A nitric oxide releasing derivative of flurbiprofen inhibits experimental autoimmune encephalomyelitis.
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.
Furlan
Roberto
R
Neuroimmunology Unit, San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milan, Italy. furlan.roberto@hsr.it
Kurne
AslI
A
Bergami
Alessandra
A
Brambilla
Elena
E
Maucci
Raffaella
R
Gasparini
Laura
L
Butti
Erica
E
Comi
Giancarlo
G
Ongini
Ennio
E
Martino
Gianvito
G
D000284:Administration, Oral; D019264:Adoptive Transfer; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000637:transplantation; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D002490:Central Nervous System / Q000187:drug effects / Q000473:pathology; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000235:genetics; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D005480:Flurbiprofen / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D006023:Glycoproteins / Q000008:administration & dosage / Q000276:immunology; D006131:Growth Inhibitors / Q000008:administration & dosage; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D016753:Interleukin-10 / Q000172:deficiency / Q000235:genetics; D037181:Lectins, C-Type; D018655:Lymphocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D063308:Myelin-Oligodendrocyte Glycoprotein; D009569:Nitric Oxide / Q000378:metabolism*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology; D012333:RNA, Messenger / Q000037:antagonists & inhibitors; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D013154:Spleen / Q000276:immunology / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D005480:Flurbiprofen; D006023:Glycoproteins; D006131:Growth Inhibitors; D007166:Immunosuppressive Agents; D016753:Interleukin-10; D037181:Lectins, C-Type; D063308:Myelin-Oligodendrocyte Glycoprotein; D009569:Nitric Oxide; D010446:Peptide Fragments; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D000099192:CD69 Antigens; C445081:myelin oligodendrocyte glycoprotein (35-55); C095631:nitroflurbiprofen