Interferon alpha and its contribution to autoimmunity.
It is now well accepted that interferon (IFN)alpha plays a critical role in the pathogenesis and perpetuation of specific autoimmune diseases, including systemic lupus erythematosus (SLE), autoimmune thyroid disease and type 1 diabetes. IFNalpha-based treatments are widely used for the treatment of chronic viral infections, particularly chronic hepatitis C virus infection; however, several case reports have emerged describing autoimmune conditions that have developed during IFNalpha therapy. The data support the pathogenic potential of IFNalpha in autoimmunity, although it is clear that genetic and environmental factors are also key to the development of autoimmune conditions. Several points of interaction between IFNalpha and immune effector cells have been experimentally defined, the functional consequences of many of which remain poorly understood. This review describes the most recent data in support of an important role for IFNalpha in autoimmunity, particularly SLE, and the potential mechanisms by which IFNalpha contributes to immune dysfunction. Future approaches to IFNalpha modulation as a therapeutic strategy for use in the treatment of autoimmune diseases are also discussed.
Selmi
Carlo
C
Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis School of Medicine, Genome and Biomedical Sciences Facility, 451 E Health Sciences Drive, Suite 6510, Davis, CA 95616, USA.
Lleo
Ana
A
Zuin
Massimo
M
Podda
Mauro
M
Rossaro
Lorenzo
L
Gershwin
M Eric
ME
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000998:Antiviral Agents / Q000009:adverse effects*; D001327:Autoimmune Diseases / Q000097:blood / Q000188:drug therapy / Q000209:etiology*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000209:etiology; D006801:Humans; D007155:Immunologic Factors / Q000009:adverse effects*; D016898:Interferon-alpha / Q000009:adverse effects* / Q000096:biosynthesis / Q000097:blood / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000209:etiology; D012859:Sjogren's Syndrome / Q000097:blood / Q000209:etiology; D013967:Thyroiditis, Autoimmune / Q000209:etiology
D000911:Antibodies, Monoclonal; D000998:Antiviral Agents; D007155:Immunologic Factors; D016898:Interferon-alpha