has a molecular weight of 55,000 Daltons. A more precise understanding of the mechanism of action IL-2, in particular its role in the induction of the IL-2 receptor, and aspects of the control of IL-2 production was also achieved. Metabolic and morphologic studies have revealed that activation of the T-cell antigen receptor renders the cells responsive to IL-2, but does not move them through the cell cycle. Rather, it appears that IL-2 stimulates G1 progression to S phase ie. blastic transformation. During this progression the cellular proto-oncogene c-myb is induced transiently to 6 to 7 times basal levels. The role of IL-2 as a growth factor for several subsets of T cells has been confirmed, and a new role as a growth factor for B cells was defined. Most importantly, IL-2 was shown to be directly mitogenic for and to expand subpopulations of peripheral blood cells, termed lymphokine-activated killer (LAK) cells and tumor-infiltrating lymphocytes (TIL). A number of pathologies of IL-2 production or activity have been defined, including Hodgkin's disease, graft versus host disease, systemic lupus erythematosus, lepromatous leprosy, acquired immune deficiency syndrome, and adult T cell leukemia. Murine and human in vivo studies reviewed here have revealed significant parameters of the therapeutic potential as well as the toxicity of this growth factor. Finally, the modulation of IL-2 receptors on human PBL's by thymosin fraction 5 and thymosin alpha 1 suggests that it might be possible to up-regulate IL-2 receptor expression in certain disease states and thus increase the efficacy of IL-2.