Bacille Calmette-Guérin inoculation induces chronic activation of peripheral and brain indoleamine 2,3-dioxygenase in mice
J INFECT DIS. 2005-08-01; 192(3): 537-544
DOI: 10.1086/431603
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1. J Infect Dis. 2005 Aug 1;192(3):537-44. Epub 2005 Jul 1.
Bacille Calmette-Guérin inoculation induces chronic activation of peripheral and
brain indoleamine 2,3-dioxygenase in mice.
Moreau M(1), Lestage J, Verrier D, Mormede C, Kelley KW, Dantzer R, Castanon N.
Author information:
(1)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.
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.
DOI: 10.1086/431603
PMID: 15995970 [Indexed for MEDLINE]