Neurochemical Research

, Volume 39, Issue 9, pp 1634–1639 | Cite as

Neuroimmunomodulation in Depression: A Review of Inflammatory Cytokines Involved in this Process

  • Helena M. Abelaira
  • Gislaine Z. Réus
  • Fabricia Petronilho
  • Tatiana Barichello
  • João Quevedo
Overview

Abstract

Depression is a debilitating mental disease that affects a large number of people globally; however the pathophysiological mechanisms of this disease remain incompletely understood. Some studies have shown that depression is associated with inflammatory activity, and the mode of action of several antidepressants appears to involve immunomodulation. In this case, the induction of a pro-inflammatory state in healthy or depressive subjects induces a ‘sickness behaviour’ resembling depressive symptomatology. Potential mechanisms of pro-inflammatory cytokines are effects on monoamine levels, disruption of the hypothalamic–pituitary–adrenal axis, activation of the pathological microglial cells, such as the macrophages and alterations in neuroplasticity and brain functions. Thus, this review will highlight the role of inflammation in depression, the possible mechanisms involved, and also explore effective treatments that act on the immune system.

Keywords

Cytokines Inflammation Antidepressants Depression 

References

  1. 1.
    Duman RS (1998) Novel therapeutic approaches beyond the serotonin receptor. Biol Psychiatry 44:324–335PubMedCrossRefGoogle Scholar
  2. 2.
    Patel A (2013) Review: the role of inflammation in depression. Psychiatr Danub 25:216–223Google Scholar
  3. 3.
    Nemeroff CB, Owens MJ (2002) Treatment of mood disorders. Nat Neurosci 5:1068–1070PubMedCrossRefGoogle Scholar
  4. 4.
    Herbert TB, Cohen S, Marsland AL et al (1994) Cardiovascular reactivity and the course of immune response to an acute psychological stressor. Psychosom Med 56:337–344PubMedCrossRefGoogle Scholar
  5. 5.
    Maes M (2001) The immunoregulatory effect of antidepressants. Hum Psychopharmacol Clin Exp 16:95–103CrossRefGoogle Scholar
  6. 6.
    Maes M (1999) Major depression and activation of the inflammatory response system. Adv Exp Med Biol 461:25–46PubMedCrossRefGoogle Scholar
  7. 7.
    Kushner I (1982) The phenomena of the acute phase response. Ann N Y Sci 389:39–48CrossRefGoogle Scholar
  8. 8.
    Smith RS (1991) The macrophage theory of depression. Med Hypotheses 35:298–306PubMedCrossRefGoogle Scholar
  9. 9.
    Sirisinha S (2011) Insight into the mechanisms regulating immune homeostasis in health and disease. Asian Pac J Allergy Immunol 1:1–14CrossRefGoogle Scholar
  10. 10.
    Suvisaari J, Mantere O (2013) Inflammation theories in psychotic disorders: a critical review. Infect Disord Drug Targets 13:59–70PubMedCrossRefGoogle Scholar
  11. 11.
    Suvisaari J, Loo BM, Saarni SE, Haukka J, Perälä J, Saarni SI, Viertiö S, Partti K, Lönnqvist J, Jula A (2011) Inflammation in psychotic disorders: a population-based study. Psychiatry Res 189:305–311PubMedCrossRefGoogle Scholar
  12. 12.
    Cruvinel WM, Mesquita DJ, Araújo JAP, Catelan TTT, Souza AW, Silva NP, Andrade LEC (2010) Sistema imunitário—parte i fundamentos da imunidade inata com ênfase nos mecanismos moleculares e celulares da resposta inflamatória. Rev Bras Reumatol 50:434–461Google Scholar
  13. 13.
    Gruys E, Toussaint MJ, Niewold TA, Koopmans SJ (2005) Acute phase reaction and acute phase proteins. J Zhejiang Univ Sci B 6:1045–1056PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Abbas AK, Lichtman AH, Pillai S (2012) Cellular and molecular immunology, 7th edn. Elsevier Saunders, Philadelphia, p 864Google Scholar
  15. 15.
    Janeway CA, Travers P (1997) Immunobiology. The immune system in health and disease, 3rd edn. Current Biol/Garland Publishing, New YorkGoogle Scholar
  16. 16.
    Kronfol Z, Remick DG (2000) Cytokines and the brain: implications for clinical psychiatry. Am J Psychiatry 157:683–694PubMedCrossRefGoogle Scholar
  17. 17.
