Skip to main content
SpringerLink
Log in

The systemic inflammatory response syndrome (SIRS): Immunology and potential immunotherapy

Das Syndrom der systemischen Entzündungsreaktion: Immunologie und Möglichkeiten der Immuntherapie

  • Review
  • Published:
Infection Aims and scope Submit manuscript

Summary

Despite widespread advances in intensive care practices, and more potent and effective antimicrobials, septic shock continues to have a mortality rate of greater than 40%. Although antimicrobials can treat the etiologic organism, they do not alter the host response. It is becoming clear that invading organisms and other insults induce the release of cytokines and secondary mediators by the host. These mediators produce alterations in cellular, metabolic and physiologic functions producing the clinical picture of septic shock. Recent advances in cellular and molecular biology have permitted the identification of some of the mediators involved in this inflammatory cascade. Potential therapies are being developed which block or interrupt their activity. Treatment populations must be meticulously defined if we are to extract useful information concerning the efficacy of these new treatment modalities. In the following, proposed definitions for clinical patterns seen in patients with sepsis, and their inherent problems when applied to pediatrics are discussed. The pathophysiology of sepsis is discussed, and specific therapies designed to interrupt the inflammatory cascade are examined.

Zusammenfassung

Die Letalität des septischen Schocks liegt trotz vielfältiger intensivtherapeutischer Fortschritte und wirksamer antimikrobieller Therapien nach wie vor über 40%. Antimikrobielle Substanzen haben Einfluß auf den kausalen Erreger, aber sie ändern nicht die Reaktion des Wirtes. Es hat sich herausgestellt, daß eindringende Erreger und andere Schädigungen die Freisetzung von Zytokinen und sekundären Mediatoren durch den Wirtsorganismus in Gang setzen. Diese Mediatoren verändern zelluläre, metabolische und physiologische Funktionen und führen zum klinischen Bild des septischen Schocks. Einige der Mediatoren, die in diese entzündliche Reaktionskette eingebunden sind, konnten durch die neuesten Fortschritte auf dem Gebiet der Zellbiologie und Molekularbiologie identifiziert werden. Wenn es gelingen soll, diese neuen Behandlungsmodalitäten wirksam einzusetzen, muß die exakte Definition der therapeutischen Zielgruppen möglich sein. Im folgenden werden Definitionen für klinische Bilder, die bei Patienten mit Sepsis beobachtet werden, vorgeschlagen und die speziellen pädiatrischen Probleme diskutiert. Die Pathophysiologie der Sepsis und Therapie, die spezifisch in die Entzündungskaskade eingreifen, werden diskutiert.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Centers for Disease Control Increase in national hospital discharge survey rates for septicemia: United States, 1970–1987. MMWR 39 (1990) 31–34.

    Google Scholar 

  2. Wenzel W. P. The mortality of hospital-acquired bloodstream infections: need for a new vital statistic? Int. J. Epidem. 17 (1988) 225–227.

    Google Scholar 

  3. Members of the American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference Committee Definitions for sepsis and organ failure and guidelines for use of innovative therapies in sepsis. Crit. Care Med. 20 (1992) 864–874.

    Google Scholar 

  4. Jacobs, R. F., Sowell, M. K., Moss, M., Fiser, D. H. Septic shock in children: bacterial etiologies and temporal relationships. Pediatr. Infect. Dis. J. 9 (1990) 196–200.

    Google Scholar 

  5. American Heart Association Recognition of respiratory failure and shock: anticipating cardiopulmonary arrest. In:Chameides, L. (ed.): Textbook of pediatric advanced life support. American Heart Association, New York 1990, pp. 3–9.

    Google Scholar 

  6. Perkin, R. M., Levin, D. L. Shock in the pediatric patient. Part I. J. Pediatr. 101 (1982) 163–169.

    Google Scholar 

  7. Fry, D. E., Pearlstein, L., Fulton, R. L. Multiple system organ failure. The role of uncontrolled infection. Arch. Surg. 115 (1980) 136–140.

