[Thalidomide as immunomodulatory drug: pharmacological actions and its indications].
Thalidomide was developed in the 1950s as a sedative drug and withdrawn in 1961 because of its teratogenic effects, but has been rediscovered as an immuno-modulatory drug.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.
Department of Pediatrics, Hiroshima City-Hospital, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Japan.
Kozo
K
Yasui
D001528:Behcet Syndrome / Q000188:drug therapy; D002648:Child; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D008297:Male; D016328:NF-kappa B / Q000502:physiology; D012507:Sarcoidosis / Q000188:drug therapy; D013792:Thalidomide / Q000494:pharmacology* / Q000627:therapeutic use
D007155:Immunologic Factors; D016328:NF-kappa B; D013792:Thalidomide