Abstract

Interferons (IFNs) are potent extracellular protein mediators of host defense and homeostasis. Type I IFNs have well-established direct antiviral, antiproliferative, and immunomodulatory properties. The worldwide, increasing and long-term use of INFalpha, particularly for the treatment of chronic hepatitis C virus infection, has drawn attention to the development or exacerbation of numerous autoimmune phenomena, including a spectrum of myopathies. Management entailed withdrawal of INFalpha with supportive, immunomodulatory, and symptomatic treatment as deemed clinically indicated. However, IFNbeta therapy for relapsing-remitting multiple sclerosis rarely triggered clinically manifest autoimmunity. The mechanisms through which type I IFNs induce autoimmunity are incompletely understood, and they likely vary depending on the inherent differences in the pathogenesis of the immune disorder on a background of patient genetic susceptibility. INFalpha therapy had unpredictable effects on hepatitis C-associated myopathies. The immunomodulating effects of IFNbeta therapy showed no clinically significant benefit during prospective controlled treatment trials of inclusion body myositis. Type I IFNs have the theoretical potential to either cause or treat autoimmune muscular disorders by altering the complicated and delicate balances within immune system networks. Muscle Nerve, 2009.