Portal vein cytokines in the early phase of acute experimental oedematous and necrotizing porcine pancreatitis

Abstract Objective. Cytokines initiate and modify systemic inflammatory response in early acute pancreatitis. The aim of this study was to analyze which cytokines are released from the pancreas to portal venous blood in the early phase of acute experimental necrotizing and oedematous pancreatitis and which of those cytokines are correlated with the more severe form of the disease. Material and methods. Fifteen pigs were randomized to develop mild oedematous pancreatitis (n = 5, saline infusion to pancreatic duct), severe necrotizing pancreatitis (n = 5, taurocholic acid infusion) along with a control group (n = 5). Arterial and venous blood samples were drawn and cytokine levels were measured from portal vein blood at 0, 120, 240 and 360 min after the induction of pancreatitis. Tissue samples from the pancreas were harvested at 0 and 360 min. Results. White blood cell count increased in necrotizing pancreatitis and the control group. The amount of neutrophils increased (p < 0.001) and the lymphocyte and eosinophil counts decreased in all groups (p < 0.001, p < 0.001). The monocyte count, as well as PDGF and IL-6 concentrations, increased only in necrotizing pancreatitis. IL-8 and eotaxin increased both in oedematous and necrotizing pancreatitis. MCP-1 increased in all groups. IL-9, IL-4, MIP-1α, IFN- γ concentrations did not change. Eotaxin and MCP-1 plasma levels from a previous series between portal venous and pulmonary arterial blood were not significantly different. Conclusions. The initial inflammatory process was diverse in oedematous and necrotizing pancreatitis. Increased monocyte count in combination with elevated PDGF and IL-6 are characteric of necrotizing pancreatitis in our model.

[1]  B. Kirkhus,et al.  Effect of the fat composition of a single high-fat meal on inflammatory markers in healthy young women , 2011, British Journal of Nutrition.

[2]  Yinfeng Shen,et al.  Immune Dysregulation in Patients with Severe Acute Pancreatitis , 2011, Inflammation.

[3]  M. Bhatia,et al.  Essential role of monocytes and macrophages in the progression of acute pancreatitis. , 2010, World journal of gastroenterology.

[4]  Heikki Repo,et al.  Inflammation and immunosuppression in severe acute pancreatitis. , 2010, World journal of gastroenterology.

[5]  M. Bhatia,et al.  The role of pro-inflammatory molecules and pharmacological agents in acute pancreatitis and sepsis. , 2010, Inflammation & allergy drug targets.

[6]  T. Joos,et al.  A biomarker panel to discriminate between systemic inflammatory response syndrome and sepsis and sepsis severity , 2010, Journal of emergencies, trauma, and shock.

[7]  D. Whitcomb,et al.  Diagnostic Accuracy of Interleukin-6 and Interleukin-8 in Predicting Severe Acute Pancreatitis: A Meta-Analysis , 2010, Pancreatology.

[8]  D. Bar-Sagi,et al.  Pathophysiology of Acute Pancreatitis , 2009 .

[9]  M. Singer,et al.  Cellular processes in sepsis. , 2008, Swiss medical weekly.

[10]  T. Liang,et al.  Different cell death modes of pancreatic acinar cells on macrophage activation in rats. , 2008, Chinese medical journal.

[11]  Z. Liu,et al.  Improvement of Monocyte Secretion Function in a Porcine Pancreatitis Model by Continuous Dose-Dependent Veno-Venous Hemofiltration , 2008, The International journal of artificial organs.

[12]  A. Uygun,et al.  Do the Changes in the Serum Levels of IL-2, IL-4, TNFα, and IL-6 Reflect the Inflammatory Activity in the Patients with Post-ERCP Pancreatitis? , 2008, Clinical & developmental immunology.

[13]  Y. Soini,et al.  Acute edematous and necrotic pancreatitis in a porcine model , 2008, Scandinavian journal of gastroenterology.

[14]  Cao Yang,et al.  Apoptosis of human trabecular meshwork cells induced by transforming growth factor-β2in vitroin vitro , 2008, Journal of Huazhong University of Science and Technology [Medical Sciences].

[15]  N. Mukaida,et al.  IFN-γ Protects Cerulein-Induced Acute Pancreatitis by Repressing NF-κB Activation1 , 2007, The Journal of Immunology.

[16]  Hao Wang,et al.  Effects of Continuous High-Volume Hemofiltration on Experimental Severe Acute Pancreatitis in Pigs , 2007, Pancreas.

