Journal of NeuroVirology

, Volume 8, Issue 6, pp 513–528 | Cite as

Glucocorticoids and central nervous system inflammation

  • Klaus Dinkel
  • William O. Ogle
  • Robert M. Sapolsky
Article

Abstract

Glucocorticoids (GCs) are well known for their anti-inflammatory and immunosuppressive properties in the periphery and are therefore widely and successfully used in the treatment of autoimmune diseases, chronic inflammation, or transplant rejection. This led to the assumption that GCs are uniformly anti-inflammatory in the periphery and the central nervous system (CNS). As a consequence, GCs are also used in the treatment of CNS inflammation. There is abundant evidence that an inflammatory reaction is mounted within the CNS following trauma, stroke, infection, and seizure, which can augment the brain damage. However an increasing number of studies indicate that the concept of GCs being universally immunosuppressive might be oversimplified. This article provides a review of the current literature, showing that under certain circumstances GCs might fail to have anti-inflammatory effects and sometimes even enhance inflammation.

Keywords

CNS inflammation corticosteroids immunosuppression neuroimmunology 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Adamson DC, Wildemann B, Sasaki M, Glass JD, McArthur JC, Christov VI, Dawson TM, Dawson VL (1996). Immunologic NO synthase: elevation in severe AIDS dementia and induction by HIV-1 gp41. Science 274: 1917–1921.PubMedCrossRefGoogle Scholar
  2. Aisen PS, Davis KL, Berg JD, Schafer K, Campbell K, Thomas RG, Weiner MF, Farlow MR, Sano M, Grundman M, Thal LJ (2000). A randomized controlled trial of prednisone in Alzheimer’s disease. Alzheimer’s Disease Cooperative Study. Neurology 54: 588–593.PubMedGoogle Scholar
  3. Akassoglou K, Probert L, Kontogeorgos G, Kollias G (1997). Astrocyte-specific but not neuron-specific transmembrane TNF triggers inflammation and degeneration in the central nervous system of transgenic mice. J Immunol 158: 438–445.PubMedGoogle Scholar
  4. Akiyama H, Tooyama I, Kondo H, Ikeda K, Kimura H, McGeer EG, McGeer PL (1994). Early response of brain resident microglia to kainic acid-induced hippocampal lesions. Brain Res 635: 257–268.PubMedCrossRefGoogle Scholar
  5. Alcorn JM, Fierer J, Chojkier M (1992). The acute-phase response protects mice from D-galactosamine sensitization to endotoxin and tumor necrosis factor-alpha. Hepatology 15: 122–129.PubMedCrossRefGoogle Scholar
  6. Andersson J (1996). Clinical and immunological considerations in Epstein-Barr virus-associated diseases. Scand J Infect Dis 100: 72–82.Google Scholar
  7. Asanuma M, Nishibayashi-Asanuma S, Miyazaki I, Kohno M, Ogawa N (2001). Neuroprotective effects of non-steroidal anti-inflammatory drugs by direct scavenging of nitric oxide radicals. J Neurochem 76: 1895–1904.PubMedCrossRefGoogle Scholar
  8. Badie B, Schartner JM, Paul J, Bartley BA, Vorpahl J, Preston JK (2000). Dexamethasone-induced abolition of the inflammatory response in an experimental glioma model: a flow cytometry study. J Neurosurg 93: 634–639.PubMedCrossRefGoogle Scholar
  9. Bailey JM, Makheja AN, Pash J, Verma M (1988). Corticosteroids suppress cyclooxygenase messenger RNA levels and prostanoid synthesis in cultured vascular cells. Biochem Biophys Res Commun 157: 1159–1163.PubMedCrossRefGoogle Scholar
  10. Banati RB, Gehrmann J, Schubert P, Kreutzberg GW (1993). Cytotoxicity of microglia. Glia 7: 111–118.PubMedCrossRefGoogle Scholar
  11. Barber AE, Coyle SM, Marano MA, Fischer E, Calvano SE, Fong Y, Moldawer LL, Lowry SF (1993). Glucocorticoid therapy alters hormonal and cytokine responses to endotoxin in man. J Immunol 150: 1999–2006.PubMedGoogle Scholar
  12. Barnes PJ, Adcock I (1993). Anti-inflammatory actions of steroids: molecular mechanisms. Trends Pharmacol Sci 14: 436–441.PubMedCrossRefGoogle Scholar
  13. Barone FC, Feuerstein GZ (1999). Inflammatory mediators and stroke: new opportunities for novel therapeutics. J Cereb Blood Flow Metab 19: 819–834.PubMedCrossRefGoogle Scholar
  14. Bauer ME, Vedhara K, Perks P, Wilcock GK, Lightman SL, Shanks N (2000). Chronic stress in caregivers of dementia patients is associated with reduced lymphocyte sensitivity to glucocorticoids. J Neuroimmunol 103: 84–92.PubMedCrossRefGoogle Scholar
  15. Baumann H, Gauldie J (1995). The acute phase response. Immunol Today 15: 74–80.CrossRefGoogle Scholar
  16. Beal MF (1992). Mechanisms of excitotoxicity in neurologic diseases. FASEB J 6: 3338–3344.PubMedGoogle Scholar
  17. Beal MF (1995). Aging, energy, and oxidative stress in neurodegenerative diseases. Ann Neurol 38: 357–366.PubMedCrossRefGoogle Scholar
  18. Beamer NB, Coull BM, Clark WM, Briley DP, Wynn M, Sexton G (1998). Persistent inflammatory response in stroke survivors. Neurology 50: 1722–1728.PubMedGoogle Scholar
  19. Becher B, Barker PA, Owens T, Antel JP (1998). CD95-CD95L: can the brain learn from the immune system? Trends Neurosci 21: 114–117.PubMedCrossRefGoogle Scholar
  20. Becker KJ (1998). Inflammation and acute stroke. CurrOpin Neurol 11: 45–49.Google Scholar
  21. Becker KJ (2001). Targeting the central nervous system inflammatory response in ischemic stroke. Curr Opin Neurol 14: 349–353.PubMedCrossRefGoogle Scholar
  22. Belvisi MG, Brown TJ, Wicks S, Foster ML (2001). New glucocorticosteroids with an improved therapeutic ratio? Pulm Pharmacol Ther 14: 221–227.PubMedCrossRefGoogle Scholar
  23. Ben-Hur T, Cialic R, Itzik A, Barak O, Yirmiya R, Weidenfeld J (2001). A novel permissive role for glucocorticoids in induction of febrile and behavioral signs of experimental herpes simplex virus encephalitis. Neurosci 108: 119–127.CrossRefGoogle Scholar