    Google Scholar 

  8. Bell, R. C., Coalson, J. J., Smith, D. D. Multiple organ system failure and infection in adult respiratory distress syndrome. Ann. Intern. Med. 99 (1983) 293–298.

    Google Scholar 

  9. Goris, R. J. A., Boekhorst, T. A. P. Multiple organ failure, generalized autodestructive inflammation. Arch. Surg. 120 (1985) 1109–1115.

    Google Scholar 

  10. Wallace, J. L., Steel, G., Whittle, B. J. R. Evidence for platelet activating factor as a mediator of endotoxin-induced gastrointestinal damage in the rat effects of three platelet-activating factor agonists. Gastroenterology 93 (1987) 765–773.

    Google Scholar 

  11. Sculier, J. P., Bron, D., Verboven, N. Multiple organ failure during interleukin 2 and LAK cell infusion. Intensive Care Med. 14 (1988) 666–667.

    Google Scholar 

  12. Beutler, B. A., Milsark, I. W., Cerami, A. C. Passive immunization against cachectin/tumor necrosis factor protects mice from lethal effect of endotoxin. Science 229 (1985) 869–871.

    Google Scholar 

  13. Tracey, K. J., Beutler, B. A., Lowry, S. F. Shock and tissue injury induced by recombinant human cachectin. Science 234 (1986) 470–474.

    Google Scholar 

  14. Tracey, K. J., Lowry, S. F., Fahey, T. J., III. Cachectin/tumor necrosis factor induces lethal shock and stress hormone responses in the dog. Surg. Gynecol. Obstet. 164 (1987) 415–442.

    Google Scholar 

  15. Girardin, E., Grau, G. E., Dayer, J. Tumor necrosis factor and interleukin-1 in the serum of children with severe infectious purpura. N. Engl. J. Med. 319 (1988) 397.

    Google Scholar 

  16. Waage, A., Halstensen, A., Espevik, T. Association between tumornecrosis-factor in serum and fatal outcome in patients with meningococcal disease. Lancet 8529 (1987) 355.

    Google Scholar 

  17. Baumgartner, J. D., Heumann, D., Gerain, J. Association between protective efficacy of anti-lipopolysaccharide (LPS) antibodies and suppression of LPS-induced tumor necrosis factor and interleukin-6 comparison of O side chain-specific antibodies with core LPS antibodies. J. Exp. Med. 171 (1990) 889–896.

    Google Scholar 

  18. Tate, W. J., Douglas, H., Braude, A. I. Protection against lethality ofE. coli endotoxin with “O” antiserum. Ann. N. Y. Acad. Sci. 133 (1966) 746–762.

    Google Scholar 

  19. Young, L. S. Human immunity toPseudomonas aeruginosa, relationship between heat-stable opsonins and type-specific lipopolysaccharides. J. Infect. Dis. 126 (1972) 227–287.

    Google Scholar 

  20. Ziegler, E. J., McCutchan, J. A., Fierer, J. Treatment of gram-negative bacteremia and shock with human antiserum to a mutantE. coli. N. Engl. J. Med. 307 (1993) 1225–1230.

    Google Scholar 

  21. J 5 Study Group Treatment of severe infectious purpura in children with human plasma from donors immunized withE. coli J5: a prospective double-blind study. J. Infect. Dis. 165 (1992) 695–701.

    Google Scholar 

  22. Calandra, T., Glauser, M. P., Schellekens, J. Treatment of gramnegative septic shock with human IgG antibody toE. coli J 5. J. Infect. Dis. 158 (1988) 312–319.

    Google Scholar 

  23. Baumgartner, J. D., Glauser, M. P., McCutchan, J. A. Prevention of gram-negative shock and death in surgical patients by an antibody to endotoxin core glycolipid. Lancet ii (1985) 59–63.

    Google Scholar 

  24. McCutchan, J. A., Wolf, J. L., Ziegler, E. J. Ineffectiveness of single-dose human antiserum to core glycolipid (E. coli J 5) for prophylaxis of bacteremic, gram-negative infection in patients with prolonged neutropenia. Schweiz. Med. Wochenschr. 113 (S 14) (1983) 40.

