Evidence for nitric oxide involvement in experimental autoimmune encephalomyelitis and adjuvant-induced arthritis in Lewis rat
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abstract
Nitric oxide (NO) has been implicated as an important pathogenic mediator in several inflammatory and autoimmune diseases. We have developed experimental autoimmune encephalomyelitis (EAE) and adjuvant-induced arthritis in the Lewis rat as experimental models for multiple sclerosis, and rheumatoid arthritis, respectively, in order to investigate the role of NO in the inflammatory process. We have used the monoclonal antibody anti-NO-cysteine (Cys)-G-bovine serum albumin (BSA) developed in our laboratory as an inhibitor of the toxic effect of NO to determine the implication of NO in the creation of neoepitopes and therefore in the symptomatology of these two diseases. In addition, we have detected a significant level of circulating endogenous antibodies directed against nitrosylated and nitrated epitopes in the sera of preimmunized rats. Our data demonstrate the ability of the monoclonal anti-NO-Cys-G-BSA antibody to modulate these diseases through NO neutralization, and further provide evidence for the in vivo synthesis of nitrosylated and nitrated neoepitopes that are stable enough to be highly immunogenic, thereby inducing inflammatory injuries and a humoral immune response. Our findings provide further evidence for the implication of the NO pathway in the pathogenesis of EAE and adjuvant-induced arthritis.