Neuroimmune Correlates of Sleep in Depression: Role of Cytokines

  • J. Szelényi
  • E.S. Vizi


Sleep is an integrate part of mammalian life, although the sleeping patterns of different species significantly differ in amounts and pattern. However, it is not an independent variable because, during sleep, almost every physiologic parameter changes relative to wakefulness (Lavie 2001). Insomnia is rather frequent; its prevalence is between 10 and 50% of the general population, depending on the methods used to assess sleep problems and on the population studied (Ohayon and Caulet 1996). In addition, many psychiatric disorders (e.g., depression) as well as various medical conditions including infectious, malignant and inflammatory diseases, are associated with disordered sleep (Benca and Quintas 1997; Bloom, Owens, McGuinn, Nobile, Schaeffer, and Alario 2002).


Proinflammatory Cytokine Sleep Deprivation Norepinephrine Transporter Sleep Regulation Cytokine Balance 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Abrass, C.K., O'Connor, S.W., Scarpace, P.J., and Abrass, I.B. (1985) Characterization of the beta-adrenergic receptor of the rat peritoneal macrophage. J Immunol 135, 1338–1341.PubMedGoogle Scholar
  2. Akiyoshi, M., Shimizu, Y., and Saito, M. (1990) Interleukin-1 increases norepinephrine turnover in the spleen and lung in rats. Biochem Biophys Res Commun 173, 1266–1270.PubMedGoogle Scholar
  3. Alexandre, C., Popa, D., Fabre, V., Bouali, S., Venault, P., Lesch, K.P., Hamon, M., and Adrien, J. (2006) Early life blockade of 5–hydroxytryptamine 1A receptors normalizes sleep and depression-like behavior in adult knock-out mice lacking the serotonin transporter. J Neurosci 26, 5554–5564.PubMedGoogle Scholar
  4. Asadullah, K., Sabat, R., Friedrich, M., Volk, H.D., and Sterry, W. (2004) Interleukin-10: An important immunoregulatory cytokine with major impact on psoriasis. Curr Drug Targets Inflamm Allergy 3, 185–192.PubMedGoogle Scholar
  5. Aszalos, Z. (2006) Effects of antidepressants on sleep. Orv Hetil 147, 773–783.PubMedGoogle Scholar
  6. Banks, W.A., Ortiz, L., Plotkin, S.R., and Kastin, A.J. (1991) Human interleukin (IL) 1 alpha, murine IL-1 alpha and murine IL-1 beta are transported from blood to brain in the mouse by a shared saturable mechanism. J Pharmacol Exp Ther 259, 988–996.PubMedGoogle Scholar
  7. Benca, R.M., and Quintas, J. (1997) Sleep and host defenses: A review. Sleep 20, 1027–1037.PubMedGoogle Scholar
  8. Benedetti, F., Lucca, A., Brambilla, F., Colombo, C., and Smeraldi, E. (2002) Interleukine-6 serum levels correlate with response to antidepressant sleep deprivation and sleep phase advance. Prog Neuropsychopharmacol Biol Psychiatry 26, 1167–1170.PubMedGoogle Scholar
  9. Besedovsky, H., del Rey, A., Sorkin, E., and Dinarello, C.A. (1986) Immunoregulatory feedback between interleukin-1 and glucocorticoid hormones. Science 233, 652–654.PubMedGoogle Scholar
  10. Besedovsky, H.O., and del Rey, A. (1996) Immune-neuro-endocrine interactions: Facts and hypotheses. Endocr Rev 17, 64–102.PubMedGoogle Scholar
  11. Besedovsky, H.O., del Rey, A., Klusman, I., Furukawa, H., Monge Arditi, G., and Kabiersch, A. (1991) Cytokines as modulators of the hypothalamus-pituitary-adrenal axis. J Steroid Biochem Mol Biol 40, 613–618.PubMedGoogle Scholar
  12. Bierhaus, A., Wolf, J., Andrassy, M., Rohleder, N., Humpert, P.M., Petrov, D., Ferstl, R., von Eynatten, M., Wendt, T., Rudofsky, G., Joswig, M., Morcos, M., Schwaninger, M., McEwen, B., Kirschbaum, C., and Nawroth, P.P. (2003) A mechanism converting psychosocial stress into mononuclear cell activation. Proc Natl Acad Sci U S A 100, 1920–1925.PubMedGoogle Scholar
  13. Bloom, B.J., Owens, J.A., McGuinn, M., Nobile, C., Schaeffer, L., and Alario, A.J. (2002) Sleep and its relationship to pain, dysfunction, and disease activity in juvenile rheumatoid arthritis. J Rheumatol 29, 169–173.PubMedGoogle Scholar
  14. Bonnet, M.H., and Arand, D.L. (1995) 24-Hour metabolic rate in insomniacs and matched normal sleepers. Sleep 18, 581–588.PubMedGoogle Scholar
