Possible Therapeutic Approaches to Deal with Bacterial/Endotoxin Translocation

  • H. Redl
  • S. Bahrami
  • G. Schlag
Conference paper
Part of the Yearbook of Intensive Care and Emergency Medicine book series (YEARBOOK, volume 1995)


In the 1950s and the early 1960s, Fine et al. [1] were the first to develop the concept that bacteria and endotoxin escaping from the gut might be a decisive factor for the development of irreversible shock and sepsis. The specific term of bacterial translocation (BT) was introduced in the field by Wolochow et al. only in 1966 [2]. Obligate anaerobic bacteria outnumber enteric gram-negative and aerobic gram-positive bacteria by thousand to ten thousand-fold and appear associated closely to the intestinal epithelium, forming in fact a physical barrier to limit a direct attachment of potential translocating bacteria to the intestinal mucosa [3]. There is now agreement that these obligate anaerobic bacteria are responsible for colonization resistance, a term created by van der Waaij et al. [4]·


Placebo Permeability Fermentation Ischemia Bacillus 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Fine J, Ruteburg SH, Schweinburg FB (1959) The role of the RES in hemorrhagic shock. J Exp Med 110: 547–551PubMedCrossRefGoogle Scholar
  2. 2.
    Wolochow H, Hildebrand GJ, Lammanna C (1966) Translocation of microorganisms across the intestinal wall in rats: Effect of microbial size and concentration. J Infect Dis 116: 523–528PubMedCrossRefGoogle Scholar
  3. 3.
    Mainous MR, Deitch EA (1993) Bacterial translocation. In: Schlag G, Redl H (eds) Pathophysiology of shock, sepsis, and organ failure. Springer-Verlag, Heidelberg, Berlin, New York. pp 263–278Google Scholar
  4. 4.
    Van der Waaij D, Berghuis-de Vries JM, Lekkerkerk-van der Wees JC (1971) Colonization resistance of the digestive tract in conventional and antibiotic treated mice. J Hyg (Camb) 69: 405–411CrossRefGoogle Scholar
  5. 5.
    Haglund U (1993) Hypoxic damage. In: Schlag G, Redl H (eds) Pathophysiology of shock, sepsis, and organ failure. Springer-Verlag, Heidelberg, Berlin, New York. pp 314–321CrossRefGoogle Scholar
  6. 6.
    Granger DN (1988) Role of xanthine oxidase and granulocytes in ischemia-reperfusion injury. Am J Physiol 255: H1269–1275PubMedGoogle Scholar
  7. 7.
    Duncker HP, Koch T, Axt R, et al (1992) Investigations of bacterial clearance and RES-phagocytosis-capacity in different shock models of the rabbit. Eur Surg Res 26: 24–42Google Scholar
  8. 8.
    Pasquale MD, Cipolle MD, Cerra FB (1994) Bacterial translocation: Myth versus reality. In: Reinhart K, Eyrich K, Sprung C (eds) Sepsis Update in Intensive Care and Emergency Medicine. Springer-Verlag, Berlin, Heidelberg, New York. pp 86–106Google Scholar
  9. 9.
    Jianxin J, Bahrami S, Leichtfried G, Redl H, Oehlinger W, Schlag G (1995) Kinetics of endotoxin and tumor necrosis factor appearence in portal and systemic circulation following hemorrhagic shock in rats. Ann Surg (In press)Google Scholar
  10. 10.
    Bahrami S, Schlag G, Yao YM, Redl H (1995) Significance of translocation/endotoxin in the development of systemic sepsis following trauma and/or hemorrhage. In: Levin J, Alving CR, Munford RS, Redl H (eds) Bacterial endotoxins: Lipopolysaccharides from genes to therapy. John Wiley & Sons, Inc. New York (In press)Google Scholar
  11. 11.
    Schlag G, Redl H, Dinges HP, Radmore K (1991) Bacterial translocation in a baboon model of hypovolemic-traumatic shock. In: Schlag G, Redl H, Siegel JH, Traber DL (eds) Springer-Verlag, Heidelberg, Berlin, New York. pp 53–90Google Scholar
  12. 12.
    Herman CM, Kraft AR, Smith KR, et al (1974) The relationship of circulating endogenous endotoxin to hemorrhagic shock in the baboon. Ann Surg 179: 910–916PubMedCrossRefGoogle Scholar
