Ulinastatin ameliorates tissue damage of severe acute pancreatitis through modulating regulatory T cells

Pan, Yu; Fang, Haizong; Lü, Fang; Pan, Minggui; Chen, Fei; Xiong, Ping; Yao, Yi; Huang, Heguang

doi:10.1186/s12950-017-0154-7

Cited by 30 publications

(22 citation statements)

References 35 publications

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“…In the present study, we found that the levels of CD4 + Foxp3 and Tregs population were significantly increased with positive correlation with the blood levels of ET, TNF-α, and IL-1β in SAP rats. The finding is inconsistent with some studies ( Ding et al, 2007 ; Pan et al, 2017 ), but is supported by others ( Xiong et al, 2012 ; Minkov et al, 2017 ). Our results indicated that the Tregs were activated under inflammatory condition and intestinal mucosal immunity was shifted from an over-inflammatory state to an immunosuppressed state in ASP rats.…”

Section: Discussioncontrasting

confidence: 71%

“…In normal condition, IL-4 secreted by Th2 cells can prevent the activation of macrophages and production of TNF-α and IL-1β to inhibit inflammation and reduce tissue damage ( Hart et al, 2015 ; Hussein and Ahmed, 2016 ). Studies have shown that Tregs were decreased and negatively correlated with serum concentration of TNF-α and the decrease of Tregs may be responsible for uncontrolled immune activation to cause excessive inflammatory response in SAP ( Ding et al, 2007 ; Pan et al, 2017 ). However, another study has showed that the Tregs are abnormal high in SAP patients and elevated circulating Tregs is an independent prognostic biomarker for patients with ASP ( Minkov et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

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Free Total Rhubarb Anthraquinones Protect Intestinal Injury via Regulation of the Intestinal Immune Response in a Rat Model of Severe Acute Pancreatitis

et al. 2018

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Intestinal mucosal immune barrier dysfunction plays a key role in the pathogenesis of severe acute pancreatitis (SAP). Rhubarb is a commonly used traditional Chinese medicine as a laxative in China. It markedly protects pancreatic acinar cells from trypsin-induced injury in rats. Free total rhubarb anthraquinones (FTRAs) isolated and extracted from rhubarb display the beneficial effects of antibacteria, anti-inflammation, antivirus, and anticancer. The principal aim of the present study was to investigate the effects of FTRAs on the protection of intestinal injury and modification of the intestinal barrier function through regulation of intestinal immune function in rats with SAP. We established a rat model of SAP by injecting 3.5% sodium taurocholate (STC, 350 mg/kg) into the biliopancreatic duct via retrograde injection and treated the rats with FTRAs (36 or 72 mg/kg) or normal saline (control) immediately and 12 h after STC injection. Then, we evaluated the protective effect of FTRAs on intestinal injury by pathological analysis and determined the levels of endotoxin (ET), interleukin 1β (IL-1β), tumor necrosis factor α (TNF-α), nitric oxide (NO), myeloperoxidase (MPO), capillary permeability, nucleotide-binding oligomerization domain-like receptors 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD domain (ASC), casepase-1, secretary immunoglobulin A (SIgA), regulatory T cells (Tregs), and the ratio of Th1/Th2 in the blood and/or small intestinal tissues or mesenteric lymph node (MLN) cells. Moreover, the chemical profile of FTRAs was analyzed by HPLC-UV chromatogram. The results showed that FTRAs significantly protected intestinal damage and decreased the levels of ET, IL-1β, TNF-α, and NO in the blood and TNF-α, IL-1β, and protein extravasation in the intestinal tissues in SAP rats. Furthermore, FTRAs significantly decreased the expressions of NLRP3, ASC, and caspase-1, the number of Tregs and the ratio of Th1/Th2, while significantly increased the expression of SIgA in the intestinal tissues and/or MLN cells in SAP rats. Our results indicate that FTRAs could protect intestinal injury and improve intestinal mucosal barrier function through regulating immune function of SAP rats. Therefore, FTRAs may have the potential to be developed as the novel agent for the treatment of SAP clinically.

