PMID- 17689526
OWN - NLM
STAT- MEDLINE
DCOM- 20080114
LR  - 20131121
IS  - 0014-2999 (Print)
IS  - 0014-2999 (Linking)
VI  - 572
IP  - 2-3
DP  - 2007 Oct 31
TI  - MDMA ("Ecstasy") suppresses the innate IFN-gamma response in vivo: a critical 
      role for the anti-inflammatory cytokine IL-10.
PG  - 228-38
AB  - Here we demonstrate that the widely abused drug methylenedioxymethamphetamine 
      (MDMA; "Ecstasy") suppresses innate interferon (IFN)-gamma production in mice 
      following an in vivo lipopolysaccharide (LPS) challenge. IFN-gamma 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-gamma inducible protein 10 (IP-10/CXCL10); a chemokine induced by 
      IFN-gamma. MDMA also suppressed production of interleukin (IL)-12 and IL-15; two 
      cytokines that induce IFN-gamma production. Our results demonstrate that in vitro 
      exposure to MDMA does not mimic the suppression of innate IFN-gamma 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 
      beta-adrenoceptor activation on immune cells. Considering that increased IL-10 
      production precedes suppression of IFN-gamma induced by MDMA, and also 
      considering that IL-10 can inhibit IL-12 and IFN-gamma production, we examined 
      the possibility that IL-10 was an essential mediator of the suppressive effect of 
      MDMA on the IFN-gamma 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- gamma production and signalling. Consistent with a role for 
      beta-adrenoceptor activation in the immunosuppressive actions of MDMA, 
      pre-treatment with the beta-adrenoceptor antagonist nadolol blocked the 
      MDMA-induced increase in IL-10, and also inhibited the suppressive action of MDMA 
      on the innate IFN-gamma response. The potential clinical significance of these 
      findings for MDMA users is discussed.
FAU - Boyle, Noreen T
AU  - Boyle NT
AD  - Neuroimmunology Research Group, Department of Physiology, School of Medicine & 
      Trinity College Institute of Neuroscience, Trinity College, Dublin 2, Ireland.
FAU - Connor, Thomas J
AU  - Connor TJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070718
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (Adrenergic beta-Antagonists)
RN  - 0 (Antibodies)
RN  - 0 (Hallucinogens)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Interleukin-10)
RN  - 130068-27-8 (Interleukin-10)
RN  - 187348-17-0 (Interleukin-12)
RN  - 42200-33-9 (Nadolol)
RN  - 82115-62-6 (Interferon-gamma)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - Adrenergic beta-Antagonists/pharmacology
MH  - Animals
MH  - Antibodies/pharmacology
MH  - Hallucinogens/*toxicity
MH  - Immunity, Innate
MH  - Interferon-gamma/*biosynthesis
MH  - Interleukin-10/biosynthesis/genetics/*physiology
MH  - Interleukin-12/biosynthesis
MH  - Lipopolysaccharides/pharmacology
MH  - Male
MH  - Mice
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*toxicity
MH  - Nadolol/pharmacology
MH  - RNA, Messenger/biosynthesis
MH  - Receptors, Interleukin-10/immunology/physiology
EDAT- 2007/08/11 09:00
MHDA- 2008/01/15 09:00
CRDT- 2007/08/11 09:00
PHST- 2007/04/28 00:00 [received]
PHST- 2007/06/28 00:00 [revised]
PHST- 2007/07/04 00:00 [accepted]
PHST- 2007/08/11 09:00 [pubmed]
PHST- 2008/01/15 09:00 [medline]
PHST- 2007/08/11 09:00 [entrez]
AID - S0014-2999(07)00778-9 [pii]
AID - 10.1016/j.ejphar.2007.07.020 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 2007 Oct 31;572(2-3):228-38. doi: 10.1016/j.ejphar.2007.07.020. 
      Epub 2007 Jul 18.