Involvement of Pro- and Anti-Inflammatory Cytokines in Sepsis

  • Jean-Marc Cavaillon
  • Minou Adib-Conquy


Septic Shock Migration Inhibitory Factor Septic Patient Leukemia Inhibitory Factor Endotoxic Shock 
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.


  1. 1.
    Okusawa S, Gelfand J, Ikejima T, et al. Interleukin 1 induces a shock like state in rabbit. Synergism with tumor necrosis factor and the effect of cyclooxygenase inhibition. J Clin Invest 1988; 81:1162–1172PubMedCrossRefGoogle Scholar
  2. 2.
    Ohlsson K, Bjökk P, Bergenfield M, et al. Interleukin-1 receptor antagonist reduces mortality from endotoxin shock. Nature 1990; 348:550–552PubMedCrossRefGoogle Scholar
  3. 3.
    Li P, Allen H, Banerjee S, et al. Mice defeficient in IL-1β converting enzyme are defective in production of mature IL-1β and resistant to endotoxic shock. Cell 1995; 80:401–411PubMedCrossRefGoogle Scholar
  4. 4.
    Fantuzzi G, Hui Z, Faggioni R, et al. Effect of endotoxin in IL-1β deficient mice. J. Immunol. 1996; 157:291–296PubMedGoogle Scholar
  5. 5.
    Van Deuren M, Van Der Ven-Jongekrijg H, Baterlink AKN, et al. Correlation between proinflammatory cytokines and antiinflammatory mediators and the severity of disease in meningococcal infections. J Infect Dis 1995; 172:433–439PubMedGoogle Scholar
  6. 6.
    Gardlund B, Sjölin J, Nilsson A, et al. Plasma levels of cytokines in primary septic shock in humans: correlation with disease severity. J Infect Dis 1995; 172:296–301PubMedGoogle Scholar
  7. 7.
    Girardin E, Grau G, Dayer J, et al. Tumor necrosis factor and interleukin-1 in the serum of children with severe infectious purpura. N Engl J Med 1988; 319:397–400PubMedCrossRefGoogle Scholar
  8. 8.
    Waage A, Brandtzaeg P, Halstensen A, et al. The complex pattern of cytokines in serum from patients with meningococcal septic shock. Association between interleukin-6, interleukin-1, and fatal outcome. J Exp Med 1989; 169:333–338PubMedCrossRefGoogle Scholar
  9. 9.
    Muñoz C, Misset B, Fitting C, et al. Dissociation between plasma and monocyte-associated cytokines during sepsis. Eur J Immunol 1991; 21:2177–2184PubMedCrossRefGoogle Scholar
  10. 10.
    Calandra T, Baumgartner JD, Grau GE, et al. Prognostic values of tumor necrosis factor/cachectin, interleukin-1, interferon-α, and interferon-γ in the serum of patients with septic shock. J Infect Dis 1990; 161:982–987PubMedGoogle Scholar
  11. 11.
    Van der Poll T, Romijn JA, Endert E, et al. Tumor necrosis factor mimics the metabolic response to acute infection in healthy humans. Am J Physiol 1991; 261:E457–465Google Scholar
  12. 12.
    Doherty GM, Lange JR, Langstein HN, et al. Evidence for IFN-gamma as a mediator of the lethality of endotoxin and tumor necrosis factor-alpha. J Immunol 1992; 149:1666–1670PubMedGoogle Scholar
  13. 13.
    Rothstein JL, Schreiber H. Synergy between tumor necrosis factor and bacterial products causes hemorrhagic necrosis and lethal shock in normal mice. Proc Natl Acad Sci USA 1988; 85:607–611PubMedCrossRefGoogle Scholar
  14. 14.
    Beutler B, Milsark IW, Cerami AC. Passive immunization against cachectin/tumor necrosis factor protects mice from lethal effect of endotoxin. Science 1985; 229:869–871PubMedCrossRefGoogle Scholar
  15. 15.
    Tracey KJ, Fong Y, D.G. H, et al. Anti-cachectin/TNF monoclonal antibodies prevent septic shock during lethal bacteraemia. Nature 1987; 330:662–664PubMedCrossRefGoogle Scholar
  16. 16.
    Caty MG, Guice KS, Oldham KT, et al. Evidence for tumor necrosis factor-induced pulmonary microvascular injury after intestinal ischemia-reperfusion injury. Ann Surg 1990; 212:694–700PubMedCrossRefGoogle Scholar
  17. 17.
    Netea MG, Kullberg BJ, Verschueren I, et al. Diferential susceptibility of cytokine knock out mice for lipopolysaccharides derived from different Gram-negative bacteria. J Endotoxin Res 2000; 6:188Google Scholar
  18. 18.
    Waage A, Espevik T, Lamvik J. Detection of tumor necrosis factor-like cytotoxicity in serum from patients with septicemia but not from untreated cancer patients. Scand. J. Immunol. 1986; 24:739–743PubMedCrossRefGoogle Scholar
  19. 19.
    Waage A, Halstensen A, Espevik T. Association between tumor necrosis factor in serum and fatal outome in patients with meningococal disease. Lancet 1987; i:355–357CrossRefGoogle Scholar
  20. 20.
    Offner F, Philippé J, Vogelaers D, et al. Serum tumor necrosis factor levels in patients with infectious diseases and septic shock. J Lab Clin Med 1990; 116:100–105PubMedGoogle Scholar
  21. 21.
    Baud L, Cadranel J, Offenstadt G, et al. Tumor necrosis factor and septic shock. Crit Care Med 1990; 18:349–350PubMedCrossRefGoogle Scholar
  22. 22.
    Pinsky MR, Vincent JL, Deviere J, et al. Serum cytokine levels in human septic shock. Relation to multiple-system organ failure and mortality. Chest 1993; 103:565–575PubMedCrossRefGoogle Scholar
  23. 23.
    Hamilton GH, Hofbauer S, Hamilton B. Endotoxin, TNF-alpha, interleukin-6 and parameters of the cellular immune system in patients with intraabdominal sepsis. Scand J Infect Dis 1992; 24:361–368PubMedCrossRefGoogle Scholar
  24. 24.
    Riche F, Panis Y, Laisne MJ, et al. High tumor necrosis factor serum level is associated with increased survival in patients with abdominal septic shock: a prospective study in 59 patients. Surgery 1996; 120:801–807PubMedCrossRefGoogle Scholar
  25. 25.
    Arditi M, Manogue KR, Caplan M, et al. Cerebrospinal fluid tumor necrosis factor-alpha and PAF concentrations and severity of bacterial meningitis in children. J Infect Dis 1990; 162:139–147PubMedGoogle Scholar
  26. 26.
    Dulkerian SJ, Kilpatrick L, Costarino AT, et al. Cytokine elevations in infants with bacterial and aseptic meningitis. J Pediatr 1995; 126:872–876PubMedCrossRefGoogle Scholar
  27. 27.
    Engelhardt R, Mackensen A, Galanos C, et al. Biological response to intravenously administered endotoxin in patients with advanced cancer. J Biol Resp Mod 1990; 9:480–491Google Scholar
  28. 28.
