An assessment of the acute effects of the serotonin releasers methylenedioxymethamphetamine, methylenedioxyamphetamine and fenfluramine on immunity in rats

The purpose of the present study was to examine the effect of the serotonin releasing amphetamine derivatives methlenedioxymethamphetamine (MDMA), met hylenedioxyamphetamine (MDA) and fenfluramine (FEN) on immunity in rats. Si milar to MDA and MDMA, FEN reduced the number of circulating lymphocytes, p rovoked a suppression of Con A-stimulated lymphocyte proliferation and tota l IFN-gamma and IL-10 production in diluted whole blood cultures. Thus the non-psychostimulant amphetamine derivative FEN, shares the ability of the p sychostimulant methylenedioxy-substituted amphetamine derivatives to alter these indices of immune function in the rat. However, when Con A-stimulated cytokine production was normalised for the number of lymphocytes in cultur e in order to examine cytokine production at a cellular level, the effect o f the amphetamine derivatives begins to diverge. FEN shares with MDMA and M DA the ability to suppress production of the Th2 type cytokine IL-10. Howev er the effect of these drugs on Th1 type cytokine secretion was much more c omplex. While the methylendioxy-substituted amphetamines increases the secr etion of the Th1 type cytokine IL-2 without altering the related Th1 type c ytokine IFN-gamma, FEN did not alter IL-2 secretion, but suppressed IFN-gam ma secretion, in addition to these effects on T-cell responses, all three d rugs inhibited LPS-induced TNF-alpha secretion from diluted whole blood cul tures suggesting that macrophage activity is impaired following treatment. In all, these data extend our previous findings concerning the effects of M DMA on the immune system and demonstrate that the related serotonin release rs MDA and FEN also provoke immunological changes in rats. (C) 2000 Elsevie r Science B.V. All rights reserved.