Evidence for an inhibitory immunomodulatory effect of selected antidepressants on rat splenocytes: possible relevance to depression and hyperactive-immune disorders.
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 microM 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--TNFalpha. 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.
Taler
Michal
M
Laboratory of Biological Psychiatry, Felsenstein Medical Research Center and Sackler Faculty of Medicine, Tel-Aviv University, Israel. michalt@post.tau.ac.il
Bar
Meytal
M
Korob
Inna
I
Lomnitski
Liat
L
Baharav
Ehud
E
Grunbaum-Novak
Nurit
N
Weizman
Abraham
A
Gil-Ad
Irit
I
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002997:Clomipramine / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D005260:Female; D007154:Immune System Diseases / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D017374:Paroxetine / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D020280:Sertraline / Q000494:pharmacology*; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
D000928:Antidepressive Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D014409:Tumor Necrosis Factor-alpha; D017374:Paroxetine; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D020928:Mitogen-Activated Protein Kinases; D002997:Clomipramine; D020280:Sertraline