  24. Bergsteindottir K, Brennan A, Jessen KR, Mirsky R (1992). In the presence of dexamethasone, gamma interferon induces rat oligodendrocytes to express major histocompatibility complex class II molecules. Proc Natl Acad Sci USA 89: 9054–9058.PubMedCrossRefGoogle Scholar
  25. Berkenbosch F, van Oers J, del Rey A, Tilders F, Besedovsky H (1987). Corticotropin-releasing factor-producing neurons in the rat activated by interleukin-1. Science 238: 524–526.PubMedCrossRefGoogle Scholar
  26. Besedovsky H, del Rey A, Sorkin E, Dinarello CA (1986). Immunoregulatory feedback between interleukin-1 and glucocorticoid hormones. Science 233: 652–654.PubMedCrossRefGoogle Scholar
  27. Bhargava A, Meijer OC, Dallman MF, Pearce D (2000). Plasma membrane calcium pump isoform 1 gene expression is repressed by corticosterone and stress in rat hippocampus. J Neurosci 20: 3129–3138.PubMedGoogle Scholar
  28. Birnstiel S, List TJ, Beck SG (1995). Chronic corticosterone treatment maintains synaptic activity of CA1 hippocampal pyramidal cells: acute high corticosterone administration increases action potential number. Synapse 20: 117–124.PubMedCrossRefGoogle Scholar
  29. Bone RC, Fisher CJ Jr, Clemmer TP, Slotman GJ, Metz CA, Balk RA (1987). A controlled clinical trial of high-dose methylprednisolone in the treatment of severe sepsis and septic shock. N Engl J Med 317: 653–658.PubMedCrossRefGoogle Scholar
  30. Boumpas DT, Chrousos GP, Wilder RL, Cupps TR, Balow JE (1993). Glucocorticoid therapy for immune-mediated diseases: basic and clinical correlates. Ann Intern Med 119: 1198–1208.PubMedGoogle Scholar
  31. Bracken MB, Shepard MJ, Collins WF, Holford TR, Young W, Baskin DS, Eisenberg HM, Flamm E, Leo-Summers L, Maroon J, et al (1990). A randomized, controlled trial of methylprednisolone or naloxone in the treatment of acute spinal-cord injury. Results of the Second National Acute Spinal Cord Injury Study. N Engl J Med 322: 1405–1411.PubMedCrossRefGoogle Scholar
  32. Bracken MB, Shepard MJ, Holford TR, Leo-Summers L, Aldrich EF, Fazl M, Fehlings M, Herr DL, Hitchon PW, Marshall LF, Nockels RP, Pascale V, Perot PL Jr, Piepmeier J, Sonntag VK, Wagner F, Wilberger JE, Winn HR, Young W (1997). Administration of methylprednisolone for 24 or 48 hours or tirilazad mesylate for 48 hours in the treatment of acute spinal cord injury. Results of the Third National Acute Spinal Cord Injury Randomized Controlled Trial. National Acute Spinal Cord Injury Study. JAMA 277: 1597–1604.PubMedCrossRefGoogle Scholar
  33. Breitner JC (1996). The role of anti-inflammatory drugs in the prevention and treatment of Alzheimer’s disease. Annu Rev Med 47: 401–411.PubMedCrossRefGoogle Scholar
  34. Bruccoleri A, Pennypacker KR, Harry GJ (1999). Effect of dexamethasone on elevated cytokine mRNA levels in chemical-induced hippocampal injury. J Neurosci Res 57: 916–926.PubMedCrossRefGoogle Scholar
  35. Bruce AJ, Boling W, Kindy MS, Peschon J, Kraemer PJ, Carpenter MK, Holtsberg FW, Mattson MP (1996). Altered neuronal and microglial responses to excitotoxic and ischemic brain injury in mice lacking TNF receptors. Nat Med 2: 788–794.PubMedCrossRefGoogle Scholar
  36. Brusaferri F, Candelise L (2000). Steroids for multiple sclerosis and optic neuritis: a meta-analysis of randomized controlled clinical trials. J Neurol 247: 435–442.PubMedCrossRefGoogle Scholar
  37. Bucala R (1996). MIF rediscovered: cytokine, pituitary hormone, and glucocorticoid-induced regulator of the immune response. FASEB J 10: 1607–1613.PubMedGoogle Scholar
  38. Burchard K (2001). A review of the adrenal cortex and severe inflammation: quest of the “eucorticoid” state. J Trauma 51: 800–814.PubMedCrossRefGoogle Scholar
  39. Burton JL, Kehril ME Jr, Kapsil S, Horst RL (1995). Regulation of L-selectin and CD18 on bovine neutrophils by glucocorticoids: effects of cortisol and dexamethasone. J Leukoc Biol 57: 317–325.PubMedGoogle Scholar
  40. Calandra T, Bernhagen J, Metz CN, Spiegel LA, Bacher M, Donnelly T, Cerami A, Bucala R (1995). MIF as a glucocorticoid-induced modulator of cytokine production. Nature 377: 68–71.PubMedCrossRefGoogle Scholar
  41. Camelo S, Lafage M, Lafon M (2000). Absence of the p55 Kd TNF-alpha receptor promotes survival in rabies virus acute encephalitis. J Neurovirol 6: 507–518.PubMedCrossRefGoogle Scholar
  42. Campbell IL, Abraham CR, Masliah E, Kemper P, Inglis JD, Oldstone MB, Mucke L (1993). Neurologic disease induced in transgenic mice by cerebral overexpression of interleukin 6. Proc Natl Acad Sci USA 90: 10061–10065.PubMedCrossRefGoogle Scholar
  43. Calogero AE, Sternberg EM, Bagdy G, Smith C, Bernardini R, Aksentijevich S, Wilder RL, Gold PW, Chrousos GP (1992). Neurotransmitter-induced hypothalamic-pituitary-adrenal axis responsiveness is defective in inflammatory disease-susceptible Lewis rats: in vivo and in vitro studies suggesting globally defective hypothalamic secretion of corticotropin-releasing hormone. Neuroendocrinology 55: 600–608.PubMedCrossRefGoogle Scholar
  44. Cato AC, Wade E (1996). Molecular mechanisms of antiinflammatory action of glucocorticoids. BioEssays 18: 371–378.PubMedCrossRefGoogle Scholar
  45. Cavallo MG, Baroni Mg, Toto A, Gearing AJ, Forsey T, Andreani D, Thorpe R, Pozzilli P (1992). Viral infections induces cytokine release by beta islet cells. Immunology 75: 664–668.PubMedGoogle Scholar
  46. Chapman GA, Moores K, Harrison D, Campbell CA, Stewart BR, Strijbos PJ (2000). Fractalkine cleavage from neuronal membranes represents an acute event in the inflammatory response to excitotoxic brain damage. J Neurosci 20: RC87.PubMedGoogle Scholar
  47. Cheng B, Christakos S, Mattson MP (1994). Tumor necrosis factors protect neurons against metabolic-excitotoxic insults and promote maintenance of calcium homeostasis. Neuron 12: 139–153.PubMedCrossRefGoogle Scholar
  48. Chrousos GP (1995). The hypothalamic-pituitary-adrenal axis and immune mediated inflammation. N Engl J Med 332: 1351–1362.PubMedCrossRefGoogle Scholar
