Bacille Calmette-Guérin inoculation induces chronic activation of peripheral and brain indoleamine 2,3-dioxygenase in mice.
BACKGROUND
Activation of the indoleamine 2,3-dioxygenase (IDO) enzyme and the resulting decrease in plasma tryptophan (TRP) levels appears to be a crucial link in the relationship between cytokines and depression. We aimed to develop an experimental model of chronic IDO activation based on bacille Calmette-Guérin (BCG) infection that elicits a robust increase in levels of interferon (IFN)- gamma, a key cytokine in the activation of IDO.


METHODS
Mice were inoculated intraperitoneally with BCG (10(7) cfu/mouse). Lung and brain IDO activity was measured over time, together with plasma levels of TRP and IFN- gamma.


RESULTS
BCG induced, over the course of several weeks, a chronic increase in serum IFN- gamma levels that was associated with a sustained enhancement of lung and brain IDO activity and with decreases in peripheral (serum and lungs) and brain concentrations of TRP, with different time courses between tissues.


CONCLUSIONS
The model of BCG-induced IDO activation will be useful for the study of the consequences of peripheral immune activation in the brain and the role of TRP metabolism in cytokine-induced mood alteration.
Moreau
Maite
M
Laboratory of Neurobiologie Integrative, Formation de Recherche en Evolution 2723 Centre National de la Recherche Scientifique-Unite Mixte de Recherche 1244 Institut National de Recherche Agronomique, Institut Francois Magendie, Bordeaux, France.
Lestage
Jacques
J
Verrier
Daniele
D
Mormede
Cecile
C
Kelley
Keith W
KW
Dantzer
Robert
R
Castanon
Nathalie
N
D000818:Animals; D001500:BCG Vaccine / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D004789:Enzyme Activation / Q000187:drug effects; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007371:Interferon-gamma / Q000097:blood; D008099:Liver / Q000201:enzymology*; D008297:Male; D051379:Mice; D014366:Tryptophan Oxygenase / Q000378:metabolism*
D001500:BCG Vaccine; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007371:Interferon-gamma; D014366:Tryptophan Oxygenase