Advertisement

The hygiene hypothesis and affective and anxiety disorders

  • Graham A. W. Rook
  • Christopher A. Lowry
Part of the Progress in Inflammation Research book series (PIR)

Abstract

Chronic inflammatory disorders are increasing in prevalence in the developed countries. The hygiene hypothesis proposes that our changing microbial environment has resulted in a deficit in immunoregulatory circuits so that there is a failure to terminate inappropriate inflammation. Several stress-related psychiatric disorders, particularly depression and anxiety disorders, are associated with raised levels of proinflammatory cytokines and of other markers of ongoing inflammation, even in the absence of any obvious inflammatory lesion. Moreover proinflammatory cytokines are known to induce depression, which is frequently seen when patients are treated with interleukin-2 (IL-2) or interferon-α (IFN-α). Therefore the occurrence of these psychiatric disorders in developed countries might be partly attributable to a failure of immunoregulation. We review the evidence that inflammation is associated with several patterns of psychiatric disturbance, and that regulatory cytokines such as IL-10 and transforming growth factor-β (TGF-β) can oppose these effects, and that anti-depressants might work in part via effects on inflammation in the periphery.

Keywords

Proinflammatory Cytokine Anxiety Disorder Panic Disorder Intestinal Permeability Biol Psychiatry 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Bach JF (2002) The effect of infections on susceptibility to autoimmune and allergic diseases. N Engl J Med 347: 911–920PubMedCrossRefGoogle Scholar
  2. 2.
    Sawczenko A, Sandhu BK, Logan RF, Jenkins H, Taylor CJ, Mian S, Lynn R (2001) Prospective survey of childhood inflammatory bowel disease in the British Isles. Lancet 357: 1093–1094PubMedCrossRefGoogle Scholar
  3. 3.
    Rook GA, Adams V, Hunt J, Palmer R, Martinelli R, Brunet LR (2004) Mycobacteria and other environmental organisms as immunomodulators for immunoregulatory disorders. Springer Semin Immunopathol 25: 237–255PubMedCrossRefGoogle Scholar
  4. 4.
    Akdis M, Verhagen J, Taylor A, Karamloo F, Karagiannidis C, Crameri R, Thunberg S, Deniz G, Valenta R, Fiebig H et al (2004) Immune responses in healthy and allergic individuals are characterized by a fine balance between allergen-specific T regulatory 1 and T helper 2 cells. J Exp Med 199: 1567–1575PubMedCrossRefGoogle Scholar
  5. 5.
    Viglietta V, Baecher-Allan C, Weiner HL, Hafler DA (2004) Loss of functional suppression by CD4+CD25+ regulatory T cells in patients with multiple sclerosis. J Exp Med 199: 971–979PubMedCrossRefGoogle Scholar
  6. 6.
    Kriegel MA, Lohmann T, Gabler C, Blank N, Kalden JR, Lorenz HM (2004) Defective suppressor function of human CD4+ CD25+ regulatory T cells in autoimmune polyglandular syndrome type II. J Exp Med 199: 1285–1291PubMedCrossRefGoogle Scholar
  7. 7.
    Duchmann R, Kaiser I, Hermann E, Mayet W, Ewe K, Meyer zum Buschenfelde KH (1995) Tolerance exists towards resident intestinal flora but is broken in active inflammatory bowel disease (IBD). Clin Exp Immunol 102: 448–455PubMedCrossRefGoogle Scholar
  8. 8.
    Kraus TA, Toy L, Chan L, Childs J, Mayer L (2004) Failure to induce oral tolerance to a soluble protein in patients with inflammatory bowel disease. Gastroenterology 126: 1771–1778PubMedCrossRefGoogle Scholar
  9. 9.
    Wildin RS, Smyk-Pearson S, Filipovich AH (2002) Clinical and molecular features of the immunodysregulation, polyendocrinopathy, enteropathy, X linked (IPEX) syndrome. J Med Genet 39: 537–545PubMedCrossRefGoogle Scholar
  10. 10.
    Babu S, Blauvelt CP, Kumaraswami V, Nutman TB (2006) Regulatory networks induced by live parasites impair both Th1 and Th2 pathways in patent lymphatic filariasis: implications for parasite persistence. J Immunol 176: 3248–3256PubMedGoogle Scholar
  11. 11.
    Van der Kleij D, Latz E, Brouwers JF, Kruize YC, Schmitz M, Kurt-Jones EA, Espevik T, de Jong EC, Kapsenberg ML, Golenbock DT et al (2002) A novel host-parasite lipid cross-talk. Schistosomal lyso-phosphatidylserine activates Toll-like receptor 2 and affects immune polarization. J Biol Chem 277: 48122–48129PubMedCrossRefGoogle Scholar
  12. 12.
    Adams VC, Hunt JR, Martinelli R, Palmer R, Rook GA, Brunet LR (2004) Mycobacterium vaccae induces a population of pulmonary CD11c+ cells with regulatory potential in allergic mice. Eur J Immunol 34: 631–638PubMedCrossRefGoogle Scholar
  13. 13.
    Smits HH, Engering A, van der Kleij D, de Jong EC, Schipper K, van Capel TM, Zaat BA, Yazdanbakhsh M, Wierenga EA, van Kooyk Y et al (2005) Selective probiotic bacteria induce IL-10-producing regulatory T cells in vitro by modulating dendritic cell function through dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin. J Allergy Clin Immunol 115: 1260–1267PubMedCrossRefGoogle Scholar
  14. 14.
    Pasare C, Medzhitov R (2003) Toll pathway-dependent blockade of CD4+CD25+ T cell-mediated suppression by dendritic cells. Science 299: 1033–1036PubMedCrossRefGoogle Scholar
  15. 15.
    Zuany-Amorim C, Sawicka E, Manlius C, Le Moine A, Brunet LR, Kemeny DM, Bowen G, Rook G, Walker C (2002) Suppression of airway eosinophilia by killed Mycobacterium vaccae-induced allergen-specific regulatory T-cells. Nat Med 8: 625–629PubMedCrossRefGoogle Scholar
  16. 16.
    Wilson MS, Taylor MD, Balic A, Finney CA, Lamb JR, Maizels RM (2005) Suppression of allergic airway inflammation by helminth-induced regulatory T cells. J Exp Med 202: 1199–1212PubMedCrossRefGoogle Scholar
  17. 17.
    Ricklin-Gutzwiller ME, Reist M, Peel JE, Seewald W, Brunet LR, Roospje PJ (2007) Intradermal injection of heat-killed Mycobacterium vaccae in dogs with atopic dermatitis: a multicentre pilot study. Vet Dermatol 18: 87–93PubMedCrossRefGoogle Scholar
  18. 18.
    Zaccone P, Fehervari Z, Jones FM, Sidobre S, Kronenberg M, Dunne DW, Cooke A (2003) Schistosoma mansoni antigens modulate the activity of the innate immune response and prevent onset of type 1 diabetes. Eur J Immunol 33: 1439–1449PubMedCrossRefGoogle Scholar
  19. 19.
    Di Giacinto C, Marinaro M, Sanchez M, Strober W, Boirivant M (2005) Probiotics ameliorate recurrent Th1-mediated murine colitis by inducing IL-10 and IL-10-dependent TGF-ta-bearing regulatory cells. J Immunol 174: 3237–3246PubMedGoogle Scholar
  20. 20.
