Evidence for an inhibitory immunomodulatory effect of selected antidepressants on rat splenocytes: Possible relevance to depression and hyperactive mmune disorders

Antidepressants have been found to possess antiprotiferative effect. In the immune system depression may activate pro-inflammatory cytokines. Therefore, the aim of this study was to assess the immunomodulatory activity of antidepressants in naive rat. Rat splenocytes were activated with con A and treated with paroxetine, sertraline or ciomipramine ex vivo. We found that the antidepressants inhibit cell viability and proliferation at IC50 of 5-8 mu M of mitogen-stimulated rat splenocytes. This inhibitory effect was accompanied by cell cycle arrest and increase in apoptotic events as assayed by FACS. Moreover, antidepressants decrease the secretion of the TH1 factor - TNF alpha. In addition, the antidepressants reduced the expression of the enzyme cyclooxygenase2 which is involved in inflammation. On the cellular level we show the up-regutation of MAPK death signaling pathway and suppression of the anti-apoptotic factor Bcl-2. These findings reveal the immunomodutatory effect of the selected antidepressants. These data suggest a novel use of antidepressants or their derivatives. (c) 2008 Elsevier B.V. All rights reserved.