ENKEPHALIN AND AZT THERAPY OF MURINE RETROVIRUS DISEASE

描述：(申请人摘要) 阿片类药物已被证明可以改变免疫功能。自然的 阿片肽蛋氨酸脑啡肽(Met-ENK)被报道可促进 T淋巴细胞数量和功能以细胞因子样的方式进行。因此，这一点 多肽已被建议作为抗病毒化疗的辅助手段。 获得性免疫缺陷综合征(艾滋病)的治疗。这两种技术的结合 抗病毒和免疫刺激物质正在接受认真的评估 几年来在治疗艾滋病方面的有效性。不过，这个 由于在设计时需要保守，该方法一直受到限制 临床方案。目前的方案使用了一种由小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 药物叠氮胸苷和Met-ENK。初步研究表明，Met-ENK可以 显著增强对小鼠反转录病毒感染的保护，因为 通过减少脾肿大和增加存活率来衡量。的用法 小鼠模型，使用不同数量的受试者进行药物治疗 组合，有利于允许研究充分评估 这些代理之间的交互。这些研究将侧重于确定： 1)用药剂量、用药时间、用药途径等方面的最佳组合 给药；2)甲硫氨酸-ENK作用是否通过阿片类药物 受体；3)如果Met-ENK的作用导致细胞因子模式(I型 细胞因子)有利于抵抗疾病；以及4)治疗是否减少 病毒载量是暂时的还是长期的，以及病毒感染是否真的 清除了老鼠的嫌疑。该模型具有很好的应用潜力。 抗病毒和免疫刺激的联合治疗是否 药物可能在未来应用于人类艾滋病或其他逆转录病毒 感染。

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.