Abstract
Endotoxin is a lipopolysaccharide (LPS) that is a major component of the outer membrane of Gram-negative bacteria. Endotoxin has strong pro-inflammatory properties and can activate multiple inflammatory cascades. It is therefore considered to play a key role in the toxic sequelae of Gram-negative sepsis [1, 2]. LPS is composed of a lipid moiety, designated lipid A, and a hydrophilic polysaccharide chain. The polysaccharide portion of LPS consists of the O-chain, that protrudes from the bacterial membrane, and a ‘core part’, connecting the O-chain with lipid A. While the O-chain consists of a series of structurally and antigenically diverse oligosaccharides that determine the many different O-specific serotypes, the core part is identical for many different bacteria. Lipid A is the highly conserved biologically active part of LPS which is completely embedded in the bacterial membrane, shielded by the O-chain. Pro-inflammatory effects of Gramnegative bacteria can, therefore, not be readily explained by the effects of cellbound LPS. However, LPS can be shed by Gram-negative bacteria via several mechanisms, including destruction of the bacterial cell wall by complement factors.
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References
Manthous CA, Hall JB, Samsel RW (1993) Endotoxin in human disease. Part 1: Biochemistry, assay, and possible role in diverse disease states. Chest 104:1572–1581
Hoffmann WD, Natanson C (1993) Endotoxin in sept ic shock. Anesth Analg 77:613–624
Starnes CO (1992) Coley’s toxin in perspective. Nature 357:11–12
Florman AL, Holzman RS (1975) Nonspecific enhancers of resistance in man. J Pediatr 87:1094–1102
Greisman SE, Woodward WE (1965) Mechanisms of en dotoxin tolerance. III. The refractory state during continuous infusions with endotoxin. J Exp Med 121:911–933
Hochstein HD, Mills DF, Outschoorn AS, Rastogi SC (1983) The processing and collaborative assay of reference endotoxin. J Biol Stand 11:251–260
Poole S, Dawson P, Gaines Das RE (1997) Second international standard for endotoxin: calibration in an international collaborative study. J Endotoxin Res 4:221–231
Engelhardt R, Mackensen A, Galanos C, Andreesen R (1990) Biological response to intravenously administered endotoxin in patients with advanced cancer. J Biol Resp Mod 9:480–491
Engelhardt R, Mackensen A, Galanos C (1991) Phase I trial of intravenously administered endotoxin (Salmonella abortus equi) in cancer patients. Cancer Res 51:2524–2530
Hesse DG, Tracey KJ, Fong Y, et al (1988) Cytokine appearance in human endotoxemia and primate bacteremia. Surg Gynecol Obstet 166:147–53
Michie HR, Manogue KR, Spriggs DR, et al (1988) Detection of circulating tumor necrosis factor after endotoxin administration. N Engl J Med 318:1481–1486
Van Deventer SJH, Büller HR, ten Cate JW, Aarden LA, Hack CE, Sturk A (1990) Experimental endotoxemia in humans: analysis of cytokine release and coagulation, fibrinolytic and complement pathways. Blood 76:2520–2526
Suffredini AF, Fromm FE, Parker MM, et al (1989) The cardiovascular response of normal humans to the administration of endotoxin. N Engl J Med 321:280–287
Martich GD, Parker MM, Cunnion RE, Suffredini AF (1992) Effects of Ibuprofen and pentoxifylline on the cardiovascular response of normal humans to endotoxin. J Appl Physiol 73:925–931
Suffredini AF, Reda D, Banks SM, Tropea M, Agosti JM, Miller R (1995) Effects of recombinant dimeric TNF receptor on human inflammatory responses following intravenous endotoxin administration. J Immunol 155:5038–5045
Preas II HL, Reda D, Tropea M, et al (1996) Effects of recombinant soluble type I interleukin-1 receptor on human inflammatory responses to endotoxin. Blood 88:2465–2472
De Winter RJ, von der Möhlen MAM, van Lieshout H, et al (1995) Recombinant endotoxinbinding protein (rBPI23) attenuates endotoxin-induced circulatory changes in humans. J Inflamm 45:193–206
Taveira da Silva AM, Kaulbach HC, Chuidian FS, Lambert DR, Suffredini AF, Danner RL (1993) Brief report: Shock and multiple organ dysfunction after self-administration of Salmonella endotoxin. N Engl J Med 328:1457–1460
Suffredini AF, Shelhamer JH, Neumann RD, Brenner M, Baltaro RJ, Parillo JE (1992) Pulmonary and oxygen transport effects of intravenously administered endotoxin in normal humans. Am Rev Respir Dis 145:1398–1403
Smith PD, Suffredini AF, Allen JB, Wahl LM, Parillo JE, Wahl SM (1994) Endotoxin administration to humans primes alveolar macrophages for increased production of inflammatory mediators. J Clin Immunol 14:141–148
Van der Poll T, van Deventer SJH (1999) Cytokines and anti-cytokines in the pathogenesis of sepsis. Infect Dis Clin North Am 13:413–426
Fong Y, Marano MA, Moldawer LL, et al (1990) The acute splanchnic and peripheral tissue metabolic response to endotoxin in humans. J Clin Invest 85:1896–1904
Martich GD, Danner RL, Ceska M, Suffredini AF (1991) Detection of interleukin 8 and tumor necrosis factor in normal humans after intraveno us endotoxin: the effect of antiinflammatory agents. J Exp Med 173:1021–1024
Van Deventer SJH, Hart M, van der Poll T, Hack CE, Aarden LA (1993) Endotoxin and TNF-induced IL-8 release in humans. J Infect Dis 167:461–464
Sylvester I, Suffredini AF, Boujoukos AJ, et al (1993) Neutrophil attractant protein-1 and monocyte chemoattractant protein-1 in human serum. J Immunol 151:3292–3298
Olszyna DP, Pajkrt D, van Deventer SJH, van der Poll T (1998) Effect of interleukin 10 on CC chemokines during human endotoxemia. 38th Inters cience Conference on Antimicrobial Agents and Chemotherapy (ICAAC). September 24–27, 1998. San Diego. Abstract G-2
Mackensen A, Galanos C, Engelhardt R (1991) Modulating activity of interferon-gamma on endotoxin-induced cytokine production in cancer patients. Blood 78:3254–3258
Granowitz EV, Porat R, Mier JW, et al (1993). Hematologic and immunomodalutory effects of an interleukin-1 receptor antagonist coinfusion during low-dose endotoxemia in healthy humans. Blood 82:2985–2990
Pajkrt D, Manten A, van der Poll T, et al (1997) Modulation of cytokine release and neutrophil function by granulocyte colony-stimulating factor during endotoxemia in humans. Blood 90:1415–1424
Spinas GA, Bloesch D, Kaufmann MT, Keller U, Dayer JM (1990) Induction of plasma inhibitors of interleukin 1 and TNF-α activity by endo toxin to normal humans. Am J Physiol 259:R993–R997
Van Zee KJ, Kohno T, Fischer E, Rock SC, Moldawer LL, Lowry SF (1992) Tumor necrosis factor soluble receptors circulate during experimen tal and clinical inflammation and can protect against excessive tumor necrosis factor α in vitro and in vivo. Proc Natl Acad Sci USA 89:4845–4849
Spinas GA, Keller U, Brockhaus M (1992) Release of soluble receptors for tumor necrosis factor (TNF) in relation to circulating TNF during experimental endotoxinemia. J Clin Invest 90:533–536
Granowitz EV, Santos AA, Poutsiaka DD, et al (1991) Production of interleukin-1-receptor antagonist during experimental endotoxaemia. Lancet 338:1423–1424
