Immunomodulation of Cell-Mediated Responses: Is It Feasible?

  • Eugen Faist
  • M. W. Wichmann


We know that the endogenous provisions of the organism to survive after major trauma are not sufficient and require exogenous support. Immunomodulatory strategies should prevent the conversion from systemic inflammatory response syndrome (SIRS) to bacterial sepsis and septic shock. Several strategies have been evaluated, including the blockade of mediators, particularly if their levels or effects become excessive and threaten the individual. Clinical trials with anti-tumor necrosis factor (TNF) antibodies, soluble TNF receptors, interleukin-1 (IL-1) receptor antagonists, and anti-lipopolysac-charide (LPS) monoclonal antibodies have been carried out, but no significant treatment benefit was observed.


Severe Sepsis Systemic Inflammatory Response Syndrome Hemorrhagic Shock Severe Trauma Immune Dysfunction 
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  1. 1.
    Faist E, Schinkel C, Zimmer S, Kremer JP, Donnersmarck GH,Schildberg FW: Inadequate interleukin-2 synthesis and interleu-kin-2 messenger expression following thermal and mechanicaltrauma in human is caused by defective transmembrane signalling. J Trauma 1993; 36: 1–9.Google Scholar
  2. 2.
    Kreuzer E, Kääb S, Piltz G, Werdan K: Early prediction of septic complications after cardiac surgery by APACHE II score. Eur J Cardiothorac Surg 1992; 6: 524–527.PubMedCrossRefGoogle Scholar
  3. 3.
    Pilz G, Kreuzer E, Kääb S, Appel R, Werdan K: Early sepsis treatment with immunoglobulins after cardiac surgery in score-identified high risk patients. Chest 1994; 105: 76–82.PubMedCrossRefGoogle Scholar
  4. 4.
    Baker CC, Oppenheimer L, Lewis FR, Trunkey DD: The epidemiology of trauma death. Am J Surg 1980; 140: 144–150.PubMedCrossRefGoogle Scholar
  5. 5.
    Chaudry IH, Ayala A: Immunological Aspects of Hemorrhage. Austin TX, Medical Intelligence Unit, R.G. Landes Company, 1992Google Scholar
  6. 6.
    Alexander JW: Mechanism of immunologic suppression in burn injury. J Trauma 1990; 30: S70–S75.PubMedCrossRefGoogle Scholar
  7. 7.
    Faist E, Kupper TS, Baker CC, Chaudry IH, Dwyer J, Baue AE: Depression of cellular immunity after major injury: its association with post traumatic complications and its restoration with immunomodulatory agents. Arch Surg 1986; 121: 1000–1005.PubMedCrossRefGoogle Scholar
  8. 8.
    Faist E, Mewes A, Strasser T, et al: Alteration of monocyte function following major injury. Arch Surg 1988; 123: 287–292.PubMedCrossRefGoogle Scholar
  9. 9.
    O’Sullivan ST, Lederer JA, Horgan AF, Chin DHL, Mannick JA, Rodriek ML: Major injury leads to predominance of the T helper-2 lymphocyte phenotype and diminished interleukm-12 production associated with decreased resistance to infection. Ann Surg 1995; 222: 482–492.PubMedGoogle Scholar
  10. 10.
    Wichmann MW, Zellweger R, Williams C, Ayala A, DeMaso CM, Chaudry IH: Immune function is more compromised following closed bone fracture and hemorrhagic shock than hemorrhage alone. Arch Surg 1996; 131: 995–1000.PubMedCrossRefGoogle Scholar
  11. 11.
    Wichmann MW, Remmers D, Ayala A, Chaudry IH: Der Beitrag von Weichteiltrauma und/oder Knochenfraktur zur Immunde-pression nach haemorrhagischem Schock im Tierexperiment [The contribution of soft-tissue trauma and/or bone fracture to depressed immunity following hemorrhagic shock in an experimental setting]. Unfallchirurg 1998; 101: 37–41.PubMedCrossRefGoogle Scholar
  12. 12.
