Laquinimod interferes with migratory capacity of T cells and reduces IL-17 levels, inflammatory demyelination and acute axonal damage in mice with experimental autoimmune encephalomyelitis

Journal of Neuroimmunology

Volumn 227, Issue 1-2, 2010, Pages 133-143

  Wegner, Christiane ^a   Stadelmann, Christine ^a   Pförtner, Ramona ^a   Raymond, Emanuel ^b   Feigelson, Sara ^c   Alon, Ronen ^c   Timan, Bracha ^b   Hayardeny, Liat ^b   Brück, Wolfgang ^a  

^a UNIVERSITY OF GÖTTINGEN   (Germany)

^b Pharmacology Unit   (Israel)

^c WEIZMANN INSTITUTE OF SCIENCE   (Israel)

Author keywords

Acute axonal damage; Cytokines; EAE; Laquinimod; Pathology; VLA 4

Indexed keywords

ALPHA4 INTEGRIN; CD3 ANTIGEN; INTERLEUKIN 17; LAQUINIMOD; MYELIN OLIGODENDROCYTE GLYCOPROTEIN; PLACEBO; SECONDARY LYMPHOID TISSUE CHEMOKINE; VASCULAR CELL ADHESION MOLECULE 1; VERY LATE ACTIVATION ANTIGEN 4; AUTACOID; QUINOLONE DERIVATIVE;

ALLERGIC ENCEPHALOMYELITIS; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; AXONAL INJURY; CELL DENSITY; CELL INFILTRATION; CELL MIGRATION; CONTROLLED STUDY; CYTOKINE PRODUCTION; DEMYELINATION; DISEASE SEVERITY; DOSE RESPONSE; DOWN REGULATION; FEMALE; HISTOPATHOLOGY; IMMUNOHISTOCHEMISTRY; LYMPHOCYTE MIGRATION; MOUSE; NONHUMAN; PRIORITY JOURNAL; SPINAL CORD; T LYMPHOCYTE; WHITE MATTER; ANIMAL; ANTAGONISTS AND INHIBITORS; C57BL MOUSE; CELL MOTION; COMPARATIVE STUDY; DEMYELINATING DISEASES; DRUG EFFECTS; ENCEPHALOMYELITIS, AUTOIMMUNE, EXPERIMENTAL; IMMUNOLOGY; METABOLISM; NERVE FIBER; PATHOLOGY; T LYMPHOCYTE SUBPOPULATION;

ANIMALS; AXONS; CELL MOVEMENT; DEMYELINATING DISEASES; DOWN-REGULATION; ENCEPHALOMYELITIS, AUTOIMMUNE, EXPERIMENTAL; FEMALE; INFLAMMATION MEDIATORS; INTERLEUKIN-17; MICE; MICE, INBRED C57BL; QUINOLONES; T-LYMPHOCYTE SUBSETS;

EID: 77956649428     PISSN: 01655728     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.jneuroim.2010.07.009     Document Type: Article

References (31)

