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Adaptive Immune Cell Dysregulation and Role in Acute Pancreatitis Disease Progression and Treatment

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Archivum Immunologiae et Therapiae Experimentalis Aims and scope

Abstract

Acute pancreatitis (AP) is an inflammation of the pancreas caused by various stimuli including excessive alcohol consumption, gallstone disease and certain viral infections. Managing specifically the severe form of AP is limited due to lack of an understanding of the complex immune events that occur during AP involving immune cells and inflammatory molecules such as cytokines. The relative abundance of various immune cells resulting from the immune dysregulation drives disease progression. In this review, we examine the literature on the adaptive immune cells in AP, the prognostic value of these cells in stratifying patients into appropriate care and treatment strategies based on cell frequency in different AP severities are discussed.

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Abbreviations

AP:

Acute pancreatitis

CARS:

Compensatory anti-inflammatory response syndrome

IPN:

Infectious pancreatic necrosis

MAP:

Mild AP

NLR:

Neutrophil–lymphocyte ratio

PMN:

Polymorphonuclear

SAP:

Severe AP

SIRS:

Systemic inflammatory response syndrome

TLRs:

Toll-like receptors

References

  • Abdulla A, Awla D, Thorlacius H et al (2011) Role of neutrophils in the activation of trypsinogen in severe acute pancreatitis. J Leukoc Biol 90:975–982

    Article  PubMed  CAS  Google Scholar 

  • Azab B, Jaglall N, Atallah JP et al (2011) Neutrophil-lymphocyte ratio as a predictor of adverse outcomes of acute pancreatitis. Pancreatology 11:445–452

    Article  PubMed  Google Scholar 

  • Banks PA, Bollen TL, Dervenis C et al (2013) Classification of acute pancreatitis—2012: revision of the Atlanta classification and definitions by international consensus. Gut 62:102–111

    Article  PubMed  Google Scholar 

  • Bhatia M (2004) Apoptosis of pancreatic acinar cells in acute pancreatitis: is it good or bad? J Cell Mol Med 8:402–409

    Article  PubMed  CAS  Google Scholar 

  • Bhatia M, Brady M, Shokuhi S et al (2000) Inflammatory mediators in acute pancreatitis. J Pathol 190:117–125

    Article  PubMed  CAS  Google Scholar 

  • Bhatia M, Wong FL, Cao Y et al (2005) Pathophysiology of acute pancreatitis. Pancreatology 5:132–144

    Article  PubMed  Google Scholar 

  • Binnetoğlu E, Akbal E, Güneş F et al (2014) The prognostic value of neutrophil-lymphocyte ratio in acute pancreatitis is controversial. J Gastrointest Surg 18:885

    Article  PubMed  Google Scholar 

  • Booth DM, Mukherjee R, Sutton R et al (2011) Calcium and reactive oxygen species in acute pancreatitis: friend or foe? Antioxid Redox Signal 15:2683–2698

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Bradley E 3rd, Murphy F, Ferguson C (1989) Prediction of pancreatic necrosis by dynamic pancreatography. Ann Surg 210:495–503

    Article  PubMed  PubMed Central  Google Scholar 

  • Broere F, Apasov SG, Sitkovsky MV et al (2011) A2 T cell subsets and T cell-mediated immunity. In: Nijkamp FP, Parnham MJ (eds) Principles of immunopharmacology, 3rd edn. Springer, Basel, pp 15–27

    Chapter  Google Scholar 

  • Büchler M, Malfertheiner P, Schoetensack C et al (1986) Value of biochemical and imaging procedures for the diagnosis and prognosis of acute pancreatitis–results of a prospective clinical study. Z Gastroenterol 24:100–109

    PubMed  Google Scholar 

  • Büchler M, Friess H, Uhl W et al (1992) Clinical relevance of experimental acute pancreatitis. Eur Surg Res 24(Suppl 1):85–88

    PubMed  Google Scholar 

  • Chen KL, Lv ZY, Yang HW et al (2016) Effects of tocilizumab on experimental severe acute pancreatitis and associated acute lung injury. Crit Care Med 44:e664–e677

