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（由申请人提供）：阿片类药物滥用是全球艾滋病流行的一个重要因素，美国超过三分之一的艾滋病毒感染可能与静脉注射药物滥用有关。最近的估计表明，近 20% 的静脉注射药物滥用者是静脉注射药物滥用者。吸烟在艾滋病毒感染者中很常见，并且在静脉注射药物滥用者中也很常见。重要的是，吸烟与许多非艾滋病疾病有关，包括慢性病。阻塞性肺病 (COPD)，这种慢性炎症性疾病可能会导致与 HIV 感染相关的神经炎症的发生。然而，人们对烟草烟雾和长期使用阿片类药物对炎症反应发生的综合影响知之甚少。对于这些临床相关药物对 HIV 感染后神经变性发展的影响知之甚少，我们描述了初步数据，这些数据表明，烟草和阿片类药物联合使用后，炎症反应在数量和质量上都有所不同。使用我们已发表的初步数据表明，血脑屏障是阿片类药物和/或药物影响的目标。或烟草，以及单核细胞和巨噬细胞的炎症活动，我们建议研究这些药物治疗对这些细胞群的综合作用的机制基础，我们相信拟议的研究将提供有关吗啡和巨噬细胞的作用的高度新颖的信息。在临床相关的免疫学背景下，烟草烟雾对艾滋病毒相关的神经变性的影响。