DRUG ABUSE & AIDS: AN IN VITRO IMMUNOLOGICAL MODEL

静脉注射(静脉注射)滥用药物是导致 艾滋病的感染。鸦片类药物和可卡因经常被滥用 静脉注射，并经常同时被虐待。大麻 酒精滥用在静脉注射中也很常见。吸毒者。结果 来自体内和体外的研究表明，这些都是 滥用药物有免疫调节作用，有时 免疫功能受损的可能性。事实上，免疫抑制通常 与静脉注射有关。即使在没有艾滋病毒的情况下也有海洛因成瘾 感染。由于这些信息，滥用药物是 涉嫌改变宿主对艾滋病的易感性。这种可能性 构成了这项研究提案的中心主题。 滥用药物对免疫功能影响的临床观察 由于参数的复杂性，参数很难解释 上瘾的环境。出于这个原因，我们选择了一个In 了解此类药物如何影响宿主免疫的体外方法。 本实验室研制的细胞荧光检测方法 药物对淋巴细胞表面抗原的调节作用 标志物(受体)将被用来定义独立和 某些药物滥用对调节的相互依赖作用 可以显示的各种淋巴细胞标记/受体分子 与艾滋病的发展有关(即CD2、CD4、CD8、CD3、 和第I类和第II类人类白细胞抗原标志物)。药理学 参与表达调控的阿片受体的特异性 这些淋巴细胞标记物将通过使用不同的 阿片激动剂、拮抗剂及其非活性对映体。这个 选定的滥用药物调节复制的能力 特异性单抗对刺激的淋巴细胞 不同类别的CD2表位和凝集素也将 已评估。药理和药理的生理基础 将研究滥用药物的免疫学影响 通过操纵跨膜血流和 主要生理相关物质的细胞内动员 阴离子(Na+、K+、Ca++)。这些研究的数据将是 分析以确定哪些抗原标记物受 滥用药物以及这些药物如何发挥作用。这 然后，信息将被用来判断滥用药物的方式 影响吸毒者对精神分裂症的易感性 艾滋病。

Intravenous (i.v.) drug abuse is a primary risk factor in contraction of AIDS. Opiates and cocaine are frequently abused intravenously, and often are abused simultaneously. Marijuana and alcohol abuse is also common with i.v. drug abusers. Results from in vivo and in vitro studies have indicated that each of these drugs of abuse have immunomodulatory, and sometimes immunocompromising potential. Indeed, immunodepression often associates with i.v. heroin addiction even in the absence of HIV infection. Because of this information, drugs of abuse are suspected of altering host susceptibility to AIDS. This possibility constitutes the central theme of this research proposal. Clinical observations of the effect of drugs of abuse on immune parameters are difficult to interpret because of the complexities of the addiction milieu. For this reason, we have selected an in vitro approach to learn how such drugs influence host immunity. Cytofluorometric assays developed in our laboratory for detection of drug-induced modulation of lymphocyte-surface antigenic markers (receptors) will be used to define the independent and interdependent effects of selected drugs of abuse on regulation of various lymphocyte marker/receptor molecules that can be shown to be relevant to development of AIDS (i.e. CD2, CD4, CD8, CD3, and Class I and Class II HLA markers). The pharmacological specificity of opiate receptors involved in modulating expression of these lymphocyte markers will be defined by using various opiate agonists, antagonists, and their inactive enantiomers. The ability of selected drugs of abuse to modulate replication of lymphocytes stimulated by monoclonal antibody pairs specific to different classes of CD2 epitopes and by lectins will also be evaluated. The physiological basis for the pharmacological and immunological effects of the abused drugs to be studied will be determined through manipulation of transmembranal flow and intracellular mobilization of the major physiologically relevant anions (Na+, K+, Ca++). The data from these studies will be analyzed to determine which antigenic markers are modulated by drugs of abuse and how these drugs exert their effects. This information will then be used in judging how drugs of abuse influence the susceptibility of drug abusers to contraction of AIDS.