Influence of chronic inflammation on the kynurenine pathway. Certain proinflammatory cytokines possess the ability to up-regulate enzymes of the kynurenine pathway, thereby increasing the rate of tryptophan (TRP) degradation and production of kynurenines in the periphery. This may result in reduced concentrations of peripheral TRP and elevated peripheral levels of kynurenines. The reduced levels of peripheral TRP may then result in insufficient levels within the brain and a corresponding serotonin (5-HT) deficit. Proinflammatory cytokines also up-regulate enzymes in the brain, housed within astrocytes, microglia, and infiltrating macrophages, which utilize the elevated kynurenine concentrations for the production of further metabolites such as quinolinic acid (QUIN) and kynurenic acid (KYNA).