delta 9-Tetrahydrocannabinol, cytokines, and immunity to Legionella pneumophila.
The major psychoactive component of marijuana, delta 9-tetrahydrocannabinol (THC), has been shown to suppress the functions of various immune cells. However, the relationship of these findings to THC-induced suppression of host resistance to infection has not been firmly established. In this report, we review the literature concerning THC's effects on cytokine production and resistance to infection with Legionella pneumophila (Lp). Recent reports have linked THC-induced immunomodulation with drug-induced modulation of the cytokine network. Specifically, THC in vivo suppresses interferon (IFN) production while in vitro modulates the production of tumor necrosis factor (TNF), interleukin-1 (IL-1), interleukin-2 (IL-2), and interleukin-2 receptor (IL-2R). These results suggested that THC treatment might alter host immunity by disrupting the cytokine network. Immunity and resistance to infection with Lp depends upon the activation of killer cells and the stimulation of the cytokine network. THC injection into rodents was observed to augment acute phase cytokine mobilization in response to a primary Lp infection; on the other hand, the drug suppressed the development of protective immunity and resistance to secondary Lp infection by causing a change in the profile of T helper cell cytokines produced by Th1 and Th2 cells. Thus, it appears that THC injection suppresses resistance to Lp infection by disrupting the cytokine network. Regarding the molecular mechanisms of these effects of THC, data is reviewed concerning the role of cannabinoid receptors (CR) in cells of the immune system. In summary, the literature to date supports the role of THC as an immunomodulator capable of suppressing resistance to infection through mechanisms involving alteration of the cytokine network. The role of CR receptors in these events has yet to be determined.
Klein
T W
TW
Department of Medical Microbiology and Immunology, University of South Florida College of Medicine, Tampa 33612, USA.
Newton
C
C
Zhu
W
W
Daaka
Y
Y
Friedman
H
H
D016207:Cytokines / Q000096:biosynthesis*; D013759:Dronabinol / Q000494:pharmacology*; D007113:Immunity, Innate / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D016952:Legionella pneumophila / Q000276:immunology*; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000502:physiology
D016207:Cytokines; D007166:Immunosuppressive Agents; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D013759:Dronabinol