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Plasma cytokines can help to identify the development of severe acute pancreatitis on admission.

ABSTRACT: Severe acute pancreatitis (AP) is associated with high morbidity and mortality. Early severity stratification remains a challenging issue to overcome to improve outcomes. We aim to find novel plasma cytokines for the early identification of severe AP according to the revised Atlanta criteria.In this prospective observational study, 30 cytokines, screened semiquantitatively with a human multicytokine array, were submitted to quantitative determination using either microparticle-based multiplex immunoassays analyzed on a Luminex 100 platform or enzyme-linked immunosorbent assay kits. The cytokine profiles of patients and the discriminative value of cytokines for severe AP were analyzed.Plasma samples of 70 patients with AP (20 mild, 30 moderately severe, and 20 severe) were selected in this study if they were admitted within 48?hours of the onset of symptoms. Plasma from healthy volunteers was collected as the healthy control. Growth differentiation factor-15 (GDF-15) and pentraxin 3 (PTX3) on admission were independent prognostic markers for the development of severe AP and had higher discriminative powers than conventional markers (GDF-15 vs hematocrit, P?=?.003; GDF-15 vs C-reactive protein, P?=?.037; GDF-15 vs creatinine, P?=?.048; GDF-15 vs Acute Physiology and Chronic Health Evaluation II, P?=?.007; PTX3 vs hematocrit, P?=?.006; PTX3 vs C-reactive protein, P?=?.047; PTX3 vs Acute Physiology and Chronic Health Evaluation II, P?=?.011; PTX3 vs Bedside Index for Severity in Acute Pancreatitis, P?=?.048).Plasma GDF-15 and PTX3 can help to identify the development of severe AP on admission. Future work should validate their accuracy in a larger, multicenter patient cohort.

SUBMITTER: Deng LH

PROVIDER: S-EPMC5515743 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Plasma cytokines can help to identify the development of severe acute pancreatitis on admission.

Deng Li-Hui LH Hu Cheng C Cai Wen-Hao WH Cai Wen-Hao WH Chen Wei-Wei WW Zhang Xiao-Xin XX Shi Na N Huang Wei W Ma Yun Y Jin Tao T Lin Zi-Qi ZQ Jiang Kun K Guo Jia J Yang Xiao-Nan XN Xia Qing Q

Medicine 20170701 28

Severe acute pancreatitis (AP) is associated with high morbidity and mortality. Early severity stratification remains a challenging issue to overcome to improve outcomes. We aim to find novel plasma cytokines for the early identification of severe AP according to the revised Atlanta criteria.In this prospective observational study, 30 cytokines, screened semiquantitatively with a human multicytokine array, were submitted to quantitative determination using either microparticle-based multiplex im ...[more]

PMID: 28700471

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Project description:IntroductionSevere acute pancreatitis (AP) is associated with high morbidity and mortality. Early prediction of severe AP is needed to improve patient outcomes. The aim of the present study was to find novel cytokines or combinations of cytokines that can be used for the early identification of patients with AP at risk for severe disease.MethodsWe performed a prospective study of 163 nonconsecutive patients with AP, of whom 25 had severe AP according to the revised Atlanta criteria. Admission serum levels of 48 cytokines and growth factors were determined using Bio-Plex Pro Human Cytokine Assay 21-plex and 27-plex magnetic bead suspension panels. Admission plasma levels of C-reactive protein (CRP), creatinine and calcium were measured for comparison. In subgroup analyses, we assessed the cytokine profiles of patients with severe AP (n = 14) who did not have organ dysfunction (OD) upon admission (modified Marshall score <2).ResultsOf 14 cytokines elevated in the severe AP group, interleukin 6 (IL-6) and hepatocyte growth factor (HGF) levels were independent prognostic markers of severe AP. IL-6, HGF and a combination of them predicted severe AP with sensitivities of 56.0%, 60.0% and 72.0%, respectively, and specificities of 90.6%, 92.8% and 89.9%, respectively. The corresponding positive likelihood ratio (LR+) values were 5.9, 8.3 and 7.1, respectively. The predictive values of CRP, creatinine and calcium were comparable to those of the cytokines. In subgroup analyses of patients with severe AP and without OD upon admission, we found that IL-8, HGF and granulocyte colony-stimulating factor (G-CSF) levels predicted the development of severe AP, with G-CSF being the most accurate cytokine at a sensitivity of 35.7%, a specificity of 96.1% and a LR+ of 9.1.ConclusionsIL-6 and HGF levels upon admission have prognostic value for severe AP which is similar to levels of CRP, creatinine and calcium. Although IL-6 and HGF, as either single or combined markers, were not perfect in identifying patients at risk for severe AP, the possibility that combining them with novel prognostic markers other than cytokines might improve prognostic accuracy needs to be studied. The accuracy of IL-8, HGF and G-CSF levels in predicting severe AP in patients without clinical signs of OD upon admission warrants larger studies.

Project description:Ferroptosis is a newly recognized form of regulatory cell death characterized by severe lipid peroxidation triggered by iron overload and the production of reactive oxygen species (ROS). However, the role of ferroptosis in severe acute pancreatitis(SAP) has not been fully elucidated. We established four severe acute pancreatitis models of rats including the sham control group, the SAP group, the Fer -1-treated SAP (SAP + Fer-1) group, the 3-MA-treated SAP (SAP + 3-MA) group. The SAP group was induced by retrograde injection of sodium taurocholate into the pancreatic duct. The other two groups were intraperitoneally injected with ferroptosis inhibitor (Fer-1) and autophagy inhibitor (3-MA), respectively. The model of severe acute pancreatitis with amylase crest-related inflammatory factors was successfully established. Then we detected ferroptosis (GPX4, SLC7A1 etc.) and autophagy-related factors (LC3II, p62 ect.) to further clarify the relationship between ferroptosis and autophagy. Our study found that ferroptosis occurs during the development of SAP, such as iron and lipid peroxidation in pancreatic tissues, decreased levels of reduced glutathione peroxidase 4 (GPX 4) and glutathione (GSH), and increased malondialdehyde(MDA) and significant mitochondrial damage. In addition, ferroptosis related proteins such as GPX4, solute carrier family 7 member 11(SLC7A11) and ferritin heavy chain 1(FTH1) were significantly decreased. Next, the pathogenesis of ferroptosis in SAP was studied. First, treatment with the ferroptosis inhibitor ferrostatin-1(Fer-1) significantly alleviated ferroptosis in SAP. Interestingly, autophagy occurs during the pathogenesis of SAP, and autophagy promotes the occurrence of ferroptosis in SAP. Moreover, 3-methyladenine (3-MA) inhibition of autophagy can significantly reduce iron overload and ferroptosis in SAP. Our results suggest that ferroptosis is a novel pathogenesis of SAP and is dependent on autophagy. This study provides a new theoretical basis for the study of SAP.

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Plasma cytokines can help to identify the development of severe acute pancreatitis on admission.

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Plasma cytokines can help to identify the development of severe acute pancreatitis on admission.

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