Intrauterine infection is still a common trigger of preterm delivery (PTD) and also a determinant risk factor for the subsequentdevelopment of neurodevelopmental abnormalities in neonates. In this study, we examined the expressional pattern of various inflammatory cytokines such as interleukin-1β (IL-1β), IL-6 and tumor necrosis factor-a (TNF-α) in placentae complicated with severe chorioamnionitis (CAM) and found that IL-6 is mainly expressed in macrophages in villous mesenchyme by immunohistochemical analysis with anti-CD-68 antibody. Using an experimental lipopolysaccharide (LPS)-induced PTD model, the therapeutic potential of targeting this cytokine was investigated.Anti-IL-6 receptor antibody (MR16-1) was delivered 6 h before LPS treatment. Mice in the MR16-1 group had a significantly lower rate of PTD(17%) than in the controls (53%, P 1/4 0.026). As a result, MR16-1 treatment significantly prolonged the gestational period (control; 18.4±1.7d,MR16-1; 19.8±1.5d, P 1/4 0.007) without any apparent adverse events on the mice and their pups. In primary human amniotic epithelial cells,pretreatment with a humanized anti-human IL-6 receptor antibody, tocilizumab, significantly inhibited the production of prostaglandin E2 induced by IL-6. In conclusion, IL-6was strongly expressed mainly in macrophages in villous mesenchyme in placentae complicated withCAM. Anti-IL-6Rantibody significantly decreased the rate of PTD in LPS-induced inflammatory model in mice, and inhibited PGE2 production from human primaryamniotic epithelial cells. Targeting IL-6 signaling could be a promising option for the prevention ofPTDand needs to be further explored for future clinical application. © The Author 2013. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.
CITATION STYLE
Wakabayashi, A., Sawada, K., Nakayama, M., Toda, A., Kimoto, A., Mabuchi, S., … Kimura, T. (2013). Targeting interleukin-6 receptorinhibits preterm delivery induced by inflammation. Molecular Human Reproduction, 19(11), 718–726. https://doi.org/10.1093/molehr/gat057
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