AIDS & OPIATES MONKEY MODEL

由于已知外源性和内源性阿片类物质调节 免疫功能和阿片类药物滥用是一个主要的病因， 人类艾滋病，有理由怀疑阿片类药物本身影响 艾滋病的进展。 由于这一问题无法得到充分解决， 在人类或小动物模型中，我们建议用 猴模型是最适合艾滋病的动物模型 它也是一个强大的成瘾模型。 我们的初步数据 来自其他实验室的数据表明， 对艾滋病的进展是有条件的，具有保护作用， 加重作用取决于体内平衡的稳定性， 阿片类药物依赖性和感染的毒力 免疫缺陷病毒（SIV）。 因此，建议的研究如下： 旨在以统计学上有意义的方式测试 我们之前在试点研究中观察到的效果是真实的。 这些 数据将补充正在进行的研究， 在一个稍微不同的模型中， 一种比我们使用的毒力更强的病毒株（SIVmac 239 vs我们的SIVsmm 9）， 在一个不太稳定的鸦片依赖环境中。 计划中的研究还将检查一些免疫神经内分泌 阿片类药物暴露和轻度应激反应中发生的变化， 一种动态的方式，这样这些变化就可以与 预计会影响阿片剂保护环境的情况 依赖猴子对抗SIV。 特别是，我们将测试我们的 假设保护作用受到能力的影响， 阿片类药物调节T细胞和其他白细胞的运输， 在T细胞亚型之间建立平衡， 抵抗病毒感染的进展。 这些研究， 因此，可能对公共卫生和治疗产生重大影响， 在处理艾滋病和药物滥用的两难境地。 资助NIDA / NIH $360，868 2/01/97 - 1/31/99出版物Donahoe，R.M.和Vlahov，D. 阿片类药物作为HIV-1感染进展至 艾滋病 J Neuroimmunol 83：77-87，1998. P51 RR 00165 -38 1998年1月1日- 12/31/1998耶基斯区域灵长类动物研究中心

Since exogenous and endogenous opioids are known to modulate immune functions, and opiate abuse is a major etiologic factor in human AIDS, there is reason to suspect that opiates themselves affect progression of AIDS. Since this issue cannot be addressed adequately in human or small animal models, we are proposing to address it with a monkey model that is the most appropriate animal model for AIDS studies and is also a powerful addiction model. Our preliminary data and data from other laboratories suggest that the effects of opiates on progression of AIDS are conditional, having variably protective and exacerbatory effects depending on the homeostatic stability of the opiate dependency and also the virulence of the infecting immunodeficiency virus (SIV). Accordingly, the proposed studies are meant to test in a statistically meaningful way whether the protective effects we previously observed in a pilot study are genuine. These data will complement ongoing studie s in anot her laboratory looking at potential exacerbatory effects in a somewhat different model using a more virulent virus strain than we use (SIVmac239 vs our SIVsmm9), in a less homeostatically stabilizing opiate dependency environment. The planned studies will also examine a number of immunoneuroendocrine changes that occur in response to opiate exposure and mild stress, in a kinetic fashion, so that these changes can be related to circumstances projected to affect a protective environment for opiate dependent monkeys against SIV. Most particularly, we will test our hypothesis that the protective effects are influenced by the ability of opiates to modulate T-cell and other leukocyte trafficking in a way that establishes a balance between T-cell subtypes that favors resistance to progression of the viral infection. These studies, therefore, may have significant public health and therapeutic impact in dealing with the AIDS/drug-abuse dilemma. FUNDING NIDA / NIH $360,868 2/01/97 - 1/31/99 PUBLICATIONS Donahoe, R.M. and Vlahov, D. Opiates as potential cofactors in progression of HIV-1 infections to AIDS. J Neuroimmunol 83:77-87, 1998. P51RR00165-38 1/1/1998 - 12/31/1998 Yerkes Regional Primate Research Center