Cytokine Production in Depressed Patients

  • Andreas Seidel
  • Matthias Rothermundt
  • Lothar Rink
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 461)


Traditionally, the nervous, endocrine, and immune systeme have been regarded as separate systems both in clinical circumstances as well as in research. A concept of an interrelationship between the immune system and the nervous system, i.e. the psychological state, has been suggested before the first studies in psychoneuroimmunology have been conducted. Several authors implicated that mood disturbances may result in an increased susceptibility to infectious or neoplastic diseases (Ader, Feiten, & Cohen, 1991; Crow 1978; King, Cooper, Earle, Martin, McFerran, Rima, & Wisdom, 1985).


Natural Killer Cell Peripheral Blood Mononuclear Cell Major Depression Cytokine Production Depressive Patient 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Abbas, A. K., Lichtman, A. H., & Pober, J. S. (1991). Cellular and molecular immunology. Saunders Company, Philadelphia/USA.Google Scholar
  2. Ader, R., Felten, D. L., & Cohen, N. (1991). Psychoneuroimmunology, 2nd edition. Academic New York/USA.Google Scholar
  3. American Psychiatric Association (1994). DSM-IV Diagnostic and Statistical Manual of Mental Disorders, 4th edition.Google Scholar
  4. Bartfai, T.& Schultzberg, M. (dy1993). Cytokines in neuronal cell types. Neurochemistry International, 22, 435–444.PubMedCrossRefGoogle Scholar
  5. Bartrop, R.W., Lazarus, L., Luckhurst, E., Kiloh, L. G., & Penny, R. (1977). Depressed lymphocyte function after bereavement. The Lancet, 834–836.Google Scholar
  6. Brambilla, F.& Maggioni, M. (1998). Blood levels of cytokines in eldery patients with major depressive disorder. Acta Psychiatrica Scandinavica, 97, 309–331.PubMedCrossRefGoogle Scholar
  7. Baumann, H.& Gauldie, J. (1994). The acute phase response. Immunology today, 15, 74–80.PubMedCrossRefGoogle Scholar
  8. Connor, T. J. & Leonard, B. E. (1997). Depression, stress and immunological activation: The role of cytokines in depressive disorders. Life Sciences, 62, 583–606.CrossRefGoogle Scholar
  9. Crow, T. J. (1978). Viral causes of psychiatric disease. Postgraduate Medical Journal, 54, 763–767.PubMedGoogle Scholar
  10. Cserr, H. F. & Knopf, P. M. (1992). Cervical lymphatics, the blood-brain barrier and the immunoreactivity of the brain: a new view. Immunology today, 13, 507–512.PubMedCrossRefGoogle Scholar
  11. Cunningham, E. T. jr & De Souza, E. B. (1993). Interleukin 1 receptors in the brain and endocrine tissues. Immunology today, 14, 171–176.PubMedCrossRefGoogle Scholar
  12. Darko, D. F., Rose, J., Gillin, J. C., Golshan, S., & Baird, S. M. (1988). Neutophilia and lymphocytopenia in major mood disorders. Psychiatry Research, 25, 243–251.PubMedCrossRefGoogle Scholar
  13. Darko, D. F., Wilson, N. W., Gillin, J. C., & Golshan, S. (1991). A critical appraisal of mitogen induced lymphocyte proliferation in depressed patients. American Journal of Psychiatry, 148, 337–344.PubMedGoogle Scholar
  14. DeGroote, D., Zangerle, P. F., Gevaert, Y., Fassotte, M. F, Beguin, Y., Noizat-Pirenne, F., Pirenne, J., Gathy, R., Lopez, M., Dehart, I., Igot, D., Baudrihaye, M., Delacroix, D., & Franchimont, P. (1992). Direct Stimulation of Cytokines in whole blood. 1. Comparison with isolated PBMC stimulation. Cytokine, 3, 239–248.CrossRefGoogle Scholar
  15. Denicoff, K. D., Rubinow, D. R., & Papa, M. Z. (1987). The neuropsychiatric effects of treatment with interleukin-2 and lymphokine-activated killer cells. Annals of Internal Medicine, 107, 293–300.PubMedGoogle Scholar
  16. Denney, D. R., Stephenson, L. A., Penick, E. C., & Weller, R. A. (1988). Lymphocyte subclasses and depression. Journal of Abnormal Psychology, 97, 499–502.PubMedCrossRefGoogle Scholar
