Liver-Lung Interactions in Critical Illness

  • G. M. Matuschak
Part of the Update in Intensive Care and Emergency Medicine book series (UICM, volume 23)


Though acknowledged to have a central role in host defense homeostasis as well as immunological, biochemical, and metabolic regulation, the liver has not been recognized as pivotal to outcome in the acute respiratory distress syndrome (ARDS) for several reasons. Patients with liver disease have often been excluded from study, and hepatic dysfunction has often been nonspecifically defined by “liver function tests” [1]. The liver is not as accessible for study as the lung and other organs, and acute liver dysfunction is not as immediately evident as is acute lung injury [2, 3]. We have proposed an expanded conception of sepsis- and trauma-related ARDS as the central pulmonary manifestation of a generalized disorder of immunoregulation; the pathogenesis and resolution of lung injury are linked to more fundamental derangements in systemic host defense [2–8]. This reorientation implies that understanding the pathways by which changes in hepatic performance affect pulmonary function in ARDS may have therapeutic utility. Here we examine the thesis that hepatic performance modulated predisposition and resolution of lung injury in ARDS by affecting four interrelated elements of host defense: (a) control of systemic endotoxemia, bacteremia, and vasoactive byproducts of sepsis and trauma, (b) regulation of the production and export of endogenous inflammatory mediators by mononuclear phagocytes (Kupffer cells), (c) metabolic inactivation and detoxification of these mediators, and (d) synthesis of acute-phase proteins essential in intermediary metabolism and control of the inflammatory response. As a corollary, we assess clinical and experimental evidence suggesting that alterations in hepatic performance augment lung inflammation and mortality owing to a cytokine:eicosanoid axis of inflammation within the intravascular compartment and lower respiratory tract.


Acute Respiratory Distress Syndrome Kupffer Cell Critical Illness Hemorrhagic Shock Hepatic Blood Flow 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Heizberg JH, Spiro HM (1986) “LFTs” test more than the liver. JAMA 256:3006–3007CrossRefGoogle Scholar
  2. 2.
    Matuschak GM (1992) Multiple systems organ failure: clinical expression, pathogenesis, and therapy. In: Hall JB, Schmidt GA, Wood LDH (eds) Principles of critical care. McGraw-Hill, New York, pp 613–636Google Scholar
  3. 3.
    American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference (1992) Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med 20:864–874CrossRefGoogle Scholar
  4. 4.
    Bell RC, Coalson JJ, Smith JD et al (1983) Multiple organ system failure and infection in adult respiratory distress syndrome. Ann Intern Med 99:293–298PubMedGoogle Scholar
  5. 5.
    Montgomery AB, Stager MA, Carrico CJ et al (1985) Causes of mortality in patients with the adult respiratory distress syndrome. Am Rev Respir Dis 132:485–489PubMedGoogle Scholar
  6. 6.
    Pinsky MR, Matuschak GM (1989) Multiple systems organ failure: failure of host defense homeostasis. Crit Care Clin 5:199–220PubMedGoogle Scholar
  7. 7.
    Matuschak GM (1988) Organ interactions in the adult respiratory distress syndrome during sepsis: role of the liver in host defense. Chest 94:400–406PubMedCrossRefGoogle Scholar
  8. 8.
    Matuschak GM, Rinaldo JE, Pinsky MR et al (1987) Effect of end-stage liver failure on the incidence and resolution of the adult respiratory distress syndrome. J Crit Care 2:162–173CrossRefGoogle Scholar
  9. 9.
    Rogers DE (1960) Host mechanisms which act to remove bacteria from the blood. Bacteriol Rev 24:50–66PubMedGoogle Scholar
  10. 10.
    Bradfield JWB (1974) Control of spillover: the importance of Kupffer cell function in clinical medicine. Lancet 2:883–886PubMedCrossRefGoogle Scholar
  11. 11.
    Saba TM (1970) Physiology and physiopathology of the reticuloendothelial system. Arch Intern Med 126:1031–1035PubMedCrossRefGoogle Scholar
  12. 12.
    Ballet F (1990) Hepatic circulation: potential for therapeutic intervention. Pharmacol Ther 47:281–328PubMedCrossRefGoogle Scholar
  13. 13.
    Saba TM (1989) Fibronectin: relevance to phagocytic host response to injury. Circ Shock 29:257–278PubMedGoogle Scholar
  14. 14.
    Mathison JC, Ulevitch RJ (1979) Clearance, tissue distribution and cellular distribution of IV injected LPS in rabbits. J Immunol 123:2133–2143PubMedGoogle Scholar
  15. 15.
    Ruiter DJ, van der Meulen J, Brouwer A et al (1981) Uptake by liver cells of endotoxin following its intravenous injection. Lab Invest 45:38–45PubMedGoogle Scholar
  16. 16.
    Katz MS, Grosfeld JL, Gross K (1984) Impaired bacterial clearance and trapping in obstructive jaundice. Am J Surg 199:14–19Google Scholar
  17. 17.
    Loegering DJ, Blumenstock FA (1985) Depressing hepatic macrophage complement receptor function causes increased susceptibility to endotoxemia and infection. Infect Immun 47:659–664PubMedGoogle Scholar
  18. 18.
    Cuddy BG, Loegering DJ, Blumenstock FA et al (1986) Hepatic macrophage complement receptor clearance function following injury. J Surg Res 40:216–224PubMedCrossRefGoogle Scholar
  19. 19.
