Skip to main content
PMC home page
Springer Nature - PMC COVID-19 Collection logoLink to Springer Nature - PMC COVID-19 Collection
. 1990;16(Suppl 3):S192–S196. doi: 10.1007/BF01709699

Mediators of multiple organ failure

R J A Goris 1
PMCID: PMC7095330  PMID: 2289989

Abstract

Multiple Organ Failure (MOF) has largely been attributed to bacterial sepsis, though conclusive evidence of an essential role for bacteria and/or their endotoxins is still lacking. On the other hand, MOF and the clinical syndrome of sepsis may be aseptically induced in germfree animals. This paper reviews the evidence that excessive activation of endogenous humoral mediators and inflammatory cells may cause this highly lethal syndrome.

Key words: Multiple organ failure, ARDS, Sepsis, Complement, Elastase, Neopterin

References

  • 1.Ashbaugh DG, Petty TL. Sepsis complicating the acute respiratory distress syndrome. Surg Gynecol Obstet. 1972;135:865–869. [PubMed] [Google Scholar]
  • 2.Goris RJA, te Boekhorst TPA, Nuytinck JKS, Gimbrere JSF. Multiple organ failure. Generalised autodestructive infalmmation? Arch Surg. 1985;120:1109–1115. doi: 10.1001/archsurg.1985.01390340007001. [DOI] [PubMed] [Google Scholar]
  • 3.Mc Ardle CS, MacDonald JAE, Ledingham IMA. A three year retrospective analysis of septic shock in a general hospital. Scott Med J. 1975;20:79–84. doi: 10.1177/003693307502000210. [DOI] [PubMed] [Google Scholar]
  • 4.Border JR, Bone LB, Steinberg SM, et al. et al. Metabolic response to trauma and sepsis. In: Border JR, et al.et al., editors. Blunt multiple trauma. New York: Dekker; 1990. pp. 191–258. [Google Scholar]
  • 5.van Deventer SJH, Buller HR, ten Cate JW, Sturk A, Pauw W. Endotoxaemia: an early predictor of septicaemia in febrile patients. Lancet. 1988;I:605–608. doi: 10.1016/s0140-6736(88)91412-2. [DOI] [PubMed] [Google Scholar]
  • 6.Schoeffel U, Lenz T, Ruf G, Mittermayer Ch, Lausen M. “Sepsis parameters” in patients with lethal burn. In: Paubert-Braquet M, editor. Lipid mediators in the immunology of shock. New York: Plenum Publishing; 1987. [Google Scholar]
  • 7.Damas P, Gijzen Ph, Lopez M, Gathy R, Vrindts Y, Reuter A, Demonty J, Lamy M, Franchimont P (1988) Cachectin (TNFa) serum levels in human during septic shock (Abstr). First Int Congress on immune consequences of trauma, shock and sepsis. Munich
  • 8.Nast-Kolb D, Waydhas Ch, Jochum M, Duswald KH, Schweiberer L. Organversagen beim Polytrauma — Wertigkeit der Infektion. Anaesthesist. 1989;38:340. [Google Scholar]
  • 9.Norton LW. Does drainage of intraabdominal pus reverse multiple organ failure? Am J Surg. 1985;149:347–350. doi: 10.1016/s0002-9610(85)80105-7. [DOI] [PubMed] [Google Scholar]
  • 10.Goris RJA, van Bebber IPT (in press) Selective decontamination of the gastrointestinal tract does not prevent Multiple Organ Failure. An experimental study. Arch Surg [DOI] [PubMed]
  • 11.Goris RJA, Boekholtz WKF, van Bebber IPT, Nuytinck JKS, Schillings PHM. Multiple organ failure and sepsis without bacteria. An experimental model. Arch Surg. 1986;121:897–901. doi: 10.1001/archsurg.1986.01400080039006. [DOI] [PubMed] [Google Scholar]
  • 12.Wilmore DW (1986) The wound as an organ. In: Little RA, Frayn KN (eds) The scientific basis for the care of the critically ill patient. Manchester University Press
  • 13.Yurt RW. Noncomplement mediators. In: Davis JM, Shires GT, editors. Advances in host defense mechanisms, vol 6. New York: Raven Press; 1986. [Google Scholar]
  • 14.Nuytinck JKS, Goris RJA, Redl H, Schlag G, van Munster PJJ. Posttraumatic complications and inflammatory mediators. Arch Surg. 1986;121:886–890. doi: 10.1001/archsurg.1986.01400080028004. [DOI] [PubMed] [Google Scholar]