    Glauser MP, Zanetti G, Baumgartner JD, Cohen J: Septic shock: pathogenesis. Lancet 1991; 338: 732–736.PubMedCrossRefGoogle Scholar
  13. 13.
    Bone RC: The pathogenesis of sepsis. Ann Intern Med 1991; 115: 457–469.PubMedGoogle Scholar
  14. 14.
    Baue AE: Multiple Organ Failure. Patient Care and Prevention. St. Louis, Mosby, 1990Google Scholar
  15. 15.
    Baue AE: The horror autotoxicus and multiple-organ failure. Arch Surg 1992; 127: 1451–1462.PubMedCrossRefGoogle Scholar
  16. 16.
    Rose S, Marzi I: Pathophysiologic des Polytraumas [Pathophysiology of polytrauma]. Zentralbl Chir 1996; 121: 896–913.PubMedGoogle Scholar
  17. 17.
    Harris BH, Gelfand JA: The immune response to trauma. Semin Pediatr Surg 1995; 4: 77–82.PubMedGoogle Scholar
  18. 18.
    Schinkel C, Faist E, Zimmer S, et al: Kinetics of circulating adhesion molecules and chemokines after mechanical trauma and bums. Eur J Surg 1996; 162: 763–768.PubMedGoogle Scholar
  19. 19.
    Guirao X, Lowry SF: Biologic control of injury and inflammation: much more than too little or too late. World J Suig 1996; 20: 437–446.CrossRefGoogle Scholar
  20. 20.
    Lampl L, Helm M, Specht A, Bock KH, Hartel W, Seifried E: Gerinnungsparameter als prognostische Faktoren beim Polytrauma: Konnen klinische Kenngrossen fruhzeitig eine diagnostische Hilfestellung geben? [Blood coagulation parameters as prognostic factors in multiple trauma: can clinical values be an early diagnostic aid?] Zentralbl Chir 1994; 119: 683–689.PubMedGoogle Scholar
  21. 21.
    Goris RJ, Te Boekhorst T, Nuytinck J, Gimbrere JS: Multiple-organ failure: generalized auto destructive inflammation. Arch Surg 1985; 120: 1109–1115.PubMedCrossRefGoogle Scholar
  22. 22.
    Hoch RC, Rodriguez R, Manning T, et al: Effects of accidental trauma on cytokine and endotoxin production. Crit Care Med 1993; 21: 839–845.PubMedCrossRefGoogle Scholar
  23. 23.
    Baue AE: MOF/MODS, SIRS: an update. Shock 1996; 6: S1–S5.PubMedCrossRefGoogle Scholar
  24. 24.
    McRitchie DI, Girotti MJ, Rotstein OD, Teodorczyk-Injeyan JA: Impaired antibody production in blunt trauma. Arch Surg 1990; 125: 91–96.PubMedCrossRefGoogle Scholar
  25. 25.
    Faist E, Ertel W, Mewes A, Alkan S, Walz A, Strasser T: Trauma-induced alterations of the lymphokine cascade. In: Faist E, Ninnemann J, Green D (eds) Immune Consequences of Trauma, Shock, and Sepsis: Mechanisms and Therapeutic Approaches. Berlin, Springer, 1989; 79–94.CrossRefGoogle Scholar
  26. 26.
    Stephan RN, Mitsuyoski S, Conrad PJ, Dean RE, Geha AS, Chaudry IH: Depressed antigen presentation function and membrane interleukin-1 activity of peritoneal macrophages after laparotomy. Surgery 1987; 102: 147–154.PubMedGoogle Scholar
  27. 27.
    Stephan RN, Kupper TS, Geha AS, Baue AS, Chaudry IH: Hemorrhage without tissue trauma produces immunosuppression and enhances susceptibility to sepsis. Arch Surg 1987; 122: 62–68.PubMedCrossRefGoogle Scholar
  28. 28.
    Chaudry IH, Ayala A, Ertel W, Stephan RN: Editorial review: hemorrhage and resuscitation: immunological aspects. Am J Physiol 1990; 259: R663–R678.PubMedGoogle Scholar
  29. 29.
