Fluoxetine treatment to rats modifies serotonin transporter and cAMP in lymphocytes, CD4+ and CD8+ subpopulations and interleukins 2 and 4

Serotonin Transporter in Lymphocytes of Rats Exposed to Physical Restraint Stress

“…Moreover, the effect of fluoxetine has been observed to be dual; depending on the degree of cell activation, it stimulates at low and inhibits at higher concentrations of mitogen [36]. This finding could result from the interaction of positive and negative regulatory factors coupled to activation of 5-HT 1A and 5-HT 7 [39] among other 5-HT receptors subtypes present in T cells and probably stimulated by the increase of extracellular 5-HT when its reuptake is inhibited by fluoxetine. Frick et al [21] observed that therapeutic doses of fluoxetine counteracts the inhibitory effect of chronic restraint stress on Con A-stimulated proliferation of murine T lymphocytes.…”

“…Although several immune modulatory effects of fluoxetine have been reported in lymphocytes [39] and dendritic cells [22], little is known about how this selective serotonin reuptake inhibitor and stress could comodulate immune function. Roman et al [47] found that concomitant administration of fluoxetine, at low doses, and amantadine (a noncompetitive glutamate NMDA receptor antagonist) can modulate the activity of peritoneal macrophages of rats subjected to forced swimming.…”

“…These observations support the idea that SERT is a key target of stress in the immune system, as it is in the central nervous system. In addition, fluoxetine has a modulatory effect on the production of cytokines and lymphocyte proliferation in response to Con A [39]. In the presence of stressful conditions, this modulation could be affected through changes in the expression and function of SERT.…”

Immunomodulatory Effect of Sertraline in a Rat Model of Rheumatoid Arthritis

“…A change in the cytokine milieu was also observed in the form of an increase in the IL-4/IL-2 ratio, indicating reduced lymphocyte activation and proliferation capacity. Exposure to fluoxetine in a more recent study decreased the concentration of cAMP [45]. In ex vivo experiments, the addition of fluoxetine and the tricyclic antidepressant amitriptyline to synovial cell cultures derived from patients with RA inhibited the production of inflammatory mediators such as nitric oxide and prostaglandin E 2 [46].…”

Fluoxetine Promotes Remission in Acute Experimental Autoimmune Encephalomyelitis in Rats

“…Fluoxetine can decrease the production of pro-inflammatory cytokines such as interferon (IFN)-γ and tumor necrosis factor (TNF)-α, and increase that of interleukin (IL)-10, an anti-inflammatory cytokine [2]. It was also demonstrated that fluoxetine decreased cAMP concentrations in lymphocytes and suppressed lymphocyte proliferation [3]. In addition, fluoxetine was also found to have anti-inflammatory effects in the CNS.…”