    Summers RW, Elliott DE, Urban JF, Jr., Thompson RA, Weinstock JV (2005) Trichuris suis therapy for active ulcerative colitis: a randomized controlled trial. Gastroenterology 128: 825–832PubMedCrossRefGoogle Scholar
  21. 21.
    Summers RW, Elliott DE, Urban JF, Jr., Thompson R, Weinstock JV (2005) Trichuris suis therapy in Crohn’s disease. Gut 54: 87–90PubMedCrossRefGoogle Scholar
  22. 22.
    Taylor A, Verhagen J, Blaser K, Akdis M, Akdis CA (2006) Mechanisms of immune suppression by interleukin-10 and transforming growth factor-beta: the role of T regulatory cells. Immunology 117: 433–442PubMedCrossRefGoogle Scholar
  23. 23.
    O’Brien SM, Scott LV, Dinan TG (2004) Cytokines: abnormalities in major depression and implications for pharmacological treatment. Hum Psychopharmacol 19: 397–403PubMedCrossRefGoogle Scholar
  24. 24.
    Schiepers OJ, Wichers MC, Maes M (2005) Cytokines and major depression. Prog. Neuropsychopharmacol. Biol Psychiatry 29: 201–217CrossRefGoogle Scholar
  25. 25.
    Capuron L, Miller AH (2004) Cytokines and psychopathology: lessons from interferon-alpha. Biol Psychiatry 56: 819–824PubMedCrossRefGoogle Scholar
  26. 26.
    Maes M (1999) Major depression and activation of the inflammatory response system. Adv Exp Med Biol 461: 25–46PubMedCrossRefGoogle Scholar
  27. 27.
    Penninx BW, Kritchevsky SB, Yaffe K, Newman AB, Simonsick EM, Rubin S, Ferrucci L, Harris T, Pahor M (2003) Inflammatory markers and depressed mood in older persons: results from the health, aging and body domposition study. Biol Psychiatry 54: 566–572PubMedCrossRefGoogle Scholar
  28. 28.
    Musselman DL, Miller AH, Porter MR, Manatunga A, Gao F, Penna S, Pearce BD, Landry J, Glover S, McDaniel JS et al (2001) Higher than normal plasma interleukin-6 concentrations in cancer patients with depression: preliminary findings. Am J Psychiatry 158: 1252–1257PubMedCrossRefGoogle Scholar
  29. 29.
    Raison CL, Miller AH (2003) Depression in cancer: new developments regarding diagnosis and treatment. Biol Psychiatry 54: 283–294PubMedCrossRefGoogle Scholar
  30. 30.
    Ferketich AK, Ferguson JP, Binkley PF (2005) Depressive symptoms and inflammation among heart failure patients. Am Heart J 150: 132–136PubMedCrossRefGoogle Scholar
  31. 31.
    Maes M, Song C, Lin A, De Jongh R, Van Gastel A, Kenis G, Bosmans E, De Meester I, Benoy I, Neels H et al (1998) The effects of psychological stress on humans: increased production of pro-inflammatory cytokines and a Th1-like response in stress-induced anxiety. Cytokine 10: 313–318PubMedCrossRefGoogle Scholar
  32. 32.
    Kohut ML, Cooper MM, Nickolaus MS, Russell DR, Cunnick JE (2002) Exercise and psychosocial factors modulate immunity to influenza vaccine in elderly individuals. J Gerontol A Biol Sci Med Sci 57: M557–562PubMedGoogle Scholar
  33. 33.
    Costanzo ES, Lutgendorf SK, Kohut ML, Nisly N, Rozeboom K, Spooner S, Benda J, McElhaney JE (2004) Mood and cytokine response to influenza virus in older adults. J Gerontol A Biol Sci Med Sci 59: 1328–1333PubMedGoogle Scholar
  34. 34.
    Maes M, Scharpe S, Van Grootel L, Uyttenbroeck W, Cooreman W, Cosyns P, Suy E (1992) Higher alpha 1-antitrypsin, haptoglobin, ceruloplasmin and lower retinol binding protein plasma levels during depression: further evidence for the existence of an inflammatory response during that illness. J Affect Disord 24: 183–192PubMedCrossRefGoogle Scholar
  35. 35.
    Maes M, De Vos N, Demedts P, Wauters A, Neels H (1999) Lower serum zinc in major depression in relation to changes in serum acute phase proteins. J Affect Disord 56: 189–194PubMedCrossRefGoogle Scholar
  36. 36.
    Kronfol Z, House JD (1989) Lymphocyte mitogenesis, immunoglobulin and complement levels in depressed patients and normal controls. Acta Psychiatr Scand 80: 142–147PubMedCrossRefGoogle Scholar
  37. 37.
    Huang TL, Lin FC (2007) High-sensitivity C-reactive protein levels in patients with major depressive disorder and bipolar mania. Prog Neuropsychopharmacol Biol Psychiatry 31: 370–372PubMedCrossRefGoogle Scholar
  38. 38.
    Kronfol Z, Turner R, House JD, Winokur G (1986) Elevated blood neutrophil concentration in mania. J Clin Psychiatry 47: 63–65PubMedGoogle Scholar
  39. 39.
    Atamas SP, Choi J, Yurovsky VV, White B (1996) An alternative splice variant of human IL-4, IL-4 delta 2, inhibits IL-4-stimulated T cell proliferation. J Immunol 156: 435PubMedGoogle Scholar
  40. 40.
    Dheda K, Chang JS, Breen RA, Kim LU, Haddock JA, Huggett JF, Johnson MA, Rook GA, Zumla A (2005) In vivo and in vitro studies of a novel cytokine, interleukin-4delta2, in Pulmonary Tuberculosis. Am J Respir Crit Care Med 172: 501–508PubMedCrossRefGoogle Scholar
  41. 41.
    Myint AM, Leonard BE, Steinbusch HW, Kim YK (2005) Th1, Th2, and Th3 cytokine alterations in major depression. J Affect Disord 88: 167–173PubMedCrossRefGoogle Scholar
  42. 42.
    Kim YK, Jung HG, Myint AM, Kim H, Park SH (2007) Imbalance between pro-inflammatory and anti-inflammatory cytokines in bipolar disorder. J Affect Disord 104: 91–95PubMedCrossRefGoogle Scholar
  43. 43.
    Berry M, Brightling C, Pavord I, Wardlaw A (2007) TNF-alpha in asthma. Curr Opin Pharmacol 7: 279–282PubMedCrossRefGoogle Scholar
  44. 44.
    Shore SA (2007) Obesity and asthma: implications for treatment. Curr Opin Pulm Med 13: 56–62PubMedCrossRefGoogle Scholar
  45. 45.
    Beuther DA, Weiss ST, Sutherland ER (2006) Obesity and asthma. Am J Respir Crit Care Med 174: 112–119PubMedCrossRefGoogle Scholar
  46. 46.
    Wyatt SB, Winters KP, Dubbert PM (2006) Overweight and obesity: prevalence, consequences, and causes of a growing public health problem. Am J Med Sci 331: 166–174PubMedCrossRefGoogle Scholar
  47. 47.
    Chapman DP, Perry GS, Strine TW (2005) The vital link between chronic disease and depressive disorders. Prev Chronic Dis 2: A14PubMedGoogle Scholar
  48. 48.
    Ortega AN, Huertas SE, Canino G, Ramirez R, Rubio-Stipec M (2002) Childhood asthma, chronic illness, and psychiatric disorders. J Nerv Ment Dis 190: 275–281PubMedCrossRefGoogle Scholar
  49. 49.
