Interleukin-6 signaling pathway involved in major depressive disorder: selective serotonin reuptake inhibitor regulates IL-6 pathway

Abstract

Abstract Background Evidence indicates that pro-inflammatory Th17 and Th1 cells are involved in major depressive disorder (MDD) pathogenesis. Development of Th17 and Th1 are regulated by IL-6 and IFN-γ, respectively. In this study, the levels of IL-6 and IFN-γ, and mRNA expression of related signaling components and, Th17/Th1 transcription factors were investigated in MDD patients with/without selective serotonin reuptake inhibitor (SSRI) medication. Materials and methods Forty-six patients and 38 healthy controls (HCs) were recruited. Twenty patients were received the SSRI (sertraline 50–200 mg/day) for at least 1 year, and 26 patients were not received medication. Expression of IL-6R, IFN-γR, JAK1, JAK2, TYK2, STAT1, STAT3, T-bet and RORγt were assessed with Real-Time-PCR. Serum and supernatant levels of IL-6 and IFN-γ were determined using ELISA. Results and discussion The serum and supernatant levels of IL-6 were increased in patients without (SSRI−) compared with HCs, while its levels was reduced in SSRI+. Elevated expressions of IL-6R, STAT3 and RORγt were observed in SSRI− compared with HCs. Expressions of IL-6R, STAT3, RORγt and IFN-γR, were decreased in SSRI+ compared to SSRI− patients. Conclusion Increased IL-6 involved in MDD, and SSRI regulates IL-6 pathway and IL-6 production. MDD patients may benefit from IL-6/IL-6R targeted therapeutic intervention.