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 nec rosis factor-alpha (TNFalpha) in immune-mediated demyelination and Wal lerian degeneration of the rat peripheral nervous system (PNS) using t eased nerve fiber preparations. In experimental autoimmune neuritis in duced by active immunization (EAN) or by adoptive transfer of autoreac tive T cells (AT-EAN), macrophages passing blood vessels as well as ma crophages 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 demyelinatio n, suggesting a pathogenic role for TNFalpha. After nerve transection only macrophages located within degenerating nerve fibers were TNFalph a-positive, while those entering and leaving nerves were negative. TNF alpha produced by macrophages seems to be involved in immune-mediated demyelination and non-immune myelin degradation after axotomy. While i nterferon-gamma (IFNgamma) is present in EAN nerves and may act as a l ocal stimulus for TNF expression, the nature of this signal in Walleri an degeneration in the absence of IFNgamma is unknown.