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.