Effector pathways in immune mediated central nervous system demyelination

Current Opinion in Neurology

Volumn 12, Issue 3, 1999, Pages 323-336

  Kieseier, Bernd C ^a   Storch, Maria K ^a   Archelos, Juan J ^a   Martino, Gianvito ^b   Hartung, Hans Peter ^a  

^a UNIVERSITY OF GRAZ   (Austria)

^b SAN RAFFAELE HOSPITAL   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIBODY; AUTOANTIBODY; CELL ADHESION MOLECULE; CHEMOKINE; COMPLEMENT; CYTOKINE; MATRIX METALLOPROTEINASE; MYELIN; NITRIC OXIDE; OXYGEN; REACTIVE OXYGEN METABOLITE;

ALLERGIC ENCEPHALOMYELITIS; AUTOIMMUNITY; CENTRAL NERVOUS SYSTEM; DEMYELINATION; HUMAN; MULTIPLE SCLEROSIS; OXIDATIVE STRESS; REVIEW; T LYMPHOCYTE;

ANIMALS; CELL ADHESION MOLECULES; CHEMOKINES; CYTOKINES; HUMANS; METALLOENDOPEPTIDASES; MULTIPLE SCLEROSIS;

EID: 0032773320     PISSN: 13507540     EISSN: None     Source Type: Journal    
DOI: 10.1097/00019052-199906000-00011     Document Type: Review

References (126)

1. Birnbaum G, Antel J. The immunology of multiple sclerosis. In: Clinical immunobiology, Antel J, Birnbaum G, Hartun H-P (editors). Malden: Blackwell; 1998. pp105-115.
2. Prineas JW, McDonald WI. Demyelinating diseases. In: Graham DI, Lantos PL (Editors). Greenfield's Neuropathology, 4th edn. London: Arnold; 1997: pp. 813-896.
3. Storch MK, Lassmann H. Pathology and pathogenesis of demyelinating diseases. Curr Opin Neurol 1997; 10:186-192.
4. Gay D, Esiri M. Blood-brain barrier damage in acute multiple sclerosis plaques. An immunocytochemical study. Brain 1991; 114:557-572.
5. Lassmann H. Pathology of multiple sclerosis. In: Compston A, Ebers G, Lassmann H, et al. (editors) McAlpine's Multiple Sclerosis. London: Churchill Livingston; 1998, pp. 323-358.
6. Gay FW, Drye TJ, Dick GWA, Esiri MM. The application of multifactorial cluster analysis in the staging of plaques in early multiple sclerosis. identification and characterization of the primary demyelinating lesion. Brain 1997; 120:1461-1483.
7. Storch M, Piddlesden S, Haltia M, Iivanainen M, Morgan P, Lassmann H. Multiple sclerosis: in situ evidence for antibody- and complement-mediated demyelination. Ann Neurol 1998; 43: 465-471.
8. Storch MK, Stefferl A, Brehm U, Weissert R, Wallström E, Kerschensteiner M, et al. Autoimmunity to myelin oligodendrocyte glycoprotein (MOG) in rats mimics the spectrum of multiple sclerosis pathology. Brain Pathol 1998; 8:681-694.
9. Qin Y, Dunquette P, Zhang Y, Talbot P, Poole R, Antel ??. Clonal expansion and somatic hypermutation of V(H) genes of B cells from cerebrospinal fluid in multiple sclerosis. J Clin Invest 1998; 102:1045-1050.
10. Archelos JJ, Trotter J, Previtali S, Weissbrich B, Toyka KV, Hartung HP. Isolation and characterization of an oligodendrocyte-precursor-derived B cell epitope in multiple sclerosis. Ann Neurol 1998; 43:15-24. The authors describe the use of a new technique to screen for unknown oligodendroglial autoantigens and autoantibodies. By the use of an oligodendroglial protein expression library considerably more antigens and rare expressed proteins can be investigated than by the use of conventional screening methods such as ELISA, western blot and immunohistochemistry.
11. Walsh MJ, Murray JM. Dual implication of 2′,3′-cyclic nucleotide 3′ phosphodiesterase as a major autoantigen and C3 complement-binding protein in the pathogenesis of multiple sclerosis, J Clin Invest 1998; 101:1923-1931. A well known myelin component rediscovered as a new myelin autoantigen in mutliple sclerosis is discussed.