  13. 13.
    Thiemermann C, Szabo C, Mitchell JA, Vane JR (1993) Vascular hyporeactivity to vasoconstrictor agents and hemodynamic decompensation in hemorrhagic shock is mediated by nitric oxide. Proc Natl Acad Sci 90: 267–271PubMedCrossRefGoogle Scholar
  14. 14.
    Ayala A, Perrin MM, Meldrum DR, Ertel W, Chaudry IH (1990) Hemorrhage induces an increase in serum TNF which is not associated with elevated levels of endotoxins. Cytokine 2: 170–174PubMedCrossRefGoogle Scholar
  15. 15.
    Chaudry IH, Ertel W, Ayala A (1993) Alterations in inflammatory cytokine production following hemorrhage and resuscitation. In: Schlag G, Redl H, Traber DL (eds) Springer-Verlag, Heidelberg, Berlin, New York. pp 72–127Google Scholar
  16. 16.
    Rush BFJ, Redan JA, Flanagan JJ, et al (1989) Does the bacteremia observed in hemorrhagic shock have clinical significance? A study in germ-free animals. Ann Surg 210: 342–347PubMedCrossRefGoogle Scholar
  17. 17.
    Goris JRA, Boekholtz W, van Bebber I, Nuytinck J, Schillings P (1986) Multiple organ failure and sepsis without bacteria. An experimental model. Arch Surg 121: 897–901PubMedCrossRefGoogle Scholar
  18. 18.
    Rush BFJ, Sori AJ, Murphy TF, Smith S, Flanagan JJ, Machiedo GW (1988) Endotoxemia and bacteremia during hemorrhagic shock: The link between trauma and sepsis? Ann Surg 207: 549–554PubMedCrossRefGoogle Scholar
  19. 19.
    Moore F, Poggetti R, McAnena O, Peterson V, Abernathy C, Parsons P (1991) Gut bacterial translocation via the portal vein: A clinical perspective with major torso trauma. J Trauma 31: 629–638PubMedCrossRefGoogle Scholar
  20. 20.
    Plaut AG, Goorbach SL, Nahas L, Weinstein L, Spauknebel G, Levitan R (1967) Studies of intestinal microflora III: The microbial flora of intestinal mucosa in fluids. Gastroenterology 53: 868–873PubMedGoogle Scholar
  21. 21.
    Spaeth G, Specian RD, Berg RD, Deitch EA (1990) Food without fiber promotes bacterial translocation from the gut. Surgery 108: 240–247PubMedGoogle Scholar
  22. 22.
    Topping DL, Illman RJ (1986) Bacterial fermentation in the human large bowel. Time to change from the roughage model of dietary fibre? Med J Aust 144: 307–309PubMedGoogle Scholar
  23. 23.
    Savage DC (1978) Factors involved in the colonization of the gut epithelial surface. Am J Clin Nutr 31: 131–135Google Scholar
  24. 24.
    Cruz N, Lu Q, Alvarez X, Deitch EA (1994) Bacterial translocation is bacterial species dependent: Results using the human Caco-2 intestinal cell line. J Trauma 36: 612–616PubMedCrossRefGoogle Scholar
  25. 25.
    Cruz N, Alvarez X, Specian RD, Berg RD, Deitch EA (1994) Role of mucin, mannose and b-1 integrin receptors in E. coli translocation across CaCO2 cell monolayers. Shock 2: 121–126PubMedCrossRefGoogle Scholar
  26. 26.
    Tomasi TB (1983) Mechanisms of immune regulation at mucosal surfaces. Rev Infect Dis 5 (Suppl 4): S784–S792PubMedCrossRefGoogle Scholar
  27. 27.
    Stoutenbeek CP, Saene van HKF, Miranda DR, et al (1984) The effect of selective decontamination of the digestive tract on colonization and infection rate in multiple trauma patients. Intensive Care Med 10: 185–192PubMedCrossRefGoogle Scholar
  28. 28.
    Sanderson PJ (1989) Selective decontamination of the digestive tract. Br Med J 299: 1413–1414CrossRefGoogle Scholar
  29. 29.
    Bertok L (1977) Physico-chemical defense of vertebrate organisms: The role of bile acids in defense against bacterial endotoxins. Perspect Biol Med 21: 70–76PubMedGoogle Scholar
  30. 30.
    Cahill CJ, Pain JA, Bailey ME (1987) Bile salts, endotoxin and renal function in obstructive jaundice. Surg Gynecol Obstet 165: 519–522PubMedGoogle Scholar
  31. 31.
    Machnicki M, Zimecki M, Zagulski T (1993) Lactoferrin regulates the release of tumor necrosis factor alpha and interleukin 6 in vivo. Int J Exp Pathol 74: 433–439PubMedGoogle Scholar
