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物质可调节免疫功能， 阿片类药物滥用是人类艾滋病的主要致病因素， 怀疑鸦片本身会影响艾滋病的发展 证据 阿片类药物在艾滋病进展中的作用尚不清楚， 然而，由于有各种合理的数据来支持任何三个， 阿片类药物对艾滋病进展的影响。 也就是说， 无作用、加重作用和保护作用。 信息的途径 实验室，使用人类艾滋病的最佳模型，猴子模型，有，在 事实上，阿片类药物有可能保护和加剧 艾滋病的进展。 这些数据中最具争议性的一点是， 没有（0/6）SIV感染的阿片类药物依赖猴在2年内死亡， 尽管艾滋病的预期死亡率接近1 在2. 然而，有证据表明， 纳洛酮促使阿片类药物戒断，导致明显的SIV 诱导和显著的免疫紊乱，这可以被视为 在艾滋病的发展过程中， 我们还发现，2/6 猴发生医源性诱导的机会性细菌性皮炎 在本研究接近结束时，在重复注射阿片类药物的部位。 这些发现使我们假设阿片类药物对 艾滋病的进展有条件地依赖于阿片类药物的稳定性 艾滋病病毒的毒力和继发性 机会性感染 不幸的是，这项猴子研究 只是一项试点研究，这意味着从这些发现中得出的结论是 毫无根据 因此，本提案旨在验证 我们先前试点研究的主要发现：预防艾滋病 进展，阿片类药物戒断后诱导SIV;以及，潜在的 抑制抗菌吞噬能力。 这个任务是要完成的 以一种具有统计意义的方式进行，不会损害动物福利。 这些研究应该提高对阿片类药物在艾滋病中作用的认识。

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.