  17. Evans, D. L., Folds, J. D., Pettito, J. M., Golden, R. N., Pedersen, C. A., Corrigan, M., Gilmore, J. H., Silva, S. G., Quade, D., & Ozer, H. (1992). Circulating natural killer cell phenotypes in men and women with major depression. Archives of General Psychiatry, 49, 388–395.PubMedGoogle Scholar
  18. Fabry, Z., Raine, C. S., & Hart, M. N. (1994). Nervous tissue as an immune compartment: the dialect of the immune response in the CNS. Immunology today, 15, 218–224.PubMedCrossRefGoogle Scholar
  19. Frombonne, E. (1995). Increased rates of depression: Update of epidemiological findings and analytical problems. Acta Psychiatrica Scandinavica, 90, 145–156.CrossRefGoogle Scholar
  20. Frommberger, U. H., Bauer, J., Haselbauer, P., Fraulin, A., Riemann, D., & Berger, M. (1997). Interleukin-6 (IL-6) plasma levels in depression and schizophrenia: comparison between the acute state and after remission. European Archives of Psychiatry and Clinical Neuroscience, 247, 228–233.PubMedGoogle Scholar
  21. Goetzel, E. J. & Sreedharan, S. P. (1992). Mediators of communication and adaptation in the neuroendocrine and immune systems. FASEB, J, 6, 2646–2652.Google Scholar
  22. Gold, P. W., Goodwin, F. K., & Chrousos, G. P. (1988). Clinical and biochemical manifestations of depression—part I & part II. New England Journal of Medicine, (part I) 319, 413–420; (part II) 319, 348–353.PubMedCrossRefGoogle Scholar
  23. Griffiths, J., Ravindran, A. V., Merali, Z., & Anisman, H. (1996). Society of Neurosciences, Abstract, 22, 1350.Google Scholar
  24. Hickey, W. F. (1991). Migration of hematogenous cells through the blood-brain barrier and the initiation of CNS inflammation. Brain Pathology, 1, 97–105.PubMedGoogle Scholar
  25. Homo-Delarche, F. & Dardenne, M. (1993). The neuroendocrine-immune axis. Springer Sem Immunopathol, 14, 221–238.Google Scholar
  26. Hopkins, S. J. & Rothwell, N. J. (1995). Interactions between cytokines and the nervous system. Trends in Neurosciences, 18, 83–88.PubMedCrossRefGoogle Scholar
  27. Irwin, M., Caldwell, C., Smith, T. L., Brown, S., Schuckit, M. A., & Gillin, J. C. (1990). Major depressive disorder, alcoholism and reduced natural killer cell cytotoxicity. Archives in General Psychiatry, 47, 713–718.Google Scholar
  28. James, K. (1990). Interactions between cytokines and α2-macroglobulin. Immunology today, 11, 163–166.PubMedCrossRefGoogle Scholar
  29. Joyce, P. R., Hawes, C. R., Mulder, R.T., Sellman, J. D., Wilson, D. A., & Boswell, D. R. (1992). Elevated levels of acute phase proteins in major depression. Biological Psychiatry, 32, 1035–1041.PubMedCrossRefGoogle Scholar
  30. King, D. J., Cooper, S. J., Earle, J. A. P., Martin, S. J., McFerran, N. V., Rima, B. K., & Wisdom, G. B. (1985). A survey of serum antibodies to eight common viruses in psychiatric patients. British Journal of Psychiatry, 147, 137–144.PubMedGoogle Scholar
  31. Kirchner, H., Kleinicke, C., & Digel, W. J. (1982). A whole blood technique for testing production of human interferon by leukocytes. Journal of Immunology Methods, 48, 213–219.CrossRefGoogle Scholar
  32. Kraepelin, E. (1899). Compendium der Psychiatrie, Leipzig.Google Scholar
  33. Kronfol, Z., Turner, R., Nasrallah, H., & Winokur, G. (1984). Leukocyte regulation in depression and schizophrenia. Psychiatry Research, 13, 13–18.PubMedCrossRefGoogle Scholar
  34. Landmann, R., Schaub, B., Link, S., & Wacker, H. R. (1997). Unaltered monocyte function in patients with major depession before and after three months of antidepressive therapy. Biological Psychiatry, 41, 675–681.PubMedCrossRefGoogle Scholar
  35. Lehtinen, V. & Joukamaa, M. (1994). Epidemiology of depression: Prevalence, risk factors and treatment situation. Acta Psychiatrica Scandinavica Supplement, 377, 157–167.Google Scholar