    Decker K (1990) Biologically active products of stimulated liver macrophages (Kupffer cells). Eur J Biochem 29:451–456Google Scholar
  20. 20.
    Fong Y, Marano M, Moldawer L et al (1990) The acute splanchnic and peripheral tissue and metabolic responses to endotoxin in humans. J Clin Invest 85:1896–1904PubMedCrossRefGoogle Scholar
  21. 21.
    Deitch EA (1993) Gut-liver axis in multiple systems organ failure: role of bacterial translocation and endotoxemia. In: Matuschak GM (ed) Multiple systems organ failure: hepatic regulation of systemic host defense. Dekker, New York, pp 39–72Google Scholar
  22. 22.
    Deitch EA, Sittig K, Li M et al (1990) Obstructive jaundice promotes bacterial translocation from the gut. Am J Surg 159:79–84PubMedCrossRefGoogle Scholar
  23. 23.
    Nolan JP, Camara DS (1989) Intestinal endotoxins as co-factors in liver injury. Immunol Invest 18:325–337PubMedCrossRefGoogle Scholar
  24. 24.
    Wilmore DW, Smith RJ, O’Dwyer ST et al (1988) The gut: a central organ after surgical stress. Surgery 104:917–923PubMedGoogle Scholar
  25. 25.
    Marshall JC, Christou NV, Horn H et al (1988) The microbiology of multiple organ failure: the proximal GI tract as an occult reservoir of pathogens. Arch Surg 123:309–315PubMedGoogle Scholar
  26. 26.
    Sori AJ, Rush BF, Lysz TW et al (1988) The gut as a source of sepsis after hemorrhagic shock. Am J Surg 155:187–192PubMedCrossRefGoogle Scholar
  27. 27.
    Koike K, Moore EE, Moore FA et al (1992) Phospholipase A2 inhibition decouples lung injury from gut ischemia-reperfusion. Surgery 112:173–180PubMedGoogle Scholar
  28. 28.
    Hechtman HB (1993) Mediators of local and remote injury following gut ischemia. J Vase Surg 18:134–135Google Scholar
  29. 29.
    Yamaguchi Y, Tamaguchi K, Babb JL et al (1982) In vivo quantitation of the rat liver’s ability to eliminate endotoxin from portal vein blood. J Reticuloendothel Soc 32:409–432PubMedGoogle Scholar
  30. 30.
    Fox ES, Thomas P, Broitman SA (1988) Uptake and modification of an 125I-lipopoly- saccharide by isolated rat Kupffer cells. Hepatology 8:1550–1554PubMedCrossRefGoogle Scholar
  31. 31.
    Hewett JA, Roth RA (1993) Hepatic and extrahepatic pathobiology of bacterial lipo- polysaccharides. Pharmacol Rev 45:381–411Google Scholar
  32. 32.
    Kaplan JE, Saba TM (1978) Platelet removal from the circulation by the liver and spleen. Am J Physiol 235: H314-H320PubMedGoogle Scholar
  33. 33.
    Schumacker PR, Saba TM (1980) Pulmonary gas exchange abnormalities following intravascular coagulation: reticuloendothelial involvement. Ann Surg 192:95–102PubMedCrossRefGoogle Scholar
  34. 34.
    Loegering DJ (1983) Intravascular hemolysis and RES phagocytic and host defense functions. Circ Shock 10:383–395PubMedGoogle Scholar
  35. 35.
    Commins LM, Loegering DJ, Gudewicz PW (1990) Effect of erythrocyte and erythrocyte ghost phagocytosis on macrophage phagocytic function and hydrogen peroxide production. Inflammation 14:705–715PubMedCrossRefGoogle Scholar
  36. 36.
    Donald DE (1983) Splanchnic circulation. In: Shepperd JT, Abbaud FM (eds) Handbook of physiology: the cardiovascular system, section 2, vol 3 peripheral circulation, part 1. American Physiological Society, Bethesda, pp 219–240Google Scholar
  37. Hanson KM, Johnson PC (1966) Local control of hepatic arterial and portal venous flow in the dog. Am J Physiol 211:712–717PubMedGoogle Scholar
  38. 38.
    McCluskey RS, Reilly FD (1993) Hepatic microvasculature: dynamic structure and its regulation. Semin Liver Disl3:l-12Google Scholar
  39. 39.
    Gutierrez G, Palizas F, Doglio G et al (1992) Gastric intramucosal pH as a therapeutic index of tissue oxygenation in critically ill patients. Lancet 339:195–199PubMedCrossRefGoogle Scholar
  40. 40.
    Steffes CP, Dahn MS, Lange MP (1994) Oxygen transport-dependent splanchnic metabolism in the sepsis syndrome. Arch Surg 129:46–52PubMedGoogle Scholar
  41. 41.
    Burton-Opitz R (1911) The vascularity of the liver: the effect of stimulation of single nerves of the hepatic plexus upon the flow in the hepatic artery. Q J Exp Physiol 4:103–116Google Scholar
  42. 42.
    Lautt WW, Legare DJ, D’Almeida MA (1985) Adenosine as a putative regulator of hepatic arterial flow (the buffer response). Am J Physiol 248:H331-H338PubMedGoogle Scholar
  43. 43.
    Greenway CV (1984) Role of splanchnic venous system in overall cardiovascular homeostasis. Fed Proc 42:1678–1684Google Scholar
  44. 44.
