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9-Tetrahydrocannabinol Treatment Suppresses Immunity and Early IFN-
, IL-12, and IL-12 Receptor ß2 Responses to Legionella pneumophila Infection1
Department of Medical Microbiology and Immunology, University of South Florida College of Medicine, Tampa, FL 33612
The marijuana cannabinoid, 
9-tetrahydrocannabinol
(THC), suppresses immunity to Legionella pneumophila and
development of Th1 activity and cell-mediated immunity. In the current
study, THC effects on cytokines regulating the development of Th1 cells
were examined. BALB/c mice showed significant increases in serum IL-12
and IFN-
within hours of infection; however, the levels of these
Th1-promoting cytokines as well as resistance to a challenge 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
Legionella infection and was further increased by THC
treatment. These results suggested 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- were suppressed equally in both knockout and normal
mice. This suggested that the drug-induced increase in IL-4 was not
responsible for the decreases in serum IL-12 and IFN-. However, THC
treatment was shown to suppress the expression of IL-12 receptor ß2
mRNA, indicating that, in addition to suppression of IL-12, THC
injection suppressed the expression of IL-12 receptors. Finally, the
role of cannabinoid receptors in Th1-promoting cytokine suppression was
examined, and results with receptor antagonists showed that both
cannabinoid receptors 1 and 2 were involved. It is suggested that
suppression of Th1 immunity to Legionella is not due to
an increase in IL-4 production but to a decrease in IFN- and IL-12.
Furthermore, both types of cannabinoid receptors are
involved.
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