Abstract
In a controlled study, such immunological parameters as whole blood production of the cytokines interleukin-6 (IL-6) and tumor-necrosis factor-α (TNF-α) were assessed in 24 inpatients with a major depressive disorder (MDD) both before and again under treatment. After a 6-week treatment period with amitriptyline, patients were classified as responders or nonresponders according to their psychopathological outcome as evaluated by the Hamilton and the Montgomery–Asberg Depression Rating Scales. Pre-treatment levels of c-reactive protein (CRP) were significantly higher in both patient subgroups than in the control subjects. In comparison to the controls, unstimulated pretreatment production of IL-6 was significantly decreased in the responders; whereas it was significantly increased in the nonresponder subgroup. Post-treatment values did not differ significantly among the patient and control groups. Pretreatment levels of TNF-α were increased in both patient subgroups, with a significant decrease during treatment only in the responder subgroup. Pretreatment levels of IL-6/105 mononuclear cells and the ratio between lymphocytes and monocytes acted as independent variables with regard to the clinical response. Our data indicate that unstimulated secretion of TNF-α is related to the psychopathological improvement; whereas, IL-6 levels might dichotomize the patients into subsequent responders and nonresponders already at admission.
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References
American Psychiatric Association. (1994): Diagnostic and Statistical Manual of Mental Disorders IV (DSM IV). Washington, DC, the American Psychiatric Association
Berk M, Wadee AA, Kuschke RH, O'Neill-Kerr A . (1997): Acute phase proteins in major depression. J Psychosom Res 43: 529–534
Brambilla F, Maggioni M . (1998): Blood levels of cytokines in elderly patients with major depressive disorder. Acta Psychiat Scand 97: 309–313
Connor TJ, Leonard BE . (1998): Depression, stress, and immunological activation: The role of cytokines in depressive disorders. Life Sci 62: 583–606
Connor TJ, Song C, Leonard BE, Merali Z, Anisman H . (1998): An assessment of the effects of central interleukin-1β, -2, -6, and tumor necrosis factor-α administration on some behavioral, neurochemical, endocrine, and immune parameters in the rat. Neuroscience 84: 923–933
De Groote D, Gevaert Y, Lopez M, Gathy R, Fauchet F, Dehart I, Jadoul M, Radoux D, Franchimont P . (1993): Novel method for the measurement of cytokine production by a one-stage procedure. J Immunol Methods 163: 259–267
Frommberger UH, Bauer J, Haselbauer P, Raulin A, Riemann D, Berger M . (1997): Interleukin-6-(IL-6) plasma levels in depression and schizophrenia: Comparison between the acute state and after remission. Eur Arch Psychiat Clin Neurosci 247: 228–233
Hamilton M . (1960): A rating scale for depression. J Neurol Neurosurg Psychiat 23: 56–62
Maes M . (1995): Evidence for an immune response in major depression: A review and hypothesis. Prog Neuro-Psychopharmacol & Biol Psychiat 19: 11–38
Maes M, Bosman E, Suy E, Vandervorst C, De Jonckheere C, Raus J . (1991): Depression-related disturbances in mitogen-induced lymphocyte responses and interleukin-1β and soluble interleukin-2 receptor production. Acta Psychiat Scand 84: 379–386
Maes M, van der Planken M, Stevens WH . (1992): Leucocytosis, monocytosis, and neutrophilia: Hallmarks of severe depression. J Psychiat Res 26: 125–134
Maes M, Bosmans E, Meltzer HY, Scharpe S, Suy E . (1993): Interleukin-1β: A putative mediator of HPA axis hyperactivity in major depression? Am J Psychiat 150: 1189–1193
Maes M, Scharpe S, Meltzer HY, Okayli G, Bosmans E, D'Hondt P, Vanden Bossche V, Cosyns P . (1994): Increased neopterin and interferon-γ secretion and lower availability of L-tryptophan in major depression: Further evidence for an immune response. Psychiat Res 54: 143–160