Fischer E, van Zee KJ, Marano MA, et al (1992) Interleukin-1 receptor antagonist circulates in experimental inflammation and in human disease. Blood 79:2196–200
Van der Poll T, de Waal Malefyt R, Coyle SM, Lowry SF (1997) Antiinflammatory cytokine responses during clinical sepsis and experimental endotoxemia: sequential measurements of plasma soluble interleukin (IL)-1 receptor type II, IL-10 and IL-13 concentrations. J Infect Dis 175:118–122
Van der Poll T, Galvano SE, Kumar A, et al (1995) Endotoxin induces downregulation of tumor necrosis factor receptors on circulating mon ocytes and granulocytes in humans. Blood 86:2754–2759
Van der Poll T, Coyle SM, Kumar A, Barbosa K, Agosti J, Lowry SF (1997) Down-regulation of surface receptors for TNF and IL-1 on circulating monocytes and granulocytes during human endotoxemia. Effect of neutralization of endotoxin-induced TNF activity by infusion of a recombinant dimeric TNF receptor. J Immunol 158:1490–1497
Richardson RP, Rhyne CD, Fong Y, et al (1989) Peripheral blood leukocyte kinetics following in vivo lipopolysaccharide (LPS) administration to normal human subjects. Ann Surg 210:239–245
Suffredini AF, Harpel PC, Parrillo JE (1989) Promotion and subsequent inhibition of plasminogen activation after administration of intrave nous endotoxin to normal subjects. N Engl J Med 320:1165–1172
Spinas GA, Bloesch D, Keller U, Zimmerli W, Cammisuli S (1991) Pretreatment with Ibuprofen augments circulating tumor necrosis factor-α, interleukin-6, and elastase during acute endotoxinemia. J Infect Dis 163:89–95
Von der Möhlen MAM, van der Poll T, Jansen J, Levi M, van Deventer SJH (1996) Release of bactericidal/permeability-increasing protein in experimental endotoxemia and cHnical sepsis: Role of tumor necrosis factor. J Immunol 156:4969–4973
Martich GD, Van Dervort AL, Danner RL, Suffredini AF (1992) Intravenous endotoxin administration to normal humans primes neutrophils for an enhanced respiratory burst. Grit Care Med 20:S100 (abst)
Moore FD, Moss NA, Revhaug A, Wilmore DW, Mannick JA, Rodrick ML (1987) A single dose of endotoxin activates neutrophils without activating complement. Surgery 102:200–205
Granowitz EV, Porat R, Mier JW, et al (1993) Intravenous endotoxin suppresses the cytokine response of peripheral blood mononuclear cells of healthy humans. J Immunol 151:1637–1645
Van der Poll T, Coyle SM, Moldawer LL, Lowry SF (1996) Changes in endotoxin-induced cytokine production by whole blood after in vivo exposure of normal humans to endotoxin. J Infect Dis 174:1356–1360
Kimmings AN, Pajkrt D, Zaaijer K, et al (1996) Factors involved in early in vitro endotoxin hyporesponsiveness in human endotoxemia. J Endotox Res 3:283–289
Von der Möhlen MAM, van Deventer SJH, Levi M, et al (1995) Inhibition of endotoxin-induced activation of the coagulation and fibrinolytic pathways using a recombinant endotoxin-binding protein (rBPI23). Blood 85:3437–3443
Van der Poll T, Coyle SM, Levi M, et al (1996) Fat emulsion infusion potentiates coagulation activation during human endotoxemia. Thromb Haemostas 75:83–86
Pajkrt D, Lerch PG, van der Poll T, et al (1997) Differential effects of reconstituted high-density lipoprotein on coagulation, fibrinolysis and platelet activation during human endotoxemia. Thromb Haemostas 77:303–307
Pajkrt D, van der Poll T, Levi M, et al (1997) Interleukin 10 inhibits activation of coagulation and fibrinolysis during human endotoxemia. Blood 89:2701–2705