    Vila G, Nollet-Clemencon C, de Blic J, Mouren-Simeoni MC, Scheinmann P (2000) Prevalence of DSM IV anxiety and affective disorders in a pediatric population of asthmatic children and adolescents. J Affect Disord 58: 223–231PubMedCrossRefGoogle Scholar
  50. 50.
    Ortega AN, McQuaid EL, Canino G, Goodwin RD, Fritz GK (2004) Comorbidity of asthma and anxiety and depression in Puerto Rican children. Psychosomatics 45: 93–99PubMedCrossRefGoogle Scholar
  51. 51.
    Goodwin RD, Messineo K, Bregante A, Hoven CW, Kairam R (2005) Prevalence of probable mental disorders among pediatric asthma patients in an inner-city clinic. J Asthma 42: 643–647PubMedCrossRefGoogle Scholar
  52. 52.
    Wamboldt MZ, Hewitt JK, Schmitz S, Wamboldt FS, Rasanen M, Koskenvuo M, Romanov K, Varjonen J, Kaprio J (2000) Familial association between allergic disorders and depression in adult Finnish twins. Am J Med Genet 96: 146–153PubMedCrossRefGoogle Scholar
  53. 53.
    Wamboldt MZ, Schmitz S, Mrazek D (1998) Genetic association between atopy and behavioral symptoms in middle childhood. J Child Psychol Psychiatry 39: 1007–1016PubMedCrossRefGoogle Scholar
  54. 54.
    Dantzer R (2001) Cytokine-induced sickness behavior: where do we stand?. Brain Behav Immun 15: 7–24PubMedCrossRefGoogle Scholar
  55. 55.
    Banasr M, Duman RS (2007) Regulation of neurogenesis and gliogenesis by stress and antidepressant treatment. CNS Neurol Disord Drug Targets 6: 311–320PubMedCrossRefGoogle Scholar
  56. 56.
    Goshen I, Kreisel T, Ben-Menachem-Zidon O, Licht T, Weidenfeld J, Ben-Hur T, Yirmiya R (2008) Brain interleukin-1 mediates chronic stress-induced depression in mice via adrenocortical activation and hippocampal neurogenesis suppression. Mol Psychiatry 13: 717–728PubMedCrossRefGoogle Scholar
  57. 57.
    Ben Menachem-Zidon O, Goshen I, Kreisel T, Ben Menahem Y, Reinhartz E, Ben Hur T, Yirmiya R (2008) Intrahippocampal transplantation of transgenic neural precursor cells overexpressing interleukin-1 receptor antagonist blocks chronic isolation-induced impairment in memory and neurogenesis. Neuropsychopharmacology 33: 2251–2262PubMedCrossRefGoogle Scholar
  58. 58.
    Muller N, Schwarz MJ (2008) COX-2 inhibition in schizophrenia and major depression. Curr Pharm Des 14: 1452–1465PubMedCrossRefGoogle Scholar
  59. 59.
    Capuron L, Ravaud A, Dantzer R (2000) Early depressive symptoms in cancer patients receiving interleukin 2 and/or interferon alfa-2b therapy. J Clin Oncol 18: 2143–2151PubMedGoogle Scholar
  60. 60.
    Capuron L, Ravaud A, Gualde N, Bosmans E, Dantzer R, Maes M, Neveu PJ (2001) Association between immune activation and early depressive symptoms in cancer patients treated with interleukin-2-based therapy. Psychoneuroendocrinology 26: 797–808PubMedCrossRefGoogle Scholar
  61. 61.
    Musselman DL, Lawson DH, Gumnick JF, Manatunga AK, Penna S, Goodkin RS, Greiner K, Nemeroff CB, Miller AH (2001) Paroxetine for the prevention of depression induced by high-dose interferon alfa. N Engl J Med 344: 961–966PubMedCrossRefGoogle Scholar
  62. 62.
    Yirmiya R, Weidenfeld J, Polak Y, Morag M, Morag A, Avitsur R, Barak O, Reichenberg A, Cohen E, Shavit Y et al (1999) Cytokines, depression due to a generalised medical condition, and antidepressant drugs. Adv Exp Med Biol 461: 283–316PubMedCrossRefGoogle Scholar
  63. 63.
    Yirmiya R (1996) Endotoxin produces a depressive-like episode in rats. Brain Res 711: 163–174PubMedCrossRefGoogle Scholar
  64. 64.
    Castanon N, Bluthé RM, Dantzer R (2001) Chronic treatment with the atypical atidepressant tianeptine attenuates sickness behaviour induced by peripheral but not central liopolysaccharide and interleukin-1β in the rat. Psychopharmacology 154: 50–60PubMedCrossRefGoogle Scholar
  65. 65.
    Wichers MC, Kenis G, Leue C, Koek G, Robaeys G, Maes M (2006) Baseline immune activation as a risk factor for the onset of depression during interferon-alpha treatment. Biol Psychiatry 60: 77–79PubMedCrossRefGoogle Scholar
  66. 66.
    Konsman JP, Parnet P, Dantzer R (2002) Cytokine-induced sickness behaviour: mechanisms and implications. Trends Neurosci 25: 154–159PubMedCrossRefGoogle Scholar
  67. 67.
    Lowry CA, Lightman SL, Nutt DL (2009) That warm fuzzy feeling: brain serotonergic neurons and the regulation of emotion. J Psychopharmacol 23: 392–400PubMedCrossRefGoogle Scholar
  68. 68.
    Capuron L, Neurauter G, Musselman DL, Lawson DH, Nemeroff CB, Fuchs D, Miller AH (2003) Interferon-alpha-induced changes in tryptophan metabolism; relationship to depression and paroxetine treatment. Biol Psychiatry 54: 906–914PubMedCrossRefGoogle Scholar
  69. 69.
    Ostensen M, Forger F, Nelson JL, Schuhmacher A, Hebisch G, Villiger PM (2005) Pregnancy in patients with rheumatic disease: anti-inflammatory cytokines increase in pregnancy and decrease post partum. Ann Rheum Dis 64: 839–844PubMedCrossRefGoogle Scholar
  70. 70.
    Maes M, Verkerk R, Bonaccorso S, Ombelet W, Bosmans E, Scharpe S (2002) Depressive and anxiety symptoms in the early puerperium are related to increased degradation of tryptophan into kynurenine, a phenomenon which is related to immune activation. Life Sci 71: 1837–1848PubMedCrossRefGoogle Scholar
  71. 71.
    Ruddick JP, Evans AK, Nutt DJ, Lightman SL, Rook GA, Lowry CA (2006) Tryptophan metabolism in the central nervous system: medical implications. Expert Rev Mol Med 8: 1–27PubMedCrossRefGoogle Scholar
  72. 72.
    Saito K, Crowley JS, Markey SP, Heyes MP (1993) A mechanism for increased quinolinic acid formation following acute systemic immune stimulation. J Biol Chem 268: 15496–15503PubMedGoogle Scholar
  73. 73.
    Steiner J, Bielau H, Brisch R, Danos P, Ullrich O, Mawrin C, Bernstein HG, Bogerts B (2008) Immunological aspects in the neurobiology of suicide: elevated microglial density in schizophrenia and depression is associated with suicide. J Psychiatr Res 42: 151–157PubMedCrossRefGoogle Scholar
  74. 74.
    Belmaker RH, Agam G (2008) Major depressive disorder. N Engl J Med 358: 55–68PubMedCrossRefGoogle Scholar
  75. 75.
