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Serum Concentration of Inflammatory Cytokines in Dogs with Suspected Acute Pancreatitis. Vet Sci 2021; 8:vetsci8030051. [PMID: 33803665 PMCID: PMC8003073 DOI: 10.3390/vetsci8030051] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2021] [Revised: 03/09/2021] [Accepted: 03/15/2021] [Indexed: 01/23/2023] Open
Abstract
Acute pancreatitis is an acute inflammatory process in the pancreas that is common in dogs. This study was designed to compare cytokines between healthy dogs and dogs with suspected acute pancreatitis. For the canine cytokine antibody array, three healthy dogs and three dogs with suspected acute pancreatitis were included. Interleukin (IL)-2, IL-6, IL-10, GM-CSF, and TNF-α were not detected in either group based on the results. Conversely, IL-8 (p = 0.035), Monocyte Chemoattractant Protein-1 (MCP)-1 (p = 0.0138), Receptor for Advanced Glycation Endproducts (RAGE) (p = 0.0079), and stem cell factor (SCF) (p = 0.034) were significantly increased in dogs with suspected acute pancreatitis. However, vascular endothelial growth factor (VEGF) (p = 0.6971) did not differ significantly between groups. For the canine serum Enzyme-Linked Immunosorbent Assay (ELISA), eight healthy dogs and eight dogs with suspected acute pancreatitis were included. ELISA revealed that IL-8 (p < 0.0001), MCP-1 (p < 0.0001), RAGE (p = 0.006), and SCF (p = 0.0002) were all significantly upregulated in the experimental group. We confirmed multiple patterns of cytokines in suspected acute pancreatitis of dogs via canine cytokine antibody array using a small quantity of serum. After this procedure, we reevaluated the cytokines, which were significantly increased in dogs with suspected acute pancreatitis, by ELISA, with more samples. Through this study, we confirmed that MCP-1, RAGE, and SCF were newly suggested factors in dogs with suspected acute pancreatitis.
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Alcohol and Smoking Mediated Modulations in Adaptive Immunity in Pancreatitis. Cells 2020; 9:cells9081880. [PMID: 32796685 PMCID: PMC7463831 DOI: 10.3390/cells9081880] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2020] [Revised: 08/05/2020] [Accepted: 08/06/2020] [Indexed: 12/12/2022] Open
Abstract
Pancreatitis is a condition of pancreatic inflammation driven by injury to the pancreatic parenchyma. The extent of acinar insult, intensity, and type of immune response determines the severity of the disease. Smoking, alcohol and autoimmune pancreatitis are some of the predominant risk factors that increase the risk of pancreatitis by differentially influencing the adaptive immune system. The overall decrease in peripheral lymphocyte (T-, B- and (natural killer T-) NKT-cell) count and increased infiltration into the damaged pancreatic tissue highlight the contribution of adaptive immunity in the disease pathology. Smoking and alcohol modulate the responsiveness and apoptosis of T- and B-cells during pancreatic insult. Acute pancreatitis worsens with smoking and alcohol, leading to the development of systemic inflammatory response syndrome and compensatory anti-inflammatory response syndrome, suggesting the critical role of adaptive immunity in fatal outcomes such as multiple organ dysfunction. The presence of CD4+ and CD8+ T-lymphocytes and perforin-expressing cells in the fibrotic tissue in chronic pancreatitis modulate the severity of the disease. Due to their important role in altering the severity of the disease, attempts to target adaptive immune mediators will be critical for the development of novel therapeutic interventions.
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Abstract
Bacterial translocation is a phenomenon in which live bacteria or their products cross the intestinal barrier to other organs or the circulatory system. Gut translocation of bacteria has been reported in both animal models, and clinical trials often accompany acute pancreatitis and are believed to be linked to patient outcome, especially in severe acute pancreatitis. Therefore, the mechanisms of intestinal bacterial translocation in acute pancreatitis have become a topic of interest in recent years. This review discusses Bacterial translocation in acute pancreatitis, identifies possible mechanisms of action, and provides an overview of the methods used to detect Bacterial translocation in acute pancreatitis. This review also highlights areas that require further research.
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Affiliation(s)
- Jinbo Liu
- Department of Hepatobiliary Surgery, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, P.R. China.,Academician (Expert) Workstation of Sichuan Province, The Affiliated Hospital of Southwest Medical University, Luzhou,Sichuan, P.R. China
| | - Lin Huang
- Department of Paediatrics, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, P.R. China
| | - Ming Luo
- Department of Hepatobiliary Surgery, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, P.R. China
| | - Xianming Xia
- Department of Hepatobiliary Surgery, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, P.R. China.,Academician (Expert) Workstation of Sichuan Province, The Affiliated Hospital of Southwest Medical University, Luzhou,Sichuan, P.R. China
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Effect of Previous High Glutamine Infusion on Inflammatory Mediators and Mortality in an Acute Pancreatitis Model. Mediators Inflamm 2016; 2016:4261419. [PMID: 28070142 PMCID: PMC5192344 DOI: 10.1155/2016/4261419] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2016] [Revised: 11/10/2016] [Accepted: 11/16/2016] [Indexed: 12/17/2022] Open
Abstract
Parenteral glutamine supplementation in acute inflammatory conditions is controversial. We evaluated the inflammatory and survival responses after parenteral glutamine infusion in sodium taurocholate-induced acute pancreatitis (AP) model. Lewis rats received 1 g/kg parenteral glutamine (n = 42), saline (n = 44), or no treatment (n = 45) for 48 h before AP induction. Blood, lung, and liver samples were collected 2, 12, and 24 h after AP to measure serum cytokines levels and tissue heat shock protein (HSP) expression. From each group, 20 animals were not sacrificed after AP for a 7-day mortality study. Serum cytokine levels did not differ among groups at any time point, but the intragroup analysis over time showed higher interferon-γ only in the nontreatment and saline groups at 2 h (versus 12 and 24 h; both p ≤ 0.05). The glutamine group exhibited greater lung and liver HSP90 expression than did the nontreatment group at 2 and 12 h, respectively; greater liver HSP90 and HSP70 expression than did the saline group at 12 h; and smaller lung HSP70 and liver HSP90 expression than did the nontreatment group at 24 h (all p ≤ 0.019). The 7-day mortality rate did not differ among groups. In experimental AP, pretreatment with parenteral glutamine was safe and improved early inflammatory mediator profiles without affecting mortality.