    Pollmächer T, Korth C, Mullington J, et al. Effects of G-CSF on plasma cytokine and cytokine receptor levels and on the in vivo host response to endotoxin in healthy men. Blood 1996; 87:900–905PubMedGoogle Scholar
  29. 29.
    van der Poll T, Coyle SM, Barbosa K, et al. Epinephrine inhibits tumor necrosis factor-alpha and potentiates interleukin-10 production during human endotoxemia. J Clin Invest 1996; 97:713–719PubMedCrossRefGoogle Scholar
  30. 30.
    Leeper-Woodford SK, Carey PD, Byrne K, et al. Tumor necrosis factor alpha and beta subtypes appear in circulation during onset of sepsis-induced lung injury. Am Rev Respir Dis 1991; 143:1076–1082PubMedGoogle Scholar
  31. 31.
    Sriskandan S, Moyes D, Cohen J. Detection of circulating bacterial superantigen and lymphotoxin-alpha in patients with streptococcal toxic-shock syndrome. Lancet 1996; 348:1315–1316PubMedCrossRefGoogle Scholar
  32. 32.
    Wagner H, Heeg K, Miethke T. T cell mediated lethal shock induced by bacterial superantigens. Behring Inst Mitt 1992; 91:46–53PubMedGoogle Scholar
  33. 33.
    Tokman MG, Carey KD, Quimby FW. The pathogenesis of experimental toxic shock syndrome: the role of interleukin-2 in the induction of hypotension and release of cytokines. Shock 1995; 3:145–151PubMedGoogle Scholar
  34. 34.
    Musso T, Calosso L, Zucca M, et al. Human monocytes constitutively express membrane-bound, biologically active, and interferon-γ upregulated interleukin-15. Blood 1999; 93:3531–3539PubMedGoogle Scholar
  35. 35.
    Lauw FN, Dekkers PE, te Velde AA, et al. Interleukin-12 induces sustained activation of multiple host inflammatory mediators systems in chimpanzees. J Infect Dis 1999; 179:646–652PubMedCrossRefGoogle Scholar
  36. 36.
    Fehniger TA, Yu H, Cooper MA, et al. IL-15 costimulates the general Shwartzman reaction and innate immune IFNγ production in vivo. J Immunol 2000; 164:1643–1647PubMedGoogle Scholar
  37. 37.
    Alleva DG, Kaser SB, Monroy MA, et al. IL-15 functions as a potent autocrine regulator of macrophage proinflammatory cytokine production. Evidence for differential receptor subunit utilization associated with stimulation or inhibition. J Immunol 1997; 159:2941–2951PubMedGoogle Scholar
  38. 38.
    Lauw FN, Simpson AJH, Prins JM, et al. Elevated Plasma Concentrations of Interferon (IFN) and the IFN-Inducing Cytokines Interleukin (IL)18, IL-12, and IL-15 in Severe Melioidosis. J Infect Dis 1999; 180:1878–1885PubMedCrossRefGoogle Scholar
  39. 39.
    Waring P, Wycherley K, Cary D, et al. Leukemia inhibitory factor levels are elevated in septic shock and various inflammatory body fluids. J Clin Invest 1992; 90:2031–2037PubMedCrossRefGoogle Scholar
  40. 40.
    Block MI, Berg M, McNamara MJ, et al. Passive immunization of mice against D factor blocks lethality and cytokine release during endotoxemia. J Exp Med 1993; 178:1085–1090PubMedCrossRefGoogle Scholar
  41. 41.
    Modur V, Feldhaus MJ, Weyrich AS, et al. Oncostanin M is a proinflammatory mediator. In vivo effects correlates with endothelial cell expression of inflammatory cytokines and adhesion molecules. J Clin Invest 1997; 100:158–168PubMedCrossRefGoogle Scholar
  42. 42.
    Villers D, Dao T, Nguyen JM, et al. Increased plasma levels of human interleukin for DA la cells / leukemia inhibitory factor in sepsis correlate with shock and poor prognosis. J Infect Dis 1995; 171:232–236PubMedGoogle Scholar
  43. 43.
    Guillet C, Fourcin M, Chevalier S, et al. ELISA detection of circulating levels of LIF, OSM and CNTF in septic shock. Ann NY Acad Sci 1995; 762:407–412PubMedGoogle Scholar
  44. 44.
    Jansen PM, de Jong IW, Hart M, et al. Release of leukemia inhibitory factor in primate sepsis. Analysis of the role of TNFα J Immunol 1996; 156:4401–4407PubMedGoogle Scholar
  45. 45.
    Broaddus VC, Boylan AM, Hoeffel JM, et al. Neutralization of IL-8 inhibits neutrophils influx in a rabbit model of endotoxin-induced pleurisy. J Immunol 1994; 152:2960–2967PubMedGoogle Scholar
  46. 46.
    Marty C, Misset B, Tamion F, et al. Circulating interleukin-8 concentrations in patients with multiple organ failure of septic and nonseptic origin. Crit. Care Med. 1994; 22:673–679PubMedGoogle Scholar
  47. 47.
    Marie C, Fitting C, Cheval C, et al. Presence of high levels of leukocyte-associated interleukin-8 upon cell activation and in patients with sepsis syndrome. Infect Immun 1997; 65:865–871PubMedGoogle Scholar
  48. 48.
    Gimbrone MA, Obin MS, Brock AF, et al. Endothelial interleukin-8:a novel inhibitor of leukocyte-endothelial interactions. Science 1989; 246:1601–1603PubMedCrossRefGoogle Scholar
  49. 49.
    Cunha FQ, Cunha Tamashiro WMS. Tumour necrosis factor-alpha and interleukin-8 inhibit neutrophil migration in vitro and in vivo. Mediators Inflam 1992; 1:397–401CrossRefGoogle Scholar
  50. 50.
    Zisman DA, Kunkel SL, Strieter RM, et al. MCP-1 protects mice in lethal endotoxemia. J Clin Invest 1997; 99:2832–2836PubMedCrossRefGoogle Scholar
  51. 51.
    Chvatchko Y, Hoogewerf AJ, Meyer A, et al. A key role for CC chemokine receptor 4 in lipopolysaccharide-induced endotoxic shock. J Exp Med 2000; 191:1755–1763PubMedCrossRefGoogle Scholar
  52. 52.
    Matsukawa A, Hogaboam CM, Lukacs NW, et al. Pivotal role of the CC chemokine, macrophage derived chemokine, in the innate immune response. J Immunol 2000; 164:5362–5368PubMedGoogle Scholar
  53. 53.
    Friedland J, Suputtamongkol Y, Remick D, et al. Prolonged elevation of interleukin-8 and interleukin-6 concentrations in plasma and of leukocyte interleukin-8 m-RNA levels during septicemic and localized Pseudomonas pseudomallei infection. Infect Immun 1992; 60:2402–2408PubMedGoogle Scholar
  54. 54.
    Hack C, Hart M, Strack van Schijndel R, et al. Interleukin-8 in sepsis:relation to shock and inflammatory mediators. Infect. Immun. 1992; 60:2835–2842PubMedGoogle Scholar
  55. 55.