    Parks DA, Jacobson ED (1985) Physiology of the splanchnic circulation. Arch Intern Med 145:1278–1281PubMedCrossRefGoogle Scholar
  45. 45.
    Baker T, Deitch EA, Ma L et al (1988) Hemorrhagic shock promotes the systemic translocation of bacteria from the gut. J Trauma 28:896–906PubMedCrossRefGoogle Scholar
  46. 46.
    Deitch EA, Bridges W, Ma L et al (1990) Hemorrhagic shock-induced bacterial translocation: the role of neutrophils and hydroxyl radicals. J Trauma 30:942–952PubMedCrossRefGoogle Scholar
  47. 47.
    Kageshima K, Miyano K, Tanifuji Y et al (1990) Effects of dopamine and dobutamine on hepatic circulation and metabolism in hemorrhagic hypotensive pigs. Masui 39:592–599PubMedGoogle Scholar
  48. 48.
    Nordin A, Makisalo H, Hockersstedt K (1994) Dopamine infusion during resuscitation of experimental hemorrhagic shock. Crit Care Med 22:151–156PubMedGoogle Scholar
  49. 49.
    Caty ML, Guice KS, Oldham KT et al (1990) Evidence for tumor necrosis factor- induced pulmonary microvascular injury after intestinal ischemia-reperfusion. Ann Surg 212:694–700PubMedCrossRefGoogle Scholar
  50. 50.
    Turnage RH, Guice KS, Oldham KT (1994) Endotoxemia and remote organ injury following intestinal reperfusion. J Surg Res 56:571–578PubMedCrossRefGoogle Scholar
  51. 51.
    Bark T, Katouli M, Ljungqvist S et al (1993) Bacterial translocation after non-lethal hemorrhage in the rat. Circ Shock 41:60–65PubMedGoogle Scholar
  52. 52.
    Deitch EA, Berg RD (1987) Endotoxin but not malnutrition promotes bacterial translocation from the gut. J Trauma 27:161–166PubMedCrossRefGoogle Scholar
  53. 53.
    Koziol JM, Rush BF Jr, Smith SM et al (1988) Occurrence of bacteremia during and after hemorrhagic shock. J Trauma 28:10–16PubMedCrossRefGoogle Scholar
  54. 54.
    Nelson DP, Samsel RW, Wood LDH et al (1988) Pathological supply dependence of systemic and intestinal 02 uptake during endotoxemia. J Appl Physiol 64:2410–2419PubMedGoogle Scholar
  55. 55.
    Tracey KJ, Lowry SF, Fahey TJ III et al (1987) Cachectin/tumor necrosis factor induces lethal shock and stress hormone responsiveness in the dog. Surgery 164:415–422Google Scholar
  56. 56.
    Tracey KJ, Fong Y, Hesse DG et al (1987) Anti-cachectin/TNF monoclonal antibodies prevent septic shock during lethal bacteremia. Nature 330:662–664PubMedCrossRefGoogle Scholar
  57. 57.
    Dinarello CA (1991) The proinflammatory cytokines interleukin-1 and tumor necrosis factor and treatment of the septic shock syndrome. J Infect Dis 163:1177–1184PubMedCrossRefGoogle Scholar
  58. 58.
    Van Zee KJ, LaForge LE, Fischer E et al (1991) IL-8 in septic shock, endotoxemia, and after IL-1 administration. J Immunol 146:3478–3482PubMedGoogle Scholar
  59. 59.
    Hagmann WE, Denzlinger C, Keppler D (1984) Role of peptide leukotrienes and their hepatobiliary elimination in endotoxin action. Circ Shock 14:233–238Google Scholar
  60. 60.
    Robbins RA, Russ WA, Rasmussen JK (1987) Activation of the complement system in the adult respiratory distress syndrome. Am Rev Respir Dis 135:651–658PubMedGoogle Scholar
  61. 61.
    Jaeschke H, Raftery MJ, Justesen U et al (1992) Serum complement mediates endo- toxin-induced cysteinyl leukotriene formation in rats in vivo. Am J Physiol (Gastroin- test Liver Physiol) 263: G947-G952Google Scholar
  62. 62.
    Bone RC (1991) The pathophysiology of sepsis. Ann Intern Med 115:457–469PubMedGoogle Scholar
  63. 63.
    Giroir BP (1993) Mediators of septic shock: new approaches for interrupting the endogenous inflammatory cascade. Crit Care Med 21:780–789PubMedCrossRefGoogle Scholar
  64. 64.
    Natanson C, Hoffman WD, Suffredini AF et al (1994) Selected treatment strategies for septic shock based on proposed mechanisms of pathogenesis. Ann Intern Med 120:771–783PubMedGoogle Scholar
  65. 65.
    Ciancio MJ, Hunt J, Jones SB et al (1991) Comparative and interactive in vivo effects of tumor necrosis factor a and endotoxin. Circ Shock 33:108–120PubMedGoogle Scholar
  66. 66.
    Prytz H, Holst-Christenson J, Korner B et al (1976) Portal venous and systemic endo- toxaemia in patients without liver disease and systemic endotoxaemia in patients with cirrhosis. Scand J Gastroenterol 11:857–863PubMedGoogle Scholar
  67. 67.
    Lumsden AB, Henderson JM, Kutner MN (1988) Endotoxin levels measured by a chromogenic assay in portal, hepatic and peripheral venous blood in patients with cirrhosis. Hepatology 8:232–236PubMedCrossRefGoogle Scholar
  68. 68.
