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.
Department of Immunology, Baylor College of Medicine, Houston, TX 77030, USA. bzheng@bcm.edu
Biao
B
Zheng
Kirsten
K
Switzer
Ekaterina
E
Marinova
Jinwu
J
Zhang
Shuhua
S
Han
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