TNF and major depressive disorder: A bidirectional mechanism of interaction between aging, cancer, and depression, which involves primarily neuro-immune-endocrine system dysregulation, was discussed by Spoletini et al. Aging is associated with sympathetic/parasympathetic deregulation, hypothalamic-pituitary-adrenal (HPA) axis activation by stress conditions, immune deregulation leading to lymphocytes T helper1/2 imbalance, up-regulation of pro-inflammatory cytokines (IL-1, TNF-α, IL-6, IL-8, and IL-18), down-regulation of anti-inflammatory cytokines (TGF-β, IL-10), and modifications of natural killer cells activity [3].