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 m any autoimmune and systemic inflammatory diseases including polymyositis (P M) 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 ra bbit myosin B (MB) fraction. In this model, the plasma level of anti-MB ant ibody was elevated, and mouse IgG and complement C3 were deposited in the m uscle fibres. Administration of IVIG dose-dependently reduced the incidence s of necrotic and inflammatory changes in the skeletal muscle. IVIG treatme nt also decreased the elevation of anti-MB antibody level, as well as the d eposition of IgG and C3. We next evaluated the effect of IVIG in adoptive E AM mice made by an intravenous injection of lymph node cells previously sti mulated with MB. Adoptive EAM mice showed similar lesions in skeletal muscl e as EAM mice and IVIG inhibited the lesion development. In vitro experimen ts demonstrated that IVIG inhibited complement-mediated lysis of human eryt hrocytes 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 E AM and adoptive EAM models by several mechanisms, such as reducing anti-myo sin antibody and by blocking complement activation. Our present findings mi ght account for the clinical efficacy of IVIG in PM and DM patients.