Skip to main content

Immunological Mechanisms in Acute Pancreatitis

  • Chapter
Pancreatic Disease

Abstract

In recent years it has become evident that both the intrapancreatic events and, even more, the extrapancreatic manifestations of severe acute pancreatitis (septic inflammatory response syndrome, whole-body inflammation) depend on immunological mechanisms. Thus far, this has not led to diagnostic or therapeutic consequences, with the exception of clinical trials with a PAF antagonist, lexipafant [1, 2]. In the following, the evidence for the importance of immunological mechanisms in the pathophysiology of severe acute pancreatitis will be presented. First the role of mediators in inflammation in general will be discussed, thereafter the role of cytokines in the pancreas itself during initial organ attack, then the role of cytokines as effectors in the systemic manifestations of acute pancreatitis, and finally possible conse quences for diagnosis and treatment.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Kingsnorth AN, Galloway SW, Formela LJ (1995) Randomized, double-blind phase II trial of lexipafant, a platelet-activating factor antagonist, in human acute pancreatitis. Br J Surg 82:1414–1420

    Article  PubMed  CAS  Google Scholar 

  2. McKay CJ, Curran F, Sharpies C, Baxter JN, Imrie CW (1997) Prospective placebo-controlled randomized trial of lexipafant in predicted severe acute pancreatitis. Br J Surg 84:1239–1243

    Article  PubMed  CAS  Google Scholar 

  3. Daig R, Andus T, Aschenbrenner E, Falk W, Schölmerich J, Gross V (1996) Increased interleukin 8 expression in the colon mucosa of patients with inflammatory bowel disease. Gut 38:216–222

    Article  PubMed  CAS  Google Scholar 

  4. Rinderknecht H (1988) Fatal pancreatitis, a consequence of excessive leukocyte stimulation. Intern J Pankreatol 3:105–112

    CAS  Google Scholar 

  5. Schölmerich J, Schümichen C, Lausen M, Gross V, Leser H-G, Lay L, Farthmann EH, Gerok W (1991) Scintigraphic assessment of leukocyte infiltration in acute pancreatitis using technetium 99m-hexamethyl propylene amine oxide as leukocyte label. Dig Dis Sci 36:65–70

    Article  PubMed  Google Scholar 

  6. Leser H-G, Gross V, Scheibenbogen C, Heinisch A, Salm R, Lausen M, Rückauer K, Andreesen R, Farthmann EH, Schölmerich J (1991) Elevation of serum interleukin-6 precedes acute-phase response and reflects severity in acute pancreatitis. Gastroenterology 101:782–785

    PubMed  CAS  Google Scholar 

  7. Gross V, Andreesen R, Leser H-G, Lausen M, Farthmann EH, Gerok W, Schölmerich J (1992) Interleukin-8 and neutrophil activation in acute pancreatitis. Eur J Clin Invest 22:200–203

    Article  PubMed  CAS  Google Scholar 

  8. Schölmerich J (1996) Interleukins in acute pancreatitis. Scand J Gastroenterol 31[Suppl 219]:37–42

    Article  Google Scholar 

  9. Gross V, Leser H-G, Heinisch A, Schölmerich J (1993) Inflammatory mediators and cytokines — new aspects of the pathophysiology and assessment of severity of acute pancreatitis. Hepatogastroenterology 40:522–530

    PubMed  CAS  Google Scholar 

  10. Denham W, Yang J, Fink G, Denham D, Carter G, Ward K, Norman J (1997) Gene targeting demonstrates additive detrimental effects of interleukin 1 and tumor necrosis factor during pancreatitis. Gastroenterology 113:1741–1746

    Article  PubMed  CAS  Google Scholar 

  11. Grady T, Liang P, Ernst SA, Logsdon CD (1997) Chemokine gene expression in rat pancreatic acinar cells is an early event associated with acute pancreatitis. Gastroenterology 113:1966–1975

    Article  PubMed  CAS  Google Scholar 

  12. Grewal HP, Mohey EDA, Gaber L, Kotb M, Gaber A (1994) Amelioration of the physiologic and biochemical changes of acute pancreatitis using an anti-TNF-alpha polyclonal antibody. Am J Surg 167:214–219

    Article  PubMed  CAS  Google Scholar 

  13. Meßmann H, Vogt W, Holstege A, Lock G, Heinisch A, Fürstenberg A, Leser H-G, Zirngibl H, Schölmerich J (1997) Post ERP pancreatitis as a model for cytokine induced acute phase response in acute pancreatitis. Gut 40:80–85

    PubMed  Google Scholar 

  14. Meßmann H, Vogt W, Falk W, Vogl D, Zirngibl H, Leser HG, Schölmerich J (1998) Interleukins and their antagonists but not TNF and its receptors are released in post-ERP pancreatitis. Eur J Gastroenterol Hepatol 10:611–617

    Article  PubMed  Google Scholar 

  15. Paajanen H, Laat N, Jaakkola N, Pulkki K, Niinikoski J, Nordbach I (1995) Serum tumor necrosis factor compared with C-reactive protein in the early assessment of severity of acute pancreatitis. Br J Surg 82:271–273

    Article  PubMed  CAS  Google Scholar 

  16. Meßmann H, Grüne S, Sitter-Heinisch A, Agha A, Schmidt J, Mann S, Mann U, Holstege A, Zirngibl H. Schölmerich J (1997) TNF and TNF-receptors p55 and p75 in acute mild and severe pancreatitis. Gastroenterology 112:A464

