Table of Contents
Advances in Psychiatry
Volume 2014, Article ID 493505, 7 pages
http://dx.doi.org/10.1155/2014/493505
Review Article

Cytokine Serum Levels as Potential Biological Markers for the Psychopathology in Schizophrenia

South Texas Veterans Health Care Systems, San Antonio, TX 78229-4404, USA

Received 25 August 2014; Accepted 27 November 2014; Published 11 December 2014

Academic Editor: Livia Carvalho

Copyright © 2014 Dimitre H. Dimitrov et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. Schizophrenia Working Group of the Psychiatric Genome Consortium, “Biological insights from 108 schizophrenia-associated genetic loci,” Nature, vol. 511, pp. 421–427, 2014. View at Publisher · View at Google Scholar
  2. E. Schwarz, P. C. Guest, H. Rahmoune et al., “Identification of a biological signature for schizophrenia in serum,” Molecular Psychiatry, vol. 17, no. 5, pp. 494–502, 2012. View at Publisher · View at Google Scholar · View at Scopus
  3. S. Horváth and K. Mirnics, “Immune system disturbances in schizophrenia,” Biological Psychiatry, vol. 75, no. 4, pp. 316–323, 2014. View at Publisher · View at Google Scholar · View at Scopus
  4. S. Potvin, E. Stip, A. A. Sepehry, A. Gendron, R. Bah, and E. Kouassi, “Inflammatory cytokine alterations in schizophrenia: a systematic quantitative review,” Biological Psychiatry, vol. 63, no. 8, pp. 801–808, 2008. View at Publisher · View at Google Scholar · View at Scopus
  5. R. R. Girgis, S. S. Kumar, and A. S. Brown, “The cytokine model of schizophrenia: emerging therapeutic strategies,” Biological Psychiatry, vol. 75, no. 4, pp. 292–299, 2014. View at Publisher · View at Google Scholar · View at Scopus
  6. D. H. Dimitrov, “Correlation or coincidence between monocytosis and worsening of psychotic symptoms in veterans with schizophrenia?” Schizophrenia Research, vol. 126, no. 1–3, pp. 306–307, 2011. View at Publisher · View at Google Scholar · View at Scopus
  7. D. H. Dimitrov, S. Lee, J. Yantis et al., “Differential correlations between inflammatory cytokines and psychopathology in veterans with schizophrenia: potential role for IL-17 pathway,” Schizophrenia Research, vol. 151, no. 1–3, pp. 29–35, 2013. View at Publisher · View at Google Scholar · View at Scopus
  8. R. C. Drexhage, E. M. Knijff, R. C. Padmos et al., “The mononuclear phagocyte system and its cytokine inflammatory networks in schizophrenia and bipolar disorder,” Expert Review of Neurotherapeutics, vol. 10, no. 1, pp. 59–76, 2010. View at Publisher · View at Google Scholar · View at Scopus
  9. T. R. Mosmann and R. L. Coffman, “TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties,” Annual Review of Immunology, vol. 7, pp. 145–173, 1989. View at Publisher · View at Google Scholar · View at Scopus
  10. M. Debnath and M. Berk, “Th17 pathway–mediated immunopathogenesis of schizophrenia: mechanisms and implications,” Schizophrenia Bulletin, vol. 40, no. 6, pp. 1412–1421, 2014. View at Publisher · View at Google Scholar
  11. D. D. Chaplin, “Overview of the immune response,” Journal of Allergy and Clinical Immunology, vol. 125, no. 2, pp. S3–S23, 2010. View at Publisher · View at Google Scholar · View at Scopus
  12. N. Muller and M. J. Schwarz, “Immune system in schizophrenia,” Current Immunology Reviews, vol. 6, pp. 213–220, 2010. View at Publisher · View at Google Scholar
  13. V. Arolt, M. Rothermundt, K.-P. Wandinger, and H. Kirchner, “Decreased in vitro production of interferon-gamma and interleukin-2 in whole blood of patients with schizophrenia during treatment,” Molecular Psychiatry, vol. 5, no. 2, pp. 150–158, 2000. View at Publisher · View at Google Scholar · View at Scopus
  14. P. A. Garay and A. K. McAllister, “Novel roles for immune molecules in neural development: implications for neurodevelopmental disorders,” Frontiers in Synaptic Neuroscience, vol. 2, pp. 136–162, 2010. View at Publisher · View at Google Scholar · View at Scopus
  15. C. T. Weaver, R. D. Hatton, P. R. Mangan, and L. E. Harrington, “IL-17 family cytokines and the expanding diversity of effector T cell lineages,” Annual Review of Immunology, vol. 25, pp. 821–852, 2007. View at Publisher · View at Google Scholar · View at Scopus