    Linthorst AC, Reul JM (1998) Brain neurotransmission during peripheral inflammation. Ann NY Acad Sci 840: 139–152PubMedCrossRefGoogle Scholar
  76. 76.
    Lavicky J, Dunn AJ (1995) Endotoxin administration stimulates cerebral catecholamine release in freely moving rats as assessed by microdialysis. J Neurosci Res 40: 407–413PubMedCrossRefGoogle Scholar
  77. 77.
    Lowry CA, Evans AK, Gasser PJ, Hale MW, Staub DR, Shekhar A (2008) Topographical organization and chemoarchitecture of the dorsal raphe nucleus and the median raphe nucleus. In: JM Monti, BL Pandi-Perumal, BL Jacobs, DL Nutt (eds): Serotonin and Sleep: Molecular, Functional and Clinical Aspects. Birkhäuser, Basel, 25–68CrossRefGoogle Scholar
  78. 78.
    Lowry CA, Hollis JH, de Vries A, Pan B, Brunet LR, Hunt JR, Paton JF, van Kampen E, Knight DM, Evans AK et al (2007) Identification of an immune-responsive mesolimbocortical serotonergic system: Potential role in regulation of emotional behavior. Neuroscience 146: 756–772PubMedCrossRefGoogle Scholar
  79. 79.
    Drevets WC, Price JL, Furey ML (2008) Brain structural and functional abnormalities in mood disorders: implications for neurocircuitry models of depression. Brain Struct Funct 213: 93–118PubMedCrossRefGoogle Scholar
  80. 80.
    Pollmacher T, Haack M, Schuld A, Reichenberg A, Yirmiya R (2002) Low levels of circulating inflammatory cytokines — do they affect human brain functions? Brain Behav Immun 16: 525–532PubMedCrossRefGoogle Scholar
  81. 81.
    Kapsimalis F, Richardson G, Opp MR, Kryger M (2005) Cytokines and normal sleep. Curr Opin Pulm Med 11: 481–484PubMedCrossRefGoogle Scholar
  82. 82.
    Mullington J, Korth C, Hermann DM, Orth A, Galanos C, Holsboer F, Pollmacher T (2000) Dose-dependent effects of endotoxin on human sleep. Am J Physiol Regul Integr Comp Physiol 278: R947–955PubMedGoogle Scholar
  83. 83.
    Wright CE, Strike PC, Brydon L, Steptoe A (2005) Acute inflammation and negative mood: mediation by cytokine activation. Brain Behav Immun 19: 345–350PubMedCrossRefGoogle Scholar
  84. 84.
    Maes M, Kubera M, Leunis JC (2008) The gut-brain barrier in major depression: intestinal mucosal dysfunction with an increased translocation of LPS from gram negative enterobacteria (leaky gut) plays a role in the inflammatory pathophysiology of depression. Neuroendocrinol Lett 29: 117–124PubMedGoogle Scholar
  85. 85.
    Meddings J (2008) The significance of the gut barrier in disease. Gut 57: 438–440PubMedCrossRefGoogle Scholar
  86. 86.
    D’Inca R, Di Leo V, Corrao G, Martines D, D’Odorico A, Mestriner C, Venturi C, Longo G, Sturniolo GC (1999) Intestinal permeability test as a predictor of clinical course in Crohn’s disease. Am J Gastroenterol 94: 2956–2960PubMedGoogle Scholar
  87. 87.
    Wyatt J, Vogelsang H, Hubl W, Waldhoer T, Lochs H (1993) Intestinal permeability and the prediction of relapse in Crohn’s disease. Lancet 341: 1437–1439PubMedCrossRefGoogle Scholar
  88. 88.
    Fasano A, Shea-Donohue T (2005) Mechanisms of disease: the role of intestinal barrier. function in the pathogenesis of gastrointestinal autoimmune diseases. Nat Clin Pract Gastroenterol Hepatol 2: 416–422PubMedCrossRefGoogle Scholar
  89. 89.
    Bosi E, Molteni L, Radaelli MG, Folini L, Fermo I, Bazzigaluppi E, Piemonti L, Pastore MR, Paroni R (2006) Increased intestinal permeability precedes clinical onset of type 1 diabetes. Diabetologia 49: 2824–2827PubMedCrossRefGoogle Scholar
  90. 90.
    Watts T, Berti I, Sapone A, Gerarduzzi T, Not T, Zielke R, Fasano A (2005) Role of the intestinal tight junction modulator zonulin in the pathogenesis of type I diabetes in BB diabetic-prone rats. Proc Natl Acad Sci USA 102: 2916–2921PubMedCrossRefGoogle Scholar
  91. 91.
    Yacyshyn B, Meddings J, Sadowski D, Bowen-Yacyshyn MB (1996) Multiple sclerosis patients have peripheral blood CD45RO+ B cells and increased intestinal permeability. Dig Dis Sci 41: 2493–2498PubMedCrossRefGoogle Scholar
  92. 92.
    Hijazi Z, Molla AM, Al-Habashi H, Muawad WM, Molla AM, Sharma PN (2004) Intestinal permeability is increased in bronchial asthma. Arch Dis Child 89: 227–229PubMedCrossRefGoogle Scholar
  93. 93.
    Benard A, Desreumeaux P, Huglo D, Hoorelbeke A, Tonnel AB, Wallaert B (1996) Increased intestinal permeability in bronchial asthma. J Allergy Clin Immunol 97: 1173–1178PubMedCrossRefGoogle Scholar
  94. 94.
    Merali Z, Du L, Hrdina P, Palkovits M, Faludi G, Poulter MO, Anisman H (2004) Dysregulation in the suicide brain: mRNA expression of corticotropin-releasing hormone receptors and GABA(A) receptor subunits in frontal cortical brain region. J Neurosci 24: 1478–1485PubMedCrossRefGoogle Scholar
  95. 95.
    Lee R, Geracioti TD, Jr., Kasckow JW, Coccaro EF (2005) Childhood trauma and personality disorder: positive correlation with adult CSF corticotropin-releasing factor concentrations. Am J Psychiatry 162: 995–997PubMedCrossRefGoogle Scholar
  96. 96.
    Gareau MG, Silva MA, Perdue MH (2008) Pathophysiological mechanisms of stress-induced intestinal damage. Curr Mol Med 8: 274–281PubMedCrossRefGoogle Scholar
  97. 97.
    Teitelbaum AA, Gareau MG, Jury J, Yang PC, Perdue MH (2008) Chronic peripheral administration of corticotropin-releasing factor causes colonic barrier dysfunction similar to psychological stress. Am J Physiol Gastrointest Liver Physiol 295: G452–459PubMedCrossRefGoogle Scholar
  98. 98.
    Stengel A, Tache Y (2009) Neuroendocrine control of the gut during stress: corticotropin-releasing factor signaling pathways in the spotlight. Annu Rev Physiol 71: 219–239PubMedCrossRefGoogle Scholar
  99. 99.
    Calcagni E, Elenkov I (2006) Stress system activity, innate and T helper cytokines, and susceptibility to immune-related diseases. Ann NY Acad Sci 1069: 62–76PubMedCrossRefGoogle Scholar
  100. 100.
    Zbytek B, Slominski AT (2007) CRH mediates inflammation induced by lipopolysaccharide in human adult epidermal keratinocytes. J Invest Dermatol 127: 730–732PubMedCrossRefGoogle Scholar
  101. 101.
