Advertisement

Activation of the Innate Immune Response in Critical Illness

  • Andreas Oberholzer
  • Caroline Oberholzer
  • Lyle L. Moldawer
Chapter
  • 130 Downloads
Part of the Molecular and Cellular Biology of Critical Care Medicine book series (MCCM, volume 3)

Abstract

Recognition molecules, inflammatory cells, and the cytokines they produce are the principle means for host tissues to recognize invading microbes, and to initiate intercellular communication between the innate and acquired immune systems. However, activation of host innate immunity may also occur in the absence of microbial recognition, through expression of internal “danger signals” produced by tissue ischemia and necrosis, or through the release of free radicals. When activation of the innate immune system is severe enough, the host response itself can propel the patient into a systemic inflammatory response syndrome (SIRS), or even multi-system organ failure (MSOF) and shock. Although the majority of patients survive the initial SIRS insult, these patients remain at increased risk of developing secondary or opportunistic infections due to the frequent onset of a compensatory anti-inflammatory response syndrome (CARS). The initial activation of the innate immune response often leads to macrophage deactivation, T-cell anergy, and the rapid apoptotic loss of lymphoid tissues, which all contribute to the development of this CARS syndrome and its associated morbidity and mortality. Initial efforts to treat the septic and critically ill patient with anti-cytokine therapies directed at the SIRS response have been disappointing, and therapeutic efforts to modify the immune response during sepsis syndromes will require a more thorough understanding of the innate and acquired immune responses.

Keywords

Natural Killer Cell Septic Shock Innate Immune Response Systemic Inflammatory Response Syndrome Innate Immune System 
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.

References

  1. 1.
    Fearon, D.T. and R.M. Locksley. 1996. The instructive role of innate immunity in the acquired immune response. Science 272:50–53.PubMedGoogle Scholar
  2. 2.
    Janeway, C.A.J. 1992. The immune system evolved to discriminate infectious nonself from noninfectious self. Immunol.Today 13:11–16.PubMedGoogle Scholar
  3. 3.
    Matzinger, P. 1994. Tolerance, danger, and the extended family. Annu.Rev.Immunol. 12:991–1045:991–1045.PubMedGoogle Scholar
  4. 4.
    Bendelac, A. and D.T. Fearon. 1997. Innate pathways that control acquired immunity [editorial]. Curr.Opin.Immunol. 9:1–3.PubMedGoogle Scholar
  5. 5.
    Brown, E., J.P. Atkinson, and D.T. Fearon. 1994. Innate immunity: 50 ways to kill a microbe. Curr.Opin.Immunol. 6:73–74.PubMedGoogle Scholar
  6. 6.
    Ezekowitz, R.B. and J.A. Hoffmann. 1996. Innate immunity. Curr.Opin.Immunol. 8:1–2.PubMedGoogle Scholar
  7. 7.
    Oberholzer, A., C. Oberholzer, and L.L. Moldawer. 2000. Cytokine signaling--regulation of the immune response in normal and critically ill states. Crit.Care Med. 28:N3–12.PubMedGoogle Scholar
  8. 8.
    Janeway, C.A.J. 2001. How the immune system works to protect the host from infection: a personal view. Proc.Natl.Acad.Sci.U.S.A. 98:7461–7468.PubMedGoogle Scholar
  9. 9.
    Beutler, B. 2000. Endotoxin, toll-like receptor 4, and the afferent limb of innate immunity. Curr.Opin.Microbiol. 3:23–28.PubMedGoogle Scholar
  10. 10.
    O’Neill, L.A. and C.A. Dinarello. 2000. The IL-1 receptor/toll-like receptor superfamily: crucial receptors for inflammation and host defense [In Process Citation]. Immunol.Today 21:206–209.PubMedGoogle Scholar
  11. 11.
    Brightbill, H.D., D.H. Libraty, S.R. Krutzik, R.B. Yang, J.T. Belisle, J.R. Bleharski, M. Maitland, M.V. Norgard, S.E. Plevy, S.T. Smale, P.J. Brennan, B.R. Bloom, P.J. Godowski, and R.L. Modlin. 1999. Host defense mechanisms triggered by microbial lipoproteins through toll-like receptors. Science 285:732–736.PubMedGoogle Scholar
  12. 12.
