Nitric oxide is a potential down-regulating molecule in autoimmune disease: inhibition of nitric oxide production renders PVG rats highly susceptible to EAE

J Neuroimmunol. 1998 Aug 1;88(1-2):1-8. doi: 10.1016/s0165-5728(98)00040-x.


Rat strains vary in their susceptibility to experimental autoimmune encephalomyelitis (EAE) and in many cases, factors other than MHC antigens are thought to play a role in this. We found that PVG rats, which have a very low susceptibility to EAE, were rendered highly susceptible to clinical disease when treated with N-methylarginine (NMA) an inhibitor of nitric oxide synthase (NOS). The clinical course of the ensuing disease in NMA-treated PVG rats was in most cases fulminating in nature and accompanied by some mortality. Following immunisation with myelin basic protein (MBP)-complete Freund's adjuvant (CFA), PVG rats developed higher serum levels of the surrogate markers of nitric oxide production, reactive nitrogen intermediates (RNI; nitrite and nitrate), than did their Lewis counterparts. This in vivo finding was reflected in vitro, where the levels of RNI produced in 24, 48 and 72 h IFN-gamma-stimulated spleen cell cultures for PVG rats were significantly higher than those for Lewis rats. A mechanism by which increased NO production might protect PVG rats against clinical EAE was suggested by the finding that lymph node cells, isolated from NMA-treated MBP-immunised PVG rats, proliferated in response to MBP at a rate approximately 3 x greater than those from MBP-immunised, saline treated rats. Thus, the greater number of MBP-specific T cells generated in the NOS inhibitor-treated vs. untreated rats could account for their increased susceptibility to developing clinical EAE. The findings in this study suggest that NO plays a role in protecting PVG rats against developing EAE.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Division / drug effects
  • Cells, Cultured
  • Encephalomyelitis, Autoimmune, Experimental / blood
  • Encephalomyelitis, Autoimmune, Experimental / genetics*
  • Encephalomyelitis, Autoimmune, Experimental / physiopathology*
  • Enzyme Inhibitors / pharmacology
  • Genetic Predisposition to Disease
  • Interferon-gamma / pharmacology
  • Lymph Nodes / cytology
  • Lymph Nodes / drug effects
  • Myelin Basic Protein / pharmacology
  • Nitrates / blood
  • Nitric Oxide / antagonists & inhibitors
  • Nitric Oxide / physiology*
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitrites / blood
  • Rats
  • Rats, Inbred Lew
  • Rats, Mutant Strains / genetics*
  • Rats, Mutant Strains / physiology*
  • Spleen / cytology
  • Spleen / drug effects
  • Spleen / metabolism
  • omega-N-Methylarginine / pharmacology


  • Enzyme Inhibitors
  • Myelin Basic Protein
  • Nitrates
  • Nitrites
  • omega-N-Methylarginine
  • Nitric Oxide
  • Interferon-gamma
  • Nitric Oxide Synthase