Methylenedioxymethamphetamine (MDMA; Ecstasy) suppresses IL-1 beta and TNF-alpha secretion following an in vivo lipopolysaccharide challenge

In this study we examined the effects of methylenedioxymethamphetamine (MDM A) administration on responsiveness to an in vivo immune challenge with lip opolysaccharide (LPS; 100 mu g/kg; i.p.). LPS produced an increase in circu lating IL-1 beta and TNF-alpha in control animals. MDMA (20 mg/kg; i.p.) si gnificantly impaired LPS-induced IL-1 beta and TNF-alpha secretion. The sup pressive effect of MDMA on IL-1 beta secretion was transient and returned t o control levels within 3 hours of administration. In contrast, the MDMA-in duced suppression of TNF-alpha secretion was evident for up to 12 hours fol lowing administration. In a second study we examined the effect of cu-admin istration of MDMA (5, 10 and 20 mg/kg; i.p.) on LPS-induced IL-1 beta and T NF-alpha secretion, and demonstrated that all three doses potently suppress ed LPS-induced TNF-alpha secretion, but only MDMA 10 and 20 mg/kg suppresse d LPS-induced IL-1 beta secretion. In addition, serum MDMA concentrations d isplayed a dose-dependent increase, with the concentrations achieved follow ing administration of 5 and 10 mg/kg being in the range reported in human M DMA abusers. In order to examine the possibility that the suppressive effec t of MDMA on IL-1 beta 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-1 beta and TNF-alpha production in LPS-stimulated diluted whole blood was evaluat ed. However IL-1 beta or TNF-alpha production were not altered by in vitro exposure to MDMA. in conclusion, these data demonstrate that acute MDMA adm inistration impairs IL-1 beta and TNF-alpha secretion following an in vivo LPS challenge, and that TNF-alpha is more sensitive to the suppressive effe cts of MDMA than is IL-1 beta. However the suppressive effect of MDMA on IL -1 beta 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. (C) 2000 Elsevier Science Inc. All rights reserved.