    Schwandner, R., R. Dziarski, H. Wesche, M. Rothe, and C.J. Kirschning. 1999. Peptidoglycan- and lipoteichoic acid-induced cell activation is mediated by toll-like receptor 2. J.Biol.Chem. 274:17406–17409.PubMedGoogle Scholar
  13. 13.
    Yoshimura, A., E. Lien, R.R. Ingalls, E. Tuomanen, R. Dziarski, and D. Golenbock. 1999. Cutting edge: recognition of Gram-positive bacterial cell wall components by the innate immune system occurs via Toll-like receptor 2. J.Immunol. 163:1–5.PubMedGoogle Scholar
  14. 14.
    Takeshita, F., C.A. Leifer, I. Gursel, K.J. Ishii, S. Takeshita, M. Gursel, and D.M. Klinman. Cutting edge: role of toll-like receptor 9 in cpg dna-induced activation of human cells. J.Immunol.2001.Oct.l.;167.(7.):3555.-8. 167:3555–3558.PubMedGoogle Scholar
  15. 15.
    Klinman, D.M., A.K. Yi, S.L. Beaucage, J. Conover, and A.M. Krieg. 1996. CpG motifs present in bacteria DNA rapidly induce lymphocytes to secrete interleukin 6, interleukin 12, and interferon gamma. Proc.Natl.Acad.Sci.U.S.A. 93:2879–2883.PubMedGoogle Scholar
  16. 16.
    Schnare, M., G.M. Barton, A.C. Holt, K. Takeda, S. Akira, and R. Medzhitov. 2001. Toll-like receptors control activation of adaptive immune responses. Nat.Immunol. 2:947–950.PubMedGoogle Scholar
  17. 17.
    Gabay, C. and I. Kushner. 1999. Acute-phase proteins and other systemic responses to inflammation. N.Engl.J.Med. 340:448–454.PubMedGoogle Scholar
  18. 18.
    Qureshi, S.T., L. Lariviere, G. Leveque, S. Clermont, K.J. Moore, P. Gros, and D. Malo. 1999. Endotoxin-tolerant mice have mutations in Toll-like receptor 4 (Tlr4) [see comments] [published erratum appears in J Exp Med 1999 May 3;189(9):following 1518]. J.Exp.Med. 189:615–625.PubMedGoogle Scholar
  19. 19.
    Poltorak, A., X. He, I. Smirnova, M.Y. Liu, C.V. Huffel, X. Du, D. Birdwell, E. Alejos, M. Silva, C. Galanos, M. Freudenberg, P. Ricciardi-Castagnoli, B. Layton, and B. Beutler. 1998. Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science 282:2085–2088.PubMedGoogle Scholar
  20. 20.
    Akira, S., K. Takeda, and T. Kaisho. 2001. Toll-like receptors: critical proteins linking innate and acquired immunity. Nat.Immunol. 2:675–680.PubMedGoogle Scholar
  21. 21.
    Kaisho, T. and S. Akira. 2001. Dendritic-cell function in Toll-like receptor- and MyD88-knockout mice. Trends.Immunol. 22:78–83.PubMedGoogle Scholar
  22. 22.
    Huang, Q., D. Liu, P. Majewski, L.C. Schulte, J.M. Korn, R.A. Young, E. Lander, and N. Hacohen. 2001. The plasticity of dendritic cell responses to pathogens and their components. Science 294:870–875.PubMedGoogle Scholar
  23. 23.
    Tobias, P.S., K. Soldau, and R.J. Ulevitch. 1986. Isolation of a lipopolysaccharide-binding acute phase reactant from rabbit serum. J.Exp.Med. 164:777–793.PubMedGoogle Scholar
  24. 24.
    Ulevitch, R.J. and P.S. Tobias. 1995. Receptor-dependent mechanisms of cell stimulation by bacterial endotoxin. Annu.Rev.Immunol. 13:437–57:437–457.Google Scholar
  25. 25.