    Google Scholar 

  25. Greenman, R. L., Schein, R. M. H., Martin, M. A. A controlled clinical trial of E 5 murine monoclonal IgM antibody to endotoxin in the treatment of gram-negative sepsis. JAMA 266 (1991) 1097–1102.

    Google Scholar 

  26. Wenzel, R., Bone, R., Fein, A.: Results of a second double-blind, randomized controlled trial of antiendotoxin antibody E 5 in gram-negative sepsis [Abstract 1170] ICAAC. 31st ICAAC 1170 (1991).

  27. Ziegler, E. J., Fisher, C. J., Sprung, C. L. Treatment of gram-negative bacteremia and septic shock with HA-1A human monoclonal antibody against endotoxin. N. Engl. J. Med. 324 (1991) 429–436.

    Google Scholar 

  28. Warren, H. S., Danner, R. L., Munford, R. S. Anti-endotoxin monoclonal antibodies — a second look. N. Engl. J. Med. 326 (1992) 1153–1157.

    Google Scholar 

  29. Bogard, W. C., Jr., Siegel, S. A. The human monoclonal antibody HA-1A: studies on the epitope location within the endotoxin molecule and epitopic exposure on the surface of viable gram-negative bacteria. Circ. Shock 34 (1991) 119 abstract.

    Google Scholar 

  30. Baumgartner, J. D., Heumann, D., Glauser, M. P. The HA-1A monoclonal antibody for gram-negative sepsis. N. Engl. J. Med. 325 (1991) 281–282.

    Google Scholar 

  31. Tobias, P. S., Mathison, J. C., Ulevitch, R. J. A family of lipopolysaccharide binding proteins involved in responses to gram-negative sepsis. J. Biol. Chem. 263 (1988) 13479–13481.

    Google Scholar 

  32. Tobias, P. S., Soldau, K., Ulevitch, R. J. Isolation of a lipopolysaccharide-binding acute phase reactant from rabbit serum. J. Exp. Med. 164 (1986) 777–793.

    Google Scholar 

  33. Schumann, R. R., Leong, S. R., Flaggs, G. W. Structure and function of lipopolysaccharide binding protein. Science 249 (1990) 1429–1431.

    Google Scholar 

  34. Wright, S. D., Ramos, R. A., Tobias, P. S. CD 14, a receptor for complexes of LPS and LPS binding protein. Science 249 (1990) 1431–1433.

    Google Scholar 

  35. Opal, S. M., Fisher, C. J., Marra, M. N.: Bactericidal/permeability-increasing protein as a novel therapeutic modality in the treatment of endotoxic shock. Clinical Res. 39 (1991) 351 A.

  36. Kruys, V., Marinx, O., Shaw, G. Translational blockade imposed by cytokine-derived UA-rich sequences. Science 245 (1989) 852–855.

    Google Scholar 

  37. Shaw, G., Kamen, R. A conserved AU sequence from the 3′ untranslated region of GM-CSF mRNA mediates selective mRNA degradation. Cell 46 (1986) 659–667.

    Google Scholar 

  38. Caput, D., Beutler, B., Hartog, K. Identification of a common nucleotide sequence in the 3′ untranslated region of mRNA molecules specifying inflammatory mediators. Proc. Natl. Acad. Sci. USA 83 (1983) 1670.

    Google Scholar 

  39. Beutler, B., Brown, T. ACAT reporter construct allows ultrasensitive estimation of TNF synthesis, and suggests that the TNF gene has been silenced in non-macrophage cell lines. J. Clin. Invest. 87 (1991) 1336–1344.

    Google Scholar 

  40. Streiter, R. M., Remick, D. G., Ward, P. A. Cellular and molecular regulation of tumor necrosis factor alpha production by pentoxifylline. Biochem. Biophys. Res. Comm. 155 (1988) 1230–1236.

