Immune activation and degradation of tryptophan in coronary heart disease

Background: Inflammation and immune activation appear to be important in the pathogenesis of coronary heart disease (CHD). Cytokine interferon-γ, which is released during cell-mediated immune responses, induces indoleamine (2,3)-dioxygenase (IDO), an enzyme degrading tryptophan to kynurenine. Therefore, immune stimulation is commonly associated with an increased kynurenine to tryptophan ratio (kyn trp^-1) indicative for activated indoleamine (2,3)-dioxygenase and a measurable decline of tryptophan. Methods: Blood concentrations of kynurenine and free tryptophan and the kynurenine to tryptophan ratio were examined in 35 patients with coronary heart disease verified by coronary angiography and compared with healthy controls. Patients were observed before percutaneus transluminal coronary angioplasty (21 patients: one with artery disease, nine with 2- or 3-artery disease, and five with restenosis). Results and conclusions: Decreased tryptophan concentrations were found in a significant proportion of coronary heart disease patients and coincided with increased kyn trp^-1 and also with increased neopterin concentrations, indicating an activated cellular immune response. We conclude that in coronary heart disease immune activation is associated with an increased rate of tryptophan degradation and thereby lowered tryptophan levels. Results may provide a basis for a better understanding of the pathogenesis of mood disturbances and depression in coronary heart disease patients.