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Section: Discussioncontrasting

confidence: 71%

Section: Discussionmentioning

confidence: 99%

Free Total Rhubarb Anthraquinones Protect Intestinal Injury via Regulation of the Intestinal Immune Response in a Rat Model of Severe Acute Pancreatitis

et al. 2018

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“…It also inhibits the generation of myocardial inhibitory factor, reducing the production of oxygen free radicals and inhibiting the excessive release of various inflammatory mediators. It is widely used in the treatment of SIRS and other diseases (29,30). The protective mechanism of ulinastatin can be attributed to the inhibited production of pro-inflammatory cytokines (31), The effect of ulinastatin on respiratory function after CPB under DHCA could improve oxygenation (32).…”

Section: Discussionmentioning

confidence: 99%

Inflammation is related to preoperative hypoxemia in patients with acute Stanford type A aortic dissection

Duan¹,

Zhao²,

Lu³

et al. 2018

J. Thorac. Dis.

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“…MSAP and SAP can develop into immunosuppression, leading to secondary infection and pancreatic necrosis [21,22]. Our study showed that compared with healthy volunteers, serum sPD-1 levels in the MSAP and SAP patients increased continuously during the early course of the disease, especially the patients with ICs.…”

Section: Discussionmentioning

confidence: 64%

Serum soluble PD-1 plays a role in predicting infection complications in patients with acute pancreatitis

Pan

Fei

et al. 2020

Preprint

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Background: Most of acute pancreatitis (AP) are mild and self-limiting, however, 15%-20% of patients develop severe AP (SAP) or moderately SAP (MSAP) with local or systemic complications. Infection complications (ICs) result in 40-70% morbidity and high mortality rates among SAP and MSAP patients. It’s require that early identification of SAP and MSAP patients at risk of developing ICs. Several studies have indicated that serum soluble programmed cell death protein (sPD-1) or programmed cell death 1 ligand (sPD-L1) levels were higher in patients with severe sepsis than in healthy volunteers, and have a predictive capacity for mortality. However, the role of serum soluble PD-1/PD-L1 in AP remains unclear. This study aimed to investigate whether the ICs of AP patients is associated with their sPD-1 and sPD-L1 levels, which were determined via enzyme-linked immunosorbent assay of peripheral blood samples from 63 MSAP and SAP patients and 30 healthy volunteers.Results: The serum sPD-1 levels in AP patients on days 1, 3 and 10 after onset were significantly increased in a time-dependent manner compared with that in healthy volunteers. Moreover, the AP patients with ICs had significantly higher serum sPD-1 levels than the AP patients without ICs. While serum sPD-L1 levels in AP patients were similar to that in healthy volunteers. Besides, serum levels of sPD-1/sPD-L1 10 were negatively correlated with circulating lymphocytes. Univariate and Multivariate regression analyses showed that the up-regulated serum sPD-1 level was an independent risk factor for ICs in AP. The area under the receiver operating characteristics (ROCs) curve indicated that combination with Acute Physiology and Chronic Health Evaluation II (APACHE II) score and serum sPD-1 level had a high accuracy in predicting ICs in AP patients.Conclusion: Serum sPD-1/sPD-L1 may be involved in the immunosuppressive process in AP. Moreover, the serum sPD-1 level may be an independent risk factor for predicting ICs in AP patients.

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Ulinastatin ameliorates tissue damage of severe acute pancreatitis through modulating regulatory T cells

Cited by 30 publications

References 35 publications

Free Total Rhubarb Anthraquinones Protect Intestinal Injury via Regulation of the Intestinal Immune Response in a Rat Model of Severe Acute Pancreatitis

Free Total Rhubarb Anthraquinones Protect Intestinal Injury via Regulation of the Intestinal Immune Response in a Rat Model of Severe Acute Pancreatitis

Inflammation is related to preoperative hypoxemia in patients with acute Stanford type A aortic dissection

Serum soluble PD-1 plays a role in predicting infection complications in patients with acute pancreatitis

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