  • 15.Aasen A. The proenzyme functional inhibition index. A new parameter for evaluation of the severely injured and septic patient. Acta Chir Scand. 1985;522(Suppl):211–233. [PubMed] [Google Scholar]
  • 16.Jose PJ, Forrest MJ, Williams TJ. Human C5a des Arg increases vascular permeability. J Immunol. 1981;127:2376–2380. [PubMed] [Google Scholar]
  • 17.Wedmore CV, Williams TJ. Control of vascular permeability by polymorphonuclear leukocytes in inflammation. Nature. 1981;89:646–650. doi: 10.1038/289646a0. [DOI] [PubMed] [Google Scholar]
  • 18.Nuytinck JKS, Goris RJA, Weerts JGE. Acute generalised microvascular injury by activated complement and hypoxia: the basis of ARDS and MOF? Br J Exp Pathol. 1986;67:537–548. [PMC free article] [PubMed] [Google Scholar]
  • 19.Nuytinck JKS, Offermans XJ, Kubat K, Goris RJA. Whole body inflammation in trauma patients. An autopsy study. Arch Surg. 1988;123:1519–1524. doi: 10.1001/archsurg.1988.01400360089016. [DOI] [PubMed] [Google Scholar]
  • 20.Dehring DJ, Steinberg SM, Wismar BL, Lowery BD, Carey LC, Cloutier CT. Complement depletion in an porcine model of septic acute respiratory distress. J Trauma. 1987;27:615–625. doi: 10.1097/00005373-198706000-00005. [DOI] [PubMed] [Google Scholar]
  • 21.Olson LM, Moss GS, Baukus O, Das Gupta T. The role of C5 in septic lung injury. Ann Surg. 1985;85:771–776. doi: 10.1097/00000658-198512000-00018. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22.Heideman M, Saravis C, Clowes GHA. Effect of non-viable tissue and abscesses on complement depletion and the development of bacteremia. J Trauma. 1982;22:527–532. doi: 10.1097/00005373-198207000-00001. [DOI] [PubMed] [Google Scholar]
  • 23.Solomkin JS, Cotta LA, Satoh PS, Hurst JM, Nelson RD. Complement activation and clearance in acute illness and injury: evidence for C5a as a cell-directed mediator of ARDS in man. Surgery. 1985;97:668–678. [PubMed] [Google Scholar]
  • 24.Slotman GJ, Burchard KW, Yelling SA, Williams JJ. Prostaglandin and complement interaction in clinical acute respiratory failure. Arch Surg. 1986;121:271–274. doi: 10.1001/archsurg.1986.01400030025002. [DOI] [PubMed] [Google Scholar]
  • 25.Heideman M, Hugli T. Anaphylatoxin generation in multiple system organ failure. J Trauma. 1984;24:1038–1043. doi: 10.1097/00005373-198412000-00006. [DOI] [PubMed] [Google Scholar]
  • 26.Hammerschmidt DE, Weave LJ, Hudson LD, Craddock PR, Jacob HS. Association of complement activation and elevated plasma-C5a with ARDS. Lancet. 1980;I:947–949. doi: 10.1016/s0140-6736(80)91403-8. [DOI] [PubMed] [Google Scholar]
  • 27.Duchateau J, Haas M, Schreyen H, Radoux L, Sprangers L, Noel X, Braun M, Lamy M. Complement activation in patients at risk of developing ARDS. Am Rev Respir Dis. 1984;130:1058–1064. doi: 10.1164/arrd.1984.130.6.1058. [DOI] [PubMed] [Google Scholar]
  • 28.Schlag G, Redl H. Posttraumatic ultrastructural changes and the role of granulocytes in the lungs, liver and skeletal muscle. Intensive Care Med. 1983;9:148. [Google Scholar]
  • 29.Heflin AC, Brigham KL. Granulocyte depletion prevents increased lung vascular permeability after endotoxemia in sheep. Clin Res. 1979;27:399A. [Google Scholar]
  • 30.Flick MR, Perel A, Staub NC. Leukocytes are required for increased lung microvascular permeability after microembolisation in sheep. Circ Res. 1981;48:344–351. doi: 10.1161/01.res.48.3.344. [DOI] [PubMed] [Google Scholar]
  • 31.Russell Martin R. In host defense, leukocytes that are counted may not count. J Lab Clin Med. 1987;109:378–379. [PubMed] [Google Scholar]
