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Qiu L, Zhou Y, Yu Q, Yu J, Li Q, Sun R. Decreased levels of regulatory B cells in patients with acute pancreatitis: association with the severity of the disease. Oncotarget 2018; 9:36067-36082. [PMID: 30546828 PMCID: PMC6281415 DOI: 10.18632/oncotarget.23911] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2017] [Accepted: 11/03/2017] [Indexed: 12/23/2022] Open
Abstract
Early stratification of the severity of acute pancreatitis (AP) is clinically important. Regulatory B cells have been found to be associated with disease activity of autoimmune diseases. However, the role of Regulatory B cells in AP remains unknown. We investigate the dynamic longitudinal changes in circulating IL-10-producing B cells (B10) and memory CD19+CD24hiCD27hi cells in patients with AP to evaluate their prediction utility for AP severity. B10, CD19+CD24hiCD27hi cells, inflammatory markers and cytokines were detected in patients with AP immediately after admission to the hospital (day 1), then on the third and seventh days. We observed decreases in lymphocytes, CD19+, B10, CD19+CD24hiCD27hi cells and lower mean fluorescence intensity (MFI) of CD80 and CD86 on B10 or CD19+CD24hiCD27hi cells in patients with AP, especially in those with severe acute pancreatitis (SAP). CD19+CD24hiCD27hi cells from patients with AP suppressed the cytokine productions of CD4+ T cells and CD14+ monocytes, but had impaired ability to induce regulatory T cells response. B10 and CD19+CD24hiCD27hi cells significantly increased in patients with mild acute pancreatitis (MAP) from day 1 to day 7, whereas these indexes remained stable in patients with SAP. B10 or CD19+CD24hiCD27hi cells were negatively correlated with the severity index (APACHE II score), inflammatory markers (C-reactive protein, CD64 index), and cytokines (IL-6, IL-17, TNF-α). Furthermore, receiver operating characteristic (ROC) curve analysis revealed that B10 and CD19+CD24hiCD27hi cells could predict the development of SAP. Thus, the detection of B10 and CD19+CD24hiCD27hi cells may be a practical way to improve the early assessment of AP severity.
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Affiliation(s)
- Liannv Qiu
- Department of Clinical Laboratory, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, 310004, China
| | - Yonglie Zhou
- Department of Clinical Laboratory, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, 310004, China
| | - Qinghua Yu
- Department of Clinical Laboratory, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, 310004, China
| | - Junde Yu
- Department of Clinical Laboratory, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, 310004, China
| | - Qian Li
- Department of Intensive Care Unit, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, 310004, China
| | - Renhua Sun
- Department of Intensive Care Unit, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, 310004, China
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Nicotine ameliorates experimental severe acute pancreatitis via enhancing immunoregulation of CD4+ CD25+ regulatory T cells. Pancreas 2015; 44:500-6. [PMID: 25742430 DOI: 10.1097/mpa.0000000000000294] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVES Activation of "nicotinic anti-inflammatory pathway" could reduce severity of inflammation and injury induced by acute pancreatitis. However, the role of regulatory T (Treg) cells in this pathway is unclear. METHODS Severe acute pancreatitis (SAP) was induced in mice through retrograde injection of 50-μL 2% Na-taurocholate into the pancreatic duct of the mouse. In nicotine treatment group, nicotine (50, 100, and 300 μg/kg) was administered 1 hour before and after SAP operation through intraperitoneal injection. We compared the properties of Treg cell percentage and specific marker such as cytotoxic T-lymphocyte antigen 4 and forkhead box transcription factor forkhead/winged helix transcription factor p3 on Treg using quantitative reverse transcription polymerase chain reaction and flow cytometry. All experiment animal serum cytokines were measured using enzyme-linked immunosorbent assay. One-way analysis of variance was applied to evaluate the experimental data and for statistical comparisons. The survival rate data were analyzed using the log-rank test. RESULTS Nicotine significantly protected mice from lethal SAP in a dose-dependent fashion by inhibiting tissue injury, digestive enzyme production, and proinflammatory cytokines production. Moreover, nicotine up-regulated the number and suppressive capacity of CD4 CD25 Treg via inducing the expression of immunoregulatory molecules and transforming growth factor β1 elevation. CONCLUSIONS Modulating immunoregulation of CD4 CD25 Treg is a critical mechanism for nicotinic anti-inflammatory pathway and it may be feasible to use selective agonists as an immunotherapy for SAP.
