ALTERATIONS IN SPLENOCYTE AND THYMOCYTE SUBPOPULATIONS IN B6C3F1 MICEEXPOSED TO COCAINE PLUS DIAZINON

Our laboratory has proposed a working model which asserts that cocaine 's effects on immunity are mediated by reactive metabolites generated by the cytochrome P-450 system. This metabolic pathway is normally a m inor one in humans, but takes on significance when metabolism of cocai ne by the P-450 system is increased, as may occur with excessive alcoh ol consumption (enzyme induction) or after exposure to organophosphate pesticides (esterase inhibition). Results from our laboratory demonst rate that cocaine exerts its most dramatic effects on immunocompetence when administered to mice that have been pretreated with diazinon, an organophosphate esterase inhibitor. Most notably, we observed decreas es in both the splenic T-dependent antibody response to sheep erythroc ytes and the splenic T-independent antibody response to DNP-ficoll and a dramatic thymic atrophy in mice exposed to cocaine + diazinon, whic h were not seen in mice exposed to cocaine alone. The primary objectiv e of the present investigation was to determine whether the exposure c onditions used to produce the changes noted above are also capable of causing changes in lymphocyte cell types by use of flow cytometric ana lysis. Administration of cocaine after pretreatment with diazinon; onl y modestly affected splenic lymphocyte subsets, which caused a slight decrease in the number of B cells. No effect was observed in the macro phage, T-helper or T-suppressor subpopulations in the spleen. These re sults suggest that changes in splenocyte subpopulations induced by coc aine + diazinon cannot account for the suppression of the antibody res ponse. In contrast, all T-cell subsets in the thymus were decreased si gnificantly, with immature double-positive thymocytes suffering the gr eatest loss in cell number. These results indicate that T cells, espec ially immature thymocytes located in the thymus, are sensitive to effe cts associated with the combined treatment of cocaine + diazinon.