Hostname: page-component-78c5997874-ndw9j Total loading time: 0 Render date: 2024-11-19T13:25:00.071Z Has data issue: false hasContentIssue false
  • English
  • Français

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: [email protected]
Get access Rights & Permissions [Opens in a new window]

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

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Matsumoto, A, Kumagai, T, Takeuchi, T, Myazaki, S, Watanabe, K. Clinical effects of thyrotropin-releasing hormone for severe epilepsy in childhood: a comparative study with ACTH therapy. Epilepsia 1987;28: 49–55.CrossRefGoogle ScholarPubMed
Tsuboyama, GK, Gabriel, SS, Davies, BM, Davison, M, Lawlor, BA, Ware, K, Davis, K, Mohs, RC. Neuroendocrine disfunction in Alzheimer's disease: results following TRH stimulation. Biol Psychiatry 1993;32: 195–198. CrossRefGoogle Scholar
Kastin, AJ, Ehrensing, Rh, Schalch, DS, Anderson, MS. Improvement in mental depression with decreased thyrotropin response after administration of thyrotropin-releasing hormone. Lancet 1972;2: 740–742.CrossRefGoogle ScholarPubMed
Philpot, VB Jr.Thyrotropin-releasing hormone in a patient with bipolar disorder [letter]. J Neuropsychiatr Clin Neurosci 1993;5: 349–350. Google Scholar
Drago, F, Pulvirenti, L, Spadaro, F, Pennisi, G. Effects of TRH and prolactin in the behavioral despair (swim) model of depression in rats. Psychoneuroendocrinol 1990;15: 349–356. CrossRefGoogle Scholar
Reny-Palasse, V, Rips, R. Potentiation by TRH of the effect of imipramine on the forced-swimming test. Br J Pharmacol 1985;85: 463–470.CrossRefGoogle Scholar
Bennett, GW, Green, AR, Lighton, C, Marsden, CA. Changes in behavioural response to a TRH analogue following chronic amitriptyline treatment and repeated electroconvulsive shock in the rat. Br J Pharmacol 1986;88: 129–139.CrossRefGoogle ScholarPubMed
Rastogi, RB, Singhal, RL, Lapierre, YD. Effects of MK-771, a novel TRH analog, on brain dopaminergic and serotonergic system. Brain Res Bull 1981;7: 307–312. Google Scholar
Mitsuma, T, Nogimori, T. Influence of the route of administration on thyrotropin-releasing hormone concentration in mouse brain. Experientia 1983;39: 620–622.CrossRefGoogle ScholarPubMed
Yirmiya, R, Weidenfeld, J, Pollak, Y, Morag, M, Morag, A, Avitsur, R, Baraqk, O, Reichenberg, A, Cohen, E, Shavit, Y, Ovadia, H. Cytokines, ‘depression due to a general medical condition’, and antidepressant drugs. In: Dantzer, R, Wollman, EE, Yirmiya, Ret al. eds. Cytokines, Stress, and Depression. New York: Kluwer Academic/Plenum Publishers, 1999: 283–316.CrossRefGoogle Scholar
Maes, M, Song, C, Lin, A, De Longh, R, Van Gastel, A, Kenis, Get al. The effect of psychological stress on humans: Increased production of pro-inflammatory cytokines and Th-1 like response in stress-induced anxiety. Cytokine 1998;10: 313–318.CrossRefGoogle Scholar
Kubera, M, Holan, V, Basta-Kaim, A, Roman, A, Borycz, J, Shani, J. Effect of desipramine on immunological parameters in mice, and their reversal by stress. Int J Immunopharmacol 1998;20: 429–438.CrossRefGoogle ScholarPubMed
Kubera, M, Lin, A-H, Kenis, G, Bosmans, E, Van Bockstaele, D, Maes, M. Anti-inflammatory effects of antidepressants through suppression of the interferon-g/interleukin-10 production ratio. J Clin Psychopharmacol 2001;21: 199–206.CrossRefGoogle Scholar