12. Zanetta JP, Tranchant C, Kuchler-Bopp S, Lehmann S, Warter JM. Presence of anti-CSL antibodies in the cerebrospinal fluid of patients: a sensitive and specific test in the diagnosis of multiple sclerosis. J Neuroimmunol 1994; 52:175-182.
13. Gao YL, Raine CS, Brosnan CF. Humoral response to hsp 65 in multiple sclerosis and other neurologic conditions. Neurology 1994; 44: 941-946.
14. Baig S, Olsson T, Yu-Ping J, Hojeberg B, Cruz M, Link H Multiple sclerosis: cells secreting antibodies against myelin-associated glycoprotein are present in cerebrospinal fluid. Scand J Immunol 1991; 33:73-79.
15. Möller JR, Johnson D, Brady RO, Tourtellotte WW, Quarles RH. Antibodies to myelin-associated glycoprotein (MAG) in the cerebrospinal fluid of multiple sclerosis patients. J Neuroimmunol 1989; 22:55-61.
16. Cruz M, Olsson T, Ernerudt J, Höjeberg B, Link H. Immunoblot detection of oligoclonal anti-myelin basic protein IgG antibodies in cerebrospinal fluid in multiple sclerosis. Neurology 1987; 37:1515-1519.
17. Warren KG, Catz I, Johnson E, Mielke B. Anti-myelin basic protein and anti-proteolipid protein specific forms of multiple sclerosis. Ann Neurol 1994; 35:280-289.
18. Garcia-Merino A, Persson MAA, Emerudh J, Diaz-Gil JJ, Olsson T. Serum and cerebrospinal fluid antibodies against myelin basic protein and their IgG subclass distribution in multiple sclerosis. J Neurol Neurosurg Psychiat 1986; 49, 1066-1070.
19. Brokstad KA, Page M, Nyland H, Haaheim LR. Autoantibodies to myelin basic protein are not present in the serum and CSF of MS patients. Acta Neurol Scand 1994; 89:407-411.
20. Xiao BG, Linington C, Link H. Antibodies to myelin-oligodendrocyte glycoprotein in cerebrospinal fluid from patients with multiple sclerosis and controls. J Neuroimmunol 1991; 31: 91-96.
21. Reindl M, Linington C, Brehm U, Egg R, Dilitz E, Deisenhammer F, et al. Antibodies against the myelin oligodendrocyte glycoprotein and the myelin basic protein in multiple sclerosis and other neurological diseases: a comparative study. Brain 1999; (in press).
22. Colombo E, Banki K, Tatum AH, Daucher J, Ferrante P, Murray RS, et al. Comparative analysis of antibody and cell-mediated autoimmunity to transaldolase and myelin basic protein in patients with multiple sclerosis. J Clin Invest 1997; 99:1238-1250.
23. Fukazawa T, Kikuchi S, Sasaki H, Hamada K, Hamada T, Miyasaka K, Tashiro K. Anti-nuclear antibodies and the optic-spinal form of multiple sclerosis. J Neurol 1997; 244, 483-488.
24. Rawes JA, Calabrese VP, Khan OA, DeVries GH. Antibodies to the axolemma-enriched fraction in the cerebrospinal fluid and serum of patients with multiple sclerosis and other neurological diseases. Multiple Scler 1998; 3, 363-369.
25. Tintore M, Fernandez AL, Rovira A, Martinez X, Direskeneli H, Khammashta M, et al. Antibodies against endothelial cells in patients with multiples sclerosis. Acta Neurol Scand 1996; 93, 416-420.
26. Bernard CCA, Johns TG, Slavin SAJ, Ichikawa M, Ewing C, Liu J, Bettadapura J. Myelin oligodendrocyte glycoprotein: a novel candidate autoantigen in multiple sclerosis. J Mol Med 1997; 75:77-88.
27. Linington C, Bradl M, Lassmann H, Brunner C, Vass K. Augmentation of demyelination in rat acute allergic encephalomyelitis by circulating mouse monoclonal antibodies directed against a myelin/oligodendrocyte glycoprotein. Am J Pathol 1988; 130: 443-454.
28. Piddlesden SJ, Lassmann H, Zimprich F, Morgan BP, Linington C. The demyelinating potential of antibodies to myelin oligodendrocyte glycoprotein is related to their ability to fix complement. Am J Pathol 1993; 143:555-564.
29. Adelmann M, Wood J, Benzel I, Fiori P, Lassmann H, Matthieu JM, et al. The N-terminal domain of the myelin oligodendrocyte glycoprotein (MOG) induces acute demyelinating experimental autoimmune encephalomyelitis in the Lewis rat. J Neuroimmunol 1995; 63:17-27.
30. Johns TG, Kerlero de Rosbo N, Menon KK, Abo S, Gonzales MF, Bernard CCA. Myelin oligodendrocyte glycoprotein induces a demyelinating encephalomyelitis resembling multiple sclerosis. J Immunol 1995; 154: 5536-5541.
31. Genain CP, Nguyen MH, Letvin NL, Pearl R, Davis RL, Adelman M, et al. Antibody facilitation of multiple sclerosis-like lesions in a nonhuman primate. J Clin Invest 1995; 96: 2966-2974.
32. Genain CP, Cannella B, Hauser SL, Raine CS. Identification of autoantibodies associated with myelin damage in multiple sclerosis. Nat Med 1999; 5:170-175.
33. Soderstrom M, Link H, Xu Z, Fredriksson S. Optic neuritis and multiple sclerosis: anti-MBP and anti-MBP peptide antibody secreting cells are accumulated in CSF. Neurology 1993; 43:1215-1222.
34. Sun JB, Olsson T, Wang WZ, Xiao BG, Kostulas V, Fredrikson S, et al. Autoreactive T and B cells responding to myelin proteolipid protein in multiple sclerosis and controls. Eur J Immunol 1991; 21:1461-1468.
35. Sun J, Link H, Olsson T, Xiao BG, Andersson G, Ekre HP, et al. T and B cell responses to myelin oligodendrocyte glycoprotein in multiple sclerosis. J Immunol 1991; 146:1490-1495.
36. Lucchinetti CF, Brück W, Rodriguez M, Lassmann H. Distinct patterns of multiple sclerosis pathology indicates heterogeneity in pathogenesis. Brain Pathol 1996; 6:259-274.
37. Archelos JJ, Hartung HP. Adhesion molecules in multiple sclerosis: a review. In: Siva, A, Kesselring J, Thompson AJ (editors). Frontiers in Multiple Sclerosis II. London: Martin Dunitz Ltd; 1999. pp. 85-116.
38. Raine CS. Multiple sclerosis: immune system molecule expression in the central nervous system. J Neuropathol Exp Neurol 1994; 53:328-337.
39. Cannella B, Raine CS. The adhesion molecule and cytokine profile of multiple sclerosis lesions. Ann Neurol 1995; 37, 424-435.
40. Sobel RA, Hinojoza JR, Maeda A, Chen M. Endothelial cell integrin laminin receptor expression in multiple sclerosis lesions. Am J Pathol 1998; 153:405-415.
41. Archelos JJ, Previtali SC, Hartung HP. The role of integrins in immune-mediated diseases of the nervous system. Trends Neurosci 1999; 22:30-38. This review summarizes the evidence for an important role of the adheision molecules of the integrin family in immune-mediated disorders in humans.
42. Stüber A, Martin R, Stone LA, Maloni H, McFarland HF Expression pattern of activation and adhesion molecules on peripheral blood CD4+ T-lymphocytes in relapsing-remitting multiple sclerosis patients: a serial analysis. J Neuroimmunol 1996; 66:147-15163.
43. Droogan AG, Crockard AD, McMillan SA, Hawkins SA. Effects of intravenous methylprednisolone therapy on leukocyte and soluble adhesion molecule expression in MS. Neurology 1998; 50:224-229.
44. Soilu-Hänninen M, Salmi A, Salonen R. Interferon-beta downregulates expression of VLA-4 antigen and antagonizes interferon-gamma-induced expression of HLA-DQ on peripheral blood monocytes. J Neuroimmunol 1996; 60:99-106.
45. Calabresi PA, Pelfrey CM, Tranquill LR, Maloni H, McFarland HF. VLA-4 expression on peripheral blood lymphocytes is downregulated after treatment of multiple sclerosis with interferon beta. Neurology 1997; 49:1111-1116.
46. Pitzalis C, Sharrack B, Gray IA, Lee A, Hughes RA. Comparison of the effects of oral versus intravenous methylprednisolone regimens on peripheral blood T lymphocyte adhesion molecule expression, T cell subset distribution and TNF alpha concentrations in multiple sclerosis. J Neuroimmunol 1997; 74:62-68.
