02164nas a2200253   4500000000100000008004100001260001300042653001200055653001800067653002300085653002600108653001600134653000900150653002500159653001600184100001400200700001600214245010200230856007200332300001000404490000700414520147500421022001401896       2005                            d  c2005 Jan10aAnimals10aCell Survival10aLeprostatic Agents10aMacrophage Activation10aMacrophages10aMice10aMycobacterium leprae10aThalidomide1 aTadesse A1 aShannon E J00aEffects of thalidomide on intracellular Mycobacterium leprae in normal and activated macrophages.  uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC540221/pdf/0255-04.pdf  a130-40 v123 a<p>Thalidomide is an effective drug for the treatment of erythema nodosum leprosum (ENL). ENL is an inflammatory reaction that may occur in multibacillary leprosy patients. Its cause(s) as well as the mechanism of thalidomide in arresting this condition are not fully understood. It has been suggested that ENL is an immune complex-mediated hypersensitivity precipitated by the release of Mycobacterium leprae from macrophages. The released antigen may complex with precipitating antibodies, initiating complement fixation and the production of inflammatory cytokines like tumor necrosis factor alpha (TNF-alpha). Thalidomide has been shown in vitro to reduce antigen- or mitogen-activated macrophage production of TNF-alpha. We investigated if thalidomide could also influence the viability of intracellular M. leprae. Mouse peritoneal macrophages were infected with M. leprae, activated with gamma interferon and endotoxin, or nonactivated, and treated with thalidomide. Intracellular bacilli were recovered, and metabolic activity was assessed by a radiorespirometric procedure. Thalidomide did not possess antimicrobial action against M. leprae in normal and activated host macrophages. This suggests that thalidomide does not retard the release of mycobacterial antigens, a possible prelude or precipitating factor for ENL. A distinct sequence of events explaining the mechanism of action for thalidomide's successful treatment of ENL has yet to be established.</p>  a1071-412X