The
tryptophan (TRP)-
kynurenine (KYN) metabolic pathway is a main player of TRP metabolism through which more than 95% of TRP is catabolized. The pathway is activated by acute and chronic immune responses leading to a wide range of illnesses including
cancer,
immune diseases,
neurodegenerative diseases and
psychiatric disorders. The presence of positive feedback loops facilitates amplifying the immune responses vice versa. The TRP-KYN pathway synthesizes multifarious metabolites including
oxidants,
antioxidants,
neurotoxins,
neuroprotectants and
immunomodulators. The
immunomodulators are known to facilitate the immune system towards a tolerogenic state, resulting in chronic low-grade
inflammation (LGI) that is commonly present in
obesity, poor nutrition, exposer to chemicals or
allergens,
prodromal stage of various illnesses and
chronic diseases. KYN,
kynurenic acid,
xanthurenic acid and
cinnabarinic acid are
aryl hydrocarbon receptor ligands that serve as
immunomodulators. Furthermore, TRP-KYN pathway
enzymes are known to be activated by the stress
hormone cortisol and inflammatory
cytokines, and genotypic variants were observed to contribute to
inflammation and thus various diseases. The
tryptophan 2,3-dioxygenase, the indoleamine 2,3-dioxygenases and the kynurenine-3-monooxygenase are main
enzymes in the pathway. This review article discusses the TRP-KYN pathway with special emphasis on its interaction with the immune system and the tolerogenic shift towards chronic LGI and overviews the major symptoms, pro- and anti-inflammatory
cytokines and toxic and protective KYNs to explore the linkage between chronic LGI, KYNs, and major
psychiatric disorders, including
depressive disorder,
bipolar disorder,
substance use disorder,
post-traumatic stress disorder,
schizophrenia and
autism spectrum disorder.