    Rezaie P, Trillo-Pazos G, Everall IP, Male DK (2002) Expression of beta-chemokines and chemokine receptors in human fetal astrocyte and microglial co-cultures: potential role of chemokines in the developing CNS. Glia 37:64–75PubMedCrossRefGoogle Scholar
  18. 18.
    Lee YB, Nagai A, Kim SU (2002) Cytokines, chemokines, and cytokine receptors in human microglia. J Neurosci Res 69:94–103PubMedCrossRefGoogle Scholar
  19. 19.
    Khairova RA, Machado-Vieira R, Du J, Manji HK (2009) A potential role for pro-inflammatory cytokines in regulating synaptic plasticity in major depressive disorder. Int J Neuropsychopharmacol 12:561–578PubMedCentralPubMedCrossRefGoogle Scholar
  20. 20.
    Tsao CW, Lin YS, Chen CC, Bai CH, Wu SR (2006) Cytokines and serotonin transporter in patients with major depression. Prog Neuropsychopharmacol Biol Psychiatry 30:899–905PubMedCrossRefGoogle Scholar
  21. 21.
    Maes M (1995) Evidence for an immune response in major depression: a review and hypothesis. Prog Neuropsychopharmacol Biol Psychiatry 19:11–38PubMedCrossRefGoogle Scholar
  22. 22.
    Felger JC, Lotrich FE (2013) Inflammatory cytokines in depression: neurobiological mechanisms and therapeutic implications. Neuroscience 246:199–229PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    Dowlati Y, Herrmann N, Swardfager W, Liu H, Sham L, Reim EK, Lanctôt KL (2010) A meta-analysis of cytokines in major depression. Biol Psychiatry 67:446–457PubMedCrossRefGoogle Scholar
  24. 24.
    Kling MA, Alesci S, Csako G, Costello R, Luckenbaugh DA, Bonne O et al (2007) Sustained low-grade pro-inflammatory state in unmedicated, remitted women with major depressive disorder as evidenced by elevated serum levels of the acute phase proteins C-reactive protein and serum amyloid A. Biol Psychiatry 62:309–313PubMedCentralPubMedCrossRefGoogle Scholar
  25. 25.
    Ford DE, Erlinger TP (2004) Depression and C-reactive protein in US adults: data from the third national health and nutrition examination survey. Arch Intern Med 164:1010–1014PubMedCrossRefGoogle Scholar
  26. 26.
    Danner M, Kasl SV, Abramson JL, Vaccarino V (2003) Association between depression and elevated C-reactive protein. Psychosom Med 65:347–356PubMedCrossRefGoogle Scholar
  27. 27.
    Kop WJ, Gottdiener JS, Tangen CM, Fried LP, McBurnie MA, Walston J et al (2002) Inflammation and coagulation factors in persons N 65 years of age with symptoms of depression but without evidence of myocardial ischemia. Am J Cardiol 89:419–424PubMedCrossRefGoogle Scholar
  28. 28.
    Himmerich H, Fulda S, Linseisen J, Seiler H, Wolfram G, Himmerich S et al (2008) Depression, comorbidities and the TNF-alpha system. Eur Psychiatry 23:421–429PubMedCrossRefGoogle Scholar
  29. 29.
    Simen BB, Duman CH, Simen AA, Duman RS (2006) TNF[alpha] signaling in depression and anxiety: behavioral consequences of individual receptor targeting. Biol Psychiatry 59:775–785PubMedCrossRefGoogle Scholar
  30. 30.
    Malynn S, Campos-Torres A, Moynagh P, Haase J (2013) The pro-inflammatory cytokine TNF-α regulates the activity and expression of the serotonin transporter (SERT) in astrocytes. Neurochem Res 38:694–704PubMedCrossRefGoogle Scholar
  31. 31.
    Reichenberg A, Yirmiya R, Schuld A, Kraus T, Haack M, Morag A et al (2001) Cytokineassociated emotional and cognitive disturbances in humans. Arch Gen Psychiatry 58:445–452PubMedCrossRefGoogle Scholar
  32. 32.
    Levine J, Barak Y, Chengappa KN, Rapoport A, Rebey M, Barak V (1999) Cerebrospinal cytokine levels in patients with acute depression. Neuropsychobiol 40:171–176CrossRefGoogle Scholar
  33. 33.
