Delta(9)-tetrahydrocannabinol treatment suppresses immunity and early IFN-gamma, IL-12, and IL-12 receptor beta 2 responses to Legionella pneumophilainfection

The marijuana cannabinoid, dg-tetrahydrocannabinol (THC), suppresses immuni ty to Legionella pneumophila and development of Th1 activity and cell-media ted immunity. In the current study, THC effects on cytokines regulating the development of Th1 cells were examined. BALB/c mice showed significant inc reases in serum IL-12 and IFN-gamma within hours of infection; however, the levels of these Th1-promoting cytokines as well as resistance to a challen ge infection were suppressed by THC (8 mg/kg) injected 18 h before priming, The Th2-promoting cytokine, IL-4, was increased within hours of a Legionel la infection and was further increased by THC treatment. These results sugg ested that THC injection suppressed the cytokine environment promoting Th1 immunity. In additional experiments, THC pretreatment and infection of IL-4 knockout mice showed that serum IL-12 and IFN-gamma were suppressed equall y in both knockout and normal mice. This suggested that the drug-induced in crease in IL-4 was not responsible for the decreases in serum IL-12 and IFN -gamma. However, THC treatment was shown to suppress the expression of IL-1 2 receptor beta 2 mRNA, indicating that, in addition to suppression of IL-1 2, THC injection suppressed the expression of IL-12 receptors, Finally, the role of cannabinoid receptors in Th1-promoting cytokine suppression was ex amined, and results with receptor antagonists showed that both cannabinoid receptors 1 and 2 were involved. It is suggested that suppression of Th1 im munity to Legionella is not due to an increase in IL-4 production but to a decrease in IFN-gamma and IL-12, Furthermore, both types of cannabinoid rec eptors are involved.