The classification of thalidomide as an orphan drug with anti-inflammatory actions has led to its off-label use in conditions refractory to other medications. Although the observed clinical effects of thalidomide suggest it to have immunomodulatory capabilities, the mechanism of action is unclear. Here we review both the positive and negative studies of thalidomide at the bench in order to improve our understanding of the possible mechanisms of this drug in treating a variety of diseases at the bedside. Studies on the effects of thalidomide on the innate and adaptive immune system as well as tumorigenesis and angiogenesis are discussed.
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