Effect of Fluoxetine and Clomipramine on T-cell Proliferation

MARÍA LAURA PALUMBO; ANDRÉS ORQUEDA; LUCIANA R FRICK; GRACIELA A CREMASCHI; ANA MARÍA GENARO

Madrid, España

Congreso; 2nd Iberoamerican Congress on Neuroimmunomodulation; 2007

International Society for Neuroimmunomodulation

Drugs that target the serotoninergic system are the most commonly prescribed therapeutic agents and are used for treatment of a wide range of behavioral and neurological disorders.  These drug effects on immune responses were described related to their capacity to inhibit serotonin reuptake. In order to ascertain if these drugs are able to modulate the proliferative response by a direct mechanism we analyzed fluoxetine and  clomipramine effects on mitogen-induced T-cell proliferation.  We observed that serotonin was able to stimulate the suboptimal Con A-induced proliferation and to inhibit the optimal one at all concentrations tested. The serotonin stimulatory, but not the inhibitory effect was suppressed by a HT-2 antagonist ketanserine. Low doses of fluoxetine were able to stimulate proliferation induced by sub-mitogenic concentrations of Con A but inhibit the optimal lectin induced proliferation.  Low and high doses of clomipramine stimulated sub-optimal and inhibited optimal proliferation. Serotonin decreased inhibitory and increased stimulatory effect of fluoxetine.  However, serotonin  only impaired the clomipramine stimulatory effect on proliferation. Also, ketanserine impaired clomipramine, but not fluoxetine, stimulatory effect. These results indicate that fluoxetine and clomipramine are able to regulate T-cell proliferation by different serotonin-dependent and independent mechanisms underlining a complex cross-talk between this drugs and serotonin pathways.