    Wilkinson SP, Moodie H, Stamatakis JD et al (1976) Endotoxaemia and renal failure in cirrhosis and obstructive jaundice. Br Med J 2:1415–1418PubMedCrossRefGoogle Scholar
  69. 69.
    Goldfarb G, Nouel O, Poynard T et al (1983) Efficiency of respiratory assistance in cirrhotic patients with liver failure. Intensive Care Med 9:271–273PubMedCrossRefGoogle Scholar
  70. 70.
    Matuschak GM, Shaw BW Jr (1987) Adult respiratory distress syndrome associated with acute liver allograft rejection: resolution following hepatic retransplantation. Crit Care Med 15:878–881PubMedCrossRefGoogle Scholar
  71. 71.
    Decamp MM, Warner AE, Molina RM et al (1992) Hepatic versus pulmonary uptake of particles injected into the portal circulation in sheep. Am Rev Respir Dis 146:224–231PubMedGoogle Scholar
  72. 72.
    Matuschak GM, Mattingly M, Tredway TL et al (1994) Liver-lung interactions during E. coli endotoxemia: TNF-a:leukotriene axis. Am J Respir Crit Care Med 149:41–49PubMedGoogle Scholar
  73. 73.
    Halvorsen L, Roth R, Gunther RA et al (1993) Liver hemodynamics during portal venous endotoxemia in swine. Circ Shock 41:166–175PubMedGoogle Scholar
  74. 74.
    Raven HA, Fine J (1962) Biological implications of intestinal endotoxin. Fed Proc 21:65–68Google Scholar
  75. 75.
    Nolan JP, Leibowitz AL (1978) Endotoxin and the liver. III. Modification of acute carbon tetrachloride injury by polymyxin B - an antiendotoxin. Gastroenterology 75:445–449PubMedGoogle Scholar
  76. 76.
    Fox ES, Broitman, Thomas P (1990) Bacterial endotoxins and the liver. Lab Invest 63:733–741PubMedGoogle Scholar
  77. 77.
    Franson TR, Hierholzer WJ Jr, LaBreque DR (1985) Frequency and characteristics of hyperbilirubinemia associated with bacteremia. Rev Infect Dis 7:1–9PubMedCrossRefGoogle Scholar
  78. 78.
    Gimson AES (1987) Hepatic dysfunction during bacterial sepsis. Intensive Care Med 13:162–166PubMedCrossRefGoogle Scholar
  79. 79.
    von Allmen D, Hasselgren P-O, Higashiguchi T et al (1992) Individual regulation of different hepatocellular functions during sepsis. Metabolism 41:961–965CrossRefGoogle Scholar
  80. 80.
    Soons PA, De Boer A, Cohen AF et al (1991) Assessment of hepatic blood flow in healthy subjects by continuous infusion of indocyanine green. Br J Clin Pharmacol 32:697–704PubMedGoogle Scholar
  81. 81.
    Suren A, Bauer FE, Rosenkranz B et al (1991) Effect of pentoxifylline on liver plasma flow in normal man. Eur J Clin Pharmacol 41:233–237PubMedCrossRefGoogle Scholar
  82. 82.
    Leen E, Angerson WJ, Warren HW et al (1993) Duplex/colour Doppler sonography: measurement of changes in hepatic arterial hemodynamics following intra-arterial angiotensin II infusion. Br J Cancer 67:1381–1384PubMedCrossRefGoogle Scholar
  83. 83.
    Dahn MS (1994) Hepatic dysfunction in the critically ill and injured. Intensive Care World 11:9–14Google Scholar
  84. 84.
    Perlik F, Janku I, Jedlicka J (1992) Functional and non-functional liver blood flow in patients with liver cirrhosis measured by indocyanine green. Meth Find Exp Clin Pharmacol 14:459–464Google Scholar
  85. 85.
    Dahn MS, Lange P, Wilson RF et al (1990) Hepatic blood flow and splanchnic oxygen consumption measurements in clinical sepsis. Surgery 107:295–301PubMedGoogle Scholar
  86. 86.
    Wang P, Zheng FBA, Chaudry IH (1991) Increase in hepatic blood flow during early sepsis is due to increased portal flow. Am J Physiol 261 (Regulatory Integrative Comp Physiol 30):R1507-R1512PubMedGoogle Scholar
  87. 87.
    Wang P, Zheng FBA, Ayala A et al (1992) Hepatocellular dysfunction persists during early sepsis despite increase volume of crystalloid resuscitation. J Trauma 32:389–397PubMedCrossRefGoogle Scholar
  88. 88.
    Wang P, Ba ZF, Burkhardt J et al (1992) Measurement of hepatic blood flow after severe hemorrhage: lack of restoration despite adequate resuscitation. Am J Physiol 262 (Gastrointest Liver Physiol 6):G92-G98PubMedGoogle Scholar
  89. 89.
    Marzi I, Bauer C, Ho wer R et al (1993) Leukocyte-endothelial interactions in the liver after hemorrhagic shock in the rat. Circ Shock 40:105–114PubMedGoogle Scholar
  90. 90.
    Jaeschke H (1991) Vascular oxidant stress and hepatic ischemia/reperfusion injury. Free Radic Res Commun 12–13:737–743PubMedCrossRefGoogle Scholar
  91. 91.
    Johnson EE, Hedley-Whyte J (1977) End-expiratory pressure ventilation and sulfo- bromophthalein sodium excretion in dogs. J Appl Physiol 43:714–720PubMedGoogle Scholar
  92. 92.