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Akay C, Yaman H, Oztosun M, Cakir E, Yildirim AO, Eyi YE, Agilli M, Akgul EO, Aydin I, Kaldirim U, Tuncer SK, Eken A, Oztas E, Poyrazoglu Y, Yasar M, Ozkan Y. The protective effects of taurine on experimental acute pancreatitis in a rat model. Hum Exp Toxicol 2013; 32:522-9. [DOI: 10.1177/0960327113482692] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
The aim of this study was to investigate the protective effects of taurine (Tau) on experimental acute pancreatitis (AP) in a rat model by measuring cytokines and oxidant stress markers. Forty rats were randomly divided into four groups: sham, AP, Tau and AP + Tau. AP was induced with sodium taurocholate. No treatment was given to the AP. All rats were killed 5 days later. Pancreatic tissues of rats and blood samples were obtained. Tau treatment significantly decreased serum amylase activity ( p < 0.001), total injury score ( p < 0.001), malondialdehyde levels ( p < 0.001) and myeloperoxidase (MPO) activity ( p < 0.001). There was no significant difference between the Tau and AP + Tau groups in serum and pancreatic tumor necrosis factor-α, interleukin (IL)-1β and IL-6 levels ( p = 1.000). Histopathologic scores in the AP + Tau and Tau groups were significantly lower compared with the AP group (both p < 0.001). These results showed that Tau reduces lipid peroxidation, amylase and MPO activities and the concentrations of proinflammatory cytokines secondary to AP and also increases superoxide dismutase and glutathione peroxidase activities in rats with sodium taurocholate-induced AP. It also has a marked ameliorative effect at histopathologic lesions. With these effects, Tau protects the cells from oxidative damage, reduces inflammation and promotes regression of pancreatic damage.
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Affiliation(s)
- C Akay
- Department of Pharmaceutical Toxicology, Gulhane Military Medical Academy, Etlik, Ankara, Turkey
| | - H Yaman
- Clinical Biochemistry, Gulhane Military Medical Academy, Etlik, Ankara, Turkey
| | - M Oztosun
- Turkish Armed Forces, Health Services Command, Etimesgut, Ankara, Turkey
| | - E Cakir
- Clinical Biochemistry, Gulhane Military Medical Academy, Etlik, Ankara, Turkey
| | - AO Yildirim
- Emergency Medicine, Gulhane Military Medical Academy, Etlik, Ankara, Turkey
| | - YE Eyi
- Emergency Medicine, Gulhane Military Medical Academy, Etlik, Ankara, Turkey
| | - M Agilli
- Clinical Biochemistry, Gulhane Military Medical Academy, Etlik, Ankara, Turkey
| | - EO Akgul
- Clinical Biochemistry, Gulhane Military Medical Academy, Etlik, Ankara, Turkey
| | - I Aydin
- Clinical Biochemistry, Gulhane Military Medical Academy, Etlik, Ankara, Turkey
| | - U Kaldirim
- Emergency Medicine, Gulhane Military Medical Academy, Etlik, Ankara, Turkey
| | - SK Tuncer
- Emergency Medicine, Gulhane Military Medical Academy, Etlik, Ankara, Turkey
| | - A Eken
- Department of Pharmaceutical Toxicology, Gulhane Military Medical Academy, Etlik, Ankara, Turkey
| | - E Oztas
- Histology and Embryology, Gulhane Military Medical Academy, Etlik, Ankara, Turkey
| | - Y Poyrazoglu
- Emergency Medicine, Gulhane Military Medical Academy, Etlik, Ankara, Turkey
| | - M Yasar
- Emergency Medicine, Gulhane Military Medical Academy, Etlik, Ankara, Turkey
| | - Y Ozkan
- Pharmaceutical Technology, Gulhane Military Medical Academy, Etlik, Ankara, Turkey
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Li CY, Yong GZ, Feng YC, He GB, Xiang JY, Ming W. Relationship of plasma levels of sICAM-1, TNF-α and D-dimer with disease severity in patients with acute pancreatitis. Shijie Huaren Xiaohua Zazhi 2010; 18:3480-3484. [DOI: 10.11569/wcjd.v18.i32.3480] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the relationship of plasma levels of soluble intercellular adhesion molecule-1 (sICAM-1), tumor necrosis factor-alpha (TNF-α) and D-dimer with disease severity in patients with acute pancreatitis (AP).