    Article  PubMed  CAS  Google Scholar 

  • Christophi C, McDermott F, Hughes ES (1985) Prognostic significance of the absolute lymphocyte count in acute pancreatitis. Am J Surgery 150:295–296

    Article  CAS  Google Scholar 

  • Criddle D, Gerasimenko JV, Baumgartner H et al (2007) Calcium signalling and pancreatic cell death: apoptosis or necrosis? Cell Death Differ 14:1285–1294

    Article  PubMed  CAS  Google Scholar 

  • Curley PJ, McMahon MJ, Lancaster F et al (1993) Reduction in circulating levels of CD4-positive lymphocytes in acute pancreatitis: relationship to endotoxin, interleukin 6 and disease severity. Br J Surg 80:1312–1315

    Article  PubMed  CAS  Google Scholar 

  • Dabrowski A, Osada J, Dabrowska M et al (2008) Monocyte subsets and natural killer cells in acute pancreatitis. Pancreatology 8:126–134

    Article  PubMed  CAS  Google Scholar 

  • Dang SC, Zhang JX, Qu JG et al (2008) Dynamic changes of IL-2/IL-10, sFas and expression of Fas in intestinal mucosa in rats with acute necrotizing pancreatitis. World J Gastroenterol 14:2246–2250

    Article  PubMed  PubMed Central  Google Scholar 

  • de Jager CP, van Wijk PT, Mathoera RB et al (2010) Lymphocytopenia and neutrophil-lymphocyte count ratio predict bacteremia better than conventional infection markers in an emergency care unit. Crit Care 14:R192

    Article  PubMed  PubMed Central  Google Scholar 

  • Demols A, Le Moine O, Desalle F et al (2000) CD4+ T cells play an important role in acute experimental pancreatitis in mice. Gastroenterology 118:582–590

    Article  PubMed  CAS  Google Scholar 

  • DiMagno MJ, DiMagno EP (2007) New advances in acute pancreatitis. Curr Opin Gastroenterol 23:494–501

    PubMed  PubMed Central  Google Scholar 

  • Dionigi R, Rovera F, Dionigi G et al (2006) Infected pancreatic necrosis. Surg Infect 7(Suppl 2):S49–S52

    Article  Google Scholar 

  • Du WD, Yuan ZR, Sun J et al (2003) Therapeutic efficacy of high-dose vitamin C on acute pancreatitis and its potential mechanisms. World J Gastroenterol 9:2565–2569

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Duffy BK, Gurm HS, Rajagopal V et al (2006) Usefulness of an elevated neutrophil to lymphocyte ratio in predicting long-term mortality after percutaneous coronary intervention. Am J Cardiol 97:993–996

    Article  PubMed  Google Scholar 

  • Escobar J, Pereda J, Lopez-Rodas G et al (2012) Redox signaling and histone acetylation in acute pancreatitis. Free Radic Biol Med 52:819–837

    Article  PubMed  CAS  Google Scholar 

  • Fakhari S, Abdulmohammadi K, Panahi Y et al (2015) Flow cytometric analysis of inflammatory cells in experimental acute pancreatitis. Arch Med Lab Sci 1:93–99

    Google Scholar 

  • Filipovich Y, Agrawal V, Crawford SE et al (2015) Depletion of polymorphonuclear leukocytes has no effect on preterm delivery in a mouse model of Escherichia coli-induced labor. Am J Obstet Gynecol 213:697 (e1–10)

    Article  PubMed  PubMed Central  Google Scholar 

  • Fink GW, Norman JG (1996) Intrapancreatic interleukin-1β gene expression by specific leukocyte populations during acute pancreatitis. J Surg Res 63:369–373

    Article  PubMed  CAS  Google Scholar 

  • Frossard JL, Saluja A, Bhagat L et al (1999) The role of intercellular adhesion molecule 1 and neutrophils in acute pancreatitis and pancreatitis-associated lung injury. Gastroenterology 116:694–701

    Article  PubMed  CAS  Google Scholar 

  • Frossard JL, Steer ML, Pastor CM (2008) Acute pancreatitis. Lancet 371:143–152

    Article  PubMed  Google Scholar 

  • Gallagher SF, Yang J, Baksh K et al (2004) Acute pancreatitis induces FasL gene expression and apoptosis in the liver 1, 2. J Surg Res 122:201–209

