PMID- 10983854
OWN - NLM
STAT- MEDLINE
DCOM- 20000922
LR  - 20190701
IS  - 0024-3205 (Print)
IS  - 0024-3205 (Linking)
VI  - 67
IP  - 13
DP  - 2000 Aug 18
TI  - Methylenedioxymethamphetamine (MDMA; Ecstasy) suppresses IL-1beta and TNF-alpha 
      secretion following an in vivo lipopolysaccharide challenge.
PG  - 1601-12
AB  - In this study we examined the effects of methylenedioxymethamphetamine (MDMA) 
      administration on responsiveness to an in vivo immune challenge with 
      lipopolysaccharide (LPS; 100 microg/kg; i.p.). LPS produced an increase in 
      circulating IL-1beta and TNF-alpha in control animals. MDMA (20 mg/kg; i.p.) 
      significantly impaired LPS-induced IL-1beta and TNF-alpha secretion. The 
      suppressive effect of MDMA on IL-1beta secretion was transient and returned to 
      control levels within 3 hours of administration. In contrast, the MDMA-induced 
      suppression of TNF-alpha secretion was evident for up to 12 hours following 
      administration. In a second study we examined the effect of co-administration of 
      MDMA (5, 10 and 20 mg/kg; i.p.) on LPS-induced IL-1beta and TNF-alpha secretion, 
      and demonstrated that all three doses potently suppressed LPS-induced TNF-alpha 
      secretion, but only MDMA 10 and 20 mg/kg suppressed LPS-induced IL-1beta 
      secretion. In addition, serum MDMA concentrations displayed a dose-dependent 
      increase, with the concentrations achieved following administration of 5 and 10 
      mg/kg being in the range reported in human MDMA abusers. In order to examine the 
      possibility that the suppressive effect of MDMA on IL-1beta and TNF-alpha could 
      be due to a direct effect of the drug on immune cells, the effect of in vitro 
      exposure to MDMA on IL-1beta and TNF-alpha production in LPS-stimulated diluted 
      whole blood was evaluated. However IL-1beta or TNF-alpha production were not 
      altered by in vitro exposure to MDMA. In conclusion, these data demonstrate that 
      acute MDMA administration impairs IL-1beta and TNF-alpha secretion following an 
      in vivo LPS challenge, and that TNF-alpha is more sensitive to the suppressive 
      effects of MDMA than is IL-1beta. However the suppressive effect of MDMA on 
      IL-1beta and TNF-alpha could not be attributed to a direct effect on immune 
      cells. The relevance of these findings to MDMA-induced immunomodulation is 
      discussed.
FAU - Connor, T J
AU  - Connor TJ
AD  - Department of Pharmacology, National University of Ireland, Galway. 
      thomas.connor@nuigalway.ie
FAU - Kelly, J P
AU  - Kelly JP
FAU - McGee, M
AU  - McGee M
FAU - Leonard, B E
AU  - Leonard BE
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Life Sci
JT  - Life sciences
JID - 0375521
RN  - 0 (Hallucinogens)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Interleukin-1)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - Animals
MH  - Dose-Response Relationship, Immunologic
MH  - Female
MH  - Hallucinogens/blood/*toxicity
MH  - Immunity, Cellular/drug effects
MH  - Immunosuppressive Agents/blood/*toxicity
MH  - Interleukin-1/blood/*metabolism
MH  - Lipopolysaccharides/antagonists & inhibitors/*pharmacology
MH  - N-Methyl-3,4-methylenedioxyamphetamine/blood/*toxicity
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Tumor Necrosis Factor-alpha/*metabolism
EDAT- 2000/09/13 11:00
MHDA- 2000/09/30 11:01
CRDT- 2000/09/13 11:00
PHST- 2000/09/13 11:00 [pubmed]
PHST- 2000/09/30 11:01 [medline]
PHST- 2000/09/13 11:00 [entrez]
AID - S0024320500007438 [pii]
AID - 10.1016/s0024-3205(00)00743-8 [doi]
PST - ppublish
SO  - Life Sci. 2000 Aug 18;67(13):1601-12. doi: 10.1016/s0024-3205(00)00743-8.