  49. Colton C, Wilt S, Gilbert D, Chernyshev O, Snell J, Dubois-Dalcq M (1996). Species differences in the generation of reactive oxygen species by microglia. Mol Chem Neuropathol 28: 15–20.PubMedCrossRefGoogle Scholar
  50. Cox G, Austin RC (1997). Dexamethasone-induced suppression of apoptosis in human neutrophils requires continuous stimulation of new protein synthesis. J Leukoc Biol 61: 224–230.PubMedGoogle Scholar
  51. Coyle PK (1999). Glucocorticoids in central nervous system bacterial infection. Arch Neurol 56: 796–801.PubMedCrossRefGoogle Scholar
  52. Craig CR, Stitzel RE (1994). Modern pharmacology, 4th ed. Boston: Little, Brown, p 737.Google Scholar
  53. Cronin L, Cook DJ, Carlet J, Heyland DK, King D, Lansang MA, Fisher CJ Jr (1998). Corticosteroid treatment for sepsis: a critical appraisal and meta-analysis of the literature. Crit Care Med 23: 1430–1439.CrossRefGoogle Scholar
  54. Cronstein BN, Kimmel SC, Levin RI, Martiniuk F, Weissmann G (1992). A mechanism for the antiinflammatory effects of corticosteroids: the glucocorticoid receptor regulates leukocyte adhesion to endothelial cells and expression of endothelial-leukocyte adhesion molecule 1 and intercellular adhesion molecule 1. Proc Natl Acad Sci USA 89: 9991–9995.PubMedCrossRefGoogle Scholar
  55. Dalakas MC (1995). Basic aspects of neuroimmunology as they relate to immunotherapeutic targets: present and future prospects. Ann Neurol 37 (Suppl 1): S2-S13.PubMedCrossRefGoogle Scholar
  56. David JR (1966). Delayed hypersensitivity in vitro: its mediation by cell-free substances formed by lymphoid cell-antigen interaction. Proc Natl Acad Sci USA 56: 72–77.PubMedCrossRefGoogle Scholar
  57. Davis JM, Albert JD, Tracy KJ, Calvano SE, Lowry SF, Shires GT, Yurt RW (1991). Increased neutrophil mobilization and decreased chemotaxis during cortisol and epinephrine infusions. J Trauma 31: 725–731; discussion 731–732.PubMedCrossRefGoogle Scholar
  58. de Bock F, Dornand J, Rondouin G (1996). Release of TNF alpha in the rat hippocampus following epileptic seizures and excitotoxic neuronal damage. Neuroreport 7: 1125–1129.PubMedCrossRefGoogle Scholar
  59. De Bosscher K, Vanden Berghe W, Haegeman G (2000). Mechanisms of antiinflammatory action and of immuno-suppression by glucocorticoids: negative interference of activated glucocorticoid receptor with transcription factors. J Neuroimmunol 109: 16–22.PubMedCrossRefGoogle Scholar
  60. De Kloet ER, Vreugdenhil E, Oitzl MS, Joels M (1998). Brain corticosteroid receptor balance in health and disease. Endocr Rev 19: 269–301.PubMedCrossRefGoogle Scholar
  61. DeGraba TJ (1998). The role of inflammation after acute stroke: utility of pursuing anti-adhesion molecule therapy. Neurology 51 (Suppl 3): S62-S68.PubMedGoogle Scholar
  62. DeGraba TJ, Pettigrew LC (2000). Why do neuroprotective drugs work in animals but not humans? Neurol Clin 18: 475–493.PubMedCrossRefGoogle Scholar
  63. De Keyser J, Sulter G, Luiten PG (1999). Clinical trials with neuroprotective drugs in acute ischaemic stroke: are we doing the right thing? Trends Neurosci 22: 535–540.PubMedCrossRefGoogle Scholar
  64. DeRijk R, Michelson D, Karp B, et al (1997). Exercise and circadian rhythm-induced variations in plasma cortisol differentially regulate interleukin-1 beta (IL-1 beta), IL-6, and tumor necrosis factor-alpha (TNF alpha) production in humans: high sensitivity of TNF alpha and resistance of IL-6. J Clin Endocrinol Metab 82: 2182–2191.PubMedCrossRefGoogle Scholar
  65. del Zoppo GJ, Becker KJ, Hallenbeck JM (2001). Inflammation after stroke: is it harmful? Arch Neurol 58: 669–672.PubMedCrossRefGoogle Scholar
  66. Dermietzel R (1975). Junctions in the central nervous system of the cat. IV. Interendothelial junctions of cerebral blood vessels from selected areas of the brain. Cell Tissue Res 164: 45–62.PubMedGoogle Scholar
  67. Dhabhar FS, Miller AH, McEwen BS, Spencer RL (1996). Stress-induced changes in blood leukocyte distribution. Role of adrenal steroid hormones. J Immunol 157: 1638–1644.PubMedGoogle Scholar
  68. Dhabhar FS, McEwen BS (1996). Stress-induced enhancement of antigen-specific cell-mediated immunity. J Immunol 156: 2608–2615.PubMedGoogle Scholar
  69. Dhabhar FS, McEwen BS (1997). Acute stress enhances while chronic stress suppresses cell-mediated immunity in vivo: a potential role for leukocyte trafficking. Brain Behav Immun 11: 286–306.PubMedCrossRefGoogle Scholar
  70. Dinkel K, Sapolsky RM (2003). Novel glucocorticoid effects on acute inflammation in the central nervous system. J Neurochem In press.Google Scholar
  71. Dirnagl U, Iadecola C, Moskowitz MA (1999). Pathobiology of ischaemic stroke: an integrated view. Trends Neurosci 22: 391–397.PubMedCrossRefGoogle Scholar
  72. Dodd DA, Giddings TH Jr, Kirkegaard K (2001). Poliovirus 3A protein limits interleukin-6 (IL-6), IL-8, and beta interferon secretion during viral infection. J Virol 75: 8158–8165.PubMedCrossRefGoogle Scholar
  73. Domachowske JB, Bonville CA, Ali-Ahmad D, Dyer KD, Easton AJ, Rosenberg HF (2001). Glucocorticoid administration accelerates mortality of pneumovirus-infected mice. J Infect Dis 184: 1518–1523.PubMedCrossRefGoogle Scholar
  74. Donnelly SC, Bucala R (1997). Macrophage migration inhibitory factor: a regulator of glucocorticoid activity with a critical role in inflammatory disease. Mol Med Today Nov: 502–507.CrossRefGoogle Scholar
  75. Elenkov IJ, Webster EL, Torpy DJ, Chrousos GP (1999). Stress, corticotropin-releasing hormone, glucocorticoids, and the immune/inflammatory response: acute and chronic effects. Ann N Y Acad Sci 876: 1–11; discussion 11–13.PubMedCrossRefGoogle Scholar
