Stewart Timothy A
Department of Molecular Biology, Genentech Inc., 1 DNA Way, South San Francisco, San Francisco, CA, USA.
Cytokine Growth Factor Rev. 2003 Apr;14(2):139-54. doi: 10.1016/s1359-6101(02)00088-6.
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.
用于治疗类风湿性关节炎的抗肿瘤坏死因子α（TNF-α）治疗性抗体以及用于治疗乳腺癌的抗人表皮生长因子受体2（HER2）受体治疗性抗体已为患者带来了显著的临床益处。这些抗体的成功也有力支持了细胞因子或生长因子活性增加与多种人类疾病存在因果关系的可能性。α干扰素（IFN-α）由病毒诱导产生（流行病学研究将其与自身免疫性疾病联系起来），对上皮细胞和免疫系统均有显著直接作用，随后可被IFN-α作用产生的自身抗体和凋亡细胞进一步诱导。对靶组织的直接有害影响、诱导自身免疫反应的能力以及诱导和损伤的自我维持循环的可能性表明，IFN-α可能是自身免疫性疾病发展的关键因素。本综述将评估将靶向α干扰素（IFN-α）作为治疗自身免疫性疾病的治疗策略的基本原理、可能的方法以及相关安全问题。虽然该方法可能适用于多种自身免疫性疾病，但将重点关注系统性红斑狼疮和胰岛素依赖型糖尿病。
