Effect of indoleamine 2,3-dioxygenase on induction of experimental autoimmune encephalomyelitis.
Experimental autoimmune encephalomyelitis (EAE) is a T cell-mediated demyelinating disease of the central nervous system (CNS). Indoleamine 2,3-dioxygenase (IDO) is an enzyme that catabolizes tryptophan, which can result in the death of T lymphocytes. This effect of IDO is inhibited by 1-methyl-tryptophan (1-MT). We used a murine model of EAE to demonstrate: (1) opposing patterns of spinal cord IDO and interferon-gamma (INF-gamma) mRNA expression through the preclinical, acute and remission I phases of EAE; (2) a change in the kynurenine-to-tryptophan (K/T) ratio during these same phases; and (3) 1-MT-induced exacerbation of clinical and histologic disease parameters during EAE. These results suggest that IDO may contribute to the regulation of T cell activity associated with the different phases of this animal model of multiple sclerosis (MS).
Sakurai
Kenichi
K
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Building 10, Room 4B36, 9000 Rockville Pike, Bethesda, MD 20892, USA.
Zou
Jian-Ping
JP
Tschetter
Jolynne R
JR
Ward
Jerrold M
JM
Shearer
Gene M
GM
D000818:Animals; D001369:Axons / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D002455:Cell Division / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000235:genetics*; D004195:Disease Models, Animal; D018450:Disease Progression; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy / Q000201:enzymology* / Q000276:immunology; D005260:Female; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007371:Interferon-gamma / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics; D007700:Kinetics; D007737:Kynurenine / Q000276:immunology / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics; D013116:Spinal Cord / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology; D016896:Treatment Outcome; D014364:Tryptophan / Q000031:analogs & derivatives* / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D014366:Tryptophan Oxygenase / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
D016207:Cytokines; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D012333:RNA, Messenger; D016753:Interleukin-10; D015847:Interleukin-4; D007737:Kynurenine; D007371:Interferon-gamma; D014364:Tryptophan; D014366:Tryptophan Oxygenase