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MARIJUANA--BACTERIAL AND TRANSPLANTATION IMMUNITY

大麻——细菌和移植免疫

基本信息

批准号：
3208287
负责人：
EDNA SUE WATSON
金额：
$ 11.55万
依托单位：
UNIVERSITY OF MISSISSIPPI
依托单位国家：
美国
项目类别：
财政年份：
1984
资助国家：
美国
起止时间：
1984-09-01 至 1988-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3208287
关键词：
Staphylococcus aureus blood chemistry carboxyhemoglobin cellular immunity gas chromatography immunosuppression microorganism immunology neoplasm /cancer immunology neoplasm /cancer transplantation neoplastic growth respiratory infections smoke inhalation

项目摘要

Conclusive evidence of immune dysfunction after exposure of experimental animals to marijuana smoke or constituents has not been demonstrated. The first aim of this proposal is to establish maximum acute and chronic marijuana smoke exposure regimens in mice and rats which will allow assessment of potential immunosuppressive effects in the absence of general systemic toxicity. Established criteria of immunoselectivity will be used in setting these maxima. A modified Walton Automatic Smoking Machine will be used to expose animals to marijuana or placebo marijuana cigarette smoke or air. Delta9-THC will be used as a dosimetric marker for estimating the magnitude (Ct product) of smoke exposure. The Ct product of different exposure regimens will be compared to the levels of Delta9/-THC in plasma in animals receiving these exposures in order to quantify the relationship between the magnitude of smoke exposure and absorption of smoke constituents. The role of carbon monoxide poisoning in any immunotoxicities which may be found will be assessed. The second and third aims of this proposal are to determine whether dose-related increases in susceptibility to microbial infection and tumor growth, respectively, occur in subjects receiving different magnitudes of marijuana or placebo cigarette smoke. Resistance to systemic infectivity will be measured by the recovery of viable S. aureus organisms from tissue homogenates and blood of experimentally infected mice using the standard plate count method. In these studies, elevated numbers of viable bacteria recovered from smoke-treated animals as compared to sham-treated controls will be taken as evidence of immunosuppression. Resistance to localized infection will be measured by the severity of dermonecrosis (necrotic index) and the amount of early fluid exudate after subcutaneous injection of S. aureus. An elevated necrotic index or decreased fluid exudate in smoke-treated animals as compared to sham-treated ones will be considered evidence of immunosuppression. To measure the effects of marijuana smoke on cellular immunity, a mouse tumor heterograft assay in rats will be used. Increased palpable tumor volume and time-to-rejection in smoke-exposed as opposed to air-exposed rats will be considered as evidence of suppressed cellular immunity. The data generated in these studies should make it possible to assess whether occasional (acute) or habitual (chronic) marijuana use causes an increase in susceptibility to infection and tumor proliferation in animals.

实验性接触后免疫功能障碍的确凿证据动物吸食大麻或大麻成分尚未得到证实。的这项建议的第一个目的是建立最大限度的急性和慢性小鼠和大鼠的大麻烟雾暴露方案将允许在缺乏一般免疫抑制剂的情况下评估潜在免疫抑制作用全身毒性将使用既定的免疫选择性标准来设定这些最大值。一个改良的沃尔顿自动吸烟机将用于将动物暴露于大麻或安慰剂大麻香烟烟雾或空气。 Delta 9-THC将用作剂量测定标记物，用于估计烟雾暴露量（Ct乘积）。不同的Ct乘积将暴露方案与血浆中Δ 9/-THC的水平进行比较在接受这些暴露的动物中，暴露在烟雾中的程度和吸收烟雾的程度之间选民。一氧化碳中毒在任何情况下的作用将评估可能发现的免疫毒性。本建议的第二和第三个目的是确定对微生物感染和肿瘤易感性的剂量相关性增加生长，分别发生在接受不同程度的大麻或安慰剂香烟烟雾。抗全身感染性将通过活S的回收来衡量。组织中金黄色微生物实验感染小鼠的匀浆和血液平板计数法在这些研究中，与假处理对照相比，从烟雾处理动物中回收将被视为免疫抑制的证据耐局部感染将通过皮肤坏死（坏死性指数）和皮下注射后早期液体渗出量色葡萄金黄色。坏死指数升高或液体渗出物减少，将考虑与假处理动物相比，烟雾处理动物免疫抑制的证据来测量大麻烟的影响在细胞免疫方面，将在大鼠中进行小鼠肿瘤异种移植试验，采用可触及肿瘤体积增加和排斥反应时间增加，暴露在烟雾中而不是暴露在空气中的老鼠将被视为证据抑制细胞免疫力这些研究产生的数据应能够评估是否偶尔（急性）或习惯性（慢性）大麻使用导致感染易感性增加和肿瘤的增殖。