Neutralizing interferon alpha as a therapeutic approach to autoimmune diseases.
Therapeutic antibodies directed against tumor necrosis factor alpha (TNF-alpha) for the treatment of rheumatoid arthritis, and against the human EGF receptor-2 (HER2) receptor for the treatment of breast cancer have provided significant clinical benefit for the patients. The success of these antibodies has also provided strong support for the possibility that increased activity of cytokines or growth factors is causally implicated in a variety of human diseases. Interferon alpha (IFN-alpha) is induced by viruses (linked by epidemiological studies to autoimmune diseases), has significant direct effects on both epithelial cells and the immune system, and then can be further induced by the autoantibodies and apoptotic cells generated by the actions of IFN-alpha. The direct and deleterious impact on target tissues, the ability to induce an autoimmune response, and the potential for a self-sustaining cycle of induction and damage suggests that IFN-alpha could be a pivotal factor in the development of autoimmune diseases. This review will evaluate the rationale for, possible approaches to, and safety concerns associated with, targeting interferon alpha (IFN-alpha) as a therapeutic strategy for the treatment of autoimmune diseases. While the approach may be applicable to several autoimmune diseases, there will be an emphasis on systemic lupus erythematosus and insulin dependent diabetes mellitus.
Stewart
Timothy A
TA
Department of Molecular Biology, Genentech Inc., 1 DNA Way, South San Francisco, San Francisco, CA, USA. tas@sulispharma.com
D000818:Animals; D001327:Autoimmune Diseases / Q000628:therapy*; D001943:Breast Neoplasms / Q000628:therapy; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology / Q000628:therapy; D004195:Disease Models, Animal; D006801:Humans; D016898:Interferon-alpha / Q000378:metabolism / Q000627:therapeutic use*; D008180:Lupus Erythematosus, Systemic / Q000503:physiopathology / Q000628:therapy; D008954:Models, Biological; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D012306:Risk
D016898:Interferon-alpha; D018719:Erb-b2 Receptor Tyrosine Kinases