The enzyme indoleamine 2,3-dioxygenase is induced in the mouse brain in response to peripheral administration of lipopolysaccharide and superantigen.
The essential amino-acid, L-tryptophan, is the precursor of serotonin. Its availability in the brain is controlled by indoleamine 2,3-dioxygenase (IDO). This enzyme is inducible by cytokines such as interferon-gamma (IFN-gamma) and is the first and rate-limiting enzyme of the catabolism pathway of tryptophan. Since induction of IDO has been proposed to mediate the influence of cytokines on mood in patients with various somatic disorders, the present study aimed at analyzing the relationships between changes in brain IDO activity and serum IFN-gamma levels in response to peripheral immune stimulation by lipopolysaccharide (LPS) and superantigen in mice. Each of these treatments induced an increase in serum IFN-gamma at 6 h post-treatment followed 24 h later by a two-fold increase in IDO activity in the brain. These results support the involvement of peripheral IFN-gamma in the control of L-tryptophan catabolism in the brain.
Lestage
J
J
INRA-INSERM U394, Rue Camille Saint-Saëns, 33077 Bordeaux Cedex, France. jacques.lestage@bordeaux.inserm.fr
Verrier
D
D
Palin
K
K
Dantzer
R
R
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007371:Interferon-gamma / Q000097:blood* / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018089:Superantigens / Q000008:administration & dosage / Q000378:metabolism*; D014364:Tryptophan / Q000378:metabolism*; D014366:Tryptophan Oxygenase / Q000187:drug effects / Q000378:metabolism*
D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D008070:Lipopolysaccharides; D018089:Superantigens; D007371:Interferon-gamma; D014364:Tryptophan; D014366:Tryptophan Oxygenase