    Article  PubMed  CAS  Google Scholar 

  • Greenfield EA, Nguyen KA, Kuchroo VK (1998) CD28/B7 costimulation: a review. Crit Rev Immunol 18:389–418

    Article  PubMed  CAS  Google Scholar 

  • Gukovskaya AS, Vaquero E, Zaninovic V et al (2002) Neutrophils and NADPH oxidase mediate intrapancreatic trypsin activation in murine experimental acute pancreatitis. Gastroenterology 122:974–984

    Article  PubMed  CAS  Google Scholar 

  • Gul’muradova NT, Geinits AV, Ziazin S (2012) The characteristics of cell and humoral immunity in patients with acute pancreatitis under impact of cold laser radiation. Klin Lab Diagn 7:46–49

    Google Scholar 

  • Guo ZZ, Wang P, Yi ZH et al (2014) The crosstalk between gut inflammation and gastrointestinal disorders during acute pancreatitis. Curr Pharm Des 20:1051–1062

    Article  PubMed  CAS  Google Scholar 

  • Habtezion A, Algül H (2016) Immune modulation in acute and chronic pancreatitis. Pancreapedia Exocrine Pancreas Knowl Base. https://doi.org/10.3998/panc.2016.30

    Article  Google Scholar 

  • Halacheva K, Minkov G, Yovtchev Y et al (2014) Changes in peripheral blood lymphocyte populations in patients with acute pancreatitis. Trakia J Sci 12:50–54

    Google Scholar 

  • Hegyi P, Rakonczay Z Jr (2011) The role of nitric oxide in the physiology and pathophysiology of the exocrine pancreas. Antioxid Redox Signal 15:2723–2741

    Article  PubMed  CAS  Google Scholar 

  • Hoque R, Malik A, Gorelick F et al (2012) The sterile inflammatory response in acute pancreatitis. Pancreas 41:353–357

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Huan C, Kim D, Ou P et al (2016) Mechanisms of interleukin-22’s beneficial effects in acute pancreatitis. World J Gastrointest Pathophysiol 7:108–116

    Article  PubMed  PubMed Central  Google Scholar 

  • Iyer SS, Pulskens WP, Sadler JJ et al (2009) Necrotic cells trigger a sterile inflammatory response through the Nlrp3 inflammasome. Proc Natl Acad Sci USA 106:20388–20393

    Article  PubMed  PubMed Central  Google Scholar 

  • Jelinek DF (2000) Regulation of B lymphocyte differentiation. Ann Allergy Asthma Immunol 84:375–385

    Article  PubMed  CAS  Google Scholar 

  • Jenkins MK, Johnson JG (1993) Molecules involved in T-cell costimulation. Curr Opin Immunol 5:361–367

    Article  PubMed  CAS  Google Scholar 

  • Kambhampati S, Park W, Habtezion A (2014) Pharmacologic therapy for acute pancreatitis. World J Gastroenterol 20:16868–16880

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kay PS, Smith M, Brand M (2017) The initiating immune response of acute pancreatitis may be mediated by the T-helper 17 pathway. JOP J Pancreas 18(1):33–37

    Google Scholar 

  • Kell MR, Kavanagh EG, Goebel A et al (1999) Injury primes the immune system for an enhanced and lethal T-cell response against bacterial superantigen. Shock 12:139–144

    Article  PubMed  CAS  Google Scholar 

  • Kim H, Seo JY, Roh KH et al (2000) Suppression of NF-κB activation and cytokine production by N-acetylcysteine in pancreatic acinar cells. Free Radic Biol Med 29:674–683

    Article  PubMed  CAS  Google Scholar 

  • Koussoulas V, Tzivras M, Karagianni V et al (2006) Monocytes in systematic inflammatory response syndrome: differences between sepsis and acute pancreatitis. World J Gastroenterol 12:6711–6714

    Article  PubMed  CAS  Google Scholar 

  • Kumar R, Bhatia M (2014) Cells and mediators of inflammation in acute pancreatitis. Clin Anti-Inflamm Anti-Allergy Drugs 1:11–23