    Lydiard RB (2005) Increased prevalence of functional gastrointestinal disorders in panic disorder: clinical and theoretical implications. CNS Spectr 10: 899–908PubMedGoogle Scholar
  102. 102.
    de la Fontaine L, Schwarz MJ, Eser. D, Muller N, Rupprecht R, Zwanzger P (2008) Effects of experimentally induced panic attacks on neuroimmunological markers. J Neural Transm Published online DOI 10.1007/s00702-00008-00140-00706Google Scholar
  103. 103.
    Lesperance F, Frasure-Smith N (2007) Depression and heart disease. Cleve Clin J Med 74 (Suppl 1): S63–66CrossRefGoogle Scholar
  104. 104.
    Capuron L, Su S, Miller AH, Bremner JD, Goldberg J, Vogt GJ, Maisano C, Jones L, Murrah NV, Vaccarino V (2008) Depressive symptoms and metabolic syndrome: is inflammation the underlying link? Biol Psychiatry 64: 896–900PubMedCrossRefGoogle Scholar
  105. 105.
    Gervasoni N, Aubry JM, Bondolfi G, Osiek C, Schwald M, Bertschy G, Karege F (2005) Partial normalization of serum brain-derived neurotrophic factor in remitted patients after a major depressive episode. Neuropsychobiology 51: 234–238PubMedCrossRefGoogle Scholar
  106. 106.
    Manni L, Nikolova V, Vyagova D, Chaldakov GN, Aloe L (2005) Reduced plasma levels of NGF and BDNF in patients with acute coronary syndromes. Int J Cardiol 102: 169–171PubMedCrossRefGoogle Scholar
  107. 107.
    Groneberg DA, Fischer TC, Peckenschneider N, Noga O, Dinh QT, Welte T, Welker P (2007) Cell type-specific regulation of brain-derived neurotrophic factor in states of allergic inflammation. Clin Exp Allergy 37: 1386–1391PubMedCrossRefGoogle Scholar
  108. 108.
    Lalive PH, Kantengwa S, Benkhoucha M, Juillard C, Chofflon M (2008) Interferon-beta induces brain-derived neurotrophic factor in peripheral blood mononuclear cells of multiple sclerosis patients. J Neuroimmunol 197: 147–151PubMedCrossRefGoogle Scholar
  109. 109.
    Warner-Schmidt JL, Duman RS (2007) VEGF is an essential mediator of the neurogenic and behavioral actions of antidepressants. Proc Natl Acad Sci USA 104: 4647–4652PubMedCrossRefGoogle Scholar
  110. 110.
    Akil H, Evans SJ, Turner CA, Perez J, Myers RM, Bunney WE, Jones EG, Watson SJ (2008) The fibroblast growth factor family and mood disorders. Novartis Found Symp 289: 94–96; discussion 97–100, 193–105PubMedCrossRefGoogle Scholar
  111. 111.
    Kardami E, Detillieux K, Ma X, Jiang Z, Santiago JJ, Jimenez SK, Cattini PA (2007) Fibroblast growth factor-2 and cardioprotection. Heart Fail Rev 12: 267–277PubMedCrossRefGoogle Scholar
  112. 112.
    Leonard BE, Song C (1999) Stress, depression, and the role of cytokines. Adv Exp Med Biol 461: 251–265PubMedCrossRefGoogle Scholar
  113. 113.
    Watkins LR, Maier SF (1999) Implications of immune-to-brain communication for sickness and pain. Proc Natl Acad Sci USA 96: 7710–7713PubMedCrossRefGoogle Scholar
  114. 114.
    Pace TW, Mletzko TC, Alagbe O, Musselman DL, Nemeroff CB, Miller AH, Heim CM (2006) Increased stress-induced inflammatory responses in male patients with major depression and increased early life stress. Am J Psychiatry 163: 1630–1633PubMedCrossRefGoogle Scholar
  115. 115.
    Ising M, Kunzel HE, Binder EB, Nickel T, Modell S, Holsboer F (2005) The combined dexamethasone/CRH test as a potential surrogate marker in depression. Prog Neuropsychopharmacol Biol Psychiatry 29: 1085–1093PubMedCrossRefGoogle Scholar
  116. 116.
    Jun TY, Pae CU, Hoon H, Chae JH, Bahk WM, Kim KS, Serretti A (2003) Possible association between-G308A tumour necrosis factor-alpha gene polymorphism and major depressive disorder in the Korean population. Psychiatr Genet 13: 179–181PubMedCrossRefGoogle Scholar
  117. 117.
    Fertuzinhos SM, Oliveira JR, Nishimura AL, Pontual D, Carvalho DR, Sougey EB, Otto PA, Zatz M (2004) Analysis of IL-1alpha, IL-1beta, and IL-1RA [correction of IL-RA] polymorphisms in dysthymia. J Mol Neurosci 22: 251–256PubMedCrossRefGoogle Scholar
  118. 118.
    Wilson AG, Gordon C, di Giovine FS, de Vries N, van de Putte LB, Emery P, Duff GW (1994) A genetic association between systemic lupus erythematosus and tumor necrosis factor alpha. Eur J Immunol 24: 191–195PubMedCrossRefGoogle Scholar
  119. 119.
    Misener VL, Gomez L, Wigg KG, Luca P, King N, Kiss E, Daroczi G, Kapornai K, Tamas Z, Mayer L et al (2008) Cytokine Genes TNF, IL1A, IL1B, IL6, IL1RN and IL10, and childhood-onset mood disorders. Neuropsychobiology 58: 71–80PubMedCrossRefGoogle Scholar
  120. 120.
    Kraus MR, Al-Taie O, Schafer A, Pfersdorff M, Lesch KP, Scheurlen M (2007) Serotonin-1A receptor gene HTR1A variation predicts interferon-induced depression in chronic hepatitis C. Gastroenterology 132: 1279–1286PubMedCrossRefGoogle Scholar
  121. 121.
    Cai W, Khaoustov VI, Xie Q, Pan T, Le W, Yoffe B (2005) Interferon-alpha-induced modulation of glucocorticoid and serotonin receptors as a mechanism of depression. J Hepatol 42: 880–887PubMedCrossRefGoogle Scholar
  122. 122.
    Neumeister A, Bain E, Nugent AC, Carson RE, Bonne O, Luckenbaugh DA, Eckelman W, Herscovitch P, Charney DS, Drevets WC (2004) Reduced serotonin type 1A receptor binding in panic disorder. J Neurosci 24: 589–591PubMedCrossRefGoogle Scholar
  123. 123.
    Lanzenberger RR, Mitterhauser M, Spindelegger C, Wadsak W, Klein N, Mien LK, Holik A, Attarbaschi T, Mossaheb N, Sacher J et al (2007) Reduced serotonin-1A receptor binding in social anxiety disorder. Biol Psychiatry 61: 1081–1089PubMedCrossRefGoogle Scholar
  124. 124.
    Hirvonen J, Karlsson H, Kajander J, Lepola A, Markkula J, Rasi-Hakala H, Nagren K, Salminen JK, Hietala J (2008) Decreased brain serotonin 5-HT1A receptor availability in medication-naive patients with major depressive disorder: an in vivo imaging study using PET and [carbonyl-11C]WAY-100635. Int J Neuropsychopharmacol 11: 465–476PubMedCrossRefGoogle Scholar
  125. 125.
