Immunomodulatory Action of Fluoxetine in Normal and in Pathological Conditions: Controversies Regarding Malignant Processes

RAPANELLI M; FRICK LUCIANA ROMINA

Antidepressants: Pharmacology, Health Effects and Controversy

Nova Publishers

Año: 2012;

Antidepressants are used to alleviate mood disorders, such as major depression, dysthymia and anxiety. Among these drugs, selective serotonin reuptake inhibitors such as fluoxetine, act on neuronal cells by targeting the serotonin transporter prolonging the availability of this neurotransmitter on the synaptic space. In the past years, controversial evidences indicate that antidepressants can modulate non-neuronal cell types. Contradictory data indicate both stimulatory and inhibitory effects of antidepressants in immune cells as well as in tumor cells. First, antidepressants are able to reverse the alterations of the immune system observed in humans suffering depression as well as in animal models of stress. However, fluoxetine also has an effect per se on the immune cells in physiological conditions. Systemic and in vitro fluoxetine administration has been shown to both enhance and inhibit the immune function. The modulatory effect of fluoxetine on the immune function appears to depend on: a) the dose of antidepressant tested and b) the degree of lymphocyte activation. At least in part, this effect is dependent of serotonin reuptake. However, novel pathways that are in part independent of the fluoxetine action on the serotonin transporter are starting to emerge. Interestingly, several antidepressants induce apoptosis in certain kinds of tumors, but also stimulate proliferation on other cancer types. Fluoxetine is one of the most studied antidepressant in this scenario, and was found to affect tumor progression by specific and compensatory mechanisms, some of them seem to be mediated by its action upon the central nervous system, but others are executed directly on peripheral cells.