Effect of the Psychoactive Metabolite of Marijuana, Δ9-Tetrahydrocannabinol (THC), on the Synthesis of Tumor Necrosis Factor by Human Large Granular Lymphocytes

The natural killer cell (NK)/3polymorphonuclear neutrophil axis has recently been identified to be important in early defense against the opportunistic fungi, Candida albicans. Repression of this system is therefore likely to contribute to susceptibility to opportunistic infections. Δ9-Tetrahydrocannabinol (THC), an active constituent of marijuana, has been reported to be immunosuppressive at concentrations that exceed attainable plasma levels. In this report, we examine the possibility that human large granular lymphocytes (LGL) can be immunosuppressed by exposure to THC at physiologically relevant concentrations and probed two functions associated with LGL i.e., cytokine production and tumoricidal activity. We find that these low levels of THC inhibit tumor necrosis factor-α (TNF) induction from LGL by C. albicans and are dependent upon THC dose (0.005-5.0 μg/ml) and length of exposure (0.05 3.0 hr). Northern blot analysis indicates that the downregulation of TNF production from LGL by THC resides at the mRNA level. Moreover, exposure of LGL to physiological THC concentrations (0.01 2.0 μg/ml) diminishes their cytolytic activity against K562 tumor cells.