Interleukin 10 aggravates experimental autoimmune myasthenia gravis through inducing Th2 and B cell responses to AChR.
The damage of acetylcholine receptor (AChR) at neuromuscular junctions of experimental autoimmune myasthenia gravis (EAMG), an animal model of human MG, is mediated by B cells which require T cell help. The Th2 associated cytokine IL-10 suppresses production of cytokines released by Th1 cells and is considered for treatment of human autoimmune diseases. To evaluate the role of IL-10 in EAMG, rhIL-10 was administered daily to Lewis rats by the subcutaneous route starting at the day of immunization and continued for 7 weeks. IL-10 failed to abrogate EAMG at low dose (0.1 or 1 microg/day) and at the dose of 3 microg/day caused earlier onset and aggravated clinical signs of EAMG when compared to EAMG rats injected with PBS only. Although Th1 responses reflected by AChR-induced lymphocyte proliferation and levels of IFN-gamma secreting cells, as well as AChR-induced Th1 cytokine mRNA expression was suppressed, augmented IL-4 mRNA expression and AChR-specific B cell responses may play an important role in the failure of IL-10 to abrogate EAMG. This study implicates a critical precaution in planning immunotherapy of IL-10 in antibody-mediated autoimmune diseases, e.g. MG.
Zhang
G X
GX
Experimental Neuroimmunology Unit, Division of Neurology, Karolinska Institute, Huddinge University Hospital, S-141 86 Huddinge, Sweden.
Xiao
B G
BG
Yu
L Y
LY
van der Meide
P H
PH
Link
H
H
D000109:Acetylcholine / Q000276:immunology*; D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002455:Cell Division / Q000276:immunology; D005260:Female; D015870:Gene Expression / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D018908:Muscle Weakness / Q000276:immunology; D020720:Myasthenia Gravis, Autoimmune, Experimental / Q000276:immunology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011917:Rats, Inbred Lew; D011950:Receptors, Cholinergic / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology*; D014101:Torpedo
D007074:Immunoglobulin G; D012333:RNA, Messenger; D011950:Receptors, Cholinergic; D016753:Interleukin-10; D000109:Acetylcholine