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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：
9976491
负责人：
Yuri Persidsky
金额：
$ 43.41万
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 2022-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9976491
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 Complex Data Deterioration Development Disease Encephalitis Endothelial Cells Endothelium Epidemic Exposure to Gene Expression HIV HIV Infections HIV-1 HIV-associated neurocognitive disorder Heroin Homing Immune response Immunity Immunocompetence Immunologics In Vitro Infectious Agent Infiltration Inflammation Inflammatory Inflammatory Response Injury Intravenous Intravenous Drug Abuse Leukocytes Link Lung Lung diseases Modeling Molecular Morphine Mus Natural Immunity Nerve Degeneration Neuronal Injury Neurons Opioid Opioid abuser Opioid agonist 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 behavior Tobacco use Toxic effect Viremia Work acquired immunity adaptive immunity aryl hydrocarbons brain endothelial cell brain tissue chemokine chemokine receptor chronic inflammatory disease clinical effect clinically relevant cytokine drug abuser experimental study humanized mouse in vivo intravenous drug user macrophage migration monocyte morphine administration mouse model neuroinflammation neuropathology neurotoxicity novel opioid abuse opioid exposure opioid injection organ injury pre-clinical research public health relevance receptor

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(申请人提供)：鸦片类药物滥用是全球艾滋病流行的关键因素，美国超过三分之一的艾滋病毒感染与静脉注射药物滥用有关。最近的估计表明，几乎20%的静脉吸毒者感染了艾滋病毒。吸烟在艾滋病毒感染者中很普遍，在静脉吸毒者中非常普遍。重要的是，吸烟与许多非艾滋病疾病密切相关，包括慢性阻塞性肺疾病(COPD)，这种慢性炎症性疾病可能导致与艾滋病毒感染相关的神经炎症的发展。然而，人们对烟草烟雾和长期服用阿片类药物对炎症反应发展的联合影响知之甚少，更不知道这些临床相关药物对艾滋病毒感染后神经变性发展的影响。我们描述的初步数据表明，烟草和阿片类药物联合给药后，炎症反应在数量和质量上都是不同的。我们建议使用人源化的小鼠进行实验，以检验慢性烟草烟雾暴露与长期注射吗啡对HIV诱导的神经炎症发展的联合影响。我们已发表的初步数据表明，血脑屏障是鸦片类药物和/或烟草影响的靶点，也是单核细胞和巨噬细胞炎症活动的靶点。我们建议调查这些药物治疗对这些细胞群联合作用的机制基础。我们相信，拟议的研究将在临床相关的免疫学背景下提供关于吗啡和烟草烟雾对艾滋病毒相关神经变性的影响的高度新颖的信息。