Yasui Kozo
Department of Pediatrics, Hiroshima City-Hospital, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Japan.
Nihon Rinsho Meneki Gakkai Kaishi. 2010;33(5):229-33. doi: 10.2177/jsci.33.229.
Thalidomide was developed in the 1950s as a sedative drug and withdrawn in 1961 because of its teratogenic effects, but has been rediscovered as an immuno-modulatory drug. It has been administered successfully for the treatment of erythema nodosum leprosum, aphthous ulceration and cachexia in HIV disease, inflammatory bowel diseases, and several malignant diseases. The suppressive effect of thalidomide on the activation of the nuclear transcription factor NF-κB may explain these effects of thalidomide. NF-κB is retained in the cytoplasm with IκBα, and is activated by a wide variety of inflammatory stimuli including TNF, IL-1 and endotoxin followed by its translocation to the nucleus. Angiogenesis and organogenesis also require gene transcription and signal translocation. The findings shed new light on the anti-inflammatory properties of thalidomide and suggest pharmaceutical actions of thalidomide via interference of transcription mechanism. I reviewed the effects of thalidomide on auto-inflammatory diseases of childhood.
沙利度胺于20世纪50年代作为一种镇静药物被研发出来，并于1961年因其致畸作用而被撤市，但后来又被重新发现具有免疫调节作用。它已成功用于治疗麻风结节性红斑、阿弗他溃疡、HIV疾病中的恶病质、炎症性肠病以及几种恶性疾病。沙利度胺对核转录因子NF-κB激活的抑制作用可能解释了沙利度胺的这些作用。NF-κB与IκBα一起保留在细胞质中，并被包括TNF、IL-1和内毒素在内的多种炎症刺激激活，随后转移到细胞核。血管生成和器官发生也需要基因转录和信号转位。这些发现为沙利度胺的抗炎特性提供了新的线索，并提示沙利度胺通过干扰转录机制发挥药理作用。我回顾了沙利度胺对儿童自身炎症性疾病的影响。
