MARIHUANA & IMMUNITY--SUPPRESSIVE MECHANISMS IN HUMANS

本提案的长期目标是了解 大麻免疫抑制活性的机制 组分δ-9-四氢大麻酚（THC）。具体目标是 确定THC抑制细胞和分子机制， 自然杀伤（NK）细胞、淋巴细胞母细胞生成和巨噬细胞 人外周血白细胞的吞噬活性，虽然 研究最初将集中于NK细胞的细胞毒性。通过这样做， 了解这种类型的免疫抑制可以被 通过免疫刺激物质的干预逆转，例如 可以获得白细胞介素2。此外，关于免疫抑制剂， 这些研究旨在确定大麻是否可能 导致艾滋病在受人类感染的个体中发病， 免疫缺陷病毒（HIV）。这些目标将通过研究 细胞因子（或其不存在）在THC诱导的介导中的重要性 抑制，检查已知的代谢途径的功能， 参与淋巴细胞和巨噬细胞的活化， 来自HIV感染者的白细胞更严重地受到抑制， 免疫反应性，并产生更多的传染性艾滋病毒。 最终，目标是克服THC的所有不利影响 使用免疫调节物质。

The long term objectives of this proposal are to gain an understanding of the mechanism(s) of the immunosuppressive activity of the marijuana component delta-9-tetrahydrocannabinol (THC). The specific aims are to determine the cellular and molecular mechanisms by which THC inhibits the natural killer (NK) cell, lymphocyte blastogenesis and macrophage phagocytic activities of human peripheral blood leukocytes, although the study will initially focus on NK cell cytotoxicity. By doing so, an understanding of ways in which this type of immune suppression can be reversed by intervention with immunostimulatory substances, such as interleukin 2 can be acquired. Also, with regard to the immunosuppressive activity of THC these studies are intended to determine if marijuana might contribute to the onset of overt AIDS in individuals infected by the human immunodeficiency virus (HIV). These goals will be reached by studying the importance of cytokines (or their absence) in the mediation of THC induced suppression, examining the function of metabolic pathways known to be involved in lymphocyte and macrophage activation, and examining whether leukocytes from HIV infected individuals are more severely depressed in immune reactivity and produce greater numbers of infectious HIV. Ultimately, the goal is to overcome all of the detrimental effects of THC using immunomodulatory substances.