OPIATE MODULATION OF PULMONARY INFECTION

阿片类药物调节肺部感染

• 批准号: 2120989
• 负责人: THOMAS William MOLITOR
• 金额: $ 22.89万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-09-01 至 1997-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2120989
• 关键词: Mycobacterium; Pasteurella multocida; artificial immunosuppression; bactericidal immunity; biological models; cellular immunity; cytokine; drug abuse; drug withdrawal; flow cytometry; gene expression; haptoglobins; histopathology; immunocytochemistry; in situ hybridization; inflammation; morphine; northern blottings; phagocytosis; pneumonia; secondary infection; suid alphaherpesvirus 1; swine; tuberculosis; virus cytopathogenic effect

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.

20世纪80年代，美国的药物滥用现象随着人口的增长而增加。 艾滋病的传播。有人认为生理变化 与药物滥用相关的药物滥用人群倾向于 增加对艾滋病毒的易感性，并有助于 艾滋病虽然人类结核病病例数量有所减少， 自1953年以来，这一趋势一直在稳步发展，但自1986年以来，这一趋势急剧逆转。的 这种高度致命的疾病的重新流行主要与艾滋病有关 艾滋病是一种流行病，在吸毒的艾滋病患者中尤其成问题。 施虐者目的是调查药物滥用和 感染性疾病，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，调查小组已经制定了一个 研究滥用药物对人类的影响的动物[猪]模型 疾病该模型评估了药物滥用对 临床相关疾病，同时避免混淆困难 滥用多种药物，卫生和营养不良。作为动物模型 对于人类呼吸道病原体的研究， 人类的平行疾病猪疱疹病毒-1（SHV-1）产生呼吸道感染。 与人类单纯疱疹病毒性肺炎相似的疾病， 牛分枝杆菌影响猪以及人类，并且是 导致肺结核的传染性微生物。 假设在长期使用阿片类药物的情况下， 肺的免疫功能，特别是涉及肺巨噬细胞， 导致免疫系统抵抗病毒的能力减弱 细菌入侵者此外，该假设扩展了该机制 阿片类药物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查长期吗啡的作用 治疗原发疱疹病毒和继发巴氏杆菌 多杀性肺炎第二阶段的研究将侧重于 分枝杆菌感染，包括原发性病毒引起的和分枝杆菌感染 只有牛第一阶段的基础是作为 以前的NIDA合同，并侧重于推定的抑制机制。 第二阶段扩大调查范围， 对吸毒人群的重要性，特别是对那些 感染了艾滋病病毒