Cytokine Regulation of Tryptophan Metabolism in the Hypothalamic-Pituitary-Adrenal (HPA) Axis: Implications for Protective and Toxic Consequences in Neuroendocrine Regulation

1. Aim: Indoleamine 2,3-dioxygenase (IDO) catalyzation of tryptophan is the first rate-limiting step of the kynurenine pathway in the majority of tissues. The kynurenine pathway produces neurotoxic metabolites such as 3-hydroxykinurenine and quinolinic acid. IDO is inducible by the cytokine interferon-γ (IFN-γ) and has been proposed to mediate the sickness behavior of patients with infectious or other inflammatory diseases.