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 evaluated 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). Citalopram administered for 1, 2 and 4 weeks stimulates the proliferative activity of splenocytes and suppresses their ability to secrete the anti-inflammatory cytokine IL-4. Fluoxetine administration for 1 and 2 weeks, but not 4 weeks, stimulates the proliferative activity of splenocytes, whereas a 4-week administration of fluoxetine suppresses the secretion of IL-4. Four weeks of prolonged administration of citalopram and fluoxetine induces a significant increase in the production of IL-6 and IL-10, a cytokine with immunosuppressive 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.
Kubera
M
M
Department of Endocrinology, Institute of Pharmacology, Polish Academy of Sciences, Smêtna 12, 31-343 Kraków, Poland.
Simbirtsev
A
A
Mathison
R
R
Maes
M
M
D000704:Analysis of Variance; D000818:Animals; D015283:Citalopram / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D016207:Cytokines / Q000096:biosynthesis* / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005473:Fluoxetine / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D007111:Immunity, Cellular / Q000187:drug effects; D007371:Interferon-gamma / Q000096:biosynthesis / Q000187:drug effects; D007375:Interleukin-1 / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*
D015283:Citalopram; D016207:Cytokines; D005473:Fluoxetine; D007371:Interferon-gamma; D007375:Interleukin-1; D016753:Interleukin-10; D007376:Interleukin-2; D015847:Interleukin-4; D015850:Interleukin-6; D017367:Selective Serotonin Reuptake Inhibitors