RÉSUMÉ
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.
Sujet(s)
Anti-inflammatoires/usage thérapeutique , Crotalus , Crotoxine/usage thérapeutique , Névrite auto-immune expérimentale/prévention et contrôle , Animaux , Prolifération cellulaire/effets des médicaments et des substances chimiques , Cellules cultivées , Chromatographie en phase liquide à haute performance , Modèles animaux de maladie humaine , Relation dose-réponse (immunologie) , Femelle , Syndrome de Guillain-Barré , Injections péritoneales , Agranulocytes/effets des médicaments et des substances chimiques , Agranulocytes/anatomopathologie , Noeuds lymphatiques/effets des médicaments et des substances chimiques , Noeuds lymphatiques/anatomopathologie , Activation des lymphocytes , Protéines de la myéline/immunologie , Protéines de la myéline/pharmacologie , Névrite auto-immune expérimentale/immunologie , Névrite auto-immune expérimentale/anatomopathologie , Rats , Rats de lignée LEW , Nerf ischiatique/effets des médicaments et des substances chimiques , Nerf ischiatique/anatomopathologie , Lymphocytes T/effets des médicaments et des substances chimiques , Lymphocytes T/immunologieSujet(s)
Traumatismes de la moelle épinière/thérapie , Animaux , Chondroitine ABC lyase/métabolisme , Chondroitine ABC lyase/pharmacologie , Protéoglycanes à chondroïtine sulfate/effets des médicaments et des substances chimiques , Protéoglycanes à chondroïtine sulfate/métabolisme , Électrophysiologie , Inhibiteurs de croissance/pharmacologie , Protéines de la myéline/pharmacologie , Régénération nerveuse/physiologie , Neurones/effets des médicaments et des substances chimiques , Neurones/métabolisme , Neurones/anatomopathologie , Protéines Nogo , Paraplégie/thérapie , Tétraplégie/thérapie , Rats , Traumatismes de la moelle épinière/métabolisme , Traumatismes de la moelle épinière/physiopathologieSujet(s)
Animaux , Rats , Traumatismes de la moelle épinière , Chondroitine ABC lyase , Protéoglycanes à chondroïtine sulfate , Électrophysiologie , Inhibiteurs de croissance , Neurones/effets des médicaments et des substances chimiques , Neurones/métabolisme , Neurones/anatomopathologie , Paraplégie , Protéines de la myéline/pharmacologie , Tétraplégie , Régénération nerveuse/physiologie , Traumatismes de la moelle épinièreRÉSUMÉ
A comprehensive biochemical, immunological, and histological study was undertaken during suppression of experimental autoimmune encephalomyelitis (EAE) induced by antigen-specific inhibition of the immune response. Pretreatment of Wistar rats by intraperitoneal administration of low doses of saline-soluble bovine myelin or myelin basic protein (MBP) but not with ovalbumin suppresses the appearance of the clinical symptoms of EAE induced by sensitization with bovine myelin in complete Freund's adjuvant. Analysis of the central nervous system (CNS) of animals pretreated with MBP or whole myelin shows inhibition of the diminution of MBP and 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNPase) activity observed in the EAE animals or in rats pretreated with ovalbumin. With respect to the CNS lipid content, these suppressive treatments abolish the increase in esterified cholesterol and partially revert the diminution in the content of cerebrosides and total cholesterol characteristic of the acute stage of the disease. Concomitantly, meningeal and parenchymal infiltration with mononuclear cells and deposits of immunoglobulins in the infiltrated regions as well as in spinal cord motor neurons were reduced. Analysis of the humoral response to myelin antigens shows that all EAE as well as treated animals developed antibodies to MBP and other myelin proteins. However, a higher incidence and level of these antibodies was observed in nontreated EAE animals and MBP- and ovalbumin-treated rats, while rats treated with total bovine myelin showed a highly reduced humoral response. The present results indicate that intraperitoneal treatment with soluble forms of myelin antigens, concomitant with the suppression of the clinical symptoms of the disease, markedly reduces the biochemical and histological alterations occurring in EAE animals and produces changes in the autoimmune humoral response.