    Miller EJ, Cohen AB, Nagao S, et al. Elevated levels of NAP-1/Interleukin-8 are present in the airspaces of patients with the adult respiratory distress syndrome and are associated with increased mortality. Am. J. Respir. Dis. 1992; 148:427–432Google Scholar
  56. 56.
    Endo S, Inada K, Ceska M, et al. Plasma interleukin 8 and polymorphonuclear leukocyte elastase concentrations in patients with septic shock. J Inflamm 1995; 45:136–142PubMedGoogle Scholar
  57. 57.
    Kragsbjerg P, Holmberg H, Vikerfors T. Dynamics of blood cytokine concentrations in patients with bacteremic infections. Scand J Infect Dis 1996; 28:391–398PubMedCrossRefGoogle Scholar
  58. 58.
    Friedland JS, Porter JC, Daryanani S, et al. Plasma proinflammatory cytokine concentrations, acute physiology and chronic health evaluation (APACHE) III scores and survival in patients in an intensive care unit. Crit Care Med 1996; 24:1775–1781PubMedCrossRefGoogle Scholar
  59. 59.
    Redl H, Schlag G, Bahrami S, et al. Plasma neutrophil-activating peptide-1/interleukin-8 and neutrophil elastase in a primate bacteremia model. J Infect Dis 1991; 164:383–388PubMedGoogle Scholar
  60. 60.
    Bossink AW, Paemen L, Jansen PM, et al. Plasma levels of the chemokines monocyte chemotactic proteins-1 and-2 are elevated in human sepsis. Blood 1995; 86:3841–3847PubMedGoogle Scholar
  61. 61.
    O’Grady NP, Tropea M, Preas HL, et al. Detection of macrophage inflammatory protein (MIP)-1α and MIP-1β during experimental endotoxemia and human sepsis. J Infect Dis. 1999; 179Google Scholar
  62. 62.
    Olszyna DP, Prins JM, Dekkers PEP, et al. Sequential measurements of chemokines in urosepsis and experimental endotoxemia. J Clin Immunol 1999; 19Google Scholar
  63. 63.
    Ryffel B. Interleukin-12:role of interferon-γ in IL-12 adverse effects. Clin Immunol Immunopath 1997; 83:18–20CrossRefGoogle Scholar
  64. 64.
    Wysocka M, Kubin M, Vieira LQ, et al. Interleukin-12 is required for interferon-gamma production and lethality in lipopolysaccharide-induced shock in mice. Eur J Immunol 1995; 25:672–676PubMedCrossRefGoogle Scholar
  65. 65.
    Steinhauser ML, Hogaboam CM, Lukacs NW, et al. Multiples roles for IL-12 in a model of acute septic peritonitis. J Immunol 1999; 162:5437–5443PubMedGoogle Scholar
  66. 66.
    Mancuso G, Cusumano V, Genovese E, et al. Role of interleukin-12 in experimental neonatal sepsis caused by group B streptococci. Infect Immun 1997; 65:3731–3735PubMedGoogle Scholar
  67. 67.
    Heinzel FP, Rerko RM, Ling P, et al. Interleukin-12 is produced in vivo during endotoxemia and stimulates synthesis of γ-interferon. Infect Immun. 1994; 62:4244–4251PubMedGoogle Scholar
  68. 68.
    Jansen PM, van der Pouw Kraan TCTM, de Jong IW, et al. Release of IL-12 in experimental Escherichia coli septic shock in baboons:relation to plasma levels to IL-10 and IFN-gamma. Blood 1996; 87:5144–5151PubMedGoogle Scholar
  69. 69.
    Zimmer S, Pollard V, Marshall GD, et al. The 1996 Moyer Award. Effects of endotoxin on the Thl/Th2 response in humans. J Burn Care Rehabil 1996; 17:491–496PubMedCrossRefGoogle Scholar
  70. 70.
    Presterl E, Staudinger T, Pettermann M, et al. Cytokine Profile and Correlation to the APACHE III and MPM II Scores in Patients with Sepsis. Am. J. Respir. Crit. Care Med. 1997; 156:825–832PubMedGoogle Scholar
  71. 71.
    Puren AJ, Razeghi P, Fantuzzi G, et al. Interleukin-18 enhances lipopolysaccharide-induced interferon-γ production in human whole blood cultures. J Infect Dis 1998; 178:1830–1834PubMedCrossRefGoogle Scholar
  72. 72.
    Bohn E, Sing A, Zumbihl R, et al. IL-18 regulates early cytokine production in, and promotes resolution of, bacterial infection in mice. J Immunol 1998; 160:299–307PubMedGoogle Scholar
  73. 73.
    Tsutsui H, Matsui K, Kawada N, et al. IL-18 accounts for both TNFα and Fas Ligand-mediated hepatotoxic pathways in endotoxin-induced liver injury in mice. J Immunol 1997; 159:3961–3967PubMedGoogle Scholar
  74. 74.
    Netea MG, Fantuzzi G, Kullberg BJ, et al. Neutralization of IL-18 reduces neutrophil tissue accumulation and protects mice against lethal Escherichia coli and Salmonella typhimurium endotoxemia. J Immunol 2000; 164:2644–2649PubMedGoogle Scholar
  75. 75.
    Hochholzer P, Lipford GB, Wagner H, et al. Role of interleukin-18 during lethal shock:decreased lipopolysaccharide sensitivity but normal surperantigen reaction in IL-18-deficient mice. Infect Immun 2000; 68:3502–3508PubMedCrossRefGoogle Scholar
  76. 76.
    Sakao Y, Takeda K, Tsutsui H, et al. IL-18-deficient mice are resistant to endotoxin-induced liver injury but highly susceptible to endotoxic shock. Intern Immunol 1999; 11:471–480CrossRefGoogle Scholar
  77. 77.
    Heinzel FP. The role of interferon-gamma in the pathology of experimental endotoxemia. J Immunol 1990; 145:2920–2924PubMedGoogle Scholar
  78. 78.
    Silva AT, Cohen J. Role of interferon-gamma in experimental Gram-negative sepsis. J Infect Dis 1992; 166:331–335PubMedGoogle Scholar
  79. 79.
    Nansen A, Pravsgaard Christensen J, Marker O, et al. Sensitization to lipopolysaccharide in mice with asymptomatic viral infection:role of T-cell-dependent production of interferon-γ. J Infect Dis 1997; 176:151–157PubMedGoogle Scholar
  80. 80.
    Kamijo R, Le J, Shapiro D, et al. Mice that lack the interferon-gamma receptor have profoundly altered responses to infection with Bacillus Calmette-Guerin and subsequent challenge with lipopolysaccharide. J Exp Med 1993; 178:1435–1440PubMedCrossRefGoogle Scholar
  81. 81.
    Car BD, Eng VM, Schnyder B, et al. Interferon-gamma receptor deficient mice are resistant to endotoxic shock. J Exp Med 1994; 179:1437–1444PubMedCrossRefGoogle Scholar
  82. 82.
    Heremans H, Dillen C, Groenen M, et al. Role of interferon-γ and nitric oxide in pulmonary edema and death induced by lipopolysaccharide. Am J Respir Crit Care Med 2000; 161:110–117PubMedGoogle Scholar
  83. 83.
