Table of Contents Author Guidelines Submit a Manuscript
Mediators of Inflammation
Volume 2013, Article ID 480739, 20 pages
http://dx.doi.org/10.1155/2013/480739
Review Article

Cytokines and Chemokines at the Crossroads of Neuroinflammation, Neurodegeneration, and Neuropathic Pain

1Division of Bacteriology and Parasitology, Tulane National Primate Research Center, Tulane University, 18703 Three Rivers Road, Covington, LA 70433, USA
2Division of Comparative Pathology, Tulane National Primate Research Center, Tulane University, 18703 Three Rivers Road, Covington, LA 70433, USA

Received 3 May 2013; Revised 11 July 2013; Accepted 12 July 2013

Academic Editor: Luc Vallières

Copyright © 2013 Geeta Ramesh 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. J. Vilcek, “The cytokines: an overview,” in The Cytokine Handbook, W. Angus and M. T. L. Thomson, Eds., pp. 1–18, Academic Press, San Diego, Calif, USA, 4th edition.
  2. A. Walz, P. Peveri, H. Aschauer, and M. Baggiolini, “Purification and amino acid sequencing of NAF, a novel neutrophil-activating factor produced by monocytes,” Biochemical and Biophysical Research Communications, vol. 149, no. 2, pp. 755–761, 1987. View at Google Scholar · View at Scopus
  3. T. Yoshimura, K. Matsushima, J. J. Oppenheim, and E. J. Leonard, “Neutrophil chemotactic factor produced by lipopolysaccharide (LPS)-stimulated human blood mononuclear leukocytes: partial characterization and separation from interleukin 1 (IL 1),” Journal of Immunology, vol. 139, no. 3, pp. 788–793, 1987. View at Google Scholar · View at Scopus
  4. B. Moser and P. Loetscher, “Lymphocyte traffic control by chemokines,” Nature Immunology, vol. 2, no. 2, pp. 123–128, 2001. View at Publisher · View at Google Scholar · View at Scopus
  5. L. A. Devi, “G-protein-coupled receptor dimers in the lime light,” Trends in Pharmacological Sciences, vol. 21, no. 9, pp. 324–326, 2000. View at Publisher · View at Google Scholar · View at Scopus
  6. W. F. Hickey, “Leukocyte traffic in the central nervous system: the participants and their roles,” Seminars in Immunology, vol. 11, no. 2, pp. 125–137, 1999. View at Publisher · View at Google Scholar · View at Scopus
  7. Y. Takeshita and R. M. Ransohoff, “Inflammatory cell trafficking across the blood-brain barrier: chemokine regulation and in vitro models,” Immunological Reviews, vol. 248, pp. 228–239, 2012. View at Google Scholar
  8. E. N. Benveniste, “Inflammatory cytokines within the central nervous system: sources, function, and mechanism of action,” American Journal of Physiology, vol. 263, no. 1, pp. C1–C16, 1992. View at Google Scholar · View at Scopus
  9. C. R. Cámara-Lemarroy, F. J. Guzmán-de La Garza, and N. E. Fernández-Garza, “Molecular inflammatory mediators in peripheral nerve degeneration and regeneration,” NeuroImmunoModulation, vol. 17, no. 5, pp. 314–324, 2010. View at Publisher · View at Google Scholar · View at Scopus
  10. L. R. Watkins and S. F. Maier, “Beyond neurons: evidence that immune and glial cells contribute to pathological pain states,” Physiological Reviews, vol. 82, no. 4, pp. 981–1011, 2002. View at Google Scholar · View at Scopus
  11. P. M. Nilupul, H. K. Ma, S. Arakawa et al., “Inflammation following stroke,” Journal of Clinical Neuroscience, vol. 13, no. 1, pp. 1–8, 2006. View at Publisher · View at Google Scholar · View at Scopus
  12. G. De Chiara, M. E. marcocci, R. Sgarbanti et al., “Infectious agents and neurodegeneration,” Molecular Neurobiology, 2012. View at Publisher · View at Google Scholar
  13. F. Vilhardt, “Microglia: phagocyte and glia cell,” International Journal of Biochemistry and Cell Biology, vol. 37, no. 1, pp. 17–21, 2005. View at Publisher · View at Google Scholar · View at Scopus
  14. H. E. Gendelman, “Neural immunity: friend or foe?” Journal of NeuroVirology, vol. 8, no. 6, pp. 474–479, 2002. View at Publisher · View at Google Scholar · View at Scopus
  15. M. Erta, A. Quintana, and J. Hidalgo, “Interleukin-6 a major cytokine in the central nervous system,” International Journal of Biological Sciences, vol. 8, pp. 1254–1266, 2012. View at Google Scholar
  16. L. Ye, Y. Huang, L. Zhao et al., “IL-1β and TNF-α induce neurotoxicity through glutamate production: a potential role for neuronal glutaminase,” Journal of Neurochemistry, vol. 125, no. 6, pp. 897–908, 2013. View at Google Scholar
  17. M. Kumar, S. Verma, and V. R. Nerurkar, “Pro-inflammatory cytokines derived from West Nile virus (WNV)-infected SK-N-SH cells mediate neuroinflammatory markers and neuronal death,” Journal of Neuroinflammation, vol. 7, article 73, 2010. View at Publisher · View at Google Scholar · View at Scopus
  18. J. Lazovic, A. Basu, H.-W. Lin et al., “Neuroinflammation and both cytotoxic and vasogenic edema are reduced in interleukin-1 type 1 receptor-deficient mice conferring neuroprotection,” Stroke, vol. 36, no. 10, pp. 2226–2231, 2005. View at Publisher · View at Google Scholar · View at Scopus
  19. J. L. Takahashi, F. Giuliani, C. Power, Y. Imai, and V. W. Yong, “Interleukin-1β promotes oligodendrocyte death through glutamate excitotoxicity,” Annals of Neurology, vol. 53, no. 5, pp. 588–595, 2003. View at Publisher · View at Google Scholar · View at Scopus
  20. C. Sherwin and R. Fern, “Acute lipopolysaccharide-mediated injury in neonatal white matter glia: role of TNF-α, IL-1β, and calcium,” Journal of Immunology, vol. 175, no. 1, pp. 155–161, 2005. View at Google Scholar · View at Scopus
  21. H. Abo-Ouf, A. W. Hooper, E. J. White, H. J. J. van Rensburg, B. L. Trigatti, and S. A. Igdoura, “Deletion of tumor necrosis factor–α ameliorates neurodegeneration in Sandhoff disease mice,” Human Molecular Genetics, pp. 1–16, 2013. View at Publisher · View at Google Scholar
  22. M. O. Lu, R. S. Duan, H. C. Quezada et al., “Aggravation of experimental autoimmune neuritis in TNF-α receptor 1 deficient mice,” Journal of Neuroimmunology, vol. 186, no. 1-2, pp. 19–26, 2007. View at Publisher · View at Google Scholar · View at Scopus
  23. M. Chertoff, N. Di Paolo, A. Schoeneberg et al., “Neuroprotective and neurodegenerative effects of the chronic expression of tumor necrosis factor α in the nigrostriatal dopaminergic circuit of adult mice,” Experimental Neurology, vol. 227, no. 2, pp. 237–251, 2011. View at Publisher · View at Google Scholar · View at Scopus
  24. L. Cartier, O. Hartley, M. Dubois-Dauphin, and K.-H. Krause, “Chemokine receptors in the central nervous system: role in brain inflammation and neurodegenerative diseases,” Brain Research Reviews, vol. 48, no. 1, pp. 16–42, 2005. View at Publisher · View at Google Scholar · View at Scopus
  25. G. Yang, Y. Meng, W. Li et al., “Neuronal MCP-1 mediates microglia recruitment and neurodegeneration induced by the mild impairment of oxidative metabolism,” Brain Pathology, vol. 21, no. 3, pp. 279–297, 2011. View at Publisher · View at Google Scholar · View at Scopus
  26. E. A. Eugenin, T. G. D'Aversa, L. Lopez, T. M. Calderon, and J. W. Berman, “MCP-1 (CCL2) protects human neurons and astrocytes from NMDA or HIV-tat-induced apoptosis,” Journal of Neurochemistry, vol. 85, no. 5, pp. 1299–1311, 2003. View at Publisher · View at Google Scholar · View at Scopus
  27. W. L. Thompson, W. J. Karpus, and L. J. Van Eldik, “MCP-1-deficient mice show reduced neuroinflammatory responses and increased peripheral inflammatory responses to peripheral endotoxin insult,” Journal of Neuroinflammation, vol. 5, article 35, 2008. View at Publisher · View at Google Scholar · View at Scopus
  28. B. Spittau, X. Zhou, M. Ming, and K. Krieglstein, “IL6 protects MN9D cells and midbrain dopaminergic neurons from MPP+-induced neurodegeneration,” NeuroMolecular Medicine, vol. 4, pp. 317–327, 2012. View at Google Scholar
  29. A. Salmaggi, E. Ciusani, M. De Rossi et al., “Expression and modulation of IFN-γ-inducible chemokines (IP-10, Mig, and I-TAC) in human brain endothelium and astrocytes: possible relevance for the immune invasion of the central nervous system and the pathogenesis of multiple sclerosis,” Journal of Interferon and Cytokine Research, vol. 22, no. 6, pp. 631–640, 2002. View at Publisher · View at Google Scholar · View at Scopus
  30. P. Cinque, A. Bestetti, R. Marenzi et al., “Cerebrospinal fluid interferon-γ-inducible protein 10 (IP-10, CXCL10) in HIV-1 infection,” Journal of Neuroimmunology, vol. 168, no. 1-2, pp. 154–163, 2005. View at Publisher · View at Google Scholar · View at Scopus
