TNF and major depressive disorder: Chronic unpredictable mild stress upregulates hippocampal IL-1β, IL-6, TNF-a, IDO, and KYN/tryptophan ratios, induces depression-like behavior, and subanesthesia doses of ketamine can reduce these inflammatory factors; therefore, its antidepressant effect is related to the downregulation of pro-inflammatory cytokines in rat hippocampus [94].