47. Svenningsson A, Hansson GK, Andersen O, Andersson R, Patarroyo M, Stemme S. Adhesion molecule expression on cerebrospinal fluid T lymphocytes: evidence for common recruitment mechanisms in multiple sclerosis, aseptic meningitis, and normal controls. Ann Neurol 1993; 34:155-161.
48. Svenningsson A, Dotevall L, Stemme S, Andersen O. Increased expression of B7-1 costimulatory molecule on cerebrospinal fluid cells of patients with multiple sclerosis and infectious central nervous system disease. J Neuroimmunol 1997; 75:59-68.
49. Hartung HP, Archelos JJ, Zielasek J, Gold R, Kolzenburg M, Reiners KH, Toyka KV. Circulating adhesion molecules and inflammatory mediators in demyelination. Neurology 1995; 45 (Suppl.6): S22-S32.
50. Giovannoni G, Lai M, Thorpe J, Kidd D, Chamoun V, Thompson AJ, et al. Longitudinal study of soluble adhesion molecules in multiple sclerosis: correlation with gadolinium enhanced magnetic resonance imaging. Neurology 1997; 48, 1557-1565.
51. Giovanonni G, Kieseier B, Hartung HP Correlating immunological and magnetic resonance imaging markers of disease activity in multiple sclerosis. J Neurol Neurosurg Psychiatry 1998; 64 (Suppl 1): S31-S36.
52. Archelos JJ, Hartung HP. The role of adhesion molecules in multiple sclerosis: biology, pathogenesis and therapeutic implications. Mol Med Today 1997; 3:310-321.
53. Woessner Jr JF. The family of matrix metalloproteinases. Ann NY Acad Sci 1994; 732:11-21.
54. Yong VW, Krekoski CA, Forsyth PA, Bell R, Edwards DR. Matrix metalloproteinases and diseases of the CNS. Trends Neurosci 1998; 21:75-80. An excellent review on the potential relevance of MMPs in the pathogenesis of diseases involving the central nervous system.
55. Gearing AJH, Beckett P, Christodoulou M, Churchill M, Clements J, Davidson AH, et al. Processing of tumor necrosis factor-α precursor by metalloproteinases. Nature 1994; 370:555-557.
56. Mohler KM, Sleath PR, Fitzner JN, Cerretti DP, Alderson M, Kerwar SS, et al. Protection against lethal dose of endotoxin by an inhibitor of tumor necrosis factor processing. Nature 1994; 370:218-220.
57. Moss ML, Jin S-LC, Milla ME, Burkhart W, Carter HL, Chen W-J, et al. Cloning of a disintegrin metalloproteinase that processes precursor tumor necrosis factor-α. Nature 1997; 385:733-736.
58. Rosenberg GA, Dencoff JE, Correa N, Reiners M, Ford CC. Effect of steroids on CSF matrix metalloproteinases in multiple sclerosis: relation to blood-brain barrier injury. Neurology 1996; 46:1626-1632.
59. Leppert D, Ford J, Stabler G, Grygar C, Lienert C, Huber S, et al. Matrix metalloproteinase-9 (gelatinase B) is electively elevated in CSF during relapses and stable phases of multiple sclerosis. Brain 1998; 121:2327-2334.
60. Lee MA, Palace J, Stabler G, Ford J, Gearing A, Miller K. Serum gelatinase B, TIMP-1 and TIMP-2 levels in multiple sclerosis: a longitudinal clinical and MRI study. Brain 1999; 122:191-197.
61. Cuzner ML, Gveric D, Strand C, Loughlin AJ, Paemen L, Opdenakker G, Newcombe J. The expression of tissue-type plasminogen activator, matrix metalloproteases and endogenous inhibitors in the central nervous system in multiple sclerosis: comparison of stages in lesion evolution. J Neuropathol Exp Neurol 1996; 55:1194-1204.
62. Maeda A, Sobel RA. Matrix metalloproteinases in the normal human central nervous system, microglial nodules, and multiple sclerosis lesions. J Neuropathol Exp Neurol 1996, 55:300-309.
63. Gijbels K, Proost P, Carton H, Billiau A, Opdenakker G. Gelatinase B is present in the cerebrospinal fluid during experimental autoimmune encephalomyelitis and cleaves myelin basic protein. J Neurosci Res 1993; 36:432-440.