    Rossaint R, Krebs M, Forther J et al (1993) Inferior vena caval pressure increase contributes to sodium and water retention during PEEP in awake dogs. J Appl Physiol 75:2484–2492PubMedGoogle Scholar
  93. 93.
    Matuschak GM, Pinsky MR (1989) Effects of positive-pressure ventilatory frequency on hepatic blood flow and performance. J Crit Care 4:153–165CrossRefGoogle Scholar
  94. 94.
    Johnson EE, Hedley-Whyte J (1972) Continuous positive-pressure ventilation and portal flow in dogs with pulmonary edema. J Appl Physiol 33:385–389PubMedGoogle Scholar
  95. 95.
    Winso O, Biber B, Gustavsson B et al (1986) Portal blood flow in man during graded positive end-expiratory pressure ventilation. Intensive Care Med 12:80–85PubMedCrossRefGoogle Scholar
  96. 96.
    Bennett TD, Rothe C (1981) Hepatic capacitance responses to changes in flow and hepatic venous pressure in dogs. Am J Physiol 239 (Heart Circ Physiol 9): H474-H481Google Scholar
  97. 97.
    Richard C, Berdeaux A, Delion F et al (1986) Effect of mechanical ventilation on hepatic drug pharmacokinetics. Chest 90:837–841PubMedCrossRefGoogle Scholar
  98. 98.
    Matuschak GM, Pinsky MR, Rogers RM (1987) Effects of positive end-expiratory pressure on hepatic blood flow and performance. J Appl Physiol 62:1377–1383PubMedGoogle Scholar
  99. 99.
    Purcell PN, Branson RD, Hurst JM et al (1992) Gut feeding and hepatic hemodynamics during PEEP ventilation for acute lung injury. J Surg Res 53:335–341PubMedCrossRefGoogle Scholar
  100. 100.
    Matuschak GM, Munoz C, Epperly NA et al (1994) TNF-a and IL-6 expression after intraportal candidemia vs. E. coli or S. aureus bacteremia. Am J Physiol (Regul Integrative Comp Physiol) 267: R446-R454Google Scholar
  101. 101.
    Matuschak GM, Lechner AJ (1993) Hepatic regulation of systemic host defense and its derangement in multiple systems organ dysfunction and failure. In: Matuschak GM (ed) Multiple systems organ failure: hepatic regulation of systemic host defense. Dek ker, New York, pp 1–38Google Scholar
  102. 102.
    Matsumoto K, Tajima H, Hamanque M et al (1992) Identification and characterization of “injurin”, an inducer of expression of the gene for hepatocyte growth factor. Proc Natl Acad Sei USA 89:3800–3804CrossRefGoogle Scholar
  103. 103.
    Shreck R, Rieber P, Baeurle PA (1991) Reactive oxygen intermediates as apparently widely used messengers in the activation of the NF- k B transcription factor and HIV -1. EMBO J 10 2247–2258 Google Scholar
  104. 104.
    Zuckerman SH, Evens GF, Guthrie L (1991) Transcriptional and post-transcriptional mechanisms involved in the differential expression of LPS-induced IL-1 and TNF mRNA. Immunology73:460–465Google Scholar
  105. 105.
    Han J, Huez G, Beutler B (1991) Interactive effects of the tumor necrosis factor promoter and 3’ -untranslated regions. J Immunol 146:1843–1848PubMedGoogle Scholar
  106. 106.
    Möhler KM, Torrance DS, Smith CA et al (1993) Soluble tumor necrosis factor (TNF) receptors are effective therapeutic agents in lethal endotoxemia and function simultaneously as both TNF carriers and TNF antagonists. J Immunol 151:1548–1561PubMedGoogle Scholar
  107. 107.
    Steinkasserer A, Estaller C, Weiss EH et al (1992) Human interleukin-1 receptor antagonist is expressed in liver. FEBS Lett 310:60–62PubMedCrossRefGoogle Scholar
  108. 108.
    Okusawa S, Yancey KB, van der Meer JWM et al (1988) C5a stimulates secretion of tumor necrosis factor from human mononuclear cells in vitro. J Exp Med 168:443–448PubMedCrossRefGoogle Scholar
  109. 109.
    Pittner RA, Spitzer JA (1992) Endotoxin and TNFa directly stimulate nitric oxide formation in cultured rat hepatocytes from chronically endotoxemic rats. Biochem Biophys Res Commun 185:430–435PubMedCrossRefGoogle Scholar
  110. 110.
    Karck U, Peters T, Decker K (1988) The release of tumor necrosis factor from endo- toxin-stimulated rat Kupffer cells is regulated by prostaglandin E2 and dexametha- sone. J Hepatol 7:352–361PubMedCrossRefGoogle Scholar
  111. 111.
    Tran-Thi, T-H, Weinhold L, Weinstock C et al (1993) Production of tumor necrosis factor-a, interleukin-1 and interleukin-6 in the perfused rat liver. Eur Cytokine Netw 4:363–370PubMedGoogle Scholar
  112. 112.
    Khoruts A, Stahnke L, McClain CJ et al (1991) Circulating tumor necrosis factor, interleukin-1 and interleukin-6 concentrations in chronic alcoholic patients. Hepatolo- gy 13:267–276CrossRefGoogle Scholar
  113. 113.
    Deviere J, Content J, Denys C et al (1990) Excessive in vitro bacterial lipopolysac- charide-induced production of monokines in cirrhosis. Hepatology 11:628–634PubMedCrossRefGoogle Scholar
  114. 114.