  31. M. Q. Xia, B. J. Bacskai, R. B. Knowles, S. X. Qin, and B. T. Hyman, “Expression of the chemokine receptor CXCR3 on neurons and the elevated expression of its ligand IP-10 in reactive astrocytes: in vitro ERK1/2 activation and role in Alzheimer's disease,” Journal of Neuroimmunology, vol. 108, no. 1-2, pp. 227–235, 2000. View at Publisher · View at Google Scholar · View at Scopus
  32. Y. Sui, L. Stehno-Bittel, S. Li et al., “CXCL10-induced cell death in neurons: role of calcium dysregulation,” European Journal of Neuroscience, vol. 23, no. 4, pp. 957–964, 2006. View at Publisher · View at Google Scholar · View at Scopus
  33. H. A. Mattison, H. Nie, H. Gao, H. Zhou, and J. S. Zhang, “Suppressed pro-inflammatory response of microglia in CX3CR1 knockout mice,” Journal of Neuroimmunology, vol. 257, no. 1-2, pp. 110–115, 2013. View at Google Scholar
  34. B. D. Semple, N. Bye, J. M. Ziebell, and M. C. Morganti-Kossmann, “Deficiency of the chemokine receptor CXCR2 attenuates neutrophil infiltration and cortical damage following closed head injury,” Neurobiology of Disease, vol. 40, no. 2, pp. 394–403, 2010. View at Publisher · View at Google Scholar · View at Scopus
  35. M. De Paola, P. Buanne, L. Biordi, R. Bertini, P. Ghezzi, and T. Mennini, “Chemokine MIP-2/CXCL2, acting on CXCR2, induces motor neuron death in primary cultures,” NeuroImmunoModulation, vol. 14, no. 6, pp. 310–316, 2007. View at Publisher · View at Google Scholar · View at Scopus
  36. M. Roy, J.-F. Richard, A. Dumas, and L. Vallières, “CXCL1 can be regulated by IL-6 and promotes granulocyte adhesion to brain capillaries during bacterial toxin exposure and encephalomyelitis,” Journal of Neuroinflammation, vol. 9, article 18, 2012. View at Publisher · View at Google Scholar · View at Scopus
  37. Y. Zhu and F. Murakami, “Chemokine CXCL12 and its receptors in the developing central nervous system: emerging themes and future perspectives,” Developmental Neurobiology, vol. 72, no. 10, pp. 1349–1362, 2012. View at Google Scholar
  38. M. Li and R. M. Ransohoff, “Multiple roles of chemokine CXCL12 in the central nervous system: a migration from immunology to neurobiology,” Progress in Neurobiology, vol. 84, no. 2, pp. 116–131, 2008. View at Publisher · View at Google Scholar · View at Scopus
  39. M. Shimoji, F. Pagan, E. B. Healton, and I. Mocchetti, “CXCR4 and CXCL12 expression is increased in the nigro-striatal system of Parkinson's disease,” Neurotoxicity Research, vol. 16, no. 3, pp. 318–328, 2009. View at Publisher · View at Google Scholar · View at Scopus
  40. C. Savarin-Vuaillat and R. M. Ransohoff, “Chemokines and chemokine receptors in neurological disease: raise, retain, or reduce?” Neurotherapeutics, vol. 4, no. 4, pp. 590–601, 2007. View at Publisher · View at Google Scholar · View at Scopus
  41. T. Owens, A. A. Babcock, J. M. Millward, and H. Toft-Hansen, “Cytokine and chemokine inter-regulation in the inflamed or injured CNS,” Brain Research Reviews, vol. 48, no. 2, pp. 178–184, 2005. View at Publisher · View at Google Scholar · View at Scopus
  42. F. Eskandari, J. I. Webster, and E. M. Sternberg, “Neural immune pathways and their connection to inflammatory diseases,” Arthritis Research and Therapy, vol. 5, no. 6, pp. 251–265, 2003. View at Google Scholar · View at Scopus
  43. J. A. Smith, A. Das, S. K. Ray, and N. L. Banik, “Role of pro-inflammatory cytokines released from microglia in neurodegenerative diseases,” Brain Research Bulletin, vol. 87, no. 1, pp. 10–20, 2012. View at Publisher · View at Google Scholar · View at Scopus
  44. C. K. Glass, K. Saijo, B. Winner, M. C. Marchetto, and F. H. Gage, “Mechanisms underlying inflammation in neurodegeneration,” Cell, vol. 140, no. 6, pp. 918–934, 2010. View at Publisher · View at Google Scholar · View at Scopus
  45. B. A. Fallon, E. S. Levin, P. J. Schweitzer, and D. Hardesty, “Inflammation and central nervous system Lyme disease,” Neurobiology of Disease, vol. 37, no. 3, pp. 534–541, 2010. View at Publisher · View at Google Scholar · View at Scopus
  46. A. K. Asbury, B. G. Arnason, and R. D. Adams, “The inflammatory lesion in idiopathic polyneuritis. Its role in pathogenesis,” Medicine, vol. 48, no. 3, pp. 173–215, 1969. View at Google Scholar · View at Scopus
  47. J. J. Halperin, “Lyme disease and the peripheral nervous system,” Muscle and Nerve, vol. 28, no. 2, pp. 133–143, 2003. View at Publisher · View at Google Scholar · View at Scopus
  48. G. Bogliun and E. Beghi, “Incidence and clinical features of acute inflammatory polyradiculoneuropathy in Lombardy, Italy, 1996,” Acta Neurologica Scandinavica, vol. 110, no. 2, pp. 100–106, 2004. View at Publisher · View at Google Scholar · View at Scopus
  49. N. Kiguchi, Y. Kobayashi, and S. Kishioka, “Chemokines and cytokines in neuroinflammation leading to neuropathic pain,” Current Opinion in Pharmacology, vol. 12, no. 1, pp. 55–61, 2012. View at Publisher · View at Google Scholar · View at Scopus
  50. W. M. Scheld, U. Koedel, B. Nathan, and H.-W. Pfister, “Pathophysiology of bacterial meningitis: mechanism(s) of neuronal injury,” Journal of Infectious Diseases, vol. 186, no. 2, pp. S225–S233, 2002. View at Publisher · View at Google Scholar · View at Scopus
  51. R. Nau and W. Brück, “Neuronal injury in bacterial meningitis: mechanisms and implications for therapy,” Trends in Neurosciences, vol. 25, no. 1, pp. 38–45, 2002. View at Publisher · View at Google Scholar · View at Scopus
  52. G. Zysk, W. Brück, I. Huitinga et al., “Elimination of blood-derived macrophages inhibits the release of interleukin-1 and the entry of leukocytes into the cerebrospinal fluid in experimental pneumococcal meningitis,” Journal of Neuroimmunology, vol. 73, no. 1-2, pp. 77–80, 1997. View at Publisher · View at Google Scholar · View at Scopus
  53. M. G. Täuber and B. Moser, “Cytokines and chemokines in meningeal inflammation: biology and clinical implications,” Clinical Infectious Diseases, vol. 28, no. 1, pp. 1–12, 1999. View at Google Scholar · View at Scopus
  54. F. Trostdorf, W. Brück, M. Schmitz-Salue et al., “Reduction of meningeal macrophages does not decrease migration of granulocytes into the CSF and brain parenchyma in experimental pneumococcal meningitis,” Journal of Neuroimmunology, vol. 99, no. 2, pp. 205–210, 1999. View at Publisher · View at Google Scholar · View at Scopus
  55. H.-W. Pfister and W. M. Scheld, “Brain injury in bacterial meningitis: therapeutic implications,” Current Opinion in Neurology, vol. 10, no. 3, pp. 254–259, 1997. View at Google Scholar · View at Scopus
  56. U. Koedel, W. M. Scheld, and H.-W. Pfister, “Pathogenesis and pathophysiology of pneumococcal meningitis,” Lancet Infectious Diseases, vol. 2, no. 12, pp. 721–736, 2002. View at Publisher · View at Google Scholar · View at Scopus
  57. R. Nau and W. Brück, “Neuronal injury in bacterial meningitis: mechanisms and implications for therapy,” Trends in Neurosciences, vol. 25, no. 1, pp. 38–45, 2002. View at Publisher · View at Google Scholar · View at Scopus
  58. U. K. Hanisch, M. Prinz, K. Angstwurm et al., “The protein tyrosine kinase inhibitor AG126 prevents the massive microglial cytokine induction by pneumococcal cell walls,” European Journal of Immunology, vol. 31, no. 7, pp. 2104–2115, 2001. View at Google Scholar
  59. R. B. Rock, G. Gekker, S. Hu et al., “Role of microglia in central nervous system infections,” Clinical Microbiology Reviews, vol. 17, no. 4, pp. 942–964, 2004. View at Publisher · View at Google Scholar · View at Scopus
  60. J. S. Braun, R. Novak, P. J. Murray et al., “Apoptosis-inducing factor mediates microglial and neuronal apoptosis caused by pneumococcus,” Journal of Infectious Diseases, vol. 184, no. 10, pp. 1300–1309, 2001. View at Publisher · View at Google Scholar · View at Scopus
  61. J. Gerber and R. Nau, “Mechanisms of injury in bacterial meningitis,” Current Opinion in Neurology, vol. 23, no. 3, pp. 312–318, 2010. View at Publisher · View at Google Scholar · View at Scopus
  62. K. Fassbender, U. Schminke, S. Ries et al., “Endothelial-derived adhesion molecules in bacterial meningitis: association to cytokine release and intrathecal leukocyte-recruitment,” Journal of Neuroimmunology, vol. 74, no. 1-2, pp. 130–144, 1997. View at Publisher · View at Google Scholar · View at Scopus
  63. M. G. Täuber and B. Moser, “Cytokines and chemokines in meningeal inflammation: biology and clinical implications,” The Journal of Infectious Diseases, vol. 151, no. 3, pp. 528–534, 1985. View at Google Scholar