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Inman KS, Francis AA, Murray NR. Complex role for the immune system in initiation and progression of pancreatic cancer. World J Gastroenterol 2014; 20:11160-11181. [PMID: 25170202 PMCID: PMC4145756 DOI: 10.3748/wjg.v20.i32.11160] [Citation(s) in RCA: 107] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2013] [Revised: 01/27/2014] [Accepted: 04/16/2014] [Indexed: 02/06/2023] Open
Abstract
The immune system plays a complex role in the development and progression of pancreatic cancer. Inflammation can promote the formation of premalignant lesions and accelerate pancreatic cancer development. Conversely, pancreatic cancer is characterized by an immunosuppressive environment, which is thought to promote tumor progression and invasion. Here we review the current literature describing the role of the immune response in the progressive development of pancreatic cancer, with a focus on the mechanisms that drive recruitment and activation of immune cells at the tumor site, and our current understanding of the function of the immune cell types at the tumor. Recent clinical and preclinical data are reviewed, detailing the involvement of the immune response in pancreatitis and pancreatic cancer, including the role of specific cytokines and implications for disease outcome. Acute pancreatitis is characterized by a predominantly innate immune response, while chronic pancreatitis elicits an immune response that involves both innate and adaptive immune cells, and often results in profound systemic immune-suppression. Pancreatic adenocarcinoma is characterized by marked immune dysfunction driven by immunosuppressive cell types, tumor-promoting immune cells, and defective or absent inflammatory cells. Recent studies reveal that immune cells interact with cancer stem cells and tumor stromal cells, and these interactions have an impact on development and progression of pancreatic ductal adenocarcinoma (PDAC). Finally, current PDAC therapies are reviewed and the potential for harnessing the actions of the immune response to assist in targeting pancreatic cancer using immunotherapy is discussed.
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Deng LH, Xia Q. Value of pancreatic antibiotic concentration in treatment of secondary infection of serve acute pancreatitis. Shijie Huaren Xiaohua Zazhi 2008; 16:3077-3082. [DOI: 10.11569/wcjd.v16.i27.3077] [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
Secondary pancreatic infection represents the most serious complication with fatal outcome in severe acute pancreatitis (SAP). Preventing and curing secondary infection of pancreas is the key obstacle to minimize the mortality of these patients. The studies on blood-pancreatic juice barrier as well as penetration and pancreatic tissue concentration of antibiotics have improved the antibiotic prophylaxis or treatment of pancreatic infection. In the future, potential therapeutics that can enhance the antibiotic concentration and efficacy may help to prevent and treat the secondary infection of SAP.
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Shirahige A, Mizushima T, Matsushita K, Sawa K, Ochi K, Ichimura M, Tanioka H, Shinji T, Koide N, Tanimoto M. Oral administration of taurine improves experimental pancreatic fibrosis. J Gastroenterol Hepatol 2008; 23:321-7. [PMID: 17764527 DOI: 10.1111/j.1440-1746.2007.05127.x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
BACKGROUND AND AIM The mechanism of pancreatic fibrosis is unclear. Taurine is used in the clinical treatment of a wide variety of diseases, but its effect on improving pancreatic fibrosis is unknown. We examined whether a diet with added taurine improves pancreatic fibrosis induced by dibutyltin dichloride (DBTC) in an experimental chronic pancreatitis rat model. In addition, we examined the influence of taurine on pancreatic stellate cells. METHODS Pancreatic fibrosis was induced by DBTC. Rats were fed a taurine-containing diet or a normal diet and were killed at 4 weeks. Pancreatic stellate cells were isolated from male Wistar rats. Cultured pancreatic stellate cells were incubated with or without taurine chloramine. Type I collagen and transforming growth factor-beta1 secretion was evaluated by ELISA, and matrix metalloproteinase activity was assessed by gelatin zymography. Interleukin-6, interleukin-2, and transforming growth factor-beta1 levels in the supernatants of pancreatic tissue homogenates were measured. RESULTS Pancreatic fibrosis induced by DBTC was improved remarkably by the oral administration of the taurine-containing diet. Taurine chloramine decreased type I collagen, transforming growth factor-beta1, and matrix metalloproteinases 2 of the pancreatic stellate cell culture supernatant. Increased interleukin-6 and decreased interleukin-2 were found in the supernatants of the pancreatic tissue homogenates of DBTC-induced pancreatitis rats compared with other groups. CONCLUSION The oral administration of taurine improves pancreatic fibrosis. Taurine chloramine inhibits transforming growth factor-beta1 produced from activated pancreatic stellate cells and improves pancreatic fibrosis.
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Affiliation(s)
- Akinori Shirahige
- Laboratory of Medicine, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan
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Abstract
OBJECTIVES In severe acute pancreatitis (SAP), immunologic impairment in the early phase may be linked to subsequent infectious complications. Immunosuppressive acidic protein (IAP) is an immunosuppressive factor to be present in serum and ascites of cancer patients, and it is used as a tumor marker and an index of immune status of cancer hosts. METHODS We measured serum IAP levels in 42 patients with SAP (Japanese severity score [JSS] > or = 2) on admission and analyzed the relationships with disease severity, pancreatic necrosis, blood biochemical parameters on admission, and clinical outcome (infection and death). RESULTS Serum IAP level increased 791 +/- 285 microg/mL (range, 159-1430 microg/mL) on admission and recognized abnormal high level (normal range, < 500 microg/mL) in 37 patients (88.1%). Serum IAP level was significantly lower in patients of stages 3 and 4 (JSS > or = 9) (678 +/- 187 microg/mL) than that in patients of stage 2 (2 < or = JSS < or = 8) (848 +/- 311 microg/mL). It was also significantly lower in patients whose Ranson score was 5 or higher (674 +/- 287 microg/mL) than that in patients whose Ranson score was 4 or less (910 +/- 287 microg/mL). Moreover, it was significantly lower in patients with pancreatic necrosis (693 +/- 194 microg/mL) than that in patients without pancreatic necrosis (922 +/- 336 microg/mL). Among the blood biochemical parameters on admission, serum IAP was significantly negatively correlated with hematocrit, serum lipase, and serum interferon gamma and was significantly positively correlated with serum total protein. Serum IAP levels in patients of stage 2 reached higher peak at 7 days after admission and decreased more rapidly than those in patients of stages 3 and 4. CONCLUSIONS Serum IAP levels were elevated in patients with SAP but were significantly lower in patients with higher grade of severity or pancreatic necrosis. These results suggest that serum IAP levels may be related to systemic inflammatory response and reflect the immunoresponsiveness in patients with SAP.