    Torre D, Zeroli C, Gioia M et al (1994) Serum levels of interleukin-la, interleukin-1 ß, interleukin-6, and tumor necrosis factor in patients with acute viral hepatitis. Clin Infect Dis 18:194–198PubMedCrossRefGoogle Scholar
  115. 115.
    Muto Y, Nouri-Aria KT, Meager A et al (1988) Enhanced tumour necrosis factor and interleukin-1 in fulminant hepatic failure. Lancet 2:72–74PubMedCrossRefGoogle Scholar
  116. 116.
    Tilg H, Wilmer A, Vogel W et al (1992) Serum levels of cytokines in chronic liver diseases. Gastroenterologyl03:264–274Google Scholar
  117. 117.
    Busam KJ, Homfeld A, Zawatsky R et al (1990) Virus vs endotoxin-induced activation of liver macrophages. Eur J Biochem 191:577–582PubMedCrossRefGoogle Scholar
  118. 118.
    Pinsky MR, Vincent J-L, Deviere J et al (1993) Serum cytokine levels in human septic shock: relation to multiple-system organ failure and mortality. Chest 103:565–575PubMedCrossRefGoogle Scholar
  119. 119.
    Bodey GP (1993) Hematogenous and major organ candidiasis. In: Bodey GP (ed) Candidiasis: pathogenesis, diagnosis and treatment. Raven, New York, pp 279–329Google Scholar
  120. 120.
    Tang E, Tang G, Berne TV (1993) Prognostic indicators in fungemia of the surgical patient. Arch Surg 128:759–763PubMedGoogle Scholar
  121. 121.
    Gianotti L, Alexander JW, Fukushima R et al (1993) Translocation of Candida albicans is related to the blood flow of individual intestinal villi. Circ Shock 40:250–257PubMedGoogle Scholar
  122. 122.
    Matuschak GM, Klein CA, Tredway TL et al (1993) TNF-a and cyclooxygenase metabolites do not modulate C. albicans septic shock with disseminated candidiasis. J Appi Physiol 74:2432–2442Google Scholar
  123. 123.
    Calderone RA, Braun PC (1991) Adherence and receptor relationships of Candida albicans. Microbiol Rev 55:1–20PubMedGoogle Scholar
  124. 124.
    Olynyk J, Matuschak GM, Lechner AJ et al (1994) Differential production of tumor necrosis factor-a by rat Kupffer cells in vitro after phagocytosis of E. coli and C. albicans. Am J Physiol (Gastrointest Liver Physiol) 267:G213-G219Google Scholar
  125. 125.
    Lechner AJ, Tredway TL, Brink D et al (1992) Differential systemic and intrapulmon- ary TNF-a production in Candida sepsis during immunosuppression. Am J Physiol (Lung Cell Mol Physiol 7) 263: L526-L535Google Scholar
  126. 126.
    Dahn MS, Wilson RF, Lange MP et al (1990) Hepatic parenchymal oxygen tension following injury and sepsis. Arch Surg 125:441–443PubMedGoogle Scholar
  127. 127.
    Schlichtig R, Klions HA, Kramer DJ et al (1992) Hepatic dysoxia commences during 02 supply dependence. J Appi Physiol 72:1499–1505Google Scholar
  128. 128.
    Fitch KA, Rink RD (1983) Hepatic oxygen supply during early and late sepsis in the rat. Circ Shock 10:51–59PubMedGoogle Scholar
  129. 129.
    Engerson TD, McKelvey TG, Rhyne DB et al (1987) Conversion of xanthine dehydrogenase to oxidase in ischemic rat tissues. J Clin Invest 79:1564–1570PubMedCrossRefGoogle Scholar
  130. 130.
    Gonzales-Flecha B, Cutrin JC, Boveris A (1993) Time course and mechanisms of oxidative stress and tissue damage in rat liver subjected to in vivo ischemia-reperfusion. J Clin Invest 91:456–464CrossRefGoogle Scholar
  131. 131.
    Chaudri G, Clark IA (1989) Reactive oxygen species facilitate the in vitro and in vivo lipopolysaccharide-induced release of tumor necrosis factor. J Immunol 143:1290–1294Google Scholar
  132. 132.
    Colletti LM, Remick DG, Burtch S et al (1990) Role of tumor necrosis factor-a in the pathophysiologic alterations after hepatic ischemia/reperfusion injury in the rat. J Clin Invest 85:1936–1943PubMedCrossRefGoogle Scholar
  133. 133.
    Jaeschke H, Farhood A (1991) Neutrophil and Kupffer cell-induced oxidant stress and ischemia-reperfusion injury in rat liver. Am J Physiol (Gastrointest Liver Physiol) 260:G355-G362Google Scholar
  134. 134.
    Jaeschke H, Farhood A, Bautista AP et al (1993) Functional inactivation of neutrophils with a Mac-1 (CDllb/CD18) monoclonal antibody protects against ischemia- reperfusion injury in rat liver. Hepatology 17:915–923PubMedCrossRefGoogle Scholar
  135. 135.
    Thorne J, Blomquist S, Elmer O et al (1989) Polymorphonuclear leukocyte sequestration in the lungs and liver following soft-tissue trauma: an in vivo study. J Trauma 29:451–456PubMedCrossRefGoogle Scholar
  136. 136.
