Aging-associated increase in indoleamine 2,3-dioxygenase (IDO) activity appears to be unrelated to the transcription of the IDO1 or IDO2 genes in peripheral blood mononuclear cells

In this study our aim was to assess whether this difference in IDO activity in the plasma was due to the differential expression of either the IDO1 or IDO2 gene in peripheral blood mononuclear cells. Our results show that IDO1 and IDO2 are not differently expressed in nonagenarians compared to controls and that the expression of IDO genes is not associated with the level of IDO activity in the plasma.The level of IDO activity in the plasma is not regulated through the expression of IDO1 or IDO2 in the peripheral blood mononuclear cells.The aging-associated decline of the immune system, termed immunosenescence, is characterized by aberrantly functioning T cell populations and an increased level of circulating pro-inflammatory cytokines (inflamm-aging). The levels of CRP, IL-6, TNF-α, among others, are increased in the blood of aged individuals and this increase is associated with a shortened lifespan [1,2]. The high levels of pro-inflammatory cytokines are also associated with several age-related conditions such as dementia, Parkinson's disease, atherosclerosis, type 2 diabetes, sarcopenia and functional disability. An age-associated increase in the production of TNF-α, IL-6 and IL-1Ra has been reported in unstimulated peripheral blood mononuclear cells (PBMCs). However, other cell types, such as endothelial, adipose and macrophage-derived cells, probably also contribute to the plasma levels of these and other pro-inflammatory cytokines. The inducers of these molecules and the mechanisms of activation of the genes associated with them remain poorly characterized [1,2].Indoleamine 2,3-dioxygenase is an immunomodulatory enzyme, the activity of which is elevated in several inflammatory conditions, such as infection, autoimmune disorders and malignancies [3]. The IDO enzyme is the first and also the rate-limiting enzyme in the pathway that converts tryptophan (trp) to kynurenine (kyn). IDO can suppress effector T cells and stimulate the differentiation of na？ve T cells t