    Ayala A, Perrin MM, Wagner MA, Chaudry IH: Enhanced susceptibility to sepsis following simple hemorrhage: depression of Fc and C3b receptor mediated phagocytosis. Arch Surg 1990; 125: 70–75.PubMedCrossRefGoogle Scholar
  30. 30.
    Wichmann MW, Zellweger R, DeMaso CM, Ayala A, Chaudry IH: Mechanisms of immunosuppression in males following trauma-hemorrhage: critical role of testosterone. Arch Surg 1996; 131: 1186–1192.PubMedCrossRefGoogle Scholar
  31. 31.
    Wichmann MW, Angele MK, Ayala A, Cioffi WG, Chaudry IH: Flutamide: a novel agent for restoring the depressed cell-mediated immunity following soft-tissue trauma and hemorrhagic shock. Shock 1997; 8: 242–248.PubMedCrossRefGoogle Scholar
  32. 32.
    Wichmann MW, Ayala A, Chaudry IH: Male Sex-steroids are responsible for depressing macrophage immune function after trauma-hemorrhage. Am J Physiol 1997; 273: C1335–C1340.PubMedGoogle Scholar
  33. 33.
    Wichmann MW, Zellweger R, DeMaso CM, Ayala A, Chaudry IH: Melatonin administration attenuates depressed immune functions after trauma-hemorrhage. J Surg Res 1996; 63: 256–262.PubMedCrossRefGoogle Scholar
  34. 34.
    Wichmann MW, Haisken JM, Ayala A, Chaudry IH: Melatonin administration following hemorrhagic shock decreases mortality from subsequent septic challenge. J Surg Res 1996; 65: 109–114.PubMedCrossRefGoogle Scholar
  35. 35.
    Zellweger R, Wichmann MW, Ayala A, DeMaso CM, Chaudry IH: Prolactin: a novel and safe immunomodulating hormone for the treatment of immunodepression following severe homorrhage. J Surg Res 1996; 63: 53–58.PubMedCrossRefGoogle Scholar
  36. 36.
    Zellweger R, Zhu XH, Wichmann MW, Ayala A, DeMaso CM, Chaudry IH: Prolactin administration following hemorrhagic shock improves macrophage cytokine release capacity and decreases mortality from subsequent sepsis. J Immunol 1996; 157: 5748–5754.PubMedGoogle Scholar
  37. 37.
    Faist E, Storck M, Hueltner L, et al: Functional analysis of monocyte activity through synthesis patterns of proinflammatory cytokines and neopterin in patients in surgical intensive care. Surgery 1992; 112: 562–572.PubMedGoogle Scholar
  38. 38.
    Casals-Stenzel J: Triazolodiazepines are potent antagonists of platelet activating factor (PAF) in vitro and in vivo. Arch Pharm (Weinheim) 1987; 335: 351–355.Google Scholar
  39. 39.
    Pullicino EA, Carli F, Poole S, Rafferty B, Malik STA, Elia M: The relationship between the circulating concentrations of interleukin 6 (IL-6), tumor necrosis factor (TNF) and the acute phase response to elective surgery and accidental injury. Lym-phokine Res 1990; 9: 231–238.Google Scholar
  40. 40.
    Yoshizaki K: Clinical significance of cytokines-interleukin 6 in disease. Rinsho Byori 1990; 38: 375–379.PubMedGoogle Scholar
  41. 41.
    Wortel CH, vanDeventer SJ, Aarden LA, et al: Interleukin-6 mediates host defense responses induced by abdominal surgery. Surgery 1993; 114: 564–570.PubMedGoogle Scholar
  42. 42.
    Svoboda P, Kantorova I, Ochmann J: Dynamics of interleukin 1, 2, and 6 and tumor necrosis factor alpha in multiple trauma patients. J Trauma 1994; 36: 336–340.PubMedCrossRefGoogle Scholar
  43. 43.
