House R V, Thomas P T, Bhargava H N
Life Sciences Department, IIT Research Institute, Chicago, IL 60616.
Toxicology. 1995 Jan 19;96(1):59-69. doi: 10.1016/0300-483x(94)02955-t.
Abuse of illicit analogs of methamphetamine (i.e., 'designer drugs') represents a growing problem. One of the most popular methamphetamine analogs is (+/-)-3,4-methylenedioxymethamphetamine (MDMA), commonly known as Ecstasy. The authors demonstrated previously that in vitro exposure to methamphetamine results in modulation of immune functional parameters necessary for host defense. The current study was performed to assess the potential direct (in vitro) immunomodulatory effect of exposure to a modified methamphetamine. Splenocytes or peritoneal macrophages from B6C3F1 mice were cultured in vitro at MDMA concentrations of 0.0001-100 microM. T-cell regulatory function was assessed by anti-CD3-mediated production of IL-2 and IL-4, B-cell function was assessed by quantitating cellular proliferation, natural immunity was assessed by quantitating natural killer (NK) cell activity, T-cell effector function was evaluated as a function of cytotoxic T-lymphocyte (CTL) activity, and macrophage function was assessed by IL-6 tumor necrosis factor (TNF) production. In vitro exposure to MDMA had no effect on B-cell proliferation at any concentration tested. In comparison, in the absence of direct cellular toxicity, production of IL-2 was enhanced at concentrations as low as 0.0001 microM. IL-4 production was not affected by exposure to any concentration of MDMA examined, suggesting a differential alteration in T-helper cell function by this compound. Basal and augmented NK cell function were enhanced at MDMA concentrations between 0.0001 and 1.0 microM when examined at an effector:target ratio of 100:1. CTL induction was significantly suppressed at a concentration of 100 microM. Finally, macrophage production of TNF was slightly suppressed at 10 and 100 microM MDMA, although this inhibition was not statistically significant.
滥用甲基苯丙胺的非法类似物（即“设计药物”）是一个日益严重的问题。最流行的甲基苯丙胺类似物之一是（±）-3,4-亚甲基二氧基甲基苯丙胺（MDMA），俗称摇头丸。作者先前证明，体外暴露于甲基苯丙胺会导致宿主防御所需的免疫功能参数发生调节。本研究旨在评估暴露于一种改良甲基苯丙胺的潜在直接（体外）免疫调节作用。将B6C3F1小鼠的脾细胞或腹腔巨噬细胞在体外以0.0001 - 100微摩尔/升的MDMA浓度进行培养。通过抗CD3介导的IL - 2和IL - 4产生来评估T细胞调节功能，通过定量细胞增殖来评估B细胞功能，通过定量自然杀伤（NK）细胞活性来评估天然免疫，将T细胞效应功能评估为细胞毒性T淋巴细胞（CTL）活性的函数，并通过IL - 6肿瘤坏死因子（TNF）产生来评估巨噬细胞功能。体外暴露于MDMA在任何测试浓度下对B细胞增殖均无影响。相比之下，在没有直接细胞毒性的情况下，低至0.0001微摩尔/升的浓度就能增强IL - 2的产生。IL - 4的产生不受所检测的任何MDMA浓度暴露的影响，表明该化合物对辅助性T细胞功能有不同的改变。当以100:1的效应细胞：靶细胞比例进行检测时，MDMA浓度在0.0001至1.0微摩尔/升之间可增强基础和增强的NK细胞功能。在100微摩尔/升的浓度下，CTL诱导受到显著抑制。最后，在10和100微摩尔/升的MDMA浓度下，巨噬细胞TNF的产生略有抑制，尽管这种抑制没有统计学意义。
