TY - JOUR
T1 - Evidence for an inhibitory immunomodulatory effect of selected antidepressants on rat splenocytes
T2 - Possible relevance to depression and hyperactive-immune disorders
AU - Taler, Michal
AU - Bar, Meytal
AU - Korob, Inna
AU - Lomnitski, Liat
AU - Baharav, Ehud
AU - Grunbaum-Novak, Nurit
AU - Weizman, Abraham
AU - Gil-Ad, Irit
PY - 2008/4
Y1 - 2008/4
N2 - Antidepressants have been found to possess antiproliferative 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 naïve rat. Rat splenocytes were activated with con A and treated with paroxetine, sertraline or clomipramine ex vivo. We found that the antidepressants inhibit cell viability and proliferation at IC50 of 5-8 μM 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 - TNFα. In addition, the antidepressants reduced the expression of the enzyme cyclooxygenase2 which is involved in inflammation. On the cellular level we show the up-regulation of MAPK death signaling pathway and suppression of the anti-apoptotic factor - Bcl-2. These findings reveal the immunomodulatory effect of the selected antidepressants. These data suggest a novel use of antidepressants or their derivatives.
AB - Antidepressants have been found to possess antiproliferative 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 naïve rat. Rat splenocytes were activated with con A and treated with paroxetine, sertraline or clomipramine ex vivo. We found that the antidepressants inhibit cell viability and proliferation at IC50 of 5-8 μM 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 - TNFα. In addition, the antidepressants reduced the expression of the enzyme cyclooxygenase2 which is involved in inflammation. On the cellular level we show the up-regulation of MAPK death signaling pathway and suppression of the anti-apoptotic factor - Bcl-2. These findings reveal the immunomodulatory effect of the selected antidepressants. These data suggest a novel use of antidepressants or their derivatives.
KW - Antidepressants
KW - Apoptosis
KW - Cytokines
KW - SSRIs
KW - Splenocytes
KW - TNFα
UR - http://www.scopus.com/inward/record.url?scp=39949085778&partnerID=8YFLogxK
U2 - 10.1016/j.intimp.2007.12.003
DO - 10.1016/j.intimp.2007.12.003
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C2 - 18328443
AN - SCOPUS:39949085778
SN - 1567-5769
VL - 8
SP - 526
EP - 533
JO - International Immunopharmacology
JF - International Immunopharmacology
IS - 4
ER -