    Lanquillon S, Krieg JC, Bening-Abu-Shach U, Vedder H (2000) Cytokine production and treatment response in major depressive disorder. Neuropsychopharmacol 22:370–379CrossRefGoogle Scholar
  34. 34.
    Mikova O, Yakimova R, Bosmans E, Kenis G, Maes M (2001) Increased serum tumor necrosis factor alpha concentrations in major depression and multiple sclerosis. Eur Neuropsychopharmacol 11:203–208PubMedCrossRefGoogle Scholar
  35. 35.
    Penninx BW, Kritchevsky SB, Yaffe K, Newman AB, Simonsick EM, Rubin S et al (2003) Inflammatory markers and depressed mood in older persons: results from the health, aging and body composition study. Biol Psychiatry 54:566–572PubMedCrossRefGoogle Scholar
  36. 36.
    Tuglu C, Kara SH, Caliyurt O, Vardar E, Abay E (2003) Increased serum tumor necrosis factor-alpha levels and treatment response in major depressive disorder. Psychopharmacol 170:429–433CrossRefGoogle Scholar
  37. 37.
    Marques-Deak AH, Neto FL, Dominguez WV, Solis AC, Kurcgant D, Sato F et al (2007) Cytokine profiles in women with different subtypes of major depressive disorder. J Psychiatr Res 41:152–159PubMedCrossRefGoogle Scholar
  38. 38.
    Palin K, McCusker RH, Strle K, Moos F, Dantzer R, Kelley KW (2008) Tumor necrosis factor-a-induced sickness behavior is impaired by central administration of an inhibitor of c-jun N-terminal kinase. Psychopharmacol 197:629–635CrossRefGoogle Scholar
  39. 39.
    Fu X, Zunich SM, O’Connor JC, Kavelaars A, Dantzer R, Kelley KW (2010) Central administration of lipopolysaccharide induces depressive-like behavior in vivo and activates brain indoleamine 2,3-dioxygenase in murine organotypic hippocampal slice cultures. J Neuroinflammation 7:43PubMedCentralPubMedCrossRefGoogle Scholar
  40. 40.
    Kent S, Bluthé RM, Kelley KW, Dantzer R (1992) Sickness behavior as a new target for drug development. Trends Pharmacol Sci 13:24–28PubMedCrossRefGoogle Scholar
  41. 41.
    Kent S, Bluthé RM, Dantzer R, Hardwick AJ, Kelley KW, Rothwell NJ, Vannice JL (1992) Different receptor mechanisms mediate the pyrogenic and behavioral effects of interleukin 1. Proc Natl Acad Sci USA 89:9117–9120PubMedCentralPubMedCrossRefGoogle Scholar
  42. 42.
    Kent S, Kelley KW, Dantzer R (1992) Effects of lipopolysaccharide on foodmotivated behavior in the rat are not blocked by an interleukin-1 receptor antagonist. Neurosci Lett 145:83–86PubMedCrossRefGoogle Scholar
  43. 43.
    Bluthé RM, Michaud B, Poli V, Dantzer R (2000) Role of IL-6 in cytokine-induced sickness behavior: a study with IL-6 deficient mice. Physiol Behav 70:367–373PubMedCrossRefGoogle Scholar
  44. 44.
    Ignatowski TA, Chou RC, Spengler RN (1996) Changes in noradrenergic sensitivity to tumor necrosis factor-alpha in brains of rats administered clonidine. J Neuroimmunol 70:55–63PubMedCrossRefGoogle Scholar
  45. 45.
    Nickola TJ, Ignatowski TA, Reynolds JL, Spengler RN (2001) Antidepressant drug-induced alterations in neuron-localized tumor necrosis factor-alpha mRNA and alpha(2)-adrenergic receptor sensitivity. J Pharmacol Exp Ther 297:680–687PubMedGoogle Scholar
  46. 46.
    Bayramg€urler D, Karson A, Ozer C, Utkan T (2013) Effects of longterm etanercept treatment on anxiety- and depression-like neurobehaviors in rats. Physiol Behav 119C:145–148CrossRefGoogle Scholar
  47. 47.
    Raison CL, Rutherford RE, Woolwine BJ, Shuo C, Schettler P, Drake DF et al (2013) A randomized controlled trial of the tumor necrosis factor antagonist infliximab for treatment-resistant depression: the role of baseline inflammatory biomarkers. JAMA Psychiatry 70:31–41PubMedCentralPubMedCrossRefGoogle Scholar
  48. 48.