  16. T. Korn, E. Bettelli, M. Oukka, and V. K. Kuchroo, “IL-17 and Th17 cells,” Annual Review of Immunology, vol. 27, pp. 485–517, 2009. View at Publisher · View at Google Scholar · View at Scopus
  17. M. J. Schwarz, S. Chiang, N. Müller, and M. Ackenheil, “T-helper-1 and T-helper-2 responses in psychiatric disorders,” Brain, Behavior, and Immunity, vol. 15, no. 4, pp. 340–370, 2001. View at Publisher · View at Google Scholar · View at Scopus
  18. D. P. van Kammen, C. G. McAllister-Sistilli, and M. E. Kelly, “Relationship between immune and behavioral measures in schizophrenia,” in Current Update in Psychoimmunology, G. Wiesselmann, Ed., New York, NY, USA, pp. 51–55, Springer, 1997. View at Google Scholar
  19. B. B. Mittleman, F. X. Castellanos, L. K. Jacobsen, J. L. Rapoport, S. E. Swedo, and G. M. Shearer, “Cerebrospinal fluid cytokines in pediatric neuropsychiatric disease,” The Journal of Immunology, vol. 159, no. 6, pp. 2994–2999, 1997. View at Google Scholar · View at Scopus
  20. B. J. Miller, P. Buckley, W. Seabolt, A. Mellor, and B. Kirkpatrick, “Meta-analysis of cytokine alterations in schizophrenia: clinical status and antipsychotic effects,” Biological Psychiatry, vol. 70, no. 7, pp. 663–671, 2011. View at Publisher · View at Google Scholar · View at Scopus
  21. F. Aloisi, G. Penna, J. Cerase, B. M. Iglesias, and L. Adorini, “IL-12 production by the central nervous system microglia is inhibited by astrocytes,” Journal of Immunology, vol. 159, no. 4, pp. 1604–1612, 1997. View at Google Scholar · View at Scopus
  22. M. Rothermundt, P. Falkai, G. Ponath et al., “Glial cell dysfunction in schizophrenia indicated by increased S100B in the CSF,” Molecular Psychiatry, vol. 9, no. 10, pp. 897–899, 2004. View at Publisher · View at Google Scholar · View at Scopus
  23. A. L. Teixeira, H. J. Reis, R. Nicolato et al., “Increased serum levels of CCL11/eotaxin in schizophrenia,” Progress in Neuropsychopharmacology and Biological Psychiatry, vol. 32, no. 3, pp. 710–714, 2008. View at Publisher · View at Google Scholar · View at Scopus
  24. T. Miyakawa, L. M. Leiter, D. J. Gerber et al., “Conditional calcineurin knockout mice exhibit multiple abnormal behaviors related to schizophrenia,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 15, pp. 8987–8992, 2003. View at Publisher · View at Google Scholar · View at Scopus
  25. A. M. Fernandez, S. Fernandez, P. Carrero, M. Garcia-Garcia, and I. Torres-Aleman, “Calcineurin in reactive astrocytes plays a key role in the interplay between proinflammatory and anti-inflammatory signals,” The Journal of Neuroscience, vol. 27, no. 33, pp. 8745–8756, 2007. View at Publisher · View at Google Scholar · View at Scopus
  26. S. A. Villeda, J. Luo, K. I. Mosher et al., “The ageing systemic milieu negatively regulates neurogenesis and cognitive function,” Nature, vol. 477, pp. 90–94, 2011. View at Publisher · View at Google Scholar · View at Scopus
  27. A. D. Bachstetter, J. M. Morganti, J. Jernberg et al., “Fractalkine and CX3CR1 regulate hippocampal neurogenesis in adult and aged rats,” Neurobiology of Aging, vol. 32, no. 11, pp. 2030–2044, 2011. View at Publisher · View at Google Scholar · View at Scopus
  28. K. Biber, H. Neumann, K. Inoue, and H. W. G. M. Boddeke, “Neuronal “on” and “off” signals control microglia,” Trends in Neurosciences, vol. 30, no. 11, pp. 596–602, 2007. View at Publisher · View at Google Scholar · View at Scopus
  29. M. Rosito, C. Lauro, G. Chece et al., “Trasmembrane chemokines CX3CL1 and CXCL16 drive interplay between neurons, microglia and astrocytes to counteract pMCAO and excitotoxic neuronal death,” Frontiers in Cellular Neuroscience, vol. 8, article 193, 2014. View at Publisher · View at Google Scholar
  30. G. K. Sheridan and K. J. Murphy, “Neuron-glia crosstalk in health and disease: fractalkine and CX3CR1 take centre stage,” Open Biology, vol. 3, no. 1, Article ID 130181, 2013. View at Publisher · View at Google Scholar · View at Scopus
