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Fluoxetine reduces murine graft-versus-host disease by induction of T cell immunosuppression

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Abstract
Serotonin reuptake inhibitors (SRIs) are widely used drugs in the treatment of depression and anxiety disorders. Although SRIs are generally regarded as safe drugs with relatively few side effects, literature suggests that high concentrations of SRIs may alter immune function. We investigated whether high-dose treatment with fluoxetine was able to suppress acute graft-versus-host disease (GvHD) in a MHC-matched, minor histocompatibility antigen mismatched murine bone marrow transplantation model. We found that high doses fluoxetine induce a significant reduction of clinical symptoms and increase survival of these animals. The amelioration of clinical GvHD was accompanied by a reduced expansion of alloreactive T cells. We further analyzed the direct in vitro effect of six SRIs on the viability and proliferation of human T cells and found an anti-proliferative and pro-apoptotic effect that was significantly larger in activated than in resting T cells. We discuss these results in the light of potential future exploration of SRIs as a novel class of T cell immunosuppressive drugs.
Keywords
INTERFERON-GAMMA, LYMPHOCYTE PROLIFERATION, BONE-MARROW CHIMERAS, SEROTONIN REUPTAKE INHIBITORS, EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS, T cells, Immunosuppression, Graft-versus-host disease, Serotonin reuptake inhibitors, Fluoxetine, ANTIDEPRESSANTS, TRANSPORTER, DEPRESSION, CITALOPRAM, SERTRALINE

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Chicago
Gobin, Veerle, Katleen Van Steendam, Sabine Fevery, Kelly Tilleman, An D Billiau, Damiaan Denys, and Dieter Deforce. 2013. “Fluoxetine Reduces Murine Graft-versus-host Disease by Induction of T Cell Immunosuppression.” Journal of Neuroimmune Pharmacology 8 (4): 934–943.
APA
Gobin, V., Van Steendam, K., Fevery, S., Tilleman, K., Billiau, A. D., Denys, D., & Deforce, D. (2013). Fluoxetine reduces murine graft-versus-host disease by induction of T cell immunosuppression. JOURNAL OF NEUROIMMUNE PHARMACOLOGY, 8(4), 934–943.
Vancouver
1.
Gobin V, Van Steendam K, Fevery S, Tilleman K, Billiau AD, Denys D, et al. Fluoxetine reduces murine graft-versus-host disease by induction of T cell immunosuppression. JOURNAL OF NEUROIMMUNE PHARMACOLOGY. 2013;8(4):934–43.
MLA
Gobin, Veerle, Katleen Van Steendam, Sabine Fevery, et al. “Fluoxetine Reduces Murine Graft-versus-host Disease by Induction of T Cell Immunosuppression.” JOURNAL OF NEUROIMMUNE PHARMACOLOGY 8.4 (2013): 934–943. Print.
@article{3208433,
  abstract     = {Serotonin reuptake inhibitors (SRIs) are widely used drugs in the treatment of depression and anxiety disorders. Although SRIs are generally regarded as safe drugs with relatively few side effects, literature suggests that high concentrations of SRIs may alter immune function. We investigated whether high-dose treatment with fluoxetine was able to suppress acute graft-versus-host disease (GvHD) in a MHC-matched, minor histocompatibility antigen mismatched murine bone marrow transplantation model. We found that high doses fluoxetine induce a significant reduction of clinical symptoms and increase survival of these animals. The amelioration of clinical GvHD was accompanied by a reduced expansion of alloreactive T cells. We further analyzed the direct in vitro effect of six SRIs on the viability and proliferation of human T cells and found an anti-proliferative and pro-apoptotic effect that was significantly larger in activated than in resting T cells. We discuss these results in the light of potential future exploration of SRIs as a novel class of T cell immunosuppressive drugs.},
  author       = {Gobin, Veerle and Van Steendam, Katleen and Fevery, Sabine and Tilleman, Kelly and Billiau, An D and Denys, Damiaan and Deforce, Dieter},
  issn         = {1557-1890},
  journal      = {JOURNAL OF NEUROIMMUNE PHARMACOLOGY},
  keyword      = {INTERFERON-GAMMA,LYMPHOCYTE PROLIFERATION,BONE-MARROW CHIMERAS,SEROTONIN REUPTAKE INHIBITORS,EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS,T cells,Immunosuppression,Graft-versus-host disease,Serotonin reuptake inhibitors,Fluoxetine,ANTIDEPRESSANTS,TRANSPORTER,DEPRESSION,CITALOPRAM,SERTRALINE},
  language     = {eng},
  number       = {4},
  pages        = {934--943},
  title        = {Fluoxetine reduces murine graft-versus-host disease by induction of T cell immunosuppression},
  url          = {http://dx.doi.org/10.1007/s11481-013-9463-7},
  volume       = {8},
  year         = {2013},
}

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