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.
The new orally active drug laquinimod (ABR-215062) was evaluated in experimental autoimmune encephalomyelitis (EAE) in the Lewis rat. EAE shares important immunological and clinical features with multiple sclerosis (MS). Doses of 16, 1.6 and 0.16 mg/kg/day laquinimod dose-dependently inhibited disease and showed better disease inhibitory effects as compared to roquinimex (Linomide). Furthermore, laquinimod inhibited the inflammation of both CD4+ T cells and macrophages into central nervous tissues, i.e. the spinal cord. It also changed the cytokine balance in favour of TH2/TH3 cytokines IL-4, IL-10 and TGF-beta. Laquinimod therefore represents a new orally active immunoregulatory drug without general immunosuppressive properties with a potential for the treatment of severe autoimmune diseases like MS.
Division of Neuroimmunology, NEUROTEC Department, Karolinska Institute, Stockholm, Sweden.
Jian-She
JS
Yang
Ling-Yun
LY
Xu
Bao-Guo
BG
Xiao
Gunnar
G
Hedlund
Hans
H
Link
D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000097:blood / Q000276:immunology / Q000517:prevention & control*; D005260:Female; D006912:Hydroxyquinolines / Q000494:pharmacology / Q000627:therapeutic use*; D015363:Quinolones; D051381:Rats; D011917:Rats, Inbred Lew; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000276:immunology
D016207:Cytokines; D006912:Hydroxyquinolines; D015363:Quinolones; D016212:Transforming Growth Factor beta; C476223:laquinimod