Van der Poll T, Levi M, Dentener M, et al (1997) Epinephrine exerts anticoagulant effects during human endotoxemia. J Exp Med 185:1143–1148
Van der Poll T, Levi M, Braxton CC, et al (1998) Parenteral nutrition facilitates activation of coagulation, but not of fibrinolysis, during human endotoxemia. J Infect Dis 177:793–795
DeLa Cadena RA, Majluf-Cruz A, Stadnicki A, et al (1998) Recombinant tumor necrosis factor receptor p75 fusion protein (TNFR:Fc) alter s endotoxin-induced activation of the kinin, fibrinolytic, and coagulation systems in normal humans. Thromb Haemostas 80:114–118
DeLa Cadena RA, Suffredini AF, Page JD, et al (1993) Activation of the kallikrein-kinin system after endotoxin administration to normal human volunteers. Blood 81:3313–3317
Zabel P, Wolter DT, Schönharting MM, Schade UF (1989) Oxpentifylline in endotoxaemia. Lancet ii: 1474–1477
Revhaug A, Michie HR, Manson JM, et al (1988) Inhibition of cyclo-oxygenase attenuates the metabolic response to endotoxin in humans. Arch Surg 123:162–170
Michie HR, Spriggs DR, Manogue KR, et al (1988) Tumor necrosis factor and endotoxin induce similar metabolic responses in human beings. Surgery104:280–286
Michie HR, Majzoub JA, O’Dwyer ST, Revhaug A, Wilmore DW (1990) Both cyclooxygenase-dependent and cyclooxygenase-independent pathways mediate the neuroendocrine response in humans. Surgery 108:254–261
Barber AE, Coyle SM, Marano MA, et al (1993) Glucocorticoid therapy alters hormonal and cytokine responses to endotoxin in man. J Immunol 150:1999–2006
Bloesch D, Keller U, Spinas GA, Kury D, Girard J, Stauffacher W (1993). Effects of endotoxin on leucine and glucose kinetics in man: contribu tion of prostaglandin E2 assessed by a cyclooxygenase inhibitor. J Clin Endocrinol Metab 77:1156–1163
Fong Y, Matthews DE, He W, Marano M, Moldawer LL, Lowry SF (1994) Whole body and splanchnic leucine, phenylalanine, and glucose kinetics during endotoxemia in man. Am J Physiol 266:R419–R425
Fong Y, Marano MA, Barber A, et al (1989) Total parenteral nutrition and bowel rest modify the metabolic response to endotoxin in humans. Ann Surg 210:449–456
Lang CH, Pollard V, Fan J, et al (1997) Acute alterations in growth hormone-insuHn-like growth factor axis in humans injected with endotoxin. Am J Physiol 273:R371–R378
Van der Poll T, van Zee KJ, Endert E, et al (1995) Interleukin-1 receptor blockade does not affect endotoxin-induced changes in plasma thyroid hormone and thyrotropin concentrations in man. J Clin Endocrinol Metab 80:1341–1346
Van der Poll T, Endert E, Coyle SM, Agosti JM, Lowry SF (1999) NeutraHzation of tumor necrosis factor does not influence endotoxin-induced changes in thyroid hormone metabolism in man. Am J Physiol 276:R357–R362
Von der Möhlen MAM, Kimmings AN, Wedel NI, et al (1995) Inhibition of endotoxin-induced cytokine release and neutrophil activation in humans by use of recombinant bactericidal/permeability-increasing protein. J Infect Dis 172:144–151
Pajkrt D, Doran JE, Koster F, et al ( 1996) Antiinflammatory effects of reconstituted high-density lipoprotein during human endotoxemia. J Exp Med 184:1601–1608
Van der Poll T, Braxton CC, Coyle SM, et al (1995) Effect of hypertriglyceridemia on endotoxin responsiveness in man. Infect Immun 63:3396–3400
Lin E, Coyle SM, Randhawa S, et al (1998) PMX-622 prevents endotoxin-induced inflammation in humans. Surg Forum 49:6–8
