Immunological Mechanisms in Acute Pancreatitis

  • J. Schölmerich


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.


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  1. 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 82:1414–1420PubMedCrossRefGoogle Scholar
  2. 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 84:1239–1243PubMedCrossRefGoogle Scholar
  3. 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 38:216–222PubMedCrossRefGoogle Scholar
  4. 4.
    Rinderknecht H (1988) Fatal pancreatitis, a consequence of excessive leukocyte stimulation. Intern J Pankreatol 3:105–112Google Scholar
  5. 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 36:65–70PubMedCrossRefGoogle Scholar
  6. 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 101:782–785PubMedGoogle Scholar
  7. 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 22:200–203PubMedCrossRefGoogle Scholar
  8. 8.
    Schölmerich J (1996) Interleukins in acute pancreatitis. Scand J Gastroenterol 31[Suppl 219]:37–42CrossRefGoogle Scholar
  9. 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 40:522–530PubMedGoogle Scholar
  10. 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 113:1741–1746PubMedCrossRefGoogle Scholar
  11. 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 113:1966–1975PubMedCrossRefGoogle Scholar
  12. 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 167:214–219PubMedCrossRefGoogle Scholar
  13. 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 40:80–85PubMedGoogle Scholar
  14. 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 10:611–617PubMedCrossRefGoogle Scholar
  15. 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 82:271–273PubMedCrossRefGoogle Scholar
  16. 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:A464Google Scholar
  17. 17.
    Pezzilli R, Billi P, Miniera R, Barakat B (1997) Serum interleukin-10 in human acute pancreatitis. Dig Dis Sci 42:1469–1472PubMedCrossRefGoogle Scholar
  18. 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 100:2022–2027PubMedCrossRefGoogle Scholar
  19. 19.
    Norman J, Fink G, Franz M (1995) Acute pancreatitis induced intrapancreatic tumor necrosis factor gene expression. Arch Surg 131:966–970Google Scholar
  20. 20.
    Schölmerich J, Heinisch A, Leser H-G (1993) Diagnostic approach to acute pancreatitis: diagnosis, assessment of etiology and prognosis. Hepatogastroenterology 40:531–537PubMedGoogle Scholar
  21. 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 40:2341–2348PubMedCrossRefGoogle Scholar
  22. 22.
    Pezzilli R, Miniero R, Cappelletti O, Barakat B (1998) Serum interleukin 6 in the prognosis of acute biliary pancreatitis. Ital J Gastroenterol Hepatol 30:291–294PubMedGoogle Scholar
  23. 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 41:832–840PubMedCrossRefGoogle Scholar
  24. 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 117:648–655CrossRefGoogle Scholar
  25. 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 43:232–239PubMedCrossRefGoogle Scholar
  26. 26.
    Lane JS, Todd KE, Mc Fadden DW, Reber HA, Ashley SW (1996) Interleukin-10 reduces severity early in the course of pancreatitis. Pancreas 13:445Google Scholar
  27. 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 108:1917–1922PubMedCrossRefGoogle Scholar
  28. 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 112:960–967PubMedCrossRefGoogle Scholar
  29. 29.
    van Deventer SJ, Elson CO, Federak RN (1997) Multiple doses of intravenous interleukin 10 in steroid refractory Crohn’s disease. Gastroenterology 113:283–289Google Scholar
  30. 30.
    Schreiber S (1997) Interleukin 10 in the intestine. Gut 41:274–275PubMedCrossRefGoogle Scholar
  31. 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 171:274–280PubMedCrossRefGoogle Scholar
  32. 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 51:495–499PubMedCrossRefGoogle Scholar
  33. 33.
    Echternacher B, Falk W, Maennel DN, Krammer PH (1990) Requirement of endogenous tumor necrosis factor/cachectin for recovery from experimental peritonitis. J Immunol 145:3762–3766Google Scholar
  34. 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:A1104Google Scholar
  35. 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 107:353–358PubMedCrossRefGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 1999

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  • J. Schölmerich

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