    Nash JR, Sargent PA, Rabiner EA, Hood SD, Argyropoulos SV, Potokar JP, Grasby PM, Nutt DJ (2008) Serotonin 5-HT1A receptor binding in people with panic disorder: positron emission tomography study. Br J Psychiatry 193: 229–234PubMedCrossRefGoogle Scholar
  126. 126.
    Drago A, Ronchi DD, Serretti A (2008) 5-HT1A gene variants and psychiatric disorders: a review of current literature and selection of SNPs for future studies. Int J Neuropsychopharmacol 11: 701–721PubMedCrossRefGoogle Scholar
  127. 127.
    Le Francois B, Czesak M, Steubl D, Albert PR (2008) Transcriptional regulation at a HTR1A polymorphism associated with mental illness. Neuropharmacology 55: 977–985PubMedCrossRefGoogle Scholar
  128. 128.
    Lesch KP, Wiesmann M, Hoh A, Muller T, Disselkamp-Tietze J, Osterheider M, Schulte HM (1992) 5-HT1A receptor-effector system responsivity in panic disorder. Psychopharmacology (Berl) 106: 111–117CrossRefGoogle Scholar
  129. 129.
    Hennig J, Becker H, Netter P (1996) 5-HT agonist-induced changes in peripheral immune cells in healthy volunteers: the impact of personality. Behav Brain Res 73: 359–363PubMedCrossRefGoogle Scholar
  130. 130.
    Yu B, Becnel J, Zerfaoui M, Rohatgi R, Boulares AH, Nichols CD (2008) Serotonin 5-hydroxytryptamine(2A) receptor activation suppresses tumor necrosis factor-alpha-induced inflammation with extraordinary potency. J Pharmacol Exp Ther 327: 316–323PubMedCrossRefGoogle Scholar
  131. 131.
    Evans SJ, Choudary PV, Vawter MP, Li J, Meador-Woodruff JH, Lopez JF, Burke SM, Thompson RC, Myers RM, Jones EG et al (2003) DNA microarray analysis of functionally discrete human brain regions reveals divergent transcriptional profiles. Neurobiol Dis 14: 240–250PubMedCrossRefGoogle Scholar
  132. 132.
    Inada Y, Yoneda H, Koh J, Sakai J, Himei A, Kinoshita Y, Akabame K, Hiraoka Y, Sakai T (2003) Positive association between panic disorder and polymorphism of the serotonin 2A receptor gene. Psychiatry Res 118: 25–31PubMedCrossRefGoogle Scholar
  133. 133.
    Unschuld PG, Ising M, Erhardt A, Lucae S, Kloiber S, Kohli M, Salyakina D, Welt T, Kern N, Lieb R et al (2007) Polymorphisms in the serotonin receptor gene HTR2A are associated with quantitative traits in panic disorder. Am J Med Genet B Neuropsychiatr Genet 144B: 424–429PubMedCrossRefGoogle Scholar
  134. 134.
    Yoon HK, Yang JC, Lee HJ, Kim YK (2008) The association between serotonin-related gene polymorphisms and panic disorder. J Anxiety Disord 22: 1529–1534PubMedCrossRefGoogle Scholar
  135. 135.
    Celada P, Puig M, Amargos-Bosch M, Adell A, Artigas F (2004) The therapeutic role of 5-HT1A and 5-HT2A receptors in depression. J Psychiatry Neurosci 29: 252–265PubMedGoogle Scholar
  136. 136.
    Pace TW, Hu F, Miller AH (2007) Cytokine-effects on glucocorticoid receptor function: relevance to glucocorticoid resistance and the pathophysiology and treatment of major depression. Brain Behav Immun 21: 9–19PubMedCrossRefGoogle Scholar
  137. 137.
    Miller AH, Pariante CM, Pearce BD (1999) Effects of cytokines on glucocorticoid receptor expression and function. Glucocorticoid resistance and relevance to depression. Adv Exp Med Biol 461: 107–116PubMedCrossRefGoogle Scholar
  138. 138.
    Pariante CM, Pearce BD, Pisell TL, Sanchez CI, Po C, Su C, Miller AH (1999) The proinflammatory cytokine, interleukin-1alpha, reduces glucocorticoid receptor translocation and function. Endocrinology 140: 4359–4366PubMedCrossRefGoogle Scholar
  139. 139.
    Lichtenstein GR, Bala M, Han C, DeWoody K, Schaible T (2002) Infliximab improves quality of life in patients with Crohn’s disease. Inflamm Bowel Dis 8: 237–243PubMedCrossRefGoogle Scholar
  140. 140.
    Tyring S, Gottlieb A, Papp K, Gordon K, Leonardi C, Wang A, Lalla D, Woolley M, Jahreis A, Zitnik R et al (2006) Etanercept and clinical outcomes, fatigue, and depression in psoriasis: double-blind placebo-controlled randomised phase III trial. Lancet 367: 29–35PubMedCrossRefGoogle Scholar
  141. 141.
    Müller N, Schwarz MJ, Dehning S, Douhe A, Cerovecki A, Goldstein-Muller B, Spellmann I, Hetzel G, Maino K, Kleindienst N et al (2006) The cyclooxygenase-2 inhibitor celecoxib has therapeutic effects in major depression: results of a double-blind, randomized, placebo controlled, add-on pilot study to reboxetine. Mol Psychiatry 11: 680–684PubMedCrossRefGoogle Scholar
  142. 142.
    Maes M, Song C, Lin AH, Bonaccorso S, Kenis G, De Jongh R, Bosmans E, Scharpe S (1999) Negative immunoregulatory effects of antidepressants: inhibition of interferongamma and stimulation of interleukin-10 secretion. Neuropsychopharmacology 20: 370–379PubMedCrossRefGoogle Scholar
  143. 143.
    Kubera M, Lin AH, Kenis G, Bosmans E, van Bockstaele D, Maes M (2001) Anti-Inflammatory effects of antidepressants through suppression of the interferon-gamma/interleukin-10 production ratio. J Clin Psychopharmacol 21: 199–206PubMedCrossRefGoogle Scholar
  144. 144.
    Leonard BE (2001) The immune system, depression and the action of antidepressants. Prog Neuropsychopharmacol Biol Psychiatry 25: 767–780PubMedCrossRefGoogle Scholar
  145. 145.
    Diamond M, Kelly JP, Connor TJ (2006) Antidepressants suppress production of the Th1 cytokine interferon-gamma, independent of monoamine transporter blockade. Eur Neuropsychopharmacol 16: 481–490PubMedCrossRefGoogle Scholar
  146. 146.
    Rapaport MH, Manji HK (2001) The effects of lithium on ex vivo cytokine production. Biol Psychiatry 50: 217–224PubMedCrossRefGoogle Scholar
  147. 147.
    Maes M, Song C, Lin AH, Pioli R, Kenis G, Kubera M, Bosmans E (1999) In vitro immunoregulatory effects of lithium in healthy volunteers. Psychopharmacology (Berl) 143: 401–407CrossRefGoogle Scholar
  148. 148.
    Lanquillon S, Krieg JC, Bening-Abu-Shach U, Vedder H (2000) Cytokine production and treatment response in major depressive disorder. Neuropsychopharmacology 22: 370–379PubMedCrossRefGoogle Scholar
  149. 149.
    Kubera M, Maes M, Holan V, Basta-Kaim A, Roman A, Shani J (2001) Prolonged desipramine treatment increases the production of interleukin-10, an anti-inflammatory cytokine, in C57BL/6 mice subjected to the chronic mild stress model of depression. J Affect Disord 63: 171–178PubMedCrossRefGoogle Scholar
  150. 150.
