ReviewsThalidomide: current and potential clinical applications
Section snippets
Immunomodulatory mechanisms of action
Thalidomide’s effects on immune function are incompletely understood; however, anti-inflammatory and immunomodulatory activities have been described (Table 1).
Thalidomide reduces phagocytosis by polymorphonuclear leukocytes. This may explain its action in inflammatory processes that involve predominantly mononuclear cell accumulation, such as chronic cutaneous lupus erythematosus (3). Thalidomide inhibits monocyte phagocytosis without any sign of cytotoxicity in monocytes or polymorphonuclear
Anti-angiogenesis activity
D’Amato and colleagues (19) first demonstrated thalidomide’s anti-angiogenic activity, which has been postulated to have clinical therapeutic applications in solid tumors and other diseases. In a rabbit model of corneal neovascularization induced by angiogenic protein basic fibroblast growth factor, thalidomide reduced the area of vascularization compared with controls. More recently, experiments have shown that a combination of thalidomide and sulindac, a nonsteroidal anti-inflammatory drug
Erythema nodosum leprosum
The rehabilitation of thalidomide began in 1965 when Sheskin (21) reported that patients with acute inflammatory lesions associated with leprosy experienced astonishingly rapid improvement after taking thalidomide for sedation. Subsequent studies, including a controlled trial conducted under the auspices of the World Health Organization, confirmed the drug’s effectiveness (22). The current approved dosage is 100 to 300 mg per day for therapy of an acute episode, with a maximum dose of 400 mg
Teratogenicity
Phocomelia is the best known congenital abnormality associated with thalidomide, but duodenal stenosis, esophageal fistulae, neural tube abnormalities, micro-ophthalmia, deformities of the ears, and mid-line hemangiomas have also been reported 85, 86. To minimize the risk of teratogenicity, Celgene Corporation (Warren, New Jersey) has developed a program (System for Thalidomide Education and Prescribing Safety [STEPS]) for controlling and monitoring access to thalidomide (87). Physicians who
Conclusion
Thalidomide may have other therapeutic applications, including the treatment of bacterial meningitis and sepsis, both of which are TNF-α related 93, 94, 95. In rabbit models of bacterial meningitis, thalidomide reduced levels of TNF-α (93) and improved survival (95). Similar results were found in a rat model of septic shock (95). Another emerging potential therapeutic target is cancer cachexia. Although the role of TNF-α in cachexia in cancer patients remains to be elucidated (96), the findings
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