  • 32.Smedley LA, Tonnesen RA, Sandhaus RA, Haslett C, Guthrie LA, Johnston RB, Henson PM, Worthen GS. Neutrophil-mediated injury to endothelial cells. J Clin Invest. 1986;77:1233–1243. doi: 10.1172/JCI112426. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 33.Henson PM, Johnston RB. Tissue injury in inflammation. J Clin Invest. 1987;79:669–674. doi: 10.1172/JCI112869. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 34.Stokke T, Burchardi H, Hensel I, Kostering H, Kathner T, Rahlf G. Continuous intravenous infusion of elastase in normal and agranulocytic minipigs-effects on the lungs and the blood coagulation system. Resuscitation. 1986;14:61–79. doi: 10.1016/0300-9572(86)90007-9. [DOI] [PubMed] [Google Scholar]
  • 35.Lang H, Jochum M, Redl H, Fritz H (1988) Validity of elastase assay in intensive care medicine (Abstr) Second Vienna Shock Forum [PubMed]
  • 36.Redl H, Pacher R, Woloszczuk W. Acute pulmonary failurecomparison of neopterin and granulocyte elastase in septic and nonseptic patients. In: Pfleiderer W, editor. Biochemical and clinical aspects of pteridines, vol. 5. New York: W de Gruyter; 1987. [Google Scholar]
  • 37.Dusswald KH, Jochum M, Schram W, Fritz H. Released granulocyte elastase: an indicator of pathobiochemical alterations in septicemia after abdominal surgery. Surgery. 1985;98:892–899. [PubMed] [Google Scholar]
  • 38.Dittmer H, Jochum M, Fritz H. Freisetzung von granulozytärere Elastase und Plasmaproteinveränderungen nach traumatischhamorrhagischem Schock. Unfallchirurgie. 1986;89:160–169. [PubMed] [Google Scholar]
  • 39.Zheutlin LM, Thonar EJ-MA, Jacobs ER, Hanley ME, Balk RA, Bone RC. Plasma elastase in the ARDS. J Crit Care. 1986;1:39–44. [Google Scholar]
  • 40.Pincemail J, Deby-Dupont G, Faymonville ML, Adam A, Deby C, Thirion A, Lamy M (1988) Early neutrophil activation in trauma: release of myeloperoxidase and leucocytic elastase in plasma (Abstr) First Int Congress on immune consequences of trauma, shock and sepsis, Munich
  • 41.Nerlich ML, Seidel Regel G, Nerlich AG, Sturm AJ. Oxidative membrane damage in severe trauma: a clinical-experimental study. In: Streicher HJ, editor. Chir Forum. Berlin: Springer; 1986. [Google Scholar]
  • 42.Nightingale P. Prostaglandins in shock. Intensive Care News. 1988;1:6–10. [Google Scholar]
  • 43.Modig J, Samuelsson T, Sandin R. Volume substitution and treatment with prostaglandin E1 in a porcine model of endotoxaemia-induced pulmonary and cardiovascular failure. Acta Chir Scand. 1987;153:165–170. [PubMed] [Google Scholar]
  • 44.Holcroft JW, Vassar MJ, Weber CJ. Prostaglandin E1 and survival in patients with the ARDS. Ann Surg. 1986;203:371–378. doi: 10.1097/00000658-198604000-00006. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 45.Faist E, Mewes A, Baker CC, Strasser Th, Alkan SS, Rieber P, Heberer G. Prostaglandin E2- dependent suppression of interleukin-2 production in patients with major trauma. J Trauma. 1987;27:837–848. doi: 10.1097/00005373-198708000-00001. [DOI] [PubMed] [Google Scholar]
  • 46.Brigham KL. Role of free radicals in lung injury. Chest. 1986;89:859–863. doi: 10.1378/chest.89.6.859. [DOI] [PubMed] [Google Scholar]
  • 47.Del Maestro RF, Bjork J, Arfors KE. Increase in microvascular permeability induced by enzymatically generated free radicals. I. In vivo study. Microvasc Res. 1981;22:239. doi: 10.1016/0026-2862(81)90095-9. [DOI] [PubMed] [Google Scholar]
  • 48.Goris RJA, Nuytinck JKS, Boekholtz WKF, van Bebber IPT, Schillings PHM. Multiple organ failure without bacteria. In: Novelli GP, editor. Oxygen free radicals in shock. Basel: Karger; 1986. [Google Scholar]
  • 49.Young S, Beswick P. A comparison of the oxidative reactions of neutrophils from a variety of species when stimulated by opsonized zymosan and F-Met-Leu-Phe. J Comp Pathol. 1986;96:189–196. doi: 10.1016/0021-9975(86)90009-5. [DOI] [PubMed] [Google Scholar]