  64. K. Saukkonen, S. Sande, C. Cioffe et al., “The role of cytokines in the generation of inflammation and tissue damage in experimental gram-positive meningitis,” Journal of Experimental Medicine, vol. 171, no. 2, pp. 439–448, 1990. View at Google Scholar · View at Scopus
  65. J. Gerber, G. Raivich, A. Wellmer et al., “A mouse model of Streptococcus pneumoniae meningitis mimicking several features of human disease,” Acta Neuropathologica, vol. 101, no. 5, pp. 499–508, 2001. View at Google Scholar · View at Scopus
  66. D. Grandgirard, O. Steiner, M. G. Täuber, and S. L. Leib, “An infant mouse model of brain damage in pneumococcal meningitis,” Acta Neuropathologica, vol. 114, no. 6, pp. 609–617, 2007. View at Publisher · View at Google Scholar · View at Scopus
  67. R. A. Saladino, A. M. Stack, G. R. Fleisher et al., “Development of a model of low-inoculum Streptococcus pneumoniae intrapulmonary infection in infant rats,” Infection and Immunity, vol. 65, no. 11, pp. 4701–4704, 1997. View at Google Scholar · View at Scopus
  68. D. Grandgirard, M. Burri, P. Agyeman, and S. L. Leib, “Adjunctive daptomycin attenuates brain damage and hearing loss more efficiently than rifampin in infant rat pneumococcal meningitis,” Antimicrob Agents Chemother, vol. 56, no. 8, pp. 4289–4295, 2012. View at Google Scholar
  69. J. Gerber, T. Böttcher, M. Hahn, A. Siemer, S. Bunkowski, and R. Nau, “Increased mortality and spatial memory deficits in TNF-α-deficient mice in ceftriaxone-treated experimental pneumococcal meningitis,” Neurobiology of Disease, vol. 16, no. 1, pp. 133–138, 2004. View at Publisher · View at Google Scholar · View at Scopus
  70. M. K. Sharief, M. Ciardi, and E. J. Thompson, “Blood-brain barrier damage in patients with bacterial meningitis: association with tumor necrosis factor-α but not interleukin-1β,” Journal of Infectious Diseases, vol. 166, no. 2, pp. 350–358, 1992. View at Google Scholar · View at Scopus
  71. P. J. G. Zwijnenburg, T. Van der Poll, S. Florquin, J. J. Roord, and A. M. Van Furth, “Interleukin-10 negatively regulates local cytokine and chemokine production but does not influence antibacterial host defense during murine pneumococcal meningitis,” Infection and Immunity, vol. 71, no. 4, pp. 2276–2279, 2003. View at Publisher · View at Google Scholar · View at Scopus
  72. P. J. G. Zwijnenburg, T. Van der Poll, S. Florquin, J. J. Roord, and A. M. Van Furth, “Interleukin-10 negatively regulates local cytokine and chemokine production but does not influence antibacterial host defense during murine pneumococcal meningitis,” Infection and Immunity, vol. 71, no. 4, pp. 2276–2279, 2003. View at Publisher · View at Google Scholar · View at Scopus
  73. C. J. Orihuela, S. Fillon, S. H. Smith-Sielicki et al., “Cell wall-mediated neuronal damage in early sepsis,” Infection and Immunity, vol. 74, no. 7, pp. 3783–3789, 2006. View at Publisher · View at Google Scholar · View at Scopus
  74. U. Koedel, A. Bernatowicz, K. Frei, A. Fontana, and H.-W. Pfister, “Systemically (but not intrathecally) administered IL-10 attenuates pathophysiologic alterations in experimental pneumococcal meningitis,” Journal of Immunology, vol. 157, no. 11, pp. 5185–5191, 1996. View at Google Scholar · View at Scopus
  75. U. Malipiero, U. Koedel, W. Pfister, and A. Fontana, “Bacterial meningitis: the role of transforming growth factor-beta in innate immunity and secondary brain damage,” Neurodegenerative Diseases, vol. 4, no. 1, pp. 43–50, 2007. View at Publisher · View at Google Scholar · View at Scopus
  76. S. Ebert, D. J. Phillips, P. Jenzewski, R. Nau, A. E. O'Connor, and U. Michel, “Activin A concentrations in human cerebrospinal fluid are age-dependent and elevated in meningitis,” Journal of the Neurological Sciences, vol. 250, no. 1-2, pp. 50–57, 2006. View at Publisher · View at Google Scholar · View at Scopus
  77. H. Wilms, T. Schwark, L.-O. Brandenburg et al., “Regulation of activin A synthesis in microglial cells: pathophysiological implications for bacterial meningitis,” Journal of Neuroscience Research, vol. 88, no. 1, pp. 16–23, 2010. View at Publisher · View at Google Scholar · View at Scopus
  78. S. Kastenbauer, B. Angele, B. Sporer, H.-W. Pfister, and U. Koedel, “Patterns of protein expression in infectious meningitis: a cerebrospinal fluid protein array analysis,” Journal of Neuroimmunology, vol. 164, no. 1-2, pp. 134–139, 2005. View at Publisher · View at Google Scholar · View at Scopus
  79. K.-S. Spanaus, D. Nadal, H.-W. Pfister et al., “C-X-C and C-C chemokines are expressed in the cerebrospinal fluid in bacterial meningitis and mediate chemotactic activity on peripheral blood-derived polymorphonuclear and mononuclear cells in vitro,” Journal of Immunology, vol. 158, no. 4, pp. 1956–1964, 1997. View at Google Scholar · View at Scopus
  80. P. J. G. Zwijnenburg, H. M. A. De Bie, J. J. Roord, T. Van Der Poll, and A. M. Van Furth, “Chemotactic activity of CXCL5 in cerebrospinal fluid of children with bacterial meningitis,” Journal of Neuroimmunology, vol. 145, no. 1-2, pp. 148–153, 2003. View at Publisher · View at Google Scholar · View at Scopus
  81. M. Holub, O. Beran, O. Dzupová et al., “Cortisol levels in cerebrospinal fluid correlate with severity and bacterial origin of meningitis,” Critical Care, vol. 11, no. 2, p. R41, 2007. View at Google Scholar
  82. M. Klein, R. Paul, B. Angele, B. Popp, H.-W. Pfister, and U. Koedel, “Protein expression pattern in experimental pneumococcal meningitis,” Microbes and Infection, vol. 8, no. 4, pp. 974–983, 2006. View at Publisher · View at Google Scholar · View at Scopus
  83. C. Stergaard, R. V. Yieng-Kow, C. G. Larsen et al., “Treatment with a monoclonal antibody to IL-8 attenuates the pleocytosis in experimental pneumococcal meningitis in rabbits when given intravenously, but not intracisternally,” Clinical and Experimental Immunology, vol. 122, no. 2, pp. 207–211, 2000. View at Publisher · View at Google Scholar · View at Scopus
  84. M. Prinz, O. Kann, H. J. Draheim et al., “Microglial activation by components of gram-positive and -negative bacteria: distinct and common routes to the induction of ion channels and cytokines,” Journal of Neuropathology and Experimental Neurology, vol. 58, no. 10, pp. 1078–1089, 1999. View at Google Scholar · View at Scopus
  85. A. Banerjee, N. M. van Sorge, T. R. Sheen, S. Uchiyama, T. J. Mitchell, and K. S. Doran, “Activation of brain endothelium by pneumococcal neuraminidase NanA promotes bacterial internalization,” Cellular Microbiology, vol. 12, no. 11, pp. 1576–1588, 2010. View at Publisher · View at Google Scholar · View at Scopus
  86. B. B. Mook-Kanamori, M. Geldhoff, T. van der Poll, and D. van de Beek, “Pathogenesis and pathophysiology of pneumococcal meningitis,” Clinical Microbiology Reviews, vol. 24, no. 3, pp. 557–591, 2011. View at Publisher · View at Google Scholar · View at Scopus
  87. G. E. Mathisen and J. P. Johnson, “Brain abscess,” Clinical Infectious Diseases, vol. 4, pp. 763–779, 1997. View at Google Scholar
  88. K. N. Prasad, A. M. Mishra, D. Gupta, N. Husain, M. Husain, and R. K. Gupta, “Analysis of microbial etiology and mortality in patients with brain abscess,” Journal of Infection, vol. 53, no. 4, pp. 221–227, 2006. View at Publisher · View at Google Scholar · View at Scopus
  89. G. C. Townsend and W. M. Scheld, “Infections of the central nervous system,” Advances in Internal Medicine, vol. 43, pp. 403–447, 1998. View at Google Scholar · View at Scopus
  90. T. Kielian, E. D. Bearden, A. C. Baldwin, and N. Esen, “IL-1 and TNF-α play a pivotal role in the host immune response in a mouse model of Staphylococcus aureus-induced experimental brain abscess,” Journal of Neuropathology and Experimental Neurology, vol. 63, no. 4, pp. 381–396, 2004. View at Google Scholar · View at Scopus
  91. A. C. Baldwin and T. Kielian, “Persistent immune activation associated with a mouse model of Staphylococcus aureus-induced experimental brain abscess,” Journal of Neuroimmunology, vol. 151, no. 1-2, pp. 24–32, 2004. View at Publisher · View at Google Scholar · View at Scopus
  92. T. Kielian, B. Barry, and W. F. Hickey, “CXC chemokine receptor-2 ligands are required for neutrophil-mediated host defense in experimental brain abscesses,” Journal of Immunology, vol. 166, no. 7, pp. 4634–4643, 2001. View at Google Scholar · View at Scopus
  93. T. Kielian, N. K. Phulwani, N. Esen et al., “MyD88-dependent signals are essential for the host immune response in experimental brain abscess,” Journal of Immunology, vol. 178, no. 7, pp. 4528–4537, 2007. View at Google Scholar · View at Scopus