    Article  CAS  Google Scholar 

  • Lanier LL (2005) NK cell recognition. Annu Rev Immunol 23:225–274

    Article  PubMed  CAS  Google Scholar 

  • Lanier L (2007) Back to the future–defining NK cells and T cells. Eur J Immunol 37:1424–1426

    Article  PubMed  CAS  Google Scholar 

  • Lankisch PG, Apte M, Banks PA (2015) Acute pancreatitis. Lancet 386:85–96

    Article  PubMed  Google Scholar 

  • LeBien TW, Tedder TF (2008) B lymphocytes: how they develop and function. Blood 112:1570–1580

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lee RK (2012) Intra-abdominal hypertension and abdominal compartment syndrome a comprehensive overview. Crit Care Nurse 32:19–31

    Article  PubMed  Google Scholar 

  • Li Z, Ma Q, Luo Y (2009) Effect of resveratrol-induced FasL up-regulation on the apoptosis of pancreatic acinar cells in rats with severe acute pancreatitis. Nan Fang Yi Ke Da Xue Xue Bao 29:454–457

    PubMed  Google Scholar 

  • Li Q, Wang C, Zhang Q et al (2012) The role of sphingosine kinase 1 in patients with severe acute pancreatitis. Ann Surg 255:954–962

    Article  PubMed  Google Scholar 

  • Li J, Yang WJ, Huang LM et al (2014) Immunomodulatory therapies for acute pancreatitis. World J Gastroenterol 20:16935–16947

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Liou GY, Storz P (2015) Inflammatory macrophages in pancreatic acinar cell metaplasia and initiation of pancreatic cancer. Oncoscience 2:247–251

    Article  PubMed  PubMed Central  Google Scholar 

  • Liu Z, Shen Y, Cui N et al (2011) Clinical observation of immunity for severe acute pancreatitis. Inflammation 34:426–431

    Article  PubMed  CAS  Google Scholar 

  • Liu Y, Wang L, Cai Z et al (2015) the decrease of peripheral blood CD4+ T cells indicates abdominal compartment syndrome in severe acute pancreatitis. PLoS One 10:e0135768

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lugli E, Troiano L, Cossarizza A (2009) Investigating T cells by polychromatic flow cytometry. Methods Mol Biol 514:47–63

    Article  PubMed  CAS  Google Scholar 

  • Makhija R, Kingsnorth AN (2002) Cytokine storm in acute pancreatitis. J Hepatobiliary Pancreat Surg 9:401–410

    Article  PubMed  Google Scholar 

  • Mareninova OA, Sung KF, Hong P et al (2006) Cell death in pancreatitis caspases protect from necrotizing pancreatitis. J Biol Chem 281:3370–3381

    Article  PubMed  CAS  Google Scholar 

  • Mayer JM, Laine VJ, Gezgin A et al (2000) Single doses of FK506 and OKT3 reduce severity in early experimental acute pancreatitis. Eur J Surgery 166:734–741

    Article  CAS  Google Scholar 

  • Mayerle J, Dummer A, Sendler M et al (2012) Differential roles of inflammatory cells in pancreatitis. J Gastroenterol Hepatol 27(Suppl 2):47–51

    Article  PubMed  CAS  Google Scholar 

  • Mentula P, Kylanpaa-Back ML, Kemppainen E et al (2003) Decreased HLA (human leucocyte antigen)-DR expression on peripheral blood monocytes predicts the development of organ failure in patients with acute pancreatitis. Clin Sci 105:409–417

    Article  PubMed  CAS  Google Scholar 

  • Mikhaylov VA (2015) The use of Intravenous Laser Blood Irradiation (ILBI) at 630–640 nm to prevent vascular diseases and to increase life expectancy. Laser Ther 24:15–26

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Mora A, Perez-Mateo M, Viedma J et al (1997) Activation of cellular immune response in acute pancreatitis. Gut 40:794–797

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Mylona V, Koussoulas V, Tzivras D et al (2011) Changes in adaptive and innate immunity in patients with acute pancreatitis and systemic inflammatory response syndrome. Pancreatology 11:475–481

    Article  PubMed  CAS  Google Scholar 

  • Nakayama S, Nishio A, Yamashina M et al (2014) Acquired immunity plays an important role in the development of murine experimental pancreatitis induced by alcohol and lipopolysaccharide. Pancreas 43:28–36

