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• W1985406002 abstract "Here we demonstrate that the widely abused drug methylenedioxymethamphetamine (MDMA; “Ecstasy”) suppresses innate interferon (IFN)-γ production in mice following an in vivo lipopolysaccharide (LPS) challenge. IFN-γ signalling was also impaired by MDMA, as indicated by reduced phosphorylation of signal transducer and activator of transcription-1 (STAT1) and reduced expression of interferon-γ inducible protein 10 (IP-10/CXCL10); a chemokine induced by IFN-γ. MDMA also suppressed production of interleukin (IL)-12 and IL-15; two cytokines that induce IFN-γ production. Our results demonstrate that in vitro exposure to MDMA does not mimic the suppression of innate IFN-γ observed in vivo, indicating that observed suppression is most likely due to the release of endogenous immunomodulatory substances following drug administration. In this regard, we previously demonstrated that MDMA increases production of the anti-inflammatory cytokine IL-10 in vivo, an event that is mediated by β-adrenoceptor activation on immune cells. Considering that increased IL-10 production precedes suppression of IFN-γ induced by MDMA, and also considering that IL-10 can inhibit IL-12 and IFN-γ production, we examined the possibility that IL-10 was an essential mediator of the suppressive effect of MDMA on the IFN-γ response. By pre-treating mice with an anti-IL-10 receptor antibody we demonstrate that IL-10 is a critical mediator of MDMA-induced suppression of IFN- γ production and signalling. Consistent with a role for β-adrenoceptor activation in the immunosuppressive actions of MDMA, pre-treatment with the β-adrenoceptor antagonist nadolol blocked the MDMA-induced increase in IL-10, and also inhibited the suppressive action of MDMA on the innate IFN-γ response. The potential clinical significance of these findings for MDMA users is discussed." @default.
• W1985406002 created "2016-06-24" @default.
• W1985406002 creator A5053996039 @default.
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• W1985406002 date "2007-10-01" @default.
• W1985406002 modified "2023-09-26" @default.
• W1985406002 title "MDMA (“Ecstasy”) suppresses the innate IFN-γ response in vivo: A critical role for the anti-inflammatory cytokine IL-10" @default.
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• W1985406002 doi "https://doi.org/10.1016/j.ejphar.2007.07.020" @default.
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