    Kraneveld AD, de Theije CG, van Heesch F, Borre Y, de Kivit S, Olivier B, Korte M, Garssen J (2014) The neuro-immune axis: prospect for novel treatments for mental disorders. Basic Clin Pharmacol Toxicol 114:128–136PubMedCrossRefGoogle Scholar
  49. 49.
    Pineda EA, Hensler JG, Sankar R, Shin D, Burke TF, Mazarati AM (2012) Interleukin-1β causes fluoxetine resistance in an animal model of epilepsy-associated depression. Neurotherapeutics 9:477–485PubMedCentralPubMedCrossRefGoogle Scholar
  50. 50.
    Barrientos RM, Higgins EA, Sprunger DB, Watkins LR, Rudy JW, Maier SF (2002) Memory for context is impaired by a post context exposure injection of interleukin-1 beta into dorsal hippocampus. Behav Brain Res 134:291–298PubMedCrossRefGoogle Scholar
  51. 51.
    Bellinger FP, Madamba S, Siggins GR (1993) Interleukin 1 beta inhibits synaptic strength and long-term potentiation in the rat CA1 hippocampus. Brain Res 628:227–234PubMedCrossRefGoogle Scholar
  52. 52.
    Curran B, O’Connor JJ (2001) The pro-inflammatory cytokine interleukin-18 impairs long-term potentiation and NMDA receptor-mediated transmission in the rat hippocampus in vitro. Neuroscience 108:83–90PubMedCrossRefGoogle Scholar
  53. 53.
    Gibertini M, Newton C, Friedman H, Klein TW (1995) Spatial learning impairment in mice infected with Legionella pneumophila or administered exogenous interleukin-1-beta. Brain Behav Immun 9:113–128PubMedCrossRefGoogle Scholar
  54. 54.
    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
  55. 55.
    Oitzl MS, van Oers H, Schobitz B, de Kloet ER (1993) Interleukin-1 beta, but not interleukin-6, impairs spatial navigation learning. Brain Res 613:160–163PubMedCrossRefGoogle Scholar
  56. 56.
    Pugh CR, Nguyen KT, Gonyea JL, Fleshner M, Wakins LR, Maier SF, Rudy JW (1999) Role of interleukin-1 beta in impairment of contextual fear conditioning caused by social isolation. Behav Brain Res 106:109–118PubMedCrossRefGoogle Scholar
  57. 57.
    Parsadaniantz SM, Batsche E, Gegout-Pottie P et al (1997) Effects of continuous infusion of interleukin 1 beta on corticotropin-releasing hormone (CRH), CRH receptors, proopiomelanocortin gene expression and secretion of corticotropin, beta-endorphin and corticosterone. Neuroendocrinology 65:53–63PubMedCrossRefGoogle Scholar
  58. 58.
    Konsman JP, Veeneman J, Combe C, Poole S, Luheshi GN, Dantzer R (2008) Central nervous action of interleukin-1 mediates activation of limbic structures and behavioural depression in response to peripheral administration of bacterial lipopolysaccharide. Eur J Neurosci 28:2499–2510PubMedCrossRefGoogle Scholar
  59. 59.
    Dantzer R (2009) Cytokine, sickness behavior, and depression. Immunol Allergy Clin North Am 29:247–264PubMedCentralPubMedCrossRefGoogle Scholar
  60. 60.
    Goshen I, Yirmiya R (2009) Interleukin-1 (IL-1): a central regulator of stress responses. Front Neuroendocrinol 30:30–45PubMedCrossRefGoogle Scholar
  61. 61.
    Borkowska P, Kucia K, Rzezniczek S et al (2011) Interleukin-1beta promoter (-31T/C and -511C/T) polymorphisms in major recurrent depression. J Mol Neurosci 44:12–16PubMedCentralPubMedCrossRefGoogle Scholar
  62. 62.
    Baune BT, Dannlowski U, Domschke K et al (2010) The interleukin 1 beta (IL-1β) gene is associated with failure to achieve remission and impaired emotion processing in major depression. Biol Psychiatry 67:543–549PubMedCrossRefGoogle Scholar
  63. 63.
    Vezzani A, Maroso M, Balosso S, Sanchez MA, Bartfai T (2011) IL-1 receptor/Toll-like receptor signaling in infection, inflammation, stress and neurodegeneration couples hyperexcitability and seizures. Brain Behav Immun 25:1281–1289PubMedCrossRefGoogle Scholar
  64. 64.
