Linomide suppresses acute experimental autoimmune encephalomyelitis in Lewis rats by counter-acting the imbalance of pro-inflammatory versus anti-inflammatory cytokines.
Linomide (quinoline-3-carboxamide) is a synthetic immunomodulator that suppresses several experimental autoimmune diseases. Here we report the effects of Linomide on experimental autoimmune encephalomyelitis (EAE), a CD4+ T cell-mediated animal model of multiple sclerosis (MS). EAE induced in Lewis 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 EAE, and reduced severity of EAE symptoms. These clinical effects were associated with dose-dependent down-modulation of myelin antigens-induced T cell responses and by suppression of the proinflammatory cytokines IFN-gamma and TNF-alpha, and upregulation IL-4, IL-10 and TGF-beta as evaluated by in situ hybridization for mRNA expression in spleen mononuclear cells and spinal cord sections. These findings suggest that Linomide could be useful in certain T cell dependent autoimmune diseases.
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Division of Neurology, Karolinska Institute, Huddinge Hospital, Stockholm, Sweden.
Michael
L
L
Wahren
B
B
Deng
G M
GM
Björk
J
J
Hedlund
G
G
Zhu
J
J
D000208:Acute Disease; D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000517:prevention & control*; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D006912:Hydroxyquinolines / Q000627:therapeutic use*; D007150:Immunohistochemistry; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000187:drug effects
D000276:Adjuvants, Immunologic; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D006912:Hydroxyquinolines; D012333:RNA, Messenger; C045282:roquinimex