64. Clements JM, Cossins JA, Wells GMA, Corkill DJ, Helfrich K, Wood LM, et al. Matrix metalloproteinase expression during experimental autoimmune encephalomyelitis and effects of a combined matrix metalloproteinase and tumor necrosis factor-α inhibitor. J Neuroimmunol 1997; 74:85-94.
65. Kieseier BC, Kiefer R, Clements JM, Miller K, Wells GMA, Schweltzer T, et al. Matrix metalloproteinase-9 and -7 are regulated in experimental autoimmune encephalomyelitis. Brain 1998; 121:159-166. See (68•).
66. Rosenberg GA, Kornfeld M, Estrada E, Kelley RO, Liotta LA, Stetler-Stevenson WG. TIMP-2 reduces proteolytic opening of blood-brain barrier by type IV collagenase. Brain Res 1992; 576:203-207.
67. Rosenberg GA, Dencoff JE, McGuire PG, Liotta LA, Stetler-Stevenson WA. Injury-induced 92-kilodalton gelatinase and urokinase expression in rat brain. Lab Invest 1994; 71:417-422.
68. Anthony DC, Miller KM, Fearn S, Townsend MJ, Opdenakker G, Wells GMA et al. Matrix metalloproteinase expression in an experimentally-induced DTH model of multiple sclerosis in the rat CNS. J Neuroimmunol 1998; 87:62-72. Two experimental studies [65•,68•] in EAE that demonstrated the selective upregulation of certain MMPs and their distribution in the inflammed central nervous system.
69. Leppert D, Waubant E, Galardy R, Bunnett NW, Hauser SL. T cell gelatinases mediate basement membrane transmigration in vitro. J Immunol 1995; 154:4379-4389.
70. Chandler S, Coates R, Gearing A, Lury J, Wells G, Bone E. Matrix metalloproteinases degrade myelin basic protein. Neurosci Lett 1995; 201:223-226.
71. Gijbels K, Galardy RE, Steinman L. Reversal of experimental autoimmune encephalomyelitis with a hydroxamate inhibitor of matrix metalloproteinases. J Clin Invest 1994; 94:2177-2182.
72. Hewson AK, Smith T, Leonard JP, Cuzner ML. Suppression of experimental allergic encephalomyelitis in the Lewis rat by the matrix metalloproteinase inhibitor Ro31-9790. Inflamm Res 1995; 44:345-349.
73. Matyszak MK, Perry VH. Delayed-type hypersensitivity lesions in the central nervous system are prevented by inhibitors of matrix metalloproteinases. J Neuroimmunol 1996; 69:141-149.
74. Liedtke W, Cannella B, Mazzaccaro RJ, Clements JM, Miller KM, Wucherpfennig KW, et al. Effective treatment of models of multiple sclerosis by matrix metalloproteinase inhibitors. Ann Neurol 1998; 44:35-46.
75. Luster AD. Chemokines-chemotactic cytokines that mediate inflammation. N Engl J Med 1998; 338:436-445. This outstanding review gathers evidence for and discusses the role of chemokines in various inflammatory diseases.
76. Ward SG, Bacon K, Westwick J. Chemokines and T lymphocytes: more than an attraction. Immunity 1998; 9:1-11. An up-to-date, critical review illuminating the functions of these pluripotent cytokines in relation to T cells.
77. Bonecchi R, Bianchi G, Bordignon PP, D'Ambrosio D, Lang R, Borsatti A, et al. Differential expression of chemokine receptors and chemotactic responsiveness of type 1 T helper cells (Th1s) and Th2s. J Exp Med 1998; 187:129-134.
78. Glabinski AR, Balasingam V, Tani M, Kunkel SL, Strieter RM, Yong VW, Ransohoff RM. Chemokine monocyte chemoattractant protein-1 is expressed by astrocytes after mechanical injury to the brain. J Immunol 1996; 156:4363-4368.
79. Tani M, Glabinski AR, Tuohy VK, Stoler MH, Estes ML, Ransohoff RM. In situ hybridization analysis of glial fibrillary acidic protein mRNA reveals evidence of biphasic astrocyte activation during acute experimental autoimmune encephalomyelitis. Ann J Pathol 1996; 148:889-896.
80. Glabinski AR, Tani M, Strieter RM, Tuohy VK, Ransohoff RM. Synchronous synthesis of alpha- and beta-chemokines by cells of diverse lineage in the central nervous system of mice with relapses of chronic experimental autoimmune encephalomyelitis. Am J Pathol 1997; 150:617-630.
