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Suppressive effect of TRH and antidepressants on human interferon-gamma production in vitro
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| Background: It has been established that thyrotropin-releasing hormone (TRH) affects several aspects of immunoreactivity, e.g. production of proinflammatory cytokines. It has been shown that TRH enhances the therapeutic efficiency of classical tricyclic antidepressants. Proinflammatory cytokines may play a role in the etiology of depression, whereas the therapeutic efficacy of antidepressants may be related to their negative immunoregulatory effects. Objective: In order to verify the hypothesis that TRH-induced increase of therapeutic efficiency of classical tricyclic antidepressants results from synergistic inhibitory effects of these agents on the secretion of proinflammatory cytokines, we determine the effect of imipramine or fluoxetine with and without TRH on the production of interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) by stimulated human whole blood cells. Methods: Diluted whole blood of 17 volunteers was incubated with imipramine or fluoxetine (both in doses of 10(-5) M) with or without TRH (in a dose of 10(-5) M). The supernatants were collected 24 h later for the assay of TNF-alpha. and after 72 h for the assays of IFN-gamma and IL-10. The three cytokines were assayed by ELISA methods. Results: A significant decrease in production of IFN-gamma was observed in cells stimulated with mitogens and co-incubated with imipramine or fluoxetine and TRH. Under the same conditions, TRH alone did not change the production of these cytokines, whereas imipramine alone significantly decreases IFN-gamma production, and fluoxetine alone significantly decreases IFN-gamma and TNF-alpha production. Conclusion: Although a significant decrease in IFN-gamma production was observed after Joint application of TRH and antidepressants, our data did not support the above-mentioned hypothesis. Indeed, we did not observe synergistic inhibitory effects of these agents on the secretion of proinflammatory cytokines. | | |
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English
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Acta neuropsychiatrica. - Leiderdorp | |
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Leiderdorp : 2002
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0924-2708
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14:5(2002), p. 226-230
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000179769100005
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