    Oberholzer, A., C. Oberholzer, and L.L. Moldawer. 2001. Sepsis syndromes: understanding the role of innate and acquired immunity. Shock 16:83–96.PubMedGoogle Scholar
  26. 26.
    Tomlinson, S. 1993. Complement defense mechanisms. Curr.Opin.Immunol. 5:83–89.PubMedGoogle Scholar
  27. 27.
    Liszewski, M.K., T.W. Post, and J.P. Atkinson. 1991. Membrane cofactor protein (MCP or CD46): newest member of the regulators of complement activation gene cluster. Annu.Rev.Immunol. 9:431–55.:431–455.PubMedGoogle Scholar
  28. 28.
    Frank, M.M. and L.F. Fries. 1991. The role of complement in inflammation and phagocytosis. Immunol.Today 12:322–326.Google Scholar
  29. 29.
    Bhakdi, S. and J. Tranum-Jensen. 1991. Complement lysis: a hole is a hole. Immunol.Today 12:318–320.Google Scholar
  30. 30.
    Kreutz, M., U. Ackermann, S. Hauschildt, S.W. Krause, D. Riedel, W. Bessler, and R. Andreesen. 1997. A comparative analysis of cytokine production and tolerance induction by bacterial lipopeptides, lipopolysaccharides and Staphyloccous aureus in human monocytes. Immunology 92:396–401.PubMedGoogle Scholar
  31. 31.
    Munoz, C., J. Carlet, C. Fitting, B. Misset, J.P. Bleriot, and J.M. Cavaillon. 1991. Dysregulation of in vitro cytokine production by monocytes during sepsis. J.Clin.Invest. 88:1747–1754.PubMedGoogle Scholar
  32. 32.
    Rosenbach, T. and B.M. Czarnetzki. 1987. Comparison of the generation in vitro of chemotactically active LTB4 and its omega-metabolites by human neutrophils and lymphocytes/monocytes. Clin.Exp.Immunol. 69:221–228.PubMedGoogle Scholar
  33. 33.
    Miyamoto, K., M. Lange, G. McKinley, C. Stavropoulos, S. Moriya, H. Matsumoto, and Y. Inada. 1996. Effects of sho-saiko-to on production of prostaglandin E2 (PGE2), leukotriene B4 (LTB4) and superoxide from peripheral monocytes and polymorphonuclear cells isolated from HIV infected individuals. Am.J.Chin.Med. 24:1–10.PubMedGoogle Scholar
  34. 34.
    Simoni, J., G. Simoni, C.D. Lox, D.E. McGunegle, and M. Feola. 1994. Cytokines and PAF release from human monocytes and macrophages: effect of hemoglobin and contaminants. Artif.Cells Blood Substit.Immobil.Biotechnol. 22:525–534.PubMedGoogle Scholar
  35. 35.
    Camussi, G., C. Tetta, R. Coda, and J. Benveniste. 1981. Release of platelet-activating factor in human pathology. I. Evidence for the occurrence of basophil degranulation and release of platelet-activating factor in systemic lupus erythematosus. Lab.Invest. 44:241–251.PubMedGoogle Scholar
  36. 36.
    Dugas, B., M.D. Mossalayi, C. Damais, and J.P. Kolb. 1995. Nitric oxide production by human monocytes: evidence for a role of CD23. Immunol.Today 16:574–580.PubMedGoogle Scholar
  37. 37.
    Campbell, J.J., J. Hedrick, A. Zlotnik, M.A. Siani, D.A. Thompson, and E.C. Butcher. 1998. Chemokines and the arrest of lymphocytes rolling under flow conditions. Science 279:381–384.PubMedGoogle Scholar
  38. 38.
    Foreman, K.E., A.A. Vaporciyan, B.K. Bonish, M.L. Jones, K.J. Johnson, M.M. Glovsky, S.M. Eddy, and P.A. Ward. 1994. C5a-induced expression of P-selectin in endothelial cells. J.Clin.Invest. 94:1147–1155.PubMedGoogle Scholar
  39. 39.
    Noble, K.E., P. Panayiotidis, P.W. Collins, A.V. Hoffbrand, and K.L. Yong. 1996. Monocytes induce E-selectin gene expression in endothelial cells: role of CD11/CD18 and extracellular matrix proteins. Eur.J.Immunol. 26:2944–2951.PubMedGoogle Scholar
  40. 40.
