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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 TH1 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, TH1 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-γ and tumor necrosis factor-α 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. © 2008 Elsevier Inc. All rights reserved.


Documento: Artículo
Título:Fluoxetine directly counteracts the adverse effects of chronic stress on T cell immunity by compensatory and specific mechanisms
Autor:Frick, L.R.; Rapanelli, M.; Cremaschi, G.A.; Genaro, A.M.
Filiación:Centro de Estudios Farmacológicos y Botánicos, Consejo Nacional de Investigaciones Científicas y Técnicas, Cátedra de Farmacología, Paraguay 2155, Buenos Aires 1121, Argentina
Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas, Vuelta de Obligado 2490, Buenos Aires, 1428, Argentina
Palabras clave:Antidepressant; B cells; CD4/CD8; Chronic stress; Cytokines; Depression; Fluoxetine; Natural killer; T cells; concanavalin A; fluoxetine; gamma interferon; interleukin 2; tumor necrosis factor alpha; animal cell; animal experiment; animal model; animal tissue; article; CD4 CD8 ratio; cell proliferation; cellular immunity; chronic stress; controlled study; depression; drug mechanism; female; in vitro study; nonhuman; priority journal; T lymphocyte; Animals; Antidepressive Agents, Second-Generation; B-Lymphocytes; CD4-CD8 Ratio; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cell Proliferation; Chronic Disease; Female; Flow Cytometry; Fluoxetine; Interferon-gamma; Interleukin-2; Killer Cells, Natural; Mice; Mice, Inbred BALB C; Restraint, Physical; Reverse Transcriptase Polymerase Chain Reaction; Stress, Psychological; T-Lymphocytes; Tumor Necrosis Factor-alpha
Página de inicio:36
Página de fin:40
Título revista:Brain, Behavior, and Immunity
Título revista abreviado:Brain Behav. Immun.
CAS:concanavalin A, 11028-71-0; fluoxetine, 54910-89-3, 56296-78-7, 59333-67-4; gamma interferon, 82115-62-6; interleukin 2, 85898-30-2; Antidepressive Agents, Second-Generation; Fluoxetine, 54910-89-3; Interferon-gamma, 82115-62-6; Interleukin-2; Tumor Necrosis Factor-alpha


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---------- APA ----------
Frick, L.R., Rapanelli, M., Cremaschi, G.A. & Genaro, A.M. (2009) . Fluoxetine directly counteracts the adverse effects of chronic stress on T cell immunity by compensatory and specific mechanisms. Brain, Behavior, and Immunity, 23(1), 36-40.
---------- CHICAGO ----------
Frick, L.R., Rapanelli, M., Cremaschi, G.A., Genaro, A.M. "Fluoxetine directly counteracts the adverse effects of chronic stress on T cell immunity by compensatory and specific mechanisms" . Brain, Behavior, and Immunity 23, no. 1 (2009) : 36-40.
---------- MLA ----------
Frick, L.R., Rapanelli, M., Cremaschi, G.A., Genaro, A.M. "Fluoxetine directly counteracts the adverse effects of chronic stress on T cell immunity by compensatory and specific mechanisms" . Brain, Behavior, and Immunity, vol. 23, no. 1, 2009, pp. 36-40.
---------- VANCOUVER ----------
Frick, L.R., Rapanelli, M., Cremaschi, G.A., Genaro, A.M. Fluoxetine directly counteracts the adverse effects of chronic stress on T cell immunity by compensatory and specific mechanisms. Brain Behav. Immun. 2009;23(1):36-40.