title: Effect of Delta-9-tetrahydrocannabinol on mouse resistance to systemic Candida albicans infection.
abstract: Delta-9-tetrahydrocannabinol (Δ9-THC), the psychoactive component of marijuana, is known to suppress the immune responses to bacterial, viral and protozoan infections, but its effects on fungal infections have not been studied. Therefore, we investigated the effects of chronic Δ9-THC treatment on mouse resistance to systemic Candida albicans (C. albicans) infection. To determine the outcome of chronic Δ9-THC treatment on primary, acute systemic candidiasis, c57BL/6 mice were given vehicle or Δ9-THC (16 mg/kg) in vehicle on days 1-4, 8-11 and 15-18. On day 19, mice were infected with 5×10(5) C. albicans. We also determined the effect of chronic Δ9-THC (4-64 mg/kg) treatment on mice infected with a non-lethal dose of 7.5×10(4) C. albicans on day 2, followed by a higher challenge with 5×10(5) C. albicans on day 19. Mouse resistance to the infection was assessed by survival and tissue fungal load. Serum cytokine levels were determine to evaluate the immune responses. In the acute infection, chronic Δ9-THC treatment had no effect on mouse survival or tissue fungal load when compared to vehicle treated mice. However, Δ9-THC significantly suppressed IL-12p70 and IL-12p40 as well as marginally suppressed IL-17 versus vehicle treated mice. In comparison, when mice were given a secondary yeast infection, Δ9-THC significantly decreased survival, increased tissue fungal burden and suppressed serum IFN-γ and IL-12p40 levels compared to vehicle treated mice. The data showed that chronic Δ9-THC treatment decreased the efficacy of the memory immune response to candida infection, which correlated with a decrease in IFN-γ that was only observed after the secondary candida challenge.
authors: Department of Biological Sciences, California State Polytechnic University, Pomona, California, United States of America.
authors: Gideon W
authors: GW
authors: Blumstein
authors: Department of Biological Sciences, California State Polytechnic University, Pomona, California, United States of America.
authors: Arya
authors: A
authors: Parsa
authors: Department of Biological Sciences, California State Polytechnic University, Pomona, California, United States of America.
authors: Anthony K
authors: AK
authors: Park
authors: Department of Biological Sciences, California State Polytechnic University, Pomona, California, United States of America.
authors: Beverly L P
authors: BL
authors: McDowell
authors: Department of Biological Sciences, California State Polytechnic University, Pomona, California, United States of America.
authors: Melissa
authors: M
authors: Arroyo-Mendoza
authors: Department of Biological Sciences, California State Polytechnic University, Pomona, California, United States of America.
authors: Marie
authors: M
authors: Girguis
authors: Department of Biological Sciences, California State Polytechnic University, Pomona, California, United States of America.
authors: Jill P
authors: JP
authors: Adler-Moore
authors: Department of Biological Sciences, California State Polytechnic University, Pomona, California, United States of America.
authors: Jon
authors: J
authors: Olson
authors: Department of Biological Sciences, California State Polytechnic University, Pomona, California, United States of America.
authors: Nancy E
authors: NE
authors: Buckley
mesh_terms: D000818:Animals; D001921:Brain / Q000382:microbiology; D002176:Candida albicans / Q000502:physiology*; D002177:Candidiasis / Q000276:immunology* / Q000382:microbiology* / Q000401:mortality; D016207:Cytokines / Q000097:blood*; D013759:Dronabinol / Q000008:administration & dosage* / Q000633:toxicity; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007668:Kidney / Q000382:microbiology; D008099:Liver / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000382:microbiology
chemical_list: D016207:Cytokines; D013759:Dronabinol