1. Alt C., Laschinger M., Engelhardt B. Functional expression of the lympohoid chemokines CCL19 (ECL) and CCL21 (SLC) at the blood-brain barrier suggests their possible involvement in lymphocyte recruitment into the central nervous system during experimental autoimmune encephalomyelitis. Eur. J. Immunol. 2002, 32:2133-2144.
2. Bjartmar C., Kidd G., Mork S., Rudick R., Trapp B.D. Neurological disability correlates with spinal cord axonal loss and reduced N-acetyl aspartate in chronic multiple sclerosis patients. Ann. Neurol. 2000, 48:893-901.
3. Brück W., Bitsch A., Kolenda H., Brück Y., Stiefel M., Lassmann H. Inflammatory central nervous system demyelination: correlation of magnetic resonance imaging findings with lesion pathology. Ann. Neurol. 1997, 42:783-793.
4. Brunmark C., Runstrom A., Ohlsson L., Sparre B., Brodin T., Astrom M., Hedlund G. The new orally active immunoregulator laquinimod (ABR-215062) effectively inhibits development and relapses of experimental autoimmune encephalomyelitis. J. Neuroimmunol. 2002, 130:163-172.
5. Comi G., Pulizzi A., Rovaris M., Abramsky O., Arbizu T., Boiko A., Gold R., Havrdova E., Komoly S., Selmaj K., Sharrack B., Filippi M. Effect of laquinimod on MRI-monitored disease activity in patients with relapsing-remitting multiple sclerosis: a multicentre, randomised, double-blind, placebo-controlled phase IIb study. Lancet 2008, 371:2085-2092.
6. Engelhardt B., Laschinger M., Schulz M., Samulowitz U., Vestweber D., Hoch G. The development of experimental autoimmune encephalomyelitis in the mouse requires alpha4-integrin but not alpha4beta7-integrin. J. Clin. Invest. 1998, 102:2096-2105.
7. Ferguson B., Matyszak M.K., Esiri M.M., Perry V.H. Axonal damage in acute multiple sclerosis lesions. Brain 1997, 120:393-399.
8. Frisullo G., Nociti V., Iorio R., Patanella A.K., Marti A., Caggiula M., Mirabella M., Tonali P.A., Batocchi A.P. IL17 and IFNgamma production by peripheral blood mononuclear cells from clinically isolated syndrome to secondary progressive multiple sclerosis. Cytokine 2008, 44:22-25.
9. Ganter P., Prince C., Esiri M.M. Spinal cord axonal loss in multiple sclerosis: a post-mortem study. Neuropathol. Appl. Neurobiol. 1999, 25:459-467.
10. Gold R., Linington C., Lassmann H. Understanding pathogenesis and therapy of multiple sclerosis via animal models: 70years of merits and culprits in experimental autoimmune encephalomyelitis research. Brain 2006, 129:1953-1971.
11. Grabovsky V., Feigelson S., Chen C., Bleijs D.A., Peled A., Cinamon G., Baleux F., Renzana-Seisdedos F., Lapidot T., van K.Y., Lobb R.R., Alon R. Subsecond induction of alpha4 integrin clustering by immobilized chemokines stimulates leukocyte tethering and rolling on endothelial vascular cell adhesion molecule 1 under flow conditions. J. Exp. Med. 2000, 192:495-506.
12. Haak S., Croxford A.L., Kreymborg K., Heppner F.L., Pouly S., Becher B., Waisman A. IL-17A and IL-17F do not contribute vitally to autoimmune neuro-inflammation in mice. J. Clin. Invest. 2009, 119:61-69.
13. Karussis D.M., Lehmann D., Slavin S., Vourka-Karussis U., Mizrachi-Koll R., Ovadia H., Ben-Nun A., Kalland T., Abramsky O. Inhibition of acute, experimental autoimmune encephalomyelitis by the synthetic immunomodulator linomide. Ann. Neurol. 1993, 34:654-660.
14. Karussis D.M., Lehmann D., Slavin S., Vourka-Karussis U., Mizrachi-Koll R., Ovadia H., Kalland T., Abramsky O. Treatment of chronic-relapsing experimental autoimmune encephalomyelitis with the synthetic immunomodulator linomide (quinoline-3-carboxamide). Proc. Natl Acad. Sci. USA 1993, 90:6400-6404.
15. Kuhlmann T., Lingfeld G., Bitsch A., Schuchardt J., Brück W. Acute axonal damage in multiple sclerosis is most extensive in early disease stages and decreases over time. Brain 2002, 125:2202-2212.