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Koussoulas V, Tzivras M, Karagianni V, Spyridaki E, Plachouras D, Giamarellou H, Giamarellos-Bourboulis EJ. Monocytes in systematic inflammatory response syndrome: differences between sepsis and acute pancreatitis. World J Gastroenterol 2006; 12:6711-4. [PMID: 17075990 PMCID: PMC4125682 DOI: 10.3748/wjg.v12.i41.6711] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2006] [Revised: 08/12/2006] [Accepted: 09/22/2006] [Indexed: 02/07/2023] Open
Abstract
AIM To unravel the differences between systematic inflammatory response syndrome (SIRS) of acute pancreatitis compared to the same syndrome in sepsis. METHODS Twenty-five patients were enrolled, 12 with sepsis and 13 acute pancreatitis. After diagnosis 20 mL blood was sampled. Half were assayed for isolation of monocytes and 10 mL was centrifuged for serum test of tumor necrosis factor alpha (TNFalpha and interleukin-6 (IL-6). Half of monocytes were incubated in the presence of patients' serum and supernatants were collected. The other half was treated for estimation of optical photometry under caspase-3 inhibition. TNFalpha and IL-6 were estimated by an enzyme immunoassay. RESULTS median+/-SE of serum IL-6 in septic patients and acute pancreatitis patients was 192.30+/-35.40 ng/L and 21.00+/-16.05 ng/L, respectively (P<0.01). Respective values of caspase-3 were 0.94+/-0.17 pmol/min 10(4) cells and 0.34+/-0.09 pmol/min 10(4) cells (P<0.05). IL-6 of monocyte supernatants of patients with sepsis was significantly increased after addition of patients' serum, while that of patients with acute pancreatitis did not show significant difference. CONCLUSION The data have shown that monocyte activity is different between acute pancreatitis and sepsis. This phenomenon might be explained as a different pathway to the pro-inflammatory cytokines release or could be a novel anti-inflammatory response in acute pancreatitis.
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Affiliation(s)
- Vassilios Koussoulas
- Department of Internal Medicine, University of Athens, Medical School, and Attikon University Hospital, 1 Rimini Str., Athens 124 62, Greece
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Ma T, Kang C, Shao H, Qi Q, Hu W. Protective effects of ulinastatin on proliferation and cytokine release of splenocytes from rats with severe acute pancreatitis. Eur Surg Res 2006; 38:445-50. [PMID: 16912483 DOI: 10.1159/000095087] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2006] [Accepted: 06/21/2006] [Indexed: 11/19/2022]
Abstract
AIM To clarify the contributions of ulinastatin to cellular immune responses in vivo, we examined the functional alterations of splenocytes and quantitatively evaluated the effects of ulinastatin on the splenocyte function during experimental severe acute pancreatitis. METHODS Severe acute pancreatitis was induced in rats by retrograde injection of 3% sodium deoxycholate. Thirty minutes after induction of pancreatitis, the rats were randomly assigned to four groups, receiving either saline or 50,000 U/kg of ulinastatin, respectively. Splenocytes were obtained aseptically and stimulated with concanavalin A for 24 h. Then the proliferative activity of cultured splenocytes was measured by using an MTT cellular proliferation assay, and the cytokine concentrations in the culture supernatants were measured by enzyme-linked immunosorbent assays. RESULTS Upon stimulation, the release of interleukin-2, interleukin-10, and interferon-gamma was significantly decreased in the splenocytes from rats with pancreatitis as compared with those from sham operation and control groups. The splenocyte proliferation was also significantly suppressed in this group. In contrast, the proliferative as well as the cytokine-releasing capacities of the splenocytes from rats treated with ulinastatin were significantly increased as compared with those from rats with pancreatitis. CONCLUSIONS The deficiencies in proliferation and cytokine release in response to antigen stimulation demonstrated an anergic state of splenocytes during severe acute pancreatitis. Treatment with ulinastatin contributed to the recovery of the immune function by improving proliferative responses and cytokine release of splenocytes. These data suggest that a protease-modulating therapy may be an effective strategy for the treatment of immunosuppression induced by severe acute pancreatitis.
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Affiliation(s)
- Tao Ma
- Department of Surgery, General Hospital of the Tianjin Medical University, Tianjin, China.
