Bacille Calmette-Guérin inoculation induces chronic activation of peripheral and brain indoleamine 2,3-dioxygenase in mice

Abstract

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)-γ, a key cytokine in the activation of IDO. Methods. Mice were inoculated intraperitoneally with BCG (107 cfu/mouse). Lung and brain IDO activity was measured over time, together with plasma levels of TRP and IFN-γ. Results. BCG induced, over the course of several weeks, a chronic increase in serum IFN-γ 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. © 2005 by the Infectious Diseases Society of America. All rights reserved.