Distribution of inducible nitric oxide synthase and tumor necrosis factor-alpha in the peripheral nervous system of Lewis rats during ascending paresis and spontaneous recovery from experimental autoimmune neuritis.

BACKGROUND: Inducible nitric oxide synthase (iNOS) and tumor necrosis factor-alpha (TNF-alpha) are pleiotropic molecules with widespread action in autoimmune diseases. OBJECTIVE: This study characterizes the distribution of iNOS and TNF-alpha 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-alpha at various stages of EAN induced by synthetic peptide 26. RESULTS: As the disease progressed, iNOS- and TNF-alpha-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-alpha-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-alpha-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-alpha in the different parts of the peripheral nervous system are involved in the development of the clinical signs observed at each stage of EAN.

Nitric oxide and TNFalpha effects in experimental autoimmune encephalomyelitis demyelination.

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 TNFalpha decreased in the periphery in both groups, an increase in the number of TNFalpha-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 TNFalpha contribute to the pathogenesis of acute EAE.

The effect of treatment with crotapotin on the evolution of experimental autoimmune neuritis induced in Lewis rats.

Biomedical research in which venom components are being investigated for their potential as novel therapeutic agents has emerged as an interesting option. Crotapotin, which is purified from the venom of the rattlesnake Crotalus durissus terrificus, has been described as an anti-inflammatory agent that acts on the innate arm of the immune response. Here we have demonstrated that intraperitoneal administration of crotapotin significantly reduces the severity of experimental autoimmune neuritis (EAN), an experimental model for Guillain-Barré syndrome. The reduction of the severity of the disease is associated with a reduction in the mononuclear cells infiltrating the sciatic nerve and a significant decrease in the lymphocyte proliferative response to neuritogenic peptide.

Crotapotin induced modification of T lymphocyte proliferative response through interference with PGE2 synthesis.

The immunosuppressive property has been demonstrated for the venom of the Crotalus durissus terrificus. Using a simple, novel method for obtaining crotapotin and phospholipase A2 isoforms from venom, it was possible to demonstrate that the addition of crotapotin to cultures of isolated lymphocytes resulted in a significant inhibition of the cellular proliferative response to Concanavalin A. This reduction in blastogenic response of lymphocytes is accompanied by a significant increase in the production of PGE2 by macrophages. This effect on the innate immune response suggests that this compound may modify the subsequent adaptative immune response.