  15. Bourne, H.R., Lichtenstein, L.M., Melmon, K.L., Henney, C.S., Weinstein, Y., and Shearer, G.M. (1974) Modulation of inflammation and immunity by cyclic AMP. Science 184, 19–28.PubMedGoogle Scholar
  16. Braat, H., Peppelenbosch, M.P., and Hommes, D.W. (2003) Interleukin-10-based therapy for inflammatory bowel disease. Expert Opin Biol Ther 3, 725–731.PubMedGoogle Scholar
  17. Breder, C.D., Hazuka, C., Ghayur, T., Klug, C., Huginin, M., Yasuda, K., Teng, M., and Saper, C.B. (1994) Regional induction of tumor necrosis factor alpha expression in the mouse brain after systemic lipopolysaccharide administration. Proc Natl Acad Sci U S A 91, 11393–11397.PubMedGoogle Scholar
  18. Bylund, D.B., Eikenberg, D.C., Hieble, J.P., Langer, S.Z., Lefkowitz, R.J., Minneman, K.P., Molinoff, P.B., Ruffolo, R.R., Jr., and Trendelenburg, U. (1994) International Union of Pharmacology nomenclature of adrenoceptors. Pharmacol Rev 46, 121–136.PubMedGoogle Scholar
  19. Capuron, L., and Miller, A.H. (2004) Cytokines and psychopathology: Lessons from interferon-alpha. Biol Psychiatry 56, 819–824.PubMedGoogle Scholar
  20. Chen, A.C., Shirayama, Y., Shin, K.H., Neve, R.L., and Duman, R.S. (2001) Expression of the cAMP response element binding protein (CREB) in hippocampus produces an antidepressant effect. Biol Psychiatry 49, 753–762.PubMedGoogle Scholar
  21. Chong, Y.H., Shin, Y.J., and Suh, Y.H. (2003) Cyclic AMP inhibition of tumor necrosis factor alpha production induced by amyloidogenic C-terminal peptide of Alzheimer's amyloid precursor protein in macrophages: Involvement of multiple intracellular pathways and cyclic AMP response element binding protein. Mol Pharmacol 63, 690–698.PubMedGoogle Scholar
  22. Clement, H.W., Buschmann, J., Rex, S., Grote, C., Opper, C., Gemsa, D., and Wesemann, W. (1997) Effects of interferon-gamma, interleukin-1 beta, and tumor necrosis factor-alpha on the serotonin metabolism in the nucleus raphe dorsalis of the rat. J Neural Transm 104, 981–991.PubMedGoogle Scholar
  23. Collier, J., and Chapman, R. (2001) Combination therapy with interferon-alpha and ribavirin for hepatitis C: Practical treatment issues. BioDrugs 15, 225–238.PubMedGoogle Scholar
  24. Connor, T.J., Dennedy, M.C., Harkin, A., and Kelly, J.P. (2001) Methylenedioxymethamphetamine- induced suppression of interleukin-1beta and tumour necrosis factor-alpha is not mediated by serotonin. Eur J Pharmacol 418, 147–152.PubMedGoogle Scholar
  25. Corcos, M., Guilbaud, O., Hjalmarsson, L., Chambry, J., and Jeammet, P. (2002) Cytokines and depression: An analogic approach. Biomed Pharmacother 56, 105–110.PubMedGoogle Scholar
  26. Dantzer, R. (2004) Cytokine-induced sickness behaviour: A neuroimmune response to activation of innate immunity. Eur J Pharmacol 500, 399–411.PubMedGoogle Scholar
  27. del Rey, A., Besedovsky, H.O., Sorkin, E., da Prada, M., and Arrenbrecht, S. (1981) Immunoregulation mediated by the sympathetic nervous system, II. Cell Immunol 63, 329–334.PubMedGoogle Scholar
  28. Denicoff, K.D., Rubinow, D.R., Papa, M.Z., Simpson, C., Seipp, C.A., Lotze, M.T., Chang, A.E., Rosenstein, D., and Rosenberg, S.A. (1987) The neuropsychiatric effects of treatment with interleukin-2 and lymphokine-activated killer cells. Ann Intern Med 107, 293–300.PubMedGoogle Scholar
  29. Dinarello, C.A. (1998) Interleukin-1, interleukin-1 receptors and interleukin-1 receptor antagonist. Int Rev Immunol 16, 457–499.PubMedGoogle Scholar
  30. Dinges, D.F., Douglas, S.D., Hamarman, S., Zaugg, L., and Kapoor, S. (1995) Sleep deprivation and human immune function. Adv Neuroimmunol 5, 97–110.PubMedGoogle Scholar
  31. Dodt, C., Breckling, U., Derad, I., Fehm, H.L., and Born, J. (1997) Plasma epinephrine and norepinephrine concentrations of healthy humans associated with nighttime sleep and morning arousal. Hypertension 30, 71–76.PubMedGoogle Scholar
  32. Dunn, A.J. (1988) Systemic interleukin-1 administration stimulates hypothalamic norepinephrine metabolism parallelling the increased plasma corticosterone. Life Sci 43, 429–435.PubMedGoogle Scholar
