IDO mediated cascade

202211201916
Status:
Tags: HPA axis

The IDO mediated cascade begins when Cortisol balance is disrupted. Elevated cortisol levels trigger the 2,3-indolimine dioxygenase enzyme, which is located in macrophages and dendritic cells, and increases its activity when interleukins & interferons are stimulated.

Proinflammatory cytokines can induce IDO, which binds to tryptophan, a serotonin precursor. Induction of IDO results in a change in the equilibrium of tryptophan catabolism, resulting in preferential synthesis of kynurenine. As inflammation increases, levels of IDO increase, resulting in more production of kynurenine. Kynurenine is metabolized by 3-HK into quinolinic acid, a neurotoxic substance which is an NMDA agonist, inducing excitotoxicity and reactive oxygen species (ROS) formation.