Management of erythema nodosum leprosum by thalidomide: thalidomide analogues inhibit M. leprae-induced TNFα production in vitro

Thalidomide is being successfully used for the treatment of erythema nodosum leprosum (ENL), among other disorders with inflammatory and immunological bases. Although the active molecules responsible for the diverse therapeutic activities of the drug and the sequence of reactions triggered inside the cells remain unclear, it was demonstrated that thalidomide (THAL) inhibits TNFα mRNA expression and protein production by stimulated monocytes and activated T lymphocytes. Patients treated with THAL experienced a reduction in serum TNFα levels and it diminished cytokine gene expression at the lesion site, with a concomitant abrogation of clinical symptoms. It has been reported that thalidomide as well as some its analogues decrease M. leprae-induced TNFα and IL-12 mRNA in vitro. THAL also reduced monocyte apoptosis in the cultures. The present data further support thalidomide’s effects on TNFα synthesis and the growing need to search for new specific TNFα inhibitors (non-teratogenic compounds) that might be potentially used in clinical disorders such as leprosy.