The role of laquinimod in modulation of the immune response in relapsing–remitting multiple sclerosis: Lessons from gene expression signatures

• Published in: Journal of neuroimmunology Vol. 283; pp. 11 - 16
• Main Authors: Zilkha-Falb, R, Gurevich, M, Hayardeny, L, Achiron, A
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.06.2015
• Subjects: Adult; Allergy and Immunology; Cell Adhesion - drug effects; Chemotaxis, Leukocyte - drug effects; Cytokines - biosynthesis; Cytokines - genetics; Down-Regulation - drug effects; Female; Gene expression microarray; Gene Expression Profiling; Gene Expression Regulation - drug effects; Humans; Immunologic Factors - pharmacology; Immunologic Factors - therapeutic use; Inflammation; Laquinimod; Male; Multiple sclerosis; Multiple Sclerosis, Relapsing-Remitting - drug therapy; Multiple Sclerosis, Relapsing-Remitting - immunology; Neurology; NF-kappa B - metabolism; Peripheral blood mononuclear cells; Quinolones - pharmacology; Quinolones - therapeutic use; RNA, Messenger - blood; Signal Transduction - drug effects; Transforming Growth Factor beta - biosynthesis; Transforming Growth Factor beta - blood; Transforming Growth Factor beta - genetics; Peripheral blood mononuclear cells; Multiple sclerosis; Laquinimod; Gene expression microarray
• ISSN: 0165-5728; 1872-8421
• DOI: 10.1016/j.jneuroim.2015.04.007

Abstract Laquinimod, is a potential oral immunomodulatory drug, for relapsing–remitting multiple sclerosis (RRMS). We analyzed the blood-transcriptional changes in RRMS patients (who participated in the ALLEGRO clinical trial) at one and six months after laquinimod treatment using gene expression microarrays. The molecular effects of laquinimod were enhanced by duration of treatment and showed down-regulation of inflammatory responses mainly via TGFb signaling, and of pro-inflammatory cytokines as well as of cellular movement, including adhesion, migration and leukocyte extravasation signaling. Our results demonstrate that laquinimod suppresses inflammation through down-regulation of inflammatory cytokines and arrest of leukocyte extravasation and thereby could attenuate disease activity in RRMS patients.