Maes M, Vandoolaeghe E, Ranjan R, Bosmans E, Bergmans R, Desnyder A . (1995a): Increased serum interleukin-1-receptor-antagonist concentrations in major depression. J Affect Disord 36: 2–36
Maes M, Meltzer HY, Bosmans E, Bergmans R, Vandoolaeghe E, Ranjan R, Desnyder R . (1995b): Increased plasma concentrations of interleukin-6, soluble interleukin-6, soluble interleukin-2, and transferrin receptor in major depression. J Affect Disord 34: 301–309
Maes M, Bosmans E, De Jongh R, Kenis G, Vandoolaeghe E, Neels H . (1997): Increased serum IL-6 and IL-1 receptor antagonist concentrations in major depression and treatment-resistant depression. Cytokine 9: 853–858
McAdams LBE . (1993): Neutrophil and monocyte phagocytosis in depressed patients. Prog Neuropsychopharmacol Biol Psychiat 17: 971–984
Montgomery SA, Asberg M . (1979): A new depression scale designed to be sensitive to change. Br J Psychiat 134: 382–389
Müller N, Ackenheil M . (1998): Psychoneuroimmunology and the cytokine action in the CNS: Implications for psychiatric disorders. Prog Neuro-Psychopharmacol & Biol Psychiat 22: 1–33
Ravindran AV, Griffiths J, Merali Z, Anisman H . (1998): Circulating lymphocyte subsets in major depression and dysthymia with typical or atypical features. Psychosom Med 60: 283–289
Seidel A, Arold V, Hunstiger M, Rink L, Behnisch A, Kirchner H . (1995): Cytokine production and serum proteins in depression. Scand J Immunol 41: 534–538
Seidel A, Arolt V, Hunstiger M, Rink L, Behnisch A, Kirchner H . (1996): Major depressive disorder is associated with elevated monocyte counts. Acta Psychiat Scand 94: 198–204
Sluzewska A, Rybakowski J, Bosmans E, Sobieska M, Berghmans R, Maes M, Wiktorowicz K . (1996): Indicators of immune activation in major depression. Psychiat Res 64: 161–167
Sluzewska A, Rybakowski JK, Laciak M, Mackiewicz A, Sobieska M . (1995a): Interleukin-6 serum levels in depressed patients before and after treatment with fluoxetine. Ann NY Acad Sci 762: 474–476
Sluzewska A, Rybakowski JK, Sobieska M, Bosmans E, Pollet H, Wiktorowicz K . (1995b): Increased levels of α-1-acidic glycoprotein and interleukin-6 in refractory depression. Depression 3: 170–175
Vedder H, Schreiber W, Yassouridis A, Gudewill S, Galanos C, Pollmächer T . (1999): Dose-dependence of bacterial lipopolysaccharide (LPS) effects on the peak response and time course of the immune-endocrine host response in humans. Inflamm Res 48: 67–74
Weizman R, Laor N, Podliszewski E, Notti I, Djaldetti M, Bessler H . (1994): Cytokine production in major depressed patients before and after clomipramine treatment. Biol Psychiat 35: 42–47
Wittchen HU, Zaudig M, Fydrich T . (1995): Strukturiertes Klinisches Interview für DSM-IV (SKID-I und SKID-II). Göttingen, Hogrefe Verlag
Xia Z, DePierre JW, Nassberger L . (1996): Tricyclic antidepressants inhibit IL-6, IL-1β and TNF-α release in human blood monocytes and IL-2 and interferon-γ in T cells. Immunopharmacology 34: 27–37
Acknowledgements
We thank Mrs. C. Salmonson for her support with the final version of the manuscript, Mrs. A. Tittmar for her secretarial assistance, and D. Fischer-Barnicol for his considerable help with the acquisition of samples. The study was supported by grants from the “Deutsche Forschungsgemeinschaft” (SFB 297, Projekt A 6) and the “P. E. Kempkes Stiftung.”
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Lanquillon, S., Krieg, JC., Bening-Abu-Shach, U. et al. Cytokine Production and Treatment Response in Major Depressive Disorder. Neuropsychopharmacol 22, 370–379 (2000). https://doi.org/10.1016/S0893-133X(99)00134-7
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DOI: https://doi.org/10.1016/S0893-133X(99)00134-7
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