  76. Emilie D, Crevon MC, Auffredou MT, Galanaud P (1988). Glucocorticosteroid-dependent synergy between interleukin 1 and interleukin 6 for human B lymphocyte differentiation. Eur J Immunol 18: 2043–2047.PubMedCrossRefGoogle Scholar
  77. Ferguson TA, Griffith TS (1997). A vision of cell death: insights into immune privilege. Immunol Rev 156: 167–184.PubMedCrossRefGoogle Scholar
  78. Fernandez-Ruiz E, Rebollo A, Nieto MA, Sanz E, Somoza C, Ramirez F, Lopez-Rivas A, Silva A (1989). IL-2 protects T cell hybrids from the cytolytic effect of glucocorticoids. Synergistic effect of IL-2 and dexamethasone in the induction of high-affinity IL-2 receptors. J Immunol 143: 4146–4151.PubMedGoogle Scholar
  79. Feuerstein GZ, Wang X (2001). Inflammation and stroke: benefits without harm? Arch Neurol 58: 672–674.PubMedCrossRefGoogle Scholar
  80. Feuerstein GZ, Wang X, Barone FC (1998). In: Cerebrovascular disease: pathophysiology, diagnosis and management. Ginsberg M, Bogousslavsky J (eds.). Blackwell Science: Oxford, UK, pp 507–531.Google Scholar
  81. Flippini G, Brusaferri F, Sibley WA, Citterio A, Ciucci G, Midgard R, Candelise L (2000). Corticosteroids or ACTH for acute exacerbations in multiple sclerosis. Cochrane Database Syst Rev 4.Google Scholar
  82. Fishman RA (1982). Steroids in the treatment of brain edema. N Engl J Med 306: 359–360.PubMedCrossRefGoogle Scholar
  83. Foss HD, Herbst H, Hummel M, Araujo I, Latza U, Rancso C, Dallenbach F, Stein H (1994). Patterns of cytokine gene expression in infectious mononucleosis. Blood 84: 707–712.Google Scholar
  84. Fox RJ, Levin MC, Jacobson S (1996). Tumor necrosis factor alpha expression in the spinal cord of human T-cell lymphotrophic virus type I associated myelopathy/ tropical spastic paraparesis patients. J Neurovirol 2: 297–298.CrossRefGoogle Scholar
  85. Galicich J, French L, Melly J (1961). Use of dexamethasone in treatment of cerebral edema associated with brain tumor. J Lancet 81: 46.PubMedGoogle Scholar
  86. Gary DS, Bruce-Keller AJ, Kindy MS, Mattson MP (1998). Ischemic and excitotoxic brain injury is enhanced in mice lacking the p55 tumor necrosis factor receptor. J Cereb Blood Flow Metab 18: 1283–1287.PubMedCrossRefGoogle Scholar
  87. Getting SJ, Flower RJ, Perretti M (1997). Inhibition of neutrophil and monocyte recruitment by endogenous and exogenous lipocortin 1. Br J Pharmacol 120: 1075–1082.PubMedCrossRefGoogle Scholar
  88. Ghosh D (1992). Glucocorticoid receptor binding site in the HIV long terminal repeat. J Virol 66: 586–590.PubMedGoogle Scholar
  89. Glaser R, Kiecolt-Glaser JK (1998). Stress-associated immune modulation: relevance to viral infections and chronic fatigue syndrome (review). Am J Med 105: 35S-42S.PubMedCrossRefGoogle Scholar
  90. Gosselin J, Flamand L, D’Addario M, Hiscott J, Menezes J (1992). Infection of peripheral blood mononuclear cells by herpes simplex and Epstien-Barr viruses. Differential induction of interleukin 6 and tumor necrosis factor-alpha. J Clin Invest 89: 1849–1856.PubMedCrossRefGoogle Scholar
  91. Gould E, McEwen B, Tanapat P, Galea L, Fuchs E (1997). Neurogenesis in the dentate gyrus of the adult tree shrew is regulated by psychosocial stress and NMDA receptor activation. J Neurosci 18: 2492.Google Scholar
  92. Gould E, Tanapat P, McEwen B, Flugge G, Fuchs E (1998). Proliferation of granule cell precursors in the dentate gyrus of adult monkeys is diminished by stress. Proc Natl Acad Sci USA 95: 3168.PubMedCrossRefGoogle Scholar
  93. Goulding NJ, Euzger HS, Butt SK, Perretti M (1998). Novel pathways for glucocorticoid effects on neutrophils in chronic inflammation. Inflamm Res 47(Suppl 3): S158-S165.PubMedCrossRefGoogle Scholar
  94. Griffin DE, Wesselingh SL, McArthur JC (1994). Elevated central nervous system prostaglandins in human immunodeficiency virus-associated dementia. Ann Neurol 35: 592–597.PubMedCrossRefGoogle Scholar
  95. Hall ED, Braughler JM (1982). Glucocorticoid mechanisms in acute spinal cord injury: a review and therapeutic rationale. Surg Neurol 18: 320–327.PubMedCrossRefGoogle Scholar
  96. Hardwicke MA, Schaffer PA (1997). Differential effects of nerve growth factor and dexamethasone on herpes simplex virus type 1 oriL and oriS dependent DNA replication in PC12 cell. J Virol 71: 3580–3587.PubMedGoogle Scholar
  97. Heim A, Zeuke S, Weiss S, Ruschewski W, Grumbach IM (2000). Transient induction of cytokine production in human myocardial fibroblasts by coxsackievirus B3. CircRes 86: 753–759.Google Scholar
  98. Hench P, Kendall EC, Slocumb CH, Polley HF (1949). The effects of a hormone of the adrenal cortex and of pituitary adrenocorticotropic hormone on rheumatoid arthritis. Proc Mayo Clin 24: 181–197.PubMedGoogle Scholar
  99. Hetier E, Ayala J, Bousseau A, Prochiantz A (1991). Modulation of interleukin-1 and tumor necrosis factor expression by beta-adrenergic agonists in mouse ameboid microglial cells. Exp Brain Res 86: 407–413.PubMedCrossRefGoogle Scholar
  100. Hildeman D, Muller D (2000). Immunopathologic weight loss in intracranial LCMV infection initiated by the anorexigenic effects of IL-1 beta. Viral Immunol 13: 273–285.PubMedCrossRefGoogle Scholar
  101. Hughes RA, van Der Meche FG (2000). Corticosteroids for treating Guillain-Barre syndrome. Cochrane Database Syst Rev 3.Google Scholar
  102. Iadecola C (1997). Bright and dark sides of nitric oxide in ischemic brain injury. Trends Neurosci 20: 132–139.PubMedCrossRefGoogle Scholar
  103. Iadecola C, Alexander M (2001). Cerebral ischemia and inflammation. Curr Opin Neurol 14: 89–94.PubMedCrossRefGoogle Scholar
  104. Ilyin SE, Plata-Salaman CR (1997). HIV-1 envelope glycoprotein 120 regulates brain IL-1 beta system and TNF-alpha mRNAs in vivo. Brain Res Bull 44: 67–73.PubMedCrossRefGoogle Scholar
  105. Inagi R, Guntapong R, Nakao M, Ishino Y, Kawanishi K, Isegawa Y, Yamanishi K (1996). Human herpesvirus 6 induces IL-8 gene expression in human hepatoma cell line, Hep G2. J Med Virol 49: 34–40.PubMedCrossRefGoogle Scholar