  33. Dunn, A.J., Wang, J., and Ando, T. (1999) Effects of cytokines on cerebral neurotransmission. Comparison with the effects of stress. Adv Exp Med Biol 461, 117–127.PubMedGoogle Scholar
  34. Dusheiko, G. (1997) Side effects of alpha interferon in chronic hepatitis C. Hepatology 26, 112S–121S.PubMedGoogle Scholar
  35. Elenkov, I.J., and Vizi, E.S. (1991) Presynaptic modulation of release of noradrenaline from the sympathetic nerve terminals in the rat spleen. Neuropharmacology 30, 1319–1324.PubMedGoogle Scholar
  36. Elenkov, I.J., Hasko, G., Kovacs, K.J., and Vizi, E.S. (1995) Modulation of lipopolysaccharide-induced tumor necrosis factor-alpha production by selective alpha- and beta-adrenergic drugs in mice. J Neuroimmunol 61, 123–131.PubMedGoogle Scholar
  37. Elenkov, I.J., Wilder, R.L., Chrousos, G.P., and Vizi, E.S. (2000) The sympathetic nerve–An integrative interface between two supersystems: The brain and the immune system. Pharmacol Rev 52, 595–638.PubMedGoogle Scholar
  38. Elenkov, I.J., Kovacs, K., Duda, E., Stark, E., and Vizi, E.S. (1992) Presynaptic inhibitory effect of TNF-alpha on the release of noradrenaline in isolated median eminence. J Neuroimmunol 41, 117–120.PubMedGoogle Scholar
  39. Gao, H.M., Jiang, J., Wilson, B., Zhang, W., Hong, J.S., and Liu, B. (2002) Microglial activation-mediated delayed and progressive degeneration of rat nigral dopaminergic neurons: Relevance to Parkinson's disease. J Neurochem 81, 1285–1297.PubMedGoogle Scholar
  40. Garcia-Garcia, F., Yoshida, H., and Krueger, J.M. (2004) Interleukin-8 promotes non-rapid eye movement sleep in rabbits and rats. J Sleep Res 13, 55–61.PubMedGoogle Scholar
  41. Gilsbach, R., Faron-Gorecka, A., Rogoz, Z., Bruss, M., Caron, M.G., Dziedzicka- Wasylewska, M., and Bonisch, H. (2006) Norepinephrine transporter knockout-induced up-regulation of brain alpha2A/C-adrenergic receptors. J Neurochem 96, 1111–1120.PubMedGoogle Scholar
  42. Gold, P.W., and Chrousos, G.P. (2002) Organization of the stress system and its dysregulation in melancholic and atypical depression: High vs low CRH/NE states. Mol Psychiatry 7, 254–275.PubMedGoogle Scholar
  43. Hasko, G., Szabo, C., Nemeth, Z.H., and Deitch, E.A. (2002) Dopamine suppresses IL-12 p40 production by lipopolysaccharide-stimulated macrophages via a beta-adrenoceptormediated mechanism. J Neuroimmunol 122, 34–39.PubMedGoogle Scholar
  44. Hasko, G., Szabo, C., Nemeth, Z.H., Salzman, A.L., and Vizi, E.S. (1998a) Stimulation of beta-adrenoceptors inhibits endotoxin-induced IL-12 production in normal and IL-10 deficient mice. J Neuroimmunol 88, 57–61.Google Scholar
  45. Hasko, G., Szabo, C., Nemeth, Z.H., Salzman, A.L., and Vizi, E.S. (1998b) Suppression of IL- 12 production by phosphodiesterase inhibition in murine endotoxemia is IL-10 independent. Eur J Immunol 28, 468–472.Google Scholar
  46. Heyes, M.P., Saito, K., Crowley, J.S., Davis, L.E., Demitrack, M.A., Der, M., Dilling, L.A., Elia, J., Kruesi, M.J., Lackner, A., and et al. (1992) Quinolinic acid and kynurenine pathway metabolism in inflammatory and non-inflammatory neurological disease. Brain 115 (Pt 5), 1249–1273.PubMedGoogle Scholar
  47. Hofstetter, C., Flondor, M., Hoegl, S., Muhl, H., and Zwissler, B. (2005) Interleukin-10 aerosol reduces proinflammatory mediators in bronchoalveolar fluid of endotoxemic rat. Crit Care Med 33, 2317–2322.PubMedGoogle Scholar
  48. Irwin, M., Thompson, J., Miller, C., Gillin, J.C., and Ziegler, M. (1999) Effects of sleep and sleep deprivation on catecholamine and interleukin-2 levels in humans: Clinical implications. J Clin Endocrinol Metab 84, 1979–1985.PubMedGoogle Scholar
  49. Irwin, M., McClintick, J., Costlow, C., Fortner, M., White, J., and Gillin, J.C. (1996) Partial night sleep deprivation reduces natural killer and cellular immune responses in humans. FASEB J 10, 643–653.PubMedGoogle Scholar
  50. Ivashkiv, L.B., Ayres, A., and Glimcher, L.H. (1994) Inhibition of IFN-gamma induction of class II MHC genes by cAMP and prostaglandins. Immunopharmacology 27, 67–77.PubMedGoogle Scholar
