Top

Published in:

01-08-2002 | Review

Clinical review: Immunodepression in the surgical patient and increased susceptibility to infection

Authors: Martin K Angele, Eugen Faist

Published in: Critical Care | Issue 4/2002

Abstract

Several studies indicate that organ failure is the leading cause of death in surgical patients. An excessive inflammatory response followed by a dramatic paralysis of cell-mediated immunity following major surgery appears to be responsible for the increased susceptibility to subsequent sepsis. In view of this, most of the scientific and medical research has been directed towards measuring the progression and inter-relationship of mediators following major surgery. Furthermore, the effect of those mediators on cell-mediated immune responses has been studied. This article will focus on the effect of blood loss and surgical injury on cell-mediated immune responses in experimental studies utilizing models of trauma and hemorrhagic shock, which have defined effects on the immunoinflammatory response. Subsequently these findings will be correlated with data generated from surgical patients. The results of these studies may generate new approaches for the treatment of immunodepression following major surgery, thus reducing the susceptibility to infection and increasing the survival rate of the critical ill surgical patient.

Carrico CJ, Meakins JL, Marshall JC: Multiple organ failure syndrome. Arch Surg 1986, 121: 196-208.CrossRefPubMed

Stahl GL, Bitterman H, Terashita Z, Lefer AM: Salutary consequences of blockade of platelet activating factor in hemorrhagic shock. Eur J Pharmacol 1988, 149: 233-240. 10.1016/0014-2999(88)90653-XCrossRefPubMed

Chaudry IH, Ayala A: Immunological Aspects of Hemorrhage. Austin: Medical Intelligence Unit, RG Landes Company; 1992.

Stephan RN, Ayala A, Chaudry IH: Monocyte and lymphocyte responses following trauma. In Pathophysiology of Shock, Sepsis and Organ Failure. (Edited by: Schlag G, Redl H). Berlin: Springer-Verlag 1993, 131-144.CrossRef

Roumen RM, Hendriks T, van der Ven-Jongekrijg J, Nieuwenhuijzen GAP, Sauerwein RW, van der Meer JW, Goris RJA: Cytokine patterns in patients after major surgery, hemorrhagic shock, and severe blunt trauma. Ann Surg 1993, 6: 769-776.CrossRef

Faist E, Baue AE, Dittmer H: Multiple organ failure in poly-trauma patients. J Trauma 1983, 23: 775-787.CrossRefPubMed

Haupt W, Riese J, Mehler C, Weber K, Zowe M, Hohenberger W: Monocyte function before and after surgical trauma. Dig Surg 1998, 15: 102-104. 10.1159/000018601CrossRefPubMed

Faist E, Storck M, Hultner L, Redl H, Ertel W, Walz A, Schildberg FW: Functional analysis of monocytes activity through synthesis patterns of proinflammatory cytokines and neopterin in patients in surgical intensive care. Surgery 1992, 112: 562-572.PubMed

Hensler T, Ecker H, Eeg K, Eidecke CD, Artels H, Arthlen W, Agner H, Iewert JR, Olzmann B: Distinct mechanisms of immunosuppression as a consequence of major surgery. Infect Immun 1997, 65: 2283-2291.PubMedCentralPubMed

10.

Fingerle-Rowson G, Auers J, Kreuzer E, Fraunberger P, Blumenstein M, Ziegler-Heitbrock LH: Expansion of CD14+CD16+ monocytes in critically ill cardiac surgery patients. Inflammation 1998, 22: 367-379. 10.1023/A:1022316815196CrossRefPubMed

11.

Ayala A, Ertel W, Chaudry IH: Trauma-induced suppression of antigen presentation and expression of major histocompati-bility class II antigen complex in leukocytes. Shock 1996, 5: 79-90.CrossRefPubMed

12.

Schinkel C, Sendtner R, Zimmer S, Faist E: Functional analysis of monocyte subsets in surgical sepsis. J Trauma 1998, 44: 743-748.CrossRefPubMed

13.

Wakefield CH, Carey PD, Foulds S, Monson JR, Guillou PJ: Changes in major histocompatibility complex class II expression in monocytes and T cells of patients developing infection after surgery. Br J Surg 1993, 80: 205-209.CrossRefPubMed

14.

MacLean LD, Meakins JL, Taguchi K, Duignan J, Dhillon KS, Gordon J: Host resistance in sepsis and trauma. Ann Surg 1975, 182: 207-211.PubMedCentralCrossRefPubMed

15.

Christou NV, Tellado JM: The impact of preexisting disease conditions for host defense integrity in traumatized and critically ill patients. In Host Defense Dysfunction in Trauma, Shock and Sepsis. (Edited by: Faist E, Meakins J, Schildberg FW). Berlin-Heidelberg: Springer-Verlag 1993, 73-82.CrossRef

16.