    Suhara T, Sudo Y, Yoshida K, Okubo Y, Fukuda H, Obata T, Yoshikawa K, Suzuki K, Sasaki Y (1998) Lung as reservoir for antidepressants in pharmacokinetic drug interactions. Lancet 351: 332–335PubMedCrossRefGoogle Scholar
  151. 151.
    Rudd ML, Nicolas AN, Brown BL, Fischer-Stenger K, Stewart JK (2005) Peritoneal macrophages express the serotonin transporter. J Neuroimmunol 159: 113–118PubMedCrossRefGoogle Scholar
  152. 152.
    O’Connell PJ, Wang X, Leon-Ponte M, Griffiths C, Pingle SC, Ahern GP (2006) A novel form of immune signaling revealed by transmission of the inflammatory mediator serotonin between dendritic cells and T cells. Blood 107: 1010–1017PubMedCrossRefGoogle Scholar
  153. 153.
    Ramamoorthy S, Ramamoorthy JD, Prasad PD, Bhat GK, Mahesh VB, Leibach FH, Ganapathy V (1995) Regulation of the human serotonin transporter by interleukin-1 beta. Biochem Biophys Res Commun 216: 560–567PubMedCrossRefGoogle Scholar
  154. 154.
    Mossner R, Heils A, Stober G, Okladnova O, Daniel S, Lesch KP (1998) Enhancement of serotonin transporter function by tumor necrosis factor alpha but not by interleukin-6. Neurochem Int 33: 251–254PubMedCrossRefGoogle Scholar
  155. 155.
    Mossner R, Daniel S, Schmitt A, Albert D, Lesch KP (2001) Modulation of serotonin transporter function by interleukin-4. Life Sci 68: 873–880PubMedCrossRefGoogle Scholar
  156. 156.
    Caspi A, Sugden K, Moffitt TE, Taylor A, Craig IW, Harrington H, McClay J, Mill J, Martin J, Braithwaite A et al (2003) Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science 301: 386–389PubMedCrossRefGoogle Scholar
  157. 157.
    Hariri AR, Holmes A (2006) Genetics of emotional regulation: the role of the serotonin transporter in neural function. Trends Cogn Sci 10: 182–191PubMedCrossRefGoogle Scholar
  158. 158.
    Botting NP (1995) Chemistry and neurochemistry of the kynurenine pathway of tryptophan metabolism. Chem Soc Rev 24: 401–412CrossRefGoogle Scholar
  159. 159.
    Mangoni A (1974) The “kynurenine shunt” and depression. Adv Biochem Psychopharmacol 11: 293–298PubMedGoogle Scholar
  160. 160.
    Badawy AA, Morgan CJ, Dacey A, Stoppard T (1991) The effects of lofepramine and desmethylimipramine on tryptophan metabolism and disposition in the rat. Biochem Pharmacol 42: 921–929PubMedCrossRefGoogle Scholar
  161. 161.
    Badawy AA, Morgan CJ (1991) Effects of acute paroxetine administration on tryptophan metabolism and disposition in the rat. Brit J Pharmacol 102: 429–433Google Scholar
  162. 162.
    Bano S, Sherkheli MA (2003) Inhibition of tryptophan — pyrrolase activity and elevation of brain tryptophan concentration by fluoxetine in rats. J Coll Physicians Surg Pak 13: 5–10PubMedGoogle Scholar
  163. 163.
    Badawy AAB, Morgan JC, Bano S, Buckland P, McGuffin P (1996) Mechanism of enhancement of rat brain serotonin synthesis by acute fluoxetine administration. J Neurochem 66: 436–437Google Scholar
  164. 164.
    Badawy AA, Evans M (1982) Inhibition of rat liver tryptophan pyrrolase activity and elevation of brain tryptophan concentration by acute administration of small doses of antidepressants. Brit J Pharmacol 77: 59–67Google Scholar
  165. 165.
    Salter M, Hazelwood R, Pogson CI, Iyer R, Madge DJ (1995) The effects of a novel and selective inhibitor of tryptophan 2,3-dioxygenase on tryptophan and serotonin metabolism in the rat. Biochem Pharmacol 49: 1435–1442PubMedCrossRefGoogle Scholar
  166. 166.
    Salter M, Hazelwood R, Pogson CI, Iyer R, Madge DJ, Jones HT, Cooper BR, Cox RF, Wang CM, Wiard RP (1995) The effects of an inhibitor of tryptophan 2,3-dioxygenase and a combined inhibitor of tryptophan 2,3-dioxygenase and 5-HT reuptake in the rat. Neuropharmacology 34: 217–227PubMedCrossRefGoogle Scholar
  167. 167.
    Reinhard JF, Jr., Flanagan EM, Madge DJ, Iyer R, Salter M (1996) Effects of 540C91 [(E)-3-[2-(4′-pyridyl)-vinyl]-1H-indole], an inhibitor of hepatic tryptophan dioxygenase, on brain quinolinic acid in mice. Biochem Pharmacol 51: 159–163PubMedCrossRefGoogle Scholar
  168. 168.
    Mellor AL, Munn DH (2003) Tryptophan catabolism and regulation of adaptive immunity. J Immunol 170: 5809–5813PubMedGoogle Scholar
  169. 169.
    Hestad KA, Tonseth S, Stoen CD, Ueland T, Aukrust P (2003) Raised plasma levels of tumor necrosis factor alpha in patients with depression: normalization during electroconvulsive therapy. J Ect 19: 183–188PubMedCrossRefGoogle Scholar
  170. 170.
    Shafique S, Dalsing MC (2006) Vagus nerve stimulation therapy for treatment of drug-resistant epilepsy and depression. Perspect Vasc Surg Endovasc Ther 18: 323–327PubMedCrossRefGoogle Scholar
  171. 171.
    Borovikova LV, Ivanova S, Zhang M, Yang H, Botchkina GL, Watkins LR, Wang H, Abumrad N, Eaton JW, Tracey KJ (2000) Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature 405: 458–462PubMedCrossRefGoogle Scholar
  172. 172.
    Ghia JE, Blennerhassett P, Collins SM (2008) Impaired parasympathetic function increases susceptibility to inflammatory bowel disease in a mouse model of depression. J Clin Invest 118: 2209–2218PubMedGoogle Scholar
  173. 173.
    Corcoran C, Connor TJ, O’Keane V, Garland MR (2005) The effects of vagus nerve stimulation on pro-and anti-inflammatory cytokines in humans: a preliminary report. Neuroimmunomodulation 12: 307–309PubMedCrossRefGoogle Scholar
  174. 174.
    Feleszko W, Jaworska J, Rha RD, Steinhausen S, Avagyan A, Jaudszus A, Ahrens B, Groneberg DA, Wahn U, Hamelmann E (2007) Probiotic-induced suppression of allergic sensitization and airway inflammation is associated with an increase of T regulatory-dependent mechanisms in a murine model of asthma. Clin Exp Allergy 37: 498–505PubMedCrossRefGoogle Scholar
  175. 175.
    Sheil B, McCarthy J, O’Mahony L, Bennett MW, Ryan P, Fitzgibbon JJ, Kiely B, Collins JK, Shanahan F (2004) Is the mucosal route of administration essential for probiotic function? Subcutaneous administration is associated with attenuation of murine colitis and arthritis. Gut 53: 694–700PubMedCrossRefGoogle Scholar
  176. 176.
