HIV-induced neuroinflammation associated with opiod abuse and tobacco smoke

艾滋病毒引起的与阿片类药物滥用和吸烟相关的神经炎症

基本信息

批准号：
9153336
负责人：
Yuri Persidsky
金额：
$ 73.35万
依托单位：
TEMPLE UNIV OF THE COMMONWEALTH
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-08-15 至 2021-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9153336
关键词：
Acquired Immunodeficiency Syndrome Address Adhesions Affect Agonist Animals Antiviral Agents Atherosclerosis Blood - brain barrier anatomy Brain CCL2 gene CCR5 gene CXCR4 gene Cell Communication Cells Chronic Chronic Obstructive Airway Disease Clinic Competence Complex Data Depressed mood Deterioration Development Disease Drug abuse Encephalitis Endothelial Cells Endothelium Epidemic Exposure to Gene Expression HIV HIV Infections HIV-1 HIV-associated neurocognitive disorder Heroin Homing Immune Immune response Immunity In Vitro Infectious Agent Infiltration Inflammation Inflammatory Inflammatory Response Injury Intravenous Intravenous Drug Abuse Lead Leukocytes Link Lung Lung diseases Modeling Molecular Morphine Mus Natural Immunity Nerve Degeneration Neuronal Injury Opiates Opioid Organ Parasites Patients Pattern Pharmaceutical Preparations Pharmacotherapy Phenotype Population Predisposition Proteins Publishing Regulation Secondary to Smoke Smoker Smoking Structure of parenchyma of lung System Systemic disease Testing Time Tissues Tobacco Tobacco smoke Tobacco smoking Toxic effect Viremia Work acquired immunity adaptive immunity aryl hydrocarbons base brain endothelial cell brain tissue chemokine chemokine receptor clinically relevant cytokine drug abuser humanized mouse in vivo intravenous drug user macrophage migration monocyte monocyte chemoattractant protein 1 receptor mouse model neuroinflammation neuropathology neurotoxicity novel pre-clinical research public health relevance research study

项目摘要

DESCRIPTION (provided by applicant): Opiate drug abuse is a critical contributor to the global AIDS epidemic, and over a third of HIV infections in the U.S. can be linked to intravenous drug abuse. Recent estimates suggest that almost 20% of intravenous drug abusers are infected with HIV. Tobacco smoking is prevalent in HIV-infected patients, and is very common among intravenous drug abusers. Importantly, smoking is strongly associated with a number of non-AIDS conditions, including chronic obstructive lung disease (COPD), and this chronic inflammatory disease may contribute to the development of neuroinflammation associated with HIV infection. However, there is very little known about the combined effects of tobacco smoke and chronic opioid administration on the development of inflammatory responses, and even less known about the effects of these clinically relevant drugs on the development of neurodegeneration following HIV infection. We describe preliminary data which shows that the inflammatory response is both quantitatively and qualitatively distinct following the combination of tobacco and opiate administration. We propose to conduct experiments using humanized mice to examine the combined effects of chronic tobacco smoke exposure with and without chronic administration of morphine on the development of HIV-induced neuroinflammation. Our published and preliminary data show that the blood-brain barrier is a target for the effects of opiates and/or tobacco, as well as the inflammatory activity of monocytes and macrophages. We propose to investigate the mechanistic basis for the combined effects of these drug treatments on these cell populations. We believe the proposed studies will provide highly novel information about the effects of morphine and tobacco smoke on HIV-associated neurodegeneration in a clinically relevant immunological context.

描述（由适用提供）：Opite药物滥用是全球艾滋病流行病的关键因素，在美国，超过三分之一的艾滋病毒感染可以与静脉注射药物滥用有关。最近的估计表明，近20％的静脉滥用药物感染了HIV。在感染HIV的患者中，烟草吸烟很普遍，并且在静脉滥用药物中非常普遍。重要的是，吸烟与许多非AID疾病密切相关，包括慢性阻塞性肺部疾病（COPD），这种慢性炎性疾病可能有助于与HIV感染相关的神经炎症的发展。但是，关于烟草烟雾和慢性阿片类药物对炎症反应发展的综合作用鲜为人知，甚至对这些临床相关药物对HIV感染后神经变性的影响的影响鲜为人知。我们描述了初步数据，该数据表明，在烟草组合并优化给药后，炎症反应既定量和相当不同。我们建议使用人源化小鼠进行实验，以检查有没有长期给予吗啡对HIV诱导神经炎症发展的慢性烟草烟雾暴露的综合作用。我们发表的初步数据表明，血脑屏障是阿片类药物和/或烟草以及单核细胞和巨噬细胞的炎症活性的目标。我们建议研究这些药物治疗对这些细胞群体的综合作用的机理基础。我们认为，拟议的研究将提供有关吗啡和烟草烟雾对在临床相关的免疫学环境中与HIV相关神经变性的影响的高度新颖信息。