Skip to main content
Log in

Autonomic Regulation of Neuroimmunological Responses: Implications for Multiple Sclerosis

  • Published:
Journal of Clinical Immunology Aims and scope Submit manuscript

Abstract

The expression of neural regulatory molecules by immune cells that infiltrate the nervous system upon injury may be a mechanism for cross regulation between the nervous system and the immune system. Several lines of evidence implicate nerve growth factor signaling through its receptors as a potential source of communication between the two systems. The expression of β-adrenergic receptors and sympathetic innervation of lymphoid organs represents another example of communication between the immune and the nervous system. In this review, we discuss mechanisms of how factors in common between the nervous system and the immune system may result in regulatory circuits which are important in both healthy and diseased states. These studies may have relevance for a number of inflammatory conditions in humans, including multiple sclerosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

REFERENCES

  1. Felten DL, Felten SY, Bellinger DL, Carlson SL, Ackerman KD, Madden KS, Olschowki JA, Livnat S: Noradrenergic sympathetic neural interactions with the immune system: Structure and function. Immunol rev 100:225–260, 1987

    Google Scholar 

  2. Madden KS, Sanders VM, Felten DL: Catecholamine influences and sympathetic neural modulation of immune responsiveness. Annu rev pharmacol toxicol 35:417–448, 1995

    Google Scholar 

  3. Kohm AP, Sanders VM: Suppression of antigen-specific Th2 cell-dependent IgM and IgG1 production following norepinephrine depletion in vivo. J immunol 162:5299–5308, 1999

    Google Scholar 

  4. Rothwell NJ, Luheshi G, Toulmond S: Cytokines and their receptors in the central nervous system: Physiology, pharmacology, and pathology. Pharmacol ther 69:85–95, 1996

    Google Scholar 

  5. Brodie C, Goldreich N, Haiman T, Kazimirsky G: Functional IL-4 receptors on mouse astrocytes: IL-4 inhibits astrocyte activation and induces NGF secretion. J neuroimmunol 81:20–30, 1998

    Google Scholar 

  6. Lovett-Racke AE, Smith ME, Arredondo LR, Bittner PS, Ratts RB, Shive CL, Forsthuber TG, Racke MK: Developmentally regulated gene expression of Th2 cytokines in the brain. BrainRes 870:27–35, 2000

    Google Scholar 

  7. Sanders VM, Baker RA, Ramer-Quinn DS, Kasprowicz DJ, Fuchs BA, Street NE: Differential expression of the beta2–adrenergic receptor by Th1 and Th2 clones: Implications for cytokine production and B cell help. J immunol 158:4200–4210, 1997

    Google Scholar 

  8. Ramer-Quinn DS, Baker RA, Sanders VM: Activated T helper 1 and T helper 2 cells differentially express the beta-2–adrenergic receptor: A mechanism for selective modulation of T helper 1 cell cytokine production. J immunol 159:4857–4867, 1997

    Google Scholar 

  9. Villoslada P, Hauser SL, Bartke I, Unger J, Heald N, Rosenberg D, Cheung SW, Mobley WC, Fisher S, Genain CP: Human nerve growth factor protects common marmosets against autoimmune encephalomyelitis by switching the balance of T helper cell type 1 and 2 cytokines within the central nervous system. J Exp Med 191:1799–1806, 2000

    Google Scholar 

  10. Arredondo LR, Deng D, Ratts RB, Lovett-Racke AE, Holtzman DM, Racke MK: Role of nerve growth factor in experimental autoimmune encepahlomyelitis. Eur J Immunol 2000 (in press)

  11. Downing JEG, Miyan JA: Neural immunoregulation: Emerging roles for nerves in immune homeostasis and disease. Immunol Today 21:281–289, 2000

    Google Scholar 

  12. Miles K, Quintans J, Chelmicka-Schorr E, Arnason BGW: the sympathetic nervous system modulates antibody response to thymus-independent antigens. J Neuroimmunol 1:101–105, 1981

    Google Scholar 

  13. Miles K, Atweh S, Otten G, Arnason BGW, Chelmicka-Schorr E: β-Adrenergic receptors on splenic lymphocytes from axotomized mice. Int J Immunopharmacol 6:171–177, 1984

