Alcohol Research Program, Stritch School of Medicine, Loyola University Chicago Health Sciences Division, Maywood, IL.
Burn and Shock Trauma Research Institute, Stritch School of Medicine, Loyola University Chicago Health Sciences Division, Maywood, IL.
Immunohorizons. 2022 Aug 16;6(8):600-613. doi: 10.4049/immunohorizons.2200032.
Alcohol intoxication combined with burn injury can lead to life-threatening complications, including sepsis, multiple organ failure, and death. After an acute burn, the gastrointestinal system becomes hypoxic because of fluid loss and reduction of intestinal blood flow. This can cause perturbations in the intestinal epithelial barrier, immune function, and the composition of the gut microbiome. Increased gut permeability leads to proinflammatory signaling, contributing to further damage to the intestinal barrier. Recent studies have suggested that IL-27 plays an anti-inflammatory role, which may be beneficial in intestinal barrier repair. Therefore, in this study, we examined the effect of ethanol and burn injury on IL-27 in the small intestine, as well as the potential beneficial role of IL-27 in restoring the intestinal barrier after intoxication and burn. Male C57BL/6 mice were gavaged with 2.9 g/kg ethanol before receiving a ∼12.5% total body surface area scald burn with or without rIL-27 in resuscitation fluid. Our results demonstrate that IL-27-producing cells are reduced in the small intestine after injury. When IL-27 is supplemented in resuscitation fluid, we were able to restore intestinal barrier integrity and transit, mediated through increased intestinal epithelial cell proliferation, reduced inflammatory cytokines, and increased anti-inflammatory cytokine IL-10. We also observed increased gene expression of tight junction proteins. These findings suggest that IL-27 may be a contributor to maintaining proper intestinal barrier function after injury through multiple mechanisms, including preventing excess inflammation and promoting intestinal epithelial cell proliferation and tight junction integrity.
酒精中毒合并烧伤可导致危及生命的并发症，包括脓毒症、多器官衰竭和死亡。急性烧伤后，由于液体流失和肠道血流减少，胃肠道系统会缺氧。这会导致肠道上皮屏障、免疫功能和肠道微生物组组成发生紊乱。肠道通透性增加会导致促炎信号转导，进一步损害肠道屏障。最近的研究表明，IL-27 发挥抗炎作用，这可能有益于肠道屏障修复。因此，在这项研究中，我们研究了乙醇和烧伤对小肠中 IL-27 的影响，以及 IL-27 在中毒和烧伤后恢复肠道屏障中的潜在有益作用。雄性 C57BL/6 小鼠在接受 12.5%总面积的烫伤烧伤前，经灌胃给予 2.9 g/kg 乙醇，并用 rIL-27 补充复苏液。我们的结果表明，损伤后小肠中产生 IL-27 的细胞减少。当 IL-27 补充到复苏液中时，我们能够通过增加肠道上皮细胞增殖、减少炎症细胞因子和增加抗炎细胞因子 IL-10 来恢复肠道屏障完整性和转运。我们还观察到紧密连接蛋白的基因表达增加。这些发现表明，IL-27 可能通过多种机制，包括防止过度炎症和促进肠道上皮细胞增殖和紧密连接完整性，有助于维持损伤后适当的肠道屏障功能。
