Linomide suppresses both Th1 and Th2 cytokines in experimental autoimmune myasthenia gravis.
Suppressive effects of the synthetic immunomodulatory drug Linomide have been shown in several autoimmune models, including antibody-mediated experimental autoimmune myasthenia gravis (EAMG), a model for human myasthenia gravis (MG). To define the mechanisms underlying EAMG suppression, we injected Linomide subcutaneously at different doses into Lewis rats immunized with Torpedo acetylcholine receptor (AChR) in complete Freund's adjuvant (CFA), and investigated AChR-specific T and B cell responses, and the levels of lymph node cells expressing mRNA of different cytokines after AChR stimulation in vitro. Both 160 and 16, but not 1.6, mg/kg/day of Linomide effectively suppressed clinical muscle weakness, accompanied by decreased AChR-induced T and B cell responses. Linomide also suppressed the mRNA expression of the Th1 cytokines IFN-gamma, IL-12 and TNF-alpha as well as the Th2 cytokines IL-4 and IL-10, which are important in the immunopathogenesis of EAMG by promoting antibody production. There were no differences for IL-1beta, IL-6, lymphotoxin or TGF-beta expression in Linomide-treated vs nontreated control EAMG rats. We conclude that Linomide suppresses clinical EAMG as well as B and T cell responses to AChR by counteracting the production of AChR-induced Th1 and Th2 cytokines.
Zhang
G X
GX
Division of Neurology, Huddinge Hospital, Sweden.
Yu
L Y
LY
Shi
F D
FD
Xiao
B G
BG
Björk
J
J
Hedlund
G
G
Link
H
H
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000906:Antibodies / Q000032:analysis; D002455:Cell Division; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000235:genetics; D005260:Female; D006912:Hydroxyquinolines / Q000494:pharmacology*; D007074:Immunoglobulin G / Q000032:analysis; D008214:Lymphocytes / Q000473:pathology; D009000:Monocytes / Q000276:immunology; D018908:Muscle Weakness; D009157:Myasthenia Gravis / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D011950:Receptors, Cholinergic / Q000276:immunology
D000276:Adjuvants, Immunologic; D000906:Antibodies; D016207:Cytokines; D006912:Hydroxyquinolines; D007074:Immunoglobulin G; D012333:RNA, Messenger; D011950:Receptors, Cholinergic; C045282:roquinimex