Acute pancreatitis (AP) is a serious condition associated with intestinal barrier disruption or inflammation of the pancreatic tissue. Specific microRNAs are involved in the pathogenesis of AP, during which IL-17-producing CD4+ T helper (Th17) cells accumulate in the pancreas. In this study, significantly increased levels of miR-155 were detected in clinical samples from patients with AP, and overexpression of miR-155 correlated with severe AP (SAP). To identify the effect of miR-155 on T cell differentiation, we isolated CD4+ T lymphocytes and in vitro experiments showed that inhibition of miR-155 significantly reversed the stress-induced increase in the Th17/Treg ratio. The results also showed that miR-155 increased the Th17-mediated inflammatory response by targeting SOCS1. The interaction between miR-155 and the 3′-UTR of SOCS1 was confirmed by a dual luciferase reporter assay and RT-PCR. Experimental AP of varying severity was induced in BALB/c mice by caerulein hyperstimulation and miR-155 expression was found to increase with disease progression. Inhibition of miR-155 expression significantly improved the pathology of the pancreas. We also observed downregulation of expression of inflammatory factors, IL-17, SOCS1 and phosphorylated STAT1 after miR-155 inhibition. In summary, miR-155 regulates the Th17/Treg ratio by targeting SOCS1, most probably via direct binding to its 3′-UTR region, indicating that this microRNA may be a potential biomarker and/or therapeutic target for AP.

Red cell distribution width (RDW) has been proposed as an early prognosis marker with increased mortality in variety of pathophysiological conditions. We hypothesized that elevated RDW could be used in judging the severity of acute pancreatitis (AP). We retrospectively and prospectively studied 545 and 72 AP patients, who were admitted to the Shanghai Tenth People's Hospital of Tongji University, respectively. Compared with mild acute pancreatitis, significantly higher RDW was observed in patients with moderately severe acute pancreatitis and sever acute pancreatitis (14.03 ± 1.74% vs. 13.23 ± 1.23%, P < 0.000). RDW values were also found positively correlated with the patient's blood urea nitrogen (r = 0.120, P = 0.026), creatinine (r = 0.182, P = 0.000), age (r = 0.099, P = 0.028), and bedside index of severity in acute pancreatitis scoring system (r = 0.147, P = 0.001), and were negatively correlated with the serum albumin (r = -0.244, P = 0.000). The area under the receiver-operating characteristics was as follows-RDW: 0.677 (95% confidence interval [CI], 0.619-0.735, P < 0.000); combination of RDW and albumin: 0.693 (95% CI, 0.625-0.761, P < 0.000); and the optimal cutoff value for RDW to predict whether patients with AP should be in intensive care unit (ICU) was 13.55 with a sensitivity of 54.5% and a specificity of 73.6%. In the validation study, AP with RDW ≥ 13.55% had significantly higher ICU admission ratio than those with RDW < 13.55% (44.4% vs. 9.8%, P < 0.000). In conclusion, RDW is positively associated with AP severity, and is likely a useful predictive parameter of AP severity.

PURPOSE:To investigate the severity of pancreatitis in lipoprotein lipase (LPL)-deficient hypertriglyceridaemic (HTG) heterozygous mice and to establish an experimental animal model for HTG pancreatitis study. METHODS:LPL-deficient HTG heterozygous mice were rescued by somatic gene transfer and mated with wild-type mice. The plasma amylase, triglyceride, and pathologic changes in the pancreas of the LPL-deficient HTG heterozygous mice were compared with those of wild-type mice to assess the severity of pancreatitis. In addition, acute pancreatitis (AP) was induced by caerulein (50 µg/kg) for further assessment. RESULTS:The levels of plasma amylase and triglyceride were significantly higher in the LPL-deficient HTG heterozygous mice.According to the pancreatic histopathologic scores, the LPL-deficient HTG heterozygous mice showed more severe pathologic damage than the wild-type mice. CONCLUSIONS:Lipoprotein lipase deficient heterozygous mice developed severe caerulein-induced pancreatitis. In addition, their high triglyceride levels were stable. Therefore, LPL-deficient HTG heterozygous mice are a useful experimental model for studying HTG pancreatitis.