The Initial Course of IL1β, IL-6, IL-8, IL-10, IL-12, IFN-γ and TNF-α with Regard to Severity Grade in Acute Pancreatitis

Sternby, Hanna; Hartman, Hannes; Thorlacius, Henrik; Regnér, Sara

doi:10.3390/biom11040591

Cited by 19 publications

(7 citation statements)

References 29 publications

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“…Activation of pancreatic proteases and dysfunction of pancreatic microcirculation in acute pancreatitis stimulate granulocytes, macrophages, and vascular endothelial cells to release IL-6, TNF-α, and other cytokines that participate in the inflammatory response and immunoregulation ( Pooran et al, 2003 ; Sternby et al, 2021 ). The release of inflammatory factors not only damages local pancreatic tissue, but also leads to a systemic inflammatory response because of the massive release of inflammatory factors into the circulation, which can result in systemic organ failure.…”

Section: Discussionmentioning

confidence: 99%

Effect of Monoacylglycerol Lipase Inhibition on Intestinal Permeability of Rats With Severe Acute Pancreatitis

Wang

Chen

et al. 2022

Front. Pharmacol.

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Background: Endocannabinoid 2-arachidonoylglycerol (2-AG) is an anti-nociceptive lipid that is inactivated through cellular uptake and subsequent catabolism by monoacylglycerol lipase (MAGL). In this study, we investigated the effects of MAGL inhibition on intestinal permeability and explored the possible mechanism.Methods: A rat model of severe acute pancreatitis (SAP) was established. Rats were divided into three groups according to treatment. We analyzed intestinal permeability to fluorescein isothiocyanate-dextran and the levels of inflammatory factors interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) and 2-AG. Hematoxylin and eosin staining was used to assess histological tissue changes. In vivo intestinal permeability was evaluated by transmission electron microscopy. We obtained ileum tissues, extracted total RNA, and applied RNA-sequencing. Sequencing data were analyzed by bioinformatics.Results: Inflammatory factor levels were higher, while 2-AG levels were lower in the SAP group compared with the control group. Administration of JZL184 to rats with SAP increased the levels of 2-AG and lowered the levels of IL-6 and TNF-α. Notably, intestinal permeability was improved by JZL184 as demonstrated by fluorescein isothiocyanate-dextran measurement, hematoxylin and eosin staining, and transmission electron microscopy. RNA-sequencing showed significant transcriptional differences in SAP and JZL184 groups compared with the control group. KEGG analysis showed that the up- or downregulated genes in multiple comparison groups were enriched in two pathways, focal adhesion and PI3K-Akt signaling pathways. Differential alternative splicing (AS) genes, such as Myo9b, Lsp1, and Git2, have major functions in intestinal diseases. A total of 132 RNA-binding proteins (RBPs) were screened by crossing the identified abnormally expressed genes with the reported RBP genes. Among them, HNRNPDL coexpressed the most AS events as the main RBP.Conclusion: MAGL inhibition improved intestinal mucosal barrier injury in SAP rats and induced a large number of differentially expressed genes and alternative splicing events. HNRNPDL might play an important role in improving intestinal mucosal barrier injury by affecting alternative splicing events.

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Section: Discussionmentioning

confidence: 99%

Effect of Monoacylglycerol Lipase Inhibition on Intestinal Permeability of Rats With Severe Acute Pancreatitis

Wang

Chen

et al. 2022

Front. Pharmacol.

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“…Among these differentially expressed cytokines, TNF-α was an early SAP event, and TNFRSF6 and FSL1 were associated with NLRP3 activation and apoptosis [ 11 , 15 , 16 , 17 , 18 ]. TNF-α participates in the activation of NK and T lymphocytes.…”

