Abstract
Depression is a common, severe and chronic psychiatric disease. Although the currently available antidepressants have been used in the treatment of depression, their beneficial effects are limited. Accumulating evidence suggests that pro-inflammatory cytokines such as interleukin-6 (IL-6) have an important role in the pathogenesis of depression. This study was undertaken to examine whether anti-mouse IL-6 receptor antibody (MR16-1) induces antidepressant effects in a social defeat stress model. Intravenous injection of MR16-1 induced rapid-onset and long-lasting antidepressant effects in susceptible mice after social defeat stress through its anti-inflammatory actions. In contrast, intracerebroventricular injection of MR16-1 induced no antidepressant effects in susceptible mice. Furthermore, treatment with MR16-1 could significantly normalize alterations in the expression of synaptic proteins (postsynaptic density protein 95 and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor 1) and dendritic spine density in the brain regions of susceptible mice. Gut microbiota analysis using 16S ribosomal RNA gene sequencing showed that MR16-1 significantly improved decreased Firmicutes/Bacteroidetes ratio in susceptible mice. It also significantly improved decreased levels of Oscillospira in susceptible mice. These findings suggest that peripheral IL-6 has a key role in the pathogenesis of depression and that the blockade of IL-6 receptor in the periphery might have rapid-onset and long-lasting antidepressant effects by normalizing the altered composition of gut microbiota in susceptible mice after social defeat stress. Therefore, the blockade of IL-6 receptor in the periphery shows promise as a novel therapeutic approach for depressed patients with higher IL-6 blood levels.
Highlights
Depression is a significant contributor to the global burden of disease and affects people in all communities across the world
The results suggest that intravenous injection of MR16-1 showed rapid and sustained antidepressant effects in a social defeat stress model
The major findings of this study are that peripheral, but not brain, IL-6 has an important role in the depression-like phenotype after social defeat stress and that gut microbiota may have a role in the antidepressant effects of anti-IL-6 receptor MR16-1
Summary
Depression is a significant contributor to the global burden of disease and affects people in all communities across the world. It is estimated to affect 350 million people, and almost 1 million lives are lost annually due to suicide. The World Health Organization predicts that depression will be the single leading cause of burden of all health conditions by 2030.1 inflammation has a central role in the pathogenesis of depression,[2,3,4,5,6,7] the precise mechanisms underlying inflammation-induced depression remain undetermined. It is likely that peripheral IL-6 might be involved in the pathogenesis of inflammation-induced depression.[12,13,18]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