METHODS: Thirty-four patients with severe acute pancreatitis (SAP), 22 patients with mild acute pancreatitis (MAP), 36 patients with systemic inflammatory response syndrome (SIRS), 20 patients with non-SIRS diseases, and 24 healthy volunteers were evaluated in this study. Plasma concentrations of sICAM-1, TNF-α and D-dimer were measured by ELISA. The data obtained were subjected to one-way ANOVA, Pearson correlation and ROC curve analyses.
RESULTS: There were significant differences in plasma sICAM-1 and D-dimer levels between SAP and MAP patients (740.18 μg/L ± 649.54 μg/L vs 481.18 μg/L ± 306.50 μg/L; 0.90 mg/L ± 0.20 mg/L vs 0.69 mg/L ± 0.19 mg/L, both P < 0.05). Significant difference was also noted in plasma TNF-α level between AP patients and healthy controls though there was no significant difference in plasma TNF-α level between SAP and MAP patients. Compared with the non-SIRS group, the plasma concentrations of sICAM-1, TNF-α and D-dimer were significantly higher in the SIRS group (741.17 µg/L ± 592.95 µg/L vs 479.65 µg/L ± 451.21 µg/L; 17.82 µg/L ± 13.84 µg/L vs 12.09 µg/L ± 3.99 µg/L; 0.90 mg/L ± 0.17 mg/L vs 0.69 mg/L ± 0.23 mg/L, all P < 0.05). Plasma sICAM-1 level was related to D-dimer level in both MAP (r = 0.738, P < 0.01) and SAP patients (r = 0.452, P < 0.01). Plasma TNF-α level was not correlated with D-dimer level (r = 0.110, P = 0.420). D-dimer had larger area under the ROC curve in diagnosing SAP.
CONCLUSION: Plasma sICAM-1 and D-dimer concentrations increase greatly in SAP patients. Highly elevated plasma sICAM-1 or D-dimer levels may help identify SAP.
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Abstract
OBJECTIVES In this study, the effects of adalimumab (ADA), a fully humanized IgG1 monoclonal antibody to tumor necrosis factor α, on experimentally acute pancreatitis (AP) were examined. METHODS Healthy Wistar rats (n = 32) were randomly divided into 4 groups: group 1, AP; group 2, AP + ADA; group 3, control (physiologic saline), and group 4, physiologic saline + ADA (n = 8/group). Acute pancreatitis was induced with a retrograde injection of 3% sodium (Na)-taurocholate into the common biliopancreatic duct. Adalimumab was simultaneously administered at 50 mg/kg intraperitoneally for groups 2 and 4. Physiologic saline was administered instead of Na-taurocholate for non-AP groups. After 24 hours, serum amylase, lactate dehydrogenase, pancreatic myeloperoxidase, and malondialdehyde activities, along with pancreatic histopathology, were examined. RESULTS Adalimumab treatment significantly decreased serum amylase activity (AP, 2778.25 ± 298.80; AP + ADA, 2143.13 ± 221.69; control, 1541.00 ± 148.39; ADA, 1143.00 ± 256.30 U/L; P < 0.001), lactate dehydrogenase activity (AP, 2978.37 ± 364.65; AP + ADA, 2582.75 ± 164.23; control 931.25 ± 135.93; ADA, 582.62 ± 99.37 U/L; P < 0.001), myeloperoxidase activity (AP, 1.44 ± 0.20; AP + ADA, 0.86 ± 0.01; control, 0.60 ± 0.17; ADA, 0.41 ± 0.00 U/g of wet tissue; P < 0.001), malondialdehyde activity (AP, 16.94 ± 3.98; AP + ADA, 7.66 ± 2.27; control, 9.07 ± 1.00; ADA, 3.58 ± 0.30 nmol/g; P < 0.01), and total histopathologic scores (AP, 2.75 ± 0.16; AP + ADA, 1.50 ± 0.19; control, 0.00 ± 0.00; ADA, 0.00 ± 0.00; P < 0.001). CONCLUSIONS These results support the idea that adalimumab might be beneficial for severity of AP.
