Interleukin-9 promotes intestinal barrier injury of sepsis: a translational research

Jia-Kui Sun,Xin-Wei Mu,Xiao Shen,Su-Ming Zhou,Jing Zhou,Dong-Mei Zhu,Xin-Pei Sun,Xiang Wang

doi:10.1186/s40560-021-00550-y

Jia-Kui Sun, Xin-Wei Mu + Show 6 more

Open Access

https://doi.org/10.1186/s40560-021-00550-y

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Abstract

BackgroundSepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Intestinal mucosal barrier injury is one of the important manifestations of sepsis. Interleukin-9 (IL-9) and IL-9-producing CD4(+) T cells were emerging pro-inflammatory mediators with development of intestinal injury. However, it is unclear whether IL-9 is related to the intestinal barrier injury of sepsis.MethodsTo investigate the roles of IL-9-producing CD4(+) T cells and IL-9 in the process of barrier injury in sepsis, serum IL-9-producing CD4(+) T cell percentages, IL-9, and D-lactate levels were measured in septic patients and controls. The markers of barrier function in serum and intestinal tissue were also collected in septic rats. Moreover, the barrier injury degree and survival rate of septic rats were also investigated after increasing or interfering with IL-9 expression.ResultsThe serum IL-9-producing CD4(+) T cell percentages, IL-9, and D-lactate levels were significantly higher in septic patients or rats than those in controls. IL-9-producing CD4(+) T cells and IL-9 levels were positively correlated with D-lactate levels and had a high predictive value of 28-day mortality in septic patients. The non-survivors had significantly higher serum T cell percentages, IL-9, and D-lactate levels compared with survivors. In septic rats, IL-9 increased the expression levels of D-lactate, whereas that decreased the expression levels of zonula occludens 1. Moreover, the barrier injury was aggravated or alleviated by increasing or interfering with IL-9 expression, respectively. Survival rate analysis also showed that IL-9 decreased the 14-day survival rate of septic rats.ConclusionIL-9 is closely related to intestinal mucosal barrier injury and mortality in sepsis. IL-9 blockade has the potential to improve the barrier injury in sepsis.Trial registrationThe study was registered at ClinicalTrials.gov (ID: NCT03791866, Date: December 2018).

Highlights

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection
Non-surviving septic patients had significantly higher serum IL-9-producing CD4(+) T cell percentages, IL-9, and D-lactate levels compared with survivors (Fig. 1c, P < 0.01)
We found that the serum IL-9-producing CD4(+) T cell percentages, IL-9, and D-lactate levels were significantly higher in septic patients or rats than that in controls

Summary

Introduction

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Intestinal mucosal barrier injury is one of the important manifestations of sepsis. Interleukin-9 (IL-9) and IL-9producing CD4(+) T cells were emerging pro-inflammatory mediators with development of intestinal injury. It is unclear whether IL-9 is related to the intestinal barrier injury of sepsis. Previous studies have indicated that immune imbalance might play an important role in the development of sepsis [3, 4], which is closely associated with the injury of intestinal mucosal barrier in sepsis [5, 6]. Intestinal barrier injury was often caused by an inflammatory reaction, severe trauma, shock, infection, pancreatitis, and other critical illnesses [3, 5]. Intestinal dysfunction is considered as “motor of multiple organ failure.” the precise mechanisms of intestinal barrier damage caused by sepsis are still unclear

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