Delta-9-tetrahydrocannabinol treatment results in a suppression of interleukin-2-induced cellular activities in human and murine lymphocytes.
Delta-9-tetrahydrocannabinol (THC), the major psychoactive component in marijuana, has been shown to suppress a variety of interleukin-2-(IL-2)-dependent cellular functions in both murine and human lymphocytes. These effects were examined in both human peripheral blood lymphocytes (hPBL) and the IL-2-dependent murine cytotoxic T-cell line CTLL-2. Interleukin-2-induced thymidine uptake and uridine uptake were suppressed in a dose related manner when cells were co-incubated for 48 h with 100 U rhIL-2/ml and 1-10 micrograms THC/ml. Interleukin-2-induced protein synthesis was also suppressed in a dose related manner over this THC concentration range, with the hPBL being more susceptible to the suppressive effect of THC than the CTLL-2 cells. Autoradiographic analysis of the synthesized proteins from hPBL cell lysates reveals a generalized suppression of all nascent proteins in THC-treated cultures. Human natural killer cell activity is only affected at the highest concentration tested (10 micrograms THC/ml) while lymphokine-(IL-2)-activated natural killer cell activity is affected throughout the range of 1-10 micrograms THC/ml. Together these results suggest that THC interferes with the IL-2:IL-2 receptor signaling cascade at one or possibly many points causing a decrease in IL-2-induced metabolic activity and cytolytic function.
Trisler
K
K
Department of Radiation Oncology, Stanford University School of Medicine.
Specter
S
S
D000818:Animals; D001798:Blood Proteins / Q000096:biosynthesis / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects; D013759:Dronabinol / Q000494:pharmacology*; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D007376:Interleukin-2 / Q000037:antagonists & inhibitors* / Q000502:physiology; D007694:Killer Cells, Natural / Q000187:drug effects; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000187:drug effects* / Q000276:immunology*; D051379:Mice; D012313:RNA / Q000096:biosynthesis / Q000187:drug effects; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects; D014407:Tumor Cells, Cultured / Q000276:immunology
D001798:Blood Proteins; D007376:Interleukin-2; D012313:RNA; D013759:Dronabinol; D004247:DNA