OPIATE MODULATION OF PULMONARY INFECTION

20世纪80年代美国的吸毒问题S与 艾滋病的传播。有人认为，生理变化 与药物滥用相关的因素使药物滥用人群容易患上 增加对艾滋病毒的易感性，并导致 艾滋病。与此同时，人类结核病病例的数量有所下降 自1953年以来，这一趋势稳步逆转，自1986年以来，这一趋势发生了戏剧性的逆转。这个 这种高致命性疾病的死灰复燃在很大程度上与艾滋病有关 流行，在吸毒的艾滋病患者中尤其成问题 施虐者。其目的是调查药物滥用和 传染病，特别是肺部感染，并建立 这种相互作用的分子和细胞基础。 在过去的三年里，调查团队开发了一种 用动物[猪]模型研究滥用药物对人类的影响 疾病。该模型评估了滥用药物对 临床相关的疾病，同时避免了混淆的困难 多种药物滥用，以及糟糕的卫生和营养状况。作为动物模型 为了研究人类呼吸道病原体，几种猪病 类似的人类疾病。猪1型疱疹病毒(SHV-1)产生呼吸道 与人类单纯疱疹病毒肺炎类似的疾病和 牛分枝杆菌对猪和人都有影响，是 引起肺结核的感染性生物。 假设是在长期使用阿片类药物的情况下，受损 肺的免疫功能，特别是涉及肺巨噬细胞， 导致免疫系统抵抗的能力减弱 细菌入侵者。此外，该假说还扩展了这种机制 阿片类免疫抑制涉及细胞因子基因的调节 表情。 第一阶段的研究将检验慢性吗啡的影响。 疱疹病毒原发和继发性巴氏杆菌感染的治疗 多杀菌素引起的肺炎。第二阶段的研究将集中在 分枝杆菌感染，包括原发病毒诱导和分枝杆菌感染 只有博维斯一个人。第一阶段建立在作为 以前的NIDA合同，重点是假定的压制机制。 第二阶段将调查扩展到危重病毒的感染 对吸毒人群的重要性，特别是对那些 感染了艾滋病毒。

Drug abuse in the U.S. in the 1980's increased concomitantly with the spread of AIDS. It has been suggested that physiological alterations associated with drug abuse predisposes the drug abuse population to increased susceptibility to HIV and contributes to the pathogenesis of AIDS. While the number of cases of tuberculosis in humans had decreased steadily since 1953, this trend has reversed dramatically since 1986. The resurgence of this highly virulent disease is largely related to the AIDS epidemic and is especially problematic in AIDS patients who are drug abusers. The goal is to investigate the association between drug abuse and infectious disease, particularly pulmonary infection, and to establish the molecular and cellular basis of this interaction. In the past three years, the team of investigators have developed an animal [swine] model to study the effect of drugs of abuse on human disease. The model evaluates of the effects of drugs of abuse on clinically- relevant diseases while it avoids the confounding difficulties of multiple drug abuse, and poor hygiene and nutrition. As an animal model for the study of human respiratory pathogens, several swine diseases parallel human disease. Suid-herpesvirus-1 (SHV-1) produces a respiratory disease similar to that of herpes simplex virus pneumonia in humans and Mycobacterium bovis affects swine as well as humans and is one of the infectious organisms which causes tuberculosis. The hypothesis is that under conditions of chronic opiate use, impaired immune function of the lung, particularly involving pulmonary macrophages, results in an attenuation of the immune system's ability to fight off bacterial invaders. Furthermore, the hypothesis extends that the mechanism of opiate immunosuppression involves modulation of cytokine gene expression. The first phase of studies will examine the effect of chronic morphine treatment on primary herpesvirus-induced and secondary Pasteurella multocida-induced pneumonia. The second phase of studies will focus on Mycobacterial infection, both primary virus-induced and Mycobacterium bovis alone. The first phase builds on work completed as part of a previous NIDA contract and focuses on putative mechanisms of suppression. The second phase extend investigations to an infection of critical importance to the drug abusing population and specifically to those infected with HIV.