    Google Scholar 

  41. Taffet, S. M., Singhel, K. J., Overholtzer, J. F. Regulation of tumor necrosis factor expression in a macrophage-like cell line by lipopolysaccharide and cyclic AMP. Cell Immunol. 120 (1989) 291–300.

    Google Scholar 

  42. Schade, U. F. Pentoxifylline increases survival in murine endotoxin shock and decreases formation of tumor necrosis factor. Circ. Shock 31 (1990) 171–181.

    Google Scholar 

  43. Giroir, B. P., Beutler, B. Effect of amrinone on tumor necrosis factor production in endotoxin shock. Circ. Shock 36 (1992) 200–207.

    Google Scholar 

  44. Beutler, B., Krochin, N., Milsark, I. W. Control of cachectin (tumor necrosis factor) synthesis: mechanisms of endotoxin resistance. Science 232 (1986) 977–980.

    Google Scholar 

  45. Bone, R. C., Fisher, C. J., Clemmer, T. P. A controlled clinical trial of high-dose methylprednisolone in the treatment of severe sepsis and spetic shock. N. Engl. J. Med. 217 (1987) 653–658.

    Google Scholar 

  46. The Veterans Administration Systemic Sepsis Cooperative Study Group Effect of high-dose glucocorticoid therapy on mortality in patients with clinical signs of systemic sepsis. N. Engl. J. Med. 317 (1987) 659–665.

    Google Scholar 

  47. Kass, E. H., Finland, M. Corticosteroids and infections. Adv. Intern. Med. 16 (1958) 422–430.

    Google Scholar 

  48. Griesman, E. G. Experimental gram-negative bacterial sepsis: optimal methylprednisolone requirements for prevention of mortality not preventable by antibiotics alone. Proc. Exp. Biol. Med. 170 (1982) 436–442.

    Google Scholar 

  49. Mustafa, M. M., Ramilo, O., Saez-Llorens, X. Cerebrospinal fluid prostaglandins, interleukin-1β, and tumor necrosis factor in bacterial meningitis, clinical and laboratory correlations in placebo-treated and dexamethasone-treated patients. Amer. J. Dis. Child 144 (8) (1990) 883–887.

    Google Scholar 

  50. Odio, C. M., Faingezicht, I., Paris, M. The beneficial effects of early dexamethasone administration in infants and children with bacterial meningitis. N. Engl. J. Med. 324 (1991) 1525–1531.

    Google Scholar 

  51. Havell, E. A. Evidence that tumor necrosis factor has an important role in antibacterial resistance. J. Immunol. 143 (1989) 2894–2899.

    Google Scholar 

  52. O'Brien, A. D., Rosentreich, D. L., Scher, I. Genetic control of susceptibility toSalmonella typhimurium in mice: role of the LPS gene. J. Immunol. 124 (1980) 20.

    Google Scholar 

  53. Tracey, K. J., Fong, Y., Hesse, D. G. Anti-cachectin/TNF monoclonal antibodies prevent septic shock during lethal bacteremia. Nature 330 (1987) 662–664.

    Google Scholar 

  54. Keogh, C., Fong, Y., Seniuk, S., He, W., Barber, A., Minei, J. P., Felson, D., Lowry, S. F., Moldawer, L. L. Identification of a novel tumor necrosis factor alpha/cachectin from the livers of burned and infected rats. Arch. Surg. 125 (1990) 79–85.

    Google Scholar 

  55. Kriegler, M., Perez, C., DeFay, K., Albert, L., Lu, S. D. A novel form of TNF/cachectin is a cell surfae cytotoxic transmembrane protein: ramifications for the complex physiology of TNF. Cell 53 (1988) 45–53.

    Google Scholar 

  56. Giroir, B. P., Johnson, J. H., Brown, T., Allen, G. L., Beutler, B. The tissue distribution of tumor necrosis factor biosynthesis during endotoxemia. J. Clin. Invest. 90 (1992) 693–698.

    Google Scholar 

  57. Okusawa, S., Gelfand, J. A., Ikejima, T. Interleukin-1 induces a shock-like state in rabbits: synergism with tumor necrosis factor and the effect of cyclooxygenase inhibition. J. Clin. Invest. 81 (1988) 1162–1172.