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Ueda T, Takeyama Y, Yasuda T, Shinzeki M, Sawa H, Nakajima T, Ajiki T, Fujino Y, Suzuki Y, Kuroda Y. Immunosuppression in patients with severe acute pancreatitis. J Gastroenterol 2006; 41:779-84. [PMID: 16988767 DOI: 10.1007/s00535-006-1852-8] [Citation(s) in RCA: 46] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2006] [Accepted: 05/11/2006] [Indexed: 02/04/2023]
Abstract
BACKGROUND In severe acute pancreatitis (SAP), immunologic impairment in the early phase may be linked to subsequent infectious complications. In this study, immunologic alterations in patients with SAP were analyzed, and immunologic parameters related to infectious complications were clarified. METHODS A total of 101 patients with SAP were analyzed retrospectively. Various immunologic parameters on admission were analyzed and compared between the infection group and noninfection group during SAP. Furthermore, chronologic change in the lymphocyte count was investigated, and its utility for predicting infection was compared with conventional scoring systems. RESULTS Serum immunoglobulin G (IgG), serum IgM, lymphokine-activated killer cell activity, and natural killer cell activity were low, and the incidence of abnormally low values was 50.0%, 65.0%, 45.5%, and 42.4%, respectively. Serum complement factor 3 was significantly negatively correlated with the APACHE II score. The lymphocyte count was decreased below the normal range, and was significantly negatively correlated with the APACHE II score. CD4-, CD8-, and CD20-positive lymphocyte counts were below the normal range, and CD4- and CD8-positive lymphocyte counts were significantly lower in the infection group. The lymphocyte count on day 14 after admission was significantly lower in the infection group and was more useful for predicting infection than conventional scoring systems. CONCLUSIONS Immunosuppression occurs from the early phase in SAP, and quantitative impairment of lymphocytes, mainly T lymphocytes, may be closely related to infectious complications during SAP. CD4- and CD8-positive lymphocyte counts on admission and the lymphocyte count on day 14 after admission may be useful for predicting infection.
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Affiliation(s)
- Takashi Ueda
- Department of Gastroenterological Surgery, Kobe University Graduate School of Medical Sciences, Chuo-ku, Kobe 650-0017, Japan
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Rau BM, Krüger CM, Hasel C, Oliveira V, Rubie C, Beger HG, Schilling MK. Effects of immunosuppressive and immunostimulative treatment on pancreatic injury and mortality in severe acute experimental pancreatitis. Pancreas 2006; 33:174-83. [PMID: 16868484 DOI: 10.1097/01.mpa.0000226895.16817.a1] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Acute pancreatitis is associated with substantial alterations of the immunologic host response which has been claimed to promote remote organ dysfunction, septic complications, and mortality. Treatment with immunomodulating substances has been subject of few experimental studies with still conflicting results. METHODS We used the taurocholate-induced model of severe acute pancreatitis (SAP) in rats which were assigned to different treatment regimen: isotonic saline (SAP-S) for nontreated controls, recombinant rat interferon-gamma for immunostimulation (SAP-IFN-gamma), and FK506 for immunosuppression (SAP-FK506). Animals were killed after 3, 6, and 24 hours as well as 3 and 7 days, and parameters of local and systemic severity were assessed. RESULTS Treatment with IFN-gamma and FK506 attenuated the progression of intrapancreatic necrosis within the first 24 hours after pancreatitis induction along with a substantial reduction of subsequent neutrophil tissue infiltration as shown by decreased myeloperoxidase activity. Enhanced cell death by apoptosis during the postacute course was reduced in FK506-treated animals only. Pancreatic interleukin (IL) 1beta messenger RNA up-regulation occurred early and was slightly suppressed in both treatment groups; tumor necrosis factor alpha (TNF-alpha) and IL-2 messenger RNA expression paralleled the onset of apoptosis and was markedly decreased in IFN-gamma- and FK506-treated rats. The 2 therapeutic regimens had similar effects on intrapancreatic and systemic IL-1beta and TNF-alpha protein release; however, the profiles of both cytokines were differently influenced. Whereas IFN-gamma and FK506 treatment lead to an enhanced intrapancreatic and systemic TNF-alpha protein release during the early course, IL-1beta concentrations were significantly reduced within the late intervals. Seven-day mortality was 44% in saline-, 29% in IFN-gamma-, and 25% in FK506-treated rats (P = not significant). CONCLUSIONS Severe acute pancreatitis is associated with early alterations of the immune response comprising overt T-cell activation and impaired monocyte/macrophage function alike. Targeting either immunologic derangement improves local pancreatic damage and systemic severity. However, because mortality was not improved, a therapeutic benefit of immunomodulating substances in clinical SAP remains to be defined.
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Affiliation(s)
- Bettina M Rau
- Department of General, Visceral, and Vascular Surgery, University of the Saarland, Homburg/Saar, Germany.
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Rahman SH, Salter G, Holmfield JHM, Larvin M, McMahon MJ. Soluble CD14 receptor expression and monocyte heterogeneity but not the C-260T CD14 genotype are associated with severe acute pancreatitis. Crit Care Med 2004; 32:2457-63. [PMID: 15599151 DOI: 10.1097/01.ccm.0000148008.99716.9c] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
OBJECTIVE Soluble CD14 is derived from a membrane glycoprotein, and it enhances endothelial cytokine responses to lipopolysaccharide. We studied the role of soluble CD14 in the pathogenesis of the systemic inflammatory response associated with acute pancreatitis, to determine whether altered expression was due to a functional C-260T polymorphism in the CD14 promoter gene or altered monocyte heterogeneity. DESIGN Prospective case-matched study. SETTING Tertiary pancreatic treatment unit in the United Kingdom. SUBJECTS Patients with pancreatitis and controls. INTERVENTIONS DNA from 117 patients with pancreatitis (34 severe) and 263 controls underwent CD14 genotyping using restriction fragment length polymorphism-polymerase chain reaction. MEASUREMENTS AND MAIN RESULTS Peripheral venous blood samples at 24 and 72 hrs after the onset of abdominal pain were analyzed for sCD14 levels. Isolated peripheral blood mononuclear cells were phenotyped for CD14/CD16 receptor expression using immunofluorescence flow cytometry. Disease severity was assessed using Atlanta criteria, Acute Physiology Scores, and C-reactive protein.Soluble CD14 levels were higher in severe (24-hr median, 66.6 ng/mL; 72-hr median, 72.2 ng/mL) compared with mild attacks (24-hr median, 50.7 ng/mL; 72-hr median, 49.7 ng/mL, p < .001), although the latter was similar to controls (median, 51 ng/mL). Furthermore, soluble CD14 levels correlated with Acute Physiology Scores (p < .001) and C-reactive protein (p = .01).Peripheral blood mononuclear cells CD14++ (p = .008), CD14+/16+ (p = .003), and CD16++ (p = .015) receptor densities were all increased in severe attacks at 24 hrs. Early CD14+/16+ receptor density correlated with sCD14 (p < .001), Acute Physiology Scores (p < .001), and C-reactive protein (p = 0.006). The CD14 genotype prevalence in acute pancreatitis was similar to controls and failed to correlate with any variables studied. CONCLUSIONS Increased soluble CD14 expression is associated with the systemic inflammatory response to acute pancreatitis and an expansion of the proinflammatory CD14+/CD16+ monocyte subset. Its targeted disruption may afford some benefit in preventing the development of systemic complications.