81. Karpus WJ, Lukacs NW, McRae BL, Strieter, RM, Kunkel, SL, Mille SD. An important role for the chemokine macrophage inflammatory protein-1a in the pathogenesis of the T cell-mediated autoimmune disease experimental autoimmune encephalomyelitis. J Immunol 1995; 155:5003-5010.
82. McManus C, Berman JW, Brett FM, Staunton H, Farrell M, Brosnan CF. MCP-1, MCP-2 and MCP-3 expression in multiple sclerosis lesions: an immunohistochemical and in situ study. J Neuroimmunol 1998; 86:20-29. See [84•].
83. Simpson JE, Newcombe J, Cuzner ML, Woodroofe MN. Expression of monocyte chemoattractant protein-1 and other beta-chemokines by resident glia and inflammatory cells in multiple sclerosis lesions. J Neuroimmunol 1998; 84:238-249. See [84•].
84. van der Voorn P, Tekstra J. Beelen RHJ, Tensen CP, van der Valk P, de Groot CJA. Expression of MCP-1 by reactive astrocytes in demyelinating multiple sclerosis lesions. Am J Pathol 1999; 154:45-51. Data from these three studies [82•-84•] underscore previous observations in animal models: Chemokine expression in multiple sclerosis lesions can be detected, with predominant localization of the chemokines investigated to astrocytes. However, mononuclear cells also appear within the lesions as chemokine sources.
85. Hvas J, McLean C, Justesen J, Kannourakis G, Steinman L, Oksenberg JR, Bernard CCA. Perivascular T cells express the pro-inflammatory chemokine RANTES mRNA in multiple sclerosis lesions. Scand J Immunol 1997; 46:195-203.
86. Sorensen TL, Tani M, Jensen J, Pierce V, Lucchinetti C, Folcik VA, et al. Expression of specific chemokines and chemokine receptors in the central nervous system of multiple sclerosis patients. J Clin Invest 1999; 103:807-815. This was the first study to investigate the expression pattern of chemokine receptors in post-mortem brain tissue from patients with multiple sclerosis. It was demonstrated that the equivalent ligands can be found in higher concentrations in the CSF of patients than non-inflammatory control individuals.
87. Biddison WE, Taub DD, Cruikshank WW, Center DM, Connor EW, Honma K. Chemokine and matrix metalloproteinase secretion by myelin proteolipid protein-specific CD8+ T cells: potential roles in inflammation. J Immunol 1997; 158:3046-3053.
88. Bernard CCA, Johns TG. The structure and function of myelin oligodendrocyte glycoprotein. J Neurochem 1999; 72:1-9.
89. Mijagishi R, Kikuchi S, Fukazawa T, Tashiro K. Macrophage inflammatory protein-1 alpha in the cerebrospinal fluid of patients with multiple sclerosis and other inflammatory neurological diseases. J Neurol Sci 1995; 129:223-227.
90. Frei K, Eugster HP, Bopst M, Constantinescu CS, Lavi E, Fontana A. Tumor necrosis factor a and lymphotoxin a are not required for induction of acute experimental autoimmune encephalomyelitis. J Exp Med 1997; 185:2177-2182.
91. Körner H, Riminton DS, Strickland DH, Lemckert FA, Pollard JD, Sedgwick JD. Critical points of tumor necrosis factor action in the central nervous system autoimmune inflammation defined by gene targeting. J Exp Med 1997; 186:260-267.
92. Suen WE, Bergman CM, Hjelmstrom P, Ruddle NH. A critical role for lymphotoxin in experimental autoimmune encephalomyelitis. J Exp Med 1997; 186:1233-1240.
93. Liu J, Marino MW, Wong G, Grail D, Dunn A, Bettadapura J, et al. TNF is a potent anti-inflammatroy cytokine in autoimmune-mediated demyelination. Nat Med 1998; 4:78-83. In this study the authors demonstrate that TNF-deficient mice develop severe inflammatory demyelination of the CNS upon immunization with MOG. These animals were treated with TNF, which dramatically reduced disease severity, underscoring that this cytokine might exhibit anti-inflammatory properties.
94. Ferber IA, Brocke S, Taylor-Edwards C, Ridgway W, Dinisco C, Steinman L, et al. Mice with a disrupted IFN-gamma gene are susceptible to the induction of experimental autoimmune encephalomyelitis (EAE). J Immunol 1996; 156:5-7.
