RESUMO
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.
Assuntos
Antidepressivos/farmacologia , Clomipramina/farmacologia , Linfócitos/efeitos dos fármacos , Paroxetina/farmacologia , Sertralina/farmacologia , Animais , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Ciclo-Oxigenase 2/metabolismo , Feminino , Doenças do Sistema Imunitário/tratamento farmacológico , Doenças do Sistema Imunitário/imunologia , Doenças do Sistema Imunitário/metabolismo , Ativação Linfocitária , Linfócitos/citologia , Linfócitos/imunologia , Linfócitos/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Ratos Endogâmicos Lew , Baço/citologia , Baço/efeitos dos fármacos , Baço/imunologia , Fator de Necrose Tumoral alfa/imunologia , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Antidepressants facilitate neuroplasticity by stimulating trophic factors. This study evaluated the effect of fluoxetine (FLX) treatment on insulin-like growth factor-1 (IGF-1) in the rat brain and its role in the effect of FLX on cognition. IGF-1 receptor (IGF-1R) protein expression and IGF-1 mRNA levels were assessed in rat frontal cortex (FC) and hippocampus, in FLX-treated [15 mg/kg, orally; 3 (acute) or 21 (repeated) days] male Wistar rats. Rats were subjected to the Morris Water Maze test. Acute FLX administration decreased IGF-1 mRNA levels in the FC and hippocampus and increased IGF-1R levels in the FC. Repeated FLX increased both mRNA and IGF-1R levels in the FC. Repeated, but not acute, FLX treatment decreased IGF-1 mRNA in the hippocampus. FLX did not affect cognitive performance. Thus, repeated FLX treatment leads to upregulation of IGF-1 system is FC. It is possible that FLX affect FC neuroplasticity through activation of the IGF-1 system.