Nitric oxide plays a critical role in the recovery of Lewis rats from experimental autoimmune encephalomyelitis and the maintenance of resistance to reinduction

Experimental autoimmune encephalomyelitis (EAE) is a T cell-mediated autoim mune disease of the CNS and an animal model for the human demyelinating dis ease, 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 acti ve reinduction of disease. In this paper, we report that rats recovering fr om MBP-CFA-induced EAE have significantly increased serum levels of reactiv e nitrogen intermediates indicative of increased NO production. These level s remain elevated after the recovery period and increase even further early after a rechallenge with MBP-CFA, and all animals are totally refractory t o a second episode of disease. Oral treatment of rats with N-methyl-L-argin ine acetate (L-NMA), beginning at peak disease on day 11 postimmunization, results in significant prolongation of disease and an alteration in the pre sentation of clinical symptoms from that of solely hind limb paresis/paraly sis to severe fore limb involvement as well. Treatment of fully recovered r ats with L-NMA 24 h before a rechallenge with MBP-CFA leads to decreased se rum reactive nitrogen intermediate levels and results in a second episode o f EAE in 100% of animals. Furthermore, L-NMA treatment of fully recovered r ats in the absence of a rechallenge immunization leads to spontaneous relap se of disease.