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: Priscila Ribeiro Andrade, Márcia Rodrigues Jardim, Ana Caroline Costa da Silva, Paula Saraiva Manhaes, Sérgio Luiz Gomes Antunes, Robson Vital, Rhana Berto da Silva Prata, Rafael Braga Petito, Roberta Olmo Pinheiro, Euzenir Nunes Sarno
• Journal: Journal of neuropathology and experimental neurology (J Neuropathol Exp Neurol) Vol. 75 Issue 3 Pg. 272-83 (Mar 2016) ISSN: 1554-6578 [Electronic] England
• PMID: 26888306 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2016 American Association of Neuropathologists, Inc. All rights reserved.

Chemical References

• Cytokines
• Nerve Tissue Proteins
• Tumor Necrosis Factor-alpha

Topics

• Adult
• Aged
• Cell Line, Transformed
• Cytokines (genetics, metabolism)
• Demyelinating Diseases (complications, metabolism, pathology)
• Electric Stimulation
• Female
• Gene Expression (drug effects, physiology)
• Humans
• Leprosy (complications)
• Male
• Middle Aged
• Mycobacterium leprae (physiology)
• Nerve Tissue Proteins (metabolism)
• Neural Conduction (physiology)
• Neuritis (complications)
• Neurologic Examination
• Reaction Time
• Schwann Cells (drug effects, metabolism)
• Tumor Necrosis Factor-alpha (pharmacology)
• Young Adult