Effects of repeated fluoxetine and citalopram administration on cytokine release in C57BL/6 mice

This study examines the effects of repeated administration of the selective serotonin reuptake inhibitors (SSRIs), fluoxetine and citalopram (10 mg/kg , i.p.), on immunoreactivity in C57BL/6 mice. Immune functions were evaluat ed by the ability of splenocytes to reduce a tetrazolium salt to formazan ( MTT test), to proliferate, and to produce cytokines, including interleukin (IL)-1, IL-2, IL-4, IL-6, IL-10 and interferon gamma (IFN gamma). Citalopra m administered for 1, 2 and 3 weeks stimulates the proliferative activity o f splenocytes and suppresses their ability to secrete the anti-inflammatory cytokine IL-4. Fluoxetine administration for 1 and 2 weeks, but not 4 week s, stimulates the proliferative activity of splenocytes, whereas a 4-week a dministration of fluoxetine suppresses the secretion of IL-4. Four weeks of prolonged administration of citaloplam and fluoxetine induces a significan t increase in the production of IL-6 and IL-10, a cytokine with immunosuppr essive and anti-inflammatory activities. The results show that, in C57BL/6 mice, the immunomodulatory effects of SSRIs depend on the SSRI used and the duration of administration. (C) 2000 Elsevier Science Ireland Ltd. All rig hts reserved.