Mechanisms of Action of Intravenous Immunoglobulin in Inflammatory Muscle Disease

Intravenous immunoglobulin (IVIG) is a unique immune-modulating therapy that has a wide range of effects on the immune system at multiple levels. This allows it to be used successfully in a variety of immune-mediated, systemic, and neurological disorders, including the inflammatory myopathies. It is likely that the specific action of IVIG varies depending on the underlying pathogenesis of a given disease. In dermatomyositis (DM), IVIG has been shown to diminish the activity of complement and deposition of membrane attack complex on capillaries and muscle fibers, the expression of adhesion molecules, and cytokine production. IVIG also appears to modify gene expression in the muscle of DM patients. The mechanism by which IVIG affects muscle in polymyositis and inclusion body myositis has not been well-studied. However, it may work via suppression of T-cell activation (including cytotoxic T cells) and migration into muscle tissue and alterations in cytokine production. IVIG generally yields the greatest therapeutic benefit in DM and is often of marginal utility in inclusion body myositis. It is generally considered as second-line or adjunctive therapy in the inflammatory myopathies.