    Melder, R.J., L.L. Munn, S. Yamada, C. Ohkubo, and R.K. Jain. 1995. Selectin- and integrin-mediated T-lymphocyte rolling and arrest on TNF-alpha-activated endothelium: augmentation by erythrocytes. Biophys.J. 69:2131–2138.PubMedGoogle Scholar
  41. 41.
    Lim, Y.C., K. Snapp, G.S. Kansas, R. Camphausen, H. Ding, and F.W. Luscinskas. 1998. Important contributions of P-selectin glycoprotein ligand-1-mediated secondary capture to human monocyte adhesion to P-selectin, E-selectin, and TNF-alpha-activated endothelium under flow in vitro. J.Immunol. 161:2501–2508.PubMedGoogle Scholar
  42. 42.
    Kuypers, T.W. and D. Roos. 1989. Leukocyte membrane adhesion proteins LFA-1, CR3 and p150,95: a review of functional and regulatory aspects. Res.Immunol. 140:461–486.PubMedGoogle Scholar
  43. 43.
    Taub, D.D. 1996. Chemokine-leukocyte interactions. The voodoo that they do so well. Cytokine.Growth Factor.Rev. 7:355–376.PubMedGoogle Scholar
  44. 44.
    Ward, S.G. and J. Westwick. 1998. Chemokines: understanding their role in T-lymphocyte biology. Biochem.J. 333:457–470.PubMedGoogle Scholar
  45. 45.
    Nelson, P.J. and A.M. Krensky. 1998. Chemokines, lymphocytes and viruses: what goes around, comes around. Curr.Opin.Immunol. 10:265–270.PubMedGoogle Scholar
  46. 46.
    Leonard, E.J., A. Skeel, T. Yoshimura, and J. Rankin. 1993. Secretion of monocyte chemoattractant protein-1 (MCP-1) by human mononuclear phagocytes. Adv.Exp.Med.Biol. 351:55–64.:55–64.PubMedGoogle Scholar
  47. 47.
    Engelhardt, E., A. Toksoy, M. Goebeler, S. Debus, E.B. Brocker, and R. Gillitzer. 1998. Chemokines IL-8, GROalpha, MCP-1, IP-10, and Mig are sequentially and differentially expressed during phase-specific infiltration of leukocyte subsets in human wound healing. Am.J.Pathol. 153:1849–1860.PubMedGoogle Scholar
  48. 48.
    Antony, V.B., S.W. Godbey, S.L. Kunkel, J.W. Hott, D.L. Hartman, M.D. Burdick, and R.M. Strieter. 1993. Recruitment of inflammatory cells to the pleural space. Chemotactic cytokines, IL-8, and monocyte chemotactic peptide-1 in human pleural fluids. J.Immunol. 151:7216–7223.PubMedGoogle Scholar
  49. 49.
    Uguccioni, M., P. Gionchetti, D.F. Robbiani, F. Rizzello, S. Peruzzo, M. Campieri, and M. Baggiolini. 1999. Increased expression of IP-10, IL-8, MCP-1, and MCP-3 in ulcerative colitis. Am.J.Pathol. 155:331–336.PubMedGoogle Scholar
  50. 50.
    Tekstra, J., H. Beekhuizen, Van De Gevel JS, B.I. Van, C.W. Tuk, and R.H. Beelen. 1999. Infection of human endothelial cells with Staphylococcus aureus induces the production of monocyte chemotactic protein-1 (MCP-1) and monocyte Chemotaxis. Clin.Exp.Immunol. 117:489–495.PubMedGoogle Scholar
  51. 51.
    Capelli, A., S.A. Di, I. Gnemmi, P. Balbo, C.G. Cerutti, B. Balbi, M. Lusuardi, and C.F. Donner. 1999. Increased MCP-1 and MIP-1beta in bronchoalveolar lavage fluid of chronic bronchitics. Eur.Respir.J. 14:160–165.PubMedGoogle Scholar
  52. 52.