    Google Scholar 

  58. Fischer, E., Marano, M. A., Barber, A. E., Hudson, A., Lee, K., Rock, C. S., Hawes, A. S., Thompson, R. C., Hayes, T. J. Comparison between effects of interleukin-1 alpha administration and sublethal endotoxemia in primates. Am. J. Physiol. 261 (1991) R 442-R 452.

    Google Scholar 

  59. Fong, Y., Tracey, K. J., Moldawer, L. L., Hesse, D. G., Manogue, K. B., Kenney, J. S., Lee, A. T., Kuo, G. C., Allison, A. C., Lowry, S. F. Antibodies to cachectin/tumor necrosis factor reduce interleukin-1 beta and interleukin-6 appearance during lethal bacteremia. J. Exp. Med. 170 (1989) 1627–1633.

    Google Scholar 

  60. Fischer, E., Marano, M. A., Van Zee, K. J., Rock, C. S., Lowry, S. F., Moldawer, L. L. Interleukin-1 receptor blockade improves survival and hemodynamic performance inE. coli septic shock, but fails to alter host responses to sublethal endotoxemia. J. Clin. Invest. 89 (1992) 1551–1557.

    Google Scholar 

  61. Preiser, J. C., Schmatz, D., Van der Linden, P., Content, J., Vanden Bussche, P., Vincent, J. L. Interleukin-6 administration has no acute hemodynamic or hematologic effect in the dog. Cytokine 3 (1991) 1–4.

    Google Scholar 

  62. Schindler, R., Mancilla, J., Endres, S., Ghorbani, R., Clark, S. C., Dinarello, C. A. Correlations and interactions in the production of interleukin-6 (IL-6), IL-1, and tumor necrosis factor (TNF) in human blood mononuclear cells: IL-6 suppresses IL-1 and TNF. Blood 75 (1990) 40–47.

    Google Scholar 

  63. Starnes, H. F., Pearce, M. K., Tewari, A., Yim, J. H., Zou, J. C., Abrams, J. S. Anti-IL-6 monoclonal antibodies protect against lethalEscherichia coli infection and lethal tumor necrosis factor alpha challenge in mice. J. Immunol. 145 (1990) 4185–4191.

    Google Scholar 

  64. Klein, C. E., Ozer, H. L., Traganos, F., Atzpodien, J., Oettgen, H. F., Old, L. J. A transformation-associated 130-kD cell surface glycoprotein is growth controlled in normal human cells. J. Exp. Med. 167 (1988) 1684–1696.

    Google Scholar 

  65. Van Zee, K. J., Kohno, T., Fischer, E., Rock, C. S., Moldawer, L. L., Lowry, S. F. Tumor necrosis factor soluble receptors circulate during experimental and clinical inflammation and can protect against excessive tumor necrosis factor alphain vitro andin vivo. Proc. Natl. Acad. Sci USA 89 (1992) 4845–4849.

    Google Scholar 

  66. Lesslauer, W., Tabuchi, H., Gentz, M. Recombinant soluble TNF receptor proteins inhibit LPS-induced lethality in mice. Cytokine 3 (1991) 497.

    Google Scholar 

  67. Peppel, K., Crawford, D., Beutler, B. A tumor necrosis factor (TNF) receptor-IgG heavy chain chimeric protein as a bivalent antagonist of TNF activity. J. Exp. Med. 174 (1991) 1483–1489.

    Google Scholar 

  68. Aiura, K., Gelfand, J. A., Wakabayashi, G. Interleukin-1 receptor antagonist blocks staphylococcal induced septic shock in rabbits. Cytokine 3 (1991) 498.

    Google Scholar 

  69. Eisenburg, S. P., Evans, R. J., Arend, W. P. Primary structure and functional expression from complementary DNA of a human interleukin-1 receptor antagonist. Nature 343 (1990) 341–346.

