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

Christiane Wegner; Christine Stadelmann; Ramona Pförtner; Emanuel Raymond; Sara Feigelson; Ronen Alon; Bracha Timan; Liat Hayardeny; Wolfgang Brück

doi:10.1016/j.jneuroim.2010.07.009

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

J Neuroimmunol. 2010 Oct 8;227(1-2):133-43. doi: 10.1016/j.jneuroim.2010.07.009. Epub 2010 Aug 3.

Authors

Christiane Wegner¹, Christine Stadelmann, Ramona Pförtner, Emanuel Raymond, Sara Feigelson, Ronen Alon, Bracha Timan, Liat Hayardeny, Wolfgang Brück

Affiliation

¹ Department of Neuropathology, University Medical Center, Georg-August University, Göttingen, Germany. chrwegner@gmx.de

PMID: 20684995
DOI: 10.1016/j.jneuroim.2010.07.009

Abstract

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.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Axons / drug effects
Axons / immunology
Axons / pathology*
Cell Movement / drug effects
Cell Movement / immunology*
Demyelinating Diseases / drug therapy*
Demyelinating Diseases / immunology
Demyelinating Diseases / pathology
Down-Regulation / drug effects
Down-Regulation / immunology
Encephalomyelitis, Autoimmune, Experimental / drug therapy*
Encephalomyelitis, Autoimmune, Experimental / immunology
Encephalomyelitis, Autoimmune, Experimental / pathology
Female
Inflammation Mediators / therapeutic use*
Interleukin-17 / antagonists & inhibitors*
Interleukin-17 / metabolism
Mice
Mice, Inbred C57BL
Quinolones / therapeutic use*
T-Lymphocyte Subsets / drug effects
T-Lymphocyte Subsets / immunology
T-Lymphocyte Subsets / pathology*

Substances

Inflammation Mediators
Interleukin-17
Quinolones
laquinimod