  51. Izeboud, C.A., Mocking, J.A., Monshouwer, M., van Miert, A.S., and Witkamp, R.F. (1999) Participation of beta-adrenergic receptors on macrophages in modulation of LPS-induced cytokine release. J Recept Signal Transduct Res 19, 191–202.PubMedGoogle Scholar
  52. Kafka, M.S., and Paul, S.M. (1986) Platelet alpha 2-adrenergic receptors in depression. Arch Gen Psychiatry 43, 91–95.PubMedGoogle Scholar
  53. Kambayashi, T., Jacob, C.O., Zhou, D., Mazurek, N., Fong, M., and Strassmann, G. (1995) Cyclic nucleotide phosphodiesterase type IV participates in the regulation of IL-10 and in the subsequent inhibition of TNF-alpha and IL-6 release by endotoxin-stimulated macrophages. J Immunol 155, 4909–4916.PubMedGoogle Scholar
  54. Kaminska, B. (2005) MAPK signalling pathways as molecular targets for anti-inflammatory therapy–From molecular mechanisms to therapeutic benefits. Biochim Biophys Acta 1754, 253–262.PubMedGoogle Scholar
  55. Katakami, Y., Nakao, Y., Koizumi, T., Katakami, N., Ogawa, R., and Fujita, T. (1988) Regulation of tumour necrosis factor production by mouse peritoneal macrophages: The role of cellular cyclic AMP. Immunology 64, 719–724.PubMedGoogle Scholar
  56. Kendler, K.S., Thornton, L.M., and Gardner, C.O. (2000) Stressful life events and previous episodes in the etiology of major depression in women: An evaluation of the “kindling” hypothesis. Am J Psychiatry 157, 1243–1251.PubMedGoogle Scholar
  57. Kiss, J.P., Zsilla, G., Mike, A., Zelles, T., Toth, E., Lajtha, A., and Vizi, E.S. (1995) Subtypespecificity of the presynaptic alpha 2-adrenoceptors modulating hippocampal norepinephrine release in rat. Brain Res 674, 238–244.PubMedGoogle Scholar
  58. Krigel, R.L., Padavic-Shaller, K.A., Rudolph, A.R., Konrad, M., Bradley, E.C., and Comis, R.L. (1990) Renal cell carcinoma: Treatment with recombinant interleukin-2 plus betainterferon. J Clin Oncol 8, 460–467.PubMedGoogle Scholar
  59. Kronfol, Z., and House, J.D. (1989) Lymphocyte mitogenesis, immunoglobulin and complement levels in depressed patients and normal controls. Acta Psychiatr Scand 80, 142–147.PubMedGoogle Scholar
  60. Kronfol, Z., and Remick, D.G. (2000) Cytokines and the brain: Implications for clinical psychiatry. Am J Psychiatry 157, 683–694.PubMedGoogle Scholar
  61. Krueger, J.M., and Majde, J.A. (1994) Microbial products and cytokines in sleep and fever regulation. Crit Rev Immunol 14, 355–379.PubMedGoogle Scholar
  62. Krueger, J.M., Walter, J., Dinarello, C.A., Wolff, S.M., and Chedid, L. (1984) Sleeppromoting effects of endogenous pyrogen (interleukin-1). Am J Physiol 246, R994–R999.PubMedGoogle Scholar
  63. Krueger, J.M., Obal, F.J., Fang, J., Kubota, T., and Taishi, P. (2001) The role of cytokines in physiological sleep regulation. Ann N Y Acad Sci 933, 211–221.PubMedGoogle Scholar
  64. Lacour, M., Arrighi, J.F., Muller, K.M., Carlberg, C., Saurat, J.H., and Hauser, C. (1994) cAMP up-regulates IL-4 and IL-5 production from activated CD4+ T cells while decreasing IL-2 release and NF-AT induction. Int Immunol 6, 1333–1343.PubMedGoogle Scholar
  65. Lanquillon, S., Krieg, J.C., Bening-Abu-Shach, U., and Vedder, H. (2000) Cytokine production and treatment response in major depressive disorder. Neuropsychopharmacology 22, 370–379.PubMedGoogle Scholar
  66. Lavie, P. (2001) Sleep-wake as a biological rhythm. Annu Rev Psychol 52, 277–303.PubMedGoogle Scholar
  67. Leonard, B.E. (2001a) Changes in the immune system in depression and dementia: Causal or co-incidental effects? Int J Dev Neurosci 19, 305–312.Google Scholar
  68. Leonard, B.E. (2001b) The immune system, depression and the action of antidepressants. Prog Neuropsychopharmacol Biol Psychiatry 25, 767–780.Google Scholar
  69. Lesch, K.P., and Mossner, R. (1998) Genetically driven variation in serotonin uptake: Is there a link to affective spectrum, neurodevelopmental, and neurodegenerative disorders? Biol Psychiatry 44, 179–192.PubMedGoogle Scholar