    Google Scholar 

  70. Hannum, C. H., Wilcox, C. J., Arend, W. P. Interleukin-1 receptor antagonist activity of a human interleukin-1 inhibitor. Nature 343 (1990) 336–340.

    Google Scholar 

  71. Kettelhut, I. C., Fiers, W., Goldberg, A. L. The toxic effects of tumor necrosisin vivo and their prevention by cyclooxygenase inhibitors. Proc. Natl. Acad. Sci. USA 84 (1987) 4273–4277.

    Google Scholar 

  72. Halushka P. V., Reines, H. D., Barrow, S. E., Blair, I. A., Dollery, C. T., Rambo, W., Cook, J. A., Wise, W. C. Elevated plasma 6-ketoprostaglandin F1 alpha in patients with septic shock. Crit. Care Med. 13 (1985) 451–453.

    Google Scholar 

  73. Turner, C. R., Quinlan, M. F., Schwartz, L. W. Therapeutic intervention in a rat model of ARDS: I. Dual inhibition of arachidonic acid metabolism. Circ. Shock 32 (1990) 231–242.

    Google Scholar 

  74. Byrne, K., Sielaff, T. D., Michna, B. Increased survival time after delayed histamine and prostaglandin blockade in a porcine model of severe sepsis-induced lung injury. Crit. Care Med. 18 (1990) 303–308.

    Google Scholar 

  75. McCord, J. M. Oxygen-derived free radicals in post-ischemic tissue injury. N. Engl. J. Med. 312 (1985) 159–163.

    Google Scholar 

  76. Petrone, W. F., English, D. K., Wong, K. Free radicals and inflammation: superoxide-dependent activation of a neutrophil chemotactic factor in plasma. Proc. Natl. Acad. Sci. USA 77 (1980) 1159–1163.

    Google Scholar 

  77. Bernard, G. R. N-acetylcysteine in experimental and clinical acute lung injury. Am. J. Med. 91 (1991) 54–59 S.

    Google Scholar 

  78. Furchgott, R. F., Zawadzki, J. V. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 288 (1980) 373–376.

    Google Scholar 

  79. Palmer, R. M. J., Ferrige, A. G., Moncada, S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature 327 (1987) 524–526.

    Google Scholar 

  80. Ignarro, L. J., Buga, G. M., Wood, K. S. Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide. Proc. Natl. Acad. Sci. USA 84 (1987) 9265–9269.

    Google Scholar 

  81. Moncada, S., Palmer, R. M. J., Higgs, E. A. Nitric oxide: physiology, pathophysiology and pharmacology. Pharmacol. Rev. 43 (1991) 109–142.

    Google Scholar 

  82. Ignarro, L. J., Kadowitz, P. J. The pharmacological and physiological role of cyclic GMP in vascular smooth muscle relaxation. Annu. Rev. Pharmacol. Toxicol. 24 (1985) 171–191.

    Google Scholar 

  83. Mellion, B. T., Ignarro, L. J., Ohlstein, E. H. Evidence for the inhibitory role of guanosine 3′5′ monophosphate in ADP induced human platelet aggregation in the presence of nitric oxide and related vasodilators. Blood 57 (1981) 946–955.

    Google Scholar 

  84. Bath, P. M., Hassall, D. G., Gladwin, A. M., Palmer, R. M., Martin, J. F. Nitric oxide and prostacyclin. Divergence of inhibitory effects on monocyte chemotaxis and adhesion to endotheliumin vitro. Arterioscler. Thromb. 11 (1991) 254–260.

    Google Scholar 

  85. Agullo, L., Garcia, A. Different receptors mediate stimulation of nitric oxide-dependent cyclic GMP formation in neurons and astrocytes in culture. Biochem. Biophys. Res. Commun. 182 (1992) 1362–1368.

    Google Scholar 

  86. Rees, D. D., Palmer, R. M., Hodson, H. F., Moncada, S. A specific inhibitor of nitric oxide formation from L-arginine attentuates endothelium-dependent relaxation. Br. J. Pharmacol. 96 (1989) 418–424.