    Mazmanian SK, Round JL, Kasper DL (2008) A microbial symbiosis factor prevents intestinal inflammatory disease. Nature 453: 620–625PubMedCrossRefGoogle Scholar
  177. 177.
    Calcinaro F, Dionisi S, Marinaro M, Candeloro P, Bonato V, Marzotti S, Corneli RB, Ferretti E, Gulino A, Grasso F et al (2005) Oral probiotic administration induces interleukin-10 production and prevents spontaneous autoimmune diabetes in the non-obese diabetic mouse. Diabetologia 48: 1565–1575PubMedCrossRefGoogle Scholar
  178. 178.
    Desbonnet L, Garrett L, Clarke G, Bienenstock J, Dinan TG (2008) The probiotic Bifidobacteria infantis: An assessment of potential antidepressant properties in the rat. J Psychiatr Res 43: 164–174PubMedCrossRefGoogle Scholar
  179. 179.
    Varghese AK, Verdu EF, Bercik P, Khan WI, Blennerhassett PA, Szechtman H, Collins SM (2006) Antidepressants attenuate increased susceptibility to colitis in a murine model of depression. Gastroenterology 130: 1743–1753PubMedCrossRefGoogle Scholar
  180. 180.
    Kubera M, Kenis G, Bosmans E, Zieba A, Dudek D, Nowak G, Maes M (2000) Plasma levels of interleukin-6, interleukin-10, and interleukin-1 receptor antagonist in depression: comparison between the acute state and after remission. Pol J Pharmacol 52: 237–241PubMedGoogle Scholar
  181. 181.
    Parissis JT, Adamopoulos S, Rigas A, Kostakis G, Karatzas D, Venetsanou K, Kremastinos DT (2004) Comparison of circulating proinflammatory cytokines and soluble apoptosis mediators in patients with chronic heart failure with versus without symptoms of depression. Am J Cardiol 94: 1326–1328PubMedCrossRefGoogle Scholar
  182. 182.
    Kushikata T, Fang J, Krueger JM (1999) Interleukin-10 inhibits spontaneous sleep in rabbits. J Interferon Cytokine Res 19: 1025–1030PubMedCrossRefGoogle Scholar
  183. 183.
    Bluthé RM, Castanon N, Pousset F, Bristow A, Ball C, Lestage J, Michaud B, Kelley KW, Dantzer R (1999) Central injection of IL-10 antagonizes the behavioural effects of lipopolysaccharide in rats. Psychoneuroendocrinology 24: 301–311PubMedCrossRefGoogle Scholar
  184. 184.
    Kanaan SA, Poole S, Saade NE, Jabbur S, Safieh-Garabedian B (1998) Interleukin-10 reduces the endotoxin-induced hyperalgesia in mice. J Neuroimmunol 86: 142–150PubMedCrossRefGoogle Scholar
  185. 185.
    Di Santo E, Sironi M, Pozzi P, Gnocchi P, Isetta AM, Delvaux A, Goldman M, Marchant A, Ghezzi P (1995) Interleukin-10 inhibits lipopolysaccharide-induced tumor necrosis factor and interleukin-1 beta production in the brain without affecting the activation of the hypothalamus-pituitary-adrenal axis. Neuroimmunomodulation 2: 149–154PubMedCrossRefGoogle Scholar
  186. 186.
    Kim WK, Ganea D, Jonakait GM (2002) Inhibition of microglial CD40 expression by pituitary adenylate cyclase-activating polypeptide is mediated by interleukin-10. J Neuroimmunol 126: 16–24PubMedCrossRefGoogle Scholar
  187. 187.
    Leon LR, Kozak W, Kluger MJ (1998) Role of IL-10 in inflammation. Studies using cytokine knockout mice. Ann NY Acad Sci 856: 69–75PubMedCrossRefGoogle Scholar
  188. 188.
    Amaral FA, Sachs D, Costa VV, Fagundes CT, Cisalpino D, Cunha TM, Ferreira SH, Cunha FQ, Silva TA, Nicoli JR et al (2008) Commensal microbiota is fundamental for the development of inflammatory pain. Proc Natl Acad Sci USA 105: 2193–2197PubMedCrossRefGoogle Scholar
  189. 189.
    Bezchlibnyk YB, Wang JF, McQueen GM, Young LT (2001) Gene expression differences in bipolar disorder revealed by cDNA array analysis of post-mortem frontal cortex. J Neurochem 79: 826–834PubMedCrossRefGoogle Scholar
  190. 190.
    Sutcigil L, Oktenli C, Musabak U, Bozkurt A, Cansever A, Uzun O, Sanisoglu SY, Yesilova Z, Ozmenler N, Ozsahin A et al (2007) Pro-and anti-inflammatory cytokine balance in major depression: effect of sertraline therapy. Clin Dev Immunol 2007: 76396PubMedGoogle Scholar
  191. 191.
    Lee KM, Kim YK (2006) The role of IL-12 and TGF-beta1 in the pathophysiology of major depressive disorder. Int Immunopharmacol 6: 1298–1304PubMedCrossRefGoogle Scholar
  192. 192.
    Raymond NC, Dysken M, Bettin K, Eckert ED, Crow SJ, Markus K, Pomeroy C (2000) Cytokine production in patients with anorexia nervosa, bulimia nervosa, and obesity. Int J Eat Disord 28: 293–302PubMedCrossRefGoogle Scholar
  193. 193.
    Dalbeth N, Yeoman S, Dockerty JL, Highton J, Robinson E, Tan PL, Herman D, McQueen FM (2004) A randomised placebo controlled trial of delipidated, deglycolipidated Mycobacterium vaccae as immunotherapy for psoriatic arthritis. Ann Rheum Dis 63: 718–722PubMedCrossRefGoogle Scholar
  194. 194.
    O’Brien ME, Anderson H, Kaukel E, O’Byrne K, Pawlicki M, Von Pawel J, Reck M (2004) SRL172 (killed Mycobacterium vaccae) in addition to standard chemotherapy improves quality of life without affecting survival, in patients with advanced non-small-cell lung cancer: phase III results. Ann Oncol 15: 906–914PubMedCrossRefGoogle Scholar
  195. 195.
    O’Brien ME, Saini A, Smith IE, Webb A, Gregory K, Mendes R, Ryan C, Priest K, Bromelow KV, Palmer RD et al (2000) A randomized phase II study of SRL172 (Mycobacterium vaccae) combined with chemotherapy in patients with advanced inoperable non-small-cell lung cancer and mesothelioma. Br J Cancer 83: 853–857PubMedCrossRefGoogle Scholar
  196. 196.
    Heim C, Nemeroff CB (1999) The impact of early adverse experiences on brain systems involved in the pathophysiology of anxiety and affective disorders. Biol Psychiatry 46: 1509–1522PubMedCrossRefGoogle Scholar
  197. 197.
    Rook GAW, Lowry CA (2008) The hygiene hypothesis and psychiatric disorders. Trends Immunol 29: 150–158PubMedCrossRefGoogle Scholar

Copyright information

© Birkhäuser Verlag Basel/Switzerland 2009

Authors and Affiliations

  • Graham A. W. Rook
    • 1
  • Christopher A. Lowry
    • 2
  1. 1.Centre for Infectious Diseases and International Health, Windeyer Institute of Medical SciencesUniversity College LondonLondonUK
  2. 2.Department of Integrative PhysiologyUniversity of ColoradoBoulderUSA

Personalised recommendations