Chronic effects of gamma-interferon on quinolinic acid and indoleamine-2,3-dioxygenase in brain of C57BL6 mice.
Chronic infections are associated with increased concentrations of the neuroactive kynurenine pathway metabolite, quinolinic acid (QUIN), in blood and cerebrospinal fluid. In the present study, repeated injections of gamma-interferon (5000 IU, every 3 days for 39 days) to C57BL6 mice were associated with persistent activation of indoleamine-2,3-dioxygenase (IDO), the first enzyme of the kynurenine pathway, in lung and brain, sustained increases in brain QUIN concentration and increases in plasma L-kynurenine and QUIN levels. Mice chronically treated with gamma-interferon offer an animal model to investigate the effects of sustained immune stimulation on kynurenine pathway metabolism.
Saito
K
K
Section on Analytical Biochemistry, National Institute of Mental Health, Bethesda, MD 20892.
Markey
S P
SP
Heyes
M P
MP
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007371:Interferon-gamma / Q000494:pharmacology*; D007737:Kynurenine / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008168:Lung / Q000187:drug effects / Q000201:enzymology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017378:Quinolinic Acid; D011805:Quinolinic Acids / Q000378:metabolism*; D011994:Recombinant Proteins; D014366:Tryptophan Oxygenase / Q000378:metabolism*
D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D011805:Quinolinic Acids; D011994:Recombinant Proteins; D007737:Kynurenine; D007371:Interferon-gamma; D014366:Tryptophan Oxygenase; D017378:Quinolinic Acid