    Mathy NL, Scheuer W, Lanzendörrfer M, et al. Interleukin-16 stimulates the expression and production of pro-inflammatory cytokines by human monocytes. Immunol 2000; 100:63–69CrossRefGoogle Scholar
  84. 84.
    Jovanovic DV, Di Battista JA, Martel-Pelletier J, et al. IL-17 stimulates the production and expression of pro-inflammatory cytokines, IL-Iβ and TNFα by human macrophages. J Immunol 1998; 160:3513–3521PubMedGoogle Scholar
  85. 85.
    Basu S, Dunn AR, Marino MW, et al. Increased tolerance to endotoxin by granulocyte-macrophage colony stimulating factor deficient mice. J Immunol 1997; 159:1412–1417PubMedGoogle Scholar
  86. 86.
    Freeman BD, Ouezado Z, Zeni F, et al. G-CSF reduces endotoxemia and improves survival during E.coli pneumonia. J Appl. Physiol 1997; 83:1467–1475PubMedGoogle Scholar
  87. 87.
    Yalcin O, Soybir G, Koksoy F, et al. Effects of granulocyte colony-stimulating factor on bacterial translocation due to burn wound sepsis. Surgery Today 1997; 27:154–158PubMedCrossRefGoogle Scholar
  88. 88.
    Zhang P, Bagby GJ, Stoltz DA, et al. Enhancement of peritoneal leukocyte function by granulocyte colony-stimulating factor in rats with abdominal sepsis. Crit Care Med 1998; 26:315–321PubMedCrossRefGoogle Scholar
  89. 89.
    Villa P, Shakle CL, Meazza C, et al. Granulocyte colony stimulating factor and antibiotics in the prophylaxis of a murine model of polymicrobial peritonitis and sepsis. J Infect Dis 1998; 178:471–477PubMedGoogle Scholar
  90. 90.
    Opal SM, Jhung JW, Keith JC, et al. Additive effects of human recombinant interleukin-11 and granulocyte colony stimulating factor in experimental gram negative sepsis. Blood 1999; 93:3467–3472PubMedGoogle Scholar
  91. 91.
    Francois B, Trimoreau F, Vignon P, et al. Thrombocytopenia in the sepsis syndrome:role of hemophagocytosis and macrophage colony-stimulating factor. Am J Med 1997; 103:114–120PubMedCrossRefGoogle Scholar
  92. 92.
    Waring PM, Presneill J, Maher DW, et al. Differential alterations in plasma colony-stimulating factor concentrations in meningococcaemia. Clin Exper Immunol 1995; 102:501–506Google Scholar
  93. 93.
    Cairo MS, Suen Y, Knoppel E, et al. Decreased G-CSF and IL-3 production and gene expression from mononuclear cells of newborn infants. Pediatric Res 1992; 31:574–578CrossRefGoogle Scholar
  94. 94.
    Kantar M, Kultursay N, Kutukculer N, et al. Plasma concentration of granulocyte-macrophage colony stimulating factor and interleukin-6 in septic and healthy preterms. Eur J Pediat 2000; 159:156–157CrossRefGoogle Scholar
  95. 95.
    Ayala A, Chung CS, Xu YX, et al. Increased inducible apoptosis in CD4+ T lymphocytes during polymicrobial sepsis is mediated by Fas ligand and not endotoxin. Immunol 1999; 97:45–55CrossRefGoogle Scholar
  96. 96.
    Hashimoto S, Kobayashi A, Kooguchi K, et al. Upregulation of two death pathways of perforin/granzyme and FasL/Fas in septic acute respiratory distress syndrome. Am J Resp Crit Care Med 2000; 161:237–243PubMedGoogle Scholar
  97. 97.
    David JR. Delayed hypersensitivity in vitro. Its mediation by cell free substances formed by lymphoid cell-antigen interaction. Proc Natl Acad Sci USA 1966; 65:72–77CrossRefGoogle Scholar
  98. 98.
    Bernhagen J, Calandra T, Mitchell RA, et al. MIF is a pituitary-derived cytokine that potentiates lethal endotoxaemia. Nature 1993; 365:756–759PubMedCrossRefGoogle Scholar
  99. 99.
    Calandra T, Bernhagen J, Mitchell RA, et al. The macrophage is an important and previously unrecognized source of macrophage migration inhibitory factor. J Exp Med 1994; 179:1895–1902PubMedCrossRefGoogle Scholar
  100. 100.
    Calandra T, Bernhagen J, Metz CN, et al. MIF as a glucocorticoid-induced modulator of cytokine production. Nature 1995; 376:68–71CrossRefGoogle Scholar
  101. 101.
    Bacher M, Meinhardt A, Lan HY, et al. Migration inhibitory factor expression in experimentally induced endotoxemia. Am J Pathol 1997; 150:235–246PubMedGoogle Scholar
  102. 102.
    Bozza M, Satoskar AR, Lin G, et al. Targeted disruption of migration inhibitory factor gene reveals its critical role in sepsis. J Exp Med 1999; 189:341–346PubMedCrossRefGoogle Scholar
  103. 103.
    Calandra T, Echtenacher B, Le Roy D, et al. Protection from septic shock by neutralization of macrophage migration inhibitory factor. Nature Med. 2000; 6:164–170PubMedCrossRefGoogle Scholar
  104. 104.
    Wang H, Bloom O, Zhang M, et al. HMG-1 as a late mediator of endotoxin lethality in mice. Science 1999; 285:248–251PubMedCrossRefGoogle Scholar
  105. 105.
    Wulczyn FG, Krappmann D, Scheidereit C. The NF-kB/Rel and IkB families: mediators of immune response and inflammation. J Mol Med 1996; 74:749–769PubMedCrossRefGoogle Scholar
  106. 106.
    Baldwin AS. The NF-κB and IκB proteins: new discoveries and insights. Ann Rev Immunol 1996; 14:649–681CrossRefGoogle Scholar
  107. 107.
    Ghosh S, May MJ, Kopp EB. NF-κB and Rel proteins: evolutionarily conserved mediators of immune responses. Ann Rev Immunol 1998; 16:225–260CrossRefGoogle Scholar
  108. 108.
    Schmitz ML, Baeuerle PA. The p65 subunit is responsible for the strong transcription activating potential of NF-κ, EMBO J 1991; 10:3805–3817PubMedGoogle Scholar
  109. 109.
    Ballard DW, Dixon EP, Peffer NJ, et al. The 65-kDa subunit of human NF-κB functions as a potent transcriptional activator and target for v-Rel-mediated repression. Proc Natl Acad Sci USA 1992; 89:1875–1879PubMedCrossRefGoogle Scholar
  110. 110.
    Bours V, Burd PR, Brown K, et al. A novel mitogen-induced gene product related to p50/p105-NF-κB participates in transactivation through a κB site. Mol Cell Biol 1992; 12:685–695PubMedGoogle Scholar
  111. 111.
    Kretzschmar M, Meisterernst M, Scheidereit C, et al. Transcriptinal regulation of the HIV-1 promoter by in vitro. Genes Developement 1992; 6:761–774CrossRefGoogle Scholar
  112. 112.