    Article  PubMed  CAS  Google Scholar 

  • Ni J, Hu G, Xiong J et al (2013) Involvement of interleukin-17A in pancreatic damage in rat experimental acute necrotizing pancreatitis. Inflammation 36:53–65

    Article  PubMed  CAS  Google Scholar 

  • Norman JG (1999) New approaches to acute pancreatitis: role of inflammatory mediators. Digestion 60(Suppl 1):57–60

    Article  PubMed  CAS  Google Scholar 

  • Oiva J, Mustonen H, Kylanpaa ML et al (2010) Acute pancreatitis with organ dysfunction associates with abnormal blood lymphocyte signaling: controlled laboratory study. Crit Care 14:R207

    Article  PubMed  PubMed Central  Google Scholar 

  • Oiva J, Mustonen H, Kylanpaa ML et al (2013) Patients with acute pancreatitis complicated by organ dysfunction show abnormal peripheral blood polymorphonuclear leukocyte signaling. Pancreatology 13:118–124

    Article  PubMed  Google Scholar 

  • Papachristou GI, Clermont G, Sharma A et al (2007) Risk and markers of severe acute pancreatitis. Gastroenterol Clin North Am 36:277–296

    Article  PubMed  Google Scholar 

  • Park JJ, Jang HJ, Oh IY et al (2013) Prognostic value of neutrophil to lymphocyte ratio in patients presenting with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention. Am J Cardiol 111:636–642

    Article  PubMed  Google Scholar 

  • Parzyan G, Geinits A (2001) Treatment of acute pancreatitis with mexidol and low-intensity laser radiation. In: Low-Level Laser Therapy, 2001. In: Proceedings of the SPIE, vol 4422, pp 92–97. https://doi.org/10.1117/12.425521

  • Pezzilli R, Billi P, Beltrandi E et al (1995) Circulating lymphocyte subsets in human acute pancreatitis. Pancreas 11:95–100

    Article  PubMed  CAS  Google Scholar 

  • Pezzilli R, Maldini M, Morselli-Labate AM et al (2003) Early activation of peripheral lymphocytes in human acute pancreatitis. J Clin Gastroenterol 36:360–363

    Article  PubMed  Google Scholar 

  • Piccinini A, Midwood K (2010) DAMPening inflammation by modulating TLR signalling. Mediators Inflamm 2010:1–21. https://doi.org/10.1155/2010/672395

    Article  CAS  Google Scholar 

  • Pichler M, Hutterer GC, Stoeckigt C et al (2013) Validation of the pre-treatment neutrophil–lymphocyte ratio as a prognostic factor in a large European cohort of renal cell carcinoma patients. Br J Cancer 108:901–907

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Pietruczuk M, Dabrowska MI, Wereszczynska-Siemiatkowska U et al (2006) Alteration of peripheral blood lymphocyte subsets in acute pancreatitis. World J Gastroenterol 12:53445351

    Article  Google Scholar 

  • Pinhu L, Qin Y, Xiong B et al (2014) Overexpression of Fas and FasL is associated with infectious complications and severity of experimental severe acute pancreatitis by promoting apoptosis of lymphocytes. Inflammation 37:1202–1212

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Qiang F, Naiqiang C, Wenli Y et al (2010) Percentages of CD4+ T regulatory cells and HLA-DR expressing monocytes in severe intra-abdominal infections. Scand J Infect Dis 42:475–478

    Article  CAS  Google Scholar 

  • Qin Y, Liao P, He S et al (2013a) Detection of FasL mRNA, sFasL and their regulatory effect on T lymphocyte subsets in patients with severe acute pancreatitis. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 29:1189–1192

    PubMed  CAS  Google Scholar 

  • Qin Y, Pinhu L, You Y et al (2013b) The role of Fas expression on the occurrence of immunosuppression in severe acute pancreatitis. Dig Dis Sci 58:3300–3307

    Article  PubMed  CAS  Google Scholar 

  • Rakonczay Z, Hegyi P, Takacs T et al (2008) The role of NF-κB activation in the pathogenesis of acute pancreatitis. Gut 57:259–267

    Article  PubMed  CAS  Google Scholar 

  • Rinderknecht H (1988) Fatal pancreatitis, a consequence of excessive leukocyte stimulation? Int J Pancreatol 3:105–112

    PubMed  CAS  Google Scholar 

  • Rotstein OD (2014) Circulating cytokines in predicting development of severe acute pancreatitis. Crit Care 18:575

    Article  PubMed  PubMed Central  Google Scholar 

  • Salomon B, Bluestone JA (2001) Complexities of CD28/B7: CTLA-4 costimulatory pathways in autoimmunity and transplantation. Annu Rev Immunol 19:225–252

    Article  PubMed  CAS  Google Scholar 

  • Schmidt AI, Kühlbrey C, Lauch R et al (2017) The predominance of a naive T helper cell subset in the immune response of experimental acute pancreatitis. Pancreatology 17:209–218

    Article  PubMed  CAS  Google Scholar 

  • Schütte K, Malfertheiner P (2008) Markers for predicting severity and progression of acute pancreatitis. Best Pract Res Clin Gastroenterol 22:75–90

    Article  PubMed  CAS  Google Scholar 

  • Shamoon M, Deng Y, Chen YQ et al (2016) Therapeutic implications of innate immune system in acute pancreatitis. Expert Opin Ther Targets 20:73–87

    Article  PubMed  CAS  Google Scholar 

  • Shang D, Qi QH, Wang BZ et al (2007) Role of polymorphonuclear neutrophil apoptosis and expression of Fas and caspase-3 in the systemic inflammatory response syndrome. Zhongguo Wei Zhong Bing Ji Jiu Yi Xue 19:11–13

    PubMed  CAS  Google Scholar 

  • Shen Y, Cui NQ (2012) Clinical observation of immunity in patients with secondary infection from severe acute pancreatitis. Inflamm Res 61:743–748

    Article  PubMed  CAS  Google Scholar 

  • Shen X, Sun J, Ke L et al (2015) Reduced lymphocyte count as an early marker for predicting infected pancreatic necrosis. BMC Gastroenterol 15:147

    Article  PubMed  PubMed Central  Google Scholar 

  • Shrivastava P, Bhatia M (2010) Essential role of monocytes and macrophages in the progression of acute pancreatitis. World J Gastroenterol 16:3995–4002

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Spiegel S, Milstien S (2003) Sphingosine-1-phosphate: an enigmatic signalling lipid. Nat Rev Mol Cell Biol 4:397–407

    Article  PubMed  CAS  Google Scholar 

  • Steinberg WM, Schlesselman SE (1987) Treatment of acute pancreatitis: comparison of animal and human studies. Gastroenterology 93:1420–1427

    Article  PubMed  CAS  Google Scholar 

  • Sun JC, Beilke JN, Lanier LL (2009) Adaptive immune features of natural killer cells. Nature 457:557–561

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Suppiah A, Malde D, Arab T et al (2013) The prognostic value of the neutrophil–lymphocyte ratio (NLR) in acute pancreatitis: identification of an optimal NLR. J Gastrointest Surg 17:675–681

    Article  PubMed  Google Scholar 

  • Sweeney K, Kell M, Coates C et al (2003) Serum antigen (s) drive the proinflammatory T cell response in acute pancreatitis. Br J Surg 90:313–319

    Article  PubMed  CAS  Google Scholar 

  • Takeyama Y (2005) Significance of apoptotic cell death in systemic complications with severe acute pancreatitis. J Gastroenterol 40:1–10

    Article  PubMed  Google Scholar 

  • Takeyama Y, Takase K, Ueda T et al (2000) Peripheral lymphocyte reduction in severe acute pancreatitis is caused by apoptotic cell death. J Gastrointest Surg 4:379–387

    Article  PubMed  CAS  Google Scholar 

  • Ueda T, Takeyama Y, Yasuda T et al (2006) Immunosuppression in patients with severe acute pancreatitis. J Gastroenterol 41:779–784

    Article  PubMed  CAS  Google Scholar 

  • Uehara S, Gothoh K, Handa H et al (2003) Immune function in patients with acute pancreatitis. J Gastroenterol Hepatol 18:363–370