    Faist E, Wichmann M, Kim C: Immunosuppression and immu-nomodulation in surgical patients. Curr Opin Crit Care 1997; 3: 293–298.CrossRefGoogle Scholar
  44. 44.
    Ayala A, Wang P, Chaudry IH: Insights into the mechanism by which interferon-gamma improves macrophage functionfollowing hemorrhage and resuscitation. J Surg Res 1993; 54: 322–327.PubMedCrossRefGoogle Scholar
  45. 45.
    Ertel W, Morrison MH, Ayala A, Dean RE, Chaudry IH: Interferon-gamma attenuates hemorrhage-induced suppression of macrophage and splenocyte functions and decreases susceptibility to sepsis. Surgery 1992; 111: 177–187.PubMedGoogle Scholar
  46. 46.
    Chaudry IH, Ohkawa M, Clemens MG: Improved mitochondrial function following ischemia and reflow by ATP-MgCl2. Am J Physiol 1984; 246: R799–R804.PubMedGoogle Scholar
  47. 47.
    Chaudry IH: Use of ATP following shock and ischemia. Ann NY Acad Sci 1990; 603: 130–141.PubMedCrossRefGoogle Scholar
  48. 48.
    Wang P, Ba ZF, Morrison MH, Ayala A, Dean RE, Chaudry IH: Mechanism of the beneficial effects of ATP-MgCl2 following trauma-hemorrhage and resuscitation: downregulation of inflammatory cytokine (TNF, IL-6) release. J Surg Res 1992; 52: 364–371.PubMedCrossRefGoogle Scholar
  49. 49.
    Ertel W, Morrison MH, Ayala A, Chaudry IH: Modulation of macrophage membrane phospholipids by n-3 polyunsaturated fatty acids increases interleukin-1 release and prevents suppression of cellular immunity following hemorrhagic shock. Arch Surg 1993; 128: 15–21.PubMedCrossRefGoogle Scholar
  50. 50.
    Ertel W, Morrison MH, Meldrum DR, Ayala A, Chaudry IH: Ibuprofen restores cellular immunity and decreases susceptibility to sepsis following hemorrhage. J Surg Res 1992; 53: 55–61.PubMedCrossRefGoogle Scholar
  51. 51.
    Ertel W, Morrison MH, Ayala A, Chaudry IH: Chloroquine attenuates hemorrhagic shock-induced immunosuppression and decreases susceptibility to sepsis. Arch Surg 1992; 127: 70–76.PubMedCrossRefGoogle Scholar
  52. 52.
    Ertel W, Morrison MH, Ayala A, Chaudry IH: Chloroquine attenuates hemorrhagic shock induced suppression of Kupffer cell antigen presentation and MHC class II antigen expression through blockade of tumor necrosis factor and prostaglandin release. Blood 1991; 78: 1781–1788.PubMedGoogle Scholar
  53. 53.
    Zhu X, Ertel W, Ayala A, Morrison MH, Perrin MM, Chaudry IH: Chloroquine inhibits macrophage tumor necrosis factor-α mRNA transcription. Immunology 1993; 80: 122–126.PubMedGoogle Scholar
  54. 54.
    Ertel W, Morrison MH, Ayala A, Perrin MM, Chaudry IH: Anti-TNF monoclonal antibodies prevent haemorrhage induced suppression of Kupffer cell antigen presentation and MHC class II antigen expression. Immunology 1991; 74: 290–297.PubMedGoogle Scholar
  55. 55.
    Meldrum DR, Ayala A, Chaudry IH: Mechanism of diltiazem’s immunomodulatory effects after hemorrhage and resuscitation. Am J Physiol 1993; 265: C412–C421.PubMedGoogle Scholar
  56. 56.
    Wang P, Ba ZF, Chaudry IH: Chemically modified heparin improves hepatocellular function, cardiac output, and microcirculation after trauma-hemorrhage and resuscitation. Surgery 1994; 116: 169–176.PubMedGoogle Scholar
  57. 57.