  32. 32.
    Nitsche D, Schulze C, Nebermann L (1993) Prevention of gut-derived endotoxemia by means of oral administration of lactoferrin. Circ Shock (Suppl) 1: 47–48Google Scholar
  33. 33.
    Liehr H, Englisch G, Rasenack U (1980) Lactulose-a drug with anti-endotoxin effect. Hepato Gastroenterology 27: 356–360PubMedGoogle Scholar
  34. 34.
    van Leeuwen PAM, Hong RW, Rounds JD, Roderick ML, Wilmore D (1991) Hepatic failure and coma after liver resection is reversed by manipulation of gut contents: The role of endotoxin. Surgery 110: 169–175PubMedGoogle Scholar
  35. 35.
    Tokyay R, Traber DL, Herndon DN (1990) Thromboxane synthese inhibition prevents the increased mesenteric vascular resistance seen after major thermal injury in a chronic porcine model. Surg Forum 41: 56–59Google Scholar
  36. 36.
    Jones WG, Minei JP, Barber AE, et al (1990) Angiotensin converting enzyme inhibitor decreases bacterial translocation after burn injury. FASEB J 9: A953 (Abst)Google Scholar
  37. 37.
    Deitch EA, Bridges W, Baker J, et al (1988) Hemorrhagic shock-induced bacterial translocation is reduced by xanthine oxidase inhibition or inactivation. Surgery 104: 191–198PubMedGoogle Scholar
  38. 38.
    Payne D, Kubes P (1993) Nitric oxide donors reduce the rise in reperfusion-induced intestinal mucosal permeability. Am J Physiol 265: 189–195Google Scholar
  39. 39.
    Wilmore DW, Smith RJ, O’Dwyer ST, Jacobs DO, Ziegler TR, Wang XD (1988) The gut: A central organ after surgical stress. Surgery 104: 917–923PubMedGoogle Scholar
  40. 40.
    Burke DJ, Alverdy JC, Aoys E, Moss GS (1989) Glutamine-supplemented total parenteral nutrition improves gut immune function. Arch Surg 124: 1396–1399PubMedCrossRefGoogle Scholar
  41. 41.
    Zeigler ST, Traber DL, Herndon D (1993) Bacterial translocation in burns. In: Schlag G, Redl H (eds) Pathophysiology of shock, sepsis, and organ failure. Springer-Verlag, Berlin, Heidelberg, pp 300–313CrossRefGoogle Scholar
  42. 42.
    Haskel Y, Dazhong X, Lu Q, Deitch EA (1994) Bombesin protects against bacterial translocation induced by three commercially available liquid enteral diets: A prospective, randomized, multigroup trial. Crit Care Med 22: 108–113PubMedGoogle Scholar
  43. 43.
    Donohoe MK, Rush BFJ, Koziol JM, Machiedo GW (1986) Role of antibiotics in late survival from hemorrhagic shock. Surg Forum 27: 62–64Google Scholar
  44. 44.
    Walker RI, Porvaynik MJ (1978) Disruption of the permeability barrier (zona occludens) between intestinal epithelial cells by lethal doses of endotoxin. Infect Immunol 21: 655–658Google Scholar
  45. 45.
    Deitch EA, Berg R, Specian R (1987) Endotoxin promotes the translocation of bacteria from the gut. Arch Surg 122: 185–190PubMedCrossRefGoogle Scholar
  46. 46.
    Navaratnam RL, Morris SE, Traber DL, et al (1990) Endotoxin (LPS) increases mesenteric vascular resistance (MVR) and bacterial translocation (BT). J Trauma 30: 1104–1113PubMedCrossRefGoogle Scholar
  47. 47.
    Yao Y, Tian H, Wang Y, Sheng Z, Shi Z, Xu S (1992) Protective effect of re-LPS antiserum on experimental multiple system organ failure. Chin Med J 105: 833–838PubMedGoogle Scholar
  48. 48.
    Bahrami S, Yao YM, Leichtfried G, Redl H, Schlag G, Di Padova FE (1995) Evidence of Enterobacteriaceae as the main source for hemorrhage-induced endotoxemia in rats using an anti-core lipopolysaccharide monoclonal antibody. Infect Immunol (In press)Google Scholar
  49. 49.
    Gaffin SL, Grinberg Z, Abraham C, et al (1981) Protection against hemorrhagic shock in the cat by human plasma containing endotoxin specific antibodies. J Surg Res 31: 18–21PubMedCrossRefGoogle Scholar
  50. 50.
    Pohlson EC, Suehiro A, Ziegler EJ, et al (1988) Antiserum to endotoxin in hemorrhagic shock. J Surg Res 45: 467–471PubMedCrossRefGoogle Scholar
