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Regulation of Murine T-Lymphocyte Function by Spleen Cell-Derived and Exogenous Serotonin
Authors:Joseph L Kut  M Rita  I Young  John W Crayton  Mark A Wright  Mel E Young
Institution:  a Departments of Research Service, Hines V.A. Hospital, Hines, IL b Department of Pathology, Loyola University Stritch School of Medicine, Maywood, IL c Departments of Biological Psychiatry, Hines V.A. Hospital, Hines, IL
Abstract:The modulatory effects of serotonin on T-cell activity were investigated. T-cell blastogenesis of normal spleen cells was slightly stimulated by the addition of low doses (1 and 10 ng/ml) of the inducer of serotonin release, fenfluramine. In contrast to the stimulatory effects of low doses of fenfluramine, high doses of fenfluramine (1 and 10 ug/ml) or of exogenously added serotonin (≥0.1 ug/ml) inhibited T-cell activation. Both the stimulation by low dose fenfluramine and the inhibition by high dose fenfluramine were accentuated by pretreating mice with tryptophan to heighten intracellular stores of serotonin and then inducing serotonin release. Pretreatment of mice with the serotonin inhibitor p-cholorphenylalanine (PCPA) abolished the fenfluramine inhibition of T-cell activation indicating that the fenfluramine inhibitory effect was mediated via endogenous spleen cell-derived serotonin. However, the PCPA treatment diminished T-cell activation. These results suggest that endogenous serotonin causes a biphasic dose-response effect on T-cell activity with serotonin being required for optimal T-cell function, low doses being immune stimulatory and higher doses being suppressive.

Con-A, concanavain A

5-HT, 5-hydroxytryptamine

LAK, lymphokine-activated killer

NK, natural killer

PCPA, p-cholorphenylalanine

PHA, phytohemagglutinin
Keywords:
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