    Hoch, R.C., R. Rodriguez, T. Manning, M. Bishop, P. Mead, W.C. Shoemaker, and E. Abraham. 1993. Effects of accidental trauma on cytokine and endotoxin production. Crit.Care Med. 21:839–845.PubMedGoogle Scholar
  53. 53.
    Zhao, Y.X., H. Zhang, B. Chiu, U. Payne, and R.D. Inman. 1999. Tumor necrosis factor receptor p55 controls the severity of arthritis in experimental Yersinia enterocolitica infection. Arthritis Rheum. 42:1662–1672.PubMedGoogle Scholar
  54. 54.
    Birdsall, H.H., D.M. Green, J. Trial, K.A. Youker, A.R. Burns, C.R. MacKay, G.J. LaRosa, H.K. Hawkins, C.W. Smith, L.H. Michael, M.L. Entman, and R.D. Rossen. 1997. Complement C5a, TGF-beta 1, and MCP-1, in sequence, induce migration of monocytes into ischemic canine myocardium within the first one to five hours after reperfusion. Circulation 95:684–692.PubMedGoogle Scholar
  55. 55.
    Ribeiro, R.A., M.V. Souza-Filho, M.H. Souza, S.H. Oliveira, C.H. Costa, F.Q. Cunha, and H.S. Ferreira. 1997. Role of resident mast cells and macrophages in the neutrophil migration induced by LTB4, fMLP and C5a des arg. Int.Arch.Allergy Immunol. 112:27–35.PubMedGoogle Scholar
  56. 56.
    Vassalli, P. 1992. The pathophysiology of tumor necrosis factors. Ann.Rev.Immunol. 10:411–452.Google Scholar
  57. 57.
    Beutler, B. and A. Cerami. 1986. Cachectin and tumour necrosis factor as two sides of the same biological coin. Nature 320:584–588.PubMedGoogle Scholar
  58. 58.
    Ksontini, R., S.L. MacKay, and L.L. Moldawer. 1998. Revisiting the role of tumor necrosis factor alpha and the response to surgical injury and inflammation. Arch Surg 133:558–567.PubMedGoogle Scholar
  59. 59.
    Tracey, K.J., B. Beutler, S.F. Lowry, J. Merryweather, S. Wolpe, I.W. Milsark, R.J. Hariri, T.J. Fahey, A. Zentella, J.D. Albert, and et al. 1986. Shock and tissue injury induced by recombinant human cachectin. Science 234:470–474.PubMedGoogle Scholar
  60. 60.
    Tracey, K.J., S.F. Lowry, and A. Cerami. 1988. Cachetin/TNF-alpha in septic shock and septic adult respiratory distress syndrome. Am.Rev.Respir.Dis. 138:1377–1379.PubMedGoogle Scholar
  61. 61.
    Tracey, K.J., Y. Fong, D.G. Hesse, K.R. Manogue, A.T. Lee, G.C. Kuo, S.F. Lowry, and A. Cerami. 1987. Anti-cachectin/TNF monoclonal antibodies prevent septic shock during lethal bacteraemia. Nature 330:662–664.PubMedGoogle Scholar
  62. 62.
    Baumann, H., V. Onorato, J. Gauldie, and G.P. Jahreis. 1987. Distinct sets of acute phase plasma proteins are stimulated by separate human hepatocyte-stimulating factors and monokines in rat hepatoma cells. J.Biol.Chem. 262:9756–9768.PubMedGoogle Scholar
  63. 63.
    Castell, J.V., M.J. Gomez-Lechon, M. David, T. Andus, T. Geiger, R. Trullenque, R. Fabra, and P.C. Heinrich. 1989. Interleukin-6 is the major regulator of acute phase protein synthesis in adult human hepatocytes. FEBS Lett. 242:237–239.PubMedGoogle Scholar
  64. 64.
    Yamada, Y., K. Kimball, S. Okusawa, G. Vachino, N. Margolis, J.W. Sohn, J.J. Li, G. Wakabayashi, K. McAdam, and J.F. Burke. 1990. Cytokines, acute phase proteins, and tissue injury. C-reactive protein opsonizes dead cells for debridement and stimulates cytokine production. Ann.N.Y.Acad.Sci. 587:351–61.:351–361.PubMedGoogle Scholar
  65. 65.