    Google Scholar 

  14. Chelmicka-Schorr E, Checinski ME, Arnason BGW: chemical sympathectomy augments the severity of experimental allergic encephalomyelitis. J Neuroimmunol 17:347–350, 1988

    Google Scholar 

  15. Chelmicka-Schorr E, Kwasniewski MN, Thomas BE, Arnason BGW: The β-adrenergic agonist isoproterenol suppresses experimental allergic encephalomyelitis in Lewis rats. J Neuroimmunol 25:203–207, 1989

    Google Scholar 

  16. Kohm AP, Tang Y, Sanders VM, Jones SB: Activation of antigen-specific CD4+ Th2 cells and B cells in vivo increases norepinephrine release in the spleen and bone marrow. J Immunol 165:725–733, 2000

    Google Scholar 

  17. Tang Y, Shankar R, Gamelli R, Jones S: Dynamic norepinephrine alterations in bone marrow: Evidence of functional innervation. J Neuroimmunol 96:182–189, 1999

    Google Scholar 

  18. Ehrhard PB, Erb P, Graumann U, Otten U: Expression of nerve growth factor and nerve growth factor receptor tyrosine kinase Trk in activated CD4–positive T-cell clones. Proc Natl Acad Sci USA 90:10984–10988, 1993

    Google Scholar 

  19. Santambrogio L, Benedetti M, Chao MV, Muzaffar R, Kulig K, Gabellini N, Hochwald G: Nerve growth factor production by lymphocytes. J Immunol 153:4488–4495, 1994

    Google Scholar 

  20. Shelton DL, Reichardt LF: Expression of β-nerve growth factor gene correlates with the density of sympathetic innervation in effector organs. Proc Natl Acad Sci USA 81:7951–7955, 1984

    Google Scholar 

  21. Carlson SL, Albers KM, Beiting DJ, Parish M, Conner JM, Davis BM: NGF modulates sympathetic innervation of lymphoid tissues. J Neurosci 15:5892–5899, 1995

    Google Scholar 

  22. Landmann R: Beta-adrenergic receptors in human leukocyte subpopulations. Eur J Clin Invest 22 (Suppl 1):30–36, 1992

    Google Scholar 

  23. Fuchs BA, Albright JW, Albright JF: Beta-adrenergic receptors on murine lymphocytes: Density varies with cell maturity and lymphocyte subtype and is decreased after antigen administration. Cell Immunol 114:231–245, 1988

    Google Scholar 

  24. Radojcic T, Baird S, Darko D, Smith D, Bulloch K: Changes in beta-adrenergic receptor distribution on immunocytes during differentiation: An analysis of T cells and macrophages. J Neurosci Res 30:328–335, 1991

    Google Scholar 

  25. Gajewski TF, Schell SR, Fitch FW: Evidence implicating utilization of different T cell receptor-associated signaling pathways by Th-1 and Th-2 clones. J Immunol 144:4110–4118, 1990

    Google Scholar 

  26. Novak TJ, Rothenberg EV: cAMP inhibits induction of interleukin 2 but not of interleukin 4 in T cells. Proc Natl Acad Sci USA 87:9353, 1990

    Google Scholar 

  27. Borger P, Hoekstra Y, Esselink MT, Postma, DS, Zaagsma J, Vellenga E, Kauffman HF: Beta-adrenoreceptor-mediated inhibition of IFN-gamma, IL-3, and GM-CSF mRNA accumulation in activated human T lymphocytes is solely mediated by the beta2–adrenoceptor subtype. Am J Respir Cell Mol Biol 19:400–407, 1998

    Google Scholar 

  28. Panina-Bordignon P, Mazzeo D, Lucia PD, D'Ambrosio D, Lang R, Fabbri L, Self C, Sinigaglia F: Beta2–agonists prevent Th1 development by selective inhibition of interleukin 12. J Clin Invest 100:1513–1519, 1997

    Google Scholar 

  29. Karaszewski JW, Reder AT, Maselli R, Brown M, Arnason BGW: Sympathetic skin responses are decreased and lymphocyte beta-adrenergic receptors are increased in progressive multiple sclerosis. Ann Neurol 27:366–372, 1990

