Tumor necrosis factor-α in peripheral nerve lesions

Abstract

Immunocytochemical expression of tumor necrosis factor-alpha (TNF-alpha) was examined in nerve biopsy samples of patients with various disorders, focusing on nerve injury. TNF-alpha was mainly associated with phagocytosing macrophages in acute axonal injury, but the staining was more frequently seen in sections from patients with vasculitis than with metabolic neuropathy. Ramifield macrophages outside nerve fibers were also positive for TNF-alpha in the acute stage of vasculitis. In active demyelinating lesions from patients with chronic inflammatory demyelinating neuropathy (CIDP), macrophages outside nerve fibers showed weak staining with TNF-alpha, but the cells adhering to myelinated nerve fibers showed definite staining. This may be due, in part, to the smouldering course of CIDP, and expression may be up-regulated transiently during the demyelinating process. These results indicate that macrophages, as the effector cells for both axonal injury and active demyelination, express TNF-alpha, buth their activation mechanisms may vary among vasculitis, metabolic axonopathy and inflammatory demyelination.

Is Periventricular Leukomalacia an Axonopathy as Well as an Oligopathy?

“…Among term infants, those who went on to develop cerebral palsy had higher circulating levels of proinflammatory cytokines just days after birth than infants who did not develop cerebral palsy (35,36). Fourth, in nerve biopsies from adults with chronic inflammatory demyelinating neuropathy, immunocytochemical expression of TNF-␣ was most prominent in phagocytosing macrophages in zones of acute axonal injury (37). This is additional support for the axon-damaging capability of proinflammatory cytokines.…”

Expression of three forms of nitric oxide synthase in peripheral nerve regeneration

“…iNOS induction requires activation of macrophages by endotoxins and cytokines (McCall and Vallance, 1992;Nathan, 1992;Morris and Billiar, 1994). Two of them, tumor necrosis factor and interleukin 1, are present in injured nerve, and secreted, at least in part, by macrophages (Nathan, 1987;Creange et al, 1997;Oka et al, 1998). In contrast to constitutive isoforms of NOS, which synthesize small quantities (picomoles) of NO, mediating messenger functions, iNOS synthesizes large quantities (nanomoles) of NO, extensively related with its cytotoxic effects in immune and inflammatory responses Moncada and Higgs, 1993;Kam and Govender, 1994;Schmidt and Walter, 1994;Kerwin et al, 1995).…”

Neurological adverse events associated with anti-tumor necrosis factor alpha treatment

“…Different cells from the CNS can synthesize TNF (mTNF and sTNF), including microglia, astrocytes, and some type of neurons [22][23][24]. On the other hand, macrophages that express TNF-a are also the effector cells producing axonal injury and active demyelination [25,26].…”