TUMOR-NECROSIS-FACTOR-ALPHA IN IMMUNE-MEDIATED DEMYELINATION AND WALLERIAN DEGENERATION OF THE RAT PERIPHERAL NERVOUS-SYSTEM

This study reports on the immunocytochemical localization of tumor necrosis factor-alpha (TNFalpha) in immune-mediated demyelination and Wallerian degeneration of the rat peripheral nervous system (PNS) using teased nerve fiber preparations. In experimental autoimmune neuritis induced by active immunization (EAN) or by adoptive transfer of autoreactive T cells (AT-EAN), macrophages passing blood vessels as well as macrophages adherent to nerve fibers were TNFalpha-positive. Large post-phagocytic macrophages at later stages of demyelination were TNFalpha-negative. Intraperitoneal application of an anti-TNFalpha antibody to EAN rats significantly reduced the degree of inflammatory demyelination, suggesting a pathogenic role for TNFalpha. After nerve transection only macrophages located within degenerating nerve fibers were TNFalpha-positive, while those entering and leaving nerves were negative. TNFalpha produced by macrophages seems to be involved in immune-mediated demyelination and non-immune myelin degradation after axotomy. While interferon-gamma (IFNgamma) is present in EAN nerves and may act as a local stimulus for TNF expression, the nature of this signal in Wallerian degeneration in the absence of IFNgamma is unknown.