    Google Scholar 

  30. Karaszewski JW, Reder AT, Anlar B, Kim WC, Arnason BGW: Increased lymphocyte beta-adrenergic receptor density in progressive multiple sclerosis is specific for the CD8+, CD28– suppressor cells. Ann Neurol 30:42–47, 1991

    Google Scholar 

  31. Baerwald, CG, Laufenberg M, Specht T, von Wichert P, Burmester GR, Krause A: Impaired sympathetic influence on the immune response in patients with rheumatoid arthritis due to lymphocyte subset-specific modulation of beta 2–adrenergic receptors. Br J Rheumatol 36:1262–1269, 1997

    Google Scholar 

  32. Malfait AM, Malik AS, Marinova-Mutafchieva L, Butler DM, Maini RN, Feldman M: The beta2–adrenergic agonist salbutamol is a potent suppressor of established collagen-induced arthritis: Mechanism of action. J Immunol 162:6278–6283, 1999

    Google Scholar 

  33. Hoekstra, MO, Hoekstra Y, de Reus D, Rutgers B, Gerritsen J, and Kauffmann HF: Interleukin-4 (IL-4), interferon-γ, and interleukin-5 (IL-5) in peripheral blood of children with atopic asthma. Clin Exp Allergy 27:1254–1260, 1997

    Google Scholar 

  34. Borger P, Jonker GJ, Vellenga E, Postma DS, DeMonchy JG, Kauffman HF: Allergen challenge primes IL-5 mRNA production and abrogates beta-adrenergic function in peripheral blood T lymphocytes from asthmatics. Clin Exp Allergy 29:933–940, 1999

    Google Scholar 

  35. Bishopric NH, Cohen HJ, Lefkowitz RJ: Beta adrenergic receptors in lymphocyte subpopulations. J Allergy Clin Immunol 65:29–33, 1980

    Google Scholar 

  36. Sanders VM, Munson AE: Norepinephrine and the antibody response. Pharmacol Rev 37:229–248, 1985

    Google Scholar 

  37. Pochet R, Delespesse G, Gausset PW, Collet H: Distrubution of beta-adrenergic receptors on human lymphocyte subpopulations. Clin Exp Immunol 38:578–584, 1979

    Google Scholar 

  38. Landmann RMA, Burgisser E, Wesp EM, Buhler FR: Betaadrenergic receptors are different in subpopulations of human circulating lymphocytes. J Receptor Res 4:37–50, 1984

    Google Scholar 

  39. Farner NL, Hank JA, Sondel PM: Interleukin-2: Molecular and clinical aspects. In Cytokines in Health and Disease, DG Remick, JS Friedland (eds). New York, Marcel Dekker, 1997, pp 29–40

    Google Scholar 

  40. deJong JLO, Farner NL, Sondel PM: Distinctions in lymphocyte responses to IL-2 and IL-15 reflect differential ligand binding interactions with the IL-2R beta chain and suggest differential roles for the IL-2R alpha and IL-15R alpha subunits. Cytokine 10:920–930, 1998

    Google Scholar 

  41. Hallek M, Kamp T, Haen E, Gohly U, Emmerich B, Remien J: Reduced responsiveness of adenylate cyclase to forskolin in human lymphoma cells. Biochem Pharmacol 42:1329–1334, 1991

    Google Scholar 

  42. Paietta E, Schwarzmeier JD: Differences in beta-adrenergic receptor density and adenylate cyclase activity between normal and leukaemic leukocytes. Eur J Clin Invest 13:339–346, 1983

    Google Scholar 

  43. Kasprowicz DJ, Kohm AP, Berton MT, Chruscinski AJ, Sharpe A, Sanders VM: Stimulation of the B cell receptor, CD86 (B7–2) and the β-adrenergic receptor intrinsically modulates the level of IgG1 and IgE produced per B cell. J Immunol 165:680–690, 2000

    Google Scholar 

  44. Yi Q, He W, Matell G, Pirskanen R, Magnusson Y, Eng H, Lefvert AK: T and B lymphocytes reacting with the extracellular loop of the β-adrenergic receptor are present in the peripheral blood of patients with myasthenia gravis. Clin Exp Immunol 103:133–140, 1996