  94. T. Kielian, P. Mayes, and M. Kielian, “Characterization of microglial responses to Staphylococcus aureus: effects on cytokine, costimulatory molecule, and Toll-like receptor expression,” Journal of Neuroimmunology, vol. 130, no. 1-2, pp. 86–99, 2002. View at Publisher · View at Google Scholar · View at Scopus
  95. T. Kielian, N. Esen, and E. D. Bearden, “Toll-like receptor 2 (TLR2) is pivotal for recognition of S. aureus peptidoglycan but not intact bacteria by microglia,” GLIA, vol. 49, no. 4, pp. 567–576, 2005. View at Publisher · View at Google Scholar · View at Scopus
  96. C. Gurley, J. Nichols, S. Liu, N. K. Phulwani, N. Esen, and T. Kielian, “Microglia and astrocyte activation by Toll-like receptor ligands: modulation by PPAR-γ agonists,” PPAR Research, vol. 2008, Article ID 453120, 15 pages, 2008. View at Publisher · View at Google Scholar · View at Scopus
  97. N. Esen and T. Kielian, “Central role for MyD88 in the responses of microglia to pathogen-associated molecular patterns,” Journal of Immunology, vol. 176, no. 11, pp. 6802–6811, 2006. View at Google Scholar · View at Scopus
  98. T. J. Rath, M. Hughes, M. Arabi, and G. V. Shah, “Imaging of cerebritis, encephalitis, and brain abscess,” Neuroimaging Clinics of North America, vol. 4, pp. 585–607, 2012. View at Google Scholar
  99. N. A. Flaris and W. F. Hickey, “Development and characterization of an experimental model of brain abscess in the rat,” American Journal of Pathology, vol. 141, no. 6, pp. 1299–1307, 1992. View at Google Scholar · View at Scopus
  100. T. Kielian and W. F. Hickey, “Proinflammatory cytokine, chemokine, and cellular adhesion molecule expression during the acute phase of experimental brain abscess development,” American Journal of Pathology, vol. 157, no. 2, pp. 647–658, 2000. View at Google Scholar · View at Scopus
  101. N. Esen, G. Wagoner, and N. Philips, “Evaluation of capsular and acapsular strains of S. aureus in an experimental brain abscess model,” Journal of Neuroimmunology, vol. 218, no. 1-2, pp. 83–93, 2010. View at Publisher · View at Google Scholar · View at Scopus
  102. T. Kielian, “Immunopathogenesis of brain abscess,” Journal of Neuroinflammation, vol. 1, no. 1, article 16, 2004. View at Publisher · View at Google Scholar · View at Scopus
  103. M. A. Cassateua, “Neutrophil-derived proteins: selling cytokines by the pound,” Advances in Immunology, no. 73, pp. 369–509, 1999. View at Google Scholar · View at Scopus
  104. W. D. Lo, R. Chen, D. R. Boue, and B. T. Stokes, “Effect of neutrophil depletion in acute cerebritis,” Brain Research, vol. 802, no. 1-2, pp. 175–183, 1998. View at Publisher · View at Google Scholar · View at Scopus
  105. T. Kielian, N. Esen, S. Liu et al., “Minocycline modulates neuroinflammation independently of its antimicrobial activity in Staphylococcus aureus-induced brain abscess,” American Journal of Pathology, vol. 171, no. 4, pp. 1199–1214, 2007. View at Publisher · View at Google Scholar · View at Scopus
  106. W. Burgdorfer, A. G. Barbour, and S. F. Hayes, “Lyme disease—a tick-borne spirochetosis?” Science, vol. 216, no. 4552, pp. 1317–1319, 1982. View at Google Scholar · View at Scopus
  107. T. A. Rupprecht, U. Koedel, V. Fingerle, and H.-W. Pfister, “The pathogenesis of Lyme neuroborreliosis: from infection to inflammation,” Molecular Medicine, vol. 14, no. 3-4, pp. 205–212, 2008. View at Publisher · View at Google Scholar · View at Scopus
  108. J. J. Halperin, “Nervous system Lyme disease,” Journal of the Royal College of Physicians of Edinburgh, vol. 40, no. 3, pp. 248–255, 2010. View at Publisher · View at Google Scholar · View at Scopus
  109. B. A. Fallon, E. S. Levin, P. J. Schweitzer, and D. Hardesty, “Inflammation and central nervous system Lyme disease,” Neurobiology of Disease, vol. 37, no. 3, pp. 534–541, 2010. View at Publisher · View at Google Scholar · View at Scopus
  110. M. Elamin, T. Monaghan, G. Mulllins et al., “The clinical spectrum of Lyme neuroborreliosis,” Irish Medical Journal, vol. 103, no. 2, pp. 46–49, 2010. View at Google Scholar · View at Scopus
  111. M. A. Lana-Peixoto, “Multiple sclerosis and positive Lyme serology,” Arquivos de Neuro-Psiquiatria, vol. 52, no. 4, pp. 566–571, 1994. View at Google Scholar · View at Scopus
  112. V. V. Brinar and M. Habek, “Rare infections mimicking MS,” Clinical Neurology and Neurosurgery, vol. 112, no. 7, pp. 625–628, 2010. View at Publisher · View at Google Scholar · View at Scopus
  113. J. Oksi, H. Kalimo, R. J. Marttila et al., “Inflammatory brain changes in Lyme borreliosis A report on three patients and review of literature,” Brain, vol. 119, no. 6, pp. 2143–2154, 1996. View at Google Scholar · View at Scopus
  114. R. Keil, R. Baron, R. Kaiser, and G. Deuschl, “Vasculitic course of neuroborreliosis with thalamic infarction,” Nervenarzt, vol. 68, no. 4, pp. 339–341, 1997. View at Publisher · View at Google Scholar · View at Scopus
  115. R. Topakian, K. Stieglbauer, K. Nussbaumer, and F. T. Aichner, “Cerebral vasculitis and stroke in Lyme neuroborreliosis: two case reports and review of current knowledge,” Cerebrovascular Diseases, vol. 26, no. 5, pp. 455–461, 2008. View at Publisher · View at Google Scholar · View at Scopus
  116. J. Kohler, “Lyme borreliosis: a case of transverse myelitis with syrinx cavity,” Neurology, vol. 39, no. 11, pp. 1553–1554, 1989. View at Google Scholar · View at Scopus
  117. J. L. Benach, D. J. Cameron, M. S. Donnenberg, B. J. Luft, and R. J. Dattwyler, “Borrelia burgdorferi in the central nervous system,” Journal of the American Medical Association, vol. 268, no. 7, pp. 872–873, 1992. View at Publisher · View at Google Scholar · View at Scopus
  118. P. H. Duray and A. C. Steere, “Clinical pathologic correlations of Lyme disease by stage,” Annals of the New York Academy of Sciences, vol. 539, pp. 65–79, 1988. View at Google Scholar · View at Scopus
  119. F. Blanc, L. Ballonzoli, C. Marcel, S. De Martino, B. Jaulhac, and J. de Seze, “Lyme optic neuritis,” Journal of the Neurological Sciences, vol. 295, no. 1-2, pp. 117–119, 2010. View at Publisher · View at Google Scholar · View at Scopus
  120. J. Durovska, S. Bazovska, J. Pancak, M. Zaborska, M. Derdakova, and P. Traubner, “Infection with B. burgdorferi s.l., and the CNS demyelinating disease. A case report,” Neuroendocrinology Letters, vol. 32, no. 4, pp. 411–414, 2011. View at Google Scholar
  121. S. Bigi, C. Aebi, C. Nauer, S. Bigler, and M. Steinlin, “Acute transverse myelitis in Lyme neuroborreliosis,” Infection, vol. 38, no. 5, pp. 413–416, 2010. View at Publisher · View at Google Scholar · View at Scopus
  122. J. M. Vallat, J. Hugon, and M. Lubeau, “Tick-bite meningoradiculoneuritis: clinical, electrophysiologic, and histologic findings in 10 cases,” Neurology, vol. 37, no. 5, pp. 749–753, 1987. View at Google Scholar · View at Scopus
  123. E. L. Logigian, “Peripheral nervous system Lyme borreliosis,” Seminars in Neurology, vol. 17, no. 1, pp. 25–28, 1997. View at Google Scholar · View at Scopus
  124. L. Meurs, D. Labeye, I. Declercq, F. Piéret, and M. Gille, “Acute transverse myelitis as a main manifestation of early stage II neuroborreliosis in two patients,” European Neurology, vol. 52, no. 3, pp. 186–188, 2004. View at Publisher · View at Google Scholar · View at Scopus
  125. F. Koc, H. Bozdemir, T. Pekoz, H. S. Aksu, S. Ozcan, and H. Kurdak, “Lyme disease presenting as subacute transverse myelitis,” Acta Neurologica Belgica, vol. 109, no. 4, pp. 326–329, 2009. View at Google Scholar · View at Scopus
  126. J. Halperin, B. J. Luft, D. J. Volkman, and R. J. Dattwyler, “Lyme neuroborreliosis: peripheral nervous system manifestations,” Brain, vol. 113, no. 4, pp. 1207–1221, 1990. View at Google Scholar · View at Scopus
  127. J. J. Halperin, “Neuroborreliosis,” American Journal of Medicine, vol. 98, no. 4, pp. 52S–56S, 1995. View at Google Scholar
  128. T. J. Sellati, M. J. Burns, M. A. Ficazzola, and M. B. Furie, “Borrelia burgdorferi upregulates expression of adhesion molecules on endothelial cells and promotes transendothelial migration of neutrophils in vitro,” Infection and Immunity, vol. 63, no. 11, pp. 4439–4447, 1995. View at Google Scholar · View at Scopus
  129. J. C. Garcia-Monco, B. Fernandez Villar, and J. L. Benach, “Lyme borreliosis: neurological features,” Neurologia, vol. 5, no. 9, pp. 315–322, 1990. View at Google Scholar · View at Scopus