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Liu SL, Liao WJ, Wu LQ. N-acetylcysteine protects against liver injury in rats with severe acute pancreatitis. Shijie Huaren Xiaohua Zazhi 2010; 18:1046-1050. [DOI: 10.11569/wcjd.v18.i10.1046] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To explore whether N-acetylcysteine (NAC) reduces liver injury in rats with severe acute pancreatitis (SAP).
METHODS: Fifty-four Sprague-Dawley rats were randomized into sham-operation group, SAP group and NAC treatment group. SAP was induced in rats by retrograde injection of 4% sodium taurocholate into the pancreatic duct. Rats in the NAC treatment group received an intravenous injection of NAC (200 mg/kg) one hour after sodium taurocholate injection. All the animals were sacrificed at 3, 6 and 12 h after SAP induction. The activation of nuclear factor-κB (NF-κB) in the liver was determined by immunohistochemistry. The hepatic expression of inducible nitric oxide synthase (iNOS) mRNA was assayed by reverse transcription-polymerase chain reaction (RT-PCR). Meanwhile, plasma amylase and liver function (ALT and AST) were measured.
RESULTS: SAP induction significantly enhanced NF-κB binding activity and up-regulated iNOS mRNA expression in the liver of rats. NAC treatment for different durations could significantly suppress the activation of NF-κB (3 h: 0.32 ± 0.05 vs 0.46 ± 0.04, 6 h: 0.56 ± 0.07 vs 0.97 ± 0.18 and 12 h: 0.87 ± 0.14 vs 1.13 ± 0.11, respectively; all P < 0.05) and reduce the levels of plasma amylase, ALT and AST.
CONCLUSION: NF-κB activation and iNOS mRNA expression are associated with liver injury in SAP. NAC protects against SAP-induced liver injury perhaps by blocking the activation of NF-κB.
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Yilmaz M, Topsakal S, Herek O, Ozmen O, Sahinduran S, Buyukoglu T, Yonetci N. Effects of etanercept on sodium taurocholate-induced acute pancreatitis in rats. Transl Res 2009; 154:241-9. [PMID: 19840765 DOI: 10.1016/j.trsl.2009.07.009] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2009] [Revised: 07/13/2009] [Accepted: 07/15/2009] [Indexed: 12/22/2022]
Abstract
In this study, we examined the effects of etanercept (ETA) on experimentally induced pancreatitis. Acute pancreatitis was induced with Na taurocholate. ETA was simultaneously administered to treatment groups. Serum amylase and lipase activity, pancreatic histopathology, apoptosis, malondialdehyde (MDA), and myeloperoxidase enzyme activity (MPO) were assessed. Although rats in the groups 1, 2, and 3 were sacrificed 24h later, groups 4, 5, and 6 were sacrificed 5 days later. ETA treatment significantly decreased serum amylase activity (nontreated, 2636.16+/-191.94; treated, 1898.71+/-262.53; control, 506.28+/-17.31 U/L, P<0.001), lipase activity (nontreated, 3049.67+/-972.65; treated, 2538.85+/-660.45; control, 88.57+/-7.54 U/L, P<0.001), histopathologic score (nontreated, 5.43+/-0.43; treated, 2.57+/-0.20; control, 0.71+/-0.18, P<0.001), MDA (nontreated, 105.77+/-13.29; treated, 92.89+/-10.39; control, 41.26+/-2.54 nmol/g, P<0.001), and MPO (nontreated, 0.64+/-1.15; treated, 0.59+/-0.13; control, 0.17+/-0.02 units/g/wet weight, P<0.001) activity in 24-h groups. In 5-day groups, ETA treatment decreased amylase activity (nontreated, 738.67+/-48.60; treated, 497.14+/-47.25; control, 389.00+/-9.17 U/L, P<0.001), lipase activity (nontreated, 101.33+/-39.32; treated, 34.57+/-7.29; control, 23.42+/-2.12 U/L, P<0.001), histopathologic score (nontreated, 5.43+/-0.43; treated, 3.71+/-0.68; control, 0.00+/-0.00, P<0.001), MDA (nontreated, 67.91+/-4.28; treated, 60.91+/-3.57; control, 14.85+/-1.16 nmol/g, P<0.001), and MPO (nontreated, 0.36+/-0.04; treated, 0.27+/-0.02; control, 0.14+/-0.02 units/g/wet weight, P<0.001) activity. Caspase-positive cells numbers around the necrosis significantly decreased by ETA treatment in both 24-h groups (nontreated, 74.28+/-3.26; treated, 67.00+/-1.15; control, 3.85+/-0.63, P<0.001) and 5-day groups (nontreated, 79.85+/-3.01; treated, 47.85+/-5.76; control, 2.22+/-0.63, P<0.001). These results showed that ETA has an ameliorating effect on sodium taurocholate-induced acute necrotic pancreatitis.
