Stimulatory effects of cocaine and its metabolites on IM-9 human B-lymphoblastoid cells.
This study examined the effect of cocaine and its metabolites benzoylecgonine, norcocaine, and cocaethylene on human B-cell proliferation using IM-9 cells. Cells were incubated with 0.01-10 micrograms/ml of cocaine or metabolite in serum-free medium or medium containing 2% FBS for 24 and 48 h, and [3H] thymidine incorporation into DNA was measured using liquid scintillation counting. Results showed incubation with cocaine and metabolites significantly increased IM-9 cell proliferation. With cocaine, maximal stimulation of 148% (compared to drug-free control) occurred at 1.0 micrograms/ml in serum-free medium at 48 h. Benzoylecgonine and norcocaine showed maximal stimulation at 0.1 micrograms/ml with 170% and 150% stimulation, respectively. Cocaethylene showed maximal stimulation of 146% at 10 micrograms/ml. Drug stability was monitored under incubation conditions using high-performance liquid chromatography (HPLC). We have shown that cocaine and its major metabolites have an immunomodulatory effect on B-cell proliferation at concentrations equivalent to serum levels produced during cocaine use in humans. Since the cocaine metabolites also show an immunomodulatory effect, the immune consequences of cocaine use may be significantly prolonged.
Phillips
D L
DL
Department of Pharmaceutics, University of Florida, Gainesville 32610, USA.
Tebbett
I R
IR
Masten
S
S
Shiverick
K T
KT
D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D003042:Cocaine / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology*; D004355:Drug Stability; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
C008671:norcocaine; C005618:benzoylecgonine; C066444:cocaethylene; D003042:Cocaine; D013755:Tetradecanoylphorbol Acetate