The involvement of inducible nitric oxide synthase (iNOS), which plays various roles in the progression of autoimmune diseases, was studied in iNOS knockout (KO) mice and wild-type (WT) controls with respect to experimental autoimmune encephalomyelitis (EAE). The iNOS (KO) mice presented a less severe form of the disease than the WT control mice. Although the levels of TNFα decreased in the periphery in both groups, an increase in the number of TNFα-positive cells was detected in the central nervous system during the acute phase of EAE in the WT mice, but not in the KO mice. These findings suggest that NO and TNFα contribute to the pathogenesis of acute EAE.

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Background: Inducible nitric oxide synthase (iNOS) and tumor necrosis factor-α (TNF-α) are pleiotropic molecules with widespread action in autoimmune diseases. Objective: This study characterizes the distribution of iNOS and TNF-α in the spinal nerve roots, dorsal root ganglia and sciatic nerve of Lewis rats during experimental autoimmune neuritis (EAN). Methods: Macrophages and neutrophils were identified by immunofluorescence as cellular sources of iNOS and TNF-α at various stages of EAN induced by synthetic peptide 26. Results: As the disease progressed, iNOS- and TNF-α-bearing cells gradually infiltrated the cauda equina, dorsal root ganglia, Th12–L3 spinal roots, and the sciatic nerve. A severer EAN profile developed when more iNOS- and TNF-α-bearing cells were present, and the recovery from EAN was related to the disappearance of these cells and the regeneration of nerve fibers. Conclusions: This is the first report to show iNOS- and TNF-α-immunoreactive cells in dorsal root ganglia during EAN, suggesting an underlying pathology for the neuropathic pain behavior in EAN. Our results suggest that the cells bearing iNOS and TNF-α in the different parts of the peripheral nervous system are involved in the development of the clinical signs observed at each stage of EAN.