title: Inflammatory Cytokines Are Involved in Focal Demyelination in Leprosy Neuritis.
abstract: Mycobacterium leprae (ML) infection causes nerve damage that often leads to permanent loss of cutaneous sensitivity and limb deformities, but understanding of the pathogenesis of leprous neuropathy that would lead to more effective treatments is incomplete. We studied reactional leprosy patients with (n = 9) and without (n = 8) acute neuritis. Nerve conduction studies over the course of the reactional episode showed the findings of demyelination in all patients with neuritis. Evaluation of patient sera revealed no correlation of the presence of antibodies against gangliosides and the clinical demyelination. In nerve biopsies of 3 patients with neuritis, we identified tumor necrosis factor (TNF), TNF receptors, and TNF-converting enzyme in Schwann cells (SCs) using immunofluorescence. To elucidate immunopathogenetic mechanisms, we performed experiments using a human SC line. ML induced transmembrane TNF and TNF receptor 1 expression in the SCs; TNF also induced interleukin (IL)- 6 and IL-8 production by the SCs; and ML induced IL-23 secretion, indicating involvement of this previously unrecognized factor in leprosy nerve damage. These data suggest that ML may contribute to TNF-mediated inflammation and focal demyelination by rendering SCs more sensitive to TNF within the nerves of patients with leprous neuropathy.
authors.affiliation: From the Leprosy Laboratory, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, Brazil (PRA, MRJ, ACCdS, SGA, RV, RBdSP, RBP, ROP, ENS); and Pedro Ernesto University Hospital, Rio De Janeiro State University, Rio de Janeiro, Brazil (MRJ, PSM).
authors.forename: Priscila Ribeiro
authors.initials: PR
authors.lastname: Andrade
authors.affiliation: From the Leprosy Laboratory, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, Brazil (PRA, MRJ, ACCdS, SGA, RV, RBdSP, RBP, ROP, ENS); and Pedro Ernesto University Hospital, Rio De Janeiro State University, Rio de Janeiro, Brazil (MRJ, PSM).
authors.forename: Márcia Rodrigues
authors.initials: MR
authors.lastname: Jardim
authors.affiliation: From the Leprosy Laboratory, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, Brazil (PRA, MRJ, ACCdS, SGA, RV, RBdSP, RBP, ROP, ENS); and Pedro Ernesto University Hospital, Rio De Janeiro State University, Rio de Janeiro, Brazil (MRJ, PSM).
authors.forename: Ana Caroline Costa
authors.initials: AC
authors.lastname: da Silva
authors.affiliation: From the Leprosy Laboratory, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, Brazil (PRA, MRJ, ACCdS, SGA, RV, RBdSP, RBP, ROP, ENS); and Pedro Ernesto University Hospital, Rio De Janeiro State University, Rio de Janeiro, Brazil (MRJ, PSM).
authors.forename: Paula Saraiva
authors.initials: PS
authors.lastname: Manhaes
authors.affiliation: From the Leprosy Laboratory, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, Brazil (PRA, MRJ, ACCdS, SGA, RV, RBdSP, RBP, ROP, ENS); and Pedro Ernesto University Hospital, Rio De Janeiro State University, Rio de Janeiro, Brazil (MRJ, PSM).
authors.forename: Sérgio Luiz Gomes
authors.initials: SL
authors.lastname: Antunes
authors.affiliation: From the Leprosy Laboratory, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, Brazil (PRA, MRJ, ACCdS, SGA, RV, RBdSP, RBP, ROP, ENS); and Pedro Ernesto University Hospital, Rio De Janeiro State University, Rio de Janeiro, Brazil (MRJ, PSM).
authors.forename: Robson
authors.initials: R
authors.lastname: Vital
authors.affiliation: From the Leprosy Laboratory, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, Brazil (PRA, MRJ, ACCdS, SGA, RV, RBdSP, RBP, ROP, ENS); and Pedro Ernesto University Hospital, Rio De Janeiro State University, Rio de Janeiro, Brazil (MRJ, PSM).
authors.forename: Rhana Berto da Silva
authors.initials: RB
authors.lastname: Prata
authors.affiliation: From the Leprosy Laboratory, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, Brazil (PRA, MRJ, ACCdS, SGA, RV, RBdSP, RBP, ROP, ENS); and Pedro Ernesto University Hospital, Rio De Janeiro State University, Rio de Janeiro, Brazil (MRJ, PSM).
authors.forename: Rafael Braga
authors.initials: RB
authors.lastname: Petito
authors.affiliation: From the Leprosy Laboratory, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, Brazil (PRA, MRJ, ACCdS, SGA, RV, RBdSP, RBP, ROP, ENS); and Pedro Ernesto University Hospital, Rio De Janeiro State University, Rio de Janeiro, Brazil (MRJ, PSM).
authors.forename: Roberta Olmo
authors.initials: RO
authors.lastname: Pinheiro
authors.affiliation: From the Leprosy Laboratory, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, Brazil (PRA, MRJ, ACCdS, SGA, RV, RBdSP, RBP, ROP, ENS); and Pedro Ernesto University Hospital, Rio De Janeiro State University, Rio de Janeiro, Brazil (MRJ, PSM). euzenir@uol.com.br.
authors.forename: Euzenir Nunes
authors.initials: EN
authors.lastname: Sarno
mesh_terms: D000328:Adult; D000368:Aged; D002461:Cell Line, Transformed; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D003711:Demyelinating Diseases / Q000150:complications* / Q000378:metabolism* / Q000473:pathology; D004558:Electric Stimulation; D005260:Female; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007918:Leprosy / Q000150:complications*; D008297:Male; D008875:Middle Aged; D009166:Mycobacterium leprae / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009431:Neural Conduction / Q000502:physiology; D009443:Neuritis / Q000150:complications*; D009460:Neurologic Examination; D011930:Reaction Time; D012583:Schwann Cells / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D055815:Young Adult
chemical_list: D016207:Cytokines; D009419:Nerve Tissue Proteins; D014409:Tumor Necrosis Factor-alpha
keywords: Demyelination; IL-23; Leprosy; Mycobacterium leprae; Neuropathy; Schwann cell; Tumor necrosis factor