Cytokines and intestinal epithelial permeability: A systematic review

Background: The intestinal mucosa is composed of a well-organized epithelium, acting as a physical barrier to harmful luminal contents, while simultaneously ensuring absorption of physiological nutrients and solutes. Increased intestinal permeability has been described in various chronic diseases, leading to abnormal activation of subepithelial immune cells and overproduction of inflammatory mediators. This review aimed to summarize and evaluate the effects of cytokines on intestinal permeability.Methods: A systematic review of the literature was performed in the Medline, Cochrane and Embase databases, up to 01/04/2022, to identify published studies assessing the direct effect of cytokines on intestinal permeability. We collected data on the study design, the method of assessment of intestinal permeability, the type of inter-vention and the subsequent effect on gut permeability.Results: A total of 120 publications were included, describing a total of 89 in vitro and 44 in vivo studies. TNF alpha, IFN gamma or IL-1 beta were the most frequently studied cytokines, inducing an increase in intestinal permeability through a myosin light-chain-mediated mechanism. In situations associated with intestinal barrier disruption, such as inflammatory bowel diseases, in vivo studies showed that anti-TNF alpha treatment decreased intestinal permeability while achieving clinical recovery. In contrast to TNF alpha, IL-10 decreased permeability in conditions associated with intestinal hyperpermeability. For some cytokines (e.g. IL-17, IL-23), results are conflicting, with both an increase and a decrease in gut permeability reported, depending on the study model, methodology, or the studied conditions (e.g. burn injury, colitis, ischemia, sepsis).Conclusion: This systematic review provides evidence that intestinal permeability can be directly influenced by cytokines in numerous conditions. The immune environment probably plays an important role, given the vari-ability of their effect, according to different conditions. A better understanding of these mechanisms could open new therapeutic perspectives for disorders associated with gut barrier dysfunction.

Automated summary

This review summarizes the effects of cytokines on intestinal permeability. It was found that certain cytokines can increase intestinal permeability and lead to excessive inflammatory response. However, the effects of different cytokines may vary under different conditions.