ENKEPHALIN AND AZT THERAPY OF MURINE RETROVIRUS DISEASE

脑啡肽和 AZT 治疗鼠逆转录病毒病

基本信息

批准号：
2749127
负责人：
KENNETH EUGENE UGEN
金额：
$ 25.4万
依托单位：
UNIVERSITY OF SOUTH FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
1996
资助国家：
美国
起止时间：
1996-09-01 至 2000-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/2749127
关键词：
AIDS therapy combination chemotherapy cytokine disease /disorder model drug administration rate /duration enkephalins laboratory mouse murine AIDSs nonhuman therapy evaluation opioid receptor splenomegaly zidovudine

项目摘要

DESCRIPTION: (Applicant's Abstract) Opioids have been demonstrated to alter immune functions. The natural opioid peptide methionine enkephalin (Met-ENK) has been reported to boost T-lymphocyte numbers and function in a cytokine-like manner. Thus, this peptide has been suggested as an adjunct to antiviral chemotherapy in the treatment of acquired immunodeficiency syndrome (AIDS). The combination of antiviral and immunostimulatory substances has been under serious evaluation for effectiveness in treating AIDS for several years. However, this approach has been limited by the need to be conservative in designing clinical protocols. The current proposal uses a murine retrovirus-induced immunodeficiency model to study various combinations of the anti-retroviral drug azidothymidine and Met-ENK. Initial studies indicate that Met-ENK can significantly enhance protection against the mouse retrovirus infection, as measured by reduced splenomegaly and increased survival. The use of the murine model, which uses various numbers of subjects treated by drug combinations, is advantageous in allowing studies that fully evaluate the interaction between these agents. These studies will focus on determining: 1) the optimal drug combination in dosing, time, and route of administration; 2) whether or not the Met-ENK effects are via opioid receptors; 3) if the effects of Met-ENK result in a cytokine pattern (type I cytokines) that favors resistance to disease; and 4) whether therapy reduces viral load temporarily or long term, and whether viral infection is actually cleared from the mice. This model has excellent potential for establishing whether the therapeutic combination of antiviral and immunostimulatory agents may be applied in the future to human AIDS or other retroviral infections.

描述：（申请人的摘要）已证明阿片类药物可以改变免疫功能。自然据报道，阿片类肽蛋氨酸Enkephalin（Met-enk）已促进 T淋巴细胞数和以细胞因子样的方式功能。因此，这个肽已被认为是抗病毒化学疗法的辅助治疗获得的免疫缺陷综合征（AIDS）。结合抗病毒和免疫刺激性物质一直在认真评估为了治疗艾滋病的有效性已有几年。但是，这个方法受到保守设计的需要而受到限制临床方案。当前的提案使用鼠逆转录病毒诱导的免疫缺陷模型研究抗逆转录病毒的各种组合药物叠氮蛋白酶和大甲烷。最初的研究表明Met-enk可以显着增强对小鼠逆转录病毒感染的保护通过减少脾肿大和增加存活率来衡量。使用鼠模型，使用药物治疗的各种受试者组合对于允许对完全评估的研究是有利的这些药物之间的相互作用。这些研究将侧重于确定： 1）剂量，时间和途径的最佳药物组合行政; 2）Met-Enk效应是否是通过阿片类药物受体； 3）如果Met-enk的影响导致细胞因子模式（I型有利于疾病抵抗的细胞因子； 4）治疗是否减少病毒负荷暂时还是长期，以及病毒感染实际上是从老鼠中清除。该模型具有建立的极大潜力抗病毒和免疫刺激的治疗组合是否将来可以将代理应用于人类艾滋病或其他逆转录病毒感染。