DRUG ABUSE & AIDS: AN IN VITRO IMMUNOLOGICAL MODEL

静脉注射（i. v.）药物滥用是一个主要的危险因素， 感染艾滋病。 鸦片和可卡因经常被滥用 静脉注射，并且经常同时被滥用。 大麻 酗酒也是静脉注射药物滥用者的常见现象。 结果 体内和体外研究表明， 滥用药物具有免疫调节作用，有时 免疫妥协潜力。 事实上，免疫抑制通常 即使没有艾滋病毒，也与静脉注射海洛因成瘾有关 感染 由于这些信息，滥用药物是 被怀疑改变了宿主对艾滋病的易感性。 这种可能性 是本研究课题的中心主题。 滥用药物对免疫功能影响的临床观察 由于复杂性， 成瘾的环境。 为此，我们选择了一个在 体外方法来了解这些药物如何影响宿主免疫力。 我们实验室开发的用于检测的细胞荧光测定法 药物诱导的淋巴细胞表面抗原调节 标记物（受体）将用于定义独立的和 某些药物滥用对管制药物滥用的相互影响 各种淋巴细胞标记物/受体分子， 与AIDS的发展相关（即CD 2，CD 4，CD 8，CD 3， 以及I类和II类HLA标记物）。 药理 参与调节表达的阿片受体的特异性 这些淋巴细胞标志物将通过使用各种 阿片激动剂、拮抗剂和它们的非活性对映体。 的 某些滥用药物调节 特异性单克隆抗体对刺激的淋巴细胞 不同类别的CD 2表位和凝集素也将被 评估。 药理学的生理基础， 将研究滥用药物的免疫作用， 通过操纵跨膜流动来确定， 细胞内动员主要的生理相关的 阴离子（Na+、K+、Ca++）。 这些研究的数据将 分析以确定哪些抗原标志物被 滥用药物以及这些药物如何发挥作用。 这 这些信息将用于判断药物滥用 影响药物滥用者对收缩的敏感性 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.