    Fujita T, Nolan GP, Liou H-C, et al. The candidate proto-oncogene bcl-3 encodes a transcriptional coactivator that activates through NF-κB p50 homodimers. Genes Development 1993; 7:1354–1363PubMedCrossRefGoogle Scholar
  113. 113.
    Moore PA, Ruben SM, Rosen CA. Conservation of transcriptional activation functions of the NF-κB p50 and p65 subunits in mammalian cells and Saccharomyces cerevisiae. Mol Cell Biol 1993; 13:1666–1674PubMedGoogle Scholar
  114. 114.
    Franzoso G, Bours V, Azarenko V, et al. The oncoprotein Bcl-3 can facilitate NF-κB-mediated transactivation by removing inhibiting p50 homodimers from select κB sites. The EMBO J 1993; 12:3893–3901Google Scholar
  115. 115.
    Medzhitov R, Preston-Hurlburt P, Janeway CA. A human homologue of the Drosophila Toll protein signals activation of adaptative immunity. Nature 1997; 388:394–397PubMedCrossRefGoogle Scholar
  116. 116.
    Shimazu R, Akashi S, Ogata H, et al. MD-2, a molecule that confers lipopolysac-charide responsiveness on Toll-like receptor 4. J Exp Med 1999; 189:1777–1782PubMedCrossRefGoogle Scholar
  117. 117.
    Malinin NL, Boldin MP, Kovalenko AV, et al. Map3k-related kinase involved in NF-κB induction by TNF, CD95 and IL-1. Nature 1997; 385:540–544PubMedCrossRefGoogle Scholar
  118. 118.
    Di Donato JA, Hayakawa M, Rothwarf DM, et al. A cytokine-responsive IκB kinase that activates the transcription factor NF-κB Nature 1997; 388:548–554CrossRefGoogle Scholar
  119. 119.
    Hirano M, Osada S-I, Aoki T, et al. MEK kinase is involved in tumor necrosis factor α-induced NF-κB activation and degradation of IκB-α. J Biol Chem 1996; 271:13234–13238PubMedCrossRefGoogle Scholar
  120. 120.
    Burns K, Clatworthy J, Martin L, et al. Tollip, a new componet of the IL-1RI pathway, links IRAK to the IL-1 receptor. Nature Cell Biol 2000; 2:346–351PubMedCrossRefGoogle Scholar
  121. 121.
    Kopp E, Medzhitov R, Carothers J, et al. ECSIT is an evolutionary conserved intermediate in the Toll/IL-1 signal transduction pathway. Genes and Development 1999; 13:2059–2071PubMedCrossRefGoogle Scholar
  122. 122.
    Westwick JK, Weitzel C, Minden A, et al. Tumor necrosis factor-α stimulates AP-1 activity through prolonged activation of the c-jun kinase. J Biol Chem 1994; 269:26396–26401PubMedGoogle Scholar
  123. 123.
    Raingeaud J, Gupta S, Rogers JS, et al. Pro-inflammatory cytokines and environmental stress cause p38 mitogen-activated protein kinase activation by dual phosphorylation on tyrosine and threonine. J Biol Chem 1995; 2070:7420–7426Google Scholar
  124. 124.
    Wesselborg S, Bauer MKA, Vogt M, et al. Activation of transcription factor NF-κB and p38 mitogen-activated protein kinase is mediated by distinct and separed stress effector pathways. J Biol Chem 1997; 272:12422–12429PubMedCrossRefGoogle Scholar
  125. 125.
    Liu ZG, Hsu HL, Goeddel DV, et al. Dissection of TNF receptor 1 effector functions: JNK activation is not linked to apoptosis while NF-kappa B activation prevents cell death. Cell 1996; 87:565–576PubMedCrossRefGoogle Scholar
  126. 126.
    Yuasa T, Ohno S, Kehrl JH, et al. Tumor necrosis factor signaling to stress-activated protein kinase (SAPK)/Jun NH2-terminal kinase (JNK) and p38. J Biol Chem 1998; 273:22681–22692PubMedCrossRefGoogle Scholar
  127. 127.
    Kanakaraj P, Schafer PH, Cavender DE, et al. Interleukin (IL)-l receptor-associated kinase (IRAK) requirement for optimal induction of multiple IL-1 signaling pathways and IL-6 production. J Exp Med 1998; 187:2073–2079PubMedCrossRefGoogle Scholar
  128. 128.
    Burns K, Martinon F, Esslinger C, et al. MyD88, an adapter protein involved in interleukin-1 signaling. J Biol Chem 1998; 273:12203–12209PubMedCrossRefGoogle Scholar
  129. 129.
    Moine P, McIntyre R, Schwartz MD, et al. NF-κB regulatory mechanisms in alveolar macrophages from patients with acute respiratory distress syndrome. Shock 2000; 13:85–91PubMedGoogle Scholar
  130. 130.
    Williams DL, Ha T, Li C, et al. Early activation of hepatic NF-κB and NFIL6 in polymicrobial sepsis correlates with bacterremia, cytokine expression and mortality. Ann Surgery 1999; 230:95–104CrossRefGoogle Scholar
  131. 131.
    Browder W, Ha T, Li C, et al. Early activation of pulmonary NF-κB and NFIL6 in polymicrobial sepsis. J Trauma Injury Infect Crit Care 1999; 46:590–596CrossRefGoogle Scholar
  132. 132.
    Shenkar R, Abraham E. Mechanisms of lung neutrophil activation after hemorrhage or endotoxeniia: roles of reactive oxygen intermediates, NF-κB and cyclic AMP response element binding protein. J Immunol 1999; 163:954–962PubMedGoogle Scholar
  133. 133.
    Annane D, Sanquer S, Sébille V, et al. Compartmentalised inducible nitric-oxide synthase activity in septic shock. The Lancet 2000; 355:1143–1148CrossRefGoogle Scholar
  134. 134.
    Keel M, Ecknauer E, Stocker R, et al. Different pattern of local and systemic release of proinflammatory and anti-inflammatory mediators in severely injured patients with chest trauma. J Trauma 1996; 40:907–914PubMedCrossRefGoogle Scholar
  135. 135.
    Jacobs RF, Tabor DR, Burks AW, et al. Elevated interleukin-1 release by human alveolar macrophages during adult respiratory distress syndrome. Am Rev Respir Dis 1989; 140:1686–1692PubMedGoogle Scholar
  136. 136.
    Fieren MWJA, Van Den Bemd GJ, Bonta IL. Endotoxin-stimulated peritoneal macrophages obtained from continuous ambulatory peritoneal dialysis patients show an increased capacity to release interleukin-1β in vitro during infectious peritonitis. Eur J Clin Invest 1990; 20:453–457PubMedCrossRefGoogle Scholar
  137. 137.
    Böhrer H, Qiu F, Zimmermann T, et al. Role of NF-κB in the mortality of sepsis. J Clin Invest 1997; 100:972–985PubMedCrossRefGoogle Scholar
  138. 138.
    Adib-Conquy M, Adrie C, Moine P, et al. NF-κB expression in mononuclear cells of septic patients resembles that observed in LPS-tolerance. Am J Respir Crit Care Med 2000; 162:1877–1883PubMedGoogle Scholar
  139. 139.
