Linomide suppresses chronic-relapsing experimental autoimmune encephalomyelitis in DA rats.
Linomide (quinoline-3-carboxamide) is a synthetic immunomodulator that suppresses several experimental autoimmune diseases. Here we report the effects of Linomide on chronic progressive and/or relapsing experimental autoimmune encephalomyelitis (PR-EAE), a CD4+ T cell mediated animal model of multiple sclerosis (MS). PR-EAE induced in DA rats by inoculation with homogenized guinea pig spinal cord and Freund's complete adjuvant, was strongly suppressed by Linomide administered daily subcutaneously from the day of inoculation. Linomide dose-dependently delayed the interval between immunization and onset of clinical PR-EAE, reduced severity and relapse of clinical PR-EAE, and shortened clinical PR-EAE. These clinical effects were associated with the down-modulation of CNS antigen-induced T cell responses and production of proinflammatory cytokines (IFN-gamma and TNF-alpha) as well as with upregulation of IL-4 (except in spleen MNC), IL-10 and TGF-beta in both spleen MNC and the spinal cord. These effects indicate that Linomide can suppress PR-EAE and may mediate its suppressive effects by regulation of cytokines.
Zhu
J
J
Division of Neurology, Karolinska Institute, Huddinge University Hospital, Sweden. jie.zhu@cnsf.ki.se
Diab
A
A
Mustafa
M
M
Levi
M
M
Wahren
B
B
Björk
J
J
Hedlund
G
G
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000517:prevention & control*; D006168:Guinea Pigs; D006912:Hydroxyquinolines / Q000627:therapeutic use*; D007963:Leukocytes, Mononuclear / Q000737:chemistry / Q000276:immunology; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013116:Spinal Cord / Q000276:immunology; D013154:Spleen / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D013997:Time Factors
D000276:Adjuvants, Immunologic; D016207:Cytokines; D006912:Hydroxyquinolines; D012333:RNA, Messenger; C045282:roquinimex