    Thiel, S., U. Holmskov, L. Hviid, S.B. Laursen, and J.C. Jensenius. 1992. The concentration of the C-type lectin, mannan-binding protein, in human plasma increases during an acute phase response. Clin.Exp.Immunol. 90:31–35.PubMedGoogle Scholar
  66. 66.
    Thiel, S., S.V. Petersen, T. Vorup-Jensen, M. Matsushita, T. Fujita, C.M. Stover, W.J. Schwaeble, and J.C. Jensenius. 2000. Interaction of C1q and mannan-binding lectin (MBL) with C1r, C1s, MBL-associated serine proteases 1 and 2, and the MBL-associated protein MAp19. J.Immunol. 165:878–887.PubMedGoogle Scholar
  67. 67.
    Fraser, I.P., H. Koziel, and R.A. Ezekowitz. 1998. The serum mannose-binding protein and the macrophage mannose receptor are pattern recognition molecules that link innate and adaptive immunity. Semin.Immunol. 10:363–372.PubMedGoogle Scholar
  68. 68.
    Movat, H.Z., M.I. Cybulsky, I.G. Colditz, M.K. Chan, and C.A. Dinarello. 1987. Acute inflammation in gram-negative infection: endotoxin, interleukin 1, tumor necrosis factor, and neutrophils. Fed.Proc. 46:97–104.PubMedGoogle Scholar
  69. 69.
    Bone, R.C. 1992. Inhibitors of complement and neutrophils: a critical evaluation of their role in the treatment of sepsis. Crit.Care Med. 20:891–898.PubMedGoogle Scholar
  70. 70.
    Welbourn, C.R. and Y. Young. 1992. Endotoxin, septic shock and acute lung injury: neutrophils, macrophages and inflammatory mediators. Br.J.Surg. 79:998–1003.PubMedGoogle Scholar
  71. 71.
    Harris, M.C., J. Stroobant, C.S. Cody, S.D. Douglas, and R.A. Polin. 1983. Phagocytosis of group B Streptococcus by neutrophils from newborn infants. Pediatr.Res. 17:358–361.PubMedGoogle Scholar
  72. 72.
    Schorlemmer, H.U., T. Hofstaetter, and F.R. Seiler. 1984. Phagocytosis of immune complexes by human neutrophils and monocytes: relative importance of Fc and C3b receptors. Behring.Inst.Mitt. 88–97.Google Scholar
  73. 73.
    Borrego, F., M. Ulbrecht, E.H. Weiss, J.E. Coligan, and A.G. Brooks. 1998. Recognition of human histocompatibility leukocyte antigen (HLA)-E complexed with HLA class I signal sequence-derived peptides by CD94/NKG2 confers protection from natural killer cell-mediated lysis. J.Exp.Med. 187:813–818.PubMedGoogle Scholar
  74. 74.
    Moretta, A., C. Bottino, M. Vitale, D. Pende, R. Biassoni, M.C. Mingari, and L. Moretta. 1996. Receptors for HLA class-I molecules in human natural killer cells. Annu.Rev.Immunol. 14:619–48.:619–648.PubMedGoogle Scholar
  75. 75.
    Biron, C.A., K.B. Nguyen, G.C. Pien, L.P. Cousens, and T.P. Salazar-Mather. 1999. Natural killer cells in antiviral defense: function and regulation by innate cytokines. Annu.Rev.Immunol. 17:189–220.:189–220.PubMedGoogle Scholar
  76. 76.
    Herberman, R.B., C.W. Reynolds, and J.R. Ortaldo. 1986. Mechanism of cytotoxicity by natural killer (NK) cells. Annu.Rev.Immunol. 4:651–80.:651–680.PubMedGoogle Scholar
  77. 77.
    Calandra, T., J.D. Baumgartner, G.E. Grau, M.M. Wu, P.H. Lambert, J. Schellekens, J. Verhoef, and M.P. Glauser. 1990. Prognostic values of tumor necrosis factor/cachectin, interleukin-1, interferon-alpha, and interferon-gamma in the serum of patients with septic shock. Swiss-Dutch J5 Immunoglobulin Study Group. J.Infect.Dis. 161:982–987.PubMedGoogle Scholar
  78. 78.