    Google Scholar 

  17. Pezzilli R, Billi P, Miniera R, Barakat B (1997) Serum interleukin-10 in human acute pancreatitis. Dig Dis Sci 42:1469–1472

    Article  PubMed  CAS  Google Scholar 

  18. Gerard C, Frossard JL, Bhatia M, Sluja A, Gerard NP, Lu B, Steer M (1997) Targeted disruption of the β-chemokine receptor CCR1 protects against pancreatitis-associated lung injury. J Clin Invest 100:2022–2027

    Article  PubMed  CAS  Google Scholar 

  19. Norman J, Fink G, Franz M (1995) Acute pancreatitis induced intrapancreatic tumor necrosis factor gene expression. Arch Surg 131:966–970

    Google Scholar 

  20. Schölmerich J, Heinisch A, Leser H-G (1993) Diagnostic approach to acute pancreatitis: diagnosis, assessment of etiology and prognosis. Hepatogastroenterology 40:531–537

    PubMed  Google Scholar 

  21. Pezzilli R, Billi P, Miniera R, Fiocchi M, Cappelletti O, Morselli-Labate AM, Barakat B, Sprovieri G, Miglioli M (1995) Serum interleukin-6, interleukin-8, and β 2-microglobulin in early assessment of severity of acute pancreatitis. Dig Dis Sci 40:2341–2348

    Article  PubMed  CAS  Google Scholar 

  22. Pezzilli R, Miniero R, Cappelletti O, Barakat B (1998) Serum interleukin 6 in the prognosis of acute biliary pancreatitis. Ital J Gastroenterol Hepatol 30:291–294

    PubMed  CAS  Google Scholar 

  23. Rau B, Steinbach G, Gansauge F, Mayer JM, Grünert A, Beger HG (1997) The potential role of procalcitonin and interleukin-8 in the prediction of infected necrosis in acute pancreatitis. Gut 41:832–840

    Article  PubMed  CAS  Google Scholar 

  24. Norman J, Franz M, Messina J, Riker A, Fabri PJ, Rosemurgy AS, Gower WR (1994) Interleukin-1 receptor antagonist decreases severity of experimental acute pancreatitis. Surgery 117:648–655

    Article  Google Scholar 

  25. Osman MO, Kristensen JU, Jacobsen NO, Lausten SB, Deleuran B, Deleuran M, Gesser B, Matsushima K, Larsen CG, Jensen SL (1998) A monoclonal anti-interleukin 8 antibody (WS-4) inhibits cytokine response and acute lung injury in experimental severe acute necrotising pancreatitis in rabbits. Gut 43:232–239

    Article  PubMed  CAS  Google Scholar 

  26. Lane JS, Todd KE, Mc Fadden DW, Reber HA, Ashley SW (1996) Interleukin-10 reduces severity early in the course of pancreatitis. Pancreas 13:445

    Google Scholar 

  27. Van Laethem JV, Marchant A, Delvaux A, Goldmann M, Robberecht P, Velu T, Deviere J (1995) Interleukin 10 prevents necrosis in murine experimental pancreatitis. Gastroenterology 108:1917–1922

    Article  PubMed  Google Scholar 

  28. Rongione AJ, Kusske AM, Kwan K, Ashley SW, Reber HA, McFadden DW (1997) Interleukin 10 reduces the severity of acute pancreatitis in rats. Gastroenterology 112:960–967

    Article  PubMed  CAS  Google Scholar 

  29. van Deventer SJ, Elson CO, Federak RN (1997) Multiple doses of intravenous interleukin 10 in steroid refractory Crohn’s disease. Gastroenterology 113:283–289

    Google Scholar 

  30. Schreiber S (1997) Interleukin 10 in the intestine. Gut 41:274–275

    Article  PubMed  CAS  Google Scholar 

  31. Hughes CB, Grewal HP, Gaber LW, Kotb M, Mohey El-din AB, Mann L, Gaber AO (1996) Anti-TNF therapy improves survival and ameliorates the pathophysiologic sequelae in acute pancreatitis in the rat. Am J Surg 171:274–280

    Article  PubMed  CAS  Google Scholar 

  32. Guice KS, Oldham KT, Remick DG, Kunkel SL, Ward PA (1991) Anti-tumor necrosis factor antibody augments edema formation in cerulein-induced acute pancreatitis. J Surg Res 51:495–499

    Article  PubMed  CAS  Google Scholar 

  33. Echternacher B, Falk W, Maennel DN, Krammer PH (1990) Requirement of endogenous tumor necrosis factor/cachectin for recovery from experimental peritonitis. J Immunol 145:3762–3766

    Google Scholar 

  34. Rongione A, Kusske A, Kwan K, Ashley S, Reber H, McFadden D (1996) Interleukin 10 protects against lethality of intraabdominal infection and sepsis. Gastroenterology 110:A1104

    Google Scholar 

  35. Kojouharoff G, Hans W, Obermeier F, Männel DN, Andus T, Schölmerich J, Groß V, Falk W (1997) Neutralization of tumour necrosis factor (TNF) but not IL-1 reduces inflammation in chronic dextran sulphate sodium-induced colitis in mice. Clin Exp Immunol 107:353–358

    Article  PubMed  CAS  Google Scholar 

Download references

Authors

Rights and permissions

Reprints and permissions

Copyright information

© 1999 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Schölmerich, J. (1999). Immunological Mechanisms in Acute Pancreatitis. In: Pancreatic Disease. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-60068-5_3

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-60068-5_3

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-65357-8

  • Online ISBN: 978-3-642-60068-5

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics