title: Fluoxetine directly counteracts the adverse effects of chronic stress on T cell immunity by compensatory and specific mechanisms.
abstract: Chronic stress and depression are widely known to down-regulate the immune system, and several antidepressants can reverse this impairment, with or without effects in normal subjects. Although the central nervous system is undoubtedly involved in these events, some psychotropic drugs can also exert direct effects on lymphoid cells. We have recently shown that the antidepressant fluoxetine enhances T cell proliferation and T(H)1 cytokine production in vivo, without changes on CD4/CD8 subsets. In vitro, a direct action of fluoxetine upon T lymphocyte reactivity by complex mechanisms was also described. In another work, we also found that chronic stress reduces T cell mediated immunity, namely a decrease of T cell response to mitogens, T(H)1 cytokine production and CD4+-but not CD8+--T lymphocytes. Here we investigated the effects of fluoxetine on chronic stress-driven immune system depression. We found that fluoxetine restored T cell proliferation and interleukin-2, interferon-gamma and tumor necrosis factor-alpha production by compensatory mechanisms. In addition, CD4/CD8 ratio was also normalized by antidepressant administration, but this seems to be a non-compensatory effect associated specifically to stress. No changes were observed in other lymphoid cells, i.e. natural killer cells and B lymphocytes. Finally, we observed that fluoxetine is able to reverse T cell reactivity impairment in vitro by a direct action at clinically relevant doses. These results highlight the relevance of pharmacological treatment of stress and depression, and may help to begin elucidating the complex events triggered--directly and/or indirectly--by antidepressants in non-neuronal cell types.
authors.affiliation: Centro de Estudios Farmacológicos y Botánicos, Consejo Nacional de Investigaciones Científicas y Técnicas, 1 degrees Cátedra de Farmacología, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina. lfrick@fmed.uba.ar
authors.forename: Luciana Romina
authors.initials: LR
authors.lastname: Frick
authors.forename: Maximiliano
authors.initials: M
authors.lastname: Rapanelli
authors.forename: Graciela Alicia
authors.initials: GA
authors.lastname: Cremaschi
authors.forename: Ana María
authors.initials: AM
authors.lastname: Genaro
mesh_terms: D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000008:administration & dosage / Q000627:therapeutic use; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002908:Chronic Disease; D005260:Female; D005434:Flow Cytometry; D005473:Fluoxetine / Q000008:administration & dosage / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000235:genetics; D007376:Interleukin-2 / Q000235:genetics; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D012149:Restraint, Physical / Q000009:adverse effects / Q000379:methods; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013315:Stress, Psychological / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D018687:Antidepressive Agents, Second-Generation; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D005473:Fluoxetine; D007371:Interferon-gamma