  36. Maes, M., Bosmans, E., Vandervorst, C., DeJonckheere, C., & Raus, J. (1990). Immune disturbances during major depression: upregulated expression of interleukin-2 receptors. Neuropsychobiology, 24, 115–120.PubMedCrossRefGoogle Scholar
  37. Maes, M., Bosmans, E., Suy, E., Vandervorst, C., DeJonckheere, C., & Raus, J. (1991). Depression-related disturbances in mitogen-induced lymphocyte responses and interleukin-lβ and soluble interleukin-2 receptor production. Acta Psychiatrica Scandinavica, 84, 379–386.PubMedCrossRefGoogle Scholar
  38. Maes, M., Lambrechts, J., Bosmans, E., Jacobs, J., Suy, E., Vandervorst, C., DeJonckheere, C., Minner, B., & Raus, J. (1992a). Evidence for a systemic immune activation during depression: results of leukocyte enumeration by flow cytometry in conjunction with monoclonal antibody staining. Psychological Medicine, 22, 45–53.PubMedCrossRefGoogle Scholar
  39. Maes, M., Van der Planken, M., Stevens, W. J., Peeters, D., DeClerck, L. S., Bridts, C. H., Schotte, C., & Cosyns, P. (1992b). Leukocytosis, monocytosis and neutrophilia: hallmarks of servere depression. Journal of Psychiatry Research, 26, 125–134.CrossRefGoogle Scholar
  40. Maes, M., Bosmans, E., Meltzer, H. Y., Scharpe, S., & Suy, E. (1993a). Interleukin-1β: a putative mediator of HPA axis hyperactivity in major depression?. American Journal of Psychiatry, 150, 1189–1193.PubMedGoogle Scholar
  41. Maes, M., Scharpe, S., Meltzer, H. Y., & Cosyns, P. (1993b). Relationship between increased haptoglobin plasma levels and activation of cell-mediated immunity in depression. Biological Psychiatry, 34, 690–701.PubMedCrossRefGoogle Scholar
  42. Maes, M., Scharpe, S., Meltzer, H. Y, Okayli, G., Bosmans, E., D’Hondt, P., Vanden Bossche, B. V., & Cosyns, P. (1994). Increased neopterin and interferon-gamma secretion and lower availability of L-tryptophan in major depression: further evidence for an immune response. Psychiatry Research, 54, 153–160.CrossRefGoogle Scholar
  43. Maes, M. (1995). Evidence for an immune response in major depression: a review and hypothesis. Progress in Neuropsychopharmacology and Biological Psychiatry, 19, 11–38.CrossRefGoogle Scholar
  44. Maes, M., Bosmans, E., DeJongh, R., Kenis, G., Vandoolaeghe, E., & Neels, H. (1997). Increased serum IL-6 and IL-1 receptor antagonist concentrations in major depression and treatment resistent depression. Cytokine, 9, 853–858.PubMedCrossRefGoogle Scholar
  45. McAdams, C. & Leonard, B. E. (1993). Neutrophil and monocyte phagocytosis in depressed patients. Progress in Neuropsychopharmacology and Biological Psychiatry, 17, 971–984.CrossRefGoogle Scholar
  46. McDonald, E. M., Mann, A. H., & Thomas, H. C. (1987). Interferons as mediators of psychiatric morbidity. The Lancet, 1175–1177.Google Scholar
  47. Meyers, C. A. & Valentine, A. D. (1995). Neurological and psychiatric adverse effects of immunological therapy. CNS drugs, 3, 56–68.Google Scholar
  48. Müller, N., Hofschuster, E., Ackenheil, M., Mempel, & Eckstein, R. (1993). Investigations of the cellular immunity during depression and the free interval: evidence for an immune activation in active psychosis. Progress in Neuropsychopharmacology and Biological Psychiatry, 17, 713–730.CrossRefGoogle Scholar
  49. Owens, T., Renno, T., Taupin, V., & Krakowski, M. (1994). Inflammatory cytokines in the brain: does the CNS shape immune responses? Immunology today, 15, 566–571.PubMedCrossRefGoogle Scholar
  50. Patrizio, M., Costa, T., & Levi, G. (1995). Interferon-γ and lipopolysaccharide reduce cAMP response in cultured glial cells: reversal by type IV phosphodiesterase inhibitor. Glia, 14, 94–100.PubMedCrossRefGoogle Scholar
  51. Powrie, F. & Coffman, R. L. (1993). Cytokine regulation of T-cell function: potential for therapeutic intervention. Immunology today, 14, 210–214.CrossRefGoogle Scholar
  52. Ravindran, A. V, Griffiths, J., Merali, Z., & Anisman, H. (1995). Lymphocyte subsets associated with major depression and dysthymia: modification by antidepressant treatment. Psychosomatic Medicine, 57, 555–563.PubMedGoogle Scholar
