Cocaine suppresses proliferation of phytohemagglutinin-activated human peripheral blood T-cells.
Cocaine has been reported to modulate the immune system of experimental animals. Also, we observed that the drug suppresses the phytohemagglutinin (PHA)-induced proliferation of human peripheral blood mononuclear cells (PBMCs) but at concentrations extremely high relative to those seen in the blood of drug abusers. This suggested that cocaine had a relatively weak effect when tested under conditions of optimum proliferation. We, therefore, decided to examine the effect of lower concentrations of cocaine on suboptimum PHA-induced proliferation. At 0.09-12 microM, cocaine had no effect on the proliferation of PBMC in response to 0.2 micrograms/ml PHA. However, depleting the population of B-cells and monocytes resulted in a drug-induced suppression of the residual T-cells. Maximum suppression by cocaine was observed at 3 microM with both higher and lower concentrations of the drug causing less suppression. Suppression of proliferation was not influenced by either the age or sex of the peripheral blood lymphocytes (PBL) donors. The suppression of T-cell-enriched PBLs induced by cocaine could be eliminated by increasing the dose of the mitogen but was enhanced by preincubating the cells with the drug for 24 h. Also, the drug suppressed cytosolic free calcium mobilization in Fura 2/AM loaded enriched T-cell populations. These results show that cocaine moderately but consistently suppresses PHA-induced proliferation of T-cells from random blood donors at drug concentrations observed in drug abusers. The suppression is only evident under conditions of suboptimum proliferation and is accompanied by a corresponding decrease in the mobilization of cytosolic free calcium. It is suggested that the weak suppressive effect of cocaine is reversed by either helper factors produced by accessory cells or increasing concentrations of mitogen. These factors when present possibly overcome a drug-induced reduction in calcium mobilization and lymphocyte activation.
Klein
T W
TW
Department of Medical Microbiology and Immunology, University of South Florida, College of Medicine, Tampa 33612.
Matsui
K
K
Newton
C A
CA
Young
J
J
Widen
R E
RE
Friedman
H
H
D000328:Adult; D000367:Age Factors; D000368:Aged; D000938:Antigen-Presenting Cells / Q000276:immunology; D002118:Calcium / Q000378:metabolism; D003042:Cocaine / Q000494:pharmacology*; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007424:Intracellular Fluid / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D010835:Phytohemagglutinins / Q000494:pharmacology; D012737:Sex Factors; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism
D007166:Immunosuppressive Agents; D010835:Phytohemagglutinins; D003042:Cocaine; D002118:Calcium