  31. T.-S. Kim, H.-K. Lim, J. Y. Lee et al., “Changes in the levels of plasma soluble fractalkine in patients with mild cognitive impairment and Alzheimer's disease,” Neuroscience Letters, vol. 436, no. 2, pp. 196–200, 2008. View at Publisher · View at Google Scholar · View at Scopus
  32. R. C. Paolicelli, G. Bolasco, F. Pagani et al., “Synaptic pruning by microglia is necessary for normal brain development,” Science, vol. 333, no. 6048, pp. 1456–1458, 2011. View at Publisher · View at Google Scholar · View at Scopus
  33. S. G. Fillman, N. Cloonan, V. S. Catts et al., “Increased inflammatory markers identified in the dorsolateral prefrontal cortex of individuals with schizophrenia,” Molecular Psychiatry, vol. 18, no. 2, pp. 206–214, 2013. View at Publisher · View at Google Scholar · View at Scopus
  34. Y. Yang, S. J. Fung, A. Rothwell, S. Tianmei, and C. S. Weickert, “Increased interstitial white matter neuron density in the dorsolateral prefrontal cortex of people with schizophrenia,” Biological Psychiatry, vol. 69, no. 1, pp. 63–70, 2011. View at Publisher · View at Google Scholar · View at Scopus
  35. U. Meyer, J. Feldon, and B. K. Yee, “A review of the fetal brain cytokine imbalance hypothesis of schizophrenia,” Schizophrenia Bulletin, vol. 35, no. 5, pp. 959–972, 2009. View at Publisher · View at Google Scholar · View at Scopus
  36. J. Doorduin, E. F. J. de Vries, A. T. M. Willemsen, J. C. de Groot, R. A. Dierckx, and H. C. Klein, “Neuroinflammation in schizophrenia-related psychosis: a PET study,” Journal of Nuclear Medicine, vol. 50, no. 11, pp. 1801–1807, 2009. View at Publisher · View at Google Scholar · View at Scopus
  37. C. Prado, F. Contreras, H. González et al., “Stimulation of dopamine receptor D5 expressed on dendritic cells potentiates Th17-mediated immunity,” Journal of Immunology, vol. 188, no. 7, pp. 3062–3070, 2012. View at Publisher · View at Google Scholar · View at Scopus
  38. K. Nakagome, M. Imamura, H. Okada et al., “Dopamine D1-like receptor antagonist attenuates Th17-mediated immune response and ovalbumin antigen-induced neutrophilic airway inflammation,” The Journal of Immunology, vol. 186, no. 10, pp. 5975–5982, 2011. View at Publisher · View at Google Scholar · View at Scopus
  39. M. E. Benros, P. R. Nielsen, M. Nordentoft, W. W. Eaton, S. O. Dalton, and P. B. Mortensen, “Autoimmune diseases and severe infections as risk factors for schizophrenia: a 30-year population-based register study,” The American Journal of Psychiatry, vol. 168, no. 12, pp. 1303–1310, 2011. View at Google Scholar · View at Scopus
  40. M. E. Benros, W. W. Eaton, and P. B. Mortensen, “The epidemiologic evidence linking autoimmune diseases and psychosis,” Biological Psychiatry, vol. 75, no. 4, pp. 300–306, 2014. View at Publisher · View at Google Scholar · View at Scopus
  41. T. A. Moseley, D. R. Haudenschild, L. Rose, and A. H. Reddi, “Interleukin-17 family and IL-17 receptors,” Cytokine and Growth Factor Reviews, vol. 14, no. 2, pp. 155–174, 2003. View at Publisher · View at Google Scholar · View at Scopus
  42. F. Jadidi-Niaragh and A. Mirshafiey, “Th17 Cell, the new player of neuroinflammatory process in multiple sclerosis,” Scandinavian Journal of Immunology, vol. 74, no. 1, pp. 1–13, 2011. View at Publisher · View at Google Scholar · View at Scopus
  43. M. Huber, S. Heink, A. Pagenstecher et al., “IL-17A secretion by CD8+ T cells supports Th17-mediated autoimmune encephalomyelitis,” Journal of Clinical Investigation, vol. 123, no. 1, pp. 247–260, 2013. View at Publisher · View at Google Scholar · View at Scopus
  44. V. Bergink, S. M. Gibney, and H. A. Drexhage, “Autoimmunity, inflammation, and psychosis: a search for peripheral markers,” Biological Psychiatry, vol. 75, no. 4, pp. 324–331, 2014. View at Publisher · View at Google Scholar · View at Scopus
  45. Z. Yao, W. C. Fanslow, M. F. Seldin et al., “Herpesvirus Saimiri encodes a new cytokine, IL-17, which binds to a novel cytokine receptor,” Immunity, vol. 3, no. 6, pp. 811–821, 1995. View at Publisher · View at Google Scholar · View at Scopus