  130. B. Meurers, W. Kohlhepp, R. Gold, E. Rohrbach, and H. G. Mertens, “Histopathological findings in the central and peripheral nervous systems in neuroborreliosis. A report of three cases,” Journal of Neurology, vol. 237, no. 2, pp. 113–116, 1990. View at Publisher · View at Google Scholar · View at Scopus
  131. P. H. Duray, “Histopathology of clinical phases of human Lyme disease,” Rheumatic Disease Clinics of North America, vol. 15, no. 4, pp. 691–710, 1989. View at Google Scholar · View at Scopus
  132. M. Weller, A. Stevens, N. Sommer, H. Wietholter, and J. Dichgans, “Cerebrospinal fluid interleukins, immunoglobulins, and fibronectin in neuroborreliosis,” Archives of Neurology, vol. 48, no. 8, pp. 837–841, 1991. View at Google Scholar · View at Scopus
  133. M. Grusell, M. Widhe, and C. Ekerfelt, “Increased expression of the Th1-inducing cytokines interleukin-12 and interleukin-18 in cerebrospinal fluid but not in sera from patients with Lyme neuroborreliosis,” Journal of Neuroimmunology, vol. 131, no. 1-2, pp. 173–178, 2002. View at Publisher · View at Google Scholar · View at Scopus
  134. M. Widhe, S. Jarefors, C. Ekerfelt et al., “Borrelia-specific interferon-γ and interleukin-4 secretion in cerebrospinal fluid and blood during Lyme borreliosis in humans: association with clinical outcome,” Journal of Infectious Diseases, vol. 189, no. 10, pp. 1881–1891, 2004. View at Publisher · View at Google Scholar · View at Scopus
  135. M. Widhe, B. H. Skogman, S. Jarefors et al., “Up-regulation of Borrelia-specific IL-4- and IFN-γ-secreting cells in cerebrospinal fluid from children with Lyme neuroborreliosis,” International Immunology, vol. 17, no. 10, pp. 1283–1291, 2005. View at Publisher · View at Google Scholar · View at Scopus
  136. S. Grygorczuk, J. Zajkowska, R. Swierzbińska, S. Pancewicz, M. Kondrusik, and T. Hermanowska-Szpakowicz, “Concentration of interferon-inducible T cell chemoattractant and monocyte chemotactic protein-1 in serum and cerebrospinal fluid of patients with Lyme borreliosis,” Roczniki Akademii Medycznej w Białymstoku, vol. 50, pp. 173–178, 2005. View at Google Scholar · View at Scopus
  137. T. A. Rupprecht, U. Koedel, B. Muhlberger, B. Wilske, A. Fontana, and H.-W. Pfister, “CXCL11 is involved in leucocyte recruitment to the central nervous system in neuroborreliosis,” Journal of Neurology, vol. 252, no. 7, pp. 820–823, 2005. View at Publisher · View at Google Scholar · View at Scopus
  138. T. A. Rupprecht, H.-W. Pfister, B. Angele, S. Kastenbauer, B. Wilske, and U. Koedel, “The chemokine CXCL13 (BLC): a putative diagnostic marker for neuroborreliosis,” Neurology, vol. 65, no. 3, pp. 448–450, 2005. View at Publisher · View at Google Scholar · View at Scopus
  139. U. Ljøstad and Å. Mygland, “CSF B—Lymphocyte chemoattractant (CXCL13) in the early diagnosis of acute Lyme neuroborreliosis,” Journal of Neurology, vol. 255, no. 5, pp. 732–737, 2008. View at Publisher · View at Google Scholar · View at Scopus
  140. M. C. Kowarik, S. Cepok, J. Sellner et al., “CXCL13 is the major determinant for B cell recruitment to the CSF during neuroinflammation,” Journal of Neuroinflammation, vol. 9, p. 93, 2012. View at Google Scholar
  141. T. Rupprecht, U. Koedel, B. Angele, V. Fingerle, and H.-W. Pfister, “Cytokine CXCL13—a possible early CSF marker for neuroborreliosis,” Nervenarzt, vol. 77, no. 4, pp. 470–473, 2006. View at Publisher · View at Google Scholar · View at Scopus
  142. D. Cadavid, “The mammalian host response to borrelia infection,” Wiener Klinische Wochenschrift, vol. 118, no. 21-22, pp. 653–658, 2006. View at Publisher · View at Google Scholar · View at Scopus
  143. J. J. Halperin and M. P. Heyes, “Neuroactive kynurenines in Lyme borreliosis,” Neurology, vol. 42, no. 1, pp. 43–50, 1992. View at Google Scholar · View at Scopus
  144. T. L. Petit, “The neurobiology of learning and memory: elucidation of the mechanisms of cognitive dysfunction,” NeuroToxicology, vol. 9, no. 3, pp. 413–428, 1988. View at Google Scholar · View at Scopus
  145. V. Chaparro-Huerta, M. C. Rivera-Cervantes, M. E. Flores-Soto, U. Gómez-Pinedo, and C. Beas-Zárate, “Proinflammatory cytokines and apoptosis following glutamate-induced excitotoxicity mediated by p38 MAPK in the hippocampus of neonatal rats,” Journal of Neuroimmunology, vol. 165, no. 1-2, pp. 53–62, 2005. View at Publisher · View at Google Scholar · View at Scopus
  146. M. T. Philipp, M. K. Aydintug, R. P. Bohm Jr. et al., “Early and early disseminated phases of Lyme disease in the rhesus monkey: a model for infection in humans,” Infection and Immunity, vol. 61, no. 7, pp. 3047–3059, 1993. View at Google Scholar · View at Scopus
  147. A. R. Pachner, E. Delaney, T. O'Neill, and E. Major, “Inoculation of nonhuman primates with the N40 strain of Borrelia burgdorferi leads to a model of Lyme neuroborreliosis faithful to the human disease,” Neurology, vol. 45, no. 1, pp. 165–172, 1995. View at Google Scholar · View at Scopus
  148. M. V. Norgard, L. L. Arndt, D. R. Akins, L. L. Curetty, D. A. Harrich, and J. D. Radolf, “Activation of human monocytic cells by Treponema pallidum and Borrelia burgdorferi lipoproteins and synthetic lipopeptides proceeds via a pathway distinct from that of lipopolysaccharide but involves the transcriptional activator NF-κB,” Infection and Immunity, vol. 64, no. 9, pp. 3845–3852, 1996. View at Google Scholar · View at Scopus
  149. G. Ramesh, A. L. Alvarez, E. D. Roberts et al., “Pathogenesis of Lyme neuroborreliosis: Borrelia burgdorferi lipoproteins induce both proliferation and apoptosis in rhesus monkey astrocytes,” European Journal of Immunology, vol. 33, no. 9, pp. 2539–2550, 2003. View at Publisher · View at Google Scholar · View at Scopus
  150. G. Ramesh and M. T. Philipp, “Pathogenesis of Lyme neuroborreliosis: mitogen-activated protein kinases Erk1, Erk2, and p38 in the response of astrocytes to Borrelia burgdorferi lipoproteins,” Neuroscience Letters, vol. 384, no. 1-2, pp. 112–116, 2005. View at Publisher · View at Google Scholar · View at Scopus
  151. A. L. F. Bernardino, T. A. Myers, X. Alvarez, A. Hasegawa, and M. T. Philipp, “Toll-like receptors: insights into their possible role in the pathogenesis of Lyme neuroborreliosis,” Infection and Immunity, vol. 76, no. 10, pp. 4385–4395, 2008. View at Publisher · View at Google Scholar · View at Scopus
  152. T. A. Myers, D. Kaushal, and M. T. Philipp, “Microglia are mediators of Borrelia burgdorferi-induced apoptosis in SH-SY5Y neuronal cells,” PLoS Pathogens, vol. 5, no. 11, Article ID e1000659, 2009. View at Publisher · View at Google Scholar · View at Scopus
  153. G. Ramesh, J. T. Borda, J. Dufour et al., “Interaction of the Lyme disease spirochete Borrelia burgdorferi with brain parenchyma elicits inflammatory mediators from glial cells as well as glial and neuronal apoptosis,” American Journal of Pathology, vol. 173, no. 5, pp. 1415–1427, 2008. View at Publisher · View at Google Scholar · View at Scopus
  154. G. Ramesh, J. T. Borda, A. Gill et al., “Possible role of glial cells in the onset and progression of Lyme neuroborreliosis,” Journal of Neuroinflammation, vol. 6, article 23, 2009. View at Publisher · View at Google Scholar · View at Scopus
  155. A. R. Pachner, K. Amemiya, E. Delaney, T. O'Neill, C. A. N. Hughes, and W.-F. Zhang, “Interleukin-6 is expressed at high levels in the CNS in Lyme neuroborreliosis,” Neurology, vol. 49, no. 1, pp. 147–152, 1997. View at Google Scholar · View at Scopus
  156. K. Narayan, D. Dail, L. Li et al., “The nervous system as ectopic germinal center: CXCL13 and IgG in Lyme neuroborreliosis,” Annals of Neurology, vol. 57, no. 6, pp. 813–823, 2005. View at Publisher · View at Google Scholar · View at Scopus
  157. A. R. Pachner and I. Steiner, “Lyme neuroborreliosis: infection, immunity, and inflammation,” Lancet Neurology, vol. 6, no. 6, pp. 544–552, 2007. View at Publisher · View at Google Scholar · View at Scopus
  158. X. H. Wei, X. D. Na, G. J. Liao et al., “The up-regulation of IL-6 in DRG and spinal horn contributes to neuopathic pain following L5 ventral horn transection,” Experimental Neurology, vol. 241, pp. 159–168, 2013. View at Google Scholar
  159. G. Ramesh, S. Benge, B. Pahar, and M. T. Philipp, “A possible role for inflammation in mediating apoptosis of oligodendrocytes as induced by the Lyme disease spirochete Borrelia burgdorferi,” Journal of Neuroinflammation, vol. 2012, p. 72, 2012. View at Publisher · View at Google Scholar · View at Scopus
  160. M. G. Grütter, “Caspases: key players in programmed cell death,” Current Opinion in Structural Biology, vol. 10, no. 6, pp. 649–655, 2000. View at Google Scholar