    Herman JP, Cullinan WE (1997) Neurocircuitry of stress: central control of the hypothalamo-pituitary-adrenocortical axis. Trends Neurosci 20:78–84PubMedCrossRefGoogle Scholar
  65. 65.
    Yu S, Holsboer F, Almeida OF (2008) Neuronal actions of glucocorticoids: focus on depression. J Steroid Biochem Mol Biol 108:300–309PubMedCrossRefGoogle Scholar
  66. 66.
    Watson S, Gallagher P, Smith MS, Ferrier IN, Young AH (2006) The DEX/CRH test-is it better than the DST? Psychoneuroendocrinology 31:889–894PubMedCrossRefGoogle Scholar
  67. 67.
    Dantzer R (2001) Cytokine-induced sickness behavior: mechanisms and implications. Ann N Y Acad Sci 933:222–234PubMedCrossRefGoogle Scholar
  68. 68.
    Larson SJ, Dunn AJ (2001) Behavioral effects of cytokines. Brain Behav Immun 15:371–387PubMedCrossRefGoogle Scholar
  69. 69.
    Maier SF, Watkins LR (1998) Cytokines for psychologists: implications of bidirectional immune-to-brain communication for understanding behavior, mood, and cognition. Psychol Rev 105:83–107PubMedCrossRefGoogle Scholar
  70. 70.
    Yirmiya R (2000) Depression in medical illness: the role of the immune system. West J Med 173:333–336PubMedCentralPubMedCrossRefGoogle Scholar
  71. 71.
    Anderson G, Kubera M, Duda W, Lasoń W, Berk M, Maes M (2013) Increased IL-6 trans-signaling in depression: focus on the tryptophan catabolite pathway, melatonin andneuroprogression. Pharmacol Rep 65:1647–1654PubMedCrossRefGoogle Scholar
  72. 72.
    Dandrea M, Donadelli M, Costanzo C, Scarpa A, Palmieri M (2009) MeCP2/H3meK9 are involved in IL-6 gene silencing in pancreatic adenocarcinoma cell lines. Nucleic Acids Res 37:6681–6690PubMedCentralPubMedCrossRefGoogle Scholar
  73. 73.
    Maes M, Bosmans E, De Jongh R, Kenis G, Vandoolaeghe E, Neels H (1997) Increased serum IL-6 and IL-1 receptor antagonist concentrations in major depression and treatment resistant depression. Cytokine 9:853–858PubMedCrossRefGoogle Scholar
  74. 74.
    Basterzi AD, Aydemir C, Kisa C, Aksaray S, Tuzer V, Yazici K et al (2005) IL-6 levels decrease SSRI treatment in patients with major depression. Hum Psychopharmacol 20:473–476PubMedCrossRefGoogle Scholar
  75. 75.
    O’Brien SM, Scully P, Fitzgerald P, Scott LV, Dinan TG (2007) Plasma cytokine profiles in depressed patients who fail to respond to selective serotonin reuptake inhibitor therapy. J Psychiatr Res 41:326–331PubMedCrossRefGoogle Scholar
  76. 76.
    Himmerich H, Milenovic S, Fulda S, Plumakers B, Sheldrick AJ, Michel TM et al (2010) Regulatory T cells increased while IL-1beta decreased during antidepressant therapy. J Psychiatr Res 44:1052–1057PubMedCrossRefGoogle Scholar
  77. 77.
    Ohgi Y, Futamura T, Kikuchi T, Hashimoto K (2013) Effects of antidepressants on alternations in serum cytokines and depressive-like behavior in mice after lipopolysaccharide administration. Pharmacol Biochem Behav 103:853–859PubMedCrossRefGoogle Scholar
  78. 78.
    Réus GZ, Dos Santos MA, Abelaira HM, Ribeiro KF, Petronilho F, Vuolo F, Colpo GD, Pfaffenseller B, Kapczinski F, Dal-Pizzol F, Quevedo J (2013) Imipramine reverses alterations in cytokines and BDNF levels induced by maternal deprivation in adult rats. Behav Brain Res 242:40–46PubMedCrossRefGoogle Scholar
  79. 79.
    Nery FG, Monkul ES, Hatch JP, Fonseca M, Zunta-Soares GB, Frey BN, Bowden CL, Soares JC (2008) Celecoxib as an adjunct in the treatment of depressive or mixed episodes of bipolar disorder: a double-blind, randomized, placebo-controlled study. Hum Psychopharmacol 23:87–94PubMedCrossRefGoogle Scholar
  80. 80.