    Google Scholar 

  87. Aisaka, K., Gross, S. S., Griffith, O. W., Levi, R. NG-methylarginine, an inhibitor of endothelium-derived nitric oxide synthesis, is a potent pressor agent in the guinea pig: does nitric oxide regulate blood pressurein vitro? Biochem. Biophys. Res. Commun. 160 (1989) 881–886.

    Google Scholar 

  88. Petros, A., Bennet, D., Vallance, P. Effect of nitric oxide synthase inhibitors on hypotension in patients with septic shock. Lancet 338 (1991) 1557–1558.

    Google Scholar 

  89. Geroulanos, S., Schilling, J., Cakmakci, M., Jung, H. H., Lariader, F. Inhibition of NO synthesis in septic shock. Lancet 339 (1992) 435.

    Google Scholar 

  90. Sun, X., Wei, H. Bowel necrosis induced by tumor necrosis factor in rats is mediated by platelet-activating factor. J. Clin. Invest. 81 (1988) 1328–1331.

    Google Scholar 

  91. Touvay, C., Vilain, B., Carre, C., Mencia-Huerta, J. M., Braquet, P. Role of a platelet-activating factor (PAF) in the bronchopulmonary alterations and beta-adrenoceptor function induced by endotoxin. Biochem. Biophys. Res. Commun. 152 (1988) 527.

    Google Scholar 

  92. Moore, J. M., Earnest, M. A., DiSimone, A. G., Abumrad, N. N., Fletcher, J. R. A PAF receptor antagonist, BN 52021, attenuates thromboxane release and improves survival in lethal canine endotoxemia. Circ. Shock 36 (1991) 53–59.

    Google Scholar 

  93. Yue, T. L., Farhat, M., Rabinovici, R., Perera P. Y., Vogel, S. N., Feuerstein, G. Protective effect of BN 50739, a new platelet-activating factor antagonist, in endotoxin-treated rabbits. J. Pharmacol. Exp. Ther. 254 (1990) 976–981.

    Google Scholar 

  94. Luger, A., Graf, H., Schwarz, H. P., Stummvoll, H. K., Luger, T. A. Decreased serum interleukin-1 activity and monocyte interleukin-1 production in patients with fatal sepsis. Crit. Care Med. 14 (1986) 458–461.

    Google Scholar 

  95. Giroir, B. P., Brown, T., Beutler, B. Constitutive synthesis of tumor necrosis factor in the thymus. Proc. Natl. Acad. Sci. USA 89 (1992) 4864–4868.

    Google Scholar 

  96. Giroir, B. P., Peppel, K., Silva, M., Beutler, B. The biosynthesis of tumor necrosis factor during pregnancy: studies with the CAT reporter transgene and TNF inhibitors. Eur. Cytokine Network 3 (1992) 533–537.

    Google Scholar 

  97. Kossodo, S., Giroir, B., Brown, T.: Constitutive expression of cachectin/TNF in the thymus: fulfillment of an essential developmental function. Clin. Res. 39 (1991) 250 A.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Dept. of Pediatrics, Div. of Infectious Diseases, Arkansas Children's Hospital, University of Arkansas for Medical Sciences, 800 Marshall Street, 72202-3591, Little Rock, AR

    Toni Darville M. D. & R. Jacobs M. D.

  2. Dept. of Pediatrics, Div. of Critical Care Medicine, Children's Medical Center, University of Texas Southwestern Medical Center, Dallas, TX, USA

    B. Giroir M. D.

Authors
  1. Toni Darville M. D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R. Jacobs M. D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. B. Giroir M. D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Supported in part by Bristol-Myers Squibb Company as a recipient of a Pediatric Infectious Diseases Fellowship Award.

Fellow of the Pediatric Scientist Development Program supported by NICHHD #HD-2297.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Darville, T., Jacobs, R. & Giroir, B. The systemic inflammatory response syndrome (SIRS): Immunology and potential immunotherapy. Infection 21, 279–290 (1993). https://doi.org/10.1007/BF01712446

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01712446

Keywords

Search

Navigation