    Reisinger EC, Kern P, Ernst M, et al. Inhibition of HIV progression by dithiocard. Lancet 1990; 335:679–682PubMedCrossRefGoogle Scholar
  140. 140.
    Liu SF, Ye X, Malik AB. In vivo inhibition of nuclear factor-κB activation prevents inducible nitric oxide synthase expression and systemic hypotension in a rat model of septic shock. J Immunol. 1997; 159:3976–3983PubMedGoogle Scholar
  141. 141.
    Schow SR, Joly A. N-acetyl-leucinyl-leucinyl-norleucinal inhibits lipopolysaccharide-induced NF-κB activation and prevents TNF and IL-6 synthesis in vivo. Cell Immunol 1997; 175:199–202PubMedCrossRefGoogle Scholar
  142. 142.
    Liu SF, Ye X, Malik AB. Pyrrolidine dithiocarbamate prevents I-κB degradation and reduces microvascular injury induced by lipopolysacchride in multiple organs. Mol Pharmacol 1999; 55:658–667PubMedGoogle Scholar
  143. 143.
    Drollinger AG, Netser JC, Rodgers GM. Dithiocarbamates ameliorate the effects of endotoxin in a rabbit model of disseminated intravascular coagulation. Sem Thromb Hemost 1999; 25:429–433CrossRefGoogle Scholar
  144. 144.
    Tilg H, Trehu E, Atkins MB, et al. Interleukin-6 (IL-6) as an anti-inflammatory cytokine: induction of circulating IL-1 receptor antagonist and soluble tumor necrosis factor receptor p55. Blood 1994; 83:113–118PubMedGoogle Scholar
  145. 145.
    Hack C, de Groot E, Felt-Bersma R, et al. Increased plasma levels of interleukin-6 in sepsis. Blood 1989; 74:1704–1710PubMedGoogle Scholar
  146. 146.
    Calandra T, Gerain J, Heumann D, et al. High circulating levels of interleukin-6 in patients with septic shock: evolution during sepsis, prognostic value, and interplay with other cytokines. Am J Med 1991; 91:23–29PubMedCrossRefGoogle Scholar
  147. 147.
    Damas P, Ledoux D, Nys M, et al. Cytokine serum level during severe sepsis in human IL-6 as a marker of severity. Ann Surg 1992; 215:356–362PubMedGoogle Scholar
  148. 148.
    Yoshimoto T, Nakanishi K, Hirose S, et al. High serum IL-6 level reflects susceptible status of the host to endotoxin and IL-1/TNF. J Immunol 1992; 148:3596–3603PubMedGoogle Scholar
  149. 149.
    Fong Y, Moldawer LL, Marano M, et al. Endotoxemia elicits increased circulating beta 2-IFN/IL-6 in man. J Immunol 1989; 142:2321–2324PubMedGoogle Scholar
  150. 150.
    van Deventer SJH, Büller HR, ten Cate JW, et al. Experimental endotoxemia in humans:analysis of cytokine release and coagulation, fibrinolytic and complement pathways. Blood 1990; 76:2520–2526PubMedGoogle Scholar
  151. 151.
    Gabay C, Singwe M, Genin B, et al. Circulating levels of IL-11 and leukaemia inhibitory factor (LIF) do not significantly participate in the production of acute-phase proteins by the liver. Clin Exp Immunol 1996; 105:260–265PubMedCrossRefGoogle Scholar
  152. 152.
    Du XX, Doerschuk CM, Orazi A, et al. A bone marrow stromal-derived growth factor, interleukin-11,, stimulates recovery of small intestinal mucosal cells after cytoablative therapy. Blood 1994; 83:33–37PubMedGoogle Scholar
  153. 153.
    Chang M, Williams A, Ishizawa L, et al. Endogenous interleukin-11 (IL-11) expression is increased and prophylactic use of exogenous IL-11 enhances platelet recovery and improves survival during thrombocytopenia associated with experimental group B streptococcal sepsis in neonatal rats. Blood Cells Mol & Dis 1996; 22:57–67CrossRefGoogle Scholar
  154. 154.
    Endo S, Inada K, Arakawa N, et al. Interleukin-11 in patients with disseminated intravascular coagulation. Res Com Mol Pathol Pharmac 1996; 91:253–256Google Scholar
  155. 155.
    Gabay C, Smith MF, Eidlen D, et al. Interleukin-1 receptor antagonist is an acute phase protein. J Clin Invest 1997; 99:2930–2940PubMedCrossRefGoogle Scholar
  156. 156.
    Aiura K, Gelgand J, Burke J, et al. Interleukin-1 receptor antagonist prevents S. epidermidis hypotension and reduces circulating levels of TNF and IL-1β in rabbits. Infect Immun 1993; 61:3342–3350PubMedGoogle Scholar
  157. 157.
    Fischer E, Marano MA, Van Zee KJ, et al. Interleukin-1 receptor blockade improves survival and hemodynamic performance in Escherichia coli septic shock, but fails to alter host responses to sublethal endotoxemia. J Clin Invest 1992; 89:1551–1557PubMedCrossRefGoogle Scholar
  158. 158.
    Mancilla J, Garcia P, Dinarello CA. The interleukin-1 receptor antagonist can either reduce or enhance the lethality of Klebsiella pneumoniae sepsis in newborn rats. Infect Immun 1993; 61:926–932PubMedGoogle Scholar
  159. 159.
    Hirsch E, Irikura VM, Paul SM, et al. Functions of interleukin 1 receptor antagonist in gene knockout and overproducing mice. Proc Natl Acad Sci Usa 1996; 93:11008–11013PubMedCrossRefGoogle Scholar
  160. 160.
    Fischer E, Van Zee KJ, Marano MA, et al. Interleukin-1 receptor antagonist circulates in experimental inflammation and in human disease. Blood 1992; 79:2196–2200PubMedGoogle Scholar
  161. 161.
    Rogy MA, Coyle SM, Oldenburg HS, et al. Persistently elevated soluble tumor necrosis factor receptor and interleukin-1 receptor antagonist levels in critically ill patients. J Am Coll Surg 1994; 178:132–138PubMedGoogle Scholar
  162. 162.
    Cavaillon JM, Müller-Alouf H, Alouf JE. Cytokines in streptococcal infections. An opening lecture. Adv Exper Med Biol 1997; 418:869–879Google Scholar
  163. 163.
    Marie C, Cavaillon JM. Negative feedback in inflammation: the role of antiinflammatory cytokines. Bull Inst Pasteur 1997; 95:41–54CrossRefGoogle Scholar
  164. 164.
    Preas HL, Reda D, Tropea M, et al. Effects of recombinant soluble type i interleukin-1 receptor on human inflammatory responses to endotoxin. Blood 1996; 88:2465–2472PubMedGoogle Scholar
  165. 165.
    Giri JG, Wells J, Dower SK, et al. Elevated levels of shed type II IL-1 receptor in sepsis. Potential role for type II receptor in regulation of IL-1 responses. J Immunol 1994; 153:5802–5809PubMedGoogle Scholar
  166. 166.
