EFFECT OF MORPHINE AND SIV ON FUNCTIONAL IMMUNE RESPONSES

吗啡和 SIV 对功能性免疫反应的影响

• 批准号: 8378169
• 负责人: Toby K. Eisenstein
• 金额: $ 5.52万
• 依托单位: TEMPLE UNIV OF THE COMMONWEALTH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至 2014-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8378169
• 关键词: Acquired Immunodeficiency Syndrome; Address; Affect; Animal Model; Animals; Area; B-Lymphocytes; Chronic; Control Groups; Data; Depressed mood; Disease Progression; Drug Exposure; Epidemic; Epidemiology; Experimental Designs; Exposure to; HIV; HIV Infections; Heroin; Human; Immune; Immune response; Immunosuppressive Agents; In Vitro; Individual; Infection; Infectious Agent; Intravenous; Laboratory Study; Life Style; Macaca; Mitogens; Modeling; Morphine; Natural Killer Cells; Neurologic; Opioid; Pathogenesis; Peripheral Blood Mononuclear Cell; Pharmaceutical Preparations; Primates; Publishing; Research; Risk; Rodent; SIV; T-Lymphocyte; Testing; Viral; Viral Load result; Viral load measurement; Virus; Virus Diseases; Work; chronic pain; clinically relevant; cytokine; drug abuser; drug addict; drug of abuse; immune function; in vivo; novel; response

This project will examine the effect of morphine on parameters of immune function in normal macaques or macaques chronically infected with Simian Immunodeficiency Virus (SIV), the best model for human infection with HIV. Peripheral blood mononuclear cells collected before and after SIV infection oropioid treatment will be used to assess Natural Killer cell activity, responses to T and B cell mitogens, and levels of proinflammatory cytokines. The effect of the drug on immune status and SIV viral load will be made longitudinally in each animal, as well as among animals in a treatment group and between groups. One third of HIV infected individuals in the U.S. are intravenous drug abusers. Morphine is the primary active metabolite of heroin, and is the classic opioid used in most laboratory studies. Morphine is known to be immunosuppressive in animal models and has been shown to up-regulate HIV replication in vitro. Yet, the effect of opioid drugs on progression of retroviral infections in vivo has never been definitively established, nor has the effect of opioids on parameters of immune function been evaluated in retrovirally infected animals. Natural Killer cell activity, mitogen responses, and cytokine profiles are the standard functional tests that have been used in the majority of published studies examining effects of opioids on immune status, and therefore have been chosen for this project. The proposed studies will provide new data on the effects of chronic treatment with morphine on immune status in uninfected macaques, as well as testing the effects of chronic morphine in SIV infected animals, on immune status and disease progression, including neurological involvement. A novel aspect of the proposed studies is that the effect of morphine will be tested on SIV infection when the drug is given before or after the virus. Also, few studies in any species have examined the effects of chronic opioid treatment on immune functional parameters. The data collected in the proposed work will be novel, and will help to answer the questions directly as to whether opioids affect progression of a retroviral infection in primates, and whether the drug alters functional immune responses.

该项目将研究吗啡对正常猕猴或猕猴免疫功能参数的影响 猕猴长期感染猿猴免疫缺陷病毒（SIV），这是人类感染的最佳模型 患有艾滋病毒。 SIV感染或阿片类药物治疗前后采集的外周血单核细胞 将用于评估自然杀伤细胞活性、对 T 细胞和 B 细胞有丝分裂原的反应以及 促炎细胞因子。将研究药物对免疫状态和 SIV 病毒载量的影响 在每只动物中以及治疗组中的动物之间和组之间进行纵向研究。三分之一 在美国，10% 的艾滋病毒感染者是静脉注射毒品滥用者。吗啡是主要活性成分 海洛因的代谢物，是大多数实验室研究中使用的经典阿片类药物。吗啡已知 在动物模型中具有免疫抑制作用，并已被证明可以在体外上调 HIV 复制。然而， 阿片类药物对体内逆转录病毒感染进展的影响尚未明确确定， 也没有评估阿片类药物对逆转录病毒感染者免疫功能参数的影响 动物。自然杀伤细胞活性、丝裂原反应和细胞因子谱是标准功能测试 已在大多数已发表的研究中使用，以检查阿片类药物对免疫状态的影响，以及 因此被选为该项目。拟议的研究将提供有关影响的新数据 使用吗啡进行长期治疗对未受感染的猕猴免疫状态的影响，并测试其效果 慢性吗啡对 SIV 感染动物的免疫状态和疾病进展（包括神经系统疾病）的影响 参与。拟议研究的一个新颖之处是，将测试吗啡对 SIV 的作用 在病毒出现之前或之后给药时发生感染。此外，很少有研究对任何物种进行过检验 长期阿片类药物治疗对免疫功能参数的影响。拟议中收集的数据 这项工作将是新颖的，并将有助于直接回答有关阿片类药物是否影响疾病进展的问题 灵长类动物的逆转录病毒感染，以及该药物是否改变功能性免疫反应。