Aminoguanidine reduces apoptosis of circulating V Beta 8.2 T lymphocytes in Lewis rats with actively induced experimental autoimmune encephalomyelitis. Association with persistent inflammation of the central nervous system and lack of recovery.
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.
Puerta
C
C
Neuroimmunology Unit, Universidad Autónoma de Madrid, Clínica Puerta de Hierro, San Martín de Porres 4, 28035, Madrid, Spain.
Martínez
I
I
Baranda
P
P
Blasco
M R
MR
Castejón
R
R
Vargas
J A
JA
García-Merino
A
A
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology*; D002455:Cell Division / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D015870:Gene Expression / Q000276:immunology; D006146:Guanidines / Q000494:pharmacology*; D006168:Guinea Pigs; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000276:immunology; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology; D004676:Myelin Basic Protein / Q000276:immunology; D009566:Nitrates / Q000097:blood; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000276:immunology; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000097:blood; D051381:Rats; D011917:Rats, Inbred Lew; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis*; D020127:Recovery of Function / Q000276:immunology; D013116:Spinal Cord / Q000737:chemistry / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000737:chemistry / Q000166:cytology* / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000276:immunology
D004791:Enzyme Inhibitors; D006146:Guanidines; D004676:Myelin Basic Protein; D009566:Nitrates; D009573:Nitrites; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D016753:Interleukin-10; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; C004479:pimagedine