  70. Lue, F.A., Bail, M., Jephthah-Ochola, J., Carayanniotis, K., Gorczynski, R., and Moldofsky, H. (1988) Sleep and cerebrospinal fluid interleukin-1-like activity in the cat. Int J Neurosci 42, 179–183.PubMedGoogle Scholar
  71. Maes, M., Van Gastel, A., Delmeire, L., and Meltzer, H.Y. (1999a) Decreased platelet alpha-2 adrenoceptor density in major depression: Effects of tricyclic antidepressants and fluoxetine. Biol Psychiatry 45, 278–284.Google Scholar
  72. Maes, M., Minner, B., Suy, E., Vandervorst, C., and Raus, J. (1991) Coexisting dysregulations of both the sympathoadrenal system and hypothalamic-pituitary-adrenal-axis in melancholia. J Neural Transm Gen Sect 85, 195–210.PubMedGoogle Scholar
  73. Maes, M., Bosmans, E., Meltzer, H.Y., Scharpe, S., and Suy, E. (1993) Interleukin-1 beta: A putative mediator of HPA axis hyperactivity in major depression? Am J Psychiatry 150, 1189–1193.PubMedGoogle Scholar
  74. Maes, M., Bosmans, E., De Jongh, R., Kenis, G., Vandoolaeghe, E., and Neels, H. (1997) Increased serum IL-6 and IL-1 receptor antagonist concentrations in major depression and treatment resistant depression. Cytokine 9, 853–858.PubMedGoogle Scholar
  75. Maes, M., Meltzer, H.Y., Bosmans, E., Bergmans, R., Vandoolaeghe, E., Ranjan, R., and Desnyder, R. (1995) Increased plasma concentrations of interleukin-6, soluble interleukin- 6, soluble interleukin-2 and transferrin receptor in major depression. J Affect Disord 34, 301–309.PubMedGoogle Scholar
  76. Maes, M., Song, C., Lin, A.H., Bonaccorso, S., Kenis, G., De Jongh, R., Bosmans, E., and Scharpe, S. (1999b) Negative immunoregulatory effects of antidepressants: Inhibition of interferon-gamma and stimulation of interleukin-10 secretion. Neuropsychopharmacology 20, 370–379.Google Scholar
  77. Maestroni, G.J., Conti, A., and Pierpaoli, W. (1986) Role of the pineal gland in immunity. Circadian synthesis and release of melatonin modulates the antibody response and antagonizes the immunosuppressive effect of corticosterone. J Neuroimmunol 13, 19–30.PubMedGoogle Scholar
  78. Maestroni, G.J., Conti, A., and Pierpaoli, W. (1987) Role of the pineal gland in immunity: II. Melatonin enhances the antibody response via an opiatergic mechanism. Clin Exp Immunol 68, 384–391.PubMedGoogle Scholar
  79. Maestroni, G.J., Cosentino, M., Marino, F., Togni, M., Conti, A., Lecchini, S., and Frigo, G. (1998) Neural and endogenous catecholamines in the bone marrow. Circadian association of norepinephrine with hematopoiesis? Exp Hematol 26, 1172–1177.PubMedGoogle Scholar
  80. Mayer, B., Holmer, S.R., Hengstenberg, C., Lieb, W., Pfeifer, M., and Schunkert, H. (2005) Functional improvement in heart failure patients treated with beta-blockers is associated with a decline of cytokine levels. Int J Cardiol 103, 182–186.PubMedGoogle Scholar
  81. Mills, P.J., and Dimsdale, J.E. (2004) Sleep apnea: A model for studying cytokines, sleep, and sleep disruption. Brain Behav Immun 18, 298–303.PubMedGoogle Scholar
  82. Moldofsky, H., Lue, F.A., Eisen, J., Keystone, E., and Gorczynski, R.M. (1986) The relationship of interleukin-1 and immune functions to sleep in humans. Psychosom Med 48, 309–318.PubMedGoogle Scholar
  83. Morikawa, O., Sakai, N., Obara, H., and Saito, N. (1998) Effects of interferon-alpha, interferon-gamma and cAMP on the transcriptional regulation of the serotonin transporter. Eur J Pharmacol 349, 317–324.PubMedGoogle Scholar
  84. Moron, J.A., Brockington, A., Wise, R.A., Rocha, B.A., and Hope, B.T. (2002) Dopamine uptake through the norepinephrine transporter in brain regions with low levels of the dopamine transporter: Evidence from knock-out mouse lines. J Neurosci 22, 389–395.PubMedGoogle Scholar
  85. Mossner, R., Daniel, S., Schmitt, A., Albert, D., and Lesch, K.P. (2001) Modulation of serotonin transporter function by interleukin-4. Life Sci 68, 873–880.PubMedGoogle Scholar
  86. Mossner, R., Heils, A., Stober, G., Okladnova, O., Daniel, S., and Lesch, K.P. (1998) Enhancement of serotonin transporter function by tumor necrosis factor alpha but not by interleukin-6. Neurochem Int 33, 251–254.PubMedGoogle Scholar
