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.