  106. Jacobson L, Sapolsky R (1991). The role of the hippocampus in feedback regulation of the hypothalamic-pituitary-adrenocortical axis. Endocr Rev 12: 118–134.PubMedCrossRefGoogle Scholar
  107. Joblonowska E, Lisiewicz J, Kuydowicz J, Pojda Z (1999). Levels of interleukin-6 in cerebrospinal fluid of patients with meningitis. Neurol Neurochir Polska 32: 161–165.Google Scholar
  108. Joels M (2001). Corticosteroid actions in the hippocampus. J Neuroendocrinol 13: 657–669.PubMedCrossRefGoogle Scholar
  109. Joels M, de Kloet E (1989). Effects of glucocorticoids and norepinephrine on the excitability in the hippocampus. Science 245: 1502–1505.PubMedCrossRefGoogle Scholar
  110. Juttner S, Bernhagen J, Metz CN, Rollinghoff M, Bucala R, Gessner A (1998). Migration inhibitory factor induces killing of Leishmania major by macrophages: dependence on reactive nitrogen intermediates and endogenous TNF-alpha. J Immunol 161: 2383–2390.PubMedGoogle Scholar
  111. Kellendonk C, Tronche F, Reichardt HM, Schutz G (1999). Mutagenesis of the glucocorticoid receptor in mice. J Steroid Biochem Mol Biol 69: 253–259.PubMedCrossRefGoogle Scholar
  112. Kern JA, Lamb RJ, Reed JC, Daniele RP, Nowell PC (1988). Dexamethasone inhibition of interleukin 1 beta production by human monocytes. Posttranscriptional mechanisms. J Clin Invest 81: 237–244.PubMedCrossRefGoogle Scholar
  113. Kerr D, Campbell L, Hao S, Landfield P (1989). Corticosteroid modulation of hippocampal potentials: increased effect with aging. Science 245: 1505–1509.PubMedCrossRefGoogle Scholar
  114. Kerschensteiner M, Gallmeier E, Behrens L, Leal VV, Misgeld T, Klinkert WE, Kolbeck R, Hoppe E, Oropeza-Wekerle RL, Bartke I, Stadelmann C, Lassmann H, Wekerle H, Hohlfeld R (1999). Activated human T cells, B cells, and monocytes produce brain-derived neurotrophic factor in vitro and in inflammatory brain lesions: a neuroprotective role of inflammation? J Exp Med 189: 865–870.PubMedCrossRefGoogle Scholar
  115. Kino T, Chrousos GP (2001). Glucocorticoid and mineralo-corticoid resistance/hypersensitivity syndromes. J Endocrinol 169: 437–445.PubMedCrossRefGoogle Scholar
  116. Kiwerski JE (1993). Application of dexamethasone in the treatment of acute spinal cord injury. Injury 24: 457–460.PubMedCrossRefGoogle Scholar
  117. Koedel U, Kohleisen B, Sporer B, Lahrtz F, Ovod V, Fontana A, Erfle V, Pfister HW (1999). HIV type 1 Nef protein is a viral factor for leukocyte recruitment into the central nervous system. J Immunol 163: 1237–1245.PubMedGoogle Scholar
  118. Koide T, Wieloch TW, Siesjo BK (1986). Chronic dexamethasone pretreatment aggravates ischemic neuronal necrosis. J Cereb Blood Flow Metab 6: 395–404.PubMedGoogle Scholar
  119. Kreutzberg GW (1996). Microglia: a sensor for pathological events in the CNS. Trends Neurosci 19: 312–318.PubMedCrossRefGoogle Scholar
  120. Kupfer SR, Summers WC (1990). Identification of a glucocorticoid-responsive element in Epstein-Barr virus. J Virol 64: 1984–1990.PubMedGoogle Scholar
  121. Landfield PW, Baskin RK, Pitler TA (1981). Brain aging correlates: retardation by hormonal-pharmacological treatments. Science 214: 581–584.PubMedCrossRefGoogle Scholar
  122. Lee JM, Zipfel GJ, Choi DW (1999). The changing landscape of ischaemic brain injury mechanisms. Nature 399(6738 Suppl): A7-A14.PubMedGoogle Scholar
  123. Leech M, Metz C, Hall P, Hutchinson P, Gianis K, Smith M, Weedon H, Holdsworth SR, Bucala R, Morand EF (1999). Macrophage migration inhibitory factor in rheumatoid arthritis: evidence of proinflammatory function and regulation by glucocorticoids. Arthritis Rheum 42: 1601–1608.PubMedCrossRefGoogle Scholar
  124. Lefering R, Neugebauer EA (1995). Steroid controversy in sepsis and septic shock: a meta-analysis. Crit Care Med 23: 1294–1303.PubMedCrossRefGoogle Scholar
  125. Leopardi R, Vainionpaa R, Hurme M, Siljander P, Salmi AA (1992). Measles virus infection enhances IL-1 beta but reduces tumor necrosis factor-alpha expression in human moncytes. J Immunol 149: 2397–2401.PubMedGoogle Scholar
  126. Liao J, Keiser JA, Scales WE, Kunkel SL, Kluger MJ (1995). Role of epinephrine in TNF and IL-6 production from isolated perfused rat liver. Am J Physiol 268 (4 Pt 2): R896-R901.PubMedGoogle Scholar
  127. Liles WC, Dale DC, Klebanoff SJ (1995). Glucocorticoids inhibit apoptosis of human neutrophils. Blood 86: 3181–3188.PubMedGoogle Scholar
  128. Lilly MP, Gann DS (1992). The hypothalamic-pituitary-adrenal-immune axis. Arch Surg 127: 1463–1474.PubMedGoogle Scholar
  129. Limoges J, Persidsky Y, Bock P, Gendelman HE (1997). Dexamethasone therapy worsens the neuropathology of human immunodeficiency virus type 1 encephalitis in SCID mice. J Infect Dis 175: 1368–1381.PubMedCrossRefGoogle Scholar
  130. Lipton SA, Rosenberg PA (1994). Excitatory amino acids as a final common pathway for neurologic disorders. N Engl J Med 330: 613–622.PubMedCrossRefGoogle Scholar
  131. Magarinos AM, Deslandes A, McEwen BS (1999). Effects of antidepressants and benzodiazepine treatments on the dendritic structure of CA3 pyramidal neurons after chronic stress. Eur J Pharmacol 371: 113–122.PubMedCrossRefGoogle Scholar
  132. Marquette C, van Dam AM, Ceccaldi PE, Weber P, Haour F, Tsiang H (1996). Induction of immunoreactive interleukin-1 beta and tumor necrosis factor alpha in the brains of rabies virus infected rats. J Neuroimmunol 68: 45–51.PubMedCrossRefGoogle Scholar
  133. Marx J (1995). Howthe glucocorticoids suppress immunity. Science 270: 232–233.PubMedCrossRefGoogle Scholar
  134. McEwen BS (1998). Protective and damaging effects of stress mediators. N Engl J Med 238: 171–179.Google Scholar
  135. McEwen BS (2000). The neurobiology of stress: from serendipity to clinical relevance. Brain Res 886: 172–189.PubMedCrossRefGoogle Scholar