    Pruitt JH, B WM, Edwards PD, et al. Increased soluble interleukin-1 type II receptor concentrations in postoperative patients and in patients with sepsis syndrome. Blood 1996; 87:3282–3288PubMedGoogle Scholar
  167. 167.
    Lesslauer W, Tabuchi H, Gentz R, et al. Recombinant soluble tumor necrosis factor receptor proteins protect mice from LPS-induced lethality. Eur. J. Immunol. 1991; 21:2883–2886PubMedCrossRefGoogle Scholar
  168. 168.
    Ashkenazi A, Marsters S, Capon D, et al. Protection against endotoxic shock by a tumor necrosis factor receptor immunoadhesin. Proc. Natl. Acad. Sci. 1991; 88:10535–10539PubMedCrossRefGoogle Scholar
  169. 169.
    Girardin E, Roux-Lombard P, Grau GE, et al. Imbalance between tumour necrosis factoralpha and soluble TNF receptor concentrations in severe meningococcaemia. Immunology 1992; 76:20–23PubMedGoogle Scholar
  170. 170.
    Van Zee KJ, Kohno T, Fischer E, et al. Tumor necrosis factor soluble receptors circulate during experimental and clinical inflammation and can protect against excessive tumor necrosis factor alpha in vitro and in vivo. Proc Natl Acad Sci U S A 1992; 89:4845–4849PubMedCrossRefGoogle Scholar
  171. 171.
    van der Poll T, Jansen J, van Leenen D, et al. Release of soluble receptors for tumor necrosis factor in clinical sepsis and experimental endotoxemia. J Infect Dis 1993; 168:955–960PubMedGoogle Scholar
  172. 172.
    van der Poll T, Fischer E, Coyle SM, et al. Interleukin-1 contributes to increased concentrations of soluble tumor necrosis factor receptor type I in sepsis. J Infect Dis 1995; 172:577–580PubMedGoogle Scholar
  173. 173.
    Lantz M, Malik S, Slevin ML, et al. Infusion of tumor necrosis factor (TNF) causes an increase in circulating TNF-binding protein in humans. Cytokine 1990; 2:402–406PubMedCrossRefGoogle Scholar
  174. 174.
    Gérard C, Bruyns C, Merchant A, et al. Interleukin-10 reduces the release of tumor necrosis factor and prevents lethality in experimental endotoxemia. J. Exp. Med. 1993; 177:547–550PubMedCrossRefGoogle Scholar
  175. 175.
    Berg D, Kühn R, Rajewsky K, et al. Interleukin-10 is a central regulator of the response to LPS in murine models of endotoxin shock and the Shwartzman reaction but not endotoxin tolerance. J. Clin. Invest. 1995; 96:2339–2347PubMedCrossRefGoogle Scholar
  176. 176.
    Standiford TJ, Strieter RM, Lukacs NW, et al. Neutralization of IL-10 lethality in endotoxemia. J Immunol 1995; 155:2222–2229PubMedGoogle Scholar
  177. 177.
    van der Poll T, Marchant A, Buurman WA, et al. Endogenous IL-10 protects mice from death during septic peritonitis. J Immunol 1995; 155:5397–5401PubMedGoogle Scholar
  178. 178.
    Donnelly SC, Strieter RM, Reid PT, et al. The association between mortality rates and decreased concentrations of interleukin-10 and interleukin-1 receptor antagonist in the lung fluids of patients with the adult respiratory distress syndrome. Ann Intern Med 1996; 125:191–196PubMedGoogle Scholar
  179. 179.
    Merchant A, Devière J, Byl B, et al. Interleukin-10 production during septicaemia. Lancet 1994; 343:707–708CrossRefGoogle Scholar
  180. 180.
    Derkx B, Marchant A, Goldman M, et al. High levels of interleukin-10 during the initial phase of fulminant meningococcal septic shock. J Infect Dis 1995; 171:229–232PubMedGoogle Scholar
  181. 181.
    Van Dissel JT, van Langevelde P, Westendorp RGJ, et al. Anti-inflammatory cytokine profile and mortality in febrile patients. Lancet 1998; 351:950–953PubMedGoogle Scholar
  182. 182.
    Bone RC, Grodzin CJ, Balk RA. Sepsis:A new hypothesis for pathogenesis of the disease process. Chest 1997; 121:235–243CrossRefGoogle Scholar
  183. 183.
    Brandtzaeg P, Osnes L, Øvstebø R, et al. Net inflammatory capacity of human septic shock plasma evaluated by a monocyte-based target cell assay: identification of interleukin-10 as a major functional deactivator of human monocytes. J Exp Med 1996; 184:51–60PubMedCrossRefGoogle Scholar
  184. 184.
    Sawyer RG, Rosenlof LK, Pruett TL. Interleukin-4 prevents mortality from acute but not chronic murine peritonitis and induces an accelarated TNF response. Eur Surg Res 1996; 28:119–123PubMedCrossRefGoogle Scholar
  185. 185.
    Brunet LR, Finkelman FD, Cheever AW, et al. IL-4 protects against TNF-α-mediated cachexia and death during acute shistosomiasis. J Immunol 1997; 159:777–785PubMedGoogle Scholar
  186. 186.
    Giampietri A, Grohmann U, Vacca C, et al. Dual effect of IL-4 on resistance to systemic gram-negative infection and production of TNFα Cytokine 2000; 12:417–421PubMedCrossRefGoogle Scholar
  187. 187.
    Cavaillon J-M, Adib-Conquy M. The pro-inflammatory cytokine cascade. In Immune response in the critically ill. In:Marshal, J.C., Vincent J.L. (Eds) Update in Intensive Care and Emergency Medicine, — Springer — 2000; Vol. 31:37–66Google Scholar
  188. 188.
    Muchamuel T, Menon S, Pisacane P, et al. IL-13 protects mice from lipopolysaccharide-induced lethal endotoxemia — Correlation with down-modulation of TNFα, IFN-γ and IL-12 production. J Immunol 1997; 158:2898–2903PubMedGoogle Scholar
  189. 189.
    Nicoletti F, Mancuso G, Cusumano V, et al. Prevention of endotoxin-induced lethality in neonatal mice by interleukin-13. Eur J Immunol 1997; 27:1580–1583PubMedCrossRefGoogle Scholar
  190. 190.
    Matsukawa A, Hogaboam CM, Lukacs NW, et al. Expression and contribution of endogenous IL-13 in an experimental model of sepsis. J Immunol 2000; 164:2738–2744PubMedGoogle Scholar
  191. 191.
    van der Poll T, de Waal Malefyt R, Coyle SM, et al. 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. J Infect Dis 1997; 175:118–122PubMedGoogle Scholar
  192. 192.
    Grohmann U, Van Snick J, Campanile F, et al. IL-9 protects mice from Gram-negative bacterial shock: suppression of TMFα IL-12 and IFNγ and induction of IL-10. J Immunol 2000; 164:4197–4203PubMedGoogle Scholar
  193. 193.
    Urbaschek R, Urbaschek B. Induction of endotoxin tolerance by endotoxin, its mediators and by monophosphoryl lipid A. In Nowotny, A. Spitzer, J.J., Ziegler, E.J. (Eds) Endotoxin Research Series, Elsevier Science Publ. 1990; 455–463Google Scholar
  194. 194.
