TNF and major depressive disorder: Activation of the immune–inflammatory response system (IRS) in MDD/MDE is shown by a pro-inflammatory cytokine profile, including activated M1 macrophage cells, as indicated by elevated levels of interleukin (IL)-1β, IL-6, IL-8 (or CXCL-8), and tumor necrosis factor-α (TNF-α); T helper-1 (Th-1) cells with increased interferon-γ (IFN-γ), IL-2, and IL-12 levels; and activated Th-17 cells with increased IL-17 and IL-6 [1,2].