Serotonin Modulates Immune Function in T Cells from HIV-Seropositive Subjects

• Published in: Clinical immunology and immunopathology 1997-08, Vol.84 (2), p.115-121
• Main Authors: Eugen-Olsen, Jesper, Afzelius, Pia, Andresen, Lars, Iversen, Johan, Kronborg, Gitte, Aabech, Peter, Nielsen, Jens Ole, Hofmann, Bo
• Format: Article
• Language: English
• Subjects: 8-Hydroxy-2-(di-n-propylamino)tetralin - pharmacology; AIDS/HIV; Biological and medical sciences; CD4-Positive T-Lymphocytes - metabolism; CD8-Positive T-Lymphocytes - metabolism; Cells, Cultured; Cyclic AMP - blood; HIV Seropositivity - blood; HIV Seropositivity - immunology; Humans; Immunity, Cellular - drug effects; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunopathology; Interferon-gamma - genetics; Interleukin-2 - genetics; Lymphocyte Activation - drug effects; Medical sciences; Polymerase Chain Reaction; Receptors, Serotonin - blood; RNA, Messenger - biosynthesis; RNA-Directed DNA Polymerase; Serotonin - blood; Serotonin - pharmacology; Serotonin Receptor Agonists - pharmacology; T-Lymphocytes - immunology
• ISSN: 0090-1229; 1090-2341
• DOI: 10.1006/clin.1997.4384

We have shown earlier increased intracellular levels of cAMP in peripheral lymphocytes from HIV-seropositive subjects and that a chemically induced decrease in this level increases cell proliferation and cytotoxicity. Others have shown that serotonin indirectly decreases intracellular cAMP levels in normal peripheral lymphocytes. In this study, we show that addition of serotonin decreases intracellular levels of cAMP in lymphocytes from HIV-seropositive subjects and significantly increases the proliferative capacityin vitro.However, the effect of serotonin varies with the initial proliferative response; e.g., those with the highest initial responses have the highest increases. An increase in IL-2 production may be a part of this mechanism since addition of serotonin toin vitrocultures of PHA-stimulated cells increases the expression of mRNA for IL-2 and IFN-γ. The effect on lymphocyte proliferation was most likely mediated through the serotonin 5HT1a receptor because similar results could be obtained by using DPAT, a specific activator of this receptor. Changes in the expression of 5HT1a receptors as judged by the expression of mRNA could not explain why serotoninin vitrohad a stronger enhancing effect on cell proliferation in some HIV-seropositive individuals than in others.