    Perrella MA, Hsieh CM, Lee WS, et al. Arrest of endotoxin induced hypotension by transforming growth factor-β1 Proc Natl Acad Sci USA 1996; 93:2054–2059PubMedCrossRefGoogle Scholar
  195. 195.
    Karres I, Kremer JP, Sterckholzer U, et al. Transforming growth factor-β1 inhibits synthesis of cytokines in endotoxin-stimulated human whole blood. Arch Surg 1996; 131:1310–1317PubMedGoogle Scholar
  196. 196.
    Astiz M, Saha D, Lustbader D, et al. Monocyte response to bacterial toxins, expression of cell surface receptors, and release of anti-inflammatory cytokines during sepsis. J Lab Clin Med 1996; 128:597–600CrossRefGoogle Scholar
  197. 197.
    Marie C, Cavaillon J-M, Losser M-R. Elevated levels of circulating transforming growth factor-β1 in patients with the sepsis syndrome. Ann Intern Med 1996; 125:520–521PubMedGoogle Scholar
  198. 198.
    Marie C, Losser MR, Fitting C, et al. Cytokines and soluble cytokines receptors in pleural effusions from septic and nonseptic patients. Am J Respir Crit Care Med 1997; 156:1515–1522PubMedGoogle Scholar
  199. 199.
    Junger WG, Hoyt DB, Redl H, et al. Tumor necrosis factor antibody treatment of septic baboons reduces the production of sustained T-cell suppressive factors. Shock 1995; 3:173–178PubMedCrossRefGoogle Scholar
  200. 200.
    Ahmad S, Choudhry MA, Shankar R, et al. Transforming growth factor-β negatively modulates T-cell responses in sepsis. FEBS letters 1997; 402:213–218PubMedCrossRefGoogle Scholar
  201. 201.
    Tzung SP, Mahl TC, Lance P, et al. Interferon-alpha prevents endotoxin-induced mortality in mice. Eur J Immunol 1992; 22:3097–3101PubMedCrossRefGoogle Scholar
  202. 202.
    Wood J, Rodrick M, O’Mahony J, et al. Inadequate interleukin 2 production. A fundamental immunological deficiency in patients with major burns. Ann. Surg. 1984; 200:311–320PubMedCrossRefGoogle Scholar
  203. 203.
    Ertel W, Keel M, Neidhardt R, et al. Inhibition of the defense system stimulating interleukin-12 interferon-γ pathway during critical illness. Blood 1997; 89:1612–1620PubMedGoogle Scholar
  204. 204.
    Muret J, Marie C, Fitting C, et al. Ex vivo T-lymphocyte derived cytokine production in SIRS patients is influenced by experimental procedures. Shock 2000; 13:169–174PubMedGoogle Scholar
  205. 205.
    Muñoz C, Carlet J, Fitting C, et al. Dysregulation of in vitro cytokine production by monocytes during sepsis. J Clin Invest 1991; 88:1747–1754PubMedCrossRefGoogle Scholar
  206. 206.
    Van Deuren M, Van Der Ven-Jongekrijg H, Demacker PNM, et al. Differential expression of proinflammatory cytokines and their inhibitors during the course of meningococcal infections. J. Infect. Dis. 1994; 169:157–161PubMedGoogle Scholar
  207. 207.
    Marchant A, Alegre M, Hakim A, et al. Clinical and biological significance of interleukin-10 plasma levels in patients with septic shock. J Clin Immunol 1995; 15:265–272CrossRefGoogle Scholar
  208. 208.
    Randow F, Syrbe U, Meisel C, et al. Mechanism of endotoxin desensitization:involvement of interleukin 10 and transforming growth factor β, J. Exp. Med. 1995; 181:1887–1892PubMedCrossRefGoogle Scholar
  209. 209.
    Luger A, Graf H, Schwarz HP, et al. Decreased serum interleukin-1 activity and monocytes interleukin-1 production in patients with fatal sepsis. Crit Care Med. 1986; 14:458–461PubMedCrossRefGoogle Scholar
  210. 210.
    Cavaillon J-M, Muñoz C, Marty C, et al. (1993). Cytokine production by monocytes from patients with sepsis syndrome and by endotoxin-tolerant monocytes, In: Levin, J, Alving, C R, Munford, R S, Stütz, P L (Eds) Bacterial endotoxin:recognition and effector mechanisms. Elsevier Sc. Publ. 1993:275–284Google Scholar
  211. 211.
    McCall CE, Grosso-Wilmoth LM, LaRue K, et al. Tolerance to endotoxin-induced expression of the interleukin-1β gene in blood neutrophils of humans with the sepsis syndrome. J Clin Invest 1993; 91:853–861PubMedCrossRefGoogle Scholar
  212. 212.
    Marie C, Muret J, Fitting C, et al. Reduced ex vivo interleukin-8 production by neutrophils in septic and non-septic systemic inflammatory response syndrome. Blood 1998; 91:3439–3446PubMedGoogle Scholar
  213. 213.
    Marie C, Muret J, Fitting C, et al. IL-1 receptor antagonist production during infectious and noninfectious systemic inflammatory response syndrome. Crit. Care Med. 2000; 28:2277–2283PubMedCrossRefGoogle Scholar
  214. 214.
    Cavaillon JM. The nonspecific nature of endotoxin tolerance. Trends Microbiol 1995; 3:320–324PubMedCrossRefGoogle Scholar
  215. 215.
    Cavaillon J-M. Possibilities and problems of cytokine measurements (IN:Redl, H. and Schlag G. (Eds). Progress in Inflammation Research. Birkäuser 1999:95–119Google Scholar
  216. 216.
    Cavaillon JM, Muñoz C, Fitting C, et al. Circulating cytokines:the tip of the iceberg? Cire Shock 1992; 38:145–152Google Scholar
  217. 217.
    Hauser CJ, Zhou X, Joshi P, et al. The immune microenvironment of human fracture/soft-tissue hematomas and its relationship to systemic immunity. J Trauma Injury Infect Critl Care 1997; 42:895–903CrossRefGoogle Scholar
  218. 218.
    Armstrong L, Thickett DR, Christie SJ, et al. Increased Expression of Functionally Active Membrane-Associated Tumor Necrosis Factor in Acute Respiratory Distress Syndrome. Am. J. Respir. Cell Mol. Biol. 2000; 22:68–74PubMedGoogle Scholar
  219. 219.
    Yentis SM, Rowbottom AW, Riches PG. Detection of cytoplasmic IL-1β in peripheral blood mononuclear cells from intensive care unit patients. Clin Exp Immunol 1995; 100:330–335PubMedGoogle Scholar
  220. 220.
    Donnelly S, Strieter R, Kunkel S, et al. Interleukin-8 and development of adult respiratory distress syndrom in at-risk patients groups. Lancet 1993; 341:643–647PubMedCrossRefGoogle Scholar

Copyright information

© Kluwer Academic Publishers 2002

Authors and Affiliations

  • Jean-Marc Cavaillon
  • Minou Adib-Conquy

There are no affiliations available

Personalised recommendations