3,4-Methylenedioxymethamphetamine (MDMA) alters acute gammaherpesvirus burden and limits interleukin 27 responses in a mouse model of viral infection.
OBJECTIVE
To test whether 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") abuse might increase the susceptibility, or alter the immune response, to murine gammaherpesvirus 68 (HV-68) and/or bacterial lipopolysaccharide.


METHODS
Groups of experimental and control mice were subjected to three day binges of MDMA, and the effect of this drug abuse on acute and latent HV-68 viral burden were assessed. In vitro and in vivo studies were also performed to assess the MDMA effect on IL-27 expression in virally infected or LPS-exposed macrophages and dendritic cells, and latently infected animals, exposed to this drug of abuse.


RESULTS
Acute viral burden was significantly increased in MDMA-treated mice when compared to controls. However the latent viral burden, and physiological and behavioral responses were not altered in infected mice despite repeated bingeing with MDMA. MDMA could limit the IL-27 response of HV-68 infected or LPS-exposed macrophages and dendritic cells in vitro and in vivo, demonstrating the ability of this drug to alter normal cytokine responses in the context of a viral infection and/or a TLR4 agonist.


CONCLUSIONS
MDMA bingeing could alter the host's immune response resulting in greater acute viral replication and reductions in the production of the cytokine, IL-27 during immune responses.
Department of Biology, University of North Carolina at Charlotte, Charlotte, NC 28223, USA.
Daniel A
DA
Nelson
Sam J
SJ
Singh
Amy B
AB
Young
Melanie D
MD
Tolbert
Kenneth L
KL
Bost
D000818:Animals; D003713:Dendritic Cells / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D018142:Gammaherpesvirinae / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D006213:Hallucinogens / Q000494:pharmacology*; D006566:Herpesviridae Infections / Q000276:immunology / Q000378:metabolism / Q000821:virology*; D020381:Interleukin-17 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology*; D051197:Toll-Like Receptor 4 / Q000819:agonists; D019562:Viral Load / Q000187:drug effects* / Q000276:immunology
D006213:Hallucinogens; D020381:Interleukin-17; D008070:Lipopolysaccharides; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D018817:N-Methyl-3,4-methylenedioxyamphetamine
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