    Levine J, Cholestoy A, Zimmerman J (1996) Possible antidepressant effect of minocycline. Am J Psychiatry 153:582PubMedGoogle Scholar
  81. 81.
    Molina-Hernandez M, Tellez-Alcantara NP, Perez-garcia J et al (2008) Antidepressant-like actions of minocycline combined with several glutamate antagonists. Prog Neuropsychopharmacol Biol Psychiatry 32:380–386PubMedCrossRefGoogle Scholar
  82. 82.
    Lichtenstein GR, Bola M, Man C, DeWoody K, Schaible T (2002) Infliximab improves the quality of life in patients with Crohn’s disease. Inflamm Bowel Dis 8:237–243PubMedCrossRefGoogle Scholar
  83. 83.
    Lindqvist D, Janelidze S, Hagell P, Erhardt S, Samuelsson M, Minthon L et al (2009) Interleukin-6 is elevated in the cerebrospinal fluid of suicide attempters and related to symptom severity. Biol Psychiatry 66:287–292PubMedCrossRefGoogle Scholar
  84. 84.
    Yoshimura R, Hori H, Ikenouchi-Sugita A, Umene-Nakano W, Ueda N, Nakamura J (2009) Higher plasma interleukin-6 (IL-6) level is associated with SSRI- or SNRI-refractory depression. Prog Neuropsychopharmacol Biol Psychiatry 33:722–726PubMedCrossRefGoogle Scholar
  85. 85.
    Leo R, Di Lorenzo G, Tesauro M, Razzini C, Forleo GB, Chiricolo G et al (2006) Association between enhanced soluble CD40 ligand and proinflammatory and prothrombotic states in major depressive disorder: pilot observations on the effects of selective serotonin reuptake inhibitor therapy. J Clin Psychiatry 67:1760–1766PubMedCrossRefGoogle Scholar
  86. 86.
    Leonard B, Maes M (2012) Mechanistic explanations how cell-mediated immune activation, inflammation and oxidative and nitrosative stress pathways and their sequels and concomitants play a role in the pathophysiology of unipolar depression. Neurosci Biobehav Rev 36:764–785PubMedCrossRefGoogle Scholar
  87. 87.
    Kubera M, Obuchowicz E, Goehler L, Brzeszcz J, Maes M (2011) In animal models, psychosocial stress-induced (neuro)inflammation, apoptosis and reduced neurogenesis are associated to the onset of depression. Prog Neuropsychopharmacol Biol Psychiatry 35:744–759PubMedCrossRefGoogle Scholar
  88. 88.
    Shenoy AR, Dehmel T, Stettner M, Kremer D, Kieseier BC, Hartung HP, Hofstetter HH (2013) Citalopram suppresses thymocyte cytokine production. J Neuroimmunol 262:46–52PubMedCrossRefGoogle Scholar
  89. 89.
    Vollmar P, Nessler S, Kalluri SR, Hartung HP, Hemmer B (2009) The antidepressant venlafaxine ameliorates murine experimental autoimmune encephalomyelitis by suppression of pro-inflammatory cytokines. Int J Neuropsychopharmacol 12:525–536PubMedCrossRefGoogle Scholar
  90. 90.
    Sacre S, Medghalchi M, Gregory B, Brennan F, Williams R (2010) Fluoxetine and citalopram exhibit potent antiinflammatory activity in human and murine models of rheumatoid arthritis and inhibit toll-like receptors. Arthritis Rheum 62:683–693PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Helena M. Abelaira
    • 1
  • Gislaine Z. Réus
    • 1
    • 2
  • Fabricia Petronilho
    • 2
    • 3
  • Tatiana Barichello
    • 1
    • 2
  • João Quevedo
    • 1
    • 2
  1. 1.Laboratório de Neurociências, Unidade Acadêmica de Ciências da Saúde, Programa de Pós-Graduação em Ciências da SaúdeUniversidade do Extremo Sul CatarinenseCriciúmaBrazil
  2. 2.Center for Experimental Models in Psychiatry, Department of Psychiatry and Behavioral SciencesThe University of Texas Medical School at HoustonHoustonUSA
  3. 3.Laboratório de Fisiopatologia Clínica e Experimental, Programa de Pós-graduação em Ciências da SaúdeUniversidade do Sul de Santa CatarinaTubarãoBrazil

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