Selective serotonin reuptake inhibitors, such as fluoxetine, have recently been shown to exert anti-inflammatory and immunosuppressive effects. Although the effects on cytokine secretion, proliferation and viability of T lymphocytes have been extensively characterized, little is known about the mechanism behind these effects. It is well known that Ca2+ signaling is an important step in the signaling transduction pathway following T cell receptor activation. Therefore, we investigated if fluoxetine interferes with Ca2+ signaling in Jurkat T lymphocytes. Fluoxetine was found to suppress Ca2+ signaling in response to T cell receptor activation. Moreover, fluoxetine was found to deplete intracellular Ca2+ stores, thereby leaving less Ca2+ available for release upon IP3- and ryanodine-receptor activation. The Ca2+-modifying effects of fluoxetine are not related to its capability to block the serotonin transporter, as even a large excess of 5HT did not abolish the effects. In conclusion, these data show that fluoxetine decreases IP3- and ryanodine-receptor mediated Ca2+ release in Jurkat T lymphocytes, an effect likely to be at the basis of the observed immunosuppression.
Gobin, V., De Bock, M., Broeckx, B. J. G., Kiselinova, M., De Spiegelaere, W., Vandekerckhove, L., … Deforce, D. (2015). Fluoxetine suppresses calcium signaling in human T lymphocytes through depletion of intracellular calcium stores. Cell Calcium, 58(3), 254–263. https://doi.org/10.1016/j.ceca.2015.06.003