    Article  PubMed  CAS  Google Scholar 

  • Vonlaufen A, Apte M, Imhof B et al (2007) The role of inflammatory and parenchymal cells in acute pancreatitis. J Pathol 213:239–248

    Article  PubMed  CAS  Google Scholar 

  • Ward NS, Casserly B, Ayala A (2008) The compensatory anti-inflammatory response syndrome (CARS) in critically ill patients. Clin Chest Med 29:617–625

    Article  PubMed  PubMed Central  Google Scholar 

  • Widdison AL, Cunningham S (1996) Immune function early in acute pancreatitis. Br J Surg 83:633–636

    Article  PubMed  CAS  Google Scholar 

  • Witko-Sarsat V, Pederzoli-Ribeil M, Hirsh E et al (2011) Regulating neutrophil apoptosis: new players enter the game. Trends Immunol 32:117–124

    Article  PubMed  CAS  Google Scholar 

  • Xue J, Nguyen DT, Habtezion A (2012) Aryl hydrocarbon receptor regulates pancreatic IL-22 production and protects mice from acute pancreatitis. Gastroenterology 143:1670–1680

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Xue J, Sharma V, Habtezion A (2014) Immune cells and immune-based therapy in pancreatitis. Immunol Res 58:378–386

    Article  PubMed  CAS  Google Scholar 

  • Yang Z, Zhang Y, Dong L et al (2015) The reduction of peripheral blood CD4+ T cell indicates persistent organ failure in acute pancreatitis. PLoS One 10:e0125529

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Yazdi AS, Guarda G, D’Ombrain MC et al (2010) Inflammatory caspases in innate immunity and inflammation. J Innate Immun 2:228–237

    Article  PubMed  CAS  Google Scholar 

  • Yubero S, Ramudo L, Manso MA et al (2009) Targeting peripheral immune response reduces the severity of necrotizing acute pancreatitis. Crit Care Med 37:240–245

    Article  PubMed  Google Scholar 

  • Zaninovic V, Gukovskaya AS, Gukovsky I et al (2000) Cerulein upregulates ICAM-1 in pancreatic acinar cells, which mediates neutrophil adhesion to these cells. Am J Physiol Gastroint Liver Physiol 279:G666–G676

    Article  CAS  Google Scholar 

  • Zhang X, Chen L, Luo L et al (2008) Study of the protective effects of dexamethasone on ileum mucosa injury in rats with severe acute pancreatitis. Pancreas 37:e74–e82

    Article  PubMed  CAS  Google Scholar 

  • Zhang Y, Wu W, Dong L et al (2016) Neutrophil to lymphocyte ratio predicts persistent organ failure and in-hospital mortality in an Asian Chinese population of acute pancreatitis. Medicine 95:e4746

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zheng X, Li S-B, Wang Y et al (2010) Changes of T lymphocyte subsets before and after treatment of acute pancreatitis and its clinical significance [J]. Mod Med J 4:027

    Google Scholar 

  • Zheng L, Xue J, Jaffee EM et al (2013) Role of immune cells and immune-based therapies in pancreatitis and pancreatic ductal adenocarcinoma. Gastroenterology 144:1230–1240

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhulai GA, Oleinik EK, Ostrovskii KA et al (2014) Alterations of lymphocyte subsets and indicators of immune suppression in patients with acute pancreatitis. Eksp Klin Gastroenterol 9:21–25

    Google Scholar 

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Acknowledgements

This Research was supported by Faculty of Health Sciences University of the Witwatersrand Individual Research Grant 001.283.8441101.5121105.5142 and Seed funding Grant 001 251 8441101 5121105 000000 0000000000 4550. The authors would like to thank Drs M. Nel and J. Devar for critical reading of the manuscript.

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  1. Department of Surgery, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown, Johannesburg, 2193, South Africa

    Pascaline Fonteh, Martin Smith & Martin Brand

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  1. Pascaline Fonteh
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  2. Martin Smith
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Correspondence to Pascaline Fonteh.

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Fonteh, P., Smith, M. & Brand, M. Adaptive Immune Cell Dysregulation and Role in Acute Pancreatitis Disease Progression and Treatment. Arch. Immunol. Ther. Exp. 66, 199–209 (2018). https://doi.org/10.1007/s00005-017-0495-1

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