Kubera, M, Symbirtsev, A, Basta-Kaim, A, Borycz, J, Roman, A, Papp, M, Claesson, M. Effect of chronic treatment with imipramine on interleukin 1 and interleukin 2 production by splenocytes obtained from rats subjected to a chronic mild stress model of depression. Pol J Pharmacol 1996;48: 503–506.Google ScholarPubMed
Kubera, M, Kenis, G, Bosmans, E, Jaworska-Feil, L, Lasoñ, W, Scharpe, S, Maes, M. Suppressive effect of TRH and imipramine on human interferon-gamma and interleukin-10 production in vitro. Pol J Pharmacol 2000;52: 481–486.Google ScholarPubMed
Xia, Z, Depierre, JW, Nassberger, L. Tricyclic antidepressants inhibit IL-6, IL-1β and TNFα release in human blood monocytes and IL-2 and interferon-γ in T cells. Immunopharmacol 1996;34: 27–37. CrossRefGoogle Scholar
Lanquillon, S, Krieg, JC, Bening-Abu-Shach, U, Vedder, H. Cytokine production and treatment response in major depressive disorder. Neuropsychopharmacol 2000;22: 370–379. CrossRefGoogle ScholarPubMed
Kubera, M, Cyrul, W, Basta-Kaim, A, Budziszewska, B, Leskiewicz, M, Holan, V. Effect of repeated desipramine and fluoxetine administration on post-adjuvant arthritis. Pol J Pharmacol 2000;52: 229–235.Google ScholarPubMed
Pawlikwski, M, Zerek-Melen, G, Winczyk, K. Thyrotropin (TRH) increases thymus cell proliferation in rats. Neuropeptides 1992;23: 199–202.CrossRefGoogle Scholar
Pierpaoli, W, Yi, C. The involvement of pineal gland and melatonin in immunity and aging. I. Thymus-mediated, immunoreconstituting and antiviral activity of thyrotropin-releasing hormone. J Neuroimmunol 1990;27: 99–109.CrossRefGoogle ScholarPubMed
Lesnikov, VA, Korneva, EA, Dall'Ara, A, Pierpaoli, W. Involvement of pineal gland and melatonin in immunity and aging. II. Thyrotropin releasing hormone and melatonin forestall involution and promote reconstitution of the thymus in the anterior hypothalamic area (AHA)-lesioned mice. Int Neurosci 1992;62: 141–153. CrossRefGoogle ScholarPubMed
Kruger, TE, Smith, LR, Harbour, DV, Blalock, JE. Thyrotropin: an endogenous regulator of the in vitro immune response. J Immunol 1989;142: 744–747.Google ScholarPubMed
Raiden, S, Polack, E, Nahmod, V, Labeur, M, Holsboer, F, Arzt, E. TRH receptor on immne cells: in vitro and in vivo stimulation of human lymphocyte and rat splenocyte synthesis by TRH. J Clin Immunol 1995;15: 242–249.CrossRefGoogle Scholar
Lersh, C, Hammer, C, Krombach, F, Dancygier, H. Effect of thyrotropin-releasing hormne (TRH) on the chemiluminescence (cl) activity of human mononuclear cells. J Clin Laboratory Immunol 1989;28: 69–71. Google Scholar
Hart, R, Wagner, F, Steffens, W, Lersch, C, Dancygier, H, Duntas, L, Classen, M. Effect of thyrotropin-releasing hormone on immune functions of peripheral blood mononuclear cells. Regul Pept 1990;27: 335–342.CrossRefGoogle ScholarPubMed
Kunert-Radek, J, Pawlikowski, M, Stêpieñ, H, Janecka, A. Inhibitory effect of thyrotropin releasing hormone on spontaneous proliferation of mouse spleen lymphocytes in vitro. Biochem Biophys Res Comm 1991;181: 562–565.CrossRefGoogle ScholarPubMed
Ramsdell, JS. Thyrotropin-releasing hormone inhibits GH4 pituitary cell proliferation by blocking entery into S phase. Endocrinology 1990;126: 472–479.CrossRefGoogle Scholar
Grasso, G, Massai, L, De Leo, V. The effect of LHRH and TRH on human interferon-γ production in vivo and in vitro. Life Sci 1998;62: 2005–2014.CrossRefGoogle ScholarPubMed