myelin-basic-protein and pimagedine

Aminoguanidine therapy delayed the onset of actively induced EAE in Lewis rats, but recovery was impaired in most animals. In the central nervous system this was correlated with persistent inflammation and production of proinflammatory cytokines. In the periphery of aminoguanidine-treated animals, T lymphocytes showed increased proliferation against myelin basic protein, and the percentage of Vbeta 8.2(+) T lymphocytes undergoing early apoptosis was markedly decreased, although it was unchanged in Vbeta 8.2(+) T cells isolated from the spinal cord. These results suggest that the prolonged survival of circulating encephalitogenic cells achieved by aminoguanidine would favor a longer lasting entry of these cells into the nervous system resulting in persistent inflammation and lack of recovery.

Topics: Animals; Apoptosis; Cell Division; Encephalomyelitis, Autoimmune, Experimental; Enzyme Inhibitors; Gene Expression; Guanidines; Guinea Pigs; Intercellular Adhesion Molecule-1; Interferon-gamma; Interleukin-10; Myelin Basic Protein; Nitrates; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Nitrites; Rats; Rats, Inbred Lew; Receptors, Antigen, T-Cell, alpha-beta; Recovery of Function; Spinal Cord; T-Lymphocytes; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha; Vascular Cell Adhesion Molecule-1

The nitric oxide (NO) synthase pathway is activated during experimental autoimmune inflammation of the central nervous system, and administration of aminoguanidine, an inhibitor of the cytokine-inducible NO synthase (NOS), ameliorated the disease course of autoimmune encephalomyelitis in the SJL mouse. We studied the role of nitric oxide synthase (NOS) in the pathogenesis of experimental autoimmune neuritis (EAN) and experimental autoimmune encephalomyelitis (EAE) in the Lewis rat. NG-L-monomethyl-arginine (L-NMMA), a competitive inhibitor of NOS, partially suppressed T cell line-mediated EAN, but not myelin-induced EAN, myelin basic protein (MBP)-induced EAE, or T cell line-mediated EAE. Aminoguanidine (AG), a selective inhibitor of the cytokine-inducible NOS, enhanced MBP-induced EAE, but had no significant effects on myelin-induced EAN. Two other NOS inhibitors, nitro-arginine methyl-ester and N-nitro arginine, had only little or no effects in EAN and EAE. The administration of NOS inhibitors showed some striking effects in EAN and EAE, but the observed diversity of actions points to a much more complex role of the NO pathway than previously suggested.

Topics: Acetates; Amino Acid Oxidoreductases; Animals; Arginine; Encephalomyelitis, Autoimmune, Experimental; Female; Guanidines; Mice; Mice, Inbred Strains; Myelin Basic Protein; Neuritis, Autoimmune, Experimental; NG-Nitroarginine Methyl Ester; Nitric Oxide Synthase; Nitroarginine; omega-N-Methylarginine; Rats; Rats, Inbred Lew