  53. Roitt, I. M., Brostoff, J., & Male, D. K. (1989). Immunology. Gower Medical Publishing, London.Google Scholar
  54. Rosenstein, E. D., Kunicka, J., Kramer, N., & Goldstein, G. (1994). Modification of cytokine production by piroxicam. Journal of Rheumatology, 21, 904–904.Google Scholar
  55. Rothwell, N. J. & Hopkins, S. J. (1995). Interactions between cytokines and the nervous system. Trends in Neurosciences, 18, 130–136.PubMedCrossRefGoogle Scholar
  56. Schleifer, S. J., Keller, S. E., Meyerson, A. T., Raskin, M. J., Davis, K. L., & Stein, M. (1984). Lymphocyte function in major depressive disorder. Archives of General Psychiatry, 41, 484–486.PubMedGoogle Scholar
  57. Seidel, A., Arolt, V., Hunstiger, M., Rink, L., Behnisch, A., & Kirchner, H. (1995). Cytokine production and serum proteins in depression. Scandinavian Journal of Immunology, 41, 434–538.CrossRefGoogle Scholar
  58. Seidel, A., Arolt, V., Hunstiger, M., Rink, L., Behnisch, A., & Kirchner, H. (1996a). Major depressive disorder is associated with elevated monocyte counts. Acta Psychiatrica Scandinavica, 94, 198–204.PubMedCrossRefGoogle Scholar
  59. Seidel, A., Arolt, V., Hunstiger, M., Rink, L., Behnisch, A., & Kirchner, H. (1996b). Increased CD56+ natural killer cells and related cytokines in major depression. Clinical Immunology and Immunopathology, 78, 83–85.PubMedCrossRefGoogle Scholar
  60. Sluzewska, A., Rybakowski, J., Bosmans, E., Sobieska, M., Berghmans, R., Maes, M., & Wiktorowicz, K. (1996). Indicators of immune activation in major depression. Psychiatry Research, 64, 161–167.PubMedCrossRefGoogle Scholar
  61. Smith, R. S. (1991). The macrophage theory of depression. Medical Hypotheses, 35, 298–306.PubMedCrossRefGoogle Scholar
  62. Stein, M., Miller, A. H., & Trestman, R. T. (1991). Depression, the immune system, and health and illness. Archives of General Psychiatry, 48, 171–177.PubMedGoogle Scholar
  63. Targum, S. D., Clarkson, L. L., Magac-Harris, K., Marshall, L. E., & Skwerer, R. G. (1990). Measurement of cortisol and lymphocyte subpopulations in depressed and conduct-disordered adolescents. Journal of Affective Disorders, 18, 91–96.PubMedCrossRefGoogle Scholar
  64. Taylor, A. W. & Mortensen, R. F. (1991). Effect of alpha-2-macroglobulin on cytokine-mediated human C-reactive protein production. Inflammation, 15, 61–70.PubMedCrossRefGoogle Scholar
  65. Ulvestad, E., Williams, K., Matre, R., Nyland, H., Olivier, A., & Antel, J. (1994). Fc receptors for IgG on cultured human microglia mediate cytotoxicity and phagocytosis of antibody-coated targets. Journal of Neuropathology and Experimental Neurology, 53, 27–36.PubMedGoogle Scholar
  66. Weizman, R., Laor, N., Podliszewski, E., Notti, I., Djaldetti, M., & Bessler, H. (1994). Cytokine production in major depressed patients before and after clomipramine treatment. Biological Psychiatry, 35, 42–41.PubMedCrossRefGoogle Scholar
  67. Wekerle, H., Engelhardt, B., Risau, W., & Meyermann, R. (1991). Interaction of lymphocytes with cerebral endothelial cells in vitro. Brain Pathology, 1, 107–114.PubMedGoogle Scholar
  68. World Health Organisation ICD-10 (1994). Mental disorders: tenth revision of the International Classification of diseases. Geneva: WHO.Google Scholar
  69. Yong, V. W. & Balasingam, V. (1995). Cytokines as mediatiors of reactive astrogliosis. Methods in Neurosciences, 24, 220–235.Google Scholar

Copyright information

© Kluwer Academic/Plenum Publishers 1999

Authors and Affiliations

  • Andreas Seidel
    • 1
  • Matthias Rothermundt
    • 2
  • Lothar Rink
    • 1
  1. 1.Institute of Immunology and Transfusion MedicineGermany
  2. 2.Department of PsychiatryUniversity of Lübeck School of MedicineLübeckGermany

Personalised recommendations