Intravenous immunoglobulin prevents experimental autoimmune myositis in SJL mice by reducing anti-myosin antibody and by blocking complement deposition.
High-dose intravenous immunoglobulin (IVIG) therapy has been effective in many autoimmune and systemic inflammatory diseases including polymyositis (PM) and dermatomyositis (DM). In the present study we evaluated the efficacy of IVIG using experimental models of PM and DM. An experimental autoimmune myositis (EAM) model was produced in SJL/J mice by an immunization with rabbit myosin B (MB) fraction. In this model, the plasma level of anti-MB antibody was elevated, and mouse IgG and complement C3 were deposited in the muscle fibres. Administration of IVIG dose-dependently reduced the incidences of necrotic and inflammatory changes in the skeletal muscle. IVIG treatment also decreased the elevation of anti-MB antibody level, as well as the deposition of IgG and C3. We next evaluated the effect of IVIG in adoptive EAM mice made by an intravenous injection of lymph node cells previously stimulated with MB. Adoptive EAM mice showed similar lesions in skeletal muscle as EAM mice and IVIG inhibited the lesion development. In vitro experiments demonstrated that IVIG inhibited complement-mediated lysis of human erythrocytes sensitized with anti-human erythrocyte antibodies. The binding of C1q, C4 and C3 to the same cells was also inhibited by IVIG. Taken together these findings suggest that IVIG prevents the development of myositis in EAM and adoptive EAM models by several mechanisms, such as reducing anti-myosin antibody and by blocking complement activation. Our present findings might account for the clinical efficacy of IVIG in PM and DM patients.
Wada
J
J
Drug Discovery Laboratories, Pharmaceutical Research Division, Welfide Corporation, Hirakata, Osaka, Japan. junko@welfide.co.jp
Shintani
N
N
Kikutani
K
K
Nakae
T
T
Yamauchi
T
T
Takechi
K
K
D019264:Adoptive Transfer; D000818:Animals; D001323:Autoantibodies / Q000097:blood; D003167:Complement Activation; D003176:Complement C3 / Q000378:metabolism*; D007074:Immunoglobulin G / Q000378:metabolism*; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D018482:Muscle, Skeletal / Q000473:pathology; D009218:Myosins / Q000276:immunology*; D009220:Myositis / Q000628:therapy*; D020721:Nervous System Autoimmune Disease, Experimental / Q000628:therapy*; D013601:T-Lymphocytes / Q000637:transplantation
D001323:Autoantibodies; D003176:Complement C3; D007074:Immunoglobulin G; D016756:Immunoglobulins, Intravenous; D009218:Myosins