Tumor necrosis factor-alpha-converting enzyme is expressed in the inflamed peripheral nervous system.

Tumor necrosis factor-alpha (TNF-alpha) is considered to play a critical role in the pathogenesis of immune-mediated inflammatory demyelinating disorders of the peripheral nervous system (PNS). Processing of membrane-bound inactive pro-TNF-alpha into the active soluble cytokine is mediated by a sheddase, the so-called TNF-alpha-converting enzyme (TACE), a member of the A Disintegrin and Metalloproteinase (ADAM) family. We explored the expression of TACE (ADAM-17) in sciatic nerves from Lewis rats with experimental autoimmune neuritis (EAN), an animal model of the Guillain-Barré syndrome (GBS), an immune-mediated polyradiculoneuropathy. To extend our study to human disease, sural nerve biopsies from GBS patients were investigated by immunohistochemistry. In EAN, T lymphocytes could be defined as the cellular source of ADAM-17 with peak expression levels at maximum clinical disease severity. Similarly, in human sural nerves, ADAM-17-expressing T cells could be localized primarily within the epi- and perineurium, whereas in control sections from patients with non-inflammatory neuropathies, no expression could be depicted. Our findings indicate that ADAM-17 is upregulated during EAN and expressed in nerves of GBS patients and thus may contribute to the pathogenesis of inflammatory demyelination of the PNS.