  51. 51.
    Weiss J, Olsson I (1987) Cellular and subcellular localization of the bactericidal/permeability increasing protein of neutrophils. Blood 69: 652–659PubMedGoogle Scholar
  52. 52.
    Marra MN, Graig G, Griffith JE, Snable J, Scott W (1990) Bactericidal/Permeability-increasing protein has endotoxin-neutralizing activity. J Immunol 144: 662–666PubMedGoogle Scholar
  53. 53.
    Dentener MA, von Asmuth EJU, Francot GJM, Marra MN, Buurman WA (1993) Antagonists effects of lipopolysaccharide binding protein and bacterial/permeability-increasing protein on lipopolysaccharide-induced cytokine release by mononuclear phagocytes. J Immunol 151: 4258–4263PubMedGoogle Scholar
  54. 54.
    Bahrami S, Redl H, Yu Y, Jiang JX, Leichtfried G, Schlag G (1993) Bactericidal/permeability-increasing protein (BPI) reduces lipopolysaccharide (LPS)-induced cytokine formation and mortality in rats. Circ Shock (Suppl) 1: 52 (Abst)Google Scholar
  55. 55.
    Yao YM, Bahrami S, Redl H, Schlag G (1995) Pathogenesis of hemorrhage/induced endotoxemia in rats: Effects of recombinant bactericidal/increasing protein (rBPI21). Ann. Surg. (In press)Google Scholar
  56. 56.
    Deitch EA, Ma L, Ma WJ, et al (1989) Inhibition of endotoxin-induced bacterial translocation in mice. J Clin Invest 84: 36–42PubMedCrossRefGoogle Scholar
  57. 57.
    Deitch EA, Specian RD, Berg RD (1991) Endotoxin-induced bacterial translocation and mucosal permeability: Role of xanthine oxidase, complement activation, and macrophage products. Crit Care Med 19: 785–791PubMedCrossRefGoogle Scholar
  58. 58.
    Bahrami S, Yao YM, Leichtfried G, Redl H, Schlag G, Foulkes R (1994) Efficacy of monoclonal antibody (mab) to tumor necrosis factor (TNF) against hemorrhage-induced mortality in rats. Intensive Care Med 20: S61 (Abst)CrossRefGoogle Scholar
  59. 59.
    Zingarelli B, Squadrito F, Altavilla D, Calapai G, Di Rosa M, Caputi AP (1994) Role of tumor necrosis factor-α in acute hypovolemic hemorrhagic shock in rats. Am J Physiol 266: H1512–H1515PubMedGoogle Scholar
  60. 60.
    Ertel W, Morrison MH, Ayala A, Perrin MM, Chaudry IH (1991) Anti-TNF monoclonal antibodies prevent hemorrhage-induced suppression of Kupffer cell antigen presentation and MHC class II antigen expression. Immunology 74: 290–297PubMedGoogle Scholar
  61. 61.
    Ertel W, Morrison MH, Ayala A, Chaudry IH (1991) Chloroquine attenuates hemorrhagic shock-induced suppression of Kupffer cell antigen presentation and major histocompatibility complex class II antigen expression through blockade of tumor necrosis factor and prostaglandin release. Blood 78: 1781–1788PubMedGoogle Scholar
  62. 62.
    Marzi M, Bauer M, Reisdorf E, Bahrami S, Redl H, Buehren V (1993) TNFα and PAF modulate leukocyte adhesion in the liver after hemorrhagic shock in vivo. Circ Shock (Suppl) 1: 23 (Abst)Google Scholar
  63. 63.
    Foulkes R, Hughes B, Kingaby R, Woodger R, Vetterlein O (1994) Anti-TNF treatment reduces severity of organ damage in a conscious rabbit model of hemorrhagic/traumatic shock. Intensive Care Med 20: 72 (Abst)Google Scholar
  64. 64.
    Deitch EA, Baker T, Berg R, Ma L (1987) Hemorrhagic shock promotes the systemic translocation of bacteria from the gut. J Trauma 27: 815–822Google Scholar
  65. 65.
    Koziol JM, Rush BF, Jr., Smith SM, Machiedo GW (1988) Occurrence of bacteremia during and after hemorrhagic shock. J Trauma 28: 10–16PubMedCrossRefGoogle Scholar
  66. 66.
    Rush BFJ (1989) Irreversibility in hemorrhagic shock is caused by sepsis. Ann Surg 55: 204–208Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1995

Authors and Affiliations

  • H. Redl
  • S. Bahrami
  • G. Schlag

There are no affiliations available

Personalised recommendations