PMID- 15331655
OWN - NLM
STAT- MEDLINE
DCOM- 20050413
LR  - 20131121
IS  - 0022-3565 (Print)
IS  - 0022-3565 (Linking)
VI  - 312
IP  - 1
DP  - 2005 Jan
TI  - Methylenedioxymethamphetamine suppresses production of the proinflammatory 
      cytokine tumor necrosis factor-alpha independent of a beta-adrenoceptor-mediated 
      increase in interleukin-10.
PG  - 134-43
AB  - Recent data suggest that 3,4-methylenedioxymethamphetamine (MDMA; "Ecstasy") has 
      marked immunosuppressive properties. In this study, we investigate the effect of 
      MDMA on production of the anti-inflammatory cytokine interleukin (IL)-10 in 
      response to an in vivo challenge with bacterial lipopolysaccharide (LPS). Our 
      data demonstrate that both acute and repeated administration of MDMA increases 
      production of LPS-induced IL-10 in vivo, and this increase correlates inversely 
      with the ability of MDMA to suppress the proinflammatory cytokine tumor necrosis 
      factor (TNF)-alpha. Despite this correlation, immunoneutralization of IL-10 does 
      not reverse the suppressive effect of MDMA on LPS-induced TNF-alpha production, 
      indicating that suppression of this proinflammatory cytokine is not mediated by 
      IL-10. In vitro exposure to MDMA does not mimic the immunosuppressive cytokine 
      phenotype induced in vivo, suggesting that these immunosuppressive effects are 
      not mediated by a direct action on monocytes per se. As MDMA activates that 
      hypothalamic pituitary adrenal axis and sympathetic nervous system, we examined 
      the role of glucocorticoids and catecholamines in its immunosuppressive actions. 
      However, the immunosuppressive cytokine phenotype induced by MDMA was not altered 
      by adrenalectomy, sympathetic denervation, or ganglionic blockade, indicating 
      that neither glucocorticoids nor adrenal/sympathetic-derived catecholamines 
      mediate these immunosuppressive effects of MDMA. Interestingly, beta-adrenoceptor 
      blockade completely inhibited the increase in IL-10 induced by MDMA without 
      altering the suppression of TNF-alpha. Taken together, these data demonstrate a 
      role for beta-adrenoceptor activation in the ability of MDMA to increase 
      LPS-induced IL-10 and highlight a mechanistic dissociation between the ability of 
      MDMA to increase IL-10 and suppress production of the proinflammatory cytokine 
      TNF-alpha.
FAU - Connor, Thomas J
AU  - Connor TJ
AD  - Department of Physiology, Trinity College, Dublin 2, Ireland. connort@tcd.ie
FAU - Harkin, Andrew
AU  - Harkin A
FAU - Kelly, John P
AU  - Kelly JP
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20040826
PL  - United States
TA  - J Pharmacol Exp Ther
JT  - The Journal of pharmacology and experimental therapeutics
JID - 0376362
RN  - 0 (Adrenergic Antagonists)
RN  - 0 (Adrenergic Uptake Inhibitors)
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Catecholamines)
RN  - 0 (Glucocorticoids)
RN  - 0 (Receptors, Adrenergic, beta)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 130068-27-8 (Interleukin-10)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - Adrenalectomy
MH  - Adrenergic Antagonists/pharmacology
MH  - Adrenergic Uptake Inhibitors/pharmacology
MH  - Animals
MH  - Anti-Inflammatory Agents/metabolism
MH  - Catecholamines/pharmacology
MH  - Glucocorticoids/pharmacology
MH  - Interleukin-10/*metabolism
MH  - Male
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Adrenergic, beta/metabolism
MH  - Sympathectomy
MH  - Time Factors
MH  - Tumor Necrosis Factor-alpha/*metabolism
EDAT- 2004/08/28 05:00
MHDA- 2005/04/14 09:00
CRDT- 2004/08/28 05:00
PHST- 2004/08/28 05:00 [pubmed]
PHST- 2005/04/14 09:00 [medline]
PHST- 2004/08/28 05:00 [entrez]
AID - jpet.104.073023 [pii]
AID - 10.1124/jpet.104.073023 [doi]
PST - ppublish
SO  - J Pharmacol Exp Ther. 2005 Jan;312(1):134-43. doi: 10.1124/jpet.104.073023. Epub 
      2004 Aug 26.