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Affiliation(s)
- Sakhawat H Rahman
- Academic Unit of Surgery, University of Leeds, General Infirmary, Leeds, West Yorkshire, UK
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Abstract
OBJECTIVE Many studies have been published on acute pancreatitis but few, if any, on extrapancreatic manifestations (EPM) in African Americans and Hispanics. We studied the effect of EPM on mortality in these 2 ethnic groups. METHODS Records of 760 acute pancreatitis patients (417 African-American and 343 Hispanic), ages 19-85 years, over a 15-year period were reviewed retrospectively. Data were analyzed for EPM and mortality. RESULTS Of the 760 patients, alcohol use was identified as the etiology in 53% of cases and gallstones in 42%. EPM were present in 148 patients (19.5%). Gastrointestinal bleeding (22%) was the most common EPM. Patients with EPM did not differ from patients without EPM on demographics or acute pancreatitis-related variables (P > 0.05). Patients with EPM had higher odds of having comorbidity relative to patients without EPM (OR = 2.9, CI = 2.0-4.2). Of 760 patients, 109 died (14%). However, mortality was significantly higher (26%) in patients with EPM in comparison to those without EPM (11%), P = 0.001. Controlling for other variables, patients with EPM had higher odds of mortality relative to patients without EPM (OR = 2.8, CI = 1.7-4.4). CONCLUSION Mortality was high in our patients compared with the literature (5%-10%). EPM increased the mortality significantly (26%).
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Affiliation(s)
- Abbasi J Akhtar
- Division of Gastroenterology, Department of Internal Medicine, Charles R. Drew University of Medicine and Science, Los Angeles, CA, USA.
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Abstract
Acute pancreatitis is a common disease with a relatively high morbidity and mortality. In contrast, chronic pancreatitis is a recurrent disease with multiple potential complications that occasionally require urgent intervention. This article focuses on the emergency complications of acute and chronic pancreatitis that require urgent intervention. Recent developments in the diagnosis and management of such complications are discussed.
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Affiliation(s)
- Ngai-Moh Law
- University of Minnesota, Division of Gastroenterology, Hennepin County Medical Center, 701 Park Avenue, Minneapolis, MN 55415, USA
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Satoh A, Masamune A, Kimura K, Kaneko K, Sakai Y, Yamagiwa T, Satoh M, Kikuta K, Asakura T, Shimosegawa T. Nuclear factor kappa B expression in peripheral blood mononuclear cells of patients with acute pancreatitis. Pancreas 2003; 26:350-6. [PMID: 12717267 DOI: 10.1097/00006676-200305000-00007] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
INTRODUCTION Although many experimental studies have implicated the activation of nuclear factor kappa B (NF-kappaB) as a pivotal step in the pathobiology of acute pancreatitis, no clinical investigations have been reported. AIMTo investigate the expression of NF-kappaB and its characteristics in peripheral blood mononuclear cells (PBMCs) of patient with acute pancreatitis. METHODOLOGY Forty-five patients were prospectively enrolled. The expression of NF-kappaB in PBMCs was measured in the patients by electrophoretic mobility shift assay at admission and 14 days after the onset of acute pancreatitis. Twelve healthy individuals were also included as control subjects. RESULTS At admission, the PBMCs from patients with acute pancreatitis showed higher levels of NF-kappaB activities than did those from control subjects. In vitro, the lipopolysaccharide (LPS) treatment of the PBMCs from the control subjects and patients with mild pancreatitis induced further activation of the NF-kappaB. The response was significantly reduced in patients with severe pancreatitis. Patients who had persistently high NF-kappaB activities, a reduced response of NF-kappaB to LPS, and a low p50p65:p50p50 ratio after LPS stimulation at 14 days developed serious systemic complications in the later clinical course. CONCLUSIONS An alteration of the characteristics of PBMCs occurs in the early phase of acute pancreatitis and may predispose patients to a higher risk of serious systemic complications.
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Affiliation(s)
- Akihiko Satoh
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Miyagi, Japan.
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Sweeney KJ, Kell MR, Coates C, Murphy T, Reynolds JV. Serum antigen(s) drive the proinflammatory T cell response in acute pancreatitis. Br J Surg 2003; 90:313-9. [PMID: 12594666 DOI: 10.1002/bjs.4080] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND Immune cells and cytokines are central to the systemic inflammatory response syndrome and multiple organ failure associated with acute pancreatitis. The specific role of T cells in this response is unclear, and this study focused on evaluating T cell activation and its regulation in patients with acute pancreatitis. METHODS Peripheral blood samples of 14 patients with acute pancreatitis were obtained within 24 h of the onset of pain, within 48 h and at 1 week. T cell expression of surface markers CD69, CD62L and CD25 was measured. The production of interleukin (IL) 10 and IL-2 in vitro in response to the superantigen Staphylococcus enterotoxin B (SEB) was assessed. Serum samples from these patients were co-cultured with peripheral blood mononuclear cells from volunteers in the presence or absence of cytotoxic T lymphocyte-associated antigen (CTLA) 4 immunoglobulin, a specific inhibitor of antigen-dependent T cell activation. RESULTS Expression of CD69 was significantly increased in CD3(+) and CD4(+) populations at 48 h and 1 week, and on CD8(+) cells at 1 week. There was a significant increase in the production of SEB-induced IL-2 compared with findings in controls, but no significant IL-10 response. Serum from patients with pancreatitis activated normal T cells. This response was abolished completely by CTLA-4. CONCLUSION Acute pancreatitis results in the systemic activation of T cells. These cells are primed for a proinflammatory response to antigen stimulation and can be inhibited by antigen-specific T cell blockade. These data indicate that the immunoinflammatory response in acute pancreatitis is fueled by one or more serum antigens and offer prospects for further understanding of the aetiogenesis of pancreatitis.
