A novel nitric oxide scavenger in combination with cyclosporine A ameliorates experimental autoimmune encephalomyelitis progression in mice.
Immunotherapy improves experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis (MS), while excessive production of nitric oxide (NO) has been implicated in the pathogenesis of this disease. Here, we show that disease progression in SJL/J mice with EAE is improved after treatment with either a subtherapeutic dose of cyclosporine A (CsA) or NOX-100, a nitric oxide scavenger. Importantly, the impact of subtherapeutic doses of CsA in combination with NOX-100 on disease progression in EAE was greater than that attained with either agent alone and led to near total protection. CNS inflammation and gene expression of proinflammatory cytokines and iNOS were also significantly reduced after treatment. These observations point to the potential therapeutic utility of NOX-100 as a dose-reducing agent for CsA in the treatment of MS.
Jolivalt
Corinne G
CG
Medinox Inc., Suite 201, 11575 Sorrento Valley Road, San Diego, CA 92121, USA.
Howard
Randy B
RB
Chen
Long S
LS
Mizisin
Andrew P
AP
Lai
Ching-San
CS
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D016572:Cyclosporine / Q000008:administration & dosage*; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D018450:Disease Progression; D004359:Drug Therapy, Combination; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D004790:Enzyme Induction / Q000187:drug effects / Q000235:genetics; D005260:Female; D016166:Free Radical Scavengers / Q000008:administration & dosage*; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007279:Injections, Subcutaneous; D051379:Mice; D008815:Mice, Inbred Strains; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D009942:Organometallic Compounds / Q000494:pharmacology*; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D013859:Thiocarbamates / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics / Q000276:immunology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D016166:Free Radical Scavengers; D007166:Immunosuppressive Agents; C116422:NOX 101; D009566:Nitrates; D009942:Organometallic Compounds; D012333:RNA, Messenger; D013859:Thiocarbamates; D009569:Nitric Oxide; D016572:Cyclosporine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse