title: Selective modulation of immune function resulting from in vitro exposure to methylenedioxymethamphetamine (Ecstasy).
abstract: 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.
authors.affiliation: Life Sciences Department, IIT Research Institute, Chicago, IL 60616.
authors.forename: R V
authors.initials: RV
authors.lastname: House
authors.forename: P T
authors.initials: PT
authors.lastname: Thomas
authors.forename: H N
authors.initials: HN
authors.lastname: Bhargava
mesh_terms: D000276:Adjuvants, Immunologic / Q000633:toxicity*; D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D007107:Immune System / Q000187:drug effects*; D007111:Immunity, Cellular / Q000187:drug effects; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000187:drug effects; D008213:Lymphocyte Activation / Q000187:drug effects; D008264:Macrophages / Q000166:cytology / Q000187:drug effects; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000737:chemistry / Q000633:toxicity*; D013154:Spleen / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D000276:Adjuvants, Immunologic; D007376:Interleukin-2; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D018817:N-Methyl-3,4-methylenedioxyamphetamine