Huang KW, et al. - Given that elevated levels of pro-inflammatory cytokines, particularly tumor necrotic factor alpha (TNF-α), and negative regulation abnormalities in Toll-like receptor (TLR) signaling pathways are correlated with major depressive disorder (MDD), researchers evaluated the mRNA levels of TNFAIP3, TNFAIP3-interacting proteins (TNIP), including TNIP1, TNIP2, and TNIP3, and TNFAIP3-like proteins, like cezanne1, cezanne2, trabid, and VCIP135, in TNF-α-secreting cells and analyzed their connection with severity of depression utilizing the 17-item Hamilton Depression Rating Scale (HAMD-17) scores from 30 MDD subjects and 30 healthy controls. After 4 weeks of antidepressant treatment, 26 patients received a second assessment. TNF-α-secreting cells showed higher expression of TNIP3 mRNA in MDD patients than in pre-treatment healthy controls, which was marginally reduced after treatment with antidepressants. Moreover, after linear regression analysis, the TNIP2 level could be effectively applied to predict changes in HAMD scores. The collective results indicate that in patients with MDD, molecules connected with negative regulation of innate immunity are aberrantly expressed and present potential therapeutic goals.