Experimental autoimmune encephalomyelitis (EAE) is a T cell-mediated autoimmune disease of the CNS and an animal model for the human demyelinating disease, multiple sclerosis. In the Lewis rat, myelin basic protein (MBP)-CFA-induced EAE is an acute monophasic disease from which animals recover fully, do not relapse, and develop a robust long-term resistance to further active reinduction of disease. In this paper, we report that rats recovering from MBP-CFA-induced EAE have significantly increased serum levels of reactive nitrogen intermediates indicative of increased NO production. These levels remain elevated after the recovery period and increase even further early after a rechallenge with MBP-CFA, and all animals are totally refractory to a second episode of disease. Oral treatment of rats with N-methyl-l-arginine acetate (l-NMA), beginning at peak disease on day 11 postimmunization, results in significant prolongation of disease and an alteration in the presentation of clinical symptoms from that of solely hind limb paresis/paralysis to severe fore limb involvement as well. Treatment of fully recovered rats with l-NMA 24 h before a rechallenge with MBP-CFA leads to decreased serum reactive nitrogen intermediate levels and results in a second episode of EAE in 100% of animals. Furthermore, l-NMA treatment of fully recovered rats in the absence of a rechallenge immunization leads to spontaneous relapse of disease.
CITATION STYLE
O’Brien, N. C., Charlton, B., Cowden, W. B., & Willenborg, D. O. (1999). Nitric Oxide Plays a Critical Role in the Recovery of Lewis Rats from Experimental Autoimmune Encephalomyelitis and the Maintenance of Resistance to Reinduction. The Journal of Immunology, 163(12), 6841–6847. https://doi.org/10.4049/jimmunol.163.12.6841
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