When activation of the peripheral immune system persists, as in chronic infections, autoimmune or tumor-related diseases, the release of pro-inflammatory cytokines such as interleukin (IL)-1, IL-6, interferon-gamma (IFNγ) and tumor necrosis factor alpha (TNF-α) in the CNS of predisposed individuals may cause persistence of disease with symptoms of depression. Here, TNF is linked to major depressive disorder.