95. Krakowski M, Owens T. Interferon-gamma confers resistance to experimental allergic encephalomyelitis. Eur J Immunol 1996; 26:1641-1646.
96. Eugster HP, Frei K, Kopf M, Lassmann H, Fontana A. IL-6-deficient mice resist myelin oligodendrocyte glycoprotein-induced autoimmune encephalomyelitis. Eur J Immunol 1998; 28:2178-2187. See [99•].
97. Mendel I, Katz A, Kozak N, Ben-Nun A, Revel M. Interleukin-6 functions in autoimmune encephalomyelitis: a study in gene-targeted mice. Eur J Immunol 1998; 28:1727-1737. [See [99•].
98. Okuda Y, Sakoda S, Bernard CC, Fujimura H, Saeki Y, Kishimoto T, Yanagihara T. IL-6-deficient mice are resistent to the induction of experimental autoimmune encephalomyelitis provoked by myelin oligodendrocyte glycoprotein. Int Immunol 1998; 10:703-708. See [99•].
99. Samoilova EB, Horton JL, Hilliard B, Liu TS, Chen Y. IL-6-deficient mice are resistant to experimental autoimmune encephalomyelitis: roles of IL-6 in the activation and differentiation of autoreactive T cells. J Immunol 1998; 161:6480-6486. Date from these studies [96•-99•] underscore the pathogenic role of IL-6 in the pathogenesis of inflammatory demyelination.
100. Betelli E, Das MP, Howard ED, Weiner HL, Sobel RA, Kuchroo VK. IL-10 is critical in the regulation of autoimmune encepahlomyelitis as demonstrated by studies of IL-10 and IL-4-deficient transgenic mice. J Immunol 1998; 161:3299-3306. Whereas IL-10-deficient mice were more susceptible and developed severe EAE, mice transgenic for IL-10 were completely resistant to the development of the disease. These observations suggest that IL-10 is a key player in the regulation of inflammatory demyelinalion.
101. Samoilova EB, Horton JL, Chen Y. Acceleration of experimental autoimmune encephalomyelitis in interleukin-1-deficient mice: roles of interleukin-10 in disease progression and recovery. Cell Immunol 1998; 188:118-124.
102. Liblau R, Steinman L, Brocke S. Experimental autoimmune encephalomyelitis in IL-4-deficient mice. Int Immunol 1997; 9:799-803.
103. Eugster HP, Frei K, Bachmann R, Bluethmann H, Lassmann H, Fontana A. Severity of symptoms and demyelination in MOG-induced EAE depends on TNFR1. Eur J Immunol 1999; 29:626-632.
104. Probert L, Akassoglou K, Pasparakis M, Kontogeorgos G, Kollias G. Spontaneous inflammatory demyetinating disease in transgenic mice showing central nervous system-specific expression of tumor necrosis factor α. Proc Natl Acad Sci USA 1995; 92:11294-11298.
105. Taupin V, Renno T, Bourbonnierre L, Peterson AC, Rodriguez M, Owens T. Increased severity of experimental autoimmune encephalomyelitis, chronic macrophage/microglia reactivity and demyelination in transgenic mice producing tumor necrosis factor-alpha in the central nervous system. Eur J Immunol 1997; 27:905-913.
106. Steinman L. Some misconceptions about understanding autoimmunity through experiments with knockouts. J Exp Med 1997; 185:2039-2041.
107. Smith KJ, Kapoor R, Felts PA. Demyelination: the role of reactive oxygen and nitrogen species. Brain Pathol 1999; 9:69-92. A timely review that summarises the accumulated scientific evidence over the past years regarding the critical role of oxidative stress in inflammatory demyelination.
108. Cross AH, Keeling RM, Goorha S, San M, Rodi C, Wyatt PS, et al. Inducible nitric oxide synthase gene expression and enzyme activity correlate with disease activity in murine experimental autoimmune encephalomyelitis. J Neuroimmunol 1996; 71:145-153.
109. Koprowski H, Zheng YM, Heber-Katz E, Fraser N, Rorke L, Fu ZF, et al. In vivo expression of inducible nitric oxide synthase in experimentally induced neurologic disease. Proc Natl Acad Sci USA. 1993; 90:3024-3027.