    Zellweger R, Ayala A, Zhu X, Holme KR, DeMaso CM, Chaudry IH: A novel nonanticoagulant heparin improves splenocyte and peritoneal macrophage immune function after trauma-hemorrhage and resuscitation. J Surg Res 1995; 59: 211–218.PubMedCrossRefGoogle Scholar
  58. 58.
    Wang P, Ba ZF, Zhou M, Chaudry IH: Pentoxifylline restores cardiac output and tissue perfusion following trauma-hemorrhage and decreases susceptibility to sepsis. Surgery 1993; 114: 352–359.PubMedGoogle Scholar
  59. 59.
    Zellweger R, Ayala A, Schmand JF, Morrison MH, Chaudry IH: PAF-antagonist administration after hemorrhage-resuscitation prevents splenocyte immunodepression. J Surg Res 1995; 59: 366–37.PubMedCrossRefGoogle Scholar
  60. 60.
    Mock GN, Dries DJ, Jurkovich GJ, Maier RV: Assessment of two clinical trials: interferon-gamma therapy in severe injury. Shock 1996; 5: 235–240.PubMedCrossRefGoogle Scholar
  61. 61.
    Deitch EA: Animal models of sepsis and shock: a review and lessons learned. Shock 1998; 9: 1–11.PubMedCrossRefGoogle Scholar
  62. 62.
    Mathiak G, Szewczyk D, Abdullah F, Ovadia P, Rabinovici R: Platelet-activating factor (PAF) in experimental and clinical sepsis. Shock 1997; 7: 391–404.PubMedCrossRefGoogle Scholar
  63. 63.
    Hoffmann H, Markewitz A, Kreuzer E, Reichert K, Jochum M, Faist E: Pentoxifylline decreases the incidence of multiple organ failure in patients after major cardiothoracic surgery. Shock 1998; 9: 235–240.PubMedCrossRefGoogle Scholar
  64. 64.
    Svtaubach KH, Schräder J, Stüber F, Gehrke K, Traumann E, Zabel P: Effect of pentoxifylline in severe sepsis: results of a randomized, double-blind, placebo-controlled study. Arch Surg 1998; 133: 94–100.CrossRefGoogle Scholar
  65. 65.
    McGowan JE, Barnes MW, Finland N: Bacteremia at Boston City Hospital: occurrence and mortality during 12 selected years (1935–1972) with special reference to hospital-acquired cases. J Infect Dis 1975; 132: 316–33.PubMedCrossRefGoogle Scholar
  66. 66.
    Centers for Disease Control: Mortality patterns—United States 1989. MMWR 1992; 41: 121–125.Google Scholar
  67. 67.
    Bone RC: Toward an epidemiology and natural history of SIRS (systemic inflammatory response syndrome). JAMA 1992; 268: 3452–3455.PubMedCrossRefGoogle Scholar
  68. 68.
    Zellweger R, Wichmann MW, Ayala A, Stein S, DeMaso CM, Chaudry IH: Females in proestrus state maintain splenic immune functions and tolerate sepsis better than males. Crit Care Med 1997; 25: 106–110.PubMedCrossRefGoogle Scholar
  69. 69.
    Wichterman KA, Baue AE, Chaudry IH: Sepsis and septic shock: a review of laboratory models and a proposal. J Surg Res 1980; 29: 189–201.PubMedCrossRefGoogle Scholar
  70. 70.
    Wichmann MW, Zellweger R, DeMaso CM, Ayala A, Chaudry IH: Enhanced immune responses in females as opposed to decreased responses in males following hemorrhagic shock and resuscitation. Cytokine 1996; 8: 853–863.PubMedCrossRefGoogle Scholar
  71. 71.
    Angele MK, Wichmann MW, Ayala A, Cioffi WG, Ghaudry IH: Testosterone receptor blockade after hemorrhage in males: restoration of the depressed immune functions and improved survival following subsequent sepsis. Arch Surg 1997; 132: 1207–1214.PubMedCrossRefGoogle Scholar
  72. 72.