  136. McEwen BS, Albeck D, Cameron H, Chao HM, Gould E, Hastings N, Kuroda Y, Luine V, Magarinos AM, McKittrick CR, et al (1995). Stress and the brain: a paradoxical role for adrenal steroids. Vitam Horm 51: 371–402.PubMedCrossRefGoogle Scholar
  137. McEwen BS, De Kloet ER, Rostene W (1986). Adrenal steroid receptors and actions in the nervous system. Physiol Rev 66: 1121–1188.PubMedGoogle Scholar
  138. McEwen BS, Magarinos AM (1997). Stress effects on morphology and function of the hippocampus. Ann N Y Acad Sci 821: 271–284.PubMedCrossRefGoogle Scholar
  139. McGaugh JL (2000). Memory—a century of consolidation. Science 287: 248–251.PubMedCrossRefGoogle Scholar
  140. McGeer EG, McGeer PL (1994). Neurodegeneration and the immune system. In: Neurodegenerative disorders. Calne DB (ed). WB Saunders: Philadelphia, PA, pp 277–300.Google Scholar
  141. McGeer EG, McGeer PL (1999). Brain inflammation in Alzheimer disease and the therapeutic implications. Curr Pharm Des 5: 821–836.PubMedGoogle Scholar
  142. McGeer PL, McGeer EG (1995). The inflammatory response system of brain: implications for therapy of Alzheimer and other neurodegenerative diseases. Brain Res Brain Res Rev 21: 195–218.PubMedCrossRefGoogle Scholar
  143. Meaney MJ (1988). The sexual differentiation of social play. Trends Neurosci 11: 54–58.PubMedCrossRefGoogle Scholar
  144. Miller G, Davis J (1991). Post-ischemic surge in corticosteroids aggravates ischemic damage to gerbil CA1 pyramidal cells. Soc Neurosci Abst 17: 302.4.Google Scholar
  145. Millikan CH, McDowell F, Easton JD (1987). Progressing stroke. In: Stroke. Millikan CH, McDowell F, Easton JD (eds). Lea & Febiger, Philadelphia, PA, pp 117–130.Google Scholar
  146. Mori N, Prager D (1996). Transactivation of the interleukin-1 alpha promoter by the human T-cell leukemia virus type I and type II Tax proteins. Blood 87: 3410–3417.PubMedGoogle Scholar
  147. Mukaida N, Zachariae CC, Gusella GL, Matsushima K (1991). Dexamethasone inhibits the induction of monocyte chemotactic-activating factor production by IL-1 or tumor necrosis factor. J Immunol 146: 1212–1215.PubMedGoogle Scholar
  148. Munck A, Guyre PM, Holbrook NJ (1984). Physiological functions of glucocorticoids in stress and their relation to pharmacological actions. Endocr Rev 5: 25–44.PubMedCrossRefGoogle Scholar
  149. Munck A, Naray-Fejes-Toth A (1994). Glucocorticoids and stress: permissive and suppressive actions. Ann N Y Acad Sci 746: 115–130.PubMedCrossRefGoogle Scholar
  150. Nelson DH (1995). Historical overview of the adrenal cortex. In: Endocrinology, vol 3. Degroot L (ed). WB Saunders: Philadelphia, PA, p 257.Google Scholar
  151. Nesathurai S (1998). Steroids and spinal cord injury: revisiting the NASCIS 2 and NASCIS 3 trials. J Trauma 45: 1088–1093.PubMedCrossRefGoogle Scholar
  152. Neumann H (2001). Control of glial immune function by neurons. Glia 36: 191–199.PubMedCrossRefGoogle Scholar
  153. Newton CJ, Bilko D, Pappa S, Atkin SL (2001). Dexamethasone blocks antioestrogen- and oxidant-induced death of pituitary tumour cells. J Endocrinol 169: 249–261.PubMedCrossRefGoogle Scholar
  154. Neznanov N, Kondratova A, Chumakov KM, Angres B, Zhumbayeva B, Agol VI, Gudkov AV (2001). Poliovirus protein 3 A inhibits tumor necrosis factor (TNF) induced apoptosis by eliminating the TNF receptor from the cell surface. J Virol 75: 10409–10420.PubMedCrossRefGoogle Scholar
  155. Nguyen KB, Biron CA (1999). Synergism for cytokine-mediated disease during concurrent endotoxin and viral challenges: roles for NK and T and IFN-gamma production. J Immunol 162: 5238–5246.PubMedGoogle Scholar
  156. Nishikawa M, Matsubara T, Yoshitomi T, Ichiyama T, Hayashi T, Furukawa S (2000). Abnormalities of brain perfusion in echovirus type 30 meningitis. J Neuro Sci 179(S1–S2): 122–126.CrossRefGoogle Scholar
  157. Nishio Y, Isshiki H, Kishimoto T, Akira S (1993). A nuclear factor for interleukin-6 expression (NF-IL6) and the glucocorticoid receptor synergistically activate transcription of the rat alpha 1-acid glycoprotein gene via direct protein-protein interaction. Mol Cell Biol 13: 1854–1862.PubMedGoogle Scholar
  158. Nogawa S, Zhang F, Ross ME, Iadecola C (1997). Cyclooxygenase-2 gene expression in neurons contributes to ischemic brain damage. J Neurosci 17: 2746–2755.PubMedGoogle Scholar
  159. Noisakran S, Halford WP, Veress L, Carr DL (1998). Role of the hypothalamic pituitary adrenal axis and IL-6 in stress-induced reactivation of latent herpes simplex virus type 1. J Immunol 160: 5441–5447.PubMedGoogle Scholar
  160. Noseworthy JH, Lucchinetti C, Rodriguez M, Weinshenker BG (2000). Multiple sclerosis. N Engl J Med 343: 938–952.PubMedCrossRefGoogle Scholar
  161. Nuovo GJ, Alfieri ML (1996). AIDS dementia is associated with massive, activated HIV-1 infection and concomitant expression of several cytokines. Mol Med 2: 358–366.PubMedCrossRefGoogle Scholar
  162. Olney JW (1978). Neurotoxicity of excitatory amino acids. In: Kainic acid as a tool in neurobiology. McGeer EG, Olney JW, McGeer PL (eds). Raven Press: New York; pp 95–121.Google Scholar
  163. O’Neill LA, Kaltschmidt C (1997). NF-kappa B: a crucial transcription factor for glial and neuronal cell function. Trends Neurosci 20: 252–258.PubMedCrossRefGoogle Scholar
  164. Ottaviani E, Franceschi C (1996). The neuroimmunology of stress from invertebrates to man. Prog Neurobiol 48: 421–440.PubMedCrossRefGoogle Scholar
  165. Pascuzzi RM, Coslett HB, Johns TR (1984). Long-term corticosteroid treatment of myasthenia gravis: report of 116 patients. Ann Neurol 15: 291–298.PubMedCrossRefGoogle Scholar
  166. Pearce BD, Biron CA, Miller AH (2001). Neuroendocrine-immune interactions during viral infections (review). Adv Virus Res 56: 469–513.PubMedCrossRefGoogle Scholar
