title: Citalopram suppresses thymocyte cytokine production.
abstract: Antidepressant drugs, in particular those targeting the serotonin (5-HT)-reuptake system via the serotonin transporter (5-HTT), are known to exhibit antiinflammatory properties and have demonstrated therapeutic efficacy in rodent models of autoimmune disease like experimental autoimmune encephalomyelitis or experimental rheumatoid arthritis. A crucial difference between animal models and the actual human autoimmune disease is the fact that in animals predominantly induced T cells are studied after sensitization with autoantigen. In humans, however, naturally occurring cytokine-producing T cells might play a significant role as well. For this reason, we investigated the effect of the selective serotonin reuptake inhibitor citalopram on cytokine-producing cells in the thymus of C57BL/6 mice, focusing on the (predominantly) T-cell-produced cytokines IL-2, IL-4 and IL-17. Citalopram was able to strongly reduce the frequency of IL-4- and IL-2-producing cells triggered by CD3 stimulation, but exhibited a less pronounced effect on IL-17-producing cells. 5-HTT expression was found to be very low in thymocytes in comparison with splenocytes, and the effect of free extracellular serotonin on CD3-induced thymocyte cytokine production did not mimic the effect of citalopram. We conclude that citalopram has a potent suppressive effect on cytokine production in the thymus, and that this effect is unlikely to be mediated by elevation of extracellular serotonin levels via the 5-HTT.
authors.affiliation: Department of Neurology, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany.
authors.forename: Aparna R
authors.initials: AR
authors.lastname: Shenoy
authors.forename: Thomas
authors.initials: T
authors.lastname: Dehmel
authors.forename: Mark
authors.initials: M
authors.lastname: Stettner
authors.forename: David
authors.initials: D
authors.lastname: Kremer
authors.forename: Bernd C
authors.initials: BC
authors.lastname: Kieseier
authors.forename: Hans Peter
authors.initials: HP
authors.lastname: Hartung
authors.forename: Harald H
authors.initials: HH
authors.lastname: Hofstetter
mesh_terms: D000818:Animals; D015283:Citalopram / Q000494:pharmacology*; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D020381:Interleukin-17 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D007376:Interleukin-2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D015847:Interleukin-4 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D060168:Thymocytes / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism
chemical_list: D016207:Cytokines; D007166:Immunosuppressive Agents; D020381:Interleukin-17; D007376:Interleukin-2; D015283:Citalopram; D015847:Interleukin-4
keywords: 5-HTT; Citalopram; Interleukin 17; Serotonin; Thymus