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Fluoxetine action upon human T lymphocyte proliferation

V Ayelli Edgar1, A M Genaro, G A Cremaschi

  • 1Centro de Estudios Farmacológicos y Botánicos (CEFYBO), Consejo Nacional de Investigaciones Científicas y Técnológicas (CONICET), Buenos Aires, Argentina.

Acta Physiologica, Pharmacologica Et Therapeutica Latinoamericana : Organo De La Asociacion Latinoamericana De Ciencias Fisiologicas Y [De] La Asociacion Latinoamericana De Farmacologia
|January 23, 1999
PubMed
Summary

Fluoxetine shows a dual effect on human T lymphocyte proliferation, inhibiting it at high activation levels while stimulating it at lower levels. This modulation involves protein kinase C (PKC) and cyclic adenosine monophosphate (cAMP) pathways.

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Area of Science:

  • Immunology
  • Pharmacology
  • Cell Biology

Background:

  • T lymphocytes play a crucial role in immune responses.
  • Fluoxetine is a selective serotonin reuptake inhibitor with potential immunomodulatory effects.
  • Understanding drug effects on immune cells is vital for therapeutic applications.

Purpose of the Study:

  • To investigate the impact of fluoxetine on human T lymphocyte proliferation.
  • To analyze early signaling events, including cyclic adenosine monophosphate (cAMP) formation, following T cell activation.
  • To assess the role of Protein Kinase C (PKC) in fluoxetine's immunomodulatory effects.

Main Methods:

  • Human T lymphocytes were isolated from normal volunteers.
  • Cells were cultured with or without Concanavalin A (Con A) and fluoxetine.

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  • Measurements included cellular proliferation, Protein Kinase C (PKC) levels, and cyclic adenosine monophosphate (cAMP) formation.
  • Main Results:

    • Fluoxetine inhibited T lymphocyte proliferation at mitogenic Con A concentrations (2 µg/ml), associated with PKC degradation and increased cAMP.
    • Fluoxetine stimulated T lymphocyte response and increased PKC translocation at submitogenic Con A concentrations (1 µg/ml).
    • Extracellular calcium mobilization and subsequent modulation of calcium influx appear to be involved in these effects.

    Conclusions:

    • Fluoxetine exhibits dose-dependent immunomodulatory effects on human T lymphocytes.
    • The mechanisms involve modulation of PKC translocation and cAMP formation, potentially influenced by calcium influx.
    • Fluoxetine may modulate the immune response through intricate signaling pathways involving T cells.