AIDS, Drugs of Abuse, and the Neuroimmune Axis pp 145-156 | Cite as
Divergent Effects of Cocaine on Cytokine Production by Lymphocytes and Monocyte/Macroophages
Abstract
Cocaine-related immunosuppression is asumed 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 counts, (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 LPSstimulated mononuclear cells; (d) increased TNF-a 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 Thl 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.
Keywords
Lower Chamber Brain Endothelial Cell Human Brain Microvascular Endothelial Cell Preferential Migration Intravenous CocainePreview
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