    Google Scholar 

  45. Li YS, Kouassi E, Revillard JP: Differential regulation of mouse B-cell activation by beta-adrenoceptor stimulation depending on type of mitogens. Immunology 69:367–372, 1990

    Google Scholar 

  46. Maestroni GJM, Cosentino M, Marino F, Togni M, Conti A, Lecchini S, Frigo G: Neural and endogenous catecholamines in the bone marrow. Circadian association of norepinephrine with hematopoiesis? Exp Hematol 26:1172–1177, 1998

    Google Scholar 

  47. Honjo T, Alt FW: Immunogobulin Genes, 2nd ed. San Diego, CA, Academic Press, 1995

    Google Scholar 

  48. Ansel KM, Ngo VN, Hyman PL, Luther SA, Forster R, Sedgwick JD, Browning JL, Lipp M, Cyster JG: A chemokine-driven positive feedback loop organizes lymphoid follicles. Nature 406:309–314, 2000

    Google Scholar 

  49. Rossi D, Zlotnik A: The biology of chemokines and their receptors. Annu Rev Immunol 18:217–242, 2000

    Google Scholar 

  50. Frohman EM, Vayuvegula B, van den Noort S, Gupta S: Norepinephrine inhibits gamma-interferon-induced MHC class II (Ia) antigen expression on cultured brain astrocytes. J Neuroimmunol 17:89–101, 1988

    Google Scholar 

  51. Frohman EM, Vayuvegula B, Gupta S, van den Noort S: Norepinephrine inhibits interferon-induced major histocompatibility class II (Ia) antigen expression on cultured astrocytes via beta2–adrenergic signal transduction mechanisms. Proc Natl Acad Sci USA 85:1292–1296, 1988

    Google Scholar 

  52. ThyagaRajan S, Madden KS, Kalvass JC, Dimitrova SS, Felten SY, Felten DL: L-Deprenyl-induced increase in IL-2 and NK cell activity accompanies restoration of nonadrenergic nerve fibers in the spleens of old F344 rats. J Neuroimmunol 92:9 -21, 1998

    Google Scholar 

  53. ThyagaRajan S, Madden KS, Stevens SY, Felten DL: Effects of L-deprenyl treatment on noradrenergic innervation and immunae reactivity in lymphoid organs of young F344 rats. J Neuroimmunol 96:57–65, 1999

    Google Scholar 

  54. Torcia M, Bracci-Laudiero L, Lucibello M, Nencioni L, Labardi D, Rubartelli A, Cozzolino F, Aloe L, Garaci E: Nerve growth factor is an autocrine survival factor for memory B lymphocytes. Cell 85:345–356, 1996

    Google Scholar 

  55. Braun A, Appel E, Baruch R, Herz U, Botchkarev V, Paus R, Brodie C, Renz H: Role of nerve growth factor in a mouse model of allergic airway inflammation and asthma. Eur J Immunol 28:3240–3251, 1998

    Google Scholar 

  56. Kimata H, Yoshida A, Ishioka C, Kusunoki T, Hosoi S, Mikawa H: Nerve growth factor specifically induces human IgG4 production. Eur J Immunol 27:137, 1991

    Google Scholar 

  57. Otten U, Ehrhand P, Peck R: Nerve growth factor induces growth and differentiation of human B lymphocytes. Proc Natl Acad Sci USA 86:10059, 1989

    Google Scholar 

  58. Kimata H, Yoshida A, Ishioka C, Mikawa H: Nerve growth factor inhibits immunoglobulin production by but not proliferation of human plasma cell lines. Clin Immunol Immunopathol 60:145, 1991

    Google Scholar 

  59. Brodie C, Franklin R, Gelfand EW: Comparative study of nerve growth factor and anti-CD40 antibody effects on Ig secretion and signal transduction pathways. FASEB J A1413, 1992

  60. Brodie C, Gelfand EW: Functional nerve growth factor receptors on human B lymphocytes. T J Immunol 148:3492–3497, 1992

    Google Scholar 

  61. Archelos J, Storch M, Hartung H: The role of B cells and autoantibodies in multiple sclerosis. Ann Neurol 47:694, 2000

    Google Scholar 

  62. Dorner T, Farner NL, Lipsky PE: Ig lambda and heavy chain usage in early untreated systemic lupus erythematosus suggests intensive B cell stimulation. J Immunol 163:1027–1036, 1999