    Ayala A, Perrin MM, Wang P et al (1992) Hemorrhage induces enhanced Kupffer cell cytotoxicity while decreasing peritoneal or splenic macrophage capacity: involvement of cell-associated TNF and reactive nitrogen. J Immunol 147:4147–4152Google Scholar
  137. 137.
    Wibbenmeyer LW, Lechner AJ, Munoz CF, Matuschak GM (1995) Downregulation of E. coli-induced TNF-a expression in perfused liver by hypoxia-reoxygenation. Am J Physiol 268 (Gastrointest Liver Physiol 31):G311-G319PubMedGoogle Scholar
  138. 138.
    Keogh C, Fong Y, Mariano MA et al (1990) Identification of a novel tumor necrosis factor-a/cachectin from the livers of burned and infected rats. Arch Surg 125:79–85PubMedGoogle Scholar
  139. 139.
    Bautista AP, Spitzer JJ (1990) Superoxide anion generation by in situ perfused rat liver: effect of in vivo endotoxin. Am J Physiol (Gastrointest Liver Physiol) 259: G907-G912Google Scholar
  140. 140.
    Hewett J A, Jean PA, Kunkel SL et al (1993) Relationship between tumor necrosis factor-a and neutrophils in endotoxin-induced liver injury. Am J Physiol (Gastrointest Liver Physiol) 265:G1011-G1015Google Scholar
  141. 141.
    Bernard GR, Artigas A, Brigham KL et al (1994) The American-European Consensus Conference on ARDS. Am J Respir Crit Care Med 149:818–824PubMedGoogle Scholar
  142. 142.
    Krowka MJ (1993) Clinical management of the hepatopulmonary syndrome. Semin Liver Dis 13:414–422PubMedCrossRefGoogle Scholar
  143. 143.
    Chang S-W, Ohara N (1992) Pulmonary circulatory dysfunction in rats with biliary cirrhosis: an animal model of the hepatopulmonary syndrome. Am Rev Respir Dis 145:798–805PubMedGoogle Scholar
  144. 144.
    Beutler BA, Milsark IW, Cerami A (1985) Cachectin/tumor necrosis factor: production, distribution, and metabolic fate in vivo. J Immunol 135:3972–3977PubMedGoogle Scholar
  145. 145.
    Denzlinger C, Rapp S, Hagmann W et al (1985) Leukotrienes as mediators in tissue trauma. Science 230:330–332PubMedCrossRefGoogle Scholar
  146. 146.
    Denzlinger C, Gohlmann A, Scheuber PH et al (1986) Metabolism and analysis of cysteinyl leukotrienes in the monkey. J Biol Chem 25:15601–15606Google Scholar
  147. 147.
    Suter PM, Suter S, Girardin E et al (1992) High bronchoalveolar levels of tumor necrosis factor and its inhibitors, interleukin-1, interferon, and elastase, in patients with adult respiratory distress syndrome after trauma, shock, or sepsis. Am Rev Respir Dis 145:1016–1022PubMedCrossRefGoogle Scholar
  148. 148.
    Stephenson AH, Lonigro AJ Hyers TM et al (1985) Increased concentrations of leukotrienes in bronchoalveolar lavage fluid of patients with ARDS or at risk for ARDS. Am Rev Respir Dis 138:714–719Google Scholar
  149. 149.
    Bernard GR, Korley V, Swindell B et al (1991) Persistent generation of peptide leukotrienes in patients with the adult respiratory distress syndrome. Am Rev Respir Dis 144:263–267PubMedCrossRefGoogle Scholar
  150. 150.
    Huber M, Kastner S, Scholmerich J et al (1989) Cysteinyl leukotriene analysis in human urine: enhanced excretion in patients with liver cirrhosis and hepatorenal syndrome. Eur J Clin Invest 19:53–60PubMedGoogle Scholar
  151. 151.
    Huber M, Beutler B, Keppler D (1988) Tumor necrosis factor-a stimulates leukotriene production in vivo. Eur J Immunol 18:2085–2088PubMedCrossRefGoogle Scholar
  152. 152.
    Lehmann V, Freudenberg MA, Galanos C (1987) Lethal toxicity of lipopolysacchar- ide and tumor necrosis factor in normal and D-galactosamine-treated mice. J Exp Med 165:657–663PubMedCrossRefGoogle Scholar
  153. 153.
    Freudenberg MA, Galanos C (1991) Tumor necrosis factor alpha mediates lethal activity of killed gram-negative and gram-positive bacteria in D-galactosamine-treated mice. Infect Immun 59:2110–2115PubMedGoogle Scholar
  154. 154.
    Matuschak GM, Pinsky MR, Klein EC et al (1990) Effects of D-galactosamine- induced acute liver injury on mortality and pulmonary responses to E. coli lipopoly- saccharide: modulation by arachidonic acid metabolites. Am Rev Respir Dis 141:1296–1306PubMedGoogle Scholar
  155. 155.
    Hagmann W (1993) The liver in leukotriene action, metabolism, and production: physiologic and pathophysiologic conditions. In: Matuschak GM (ed) Multiple systems organ failure: hepatic regulation of systemic host defense. Dekker, New York, pp 165–191Google Scholar
  156. 156.
    Perlmutter DH, Dinarello CA, Punsai PI et al (1986) Cachectin/tumor necrosis factor regulates hepatic acute-phase gene expression. J Clin Invest 78:1349–1354PubMedCrossRefGoogle Scholar
  157. 157.
