delta-9-Tetrahydrocannabinol (THC) decreases the number of high and intermediate affinity IL-2 receptors of the IL-2 dependent cell line NKB61A2.
Treatment of the cloned NK-cell line (NKB61A2) with the major psychoactive marijuana component, delta-9-tetrahydrocannabinol (THC), for 24 h suppressed IL-2-induced proliferation of these cells in the cytokine concentration range of 0.25-10 pM suggesting that the drug inhibits the functional activity of the high affinity IL-2R. The proliferation inhibitory effect of THC was accompanied by a decrease in the number of high and intermediate affinity IL-2 binding sites as measured by equilibrium binding studies. However, the expression of Tac protein on the surface of these cells was increased as determined by flow cytometry analysis. THC was also shown to decrease proliferation and the number of IL-2 binding sites of cells previously pulsed with IL-2 and then treated with the drug in the absence of IL-2. These results suggest that THC inhibits IL-2-induced proliferation by modulating the expression of high affinity IL-2 receptors (alpha/beta) required for cell activation and also suppresses the ongoing process of functional receptor expression and clonal expansion of cells previously activated by IL-2. Because the number of intermediate binding sites is decreased following drug treatment along with an increase in the expression of Tac protein (alpha chain), the lowering of high affinity sites possibly results from a drug-induced depression of beta chain expression.
Department of Medical Microbiology and Immunology, University of South Florida, College of Medicine, Tampa 33612.
W
W
Zhu
T
T
Igarashi
Z T
ZT
Qi
C
C
Newton
R E
RE
Widen
H
H
Friedman
T W
TW
Klein
D000818:Animals; D002460:Cell Line; D013759:Dronabinol / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D015375:Receptors, Interleukin-2 / Q000032:analysis / Q000187:drug effects*
D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D013759:Dronabinol