Section: Discussionmentioning

confidence: 99%

Dynamic Changes in Serum Cytokine Profile in Rats with Severe Acute Pancreatitis

Zhou

Fan

et al. 2023

Medicina

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Background and Objectives: Most published research has only investigated a single timepoint after the onset of severe acute pancreatitis (SAP), meaning that they have been unable to observe the relationship between the dynamic changes in cytokines and SAP progression. In this study, we attempted to reveal the relationship between dynamic changes in cytokine expression levels and SAP disease progression and the relationship between cytokines, using continuous large-scale cytokine detection. Materials and Methods: Seventy rats were randomly assigned to control (Con), sham operation (SO) and SAP groups. The SAP group was randomly allocated to five subgroups at 3, 6, 9, 12 and 15 h after the operation. In the SAP group, 5% sodium taurocholate was injected retrograde into the pancreatic bile duct. Animals in the SO group received a similar incision, a turning over of the pancreas. Control animals did not receive any treatment. We observed the survival, ascites fluid amount, pancreatic histopathological scores and serum amylase activity of SAP rats. We used the cytokine microarray to simultaneously detect 90 cytokines and the dynamic changes in one experiment and to analyze the correlation between cytokine expression and disease progression. Results: The mortality of SAP rats increased with an increase in time. Serum amylase activity, pancreatic histopathological scores and ascites fluid amount were time-dependent. Compared with normal rats, 69 cytokines in SAP rats were significantly changed for at least one timepoint, and 49 cytokines were significantly changed at different timepoints after SAP induction. The changes in inflammatory cytokines were significantly upregulated at 6 and 9 h and 12 h and then significantly decreased. Conclusions: The trend of cytokine expression in SAP rats was not consistent with the disease progression. The cytokine–cytokine receptor interaction and MAPK signal’s dominant cytokines were always highly expressed at various time points over the course of SAP.

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“…The cause might be attributed to the interference with IL-6 cytokine. Currently, serum IL-6 cytokine has been proposed as a valuable prognostic biomarker for the early prediction of AP severity [20,21]. The other various biomarkers, such as CRP and PCT, have been tested for the early prediction of AP severity, while they have not shown a flawless performance [22].…”

Section: Discussionmentioning

confidence: 99%

Serum soluble T cell immunoglobulin mucin domain-3 as an early predictive marker for severity of acute pancreatitis; a retrospective analysis

et al. 2022

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Background Early prediction of severe acute pancreatitis (SAP) plays an important role in timely treatment decisions. Soluble T cell immunoglobulin and mucin domain-3 (sTIM-3) has been applied as a potential biomarker for the prediction of many diseases, while its predictive ability for AP severity remains largely unexplored. In this study, we aimed to identify whether serum sTIM-3 could be used as an indicator of AP severity in the early stage of the disease. Methods A retrospective study was conducted. The enrolled AP patients should meet the 2012 Atlanta guideline and have an onset to admission ≤ 48 h. Results A total of 94 AP patients were enrolled in the current analysis, including 42 (45%), 35 (37%), and 17 (18%) patients were diagnosed as mild AP (MAP), moderately SAP (MSAP), and SAP, respectively. SAP patients had significantly higher the white blood cells (WBCs) count, red blood cells (RBCs) count, C-reactive protein (CRP) level, direct bilirubin level, creatinine and procalcitonin levels compared with MAP and MSAP patients. Among SAP and MSAP patients, significantly higher APACHE II, BISAP, and MCTSI scores were observed compared with MAP patients, and there was significant difference in APACHE II and BISAP scores between SAP and MSAP patients. Stepwise multivariate linear regression analysis showed that the concentrations of serum sTIM-3, as well as the BISAP and MCTSI scores, were significantly associated with the severity of AP. The areas under the ROC curve were 0.914 (95% CI, 0.865-0.963), 0.855 (95%CI, 0.742-0.968) 0.853 (95%CI, 0.768-0.938), and 0.746 (95%CI, 0.633-0.860) for BISAP score, APACHE II score, sTIM-3 level, and MCTSI score, respectively. Conclusions Serum sTIM-3 might be ultimately incorporated into a predictive system for assessing the severity of AP.

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The Initial Course of IL1β, IL-6, IL-8, IL-10, IL-12, IFN-γ and TNF-α with Regard to Severity Grade in Acute Pancreatitis

Cited by 19 publications

References 29 publications

Effect of Monoacylglycerol Lipase Inhibition on Intestinal Permeability of Rats With Severe Acute Pancreatitis

Effect of Monoacylglycerol Lipase Inhibition on Intestinal Permeability of Rats With Severe Acute Pancreatitis

Dynamic Changes in Serum Cytokine Profile in Rats with Severe Acute Pancreatitis

Serum soluble T cell immunoglobulin mucin domain-3 as an early predictive marker for severity of acute pancreatitis; a retrospective analysis

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