AIDS AND OPIATES--A MONKEY MODEL

描述：(申请人摘要) 由于已知外源性和内源性阿片类药物可以调节免疫功能 而阿片类药物滥用是人类艾滋病的主要致病因素，有其原因 怀疑鸦片类药物本身会影响艾滋病的进展。证据 关于鸦片类药物在艾滋病进展中的作用还不是很清楚， 然而，由于有各种合理的数据支持三种情况中的任何一种 与阿片类药物对艾滋病进展的影响有关的可能结果。那是, 无影响、加重作用和保护作用。数据来自我们的 实验室使用了最好的人类艾滋病模型--猴子模型，在 事实表明，鸦片类药物既有保护作用，也有加重作用 艾滋病的进展。这些数据最具挑衅性的方面是 我们的感染SIV的阿片依赖猴子中没有一只(0/6)在两年内死亡 研究过程中，即使艾滋病的预期死亡率接近1 2.然而，有证据表明，抵消了这些表面上的保护作用 由纳洛酮沉淀的阿片类药物的戒断导致了明显的SIV 诱导和显著的免疫紊乱，可以被认为是 艾滋病进展中的加剧因素。我们还发现，2/6 猴子患上医源性条件下细菌性皮炎 在这项研究接近尾声时，在重复注射鸦片的地方。 这些发现使我们假设鸦片类药物对 艾滋病的进展有条件地依赖于阿片类药物的稳定性 艾滋病病毒的依赖性、毒力和继发性 机会性感染。不幸的是，这只猴子的研究 仅仅是一项试点研究意味着从这些发现中得出的坚定结论是 毫无根据。因此，本提案的目的是验证 我们先前先导研究的主要发现：预防艾滋病 阿片类药物戒断后SIV的进展和诱发；以及 抗菌吞噬能力下降。这项任务必须完成 以一种统计上有意义的方式，这不会损害动物的福利。 这些研究应该会提高对鸦片类药物在艾滋病中的作用的理解。

DESCRIPTION: (Applicant's Abstract) Since exogenous and endogenous opioids are known to modulate immune function and opiate abuse is a major etiologic factor in human AIDS, there is reason to suspect that opiates themselves affect progression of AIDS. Evidence defining the role of opiates in progression of AIDS is less than clear, however, since there are various reasonable data to support any of three possible outcomes relative to opiate effects on AIDS progression. That is, no effects, exacerbatory effects, and protective effects. Data from our laboratory, using the best model of human AIDS, a monkey model, have, in fact, shown the potential of opiates to protect as well as exacerbate progression of AIDS. The most provocative aspect of these data was that none (0/6) of our SIV-infected opiate-dependent monkeys died over a 2-yr course of study, even though the expected death rate from AIDS was near to 1 in 2. Countering these seeming protective effects, however, was evidence that withdrawal of opiates, precipitated by naloxone, caused apparent SIV induction and prominent immune disturbance, that could be regarded as exacerbatory forces in the progression of AIDS. We also found that 2/6 monkeys developed iatrogenically induced opportunistic bacterial dermatitis near the end of this study, at the site of repeated opiate injections. These findings led us to hypothesize that the effects of opiates on progression of AIDS are conditionally dependent on the stability of opiate dependency, virulence of the AIDS virus, and the nature of secondary opportunistic infections. Unfortunately, the fact that this monkey study was only a pilot study meant that firm conclusions from these findings are unwarranted. The present proposal, therefore, is aimed at validating the main findings of our previous pilot study: protection against AIDS progression, induction of SIV upon opiate withdrawal; and, potential depression of anti-bacterial phagocytic capacity. This task is to be done in a statistically meaningful way that will not compromise animal welfare. These studies should improve understanding of the role of opiates in AIDS.