    Google Scholar 

  63. Hayashida K, Shimaoka Y, Ochi T, Lipsky PE: Rheumatoid arthritis synovial stromal cells inhibit apoptosis and up-regulate Bcl-XL expression by B cells in a CD49/CD29–CD106–dependent mechanism. J Immunol 164:1110–1116, 2000

    Google Scholar 

  64. Melamed I, Kelleher CA, Franklin RA, Brodie C, Hempstead B, Kaplan D, Gelfand EW: Nerve growth factor signal transduction in human B lymphocytes is mediated by gp140. Eur J Immunol 26:1985–1992, 1996

    Google Scholar 

  65. Melamed I, Patel H, Brodie C, Gelfand EW: Activation of Vav and Ras through the nerve growth factor and B cell receptors by different kinases. Cell Immunol 191:83–89, 1999

    Google Scholar 

  66. Franklin RA, Brodie C, Melamed I, Terada N, Lucas JJ, Gelfand EW: Nerve growth factor induces activation of MAP-kinase and p90 in human B lymphocytes. J Immunol 154:4965–4972, 1995

    Google Scholar 

  67. Brodie C, Gelfand EW: Regulation of immunoglobulin production by nerve growth factor: Comparison with anti-CD40. J Neuroimmunol 52:87–96, 1994

    Google Scholar 

  68. Brodie C, Oshiba A, Renz H, Bradley K, Gelfand EW: Nerve growth factor and anti-CD40 provide opposite signals for the production of IgE in interleukin-4–treated lymphocytes. Eur J Immunol 26:171–178, 1996

    Google Scholar 

  69. Stamenkovic I, Clark EA, Seed B: A B-lymphocyte activation molecule related to the nerve growth factor receptor and induced by cytokines in carcinomas. EMBO J 8:1403, 1989

    Google Scholar 

  70. Eng LF, Vanderhaeghen JJ, Bignami A, Gerstl B: An acidic protein isolated from fibrous astrocytes. Brain Res 28:351–354, 1971

    Google Scholar 

  71. Rakic P: Guidance of neurons migrating to the fetal monkey neocortex. Brain Res 33:471–476, 1971

    Google Scholar 

  72. Rakic P: neuron-glia relationship during granule cell migration in developing cerebellar cortex. A golgi and electron microscopic study in macacus rhesus. J Comp Neurol 141:283–312, 1971

    Google Scholar 

  73. Manthorpe M, Rudge JJ, Varon S: Astroglial cell contributions to neuronal survival and neuritic growth. In Biochem Physiol Pharm Astrocytes. Orlando, FL, Academic Press, 1986, pp 315–376

    Google Scholar 

  74. French-Constant C, Miller RH, Schachner M, Raff MC: Molecular specialization of astrocyte processes at nodes of Ranvier in rat optic nerve. J Cell Biol 102:844–852, 1986

    Google Scholar 

  75. Lauder J: Neuronal-glial interactions. In Biochem Physiol Pharm Astrocytes. Orlando, FL, Academic Press, 1986, pp 295–314

    Google Scholar 

  76. Hertz L, Schousboe A: Role of astrocytes in compartmentalization of amino acid and energy metabolism. In Biochem Physiol Pharm Astrocytes. Orlando, FL, Academic Press, 1986, pp 179–208

    Google Scholar 

  77. Murphy S, Pearce B: Functional receptors for neurotransmitters on astroglial cells. Neuroscience 22:381–394, 1987

    Google Scholar 

  78. Reier PL: Gliosis following CNS injury: The anatomy of astrocytic scars and their influences on axonal elongation. In Cell Biol Pathol Astrocytes. Orlando, FL, Academic Press, 1986, pp 263–324

    Google Scholar 

  79. Frohman EM, van den Noort S, Gupta S: Astrocytes and intracerebral immune responses. J Clin Immunol 9:1–9, 1989

    Google Scholar 

  80. Trapp BD, Peterson J, Ransohoff RM, et al.: Axonal transection in the lesions of multiple sclerosis. N Engl J Med 338:278–285, 1998