[17]  N. Mukaida,et al.  IFN-gamma protects cerulein-induced acute pancreatitis by repressing NF-kappa B activation. , 2007, Journal of immunology.

[18]  K. Shimizu [Pancreatic stellate cells: molecular mechanism of pancreatic fibrosis]. , 2006, Nihon Shokakibyo Gakkai zasshi = The Japanese journal of gastro-enterology.

[19]  Javed Siddiqui,et al.  Circulating Cytokine/Inhibitor Profiles Reshape the Understanding of the SIRS/CARS Continuum in Sepsis and Predict Mortality1 , 2006, The Journal of Immunology.

[20]  Hong Wang,et al.  Effects of High-Volume Continuous Hemofiltration on Experimental Pancreatitis Associated Lung Injury in Pigs , 2006, The International journal of artificial organs.

[21]  F. Marra Renaming cytokines: MCP-1, Major Chemokine in Pancreatitis , 2005, Gut.

[22]  M. Barmada,et al.  Is the monocyte chemotactic protein-1 -2518 G allele a risk factor for severe acute pancreatitis? , 2005, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[23]  S. Sarna,et al.  Plasma anti‐inflammatory cytokines and monocyte human leucocyte antigen‐DR expression in patients with acute pancreatitis , 2004, Scandinavian journal of gastroenterology.

[24]  J. Xiong,et al.  Effect of early hemofiltration on pro- and anti-inflammatory responses and multiple organ failure in severe acute pancreatitis. , 2004, Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban.

[25]  B. Rau,et al.  CC-chemokine activation in acute pancreatitis: enhanced release of monocyte chemoattractant protein-1 in patients with local and systemic complications , 2003, Intensive Care Medicine.

[26]  J. Izbicki,et al.  Impact of different modalities of continuous venovenous hemofiltration on sepsis-induced alterations in experimental pancreatitis. , 2002, Kidney international.

[27]  J. Izbicki,et al.  Attenuation of sepsis-related immunoparalysis by continuous veno-venous hemofiltration in experimental porcine pancreatitis , 2001, Critical care medicine.

[28]  B. Rau,et al.  Early Severe Acute Pancreatitis: Characteristics of a New Subgroup , 2001, Pancreas.

[29]  J. Neoptolemos,et al.  Double blind, randomised, placebo controlled study of a platelet activating factor antagonist, lexipafant, in the treatment and prevention of organ failure in predicted severe acute pancreatitis , 2001, Gut.

[30]  S. Opal,et al.  Anti-inflammatory cytokines. , 2000, Chest.

[31]  F. Gansauge,et al.  The role of immunocytes in acute and chronic pancreatitis: when friends turn into enemies. , 2000, Gastroenterology.

[32]  B R Johansson,et al.  Pericyte loss and microaneurysm formation in PDGF-B-deficient mice. , 1997, Science.

[33]  M. Davies,et al.  Systemic inflammatory response syndrome , 1997, The British journal of surgery.

[34]  J. Sánchez-Payá,et al.  Activation of cellular immune response in acute pancreatitis. , 1997, Gut.

[35]  A. Abbas,et al.  T-cell subsets: Recruiting the right kind of help , 1997, Current Biology.

[36]  S. Rankin,et al.  The role of the eosinophil-selective chemokine, eotaxin, in allergic and non-allergic airways inflammation. , 1997, Memorias do Instituto Oswaldo Cruz.

[37]  J. Schölmerich,et al.  lnterleukin‐8 and neutrophil activation in acute pancreatitis , 1992, European journal of clinical investigation.

[38]  P. Heinrich,et al.  Interleukin‐6 is the major regulator of acute phase protein synthesis in adult human hepatocytes , 1989, FEBS letters.

[39]  W. Baumgartner,et al.  Anatomic and anesthetic considerations in experimental cardiopulmonary surgery in swine. , 1986, Laboratory animal science.

[40]  M. Büchler,et al.  Bacterial contamination of pancreatic necrosis. A prospective clinical study. , 1986, Gastroenterology.

[41]  T. Deuel,et al.  Platelet-derived growth factor. Structure, function, and roles in normal and transformed cells. , 1984, The Journal of clinical investigation.

[42]  T. Deuel,et al.  Platelet-derived growth factor: purification, properties, and biological activities. , 1983, Progress in hematology.

[43]  R. Senior,et al.  Chemotaxis of monocytes and neutrophils to platelet-derived growth factor. , 1982, The Journal of clinical investigation.