Divergent effects of cocaine on cytokine production by lymphocytes and monocyte/macrophages: HIV-1 enhancement by cocaine within the blood-brain barrier

Cocaine-related immunosuppression is assumed to have serious consequences, but its evaluation in drug-addicted subjects is lacking. In this study performed with materials from addicted subjects receiving intravenous cocaine and normal control subjects, acute cocaine effects on cytokine production in vivo and in mononuclear cells in vitro were determined. Acute intravenous cocaine administration resulted in (a) increased white blood cell and lymphocyte courts, (b) decreased tumor necrosis factor-α (TNF-α) and interleukin (IL)-10 serum levels; (c) depressed TNF-α, IL-10 and IL-12 production by unstimulated or LPS- stimulated mononuclear cells; (d) increased TNF-α production by PHA- stimulated mononuclear cells. These observations suggest that cocaine has stimulatory effect on TNF-α production by lymphocytes but inhibitory action on TNF-α production by monocyte/macrophages. In vitro cocaine treatment of monocyte-enriched preparations of mononuclear cells from normal donors resulted in suppression of cytokine production. A blood-brain barrier model was constructed using human brain microvascular endothelial cells. In this model mononuclear cell transmigration was correctly regulated by Th1 and Th2 cytokines and preferential migration of 'memory' T cells was inhibited by cocaethylene. TNF-α and cocaethylene increased HIV-1 titers in the brain- side of the model.