  87. Mulder, R.T., Ang, M., Chapman, B., Ross, A., Stevens, I.F., and Edgar, C. (2000) Interferon treatment is not associated with a worsening of psychiatric symptoms in patients with hepatitis C. J Gastroenterol Hepatol 15, 300–303.PubMedGoogle Scholar
  88. Murray, D.R., Prabhu, S.D., and Chandrasekar, B. (2000) Chronic beta-adrenergic stimulation induces myocardial proinflammatory cytokine expression. Circulation 101, 2338–2341.PubMedGoogle Scholar
  89. Musselman, D.L., Lawson, D.H., Gumnick, J.F., Manatunga, A.K., Penna, S., Goodkin, R.S., Greiner, K., Nemeroff, C.B., and Miller, A.H. (2001) Paroxetine for the prevention of depression induced by high-dose interferon alfa. N Engl J Med 344, 961–966.PubMedGoogle Scholar
  90. Nemeth, Z.H., Hasko, G., Szabo, C., and Vizi, E.S. (1997) Amrinone and theophylline differentially regulate cytokine and nitric oxide production in endotoxemic mice. Shock 7, 371–375.PubMedGoogle Scholar
  91. Nickola T.J., Ignatowski, T.A., Reynolds, J.L., and Spengler, R.N. (2001) Antidepressant drug-induced alterations in neuron-localized tumor necrosis factor-alpha mRNA and alpha(2)-adrenergic receptor sensitivity. J Pharmacol Exp Ther 297, 680–687.PubMedGoogle Scholar
  92. Novogrodsky, A., Patya, M., Rubin, A.L., and Stenzel, K.H. (1983) Agents that increase cellular cAMP inhibit production of interleukin-2, but not its activity. Biochem Biophys Res Commun 114, 93–98.PubMedGoogle Scholar
  93. Ohayon, M.M., and Caulet, M. (1996) Psychotropic medication and insomnia complaints in two epidemiological studies. Can J Psychiatry 41, 457–464.PubMedGoogle Scholar
  94. Papanicolaou, D.A., Wilder, R.L., Manolagas, S.C., and Chrousos, G.P. (1998) The pathophysiologic roles of interleukin-6 in human disease. Ann Intern Med 128, 127–137.PubMedGoogle Scholar
  95. Pavlov, V.A., and Tracey, K.J. (2005) The cholinergic anti-inflammatory pathway. Brain Behav Immun 19, 493–499.PubMedGoogle Scholar
  96. Plata-Salaman, C.R. (1991) Immunoregulators in the nervous system. Neurosci Biobehav Rev 15, 185–215.PubMedGoogle Scholar
  97. Platzer, C., Meisel, C., Vogt, K., Platzer, M., and Volk, H.D. (1995) Up-regulation of monocytic IL-10 by tumor necrosis factor-alpha and cAMP elevating drugs. Int Immunol 7, 517–523.PubMedGoogle Scholar
  98. Potter, W.Z., Scheinin, M., Golden, R.N., Rudorfer, M.V., Cowdry, R.W., Calil, H.M., Ross, R.J., and Linnoila, M. (1985) Selective antidepressants and cerebrospinal fluid. Lack of specificity on norepinephrine and serotonin metabolites. Arch Gen Psychiatry 42, 1171–1177.PubMedGoogle Scholar
  99. Raison, C.L., and Miller, A.H. (2003) When not enough is too much: The role of insufficient glucocorticoid signaling in the pathophysiology of stress-related disorders. Am J Psychiatry 160, 1554–1565.PubMedGoogle Scholar
  100. Raison, C.L., Capuron, L., and Miller, A.H. (2006) Cytokines sing the blues: Inflammation and the pathogenesis of depression. Trends Immunol 27, 24–31.PubMedGoogle Scholar
  101. Redwine, L., Hauger, R.L., Gillin, J.C., and Irwin, M. (2000) Effects of sleep and sleep deprivation on interleukin-6, growth hormone, cortisol, and melatonin levels in humans. J Clin Endocrinol Metab 85, 3597–3603.PubMedGoogle Scholar
  102. Ritchie, P.K., Ashby, M., Knight, H.H., and Judd, A.M. (1996) Dopamine increases interleukin 6 release and inhibits tumor necrosis factor release from rat adrenal zona glomerulosa cells in vitro. Eur J Endocrinol 134, 610–616.PubMedGoogle Scholar
  103. Rogers, N.L., Szuba, M.P., Staab, J.P., Evans, D.L., and Dinges, D.F. (2001) Neuroimmunologic aspects of sleep and sleep loss. Semin Clin Neuropsychiatry 6, 295–307.PubMedGoogle Scholar
  104. Rothwell, N.J. (1997) Sixteenth Gaddum Memorial Lecture December 1996. Neuroimmune interactions: The role of cytokines. Br J Pharmacol 121, 841–847.PubMedGoogle Scholar
  105. Schildkraut, J.J. (1965) The catecholamine hypothesis of affective disorders: A review of supporting evidence. Am J Psychiatry 122, 509–522.PubMedGoogle Scholar