  161. L. Bø, C. A. Vedeler, H. I. Nyland, B. D. Trapp, and S. J. Mørk, “Subpial demyelination in the cerebral cortex of multiple sclerosis patients,” Journal of Neuropathology and Experimental Neurology, vol. 62, no. 7, pp. 723–732, 2003. View at Google Scholar · View at Scopus
  162. M. Bradl and H. Lassmann, “Oligodendrocytes: biology and pathology,” Acta Neuropathologica, vol. 119, no. 1, pp. 37–53, 2010. View at Publisher · View at Google Scholar · View at Scopus
  163. S. Hisahara, H. Okano, and M. Miura, “Caspase-mediated oligodendrocyte cell death in the pathogenesis of autoimmune demyelination,” Neuroscience Research, vol. 46, no. 4, pp. 387–397, 2003. View at Publisher · View at Google Scholar · View at Scopus
  164. C. Stadelmann, C. Wegner, and W. Brück, “Inflammation, demyelination, and degeneration—recent insights from MS pathology,” Biochimica et Biophysica Acta, vol. 1812, no. 2, pp. 275–282, 2011. View at Publisher · View at Google Scholar · View at Scopus
  165. G. Conductier, N. Blondeau, A. Guyon, J.-L. Nahon, and C. Rovère, “The role of monocyte chemoattractant protein MCP1/CCL2 in neuroinflammatory diseases,” Journal of Neuroimmunology, vol. 224, no. 1-2, pp. 93–100, 2010. View at Publisher · View at Google Scholar · View at Scopus
  166. C. Gerard and B. J. Rollins, “Chemokines and disease,” Nature Immunology, vol. 2, no. 2, pp. 108–115, 2001. View at Publisher · View at Google Scholar · View at Scopus
  167. B. J. Rollins, “Monocyte chemoattractant protein 1: a potential regulator of monocyte recruitment in inflammatory disease,” Molecular Medicine Today, vol. 2, no. 5, pp. 198–204, 1996. View at Publisher · View at Google Scholar · View at Scopus
  168. J. E. Simpson, J. Newcombe, M. L. Cuzner, and M. N. Woodroofe, “Expression of monocyte chemoattractant protein-1 and other β- chemokines by resident glia and inflammatory cells in multiple sclerosis lesions,” Journal of Neuroimmunology, vol. 84, no. 2, pp. 238–249, 1998. View at Publisher · View at Google Scholar · View at Scopus
  169. R. M. Ransohoff, T. A. Hamilton, M. Tani et al., “Astrocyte expression of mRNA encoding cytokines IP-10 and JE/MCP-1 in experimental autoimmune encephalomyelitis,” FASEB Journal, vol. 7, no. 6, pp. 592–600, 1993. View at Google Scholar · View at Scopus
  170. A. E. Hinojosa, B. Garcia-Bueno, J. C. Leza, and J. L. M. Madrigal, “CCL2/MCP-1 modulation of microglial activation and proliferation,” Journal of Neuroinflammation, vol. 8, article 77, 2011. View at Publisher · View at Google Scholar · View at Scopus
  171. F. E. Perrin, S. Lacroix, M. Avilés-Trigueros, and S. David, “Involvement of moncyte chemo-attractant protein-1, macrophage inflammatory protein-1 alpha and interleukin-1 beta in Wallerian degeneration,” Brain, vol. 128, part 4, pp. 854–866, 2005. View at Google Scholar
  172. E. Kindstrand, B. Y. Nilsson, A. Hovmark et al., “Polyneuropathy in late Lyme borreliosis—a clinical, neurophysiological and morphological description,” Acta Neurologica Scandinavica, vol. 101, no. 1, pp. 47–52, 2000. View at Publisher · View at Google Scholar · View at Scopus
  173. J. E. Merrill and E. N. Benveniste, “Cytokines in inflammatory brain lesions: helpful and harmful,” Trends in Neurosciences, vol. 19, no. 8, pp. 331–338, 1996. View at Publisher · View at Google Scholar · View at Scopus
  174. N. J. Rothwell and P. J. L. M. Strijbos, “Cytokines in neurodegeneration and repair,” International Journal of Developmental Neuroscience, vol. 13, no. 3-4, pp. 179–185, 1995. View at Publisher · View at Google Scholar · View at Scopus
  175. G. Raivich, L. L. Jones, A. Werner, H. Blüthmann, T. Doetschmann, and G. W. Kreutzberg, “Molecular signals for glial activation: pro- and anti-inflammatory cytokines in the injured brain,” Acta Neurochirurgica, Supplement, vol. 1999, no. 73, pp. 21–30, 1999. View at Google Scholar · View at Scopus
  176. L. Minghetti, “Role of inflammation in neurodegenerative diseases,” Current Opinion in Neurology, vol. 18, no. 3, pp. 315–321, 2005. View at Google Scholar · View at Scopus
  177. T. Schmitz and L.-J. Chew, “Cytokines and myelination in the central nervous system,” The Scientific World Journal, vol. 8, pp. 1119–1147, 2008. View at Publisher · View at Google Scholar · View at Scopus
  178. A. Spooren, K. Kolmus, G. Laureys et al., “Interleukin-6, a mental cytokine,” Brain Research Reviews, vol. 67, no. 1-2, pp. 157–183, 2011. View at Publisher · View at Google Scholar · View at Scopus
  179. M. Pizzi, I. Sarnico, F. Boroni et al., “Prevention of neuron and oligodendrocyte degeneration by interleukin-6 (IL-6) and IL-6 receptor/IL-6 fusion protein in organotypic hippocampal slices,” Molecular and Cellular Neuroscience, vol. 25, no. 2, pp. 301–311, 2004. View at Publisher · View at Google Scholar · View at Scopus
  180. B. A. Barres, R. Schmid, M. Sendnter, and M. C. Raff, “Multiple extracellular signals are required for long-term oligodendrocyte survival,” Development, vol. 118, no. 1, pp. 283–295, 1993. View at Google Scholar · View at Scopus
  181. S. Grygorczuk, S. Pancewicz, J. Zajkowska, M. Kondrusik, R. Świerzbińska, and T. Hermanowska-Szpakowicz, “Concentrations of macrophage inflammatory proteins MIP-1α and MIP-1β and interleukin 8 (Il-8) in Lyme borreliosis,” Infection, vol. 32, no. 6, pp. 350–355, 2004. View at Publisher · View at Google Scholar · View at Scopus
  182. T. Kossmann, P. F. Stahel, P. M. Lenzlinger et al., “Interleukin-8 released into the cerebrospinal fluid after brain injury is associated with blood-brain barrier dysfunction and nerve growth factor production,” Journal of Cerebral Blood Flow and Metabolism, vol. 17, no. 3, pp. 280–289, 1997. View at Google Scholar · View at Scopus
  183. R. A. Dumont, B. D. Car, N. N. Voitenok et al., “Systemic neutralization of interleukin-8 markedly reduces neutrophilic pleocytosis during experimental lipopolysaccharide-induced meningitis in rabbits,” Infection and Immunity, vol. 68, no. 10, pp. 5756–5763, 2000. View at Publisher · View at Google Scholar · View at Scopus
  184. L. Thirumangalakudi, L. Yin, H. V. Rao, and P. Grammas, “IL-8 induces expression of matrix metalloproteinases, cell cycle and pro-apoptotic proteins, and cell death in cultured neurons,” Journal of Alzheimer's Disease, vol. 11, no. 3, pp. 305–311, 2007. View at Google Scholar · View at Scopus
  185. M. Nordberg, P. Forsberg, A. Johansson et al., “Cytotoxic mechanisms may play a role in the local immune response in the central nervous system in neuroborreliosis,” Journal of Neuroimmunology, vol. 232, no. 1-2, pp. 186–193, 2011. View at Publisher · View at Google Scholar · View at Scopus
  186. C. Ekerfelt, S. Jarefors, N. Tynngård et al., “Phenotypes indicating cytolytic properties of Borrelia-specific interferon-γ secreting cells in chronic Lyme neuroborreliosis,” Journal of Neuroimmunology, vol. 145, no. 1-2, pp. 115–126, 2003. View at Publisher · View at Google Scholar · View at Scopus
  187. A. Rasley, S. L. Tranguch, D. M. Rati, and I. Marriott, “Murine glia express the immunosuppressive cytokine, interleukin-10, following exposure to Borrelia burgdorferi or Neisseria meningitidis,” GLIA, vol. 53, no. 6, pp. 583–592, 2006. View at Publisher · View at Google Scholar · View at Scopus
  188. A. L. F. Bernardino, D. Kaushal, and M. T. Philipp, “The antibiotics doxycycline and minocycline inhibit the inflammatory responses to the Lyme disease spirochete borrelia burgdorferi,” Journal of Infectious Diseases, vol. 199, no. 9, pp. 1379–1388, 2009. View at Publisher · View at Google Scholar · View at Scopus
  189. J. C. McArthur, B. J. Brew, and A. Nath, “Neurological complications of HIV infection,” Lancet Neurology, vol. 4, no. 9, pp. 543–555, 2005. View at Publisher · View at Google Scholar · View at Scopus
  190. N. A. C. H. Brabers and H. S. L. M. Nottet, “Role of the pro-inflammatory cytokines TNF-α and IL-1β in HIV-associated dementia,” European Journal of Clinical Investigation, vol. 36, no. 7, pp. 447–458, 2006. View at Publisher · View at Google Scholar · View at Scopus
  191. M. B. Hallett and D. Lloyds, “Neutrophil priming: the cellular signals that say “amber” but not “green”,” Immunology Today, vol. 16, no. 6, pp. 264–268, 1995. View at Publisher · View at Google Scholar · View at Scopus
  192. C. Elbim, S. Pillet, M. H. Prevost et al., “Redox and activation status of monocytes from human immunodeficiency virus-infected patients: relationship with viral load,” Journal of Virology, vol. 73, no. 6, pp. 4561–4566, 1999. View at Google Scholar · View at Scopus
