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.

Host immune responses induced by specific Mycobacterium leprae antigens in an overnight whole-blood assay correlate with the diagnosis of paucibacillary leprosy patients in China

“…The presence of the neutrophil chemoattractant IL-8 in leprosy lesions, which do not contain neutrophils, strongly suggests a role of IL-8 in monocyte and lymphocyte recruitment in leprosy lesions [26]. TNF-induced IL-8 can be produced by Schwann cells (SCs), indicating involvement of this factor in leprosy-associated nerve damage [27].…”

Innate Immune Responses in Leprosy

“…The pathogenesis of nerve destruction varies accordingly the clinical form of the disease ( 25 ); although the understanding of mechanisms associated with nerve damage and regeneration in leprosy-associated neuropathy are not fully understood ( 26 ). In the pure neural leprosy, bacilli are rarely detected despite the clinical neurological impairment.…”

“…Schwann cells in skin lesions from leprosy patients express TLR2 ( 112 , 113 ). In nerve biopsies from patients with neuritis, it was identified TNF, TNF receptors and TNF-converting enzyme in Schwann cells ( 26 ). It was speculated that M. leprae ligands induce Schwann cell death by a pathway that involves both TLR2 and TNF.…”

Modulation of Interleukin-8 Production by Vitamin D Supplementation in Indonesian Patients with Diabetic Polyneuropathy: A Randomized Clinical Trial

“…Tumor necrosis factor induces IL-6 and IL-8 production by schwann cells. 21 Myelin damage affects nerve conduction, resulting in prolonged DL and slowing NCV. 22 The most common compression neuropathies in DM patients are carpal tunnel syndrome (30%) and ulnar neuropathy (2.1%).…”