  167. Perretti M, Flower RJ (1994). Cytokines, glucocorticoids and lipocortins in the control of neutrophil migration. Pharmacol Res 30: 53–59.PubMedCrossRefGoogle Scholar
  168. Perry VH, Gordon S (1991). Macrophages and the nervous system. Int Rev Cytol 125: 203–244.PubMedCrossRefGoogle Scholar
  169. Peterson PK, Gekker G, Hu S, Chao CC (1997). Microglia: a “double-edged sword.” In: In defense of the brain. Peterson PK, Remington JS (eds). Blackwell Science: Oxford, UK, pp 31–55.Google Scholar
  170. Pietzko D, Zohlnhofer D, Graeve L, Fleischer D, Stoyan T, Schooltink H, Rose-John S, Heinrich PC (1993). The hepatic interleukin-6 receptor. Studies on its structure and regulation by phorbol 12-myristate 13-acetate-dexamethasone. J Biol Chem 268: 4250–4258.PubMedGoogle Scholar
  171. Ransohoff RM, Tani M (1998). Do chemokines mediate leukocyte recruitment in post-traumatic CNS inflammation? Trends Neurosci 21: 154–159.PubMedCrossRefGoogle Scholar
  172. Rapalino O, Lazarov-Spiegler O, Agranov E, Velan GJ, Yoles E, Fraidakis M, Solomon A, Gepstein R, Katz A, Belkin M, Hadani M, Schwartz M (1998). Implantation of stimulated homologous macrophages results in partial recovery of paraplegic rats. Nat Med 4: 814–821.PubMedCrossRefGoogle Scholar
  173. Risau W, Wolburg H (1990). Development of the blood-brain barrier. Trends Neurosci 13: 174–178.PubMedCrossRefGoogle Scholar
  174. Rothwell NJ, Luheshi G, Toulmond S (1996). Cytokines and their receptors in the central nervous system: physiology, pharmacology, and pathology. Pharmacol Ther 69: 85–95.PubMedCrossRefGoogle Scholar
  175. Ruscher K, Isaev N, Trendelenburg G, Weih M, Iurato L, Meisel A, Dirnagl U (1998). Induction of hypoxia inducible factor 1 by oxygen glucose deprivation is attenuated by hypoxic preconditioning in rat cultured neurons. Neurosci Lett 254: 117–120.PubMedCrossRefGoogle Scholar
  176. Ruzek MC, Miller AH, Opal SM, Pearce BD, Biron CA (1997). Characterization of early cytokine responses and an interleukin (IL)-6-dependent pathway of endogenous glucocorticoid induction during murine cytomegalovirus infection. J Exp Med 185: 1185–1192.PubMedCrossRefGoogle Scholar
  177. Ruzek MC, Pearce BD, Miller AH, Biron CA (1999). Endogenous glucocorticoids protect against cytokine-mediated lethality during viral infection. J Immunol 162: 3527–3533.PubMedGoogle Scholar
  178. Sanderson KL, Raghupathi R, Saatman KE, Martin D, Miller G, McIntosh TK (1999). Interleukin-1 receptor antagonist attenuates regional neuronal cell death and cognitive dysfunction after experimental brain injury. J Cereb Blood-Flow Metab 19: 1118–1125.PubMedCrossRefGoogle Scholar
  179. Sapolsky RM (1985). A mechanism for glucocorticoid toxicity in the hippocampus: increased neuronal vulnerability to necrotic insults. J Neurosci 5: 1228–1232.PubMedGoogle Scholar
  180. Sapolsky RM (1992). Stress, the aging brain and the mechanisms of neuron death, vol 1. MIT Press: Cambridge, MA, p 423.Google Scholar
  181. Sapolsky RM (1994). The physiological relevance of glucocorticoid endangerment of the hippocampus. Ann N Y Acad Sci 746: 294–304; discussion 304–307.PubMedCrossRefGoogle Scholar
  182. Sapolsky RM (1996). Why stress is bad for your brain. Science 273: 749–750.PubMedCrossRefGoogle Scholar
  183. Sapolsky RM, Krey LC, McEwen BS (1985). Prolonged glucocorticoid exposure reduces hippocampal neuron number: implications for aging. J Neurosci 5: 1222–1227.PubMedGoogle Scholar
  184. Sapolsky RM, Pulsinelli WA (1985). Glucocorticoids potentiate ischemic injury to neurons: therapeutic implications. Science 229: 1397–1400.PubMedCrossRefGoogle Scholar
  185. Sapolsky RM, Rivier C, Yamamoto G, Plotsky P, Vale W (1987). Interleukin-1 stimulates the secretion of hypothalamic corticotropin-releasing factor. Science 238: 522–524.PubMedCrossRefGoogle Scholar
  186. Sapolsky RM, Romero LM, Munck A (2000). How do glucocorticoids influence stress responses? Integrating permissive, suppressive, stimulatory, and preparative actions. Endocr Rev 21: 55–89.PubMedCrossRefGoogle Scholar
  187. Sauder C, Wolfer DP, Lipp HP, Staeheli P, Hausmann J (2001). Learning deficits in mice with persisent Borna disease virus infection of the CNS associated with elevated chemokine expression. Behav Brain Res 120: 189–201.PubMedCrossRefGoogle Scholar
  188. Schneider-Schaulies J, Schneider-Schaulies S, Ter Meulen V (1993). Differential induction of cytokines by primary and persistent measles virus infection in human glial cells. Virology 195: 219–228.PubMedCrossRefGoogle Scholar
  189. Schooltink H, Schmitz-Van de Leur H, Heinrich PC, Rose-John S (1992). Up-regulation of the interleukin-6-signal transducing protein (gp130) by interleukin-6 and dexa-methasone in HepG2 cells. FEBS Lett 297: 263–265.PubMedCrossRefGoogle Scholar
  190. Schwartz M, Moalem G (2001). Beneficial immune activity after CNS injury: prospects for vaccination. J Neuroimmunol 113: 185–192.PubMedCrossRefGoogle Scholar
  191. Segatore M (1999). Corticosteroids and traumatic brain injury: status at the end of the decade of the brain. J Neurosci Nurs 31: 239–250.PubMedCrossRefGoogle Scholar
  192. Selye H (1936). A syndrome produced by diverse nocous agents. Nature 138: 32.CrossRefGoogle Scholar
  193. Selye H (1978). The stress of life. McGraw-Hill: New York.Google Scholar
  194. Stein-Behrens BA, Elliott EM, Miller CA, Schilling JW, Newcombe R, Sapolsky RM (1992). Glucocorticoids exacerbate kainic acid-induced extracellular accumulation of excitatory amino acids in the rat hippocampus. J Neurochem 58: 1730–1735.PubMedCrossRefGoogle Scholar
  195. Sternberg EM, Hill JM, Chrousos GP, Kamilaris T, Listwak SJ, Gold PW, Wilder RL (1989). Inflammatory mediator-induced hypothalamic-pituitary-adrenal axis activation is defective in streptococcal cell wall arthritis-susceptible Lewis rats. Proc Natl Acad Sci USA 86: 2374–2378.PubMedCrossRefGoogle Scholar
