A nitric oxide releasing derivative of flurbiprofen inhibits experimental autoimmune encephalomyelitis |
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Authors: | Furlan Roberto Kurne AslI Bergami Alessandra Brambilla Elena Maucci Raffaella Gasparini Laura Butti Erica Comi Giancarlo Ongini Ennio Martino Gianvito |
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Institution: | Neuroimmunology Unit, San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milan, Italy. furlan.roberto@hsr.it |
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Abstract: | Nitric oxide (NO)-releasing non-steroidal anti-inflammatory drugs (NSAIDs) have been reported to have a safer profile and additional anti-inflammatory and immuno-modulatory properties compared to parent compounds. Preventive treatment of experimental autoimmune encephalomyelitis (EAE)-induced in C57BL/6 mice by immunization with myelin oligodendrocyte glycoprotein (MOG) peptide 35-55-with the NO-releasing derivative of flurbiprofen HCT1026 delayed disease onset and significantly decreased disease severity. HCT1026 treatment was associated to (i) decreased mRNA levels of pro-inflammatory cytokines, caspase-1, and iNOS in blood cells; (ii) decreased ability of encephalitogenic T cells to proliferate; (iii) reduced number of central nervous system (CNS)-infiltrating T cells; (iv) decreased axonal loss and demyelination; (v) increased CD4(+) CD69(-) CD25(+) regulatory T cells in the spleen. |
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