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

J Neuroimmunol. 2015 Jun 15:283:11-6. doi: 10.1016/j.jneuroim.2015.04.007. Epub 2015 Apr 11.

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.

Keywords: Gene expression microarray; Laquinimod; Multiple sclerosis; Peripheral blood mononuclear cells.

MeSH terms

  • Adult
  • Cell Adhesion / drug effects
  • Chemotaxis, Leukocyte / drug effects
  • Cytokines / biosynthesis*
  • Cytokines / genetics
  • Down-Regulation / drug effects
  • Female
  • Gene Expression Profiling*
  • Gene Expression Regulation / drug effects*
  • Humans
  • Immunologic Factors / pharmacology*
  • Immunologic Factors / therapeutic use
  • Inflammation
  • Male
  • Multiple Sclerosis, Relapsing-Remitting / drug therapy*
  • Multiple Sclerosis, Relapsing-Remitting / immunology
  • NF-kappa B / metabolism
  • 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

Substances

  • Cytokines
  • Immunologic Factors
  • NF-kappa B
  • Quinolones
  • RNA, Messenger
  • Transforming Growth Factor beta
  • laquinimod