    Wichmann MW, Inthorn D, Sehildberg FW: Incidence and mortality of severe sepsis in surgical intensive care: influence of gender on disease process and out-come [abstract]. Shock, 1998; 10: 3.CrossRefGoogle Scholar
  73. 73.
    Schröder J, Kahlke V, Staubach KH, Zabel P, Stüber F: Gender differences in human sepsis. Arch Surg 1998; 133: 1200–1205.PubMedCrossRefGoogle Scholar
  74. 74.
    Qiu Y, Peng Y, Wang J: Immunoregulatory role of neurotransmitters. Adv Neuroimmunol 1996; 6: 223–231.PubMedCrossRefGoogle Scholar
  75. 75.
    Quattrocchi KB, Frank EH, Miller CH, Dull ST, Howard RR, Wagner FC Jr: Severe head injury: effect upon cellular immune function, Neurol Res 1991; 13: 13–20.PubMedGoogle Scholar
  76. 76.
    Brinkman WJ, Hall DM, Suo JL, Weber RJ: Centrally-mediated opioid-induced immunosuppression: elucidation of sympathetic nervous system involvement. Adv Exp Med Biol 1998; 437: 43–49.PubMedCrossRefGoogle Scholar
  77. 77.
    Wichmann MW, Faist E, Chaudry IH: Naloxon verschlechtert die zellvermittelte Immunftmktion nach haemorrhagischem Schock [abstract]. Langenbecks Arch Chir 1997; 585–588.Google Scholar
  78. 78.
    Carr DJ, Carpenter GW, Garza HH Jr, Baker ML, Gebhardt BM: Cellular mechanisms involved in morphine-mediated suppression of CTL activity. Adv Exp Med Biol 1995; 373: 131–139.PubMedCrossRefGoogle Scholar
  79. 79.
    Jankovic BD, Radulovic J: Enkephalins, brain and immunity: modulation of immune responses by methionine-enkephalininjected into the cerebral cavity. Int J Neurosci 1992; 67: 241–270.PubMedCrossRefGoogle Scholar
  80. 80.
    Zellweger R, Wichmann MW, Ayala A, Chaudry IH: Metoclo-pramide: a novel and safe imunomodulating agent for restoringthe depressed macrophage immune function following hemorrhage. J Trauma 1998; 44: 70–77.PubMedCrossRefGoogle Scholar
  81. 81.
    Kim C, Schinkel C, Fuchs D, et al: Interleukin-13 effectively down-regulates the monocyte inflammatory potential during traumatic stress. Arch Surg 1995; 130: 1330–1336.PubMedCrossRefGoogle Scholar
  82. 82.
    DeWaalMalefyt R, Figdor CG, Huijbens R, et al: Effects of IL-13 on phenotype, cytokine production, and cytotoxic function of human monocytes. J Immunol 1993; 151: 6370–6381.Google Scholar
  83. 83.
    DeWaalMalefyt R, Yssel H, Roncaralo MG, Spits H, deVries J: Interleukin-10. Curr Opin Immunol 1992; 4: 314–320.CrossRefGoogle Scholar
  84. 84.
    Ayala A, Lehman DL, Herdon CD, Chaudry IH: Mechanism of enhanced susceptibility to sepsis following hemorrhage: interleu-kin (IL)-10 suppression of T-cell response is mediated by eicosanoid induced IL-4 release. Arch Surg 1994; 129: 1172–1178.PubMedCrossRefGoogle Scholar
  85. 85.
    Napolitano LM, Campbell C: Nitric oxide inhibition normalizes splenocyte interleukin-10 synthesis in murine thermal injury. Arch Surg 1994; 129: 1276–1282.PubMedCrossRefGoogle Scholar
  86. 86.
    Polk HC Jr, Cheadle WG, Livingston DH, et al: A randomized prospective clinical trial to determine the efficacy of interferon-gamma in severely injured patients. Am J Surg 1992; 163: 191–196.PubMedCrossRefGoogle Scholar
  87. 87.