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Affiliation(s)
- K J Sweeney
- Academic Department of Surgery, St James's Hospital and Trinity College Dublin, Dublin, Ireland
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18
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Abstract
INTRODUCTION The pathogenesis of acute pancreatitis remains elusive. Sepsis and multiple organ failure continue to cause death (overall mortality rate, approximately 10%) despite immense improvements in supportive, radiologic, and surgical therapy. The gut appears to play a key role in the development of these complications. AIM To critically review the evidence implicating the gut in the pathogenesis of acute pancreatitis. METHODS Relevant English-language literature or abstracts cited in the MEDLINE database were reviewed. RESULTS AND CONCLUSION Gram-negative enteric organisms account for most infections of pancreatic necrosis and subsequent sepsis, which suggests the gut as a source. Intestinal permeability is increased early in patients with severe acute pancreatitis and correlates with endotoxemia, which suggests translocation as a possible mechanism. The pathogenesis of the deranged function of the gut mucosal barrier and the possible sites of increase in intestinal permeability are discussed. The gut also plays a role in priming neutrophils and the release of inflammatory cytokines, which initiate and propagate nearly all the detrimental consequences of severe inflammation and sepsis. Future research avenues and potential therapeutic measures that may restore and preserve gut barrier function are explored.
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Affiliation(s)
- Basil J Ammori
- Division of Surgery, The University of Leeds, and the Center for Digestive Diseases, The General Infirmary, Leeds, United Kingdom.
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19
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Mao EQ, Tang YQ, Zhang SD. Effects of time interval for hemofiltration on the prognosis of severe acute pancreatitis. World J Gastroenterol 2003; 9:373-376. [PMID: 12532470 PMCID: PMC4611350 DOI: 10.3748/wjg.v9.i2.373] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2002] [Revised: 08/24/2002] [Accepted: 10/18/2002] [Indexed: 02/07/2023] Open
Abstract
AIM To evaluate the impact of time interval for hemofiltration (HF) on the prognosis of severe acute pancreatitis (SAP). METHODS Thirty-six consecutive patients with severe acute pancreatitis were included in the study. Atlanta classification system was applied for stratification. They were randomly divided into short veno-venous HF group, (SVVH, Group 1, 20 patients); and long veno-venous HF group (LVVH, Group 2, 16 patients). In group 1, SVVH was stopped when the abdominal signs disappeared, and heart rate and breath rate were less than 90 beats/min and 20 times/min, respectively. HF was stopped if SVVH was continued, and when heart rate and breath rate were more than 90 beats/min and 20 times/min again (Group 2). Except that the time interval for HF was different, other parameters for HF were the same. And conservative curing rate, survival rate, cost for hospital stay and length of hospital stay were observed. RESULTS Time interval for HF in Group 1 (3.81+/-1.3 hr) was shorter than that of in Group 2 (9.38+/-2.9 hr), P<0.01. Conservative curing rate (90 %) in Group 1 was much higher than that in Group 2 (56.3 %) (P<0.05); but cost in Group 1 (RMB 56 600+/-56 400 Yuan) was lower than that in Group 2 (RMB 137 000+/-105 000 Yuan) (P<0.05). And the survival rate (95 %) in Group 1 was higher than that in Group 2 (81.3 %) (P<0.25); however, hospital stay in Group 1 (44.3+/-41 days) was shorter than that in Group 2 (55.2+/-39.5 days) (P<0.2). So, the prognosis was not improved through the prolongation of time interval for HF, but side-effects were seen. CONCLUSION The prognosis was not further improved by LVVH in the treatment of SAP, with side-effects. Time interval for HF plays an important role in treatment of SAP in early stage. SVVH is thought to be superior to LVVH; and LVVH is superior to CVVH in early (72 hrs) treatment of SAP.
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Affiliation(s)
- En-Qiang Mao
- Department of Surgery, Ruijin Hospital, Shanghai Second Medical University, Shanghai 200025, China.
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20
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Ammori BJ, Fitzgerald P, Hawkey P, McMahon MJ. The early increase in intestinal permeability and systemic endotoxin exposure in patients with severe acute pancreatitis is not associated with systemic bacterial translocation: molecular investigation of microbial DNA in the blood. Pancreas 2003; 26:18-22. [PMID: 12499912 DOI: 10.1097/00006676-200301000-00004] [Citation(s) in RCA: 76] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Sepsis is the main cause of late mortality in patients with severe acute pancreatitis and is largely attributed to secondary infection of pancreatic necrosis with gram-negative enteric organisms. This is commonly preceded by a significant increase in intestinal colonization with such microbes and with early increases in intestinal permeability, thus suggesting a mechanism of bacterial translocation. Whilst cultures of blood specimens from these patients often remain sterile, it is conceivable that bacteria might translocate in small volumes with detrimental effects but elude detection by standard microbial culture techniques. AIMS To investigate the incidence and frequency with which bacterial DNA may exist in the systemic circulation of patients with acute pancreatitis and to relate that to disease severity, changes in intestinal permeability, and systemic endotoxin exposure. METHODOLOGY Blood samples were obtained at admission and on days 3 and 7 from 26 patients with acute pancreatitis (seven with severe cases) and from 10 healthy controls for DNA extraction and standard microbial cultures. Polymerase chain reaction techniques were used to amplify a gene region (16S ribosomal RNA) found in all bacteria. Levels of serum endotoxin and antibodies to endotoxin core (EndoCAb) were measured at admission, and intestinal permeability to the macromolecule polyethylene glycol 3350 was determined within 72 hours of the onset of symptoms. RESULTS Blood cultures yielded and enterococci for one patient with a severe attack and coagulase-negative staphylococci for another patient with a mild attack. No bacterial DNA was found in any of the samples. Endotoxemia was detected in 20 patients (five with severe cases), and levels of serum IgM EndoCAb were depleted in patients with severe attacks but remained relatively unchanged during mild attacks (p = 0.033). Intestinal permeability was significantly increased in patients with severe attacks of acute pancreatitis but remained unchanged during mild attacks (p < 0.05). CONCLUSIONS Whilst severe attacks of acute pancreatitis are associated with early derangement in gut barrier function and systemic endotoxin translocation, there is no molecular evidence for associated bacterial "translocation."