  193. N. A. Renner, N. S. Ivey, R. K. Redmann, A. A. Lackner, and A. G. MacLean, “MCP-3/CCL7 production by astrocytes: implications for SIV neuroinvasion and AIDS encephalitis,” Journal of NeuroVirology, vol. 17, no. 2, pp. 146–152, 2011. View at Publisher · View at Google Scholar · View at Scopus
  194. W. L. Thompson and L. J. Van Eldik, “Inflammatory cytokines stimulate the chemokines CCL2/MCP-1 and CCL7/MCP-7 through NFκB and MAPK dependent pathways in rat astrocytes,” Brain Research, vol. 1287, pp. 47–57, 2009. View at Publisher · View at Google Scholar · View at Scopus
  195. M. S. Orandle, A. G. MacLean, V. G. Sasseville, X. Alvarez, and A. A. Lackner, “Enhanced expression of proinflammatory cytokines in the central nervous system is associated with neuroinvasion by simian immunodeficiency virus and the development of encephalitis,” Journal of Virology, vol. 76, no. 11, pp. 5797–5802, 2002. View at Publisher · View at Google Scholar · View at Scopus
  196. A. E. Cardona, P. A. Gonzalez, and J. M. Teale, “CC chemokines mediate leukocyte trafficking into the central nervous system during murine neurocysticercosis: role of γδ T cells in amplification of the host immune response,” Infection and Immunity, vol. 71, no. 5, pp. 2634–2642, 2003. View at Publisher · View at Google Scholar · View at Scopus
  197. R. R. Voskuhl, R. S. Peterson, B. Song et al., “Reactive astrocytes form scar-like perivascular barriers to leukocytes during adaptive immune inflammation of the CNS,” Journal of Neuroscience, vol. 29, no. 37, pp. 11511–11522, 2009. View at Publisher · View at Google Scholar · View at Scopus
  198. T. Kielian, “Immunopathogenesis of brain abscess,” Journal of Neuroinflammation, vol. 1, no. 1, article 16, 2004. View at Publisher · View at Google Scholar · View at Scopus
  199. M. Cota, A. Kleinschmidt, F. Ceccherini-Silberstein et al., “Upregulated expression of interleukin-8, RANTES and chemokine receptors in human astrocytic cells infected with HIV-1,” Journal of NeuroVirology, vol. 6, no. 1, pp. 75–83, 2000. View at Google Scholar · View at Scopus
  200. E. A. Eugenin, K. Osiecki, L. Lopez, H. Goldstein, T. M. Calderon, and J. W. Berman, “CCL2/monocyte chemoattractant protein-1 mediates enhanced transmigration of human immunodeficiency virus (HIV)-infected leukocytes across the blood-brain barrier: a potential mechanism of HIV-CNS invasion and NeuroAIDS,” Journal of Neuroscience, vol. 26, no. 4, pp. 1098–1106, 2006. View at Publisher · View at Google Scholar · View at Scopus
  201. M. Hauwel, E. Furon, C. Canova, M. Griffiths, J. Neal, and P. Gasque, “Innate (inherent) control of brain infection, brain inflammation and brain repair: the role of microglia, astrocytes, “protective” glial stem cells and stromal ependymal cells,” Brain Research Reviews, vol. 48, no. 2, pp. 220–233, 2005. View at Publisher · View at Google Scholar · View at Scopus
  202. E. J. Park, S. Y. Park, E.-H. Joe, and I. Jou, “15d-PGJ2 and rosiglitazone suppress Janus kinase-STAT inflammatory signaling through induction of suppressor of cytokine signaling 1 (SOCS1) and SOCS3 in glia,” Journal of Biological Chemistry, vol. 278, no. 17, pp. 14747–14752, 2003. View at Publisher · View at Google Scholar · View at Scopus
  203. T. Fischer-Smith and J. Rappaport, “Evolving paradigms in the pathogenesis of HIV-1-associated dementia,” Expert Reviews in Molecular Medicine, vol. 7, no. 27, pp. 1–26, 2005. View at Publisher · View at Google Scholar · View at Scopus
  204. V. G. Sasseville, J. H. Lane, D. Walsh, D. J. Ringler, and A. A. Lackner, “VCAM-1 expression and leukocyte trafficking to the CNS occur early in infection with pathogenic isolates of SIV,” Journal of Medical Primatology, vol. 24, no. 3, pp. 123–131, 1995. View at Google Scholar · View at Scopus
  205. V. G. Sasseville, W. A. Newman, A. A. Lackner et al., “Elevated vascular cell adhesion molecule-1 in AIDS encephalitis induced by simian immunodeficiency virus,” American Journal of Pathology, vol. 141, no. 5, pp. 1021–1030, 1992. View at Google Scholar · View at Scopus
  206. J. S. Mathew, S. V. Westmoreland, X. Alvarez et al., “Expression of peripherin in the brain of macaques (Macaca mulatta and Macaca fascicularis) occurs in astrocytes rather than neurones and is associated with encephalitis,” Neuropathology and Applied Neurobiology, vol. 27, no. 6, pp. 434–443, 2001. View at Publisher · View at Google Scholar · View at Scopus
  207. V. G. Sasseville, M. M. Smith, C. R. Mackay et al., “Chemokine expression in simian immunodeficiency virus-induced AIDS encephalitis,” American Journal of Pathology, vol. 149, no. 5, pp. 1459–1467, 1996. View at Google Scholar · View at Scopus
  208. C. S. McKimmie and G. J. Graham, “Astrocytes modulate the chemokine network in a pathogen-specific manner,” Biochemical and Biophysical Research Communications, vol. 394, no. 4, pp. 1006–1011, 2010. View at Publisher · View at Google Scholar · View at Scopus
  209. S. Sopper, M. Demuth, C. Stahl-Hennig et al., “The effect of simian immunodeficiency virus infection in vitro and in vivo on the cytokine production of isolated microglia and peripheral macrophages from Rhesus monkey,” Virology, vol. 220, no. 2, pp. 320–329, 1996. View at Publisher · View at Google Scholar · View at Scopus
  210. C. Köhler, “Allograft inflammatory factor-1/Ionized calcium-binding adapter molecule 1 is specifically expressed by most subpopulations of macrophages and spermatids in testis,” Cell and Tissue Research, vol. 330, no. 2, pp. 291–302, 2007. View at Publisher · View at Google Scholar · View at Scopus
  211. K. Ohsawa, Y. Imai, Y. Sasaki, and S. Kohsaka, “Microglia/macrophage-specific protein Iba1 binds to fimbrin and enhances its actin-bundling activity,” Journal of Neurochemistry, vol. 88, no. 4, pp. 844–856, 2004. View at Google Scholar · View at Scopus
  212. M. Tassi, R. Calvente, J. L. Marín-Teva et al., “Behavior of in vitro cultured ameboid microglial cells migrating on Müller cell end-feet in the quail embryo retina,” GLIA, vol. 54, no. 5, pp. 376–393, 2006. View at Publisher · View at Google Scholar · View at Scopus
  213. N. A. Renner, H. A. Sansing, L. A. Morici, F. M. Inglis, A. A. Lackner, and A. G. Maclean, “Microglia activation by SIV-infected macrophages: alterations in morphology and cytokine secretion,” Journal For Neurovirology, vol. 18, no. 3, pp. 213–221, 2012. View at Google Scholar
  214. K. T. Y. Shaw and N. H. Greig, “Chemokine receptor mRNA expression at the in vitro blood-brain barrier during HIV infection,” NeuroReport, vol. 10, no. 4, pp. 53–56, 1999. View at Google Scholar · View at Scopus
  215. N. A. Renner, H. A. Sansing, F. M. Inglis et al., “Transient acidification and subsequent proinflammatory cytokine stimulation of astrocytes induce distinct activation phenotypes,” Journal of Cellular Physiology, vol. 228, no. 6, pp. 1284–1294, 2013. View at Google Scholar
  216. J. Nyagol, G. De Falco, S. Lazzi et al., “HIV-1 Tat mimetic of VEGF correlates with increased microvessels density in AIDS-related diffuse large B-cell and Burkitt lymphomas,” Journal of Hematopathology, vol. 1, no. 1, pp. 3–10, 2008. View at Publisher · View at Google Scholar · View at Scopus
  217. C. A. Garces, E. V. Kurenova, V. M. Golubovskaya, and W. G. Cance, “Vascular endothelial growth factor receptor-3 and focal adhesion kinase bind and suppress apoptosis in breast cancer cells,” Cancer Research, vol. 66, no. 3, pp. 1446–1454, 2006. View at Publisher · View at Google Scholar · View at Scopus
  218. N. S. Ivey, N. A. Renner, T. Moroney et al., “Association of FAK activation with lentivirus-induced disruption of blood-brain barrier tight junction-associated ZO-1 protein organization,” Journal for Neurovirology, vol. 10, pp. 1–12, 2009. View at Google Scholar
  219. E. S. Roberts, E. M. E. Burudi, C. Flynn et al., “Acute SIV infection of the brain leads to upregulation of IL6 and interferon-regulated genes: expression patterns throughout disease progression and impact on neuroAIDS,” Journal of Neuroimmunology, vol. 157, no. 1-2, pp. 81–92, 2004. View at Publisher · View at Google Scholar · View at Scopus
  220. K. C. Williams and W. F. Hickey, “Central nervous system damage, monocytes and macrophages, and neurological disorders in AIDS,” Annual Review of Neuroscience, vol. 25, pp. 537–562, 2002. View at Publisher · View at Google Scholar · View at Scopus