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Affiliation(s)
- Mustafa Yilmaz
- Department of Internal Medicine, University of Pamukkale, Denizli, Turkey
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Shi C, Wang X, Zhao X, Andersson R. Cellular and molecular events in acute pancreatitis. ACTA ACUST UNITED AC 2009. [DOI: 10.1080/17471060600776858] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
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Blocking of monocyte chemoattractant protein-1 (MCP-1) activity attenuates the severity of acute pancreatitis in rats. J Gastroenterol 2008; 43:79-85. [PMID: 18297440 DOI: 10.1007/s00535-007-2126-9] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2007] [Accepted: 10/08/2007] [Indexed: 02/04/2023]
Abstract
BACKGROUND Monocyte chemoattractant protein-1 (MCP-1) has been shown to affect the progression of various inflammatory disorders, including pancreatitis. To investigate the role of MCP-1 in acute pancreatitis and to seek possible therapeutic means, we evaluated the effect of a plasmid expression vector containing a dominant-negative mutant MCP-1 gene (mMCP-1). METHODS Two rat models of acute pancreatitis were employed that used either cerulein (for mild pancreatitis) or a mixture of 5% taurocholic acid and trypsin (for severe pancreatitis). At 6 h after induction of acute pancreatitis with or without injection of mMCP-1, serum amylase levels and cytokine levels, as well as morphological evaluation of the pancreas, were determined. Survival rates were also evaluated. RESULTS Severe pancreatitis was significantly reduced by mMCP-1 injection. mMCP-1 decreased serum levels of amylase, IL-6, IL-10, and LDH, and improved the survival rate 48 h after disease onset. Histopathological changes of pancreas and lungs were also improved by mMCP-1. CONCLUSIONS MCP-1 appears to be involved in the progression of severe forms of acute pancreatitis. Our data suggested that MCP-1 is a candidate as a therapeutic target to treat acute pancreatitis.
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Zou S, Tian FZ, Tang LJ, Li DX, Wang T, Shi L. Early growth response factor 1 expression in rat lungs and alveolar macrophages during acute pancreatitis. Shijie Huaren Xiaohua Zazhi 2007; 15:3690-3696. [DOI: 10.11569/wcjd.v15.i35.3690] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the possible role of early growth response factor 1 (EGR-1) in a rat model of lung injury complicated by taurocholate sodium-induced acute pancreatitis.
METHODS: Forty male Wistar rats were randomly divided into four groups. Normal saline was injected into the common bile duct (CBD) of rats in group A, and taurocholate sodium was injected into the CBD of rats in groups B, C and D. Three hours after injection, all animals were sacrificed, and blood, pancreas and lungs were harvested. Serum levels of tumor necrosis factor (TNF)-α and interleukin (IL)-1β were measured. Pathological scoring of the pancreas was analyzed, and the pulmonary wet to dry weight ratio was measured. Immunohistochemical staining of EGR-1 on lung paraffin sections was observed and assayed semi-quantitatively. Immunocytochemical staining of EGR-1 of AMs was observed and assayed semi-quantitatively, and the concentration of TNF-α and IL-1β in culture fluid was measured. AMs were divided into four groups and treated with elastase as above. EGR-1, TNF-α and IL-1β mRNA expressions were assessed using RT-PCR.
RESULTS: Pulmonary positive staining of EGR-1 was more intense in the model of severe acute pancreatitis. Furthermore, EGR-1 staining differed among acute pancreatitis models with different severities. EGR-1 expressed in lungs correlated with the parameters that demonstrated pancreatitis severity and pulmonary injury: pathological scoring of pancreatitis (r = 0.59), pulmonary wet to dry weight ratio (r = 0.61), and serum TNF-α (r = 0.63) and IL-1β (r = 0.58). EGR-1 protein and mRNA expressed in AMs were correlated with the TNF-α and IL-1β protein (r = 0.64, 0.51, P < 0.01) and mRNA levels (r = 0.62, 0.59, P < 0.01), and were partly dependent on the ERK 1/2 pathway.
