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 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.
O'Brien
N C
NC
Neurosciences Research Unit, Canberra Hospital, Australian Capitol Territory. Nikki.O'Brien@anu.edu.au
Charlton
B
B
Cowden
W B
WB
Willenborg
D O
DO
D000284:Administration, Oral; D000818:Animals; D000941:Antigens / Q000008:administration & dosage / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D005260:Female; D005609:Free Radicals / Q000097:blood; D005620:Freund's Adjuvant / Q000008:administration & dosage / Q000276:immunology; D006168:Guinea Pigs; D007113:Immunity, Innate; D007271:Injections, Intradermal; D004676:Myelin Basic Protein / Q000008:administration & dosage / Q000276:immunology; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D009573:Nitrites / Q000097:blood; D051381:Rats; D011917:Rats, Inbred Lew; D012008:Recurrence; D014611:Vaccination
D000941:Antigens; D005609:Free Radicals; D004676:Myelin Basic Protein; D009573:Nitrites; D009569:Nitric Oxide; D005620:Freund's Adjuvant; D019331:NG-Nitroarginine Methyl Ester