Cannabinoid-mediated exacerbation of brain infection by opportunistic amebae.
Recent reports indicate a higher frequency of brain infections with opportunistic amebae of the genus Acanthamoeba among immune compromised individuals, including AIDS patients. We have demonstrated, using a murine model of Granulomatous Amebic Encephalitis (GAE), that the major psychoactive and immune suppressive component in marijuana delta-9-tetrahydrocannabinol (THC) exacerbates infection by these amebae. Mice administered THC and infected with Acanthamoeba exhibited dose-related higher mortalities than infected vehicle controls. The greater severity of disease for THC-treated mice was accompanied by decreased accumulation of macrophage-like cells at focal sites of infection in the brain. Furthermore, THC administration resulted in decreased levels of mRNA for the pro-inflammatory cytokines interleukin-1 alpha, interleukin-1 beta, and tumor necrosis factor alpha for neonatal rat microglia co-cultured with Acanthamoeba. These results indicate a potential for marijuana to alter the capacity of brain macrophage-like cells to mount a full complement of immune responsiveness to brain infection by opportunistic amebae.
Cabral
Guy A
GA
Department of Microbiology and Immunology, Virginia Commonwealth University, School of Medicine, Richmond, VA 23298-0678, USA. gacabral@hsc.vcu.edu
Marciano-Cabral
Francine
F
D000048:Acanthamoeba / Q000378:metabolism / Q000472:pathogenicity; D000562:Amebiasis / Q000209:etiology*; D000656:Amoeba; D000818:Animals; D015153:Blotting, Western; D001927:Brain Diseases / Q000209:etiology* / Q000469:parasitology; D002186:Cannabinoids / Q000009:adverse effects* / Q000494:pharmacology; D002478:Cells, Cultured; D003520:Cyclophosphamide / Q000494:pharmacology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000494:pharmacology; D005260:Female; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008169:Lung Abscess / Q000150:complications / Q000378:metabolism; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism; D009894:Opportunistic Infections / Q000469:parasitology*; D011619:Psychotropic Drugs / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
D002186:Cannabinoids; D016207:Cytokines; D007166:Immunosuppressive Agents; D009687:Nuclear Proteins; D011619:Psychotropic Drugs; D012333:RNA, Messenger; D014157:Transcription Factors; D013759:Dronabinol; D003520:Cyclophosphamide