110. Okuda Y, Nakatsuji Y, Fujimura H, Esumi H, Ogura T, Yanagihara T, Sakoda S. Expression of the inducible isoform of nitric oxide synthase in the central nervous system of mice correlates with the severity of actively induced experimental allergic encephalomyelitis. J Neuroimmunol. 1995; 62:103-112.
111. Cross AH, Manning PT, Stern MK, Misko TP. Evidence for the production of peroxynitrite in inflammatory CNS demyelination. J Neuroimmunol 1997; 80:121-130
112. van der Veen RC, Hinton DR, Incardonna F, Hofmann FM. Extensive peroxynitrite activity during progressive stages of central nervous system inflammation. J Neuroimmunol. 1997; 77:1-7.
113. Bö L, Dawson TM, Wesselingh S, Sverre M, Choi S, Kong PA, et al. Induction of nitric oxide synthase in demyelinating regions of multiple sclerosis brains. Ann Neurol 1994; 36:778-786.
114. De Groot CJ, Ruuls SR, Theeuwes JW, Dijkstra CD, van der Valk P. Immunocytochemical characterization of the expression of inducible and constitutive isoforms of nitric oxide synthase in demyelinating multiple sclerosis lesions. J Neuropathol Exp Neurol 1997; 56:10-20.
115. Bagasra O, Michaels FH, Zheng YM, Bobroski LE, Spitsin SV, Fu ZF, et al. Avtivation of the inducible form of nitric oxide synthase in the brains of patients with multiple sclerosis. Proc Natl Acad Sci USA. 1995; 92:12041-12045.
116. Cross AH, Manning PT, Keeling RM, Schmidt RE, Misko TP. Peroxynitrite formation within the central nervous system in active multiple sclerosis. J Neuroimmunol 1998; 88:45-56.
117. Zielasek J, Jung S, Gold R, Liew FY, Toyka KV, Hartung HP. Administration of nitric oxide synthase inhibitors in experimental autoimmune neuritis and experimental autoimmune encephalomyelitis. J Neuroimmunol 1995; 58:81-88.
118. Okuda Y, Sakoda S, Fujimura H, Yanagihara T. Aminoguanidine, a selective inhibitor of the inducible nitric oxide synthase, has different effects on experimental allergic encephalomyelitis in the induction and progression phase. J Neuroimmunol 1998; 81:201-210. The effect of NOS inhibitors on EAE has been controversial during recent years. The present study suggests that the timing of the administration of NOS inhibitors might be crucial. Animals receiving aminoguanidin from days 2 to 12 after administration developed a delay in the onset of EAE, whereas animals in which administration started at day 10 after induction of the disease revealed a more severe clinical form.
119. Ding MZ, Zhang M, Wong JL, Rogers NE, Ignarro LJ, Voskuhl RR. Antisense knockdown of inducible nitric oxide synthase inhibits induction of experimental autoimmune encephalomyelitis in SJL/J mice. J Immunol 1998; 160:2560-2564.
120. FenykMelody JE, Garrison AE, Brunnert SR, Weidner JR, Shen F, Shelton BA, Mudgett JS. Experimental autoimmune encephalomyelitis is exacerbated in mice lacking the NOS2 gene. J Immunol 1998; 160:2940-2946.
121. Redford EJ, Kapoor R, Smith KJ. Nitric oxide donors reversibly block axonal conduction: demyelinated axons are especially susceptible. Brain 1997; 120:2149-2157.
122. Shrager P, Custer AW, Kazarinova K, Rasband MN, Mattson D. Nerve conduction block by nitric oxide that is mediated by the axonal environment. J Neurophysiol 1998; 56:542-550.
123. Bongarzone ER, Pasquini JM, Soto EF. Oxidative damage to proteins and lipids of CNS myelin produced by in vitro generated reactive oxygen species. J Neurosci Res 1995; 41:213-221.
124. LeVine SM, Wetzel DL. Chemical analysis of multiple sclerosis lesions by FT-IR microspectroscopy. Free Radic Biol Med 1998; 25:33-41.
125. Jaworowicz DJ, Korytko PJ, Lakhman SS, Boje KMK. Nitric oxide and prostaglandin E2 formation parallels blood-brain barrier disruption in an experimental rat model of bacterial meningitis. Brain Res Bull 1998; 46:541-546.
126. Maeda H, Okamoto T, Akaike T. Human matrix metalloproteinase activation by insults of bacterial infection involving proteases and free radicals. Biol Chem 1998; 379:193-200.