  46. J. Witowski, K. Ksia̧zek, and A. Jörres, “Interleukin-17: a mediator of inflammatory responses,” Cellular and Molecular Life Sciences, vol. 61, no. 5, pp. 567–579, 2004. View at Publisher · View at Google Scholar · View at Scopus
  47. I. Kryczek, E. Zhao, Y. Liu et al., “Human TH17 cells are long-lived effector memory cells,” Science Translational Medicine, vol. 3, no. 104, pp. 104–ra100, 2011. View at Google Scholar · View at Scopus
  48. I. M. Stromnes, L. M. Cerretti, D. Liggitt, R. A. Harris, and J. M. Goverman, “Differential regulation of central nervous system autoimmunity by TH1 and TH17 cells,” Nature Medicine, vol. 14, no. 3, pp. 337–342, 2008. View at Publisher · View at Google Scholar · View at Scopus
  49. Y. Hu, F. Shen, N. K. Crellin, and W. Ouyang, “The IL-17 pathway as a major therapeutic target in autoimmune diseases,” Annals of the New York Academy of Sciences, vol. 1217, no. 1, pp. 60–76, 2011. View at Publisher · View at Google Scholar · View at Scopus
  50. F. J. Dumont, “IL-17 cytokine/receptor families: emerging targets for the modulation of inflammatory responses,” Expert Opinion on Therapeutic Patents, vol. 13, no. 3, pp. 287–303, 2003. View at Publisher · View at Google Scholar · View at Scopus
  51. S. Shahrara, S. R. Pickens, A. M. Mandelin II et al., “IL-17-mediated monocyte migration occurs partially through CC chemokine ligand 2/monocyte chemoattractant protein-1 induction,” The Journal of Immunology, vol. 184, no. 8, pp. 4479–4487, 2010. View at Publisher · View at Google Scholar · View at Scopus
  52. P. I. Johansson, A. M. Sørensen, A. Perner et al., “High sCD40L levels early after trauma are associated with enhanced shock, sympathoadrenal activation, tissue and endothelial damage, coagulopathy and mortality,” Journal of Thrombosis and Haemostasis, vol. 10, no. 2, pp. 207–216, 2012. View at Publisher · View at Google Scholar · View at Scopus
  53. H. Kebir, K. Kreymborg, I. Ifergan et al., “Human TH17 lymphocytes promote blood-brain barrier disruption and central nervous system inflammation,” Nature Medicine, vol. 13, no. 10, pp. 1173–1175, 2007. View at Publisher · View at Google Scholar · View at Scopus
  54. A. Reboldi, C. Coisne, D. Baumjohann et al., “C-C chemokine receptor 6-regulated entry of TH-17 cells into the CNS through the choroid plexus is required for the initiation of EAE,” Nature Immunology, vol. 10, no. 5, pp. 514–523, 2009. View at Publisher · View at Google Scholar · View at Scopus
  55. Y. Lee, A. Awasthi, N. Yosef et al., “Induction and molecular signature of pathogenic TH17 cells,” Nature Immunology, vol. 13, no. 10, pp. 991–999, 2012. View at Publisher · View at Google Scholar · View at Scopus
  56. T. Yamazaki, X. O. Yang, Y. Chung et al., “CCR6 regulates the migration of inflammatory and regulatory T cells,” Journal of Immunology, vol. 181, no. 12, pp. 8391–8401, 2008. View at Publisher · View at Google Scholar · View at Scopus
  57. L. R. Frick, K. Williams, and C. Pittenger, “Microglial dysregulation in psychiatric disease,” Clinical and Developmental Immunology, vol. 2013, Article ID 608654, 10 pages, 2013. View at Publisher · View at Google Scholar · View at Scopus
  58. S. M. Kurian, H. Le-Niculescu, S. D. Patel et al., “Identification of blood biomarkers for psychosis using convergent functional genomics,” Molecular Psychiatry, vol. 16, no. 1, pp. 37–58, 2011. View at Publisher · View at Google Scholar · View at Scopus
  59. M. Nedergaard, B. Ransom, and S. A. Goldman, “New roles for astrocytes: redefining the functional architecture of the brain,” Trends in Neurosciences, vol. 26, no. 10, pp. 523–530, 2003. View at Publisher · View at Google Scholar · View at Scopus
  60. C.-R. Yu, Y. S. Lee, R. M. Mahdi, N. Surendran, and C. E. Egwuagu, “Therapeutic targeting of STAT3 (signal transducers and activators of transcription 3) pathway inhibits experimental autoimmune uveitis,” PLoS ONE, vol. 7, no. 1, Article ID e29742, 2012. View at Publisher · View at Google Scholar · View at Scopus