    Google Scholar 

  81. Nesbit GM, Forbes GS, Scheithauer BW, et al.: MS Histopathologic and MR and/or CT correlation in 37 cases at biopsy and three cases at autopsy. Radiology 180:467–474, 1991

    Google Scholar 

  82. Sriram S, Rodriquez M: Indictment of the microglia as the villain in multiple sclerosis. Neurology 48:464–470, 1997

    Google Scholar 

  83. Sriram S, Carroll L, Fortin S, et al.: In vivo immunomodulation by monoclonal anti-CD4 antibody. II. effect on T cell response to myelin basic protein and experimental allergic encephalomyelitis. J Immunol 141:464–468, 1988

    Google Scholar 

  84. Steinman L: Multiple sclerosis and its animal models: the role of the major histocompatibility complex and the T cell receptor repertoire. Semin Immunopathol 14:79–93, 1992

    Google Scholar 

  85. Renno T, Krakowski M, Piccirillo C, et al.: TNF alpha expression by resident microglial and infiltrating leukocytes in the central nervous system of mice with EAE. J Immunol 154:944–953, 1995

    Google Scholar 

  86. Huitinga I, Rooijen NV, Groot CJD, et al.: Suppression of EAE in Lewis rats after elimination of macrophages. J Exp Med 172:1025–1033, 1990

    Google Scholar 

  87. McGeer PL, Itagaki S, McGeer EG: Expression of the histocompatibility glycoproein HLA-DR in neurological disease. Acta Neuropathol 76:550–557, 1988

    Google Scholar 

  88. Frohman EM, Frohman TC, Dustin ML, et al.: The induction of intercellular adhesion molecule 1 (ICAM-1) expression on human fetal astrocytes by interferon-γ, tumor necrosis factor α, lymphotoxin, and interleukin-1: relevance to intracerebral antigen presentation. J Neuroimmunol 23:117–124, 1989

    Google Scholar 

  89. Aschner M: Astrocytes as mediators of immune and inflammatory responses in the CNS. Neurotoxicology 19:269–282, 1988

    Google Scholar 

  90. Lee SH, Brosnan CF: Molecular biology of glia:astrocytes. In Molecular Biology of Multiple Sclerosis. London, John Wiley, 1997, pp 71–96

    Google Scholar 

  91. Tan L, Gorodon K, Mueller JP, et al.: Presentation of proteolipid protein epitopes and B7–1–dependent activation of encephalogenic T cells by IFN-γ-activated SJL/J astrocytes. J Immunol 160:4271–4279, 1998

    Google Scholar 

  92. Nikcevich KM, Gordon KB, Tan L, et al.: IFN-γ-activated primary murine astrocytes express B7 costimulatory molecules and prime naïve antigen-specific T cells. J Immunol 158:614–621, 1997

    Google Scholar 

  93. Traugott U, Lebon P: Interferon-gamma and Ia antigen are present on astrocytes in active chronic multiple sclerosis lesions. J Neurol Sci 84:257–264, 1988

    Google Scholar 

  94. Lee SC, Moore GRW, Golenwky G, et al.: Multiple sclerosis:a role for astroglia in active demyelination suggested by class II MHC expression and ultrastructural study. J Neuropathol Exp Neurol 49:122–136, 1990

    Google Scholar 

  95. Ransohoff RM, Estes ML: Astrocyte expression of major histocompatibility complex gene products in multiple sclerosis brain tissue obtained by stereotactic biopsy. Arch Neurol 48:1244–1246, 1991

    Google Scholar 

  96. De Keyser J, Wilczak N, Leta R, et al.: Astrocytes in multiple sclerosis lack beta-2 adrenergic receptors. Neurology 53:1628–1633, 1999

    Google Scholar 

  97. Bouvier M, Fredrik, Leeb-Lundberg LM, Benovic JL, et al.: Regulation of adrenergic receptor function by phosphorylation. J Biol Chem 262:3106–3113, 1987

    Google Scholar 

  98. Fontana A, Kristensen F, Dubs R, et al.: Production of prostaglandin E and interleukin 1–like factors by cultures of astrocytes and C-6 glioma cells. J Immunol 129:2413–2419, 1982

    Google Scholar 

  99. Van Calker D, Muller M, Hamprecht B: Receptors regulating the level of cyclic AMP in primary cultures of perinatal mouse brain. In Neural Growth and Differentiation, New York, Raven, 1979, pp 11–25

