Interleukin-27 as a Negative Regulator of Human Neutrophil Function

Interleukin-27 (IL-27) is a novel cytokine of the IL-6/12 family with a broad range of immune regulation properties, which has been considered as a potential therapeutic agent for immune diseases and cancers. However, little is known about the effect of IL-27 on human neutrophils before its clinical administration. In this study, we investigated the effects of IL-27 on human neutrophil functions including adhesion, reactive oxygen species (ROS)/cytotoxic granule components production, inflammatory cytokines production, major histocompatibility complex (MHC) molecules expression and neutrophils' survival. We showed that IL-27 receptor complex, WSX-1/TCCR and gp130, is constitutively expressed on human neutrophils. In vitro, IL-27 suppressed neutrophil adhesion in response to fMLP, which might depend on the down-regulation of Mac-1. IL-27 also suppressed lipopolysaccharide-induced ROS production and attenuated cytotoxic granule components production in the cytoplasm of human neutrophils. In addition, IL-27 enhanced the production of IL-1 beta but not TNF-alpha from neutrophils. However, IL-27 failed to regulate the expression of MHC molecules and the survival of human neutrophils. In conclusion, our data demonstrate that IL-27 mainly down-modulates human neutrophil function, which might extend our understanding of the role of IL-27 in the innate immune response.