Neutralizing interferon alpha as a therapeutic approach to autoimmune diseases

被引:74
作者
Stewart, TA [1 ]
机构
[1] Genentech Inc, Dept Mol Biol, San Francisco, CA 94080 USA
关键词
IFN-alpha; SLE; IDDM; therapy; autoimmunity;
D O I
10.1016/S1359-6101(02)00088-6
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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. (C) 2003 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:139 / 154
页数:16
相关论文
共 180 条
[31]   Control of islet intercellular adhesion molecule-1 expression by interferon-alpha and hypoxia [J].
Chakrabarti, D ;
Huang, XJ ;
Beck, J ;
Henrich, J ;
McFarland, N ;
James, RFL ;
Stewart, TA .
DIABETES, 1996, 45 (10) :1336-1343
[32]  
Chakrabarti D, 1996, J IMMUNOL, V157, P522
[33]   Treatment of lupus with corticosteroids [J].
Chatham, WW ;
Kimberly, RP .
LUPUS, 2001, 10 (03) :140-147
[34]   INDUCTION BY VASOACTIVE-INTESTINAL-PEPTIDE OF INTERFERON-ALPHA/BETA SYNTHESIS IN GLIAL-CELLS BUT NOT IN NEURONS [J].
CHELBIALIX, MK ;
BROUARD, A ;
BOISSARD, C ;
PELAPRAT, D ;
ROSTENE, W ;
THANG, MN .
JOURNAL OF CELLULAR PHYSIOLOGY, 1994, 158 (01) :47-54
[35]   Increased levels of antiviral MxA protein in peripheral blood of patients with a chronic disease of unknown etiology [J].
Chieux, V ;
Chehadeh, W ;
Hautecoeur, P ;
Harvey, J ;
Wattré, P ;
Hober, D .
JOURNAL OF MEDICAL VIROLOGY, 2001, 65 (02) :301-308
[36]   Characterization and humanization of a monoclonal antibody that neutralizes human leukocyte interferon: A candidate therapeutic for IDDM and SLE [J].
Chuntharapai, A ;
Lai, J ;
Huang, XJ ;
Gibbs, V ;
Kim, KJ ;
Presta, LG ;
Stewart, TA .
CYTOKINE, 2001, 15 (05) :250-260
[37]   The double-stranded RNA-dependent protein kinase PKR: Structure and function [J].
Clemens, MJ ;
Elia, A .
JOURNAL OF INTERFERON AND CYTOKINE RESEARCH, 1997, 17 (09) :503-524
[38]  
CONLON KC, 1990, CANCER, V65, P2237, DOI 10.1002/1097-0142(19900515)65:10<2237::AID-CNCR2820651013>3.0.CO
[39]  
2-5
[40]   Severe Raynaud's syndrome associated with interferon therapy - A case history [J].
Creutzig, A ;
Freund, M .
ANGIOLOGY, 1996, 47 (02) :185-187