  106. Selmeczy, Z., Szelenyi, J., and Vizi, E.S. (2003) Intact noradrenaline transporter is needed for the sympathetic fine-tuning of cytokine balance. Eur J Pharmacol 469, 175–181.PubMedGoogle Scholar
  107. Shakhar, G., and Ben-Eliyahu, S. (1998) In vivo beta-adrenergic stimulation suppresses natural killer activity and compromises resistance to tumor metastasis in rats. J Immunol 160, 3251–3258.PubMedGoogle Scholar
  108. Shimizu, N., Hori, T., and Nakane, H. (1994) An interleukin-1 beta-induced noradrenaline release in the spleen is mediated by brain corticotropin-releasing factor: An in vivo microdialysis study in conscious rats. Brain Behav Immun 8, 14–23.PubMedGoogle Scholar
  109. Siegel, M.D., Zhang, D.H., Ray, P., and Ray, A. (1995) Activation of the interleukin-5 promoter by cAMP in murine EL-4 cells requires the GATA-3 and CLE0 elements. J Biol Chem 270, 24548–24555.PubMedGoogle Scholar
  110. Silverman, M.N., Pearce, B.D., Biron, C.A., and Miller, A.H. (2005) Immune modulation of the hypothalamic-pituitary-adrenal (HPA) axis during viral infection. Viral Immunol 18, 41–78.PubMedGoogle Scholar
  111. Spengler, R.N., Allen, R.M., Remick, D.G., Strieter, R.M., and Kunkel, S.L. (1990) Stimulation of alpha-adrenergic receptor augments the production of macrophage-derived tumor necrosis factor. J Immunol 145, 1430–1434.PubMedGoogle Scholar
  112. Staley, J.K., Malison, R.T., and Innis, R.B. (1998) Imaging of the serotonergic system: Interactions of neuroanatomical and functional abnormalities of depression. Biol Psychiatry 44, 534–549.PubMedGoogle Scholar
  113. Sternberg, E.M. (1997) Neural-immune interactions in health and disease. J Clin Invest 100, 2641–2647.PubMedGoogle Scholar
  114. Sternberg, E.M., Wedner, H.J., Leung, M.K., and Parker, C.W. (1987) Effect of serotonin (5- HT) and other monoamines on murine macrophages: Modulation of interferon-gamma induced phagocytosis. J Immunol 138, 4360–4365.PubMedGoogle Scholar
  115. Surprenant, A., Rassendren, F., Kawashima, E., North, R.A., and Buell, G. (1996) The cytolytic P2Z receptor for extracellular ATP identified as a P2X receptor (P2X7). Science 272, 735–738.PubMedGoogle Scholar
  116. Szelenyi, J. (2001) Cytokines and the central nervous system. Brain Res Bull 54, 329–338.PubMedGoogle Scholar
  117. Szelenyi, J., and Selmeczy, Z. (2002) Immunomodulatory effect of antidepressants. Curr Opin Pharmacol 2, 428–432.PubMedGoogle Scholar
  118. Szelenyi, J., Kiss, J.P., and Vizi, E.S. (2000a) Differential involvement of sympathetic nervous system and immune system in the modulation of TNF-alpha production by alpha2- and beta-adrenoceptors in mice. J Neuroimmunol 103, 34–40.Google Scholar
  119. Szelenyi, J., Selmeczy, Z., and Vizi, E.S. (2004) Effect of monoamine transporter inhibitors on the LPS-induced cytokine production. Fundam Clin Pharmacol 18, 95.Google Scholar
  120. Szelenyi, J., Kiss, J.P., Puskas, E., Szelenyi, M., and Vizi, E.S. (2000b) Contribution of differently localized alpha 2- and beta-adrenoceptors in the modulation of TNF-alpha and IL-10 production in endotoxemic mice. Ann N Y Acad Sci 917, 145–153.Google Scholar
  121. Szelenyi, J., Selmeczy, Z., Brozik, A., Medgyesi, D., and Magocsi, M. (2006) Dual betaadrenergic modulation in the immune system: Stimulus-dependent effect of isoproterenol on MAPK activation and inflammatory mediator production in macrophages. Neurochem Int 49, 94–103.PubMedGoogle Scholar
  122. Szelenyi, J., Kiss, J.P., Puskas, E., Selmeczy, Z., Szelenyi, M., and Vizi, E.S. (2000c) Opposite role of alpha2- and beta-adrenoceptors in the modulation of interleukin-10 production in endotoxaemic mice. Neuroreport 11, 3565–3568.Google Scholar
  123. Thase, M.E. (1999) Antidepressant treatment of the depressed patient with insomnia. J Clin Psychiatry 60(Suppl 17), 28–31; discussion 46–28.PubMedGoogle Scholar
  124. Thase, M.E., Simons, A.D., and Reynolds, C.F., 3rd. (1996) Abnormal electroencephalographic sleep profiles in major depression: Association with response to cognitive behavior therapy. Arch Gen Psychiatry 53, 99–108.PubMedGoogle Scholar