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Affiliation(s)
- B J Ammori
- Division of Surgery, The University of Leeds, Leeds, United Kingdom.
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21
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Yekebas EF, Strate T, Zolmajd S, Eisenberger CF, Erbersdobler A, Saalmüller A, Steffani K, Busch C, Elsner HA, Engelhardt M, Gillesen A, Meins J, The M, Knoefel WT, Izbicki JR. Impact of different modalities of continuous venovenous hemofiltration on sepsis-induced alterations in experimental pancreatitis. Kidney Int 2002; 62:1806-18. [PMID: 12371983 DOI: 10.1046/j.1523-1755.2002.00607.x] [Citation(s) in RCA: 48] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND Continuous venovenous hemofiltration (CVVH) is assumed to attenuate systemic complications in septic diseases. The impact of different treatment intensities of CVVH on immunologic and systemic alterations in experimental pancreatitis was evaluated. METHODS Eighty-four minipigs were allocated either to an untreated control group (group 1) or to one of six treatment groups (groups 2 to 7) that underwent CVVH in different modalities: (1): "late" CVVH, started after a decline of total peripheral resistance of 30% versus "prophylactic" CVVH started immediately after the induction of pancreatitis; (2) no change of hemofilters versus a periodic change of filters every 12 hours; (3) low-volume CVVH with a filtrate turnover of 20 mL/kg body weight (BW)/h versus high-volume CVVH (100 mL/kg/h). Pancreatitis was induced by intraductal injection of sodium-taurocholate (3%, 1 mL/kg BW) and enterokinase (2 U/kg BW). We focused on the occurrence of sepsis, serum cytokines, down-regulation of major histocompatibility complex II (MHC II) and the endotoxin receptor CD14 expression, bacterial translocation/endotoxemia, and pulmonary and renal histologic alterations. RESULTS CVVH delayed or definitively prevented the occurrence of sepsis. Pancreatitis was associated with a tremendous initial tumor necrosis factor-alpha (TNF-alpha) response prior to a return to near baseline levels in the late course of sepsis. Endotoxin hyporesponsiveness, suggested by the dissociation of decreasing TNF-alpha levels and increasing endotoxemia in end-stage sepsis, was favorably influenced by CVVH. Down-regulation of MHC II and CD14 expression was prevented in non-septic animals. CVVH-related sepsis-protection led to a significant attenuation of histological injury in lungs and kidneys. "Prophylactic" CVVH prevented histological changes more effectively than "late" CVVH. CONCLUSIONS CVVH offers a therapeutic option for supportive treatment in severe pancreatitis. The efficiency of CVVH is associated with the duration of filter use and cumulative plasma turnover. Since CVVH may lead to sepsis-protection and long-term survival, further evaluation in controlled, clinical trials is warranted.
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Affiliation(s)
- Emre F Yekebas
- Department of Surgery, University Hospital Eppendorf, Hamburg, Germany.
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Ueda T, Takeyama Y, Yasuda T, Takase K, Nishikawa J, Kuroda Y. Functional alterations of splenocytes in severe acute pancreatitis. J Surg Res 2002; 102:161-8. [PMID: 11796014 DOI: 10.1006/jsre.2001.6291] [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: 01/27/2023]
Abstract
BACKGROUND AND AIMS Recently, the concept of "Th1 (T helper cell type 1)/Th2 (T helper cell type 2) balance" was introduced for understanding the pathophysiologic response during septic or preseptic conditions. To clarify unknown Th1/Th2 balance during acute pancreatitis, functional alterations of the splenocyte were investigated in rat experimental severe acute pancreatitis. METHODS Spleens were removed from rats 24 h after the induction of severe necrotizing pancreatitis by retrograde injection of 3% sodium deoxycholate. Total splenocytes were harvested and cultured in the presence or absence of concanavalin A (con A) for 24 h. Proliferative capacities and cytokine-releasing capacities were evaluated. RESULTS In splenocytes harvested 24 h after the induction of pancreatitis, proliferative capacity with con A stimulation was significantly lower than that of sham operation. Interleukin-2 (IL-2) release with con A stimulation and interferon-gamma release with or without con A stimulation were significantly decreased in splenocytes from the rats with pancreatitis compared with those from sham operation. Interleukin-10 (IL-10) release with con A stimulation was also significantly decreased in splenocytes from the rats with pancreatitis compared with those from sham operation. The IL-2/IL-10 concentration ratio secreted by the splenocytes from the rats with pancreatitis was significantly lower than that from those undergoing the sham operation. CONCLUSIONS These results suggest that splenocyte function is markedly suppressed in experimental severe acute pancreatitis and that Th1/Th2 balance tends to Th1 suppression as a whole. Dysfunction of lymphocytes including splenocytes may play a certain role in the development of subsequent septic complications in this disease.