CONCLUSION: EGR-1 may play an important role in lung injury during acute pancreatitis, and the possible mechanism relates to its mediation of production of inflammatory cytokines.
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De Campos T, Deree J, Coimbra R. From acute pancreatitis to end-organ injury: mechanisms of acute lung injury. Surg Infect (Larchmt) 2007; 8:107-20. [PMID: 17381402 DOI: 10.1089/sur.2006.011] [Citation(s) in RCA: 50] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Multi-organ dysfunction, and in particular lung injury, is often responsible for the unfavorable outcome of patients with severe acute pancreatitis. Understanding of the mechanisms by which local inflammation in the pancreas leads to end-organ injury is crucial for the development of new therapeutic strategies. METHODS A MEDLINE search was performed with the terms "acute pancreatitis," "lung injury," "inflammatory response," "SIRS," and "multi-organ dysfunction." Pertinent articles were selected for analysis. RESULTS Modulation of the inflammatory response using a combination of immunomodulatory agents may decrease the incidence of severe pancreatitis-related acute lung injury and acute respiratory distress syndrome. CONCLUSION Clinical trials are of utmost importance to establish the validity of such strategies.
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Affiliation(s)
- Tercio De Campos
- Division of Trauma, University of California-San Diego, 200 W. Arbor Drive, San Diego, CA 92103, USA
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Ohashi S, Nishio A, Nakamura H, Kido M, Ueno S, Uza N, Inoue S, Kitamura H, Kiriya K, Asada M, Tamaki H, Matsuura M, Kawasaki K, Fukui T, Watanabe N, Nakase H, Yodoi J, Okazaki K, Chiba T. Protective roles of redox-active protein thioredoxin-1 for severe acute pancreatitis. Am J Physiol Gastrointest Liver Physiol 2006; 290:G772-81. [PMID: 16322089 DOI: 10.1152/ajpgi.00425.2005] [Citation(s) in RCA: 56] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Severe acute pancreatitis is a disease with high mortality, and infiltration of inflammatory cells and reactive oxygen species have a crucial role in the pathophysiology of this disease. Thioredoxin-1 (TRX-1) is an endogenous redox-active multifunctional protein with antioxidant and anti-inflammatory effects. TRX-1 is induced in various inflammatory conditions and shows cytoprotective effects. The aim of the present study was to clarify the protective roles of TRX-1 in the host defense mechanism against severe acute pancreatitis. Experimental acute pancreatitis was induced by intraperitoneal administration of cerulein, a CCK analog, and aggravated by lipopolysaccharide injection in transgenic mice overexpressing human TRX-1 (hTRX-1) and control C57BL/6 mice. Transgenic overexpression of hTRX-1 strikingly attenuated the severity of experimental acute pancreatitis. TRX-1 overexpression suppressed neutrophil infiltration as determined by myeloperoxidase activity, oxidative stress as determined by malondialdehyde concentration, and cytoplasmic degradation of inhibitor of kappaB-alpha, thereby suppressing proinflammatory cytokines, tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6; a neutrophil chemoattractant, keratinocyte-derived chemokine; and inducible nitric oxide synthase in the pancreas. Administration of recombinant hTRX-1 also suppressed neutrophil infiltration, reduced the inflammation of the pancreas and the lung, and improved the mortality rate. The present study suggests that TRX-1 has potent antioxidant and anti-inflammatory actions in experimental acute pancreatitis and might be a new therapeutic strategy to improve the prognosis of severe acute pancreatitis.
