EFFECTS OF MORPHINE ON PULMONARY INFLUENZA INFECTION

吗啡对肺部流感感染的影响

• 批准号: 6084907
• 负责人: Mary E Coussons-Read
• 金额: $ 13.5万
• 依托单位: UNIVERSITY OF COLORADO DENVER/HSC DENVER
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-04-01 至 2005-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6084907
• 关键词: cell type; cytotoxic T lymphocyte; dosage; drug adverse effect; drug interactions; immunity; immunotoxicity; inflammation; influenza; laboratory rat; lymphocyte proliferation; morphine; natural killer cells; opioid receptor; pharmacokinetics; receptor expression; respiratory infections; virus replication

DESCRIPTION: (Adapted from the Applicant's Abstract): Respiratory illness is a leading cause of death among HIV-positive intravenous opioid users. It is critical to understand the effects of opioid use on respiratory immunity and how such effects may impact HIV disease. The proposed AREA project uses an animal model to address this issue by characterizing the effects of morphine on pulmonary immunity and influenza virus infection in rats. The project will be conducted at the University of Colorado at Denver (UCD), which is an urban university that serves many nontraditional students, trains significant numbers of graduates who pursue careers in the biomedical sciences, and is not a major recipient of NIH support. This AREA project utilizes a Rat-Adapted Influenza Virus (RAIV) model, and preliminary data show that morphine treatment impairs both resting pulmonary immunity and the innate pulmonary immune response to RAIV. Specific Aim 1 extends these findings by examining dose-effect relationships in the impact of sub-chronic and chronic morphine treatment on resting pulmonary immunity. Lymphocyte proliferation to mitogen and superantigen, natural killer cell activity, and phenotypic distribution of lymphocytes will be used to assess resting pulmonary immune status. Specific Aim 2 will assess the dose-dependency and mechanism of morphine's effects on the innate pulmonary immune response to RAIV infection. Viral replication, pulmonary inflammation, and characterization of pulmonary cell types after infection will be used to measure the response to RAIV. Specific Aim 3 will test the hypothesis that morphine treatment will cause dose-dependent reductions in RAIV-specific acquired immunity, and that activation of opioid receptors is responsible for these effects. Measurements of anti-RAIV antibodies, RAIV-specific lymphocyte proliferation, and RAIV-specific CTL activity in the lungs and peripheral blood will be used to assess acquired immunity. Future studies will utilize RAIV and bacterial infection to increase understanding of how interactions between infection, drug use, and the immune system may adversely affect HIV infection in humans. Importantly, this project will establish a new and meritorious research program that will provide increased research opportunities for UCD students.

描述：（改编自申请人的摘要）：呼吸疾病是 HIV阳性静脉阿片类药物使用者的主要死亡原因。这是 了解阿片类药物使用对呼吸免疫的影响至关重要 这种影响如何影响艾滋病毒疾病。拟议的区域项目使用 动物模型通过表征吗啡的影响来解决此问题 大鼠的肺免疫和流感病毒感染。该项目将是 在科罗拉多大学丹佛分校（UCD）进行，这是一个城市 为许多非传统学生服务，培训大量的大学 从事生物医学科学从事职业的毕业生，不是主要的 NIH支持的接受者。该区域项目利用了小鼠适应的流感 病毒（RAIV）模型，初步数据表明吗啡治疗会损害 静止的肺免疫和先天肺免疫反应 莱夫。特定目标1通过检查剂量效应扩展了这些发现 亚尚元和慢性吗啡治疗对影响的关系 静止的肺免疫。淋巴细胞增殖到有丝分裂原和 超抗原，天然杀伤细胞活性和表型分布 淋巴细胞将用于评估静息肺免疫状态。具体的 AIM 2将评估吗啡对吗啡影响的剂量依赖性和机制 先天肺对RAIV感染的免疫反应。病毒复制， 肺部炎症和肺细胞类型的表征 感染将用于测量对RAIV的反应。具体的目标3将 检验吗啡治疗将导致剂量依赖性的假设 降低了RAIV特异性获得的免疫力，而阿片类药物的激活 受体负责这些影响。抗RAIV的测量 抗体，RAIV特异性淋巴细胞增殖和RAIV特异性CTL 肺和外周血的活性将用于评估所获得的 免疫。未来的研究将利用RAIV和细菌感染来增加 了解感染，吸毒和免疫之间的相互作用如何 系统可能会对人类的艾滋病毒感染产生不利影响。重要的是，这个项目 将建立一个新的和有功的研究计划，将提供 增加了UCD学生的研究机会。