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.
We investigated the effect of laquinimod on inflammatory demyelination, axonal damage, cytokine profiles and migratory capacities of lymphocytes in C57BL/6 mice with active EAE induced with MOG(35-55) peptide. The mice were treated at disease induction and after disease onset. Spinal cords were assessed histologically. Cytokines and adhesive properties were analyzed in splenocytes. Preventive and therapeutic laquinimod treatment reduced clinical signs, inflammation, and demyelination. VLA-4-mediated adhesiveness and pro-inflammatory cytokines such as IL-17 were down-regulated in treated animals. Within lesions, treated mice showed similar axonal densities, but less acute axonal damage than controls. Laquinimod might thus protect myelin and axons by decreasing pro-inflammatory cytokines and impairing the migratory capacity of lymphocytes.
Wegner
Christiane
C
Department of Neuropathology, University Medical Center, Georg-August University, Göttingen, Germany. chrwegner@gmx.de
Stadelmann
Christine
C
Pförtner
Ramona
R
Raymond
Emanuel
E
Feigelson
Sara
S
Alon
Ronen
R
Timan
Bracha
B
Hayardeny
Liat
L
Brück
Wolfgang
W
D000818:Animals; D001369:Axons / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology*; D003711:Demyelinating Diseases / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D005260:Female; D018836:Inflammation Mediators / Q000627:therapeutic use*; D020381:Interleukin-17 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D015363:Quinolones / Q000627:therapeutic use*; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000473:pathology*
D018836:Inflammation Mediators; D020381:Interleukin-17; D015363:Quinolones; C476223:laquinimod