  125. van der Poll, T., Jansen, J., Endert, E., Sauerwein, H.P., and van Deventer, S.J. (1994) Noradrenaline inhibits lipopolysaccharide-induced tumor necrosis factor and interleukin 6 production in human whole blood. Infect Immun 62, 2046–2050.PubMedGoogle Scholar
  126. van der Pouw Kraan, T.C., Boeije, L.C., Smeenk, R.J., Wijdenes, J., and Aarden, L.A. (1995) Prostaglandin-E2 is a potent inhibitor of human interleukin 12 production. J Exp Med 181, 775–779.PubMedGoogle Scholar
  127. Vizi, E.S. (1979) Presynaptic modulation of neurochemical transmission. Prog Neurobiol 12, 181–290.PubMedGoogle Scholar
  128. Vizi, E.S. (1998) Receptor-mediated local fine-tuning by noradrenergic innervation of neuroendocrine and immune systems. Ann N Y Acad Sci 851, 388–396.PubMedGoogle Scholar
  129. Vizi, E.S. (2000) Role of high-affinity receptors and membrane transporters in nonsynaptic communication and drug action in the central nervous system. Pharmacol Rev 52, 63–89.PubMedGoogle Scholar
  130. Vizi, E.S., Zsilla, G., Caron, M.G., and Kiss, J.P. (2004) Uptake and release of norepinephrine by serotonergic terminals in norepinephrine transporter knockout mice: Implications for the action of selective serotonin reuptake inhibitors. J Neurosci 24, 7888–7894.PubMedGoogle Scholar
  131. Wang, X., Wu, H., and Miller, A.H. (2004) Interleukin 1alpha (IL-1alpha) induced activation of p38 mitogen-activated protein kinase inhibits glucocorticoid receptor function. Mol Psychiatry 9, 65–75.PubMedGoogle Scholar
  132. Watkins, L.R., Maier, S.F., and Goehler, L.E. (1995) Cytokine-to-brain communication: A review and analysis of alternative mechanisms. Life Sci 57, 1011–1026.PubMedGoogle Scholar
  133. Weizman, R., Laor, N., Podliszewski, E., Notti, I., Djaldetti, M., and Bessler, H. (1994) Cytokine production in major depressed patients before and after clomipramine treatment. Biol Psychiatry 35, 42–47.PubMedGoogle Scholar
  134. Wichers, M., and Maes, M. (2002) The psychoneuroimmuno-pathophysiology of cytokineinduced depression in humans. Int J Neuropsychopharmacol 5, 375–388.PubMedGoogle Scholar
  135. Woiciechowsky, C., Asadullah, K., Nestler, D., Eberhardt, B., Platzer, C., Schoning, B., Glockner, F., Lanksch, W.R., Volk, H.D., and Docke, W.D. (1998) Sympathetic activation triggers systemic interleukin-10 release in immunodepression induced by brain injury. Nat Med 4, 808–813.PubMedGoogle Scholar
  136. Wong, M.L., Kling, M.A., Munson, P.J., Listwak, S., Licinio, J., Prolo, P., Karp, B., McCutcheon, I.E., Geracioti, T.D., Jr., DeBellis, M.D., Rice, K.C., Goldstein, D.S., Veldhuis, J.D., Chrousos, G.P., Oldfield, E.H., McCann, S.M., and Gold, P.W. (2000) Pronounced and sustained central hypernoradrenergic function in major depression with melancholic features: Relation to hypercortisolism and corticotropin-releasing hormone. Proc Natl Acad Sci U S A 97, 325–330.PubMedGoogle Scholar
  137. Xu, F., Gainetdinov, R.R., Wetsel, W.C., Jones, S.R., Bohn, L.M., Miller, G.W., Wang, Y.M., and Caron, M.G. (2000) Mice lacking the norepinephrine transporter are supersensitive to psychostimulants. Nat Neurosci 3, 465–471.PubMedGoogle Scholar
  138. Yirmiya, R., Pollak, Y., Barak, O., Avitsur, R., Ovadia, H., Bette, M., Weihe, E., and Weidenfeld, J. (2001) Effects of antidepressant drugs on the behavioral and physiological responses to lipopolysaccharide (LPS) in rodents. Neuropsychopharmacology 24, 531–544.PubMedGoogle Scholar
  139. Zhu, C.B., Carneiro, A.M., Dostmann, W.R., Hewlett, W.A., and Blakely, R.D. (2005) p38 MAPK activation elevates serotonin transport activity via a trafficking-independent, protein phosphatase 2A-dependent process. J Biol Chem 280, 15649–15658.PubMedGoogle Scholar
  140. Zhu, J., Mix, E., and Winblad, B. (2001) The antidepressant and antiinflammatory effects of rolipram in the central nervous system. CNS Drug Rev 7, 387–398.PubMedGoogle Scholar

Copyright information

© Springer 2007

Authors and Affiliations

  • J. Szelényi
  • E.S. Vizi

There are no affiliations available

Personalised recommendations