    Drost, A.C., D.G. Burleson, W.G. Cioffi, Jr., B.S. Jordan, A.D. Mason, Jr., and B.A.J. Pruitt. 1993. Plasma cytokines following thermal injury and their relationship with patient mortality, burn size, and time postburn. J.Trauma. 35:335–339.PubMedGoogle Scholar
  79. 79.
    Casey, L.C., R.A. Balk, and R.C. Bone. 1993. Plasma cytokine and endotoxin levels correlate with survival in patients with the sepsis syndrome [see comments]. Ann Intern.Med. 119:771–778.PubMedGoogle Scholar
  80. 80.
    Sherry, R.M., J.I. Cue, J.K. Goddard, J.B. Parramore, and J.T. DiPiro. 1996. Interleukin-10 is associated with the development of sepsis in trauma patients. J.Trauma. 40:613–616.PubMedGoogle Scholar
  81. 81.
    Neidhardt, R., M. Keel, U. Steckholzer, A. Safret, U. Ungethuem, O. Trentz, and W. Ertel. 1997. Relationship of interleukin-10 plasma levels to severity of injury and clinical outcome in injured patients. J.Trauma. 42:863–870.PubMedGoogle Scholar
  82. 82.
    Suter, P.M., S. Suter, E. Girardin, P. Roux Lombard, G.E. Grau, and J.M. Dayer. 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. 145:1016–1022.PubMedGoogle Scholar
  83. 83.
    Holzheimer, R.G., M. Schein, and D.H. Wittmann. 1995. Inflammatory response in peritoneal exudate and plasma of patients undergoing planned relaparotomy for severe secondary peritonitis..Arch.Surg. 130:1314–1319.PubMedGoogle Scholar
  84. 84.
    American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference. 1992. Definitions for sepsis and the response to surgical injury and inflammation. Crit.Care Med. 20:864–871.Google Scholar
  85. 85.
    Bone, R.C. 1996. Toward a theory regarding the pathogenesis of the systemic inflammatory response syndrome: what we do and do not know about cytokine regulation. Crit.Care Med. 24:163–172.PubMedGoogle Scholar
  86. 86.
    Bone, R.C. 1996. Sir Isaac Newton, sepsis, SIRS, and CARS. Crit.Care Med. 24:1125–1128.PubMedGoogle Scholar
  87. 87.
    Wessels, M.R., P. Butko, M. Ma, H.B. Warren, A.L. Lage, and M.C. Carroll. 1995. Studies of group B streptococcal infection in mice deficient in complement component C3 or C4 demonstrate an essential role for complement in both innate and acquired immunity. Proc.Natl.Acad.Sci.U.S.A. 92:11490–11494.PubMedGoogle Scholar
  88. 88.
    Czermak, B.J., V. Sarma, C.L. Pierson, R.L. Warner, M. Huber-Lang, N.M. Bless, H. Schmal, H.P. Friedl, and P.A. Ward. 1999. Protective effects of C5a blockade in sepsis. Nat.Med. 5:788–792.PubMedGoogle Scholar
  89. 89.
    Bengtsson, A., H. Redl, E. Paul, G. Schlag, T.E. Mollnes, and J. Davies. 1993. Complement and leukocyte activation in septic baboons. Circ.Shock 39:83–88.PubMedGoogle Scholar
  90. 90.
    Friedman, G., S. Jankowski, M. Shahla, M. Goldman, R.M. Rose, R.J. Kahn, and J.L. Vincent. 1996. Administration of an antibody to E-selectin in patients with septic shock. Crit.Care Med. 24:229–233.PubMedGoogle Scholar
  91. 91.
    Cummings, C.J., C.N. Sessler, L.D. Beall, B.J. Fisher, A.M. Best, and A.A. Fowler. 1997. Soluble E-selectin levels in sepsis and critical illness. Correlation with infection and hemodynamic dysfunction. Am.J.Respir.Crit.Care Med. 156:431–437.PubMedGoogle Scholar
  92. 92.
