TNF and major depressive disorder: Third, the 'macrophage theory of depression' suggests that upregulated monocyte/macrophage production of pro-inflammatory cytokines such as IL-1β, tumor necrosis factor-α and IL-6 activates CNS sickness behavior functions in a manner analogous to that hypothesized for Type I interferons.102, 103, 104 This hypothesis would predict that MDD should be linked to TFs involved in monocyte/macrophage activation such as NF-κB and EGR family factors.