No abstract

Intestinal barrier dysfunction plays a critical role in the pathophysiology of many diseases including severe acute pancreatitis (SAP). Interleukin‐22 (IL‐22) is a critical regulator of intestinal epithelial homeostasis. However, the mechanism, origin site, and characteristics of IL‐22 in the intestinal barrier dysfunction remains elusive. Studies were conducted in patients with SAP and SAP mice model. SAP mice model was induced by intraductal infusion of 5% taurocholic acid. The level and source of IL‐22 were analyzed by flow cytometry. The effect of IL‐22 in SAP‐associated intestinal injury were examined through knockout of IL‐22 (IL‐22−/−) or administration of recombinant IL‐22 (rIL‐22). IL‐22 increased in the early phase of SAP but declined more quickly than that of proinflammatory cytokines, such as IL‐6 and TNF‐α. CD177+ neutrophils contributed to IL‐22 expression in SAP. IL‐22 was activated in the colon rather than the small intestine during SAP. Deletion of IL‐22 worse the severity of colonic injury, whereas administration of rIL‐22 reduced colonic injury. Mechanistically, IL‐22 ameliorates the intestinal barrier dysfunction in SAP through decreasing colonic mucosal permeability, upregulation of E‐cadherin and ZO‐1 expression, activation of pSTAT3/Reg3 pathway and restoration of fecal microbiota abundance. This study revealing that early decreased colonic IL‐22 aggravates intestinal mucosal barrier dysfunction and microbiota dysbiosis in SAP. Colonic IL‐22 is likely a promising treating target in the early phase of SAP management. Research in context Evidence before this study Intestinal barrier dysfunction plays a critical role in the pathophysiology of severe acute pancreatitis (SAP). Interleukin‐22 (IL‐22) is a critical regulator of intestinal epithelial homeostasis. However, the mechanism, origin site and characteristics of IL‐22 in the intestinal barrier dysfunction remains elusive. Added value of this study Firstly, we determined the dynamic expression profile of IL‐22 in SAP and found that IL‐22 was mostly activated in the pancreas and colon and decreased earlier than proinflammatory cytokines. CD177+ neutrophils contributed to IL‐22 expression in SAP. Furthermore, we found that IL‐22 ameliorates intestinal barrier dysfunction in SAP through decreasing colonic mucosal permeability, upregulation of E‐cadherin and ZO‐1 expression, activation of pSTAT3/Reg3 pathway and restoration of fecal microbiota abundance. Implications of all the available evidence This study highlights the role of colonic injury and colonic IL‐22 in SAP. IL‐22 is likely a promising treating target in the early phase of SAP management.

Background We aimed to characterize the trends of prognosis in ulcerative colitis (UC) and Crohn’s disease (CD) in a Chinese tertiary hospital. Methods A 30-year retrospective cohort analysis was conducted at Peking Union Medical College Hospital. Consecutive patients newly diagnosed with UC or CD from 1985 to 2014 were included. The primary outcome was in-hospital mortality. The secondary outcomes included surgery and length of stay in hospital. The Pearson correlation coefficient was applied to determine the relationship between time and prognosis. Multivariable logistic regression analysis was performed to determine the risk factors for in-hospital mortality and surgery. Results In total, 1467 patients were included in this study (898 cases with UC and 569 cases with CD). Annual admissions for UC and CD have increased significantly over the last 30 years (UC, r = 0.918, P < 0.05; CD, r = 0.898, P < 0.05). Decreased in-hospital mortality was observed both in patients with UC and CD (UC, from 2.44 to 0.27%, r = − 0.827, P < 0.05; CD, from 12.50 to 0.00%, r = − 0.978, P < 0.05). A decreasing surgery rate was observed in patients with CD (r = − 0.847, P < 0.05), while an increasing surgery rate was observed in patients with UC (r = 0.956, P < 0.05). Shortened average lengths of hospital stay were observed in both UC and CD patients (UC, from 47.83 ± 34.35 to 23.58 ± 20.05 days, r = − 0.970, P < 0.05; CD, from 65.50 ± 50.57 to 26.41 ± 18.43 days, r = − 0.913, P < 0.05). Toxic megacolon and septic shock were independent risk factors for in-hospital mortality in patients with UC. Intestinal fistula and intestinal perforation were independent risk factors for in-hospital mortality in patients with CD. Conclusions In this cohort, the admissions of patients with UC and CD were increased, with significantly improved prognoses during the past 30 years.