  221. A. Shah, A. S. Verma, K. H. Patel et al., “HIV-1 gp120 induces expression of IL-6 through a nuclear factor-kappa B-dependent mechanism: suppression by gp120 specific small interfering RNA,” PLoS ONE, vol. 6, no. 6, Article ID e21261, 2011. View at Publisher · View at Google Scholar · View at Scopus
  222. S. Sugama, T. Takenouchi, B. P. Cho, T. H. Joh, M. Hashimoto, and H. Kitani, “Possible roles of microglial cells for neurotoxicity in clinical neurodegenerative diseases and experimental animal models,” Inflammation and Allergy, vol. 8, no. 4, pp. 277–284, 2009. View at Publisher · View at Google Scholar · View at Scopus
  223. T. G. D'Aversa, E. A. Eugenin, and J. W. Berman, “CD40-CD40 ligand interactions in human microglia induce CXCL8 (interleukin-8) secretion by a mechanism dependent on activation of ERK1/2 and nuclear translocation of nuclear factor-κB (NFκB) and activator protein-1 (AP-1),” Journal of Neuroscience Research, vol. 86, no. 3, pp. 630–639, 2008. View at Publisher · View at Google Scholar · View at Scopus
  224. A. Shah and A. Kumar, “HIV-1 gp120-mediated increases in IL-8 production in astrocytes are mediated through the NF-κB pathway and can be silenced by gp120-specific siRNA,” Journal of Neuroinflammation, vol. 7, article 96, 2010. View at Publisher · View at Google Scholar · View at Scopus
  225. H. Xiong, J. Boyle, M. Winkelbauer et al., “Inhibition of long-term potentiation by interleukin-8: implications for human immunodeficiency virus-1-associated dementia,” Journal of Neuroscience Research, vol. 71, no. 4, pp. 600–607, 2003. View at Publisher · View at Google Scholar · View at Scopus
  226. G. Penton-Rol, M. Cota, N. Polentarutti et al., “Up-regulation of CCR2 chemokine receptor expression and increased susceptibility to the multitropic HIV strain 89.6 in monocytes exposed, to glucocorticoid hormones,” Journal of Immunology, vol. 163, no. 6, pp. 3524–3529, 1999. View at Google Scholar · View at Scopus
  227. K. W. Witwer, L. Gama, M. Li et al., “Coordinated regulation of SIV replication and immune responses in the CNS,” PLoS ONE, vol. 4, no. 12, p. e8129, 2009. View at Google Scholar · View at Scopus
  228. E. A. Eugenin, T. G. D'Aversa, L. Lopez, T. M. Calderon, and J. W. Berman, “MCP-1 (CCL2) protects human neurons and astrocytes from NMDA or HIV-tat-induced apoptosis,” Journal of Neurochemistry, vol. 85, no. 5, pp. 1299–1311, 2003. View at Publisher · View at Google Scholar · View at Scopus
  229. S. A. Kolb, B. Sporer, F. Lahrtz, U. Koedel, H.-W. Pfister, and A. Fontana, “Identification of a T cell chemotactic factor in the cerebrospinal fluid of HIV-1-infected individuals as interferon-γ inducible protein 10,” Journal of Neuroimmunology, vol. 93, no. 1-2, pp. 172–181, 1999. View at Publisher · View at Google Scholar · View at Scopus
  230. J. L. Mankowski, S. E. Queen, J. E. Clements, and M. C. Zink, “Cerebrospinal fluid markers that predict SIV CNS disease,” Journal of Neuroimmunology, vol. 157, no. 1-2, pp. 66–70, 2004. View at Publisher · View at Google Scholar · View at Scopus
  231. K. C. Williams and W. F. Hickey, “Traffic of hematogenous cells through the central nervous system,” Current Topics in Microbiology and Immunology, vol. 202, pp. 221–245, 1995. View at Google Scholar · View at Scopus
  232. J. Scholz and C. J. Woolf, “The neuropathic pain triad: neurons, immune cells and glia,” Nature Neuroscience, vol. 10, no. 11, pp. 1361–1368, 2007. View at Publisher · View at Google Scholar · View at Scopus
  233. P. Dubový, “Wallerian degeneration and peripheral nerve conditions for both axonal regeneration and neuropathic pain induction,” Annals of Anatomy, vol. 193, no. 4, pp. 267–275, 2011. View at Publisher · View at Google Scholar · View at Scopus
  234. F. Seifert and C. Maihöfner, “Functional and structural imaging of pain-induced neuroplasticity,” Current Opinion in Anaesthesiology, vol. 24, no. 5, pp. 515–523, 2011. View at Publisher · View at Google Scholar · View at Scopus
  235. C. Abbadie, “Chemokines, chemokine receptors and pain,” Trends in Immunology, vol. 26, no. 10, pp. 529–534, 2005. View at Publisher · View at Google Scholar · View at Scopus
  236. C. Abbadie, J. A. Lindia, A. M. Cumiskey et al., “Impaired neuropathic pain responses in mice lacking the chemokine receptor CCR2,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 13, pp. 7947–7952, 2003. View at Publisher · View at Google Scholar · View at Scopus
  237. F. A. White, S. K. Bhangoo, and R. J. Miller, “Chemokines: integrators of pain and inflammation,” Nature Reviews Drug Discovery, vol. 4, no. 10, pp. 834–844, 2005. View at Publisher · View at Google Scholar · View at Scopus
  238. F. A. White, P. Feldman, and R. J. Miller, “Chemokine signaling and the management of neuropathic pain,” Molecular Interventions, vol. 9, no. 4, pp. 188–195, 2009. View at Publisher · View at Google Scholar · View at Scopus
  239. K. Ren and R. Dubner, “Interactions between the immune and nervous systems in pain,” Nature Medicine, vol. 16, no. 11, pp. 1267–1276, 2010. View at Publisher · View at Google Scholar · View at Scopus
  240. F. E. Holmes, N. Arnott, P. Vanderplank et al., “Intra-neural administration of fractalkine attenuates neuropathic pain-related behaviour,” Journal of Neurochemistry, vol. 106, no. 2, pp. 640–649, 2008. View at Publisher · View at Google Scholar · View at Scopus
  241. G. Moalem and D. J. Tracey, “Immune and inflammatory mechanisms in neuropathic pain,” Brain Research Reviews, vol. 51, no. 2, pp. 240–264, 2006. View at Publisher · View at Google Scholar · View at Scopus
  242. J. A. M. Coull, S. Beggs, D. Boudreau et al., “BDNF from microglia causes the shift in neuronal anion gradient underlying neuropathic pain,” Nature, vol. 438, no. 7070, pp. 1017–1021, 2005. View at Publisher · View at Google Scholar · View at Scopus
  243. K. Miyoshi, K. Obata, T. Kondo, H. Okamura, and K. Noguchi, “Interleukin-18-mediated microglia/astrocyte interaction in the spinal cord enhances neuropathic pain processing after nerve injury,” Journal of Neuroscience, vol. 28, no. 48, pp. 12775–12787, 2008. View at Publisher · View at Google Scholar · View at Scopus
  244. A. M. Binshtok, H. Wang, K. Zimmermann et al., “Nociceptors are interleukin-1β sensors,” Journal of Neuroscience, vol. 28, no. 52, pp. 14062–14073, 2008. View at Publisher · View at Google Scholar · View at Scopus
  245. A. M. Skoff, C. Zhao, and J. E. Adler, “Interleukin-1α regulates substance P expression and release in adult sensory neurons,” Experimental Neurology, vol. 217, no. 2, pp. 395–400, 2009. View at Publisher · View at Google Scholar · View at Scopus
  246. X.-J. Xu, J.-X. Hao, S. Andell-Jonsson, V. Poli, T. Bartfai, and Z. Wiesenfeld-Hallin, “Nociceptive responses in interleukin-6-deficient mice to peripheral inflammation and peripheral nerve section,” Cytokine, vol. 9, no. 12, pp. 1028–1033, 1997. View at Publisher · View at Google Scholar · View at Scopus
  247. E. Dominguez, A. Mauborgne, J. Mallet, M. Desclaux, and M. Pohl, “SOCS3-mediated blockade of JAK/STAT3 signaling pathway reveals its major contribution to spinal cord neuroinflammation and mechanical allodynia after peripheral nerve injury,” Journal of Neuroscience, vol. 30, no. 16, pp. 5754–5766, 2010. View at Publisher · View at Google Scholar · View at Scopus
  248. R. R. Myers and V. I. Shubayev, “The ology of neuropathy: an integrative review of the role of neuroinflammation and TNF-α axonal transport in neuropathic pain,” Journal of the Peripheral Nervous System, vol. 16, no. 4, pp. 277–286, 2011. View at Publisher · View at Google Scholar · View at Scopus
  249. C. F. Kim and G. Moalem-Taylor, “Interleukin-17 contributes to neuroinflammation and neuropathic pain following peripheral nerve injury in mice,” Journal of Pain, vol. 12, no. 3, pp. 370–383, 2011. View at Publisher · View at Google Scholar · View at Scopus
  250. S. Nũnéz, J.-S. Lee, Y. Zhang, G. Bai, and J. Y. Ro, “Role of peripheral μ-opioid receptors in inflammatory orofacial muscle pain,” Neuroscience, vol. 146, no. 3, pp. 1346–1354, 2007. View at Publisher · View at Google Scholar · View at Scopus
  251. Y. K. Lee, D. Y. Choi, Y. Y. Jung et al., “Decreased pain responses of C-C chemokine receptor 5 knockout mice to chemical or inflammatory stimuli,” Neuropharmacology, vol. 67, pp. 57–65, 2013. View at Google Scholar
  252. N. Kiguchi, Y. Kobayashi, and S. Kishioka, “Chemokines and cytokines in neuroinflammation leading to neuropathic pain,” Current Opinion in Pharmacology, vol. 12, no. 1, pp. 55–61, 2012. View at Publisher · View at Google Scholar · View at Scopus