  • 50.Westaby S, Fleming J, Royston D. Acute lung injury during cardiopulmonary bypass, the role of neutrophil sequestration and lipid peroxidation. Trans Am Soc Artif Intern Organs. 1986;31:604–609. [PubMed] [Google Scholar]
  • 51.Nerlich ML, Seidel J, Regel G, Nerlich AG, Sturm JA (1986) Klinische experimentelle Untersuchungen zum oxidativen Membranschaden nach schwerem Trauma. Langenbecks Arch Chir [Suppl] 217–222
  • 52.West MA. Macrophage effector function in sepsis. Arch Surg. 1987;122:242–247. [Google Scholar]
  • 53.Nathan CF. Secretory products of macrophages. J Clin Invest. 1987;79:319–326. doi: 10.1172/JCI112815. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 54.Dinarello CA. Interleukin-1. Rev Infect Dis. 1984;6:51–95. doi: 10.1093/clinids/6.1.51. [DOI] [PubMed] [Google Scholar]
  • 55.Okusawa S, Gelfland JA, Ikejima T, Connolly RJ, Dinarello CA. Interleukin 1 induces a shock-like state in rabbits. J Clin Invest. 1988;81:1162–1172. doi: 10.1172/JCI113431. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 56.Beutler B, Cerami A. Cachectin and tumor necrosis factor as two sides of the same biological coin. Nature. 1986;320:584–588. doi: 10.1038/320584a0. [DOI] [PubMed] [Google Scholar]
  • 57.Tracey KJ, Beutler B, Lowry SF, Merryweather J, Wolpe S, Milsark IW, Haviri RJ, Fahey TJ, Zentella A, Albert JD, Shires GT, Cerami A. Shock and tissue injury induced by recombinant human cachectin. Science. 1986;234:446–45. doi: 10.1126/science.3764421. [DOI] [PubMed] [Google Scholar]
  • 58.Gaskill HV. continous infusion of TNF: mechanisms of toxicity in the rat. J Surg Res. 1988;44:664–671. doi: 10.1016/0022-4804(88)90098-4. [DOI] [PubMed] [Google Scholar]
  • 59.Michie HR, Spriggs DR, Manogue KR, Sherman ML, Revhaug A, O'Dwyer ST, Arthur K, Dinarello CA, Cerami A, Wolff SM, Kufe DW, Wilmore DW. Tumor necrosis factor and endotoxin induce similar metabolic responses in human beings. Surgery. 1988;104:280–286. [PubMed] [Google Scholar]
  • 60.Girardin E, Grau GE, Dayer JM, Roux-Lombard P, the J5-study group. Lambert PH. TNF and interleukin-1 in the serum of children with severe infections purpura. N Engl J Med. 1988;319:397–400. doi: 10.1056/NEJM198808183190703. [DOI] [PubMed] [Google Scholar]
  • 61.De Groote MA, Martin MA, Densen P, Pfaller MA, Wenzel RP. Plasma Tumor Necrosis Factor levels in patients with presumed sepsis. JAMA. 1989;262:249–251. doi: 10.1001/jama.262.2.249. [DOI] [PubMed] [Google Scholar]
  • 62.Huber Ch, Troppmair J, Rokos H, Curtius H-Ch. Neopterin heute. Dtsch Med Wochenschr. 1987;112:107–113. doi: 10.1055/s-2008-1068015. [DOI] [PubMed] [Google Scholar]
  • 63.Redl H, Strohmaier W, Pacher R, Woloszczuk W, Inthorn D, Troppmaier J (1988) Possible use of the monocyte/macrophage activation marker neopterin for the clinical monitoring of sepsis related multi-organ failure (Abstr) First Int Congress on the immune consequences of trauma, shock and sepsis, Munich
  • 64.Aasen AO (1988) Role of endotoxin and proteases in MOF (Abstr) Second Vienna Shock Forum
  • 65.Strohmaier W, Redl H, Schlag G, Inthorn D. D-erythroneopterin plasma levels in intensive care patients with and without septic complications. Crit Care Med. 1987;15:757–760. doi: 10.1097/00003246-198708000-00009. [DOI] [PubMed] [Google Scholar]
  • 66.Pacher R, Redl H, Woloszczuk W. Neopterin and granulocyte elastase in septicemic patients prone to develop multi-organ failure. In: Pfleiderer W, editor. Biochemical and clinical aspects of pteridines, vol 5. New York: de Gruyter; 1987. [Google Scholar]

Articles from Intensive Care Medicine are provided here courtesy of Nature Publishing Group

RESOURCES