title: Management of erythema nodosum leprosum by thalidomide: thalidomide analogues inhibit M. leprae-induced TNFalpha production in vitro.
abstract: 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 TNFalpha mRNA expression and protein production by stimulated monocytes and activated T lymphocytes. Patients treated with THAL experienced a reduction in serum TNFalpha 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 TNFalpha and IL-12 mRNA in vitro. THAL also reduced monocyte apoptosis in the cultures. The present data further support thalidomide's effects on TNFa synthesis and the growing need to search for new specific TNFalpha inhibitors (non-teratogenic compounds) that might be potentially used in clinical disorders such as leprosy.
authors.affiliation: Leprosy Laboratory, Oswaldo Cruz Institute, FIOCRUZ, Manguinhos, Rio de Janeiro, Brazil. esampaio@gene.dbbm.fiocruz.br
authors.forename: E P
authors.initials: EP
authors.lastname: Sampaio
authors.forename: M O
authors.initials: MO
authors.lastname: Hernandez
authors.forename: D S
authors.initials: DS
authors.lastname: Carvalho
authors.forename: E N
authors.initials: EN
authors.lastname: Sarno
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000235:genetics; D004893:Erythema Nodosum / Q000188:drug therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D018664:Interleukin-12 / Q000037:antagonists & inhibitors; D009000:Monocytes / Q000187:drug effects; D009166:Mycobacterium leprae / Q000187:drug effects / Q000235:genetics; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D013792:Thalidomide / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000235:genetics
chemical_list: D016207:Cytokines; D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D013792:Thalidomide