    Perlmutter DH (1993) Cytokines and the hepatic acute-phase response. In: Matuschak GM (ed) Multiple systems organ failure: hepatic regulation of systemic host defense. Dekker, New York, pp 229–265Google Scholar
  158. 158.
    Scanga G, Siegal JH, Brown G et al (1985) Reprioritization of hepatic plasma protein release in trauma and sepsis. Arch Surg 120:187–199Google Scholar
  159. 159.
    Cereghini S, Raymonjean M, Carranca AG et al (1987) Factors involved in control of tissue-specific expression of albumin gene. Cell 50:627–638PubMedCrossRefGoogle Scholar
  160. 160.
    Castell JV, Andus T, Kunz D et al (1989) Interleukin-6:the major regulator of acute- phase protein synthesis in man and rat. Ann NY Acad Sci 169:333–338Google Scholar
  161. 161.
    Korber B, Merod N, Hood L et al (1988) Regulation of gene expression by interferons: control of H-2 promoter responses. Science 239:1302–1306PubMedCrossRefGoogle Scholar
  162. 162.
    Billiar TR, Curran RD, Stuehr DJ et al (1990) Kupffer celkhepatocyte cocultures produce nitric oxide in response to bacterial endotoxin. J Surg Res 48:349–355PubMedCrossRefGoogle Scholar
  163. 163.
    Curran RD, Billiar TR, Stuehr DJ et al (1990) Multiple cytokines are required to induce hepatocyte nitric oxide production and inhibit total protein synthesis. Ann Surg 212:462–471PubMedCrossRefGoogle Scholar
  164. 164.
    Peters T, Karck U, Decker K (1990) Interdependence of tumor necrosis factor, prostaglandin E2, and protein synthesis in lipopolysaccharide-exposed rat Kupffer cells. Eur J Biochem 191:583–589PubMedCrossRefGoogle Scholar
  165. 165.
    Goldstein SA, Elwyn DH (1989) The effects of injury and sepsis on fuel utilization. Annu Rev Nutr 9:445–473PubMedCrossRefGoogle Scholar
  166. 166.
    Lowry SF (1992) Modulating the metabolic response to injury and infection. Proc Nutr Soc 51:267–277PubMedCrossRefGoogle Scholar
  167. 167.
    Gelfand RA, Matthews DE, Bier DM et al (1984) Role of counter-regulatory hormones in the catabolic response to stress. J Clin Invest 200:2238–2248CrossRefGoogle Scholar
  168. 168.
    Pittiruti M, Siegel JH, Sganga G et al (1989) Determinants of urea-production in sepsis: muscle catabolism, TPN, and hepatic clearance of amino acids. Arch Surg 124:362–372PubMedGoogle Scholar
  169. 169.
    Vary TC, Siegel JH, Nakatani T et al (1986) Effect of sepsis on activity of pyruvate dehydrogenase complex in skeletal muscle and liver. Am J Physiol 13:E634-E640Google Scholar
  170. Sottrup-Jensen L (1989) a-Macroglobulins: structure, shape, and mechanism of proteinase complex formation. J Biol Chem 264:11539–11542PubMedGoogle Scholar
  171. 171.
    Wollenberg GK, LaMarre J, Hayes MA (1993) Cytokine interactions with a2-macro- globulin. In: Matuschak GM (ed) Multiple systems organ failure: hepatic regulation of systemic host defense. Dekker, New York, pp 293–320Google Scholar
  172. 172.
    Wollenberg GK, LaMarre J, Rosendal S et al (1991) Binding of tumor necrosis factor alpha to activated forms of human plasma alpha2 macroglobulin. Am J Pathol 138:265–272PubMedGoogle Scholar
  173. 173.
    Borth W, Luger TA (1989) Identification of a2-macroglobulin as a cytokine binding plasma protein. Binding of interleukin-lß to “F” a2-macroglobulin. J Biol Chem 264:5818–5825PubMedGoogle Scholar
  174. 174.
    Tillet WS, Francis T Jr (1930) Serologic reactions in pneumonia with a non-protein somatic fraction of pneumococcus. J Exp Med 52:561–571CrossRefGoogle Scholar
  175. 175.
    Kew RR, Hyers TM, Webster RO (1990) Human C-reactive protein inhibits neutrophil Chemotaxis in vitro: possible implications for the adult respiratory distress syndrome. J Lab Clin Med 115:339–345PubMedGoogle Scholar
  176. 176.
    Heuertz RM, Piquette CA, Webster RO (1993) Rabbits with elevated serum C-reac- tive protein exhibit diminished neutrophil infiltration and vascular permeability in C5a-induced alveolitis. Am J Pathol 142:319–328PubMedGoogle Scholar
  177. 177.
    Heuertz RM, Xia D, Samols D et al (1994) Inhibition of C5a des arg-induced neutrophil alveolitis in transgenic mice expressing C-reactive protein. Am J Physiol (Lung Cell Mol Physiol) 266: L649-L654Google Scholar
  178. 178.
    Siegel J, Rent R, Gerwurz H (1975) Interactions of C-reactive protein with the complement system. J Exp Med 142:709–721PubMedCrossRefGoogle Scholar
  179. 179.
    Geller DA, Kispert PH, Su GL et al (1993) Induction of hepatocyte lipopolysacchar- ide binding protein in models of sepsis and the acute-phase response. Arch Surg 128:22–28PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1995

Authors and Affiliations

  • G. M. Matuschak

There are no affiliations available

Personalised recommendations