Exacerbation of autoimmune arthritis by copolymer-I through promoting type 1 immune response and autoantibody production.
Copolymer-I (COP-I) is an unique immune regulatory polymer that has been shown to suppress experimental autoimmune encephalomyelitis (EAE) and is a treatment option for multiple sclerosis (MS). To investigate whether its immune suppressive effects can be extended to other autoimmune diseases, we treated mice with COP-I during the induction of collagen-induced arthritis (CIA). Our results show that COP-I treatment exacerbated CIA, leading to faster onset, more severe and longer-lasting disease. The mechanisms underlying the exacerbation of CIA by COP-I treatment include enhanced activation and inflammatory cytokine production by autoreactive T cells and elevated production of autoreactive antibodies. In addition, germinal center response was significantly enhanced by COP-I treatment. Thus, great caution should be taken when COP-I is to be used in MS patients with other autoimmune complications or its potential therapeutic effects are to be extended beyond autoimmune demyelinating diseases.
Zheng
Biao
B
Department of Immunology, Baylor College of Medicine, Houston, TX 77030, USA. bzheng@bcm.edu
Switzer
Kirsten
K
Marinova
Ekaterina
E
Zhang
Jinwu
J
Han
Shuhua
S
D000818:Animals; D001169:Arthritis, Experimental / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology; D001323:Autoantibodies / Q000096:biosynthesis*; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D003094:Collagen / Q000276:immunology; D018858:Germinal Center / Q000187:drug effects; D000068717:Glatiramer Acetate; D007111:Immunity, Cellular; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D010455:Peptides / Q000009:adverse effects*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects; D018417:Th1 Cells / Q000187:drug effects
D001323:Autoantibodies; D007166:Immunosuppressive Agents; D010455:Peptides; D016753:Interleukin-10; D015847:Interleukin-4; D000068717:Glatiramer Acetate; D007371:Interferon-gamma; D003094:Collagen