Opioid Dependence, Immunity and Infection

阿片类药物依赖、免疫和感染

• 批准号: 6348399
• 负责人: Toby K. Eisenstein
• 金额: $ 33.75万
• 依托单位: TEMPLE UNIV OF THE COMMONWEALTH
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-03-15 至 2006-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6348399
• 关键词: Listeria infections; RNase protection assay; Salmonella infections; Streptococcus infection; Streptococcus pneumoniae; antigen presentation; artificial immunosuppression; drug addiction; drug withdrawal; endotoxins; enzyme linked immunosorbent assay; flow cytometry; gene targeting; genetically modified animals; hypothalamic pituitary adrenal axis; immunopharmacology; laboratory mouse; macrophage; mitogens; morphine; natural killer cells; nitric oxide; opioid receptor; phagocytosis; polymerase chain reaction; spleen

DESCRIPTION: (provided by applicant) There is now unequivocal evidence that immune responses are modulated by opioids. Most acute and subacute drug administration paradigms result in immunosuppression. There have been few studies examining the effects of chronic drug administration on immune function and even fewer published reports of effects of withdrawal on the immune system. Since intravenous drug abusers frequently go through periods of highs followed by periods of partial or full withdrawal, studies of alterations in immune competence during abstinence are of significant import. In preliminary studies, we have examined the effect of abrupt or precipitated withdrawal (AW or PW) from morphine administered by slow-release pellet on the capacity of mouse spleen cells to mount an ex vivo antibody response. We observed profound alterations in immune function in both withdrawal paradigms. At 3 hr after PW, but not AW, there was immunopotentiation. By 24 hr after initiation of either withdrawal paradigm, mice were >60 percent immunosuppressed, and in AW, suppression was 70 percent at 48 hr, with >50 percent suppression still evident at 144 hr. It is proposed to investigate these two interesting models of robust immune modulation resulting from the two abstinence syndromes. Specifically, we will use AW and PW to: 1) determine the effect of withdrawal on function on various immune cell subsets; 2) assess the effect of withdrawal on resistance to Salmonella, Listeria, and pneumococcal infection; 3) determine which type of opioid receptor mediates alterations in immune function during AW and PW; and 4) investigate the role of pro-inflammatory cytokines nitric oxide, and/or the HPA axis in mediating immunosuppression following withdrawal. These studies should elucidate the mechanisms by which withdrawal alters immune function and determine if immunosuppression leads to increased susceptibility to infection. Investigation of the effects of withdrawal on immune system function has practical and theoretical implications. Alterations in immune status during the abstinence syndrome may provide a heightened sensitivity to infection or reactivation of latent infection, such as HIV or tuberculosis. Dissection of the mechanisms and pathways by which opioids interface with the immune system during withdrawal should elucidate fundamental interconnections between the neural and immune systems.

描述：（由申请人提供）现在有明确的证据表明 免疫反应由阿片类药物调节。最急性和亚急性药物 给药模式会导致免疫抑制。已经有少数 研究长期用药对免疫功能的影响 关于戒断对免疫系统影响的公开报道就更少了。 由于静脉注射药物滥用者经常会经历高潮期 通过部分或全部戒断期，免疫改变的研究 禁欲期间的能力非常重要。在初步研究中， 我们研究了突然或突然戒断（AW 或 PW）的影响 吗啡缓释颗粒对小鼠能力的影响 脾细胞产生离体抗体反应。我们观察深刻 两种戒断模式中免疫功能的改变。产后 3 小时， 但AW没有，有免疫增强作用。开始后 24 小时 戒断范例中，小鼠的免疫抑制率超过 60%，并且在 AW 中， 48 小时时抑制率为 70%，抑制率仍>50% 144 点建议研究这两个有趣的鲁棒模型 两种戒断综合症导致的免疫调节。具体来说，我们 将使用 AW 和 PW 来： 1) 确定退出对功能的影响 各种免疫细胞亚群； 2）评估戒断对抵抗力的影响 沙门氏菌、李斯特菌和肺炎球菌感染； 3）确定属于哪种类型 阿片受体介导 AW 和 PW 期间免疫功能的改变；和 4) 研究促炎细胞因子一氧化氮的作用，和/或 HPA 轴介导戒断后的免疫抑制。这些研究 应阐明戒断改变免疫功能的机制 确定免疫抑制是否会导致感染易感性增加。 戒断对免疫系统功能影响的研究已 实际和理论意义。期间免疫状态的变化 戒断综合症可能会增加对感染的敏感性或 潜伏感染的重新激活，例如艾滋病毒或结核病。解剖 阿片类药物与免疫系统相互作用的机制和途径 撤回期间应阐明各组织之间的基本相互联系 神经和免疫系统。