title: Ethanol enhances immunosuppression induced by cocaine.
abstract: Use of cocaine concurrently with alcohol is prevalent among cocaine addicts. Cocaine has been shown to inhibit phytohemagglutinin- and ConA-induced proliferation of T-lymphocytes, NK cell cytotoxicity, and phagocytic activity of peritoneal macrophages. In some studies no effects of cocaine on the immune response have been observed, although on the contrary, others show it increased the NK cell activity and serum antibody response to T-dependent antigen. Effects of cocaine on the immune system may be mediated by its neurostimulatory action on the hypothalamo-pituitary-adrenal axis. ACTH, beta-endorphine, and corticosterone released under the action of cocaine exert various inhibitory effects on the immune function. We studied the immunotoxic effect of cocaine, combination of cocaine with ethanol, and cocaethylene, a derivative formed from cocaine and ethanol in the body, on the mitogen-stimulated production of cytokines by splenocytes. C57BL mice were injected twice daily with 20 mg/kg cocaine or equivalent dose of cocaethylene and received a liquid Lieber-DeCarli diet containing ethanol (26% of total calories) or isocaloric amount of maltose-dextrin. After 3 weeks of treatment, cocaine and cocaethylene caused a significant decrease of the spleen weight and total number of splenocytes. In splenocytes isolated from the cocaine- or cocaethylene-treated mice, mitogen-stimulated production of gamma-interferon, tumor necrosis factor, and interleukin-2 was suppressed, in all cases more severely when cocaethylene was used. Thus, formation of cocaethylene during simultaneous consumption of cocaine and ethanol may enhance the immunotoxicity of cocaine.
authors: Research Institute for Medico-Biological Problems of Addictions, Moscow, Russia.
authors: S V
authors: SV
authors: Pirozhkov
authors: R R
authors: RR
authors: Watson
authors: G J
authors: GJ
authors: Chen
mesh_terms: D000818:Animals; D003042:Cocaine / Q000031:analogs & derivatives / Q000633:toxicity*; D004357:Drug Synergism; D000431:Ethanol / Q000633:toxicity*; D007108:Immune Tolerance / Q000187:drug effects*; D007371:Interferon-gamma / Q000096:biosynthesis; D007375:Interleukin-1 / Q000096:biosynthesis; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D007375:Interleukin-1; D000431:Ethanol; D007371:Interferon-gamma; C066444:cocaethylene; D003042:Cocaine