EFFECT OF MORPHINE ON IMMUNE RESISTANCE TO T GONDII

吗啡对弓形虫免疫抵抗力的影响

• 批准号: 6523281
• 负责人: Lawrence L. Johnson
• 金额: $ 17.3万
• 依托单位: TRUDEAU INSTITUTE, INC.
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-30 至 2003-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6523281
• 关键词: RNase protection assay; Toxoplasma gondii; chemokine; cytokine receptors; embryo /fetus toxicology; enzyme linked immunosorbent assay; flow cytometry; genetic strain; immunopharmacology; laboratory mouse; leukocyte activation /transformation; microorganism immunology; morphine; neuroimmunomodulation; protozoal infection; protozoal vaccine

DESCRIPTION: (Applicant's Abstract) The broad goal of the proposed studies is to determine the effect of morphine on the generation and expression of immunity to the protozoan parasite, Toxoplasma gondii, a major opportunistic pathogen of the CNS in AIDS patients. The work will focus on the impact of morphine in three physiologically pertinent experimental models of Toxoplasma infection: (i) chronic primary CNS infection, (11) a vaccination model, and (iii) exposure to morphine in utero. We will examine the effect of morphine on parameters of immune resistance in mice chronically infected with an ordinarily avirulent strain of T. gondil. Lymphocytes in peripheral blood, spleen, and the brain of morphine-treated and untreated mice with or without established chronic infections will be analyzed with regard to numbers, expression of markers of activation, and capacity to produce relevant cytokines and chemokines. We will also determine the effect of morphine on the generation and expression of immunity in mice given a Toxoplasma vaccine. Morphine-treated or untreated mice will be vaccinated with an avirulent strain of T. gondii, and the quality of their subsequent acquired immunity evaluated. In other experiments, mice will first be vaccinated then treated later with morphine to evaluate the effect of morphine on the expression of immunity that has already been generated. Finally, we will determine the effect of morphine on the development of immunity in mice exposed to morphine in utero. Pregnant mice will be treated with morphine and the immunological development and functional capabilities of their offspring evaluated postnatally and as adults in the context of anti-Toxoplasma immunity. Together, these studies will provide a comprehensive immunological foundation upon which to build detailed further analyses of the effects of an opioid drug on immunity to opportunistic infection.

描述：（申请人的摘要） 拟议研究的广泛目标是确定吗啡的作用 关于原生动物寄生虫免疫的产生和表达， Toxoplasma gondii，是艾滋病患者中枢神经系统的主要机会病原体。 这项工作将重点介绍吗啡在三个生理上的影响 弓形虫感染的相关实验模型：（i）慢性初级中枢神经系统 感染，（11）疫苗接种模型，（iii）在子宫内暴露于吗啡。 我们将检查吗啡对免疫抗性参数的影响 小鼠长期感染了T. gondil的通常无毒的菌株。 外周血，脾和吗啡治疗的大脑中的淋巴细胞 将分析有或没有建立的慢性感染的未经治疗的小鼠 关于数量，激活标记的表达以及能力 产生相关的细胞因子和趋化因子。我们还将确定 关于小鼠免疫产生和表达的吗啡 弓形虫疫苗。吗啡治疗或未经处理的小鼠将接种疫苗 T. gondii的无毒菌株及其随后获得的质量 评估免疫力。在其他实验中，小鼠然后首先接种疫苗 稍后用吗啡处理以评估吗啡对 已经生成的免疫表达。最后，我们会的 确定吗啡对暴露小鼠免疫发展的影响 在子宫内到吗啡。怀孕的小鼠将用吗啡治疗 后代的免疫发展和功能能力 在抗肺泡免疫的背景下，通过产后和成年人进行评估。 这些研究将共同​​提供全面的免疫学基础 在其中详细介绍了阿片类药物的影响的进一步分析 对机会性感染的免疫力。