Kiani A, Tschiersch A, Gaboriau E, et al (1997) Downregulation of the proinflammatory cytokine response to endotoxin by pretreatment wit h the nontoxic lipid A analog SDZ MRL 953 in cancer patients. Blood 90:1673–1683
Van der Poll T, Coyle SM, Levi M, et al (1997) Effect of a recombinant dimeric tumor necrosis factor receptor on inflammatory responses to intravenous endotoxin in normal humans. Blood 89:3727–3734
Granowitz EV, Porat R, Mier JW, et al (1993) Hematologic and immunomodulatory effects of an interleukin-1 receptor antagonist coinfusion during low-dose endotoxemia in healthy humans. Blood 82:2985–2990
Van Zee KJ, Coyle SM, Calvano SE, et al (1995) Influence of interleukin-1 receptor blockade on the human response to endotoxemia. J Immunol 154:1499–1507
Pajkrt D, Camoglio L, Tiel-van Buul MCM, et al (1997)Attenuation of proinflammatory response by recombinant human IL-10 in human endotoxemia; the effect of timing of rhIL-10 administration. J Immunol 158:3971–3977
Pollmächer T, Korth C, Mullington J, et al (1996) Effects of granulocyte colony-stimulating factor on plasma cytokine receptor levels and on the in vivo host response to endotoxin in healthy men. Blood 87:900–905
Santos AA, Scheltinga MR, Lynch E, et al (1993) Elaboration of interleukin 1-receptor antagonist is not attenuated by glucocorticoids after endotoxemia. Arch Surg 128:138–144
Barber AE, Coyle SM, Fischer E, et al (1995) Influence of hypercortisolemia on soluble TNF receptor II and interleukin-1 receptor antagonist responses to endotoxin in human beings. Surgery 118:406–411
Van der Poll T, Barber AE, Coyle SM, Lowry SF (1996) Hypercortisolemia increases plasma interleukin 10 concentrations during human en dotoxemia. J Clin Endocrin Metab 81:3604–3606
Van der Poll T, Coyle SM, Barbosa K, Braxton CC, Lowry SF (1996) Epinephrine inhibits tumor necrosis factor α and potentiates interleukin 10 production during human endotoxemia. J Clin Invest 97:713–719
Van der Poll T, Galvano SE, Kumar A, Coyle SM, Lowry SF (1997) Epinephrine attenuates downregulation of monocyte tumor necrosis factor receptors during human endotoxemia. J Leukoc Biol 61:156–160
Van der Poll T, van Deventer SJH, Büller HR, Sturk A, ten Cate JW (1991) Comparison of the early dynamics of systematic prostacyclin release after administration of tumor necrosis factor and endotoxin to healthy humans. J Infect Dis 164:599–601
Thompson WA, Coyle SM, van Zee K, et al (1994) The metabolic effects of platelet-activating factor antagonism in endotoxemic man. Arch Surg 129:72–79
Dekkers PEP, Lauw FN, ten Hove T, et al (1998) Effect of a metalloproteinase inhibitor (GI4502) in endotoxemia in healthy subjects. 38th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC). September 24–27, 1998. San Diego. Abstract G-4
Braxton CC, Coyle SM, Montegut WJ, et al (1995) Parenteral nutrition alters monocyte TNF receptor activity J Surg Res 59:23–28
Pollmächer T, Mullington J, Korth C, et al (1996) Diurnal variations in the human host response to endotoxin. J Infect Dis 174:1040–1045
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van der Poll, T., van Deventer, S.J.H. (2002). Endotoxemia in Healthy Subjects as a Human Model of Inflammation. In: Marshall, J.C., Cohen, J. (eds) Immune Response in the Critically Ill. Update in Intensive Care Medicine, vol 31. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-57210-4_22
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DOI: https://doi.org/10.1007/978-3-642-57210-4_22
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