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Affiliation(s)
- Takashi Ueda
- First Department of Surgery, Kobe University School of Medicine, Kobe 650-0017, Japan
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23
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Osman MO, Gesser B, Mortensen JT, Matsushima K, Jensen SL, Larsen CG. Profiles of pro-inflammatory cytokines in the serum of rabbits after experimentally induced acute pancreatitis. Cytokine 2002; 17:53-9. [PMID: 11886171 DOI: 10.1006/cyto.2001.0977] [Citation(s) in RCA: 36] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
In a recent study we have demonstrated that interleukin 8 (IL-8) and tumour necrosis factor alpha (TNF-alpha) serum levels correlate positively with the severity of acute pancreatitis (AP), induced by bile acid injected into the pancreatic duct of rabbits. In this article we describe the effect of an IL-10 analogue IT9302 and a monoclonal anti-IL-8 (mon. IL-8) antibody on the content of several pro-inflammatory cytokines in the serum of rabbits, after induction of AP. We found that the serum content of inflammatory cytokines IL-8, IL-1beta, TNF-alpha and monocyte chemoattractant protein 1 (MCP-1) are increased during AP. Injection of IT9302 or mon. IL-8 antibody, diminish the concentration of these cytokines in the serum, with the exception that mon. IL-8 antibody actually increased the circulating level of MCP-1. In addition, intravenous administration of IT9302 increased the serum levels of IRAP, an IL-1beta receptor antagonistic cytokine. Furthermore, intravenous injection of mon. IL-8 antibody increased serum levels of IL-4. It can be concluded that both the human IL-10 analogue IT9302 and mon. IL-8 antibody are able to alter the pro-inflammatory cytokine levels in rabbits suffering from experimentally induced AP.
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Affiliation(s)
- Maher O Osman
- Department of Surgery, Aarhus University Hospital, Aarhus University, Denmark
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24
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Yekebas EF, Eisenberger CF, Ohnesorge H, Saalmüller A, Elsner HA, Engelhardt M, Gillesen A, Meins J, The M, Strate T, Busch C, Knoefel WT, Bloechle C, Izbicki JR. Attenuation of sepsis-related immunoparalysis by continuous veno-venous hemofiltration in experimental porcine pancreatitis. Crit Care Med 2001; 29:1423-30. [PMID: 11445702 DOI: 10.1097/00003246-200107000-00021] [Citation(s) in RCA: 90] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
OBJECTIVES In light of evidence suggesting that hemofiltration favorably influences septic diseases by removing sepsis mediators, the impact of different modalities of continuous veno-venous hemofiltration (CVVH) on outcome and immunologic derangements in porcine pancreatogenic sepsis was evaluated. DESIGN Randomized, controlled intervention trial. SUBJECTS Forty-eight minipigs of either sex. INTERVENTIONS Pancreatitis was induced by intraductal injection of sodium taurocholate (4%, 1 mL/kg body weight [BW]) and enterokinase (2 U/kg BW). Animals were allocated either to untreated controls-group 1-or to one of three treatment groups-group 2: low-volume CVVH (20 mL/kg BW), no change of hemofilters; group 3: low-volume CVVH, filters changed every 12 hrs; and group 4: high-volume CVVH (100 mL/kg BW), filters changed every 12 hrs. Survival represented the major parameter of the study. Serum cytokine levels, sepsis-related down-regulation of major histocompatibility complex II and CD14 expression on leukocytes, bacterial translocation, and endotoxemia were further parameters evaluated in the study. MEASUREMENTS AND MAIN RESULTS High-volume CVVH combined with periodic filter change was significantly superior compared with less intensive treatment modalities (low-volume CVVH, no filter change) in sepsis protection. Long-term survival (>60 hrs) was found in 67% of group 4 and 33% of group 3 animals (p <.05), whereas in controls and group 2 no animal survived. CVVH ameliorated the initial serum tumor necrosis factor-alpha response and prevented sepsis-induced in vitro endotoxin hyporesponsiveness. Down-regulation of major histocompatibility complex II and CD14 expression on monocytes was significantly improved by CVVH. Improved oxidative burst and phagocytosis capacity in polymorphonuclear leukocytes suggested that leukocyte function was stabilized by CVVH. Also, CVVH significantly reduced bacterial translocation and endotoxemia. CONCLUSIONS Hemofiltration reversed sepsis-induced immunoparalysis in a porcine model of bile acid-induced pancreatitis. Implications for human pancreatitis must be validated in prospective, clinical protocols.
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Affiliation(s)
- E F Yekebas
- Department of Surgery, University Hospital Eppendorf, Hamburg, Germany
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Beger HG, Gansauge F, Mayer JM. The role of immunocytes in acute and chronic pancreatitis: when friends turn into enemies. Gastroenterology 2000; 118:626-9. [PMID: 10702216 DOI: 10.1016/s0016-5085(00)70271-x] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
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Abstract
The response against tissue injury and infection begins with the early activation of molecular and cellular elements of the inflammatory and immune response. Severe tissue injury, necrosis, and infection induce imbalanced inflammation associated with leukocyte over-stimulation and excessive or dysregulated release of cellular mediators. Clinical and experimental studies have shown that these mediators are directly related to progressive post-injury complications. Persistent increased levels of pro-inflammatory mediators produce tissue injury. Excessive production and activity of anti-inflammatory mediators cause anergy and/or immune dysfunction with increased susceptibility to infection. Leukocyte activation is assessed by cell surface phenotype expression, cellular mediators determination, or by measuring functional responses using isolated cells. Potential routine clinical uses are: evaluation of severity and prognosis in critically ill patients, immunomonitoring of sepsis, and detection of tissue injury, necrosis, and infection. In practice, the determination of cellular activation markers is restricted by a limited number of automated methods and by the cost of reagents. The availability of flow cytometry and immunoassay automated systems can contribute to a wider use in practice. Here we review the immunopathophysiology of polymorphonuclear neutrophil, monocyte, macrophage, and lymphocyte activation in response to tissue injury and infection. In addition, laboratory methods for their determination, and clinical applications in practice, are discussed.
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Affiliation(s)
- J A Viedma Contreras
- Clinical Chemistry Department, Hospital General y Universitario de Elche, Spain. j-viedma.000@recol-es
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Pezzilli R, Barakat B, Morselli-Labate AM. Evaluation of the immunomodulatory effect of gabexate mesilate in patients with severe acute pancreatitis. Curr Ther Res Clin Exp 1998. [DOI: 10.1016/s0011-393x(98)85029-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
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