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.