  196. Stoll G, Jander S, Schroeter M (1998). Inflammation and glial responses in ischemic brain lesions. Prog Neurobiol 56: 149–171.PubMedCrossRefGoogle Scholar
  197. Straub RH, Miller LE, Scholmerich J, Zietz B (2000). Cytokines and hormones as possible links between endocrinosenescence and immunosenescence. J Neuroimmunol 109: 10–15.PubMedCrossRefGoogle Scholar
  198. Takikita S, Takano T, Narita T, Takikita M, Ohno M, Shimada M (2001). Neuronal apoptosis mediated by IL-1 beta expression in viral encephalitis caused by a neuroadapted strain of the mumps virus (Kilham strain) in hamsters. Exp Neurol 172: 47–59.PubMedCrossRefGoogle Scholar
  199. Tanaka J, Ogura T, Kamiya S, Sato H, Yoshie T, Ogura H, Hatano M (1984). Enhanced replication of human cytomegalovirus in human fibroblasts treated with dexamethasone. J Gen Virol 65: 1759–1767.PubMedCrossRefGoogle Scholar
  200. Thompson KA, Blessing WW, Wesselingh SL (2000). Herpes simplex replication and dissemination is not increased by corticosteroid treatment in a rat model of focal herpes encephalitis. J NeuroVirol 6: 25–32.PubMedCrossRefGoogle Scholar
  201. Tominaga T, Katagi H, Ohnishi ST (1988). Is Ca2+-activated potassium efflux involved in the formation of ischemic brain edema? Brain Res 460: 376–378.PubMedCrossRefGoogle Scholar
  202. Trainer PJ, Faria M, Newell-Price J, et al (1995). A comparison of the effects of human and ovine corticotrophin-releasing hormone on the pituitary-adrenal axis. J Clin Endocrinol Metab 80: 412–417.PubMedCrossRefGoogle Scholar
  203. Tyrrell JB, Aron DC, Forsham PH (1994). Glucocorticoids and adrenal androgens. In: Basic and clinical endocrinology. Greenspan FS, Baxter JD (eds). Appleton and Lange: Norwalk, CT, p 307.Google Scholar
  204. Uz T, Pesold C, Longone P, Manev H (1998). Aging-associated up-regulation of neuronal 5-lipoxygenase expression: putative role in neuronal vulnerability. FASEB J 12: 439–449.PubMedGoogle Scholar
  205. Uz T, Dwivedi Y, Savani PD, Impagnatiello F, Pandey G, Manev H (1999). Glucocorticoids stimulate inflammatory 5-lipoxygenase gene expression and protein translocation in the brain. J Neurochem 73: 693–699.PubMedCrossRefGoogle Scholar
  206. van der Velden VH (1998). Glucocorticoids: mechanisms of action and anti-inflammatory potential in asthma. Mediators Inflamm 7: 229–237.PubMedCrossRefGoogle Scholar
  207. Vecht CJ (1998). Clinical management of brain metastasis. J Neurol 245: 127–131.PubMedCrossRefGoogle Scholar
  208. Vedhara K, Cox NK, Wilcock GK, Perks P, Hunt M, Anderson S, Lightman SL, Shanks NM (1999). Chronic stress in elderly carers of dementia patients and antibody response to influenza vaccination. Lancet 353: 627–631.PubMedCrossRefGoogle Scholar
  209. Vila N, Castillo J, Davalos A, Chamorro A (2000). Pro-inflammatory cytokines and early neurological worsening in ischemic stroke. Stroke 31: 2325–2329.PubMedGoogle Scholar
  210. Vincent A, Palace J, Hilton-Jones D (2001). Myasthenia gravis. Lancet 357: 2122–2128.PubMedCrossRefGoogle Scholar
  211. Vreugdenhil GR, Wijnands PG, Netea MG, van der Meer JW, Melchers WJ, Galama JM (2000). Enterovirus-induced production of pro-inflammatory and T-helper cytokines by human leukocytes. Cytokines 12: 1793–1796.CrossRefGoogle Scholar
  212. Walker DG, Kim SU, McGeer PL (1995). Complement and cytokine gene expression in cultured microglial derived from postmortem human brains. J Neurosci Res 40: 478–493.PubMedCrossRefGoogle Scholar
  213. Wekerle H, Linington C, Lassmann H, Meyermann R (1986). Cellular immune reactivity within the CNS. Trends Neurosci 9: 271–277.CrossRefGoogle Scholar
  214. Whetsell WO Jr (1996). Current concepts of excitotoxicity. J Neuropathol Exp Neurol 55: 1–13.PubMedCrossRefGoogle Scholar
  215. Wiegers GJ, Reul JM (1998). Induction of cytokine receptors by glucocorticoids: functional and pathological significance. Trends Pharmacol Sci 19: 317–321.PubMedCrossRefGoogle Scholar
  216. Wilckens T, De Rijk R (1997). Glucocorticoids and immune function: unknown dimensions and new frontiers. Immunol Today 18: 418–424.PubMedCrossRefGoogle Scholar
  217. Yamabe T, Dhir G, Cowen EP, Wolf AL, Bergey GK, Krumholz A, Barry E, Hoffman PM, Dhib-Jalbut S (1994). Cytokine-gene expression in measles-infected adult human glial cells. J Neuroimmunol 49: 171–179.PubMedCrossRefGoogle Scholar
  218. Yamamura M, Yamada Y, Momita S, Kamihira S, Tomonaga M (1998). Circulating interleukin-6 levels are elevated in adult T-cell leukaemia/lymphoma patients and correlate with adverse clinical features and survival. Br J Haematol 100: 129–134.PubMedCrossRefGoogle Scholar
  219. Yoles E, Hauben E, Palgi O, Agranov E, Gothilf A, Cohen A, Kuchroo V, Cohen IR, Weiner H, Schwartz M (2001). Protective autoimmunity is a physiological response to CNS trauma. J Neurosci 21: 3740–3748.PubMedGoogle Scholar
  220. Zidovetzki R, Wang JL, Chen P, Jeyaseelan R, Hofman F (1998). Human immunodeficiency virus Tat protein induces interleukin 6 mRNA expression in human brain endothelial cells via protein kinase C and Camp dependent protein kinase pathways. AIDS Res Hum Retrovir 14: 825–833.PubMedCrossRefGoogle Scholar
  221. Zuckerman SH, Shellhaas J, Butler LD (1989). Differential regulation of lipopolysaccharide-induced interleukin 1 and tumor necrosis factor synthesis: effects of endogenous and exogenous glucocorticoids and the role of the pituitary-adrenal axis. Eur J Immunol 19: 301–305.PubMedCrossRefGoogle Scholar

Copyright information

© Journal of NeuroVirology, Inc. 2002

Authors and Affiliations

  • Klaus Dinkel
    • 1
  • William O. Ogle
    • 1
  • Robert M. Sapolsky
    • 1
  1. 1.Department of Biological Sciences, Gilbert HallStanford UniversityStanfordUSA

Personalised recommendations