    Babcock GF, Rodeberg DA, White-Owen C: Changes in neutrophil function following major trauma or thermal injury [abstract]. J Intensive Care Med 1994; 20: 172.Google Scholar
  88. 88.
    Silva AT, Cohen J: Role of Interferon-gamma in experimental gram-negative sepsis. J Infect Dis 1992; 166: 331–335.PubMedCrossRefGoogle Scholar
  89. 89.
    Faist E, Ertel W, Salmen B, et al: The immune-enhancing effect of perioperative thymopentin administration in elderly patients undergoing major surgery. Arch Surg 1988; 123: 1449–1453.PubMedCrossRefGoogle Scholar
  90. 90.
    Faist E, Ertel W, Cohnert T, Huber P, Inthorn D, Heberer G: Immunoprotective effects of cyclooxygenase inhibition in patients with major surgical trauma. J Trauma 1990; 30: 8–18.PubMedCrossRefGoogle Scholar
  91. 91.
    Faist E, Markewitz A, Fuchs D, Lang S, Zarius S, Schildberg FW: Immunomodulatory therapy with thymopentin and indomethacin: successful restoration of interleukin-2 synthesis in patients with major surgery. Ann Surg 1991; 214: 264–274.PubMedCrossRefGoogle Scholar
  92. 92.
    Markewitz A, Faist E, Weinhold C, et al: Alterations of cell-mediated immune response following cardiac surgery. Eur J Cardiothorac Surg 1993; 7: 193–199.PubMedCrossRefGoogle Scholar
  93. 93.
    VanFurth R: Cell biology of mononuclear phagocytes. In: VanFurth R (ed) Hemopoietic Growth Factors and Mononuclear Phagocytes. Basel, R. Karger, 1993; 1–9.Google Scholar
  94. 94.
    Hartung T, Döcke WD, Gantner F, et al: Effect of granulocyte colony-stimulating factor treatment on ex-vivo blood cytokines response in human volunteers. Blood 1995; 85: 2482–2489.PubMedGoogle Scholar
  95. 95.
    Bonilla MA, Gillio AP, Ruggeiro M, et al: Effects of recombinant human granulocyte colony-stimulating factor on neutropenia in patients with congenital agranulocytosis. N Engl J Med 1989; 320: 1574–1580.PubMedCrossRefGoogle Scholar
  96. 96.
    Cioffi WG Jr, Burleson DG, Jordan BS, et al: Effects of granulocyte-macrophage colony-stimulating factor in burn patients. Arch Surg 1991; 126: 74–79.PubMedCrossRefGoogle Scholar
  97. 97.
    Mandell G: ARDS, neutrophils, and pentoxifylline. Am Rev Respir Dis 1988; 136: 1103–1105.CrossRefGoogle Scholar
  98. 98.
    Strieter RM, Remick DG, Ward PA, et al: Cellular and molecular regulation of tumor necrosis factor-alpha production by pentoxifylline. Biochem Biophys Resun Commun 1998; 155: 1230–1236.CrossRefGoogle Scholar
  99. 99.
    Endres S, Fulle HJ, Sinha B, et al: Cyclic nucleotides differentially regulate the synthesis of tumour necrosis factor-alpha and interleukin-1 beta by human mononuclear cells. Immunology 1991; 72: 56–60.PubMedGoogle Scholar
  100. 100.
    Bacher A, Mayer N, Klimscha W, Oismüller C, Steltzer H, Hammerle A: Effects of pentoxifylline on hemodynamics andoxygenation in septic and nonseptic patients. Crit Care Med 1997; 25: 795–800.PubMedCrossRefGoogle Scholar
  101. 101.
    Inthorn D, Hoffmann JN, Hartl WH, Mühlbayer D, Jochum M: Antithrombin III supplementation in severe sepsis: beneficial effects on organ dysfunction. Shock 1997; 8: 328–334.PubMedCrossRefGoogle Scholar

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© Springer Science+Business Media New York 2000

Authors and Affiliations

  • Eugen Faist
  • M. W. Wichmann

There are no affiliations available

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