16. Noseworthy J.H., Wolinsky J.S., Lublin F.D., Whitaker J.N., Linde A., Gjorstrup P., Sullivan H.C. Linomide in relapsing and secondary progressive MS: part I: trial design and clinical results. North American Linomide Investigators. Neurology 2000, 54:1726-1733.
17. Ochi H., Osoegawa M., Wu X.M., Minohara M., Horiuchi I., Murai H., Furuya H., Kira J. Increased IL-13 but not IL-5 production by CD4-positive T cells and CD8-positive T cells in multiple sclerosis during relapse phase. J. Neurol. Sci. 2002, 201:45-51.
18. Polman C., Barkhof F., Sandberg-Wollheim M., Linde A., Nordle O., Nederman T. Treatment with laquinimod reduces development of active MRI lesions in relapsing MS. Neurology 2005, 64:987-991.
19. Runstrom A., Leanderson T., Ohlsson L., Axelsson B. Inhibition of the development of chronic experimental autoimmune encephalomyelitis by laquinimod (ABR-215062) in IFN-beta k.o. and wild type mice. J. Neuroimmunol. 2006, 173:69-78.
20. Shulman Z., Pasvolsky R., Woolf E., Grabovsky V., Feigelson S.W., Erez N., Fukui Y., Alon R. DOCK2 regulates chemokine-triggered lateral lymphocyte motility but not transendothelial migration. Blood 2006, 108:2150-2158.
21. Sinha S., Kaler L.J., Proctor T.M., Teuscher C., Vandenbark A.A., Offner H. IL-13-mediated gender difference in susceptibility to autoimmune encephalomyelitis. J. Immunol. 2008, 180:2679-2685.
22. Steinman L., Zamvil S.S. Virtues and pitfalls of EAE for the development of therapies for multiple sclerosis. Trends Immunol. 2005, 26:565-571.
23. Teitelbaum D., Fridkis-Hareli M., Arnon R., Sela M. Copolymer 1 inhibits chronic relapsing experimental allergic encephalomyelitis induced by proteolipid protein (PLP) peptides in mice and interferes with PLP-specific T cell responses. J. Neuroimmunol. 1996, 64:209-217.
24. Trapp B.D., Peterson J., Ransohoff R.M., Rudick R., Mork S., Bo L. Axonal transection in the lesions of multiple sclerosis. New Engl. J. Med. 1998, 338:278-285.
25. Tsukimoto M., Nakatsukasa H., Sugawara K., Yamashita K., Kojima S. Repeated 0.5-Gy gamma irradiation attenuates experimental autoimmune encephalomyelitis with up-regulation of regulatory T cells and suppression of IL17 production. Radiat. Res. 2008, 170:429-436.
26. Vajkoczy P., Laschinger M., Engelhardt B. Alpha4-integrin-VCAM-1 binding mediates G protein-independent capture of encephalitogenic T cell blasts to CNS white matter microvessels. J. Clin. Invest. 2001, 108:557-565.
27. Wang G.Y., Sun B., Kong Q.F., Zhang Y., Li R., Wang J.H., Wang D.D., Lv G.X., Li H.L. IL-17 eliminates the therapeutic effects of myelin basic protein-induced nasal tolerance in experimental autoimmune encephalomyelitis by activating IL-6. Scand. J. Immunol. 2008, 68:589-597.
28. Wolinsky J.S., Narayana P.A., Noseworthy J.H., Lublin F.D., Whitaker J.N., Linde A., Gjorstrup P., Sullivan H.C. Linomide in relapsing and secondary progressive MS: part II: MRI results. MRI Analysis Center of the University of Texas-Houston, Health Science Center, and the North American Linomide Investigators. Neurology 2000, 54:1734-1741.
29. Yang J.S., Xu L.Y., Xiao B.G., Hedlund G., Link H. Laquinimod (ABR-215062) suppresses the development of experimental autoimmune encephalomyelitis, modulates the Th1/Th2 balance and induces the Th3 cytokine TGF-beta in Lewis rats. J. Neuroimmunol. 2004, 156:3-9.
30. Yasuda C.L., Al-Sabbagh A., Oliveira E.C., B.M.az-Bardales,, Garcia A.A., Santos L.M. Interferon beta modulates experimental autoimmune encephalomyelitis by altering the pattern of cytokine secretion. Immunol. Invest. 1999, 28:115-126.
31. Zou L.P., Abbas N., Volkmann I., Nennesmo I., Levi M., Wahren B., Winblad B., Hedlund G., Zhu J. Suppression of experimental autoimmune neuritis by ABR-215062 is associated with altered Th1/Th2 balance and inhibited migration of inflammatory cells into the peripheral nerve tissue. Neuropharmacology 2002, 42:731-739.