title: Suppressive effect of TRH and antidepressants on human interferon-γ production in vitro.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 1Department of Endocrinology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Kubera
authors.affiliation: 2Department of Psychiatry, University Hospital of Maastricht, the Netherlands.
authors.forename: Gunter
authors.initials: G
authors.lastname: Kenis
authors.affiliation: 1Department of Endocrinology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Basta-Kaim
authors.affiliation: 3Eurogenetics, Tessenderlo, Belgium.
authors.forename: Eugene
authors.initials: E
authors.lastname: Bosmans
authors.affiliation: 1Department of Endocrinology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
authors.forename: Bogustawa
authors.initials: B
authors.lastname: Budziszewska
authors.affiliation: 4Department of Medical Biochemistry, University of Antwerp, Edegem, Belgium.
authors.forename: Simone
authors.initials: S
authors.lastname: Scharpe
authors.affiliation: 2Department of Psychiatry, University Hospital of Maastricht, the Netherlands.
authors.forename: Michael
authors.initials: M
authors.lastname: Maes