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Suppressive effect of TRH and antidepressants on human interferon-γ production in vitro

Published online by Cambridge University Press:  24 June 2014

Marta Kubera ,
Gunter Kenis ,
Agnieszka Basta-Kaim ,
Eugene Bosmans ,
Bogustawa Budziszewska ,
Simone Scharpe  and
Michael Maes
Marta Kubera*
Affiliation:
Department of Endocrinology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland
Gunter Kenis
Affiliation:
Department of Psychiatry, University Hospital of Maastricht, the Netherlands
Agnieszka Basta-Kaim
Affiliation:
Department of Endocrinology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland
Eugene Bosmans
Affiliation:
Eurogenetics, Tessenderlo, Belgium
Bogustawa Budziszewska
Affiliation:
Department of Endocrinology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland
Simone Scharpe
Affiliation:
Department of Medical Biochemistry, University of Antwerp, Edegem, Belgium
Michael Maes
Affiliation:
Department of Psychiatry, University Hospital of Maastricht, the Netherlands Clinical Research Center for Mental Health, Limburg, Belgium Department of Psychiatry, Vanderbilt University, Nashville, USA
*
Marta Kubera, Department of Endocrinology, Institute of Pharmacology, Polish Academy of Sciences, Smêtna 12, PL 31-343 Kraków, Poland. Tel: 48-12 637 40 22; E-mail: kubera@if-pan.krakow.pl
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Abstract

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-γ), tumor necrosis factor-alpha (TNF-α) 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-α and after 72 h for the assays of IFN-γ and IL-10. The three cytokines were assayed by ELISA methods.

Results:

A significant decrease in production of IFN-γ 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-γ production, and fluoxetine alone significantly decreases IFN-γ and TNF-α production.

Conclusion:

Although a significant decrease in IFN-γ 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.

Keywords

TRHantidepressantsTNF-αIFN-γIL-10
Type
Original Article
Information
Acta Neuropsychiatrica , Volume 14 , Issue 5 , October 2002 , pp. 226 - 230
Copyright
Copyright © Acta Neuropsychiatrica 2002

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