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Affiliation(s)
- Shinya Ohashi
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Institute for Virus Research, Kyoto University, Japan
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Ohashi S, Nishio A, Nakamura H, Kido M, Kiriya K, Asada M, Tamaki H, Fukui T, Kawasaki K, Watanabe N, Yodoi J, Okazaki K, Chiba T. Clinical significance of serum thioredoxin 1 levels in patients with acute pancreatitis. Pancreas 2006; 32:264-70. [PMID: 16628081 DOI: 10.1097/01.mpa.0000203958.93758.bd] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVE Thioredoxin 1 (TRX-1), a redox-regulating protein with antioxidant activity, is induced by oxidative stress, and serum TRX-1 levels are recognized as an oxidative-stress marker. The aim of this study was to clarify the clinical significance of serum TRX-1 levels in patients with acute pancreatitis (AP) and evaluate the usefulness of this measurement in assessing disease severity. METHODS Serum TRX-1 levels were determined on admission in 18 patients with severe AP and 36 patients with mild AP. We also investigated the relationship between serum TRX-1 levels and clinical and laboratory data. RESULTS The median serum TRX-1 levels on admission were 54.9 ng/mL in mild AP and 118.8 ng/mL in severe AP. When the cutoff value for TRX-1 in predicting severe AP was determined to be 100 ng/mL, its sensitivity, specificity, and accuracy were 83.3%, 94.4%, and 90.7%, respectively. A significant correlation was observed between serum TRX-1 levels and Ranson score (r = 0.674), C-reactive protein (r = 0.718), interleukin 6 (r = 0.712), leukocyte count (r = 0.642), and serum amylase (r = 0.436). CONCLUSIONS Serum TRX-1 levels significantly correlate with AP severity. TRX-1 should constitute a reliable oxidative-stress marker for the evaluation of AP severity in relation to oxidative stress.
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Affiliation(s)
- Shinya Ohashi
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
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Yang YL, Li JP, Li KZ, Dou KF. Tumor necrosis factor α antibody prevents brain damage of rats with acute necrotizing pancreatitis. World J Gastroenterol 2004; 10:2898-900. [PMID: 15334696 PMCID: PMC4572128 DOI: 10.3748/wjg.v10.i19.2898] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
AIM: To study the protective effects of tumor necrosis factor α (TNFα ) antibody on pancreatic encephalopathy in rats.
METHODS: One hundred and twenty SD rats were randomly divided into normal control group, acute necrotizing pancreatitis group and TNFα antibody treated group. Acute hemorrhage necrotizing pancreatitis model in rats was induced by retrograde injection of 50 g/L sodium taurocholate into the pancreatobiliary duct. Serum TNFα was detected and animals were killed 12 h after drug administration. Changes in content of brain water, MDA and SOD as well as leucocyte adhesion of brain microvessels were measured.
RESULTS: In TNFα antibody treated group, serum TNFα level was decreased. Content of brain water, MDA and SOD as well as leucocyte adhesion were decreased significantly in comparison with those of acute necrotizing pancreatitis group (P < 0.05).
CONCLUSION: TNFα antibody can alleviate the brain damage of rats with acute hemorrhage necrotizing pancreatitis.
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Affiliation(s)
- Yan-Ling Yang
- Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China
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Axelsson J, Wang X, Andersson R. Novel understanding of pathophysiology and potential intervention in acute pancreatitis based on studies of gene-modified mice. Scand J Gastroenterol 2004; 39:409-15. [PMID: 15180175 DOI: 10.1080/00365520310008421] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Affiliation(s)
- J Axelsson
- Dept. of Surgery and Gastroenterology, Lund University Hospital, Lund, Sweden
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Liu HS, Pan CE, Liu QG, Yang W, Liu XM. Effect of NF-κB and p38 MAPK in activated monocytes/macrophages on pro-inflammatory cytokines of rats with acute pancreatitis. World J Gastroenterol 2003; 9:2513-8. [PMID: 14606087 PMCID: PMC4656531 DOI: 10.3748/wjg.v9.i11.2513] [Citation(s) in RCA: 59] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: Proinflammatory cytokines TNF-α and IL-6 play a main role in acute pancreatitis (AP). Cytokine biosynthesis runs through two major signaling pathways at the level of proteins: nuclear transcription factor-κB (NF-κB) and p38 mitogen-activated protein kinase (p38 MAPK). The aim of the study was to investigate the effect of NF-κB and p38 MAPK in activated monocytes/macrophages on cytokines of rats with acute pancreastitis.