    Google Scholar 

  100. Massa PT, ter Meulen V: Analysis of Ia induction of Lewis rat astrocytes in vitro by virus particles and bacterial adjuvants. J Neuroimmunol 13:259 -271, 1987

    Google Scholar 

  101. Bronsnan CF, Goldmuntz EA, Crammer W, et al.: Prazosin an alpha-1–adrenergic receptor antagonist, suppresses experimental autoimmune encephalomyelitis in the Lewis rat. Proc Natl Acad Sci USA 82:5915–5919, 1985

    Google Scholar 

  102. Wong GHW, Bartlett PF, Clark-Lewis I, et al.: Inducible expression of H-2 and Ia antigens on brain cells. Nature 310:688–691, 1984

    Google Scholar 

  103. Pearce G, Cambray-Deakin M, Morrow C, et al.: Activation of muscarinic and of alpha-1–adrenrgic receptors on astrocytes results in the accumulation of inositol phosphates. J Neurochem 45:1534–1540, 1985

    Google Scholar 

  104. Lee SC, Collins M, Vanguri P, et al.: Glutamate differentially inhibits the expression of class II MHC antigens on astrocytes and microglia. J Immunol 148:3391–3397, 1992

    Google Scholar 

  105. Bo L, Dawson TM, Wesselingh S, et al.: Induction of nitric oxide synthase in demyelinating regions of multiple sclerosis brains. Ann Neurol 36:778–786, 1994

    Google Scholar 

  106. Galea E, Feinstein DL, Reis DJ: Induction of calciumindependent nitric oxide synthase activity in primary rat glial cultures. Proc Natl Acad Sci USA 89:10945–10949, 1992

    Google Scholar 

  107. Lee SC, Dickson DW, Liu W, et al.: Induction of nitric oxide synthase activity in human astrocytes by interleukin-1–beta and interferon-gamma. J Neuroimmunol 46:19–24, 1993

    Google Scholar 

  108. Xie Q-W, Cho HJ, Calaycay J, et al.: Cloning and characterization of inducible nitric oxide synthase from mouse macrophages. Science 256:225–228, 1992

    Google Scholar 

  109. Nussler AK, Di Silvio M, Billiar TR, et al.: Stimulation of the nitric oxide synthase pathway in human hepatocytes by cytokines and endotoxin. J Exp Med 176:261–264, 1992

    Google Scholar 

  110. Tyor WR, Glass JD, Griffin JW, et al.: Cytokine expression in the brain during the acquired immunodeficiency syndrome. Ann Neurol 31:349 -360, 1992

    Google Scholar 

  111. Giulian D, Baker TJ, Shih, L-CN, et al.: Interleukin-1 of the central nervous system is produced by ameboid microglia. J Exp Med 164:594–604, 1986

    Google Scholar 

  112. Dickson DW, Lee SC, Mattiace LA, et al.: Microglia and cytokines in neurological disease, with special reference to AIDS and Alzheimer's disease. Glia 7:75–83, 1993

    Google Scholar 

  113. Merrill JE, Ignarro LJ, Sherman MP, et al.: Microglial cell cytotoxicity of oligodendrocytes is mediated through nitric oxide. J Immunol 151:2132–2141, 1993

    Google Scholar 

  114. Rohowsky-Kochan C, Dowling PC, Cook SD: Canine distemper virus-specific antibodies in multiple sclerosis. Neurology 45: 1554–1560, 1995

    Google Scholar 

  115. Mutinelli F, Vandevelede M, Griot C, et al.: Astrocytic infection in canine distemper virus-induced demyelination. Acta Neuropathol 77:333–335, 1989

    Google Scholar 

  116. Koschel K, Muenzel P: Persistent paramyxovirus infections and behavior of beta-adrenergic receptors in C-rat glioma cells. J Gen Virol 47:513–517, 1980

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Frohman, E.M., Monson, N.L., Lovett-Racke, A.E. et al. Autonomic Regulation of Neuroimmunological Responses: Implications for Multiple Sclerosis. J Clin Immunol 21, 61–73 (2001). https://doi.org/10.1023/A:1011016124524

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1011016124524

Navigation