Evolução clinica da encefalomielite experimental auto-imune em camundongos geneticamente modificados (knockout) para a oxido nitrico sintase induzida

AUTOR(ES)
DATA DE PUBLICAÇÃO

2004

RESUMO

Multiple sclerosis (MS) is the most common human demyelinating disease of the central nervous system (CNS). Based on the fact that it shares similarities in relation to course of the disease and histology, Experimental auto-immune encephalomyelitis (EAE) has been used extensively as an animal model for MS. EAE is a Thl cell-mediated autoimmune disease induced by immumzation with myelin components or by adoptive transfer of autoreactive T cells. This leads to a characteristic relapsing and remitting paralytic disease in mice model of EAE. The Thl cells, characteristically produce IL2, IFNy, TNFa and lymphotoxin (TNFp), which participate in the inflammatory reactions. Histological examination of the CNS generally reveals the presence of both a rich inflammatory mononuclear cell infiltrate and demyelination resulting from bystander activation of resident microglia and recruited, infiltrating monocytes. Antigen-presenting cells generate the reactive oxygen and nitrogen species that may damage different cell types. Despite knowledge about the induction and regulation of NO production, the role of NO in tissue in demyelination is highly controversial. While many investigators have concluded that NO is involved in the pathogenesis of EAE, others have reported quite oppositing protective effects. The present study was conducted to investigate the specific role of NO induced by iNOS in the regulation of EAE in iNOS knockout C57BL/6 and wild-type mice. A less severe form of the disease than did the wild type control mice was observed in the iNOS -/- mice. Although the levels of TNFa diminished in the periphery for both groups, an increase in the number of TNFa positive cells was detected in the central nervous system during the acute phase of EAE induced in the WT mice, whereas no production of TNFa was detected in the KO mice. These findings suggest that NO and TNFa contribute to the pathogenesis during acute EAE

ASSUNTO(S)

esclerose multipla resposta imune macrofagos

ACESSO AO ARTIGO

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