METHODS: Taurocholate (3% and 5%) at doses of 1 mL/kg was administered into the biliopancreatic duct of male Sprague-Dawley (SD) rats to reduce acute edematous pancreariris (AEP) and acute necrotizing pancreatitis (ANP). Pancreatic tissues were prepared immediately after death. At this point, blood was obtained for determination of serum amylase and pro-inflammatory TNF-α and IL-6. Activated monocytes/macrophages were captured from blood and so were ascites. NF-κB and p38 MAPK in activated monocytes/macrophages were measured by immunohistochemistry method. Pancreatic tissue samples were prepared for routine light microscopy, using hematoxylin and eosin (HE) staining.
RESULTS: The serum levels of amylase were 3056.00 ± 1232.35 IU/L and 4865.12 ± 890.34 IU/L at 3 and 6 h in ANP group, which were significantly higher than those (3056.00 ± 1232.35 IU/L and 3187.17 ± 821.16 IU/L) (P < 0.05, respectively) in AEP group. In ascites the levels were 3.32 ± 1.01 g and 3.76 ± 1.12 g at 3 and 6 h in ANP group, which were significantly higher than those (1.43 ± 1.02 g and 2.56 ± 1.21 g) (P < 0.05, respectively) in AEP group. The serum levels of TNF-α were 54.27 ± 23.48 pg/mL and 67.83 ± 22.02 pg/mL in AEP group and 64.28 ± 20.79 pg/mL and 106.59 ± 43.71 pg/mL in ANP group, and the serum levels of IL-6 were 428.12 ± 140.30 pg/mL and 420.13 ± 139.40 pg/mL in AEP group and 1600.32 ± 309.78 pg/mL and 2203.76 ± 640.85 pg/mL in ANP group, which were far significantly higher than those in sham group (P < 0.001, respectively). The serum level of TNF-α 6 h after establishment of the studied model and that of IL-6 at 3 and 6 h in ANP group were significantly higher than those in AEP (P < 0.05, P < 0.001, P < 0.05). In ANP group, the levels of serum TNF-α and IL-6 6 h after establishment of the studied model were significantly higher than those 3 h after establishment of studied model (P < 0.05, P < 0.05, respectively). Three and 6 h after establishment of the model, typical pathological changesof AEP and ANP were found, such as large numbers of inflammatory cells, edema, hemorrhage, necrosis, large amount of ascites. In AEP, NF-κB and p38 MAPK in activated monocytes/macrophages were moderately found at 3 and 6 h after introduction of the model. However, in ANP, the expression of NF-κB and p38 MAPK in activated monocytes/macrophages was upregulated evidently at 3 and 6 h after introduction of the model, reaching their highest levels at 6 h after introduction of the model, which were consistent with the levels of TNF-α and IL-6.
CONCLUSION: Cytokine TNF-α and IL-6 play a main role in acute pancreatitis, expression of NF-κB and p38 MAPK in activated monocytes/macrophages might play a major role in cytokine transcription and biosynthesis.
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Affiliation(s)
- Hong-Shan Liu
- Department of Hepatobiliary Surgery, First Affiliated Hospital, Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China
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Moriguchi T, Hirasawa H, Oda S, Shiga H, Nakanishi K, Matsuda KI, Nakamura M, Yokohari K, Hirano T, Hirayama Y, Watanabe E. A patient with severe acute pancreatitis successfully treated with a new critical care procedure. Ther Apher Dial 2002; 6:221-4. [PMID: 12109947 DOI: 10.1046/j.1526-0968.2002.00435.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
It has been accepted widely that excessive humoral mediators play important roles in the pathogenesis of organ failure in patients with severe acute pancreatitis (SAP) and that infection of the pancreas due to bacterial translocation (BT) is the most frequent cause of death in SAP. On the other hand, it has been reported that continuous hemodiafiltration (CHDF) removes humoral mediators on hypercytokinemic patients such as those with systemic inflammatory response syndrome. Furthermore, several clinical studies have demonstrated that selective digestive decontamination (SDD) effectively eliminates aerobic Gram-negative bacteria from the intestinal tract and reduces the incidence of septic complications in SAP. Herein we report a case of SAP who was treated successfully with intensive care including CHDF and SDD. Thus, this case report suggests that CHDF aimed at removing causative humoral mediators and SDD for the prevention of BT are useful new tools for the management of SAP.
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Affiliation(s)
- Takeshi Moriguchi
- Department of Emergency and Critical Care Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan.
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