Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/17952
Title: Inflammatory Cytokines Are Involved in Focal Demyelination in Leprosy Neuritis
Authors: Andrade, Priscila Ribeiro
Jardim, Márcia Rodrigues
Silva, Ana Caroline Costa da
Manhaes, Paula Saraiva
Antunes, Sérgio Luiz Gomes
Vital, Robson
Prata, Rhana Berto da Silva
Petito, Rafael Braga
Pinheiro, Roberta Olmo
Sarno, Euzenir Nunes
Affilliation: Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil / Universidade do Estado do Rio de Janeiro. Hospital Universitário Pedro Ernesto. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.
Universidade do Estado do Rio de Janeiro. Hospital Universitário Pedro Ernesto. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.
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.
Keywords: Demyelination
IL-23
Leprosy
Mycobacterium leprae
Neuropathy
Schwann cells
Tumor necrosis factor
keywords: Mycobacterium leprae
Fator de Necrose Tumoral alfa 
Neuropatia
Células de Schwann 
IL-23
Hanseníase
Issue Date: 2016
Publisher: Oxford University Press
Citation: ANDRADE, Priscila Ribeiro; et al. Inflammatory Cytokines Are Involved in Focal Demyelination in Leprosy Neuritis. J. Neuropathol Exp Neurol, v.75, n.3, p.272-283, Mar. 2016.
DOI: 10.1093/jnen/nlv027
ISSN: 0022-3069
Copyright: restricted access
Appears in Collections:IOC - Artigos de Periódicos

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