    Schlag, G., H.R. Redi, G.O. Till, J. Davies, U. Martin, and L. Dumont. 1999. Anti-L-selectin antibody treatment of hemorrhagic-traumatic shock in baboons. Crit.Care Med. 27:1900–1907.PubMedGoogle Scholar
  93. 93.
    Essani, N.A., M.A. Fisher, C.A. Simmons, J.L. Hoover, A. Farhood, and H. Jaeschke. 1998. Increased P-selectin gene expression in the liver vasculature and its role in the pathophysiology of neutrophil-induced liver injury in murine endotoxin shock. J.Leukoc.Biol. 63:288–296.PubMedGoogle Scholar
  94. 94.
    Ohlsson, K., P. Bjork, M. Bergenfeldt, R. Hageman, and R.C. Thompson. 1990. Interleukin-1 receptor antagonist reduces mortality from endotoxin shock. Nature 348:550–552.PubMedGoogle Scholar
  95. 95.
    Fischer, E., M.A. Marano, Z.K. Van, C.S. Rock, A.S. Hawes, W.A. Thompson, L. DeForge, J.S. Kenney, D.G. Remick, and D.C. Bloedow. 1992. 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. 89:1551–1557.PubMedGoogle Scholar
  96. 96.
    Zeni, F., B. Freeman, and C. Natanson. 1997. Anti-inflammatory therapies to treat sepsis and septic shock: a reassessment [editorial; comment]. Crit.Care Med. 25:1095–1100.PubMedGoogle Scholar
  97. 97.
    Baue, A.E. 1997. Multiple organ failure, multiple organ dysfunction syndrome, and systemic inflammatory response syndrome. Why no magic bullets? Arch Surg 132:703–707.Google Scholar
  98. 98.
    Ertel, W., J.P. Kremer, J. Kenney, U. Steckholzer, D. Jarrar, O. Trentz, and F.W. Schildberg. 1995. Downregulation of proinflammatory cytokine release in whole blood from septic patients. Blood 85:1341–1347.PubMedGoogle Scholar
  99. 99.
    Zheng, L., G. Fisher, R.E. Miller, J. Peschon, D.H. Lynch, and M.J. Lenardo. 1995. Induction of apoptosis in mature T cells by tumour necrosis factor. Nature 377:348–351.PubMedGoogle Scholar
  100. 100.
    Dhein, J., H. Walczak, C. Baumler, K.M. Debatin, and P.H. Krammer. 1995. Autocrine T-cell suicide mediated by APO-l/(Fas/CD95) [see comments]..Nature 373:438–441.PubMedGoogle Scholar
  101. 101.
    Jimenez, M.F., R.W. Watson, J. Parodo, D. Evans, D. Foster, M. Steinberg, O.D. Rotstein, and J.C. Marshall. 1997. Dysregulated expression of neutrophil apoptosis in the systemic inflammatory response syndrome [In Process Citation]. Arch Surg 132:1263–1269.PubMedGoogle Scholar
  102. 102.
    Keel, M., U. Ungethum, U. Steckholzer, E. Niederer, T. Hartung, O. Trentz, and W. Ertel. 1997. Interleukin-10 counterregulates proinflammatory cytokine-induced inhibition of neutrophil apoptosis during severe sepsis. Blood 90:3356–3363.PubMedGoogle Scholar
  103. 103.
    Matute-Bello, G., W.C. Liles, F. Radella, K.P. Steinberg, J.T. Ruzinski, M. Jonas, E.Y. Chi, L.D. Hudson, and T.R. Martin. 1997. Neutrophil apoptosis in the acute respiratory distress syndrome. Am.J.Respir.Crit.Care Med. 156:1969–1977.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2003

Authors and Affiliations

  • Andreas Oberholzer
    • 1
  • Caroline Oberholzer
    • 1
  • Lyle L. Moldawer
    • 2
  1. 1.The Department of Trauma and Reconstructive Surgery, Benjamin Franklin Medical CenterFreie Universität BerlinGermany
  2. 2.The Department of SurgeryUniversity of Florida College of MedicineGainesvilleUSA

Personalised recommendations