Neutralization of interleukin-17A alleviates burn-induced intestinal barrier disruption via reducing pro-inflammatory cytokines in a mouse model

Abstract

Background The intestinal barrier integrity can be disrupted due to burn injury, which is responsible for local and systemic inflammatory responses. Anti-inflammation strategy is one of the proposed therapeutic approaches to control inflammatory cascade at an early stage. Interleukin-17A (IL-17A) plays a critical role in inflammatory diseases. However, the role of IL-17A in the progression of burn-induced intestinal inflammation is poorly understood. In this study, we aimed to investigate the effect of IL-17A and associated pro-inflammatory cytokines that were deeply involved in the pathogenesis of burn-induced intestinal inflammatory injury, and furthermore, we sought to determine the early source of IL-17A in the intestine. Methods Mouse burn model was successfully established with infliction of 30% total body surface area scald burn. The histopathological manifestation, intestinal permeability, zonula occludens-1 expression, pro-inflammatory cytokines were determined with or without IL-17A-neutralization. Flow cytometry was used to detect the major source of IL-17A+ cells in the intestine. Results Burn caused intestinal barrier damage, increase of intestinal permeability, alteration of zonula occludens-1 expressions, elevation of IL-17A, IL-6, IL-1β and tumor necrosis factor-α (TNF-α), whereas IL-17A neutralization dramatically alleviated burn-induced intestinal barrier disruption, maintained zonula occludens-1 expression, and noticeably, inhibited pro-inflammatory cytokines elevation. In addition, we observed that the proportion of intestinal IL-17A+Vγ4+ T subtype cells (but not IL-17A+Vγ1+ T subtype cells) were increased in burn group, and neutralization of IL-17A suppressed this increase. Conclusions The main original findings of this study are intestinal mucosa barrier is disrupted after burn through affecting the expression of pro-inflammatory cytokines, and a protective role of IL-17A neutralization for intestinal mucosa barrier is determined. Furthermore, Vγ4+ T cells are identified as the major early producers of IL-17A that orchestrate an inflammatory response in the burn model. These data suggest that IL-17A blockage may provide a unique target for therapeutic intervention to treat intestinal insult after burn.