Levy EM, Alharbi SA, Grindlinger G, Black PH: Changes in mitogen responsiveness lymphocyte subsets after traumatic injury: relation to development of sepsis. Clin Immunol Immunopathol 1984, 32: 224-233.CrossRefPubMed

17.

Keane RM, Birmingham W, Shatney CM, Winchurch RA, Munster AM: Prediction of sepsis in the multitraumatic patient by assays of lymphocyte responsiveness. Surg Gynecol Obstet 1983, 156: 163-167.PubMed

18.

Ayala A, Lehman DL, Herdon CD, Chaudry IH: Mechanism of enhanced susceptibility to sepsis following hemorrhage: interleukin (IL)-10 suppression of T-cell response is mediated by eicosanoid induced IL-4 release. Arch Surg 1994, 129: 1172-1178.CrossRefPubMed

19.

Stephan RN, Kupper TS, Geha AS, Baue AE, Chaudry IH: Hemorrhage without tissue trauma produces immunosuppression and enhances susceptibility to sepsis. Arch Surg 1987, 122: 62-68.CrossRefPubMed

20.

Riddle PR, Berenbaum MC: Postoperative depression of the lymphocyte response to phytohaemagglutinin. Lancet 1967, i: 746-748.CrossRef

21.

O'Mahony JB, Palder SB, Wood JJ, McIrvine A, Rodrick ML, Demling RH, Mannick JA: Depression of cellular immunity after multiple trauma in the absence of sepsis. J Trauma 1984, 24: 869-875.CrossRefPubMed

22.

Daniels JC, Sakai H, Cobb EK, Lewis SR, Larson DL, Ritzmann SE: Evaluation of lymphocyte reactivity studies in patients with thermal burns. J Trauma 1971, 11: 595-607.CrossRefPubMed

23.

Sakai H, Daniels JC, Lewis SR, Lynch JB, Watson DL, Ritzmann SE: Reversible alterations of nucleic acid synthesis in lymphocytes after thermal burns. J Reticuloendothelial Soc 1972, 11: 19-28.

24.

Abraham E, Chang YH: The effects of hemorrhage on mitogen-induced lymphocyte proliferation. Circ Shock 1985, 15: 141-149.PubMed

25.

Angele MK, Ayala A, Cioffi WG, Bland KI, Chaudry IH: Testosterone: the culprit for producing splenocyte depression following trauma-hemorrhage. Am J Physiol 1998, 274: C1530-C1536.PubMed

26.

Zellweger R, Ayala A, DeMaso CM, Chaudry IH: Trauma-hemorrhage causes prolonged depression in cellular immunity. Shock 1995, 4: 149-153.CrossRefPubMed

27.

Lyons A, Goebel A, Mannick JA, Lederer JA: Protective effects of early interleukin 10 antagonism on injury-induced immune dysfunction. Arch Surg 1999, 134: 1317-1323. 10.1001/archsurg.134.12.1317CrossRefPubMed

28.

van der Poll T, Marchant A, Buurman WA, Berman L, Keogh CV, Lazarus DD, Nguyen L, Goldman M, Moldawer LL, Lowry SF: Endogenous IL-10 protects mice from death during septic peritonitis. J Immunol 1995, 155: 5397-5401.PubMed

29.

Feeney C, Bryzman S, Kong L, Brazil H, Deutsch R, Fritz LC: T-lymphocyte subsets in acute illness. Crit Care Med 1995, 23: 1680-1685. 10.1097/00003246-199510000-00012CrossRefPubMed

30.

O'Mahony JB, Wood JJ, Rodrick ML, Mannick JA: Changes in T lymphocyte subsets following injury. Assessment by flow cytometry and relationship to sepsis. Ann Surg 1985, 202: 580-586.PubMedCentralCrossRefPubMed

31.

Abraham E, Freitas AA: Hemorrhage in mice induces alterations in immunoglobulin-secreting B-cells. Crit Care Med 1989, 17: 1015-1019.CrossRefPubMed

32.

Abraham E, Freitas AA: Hemorrhage produces abnormalities in lymphocyte function and lymphokine generation. J Immunol 1989, 142: 899-906.PubMed

33.

Fuchs D, Gruber A, Wachter H, Faist E: Activated cell-mediated immunity and immunodeficiency in trauma and sepsis. In The Immune Consequences of Trauma, Shock and Sepsis. Mechanisms and Therapeutic Approaches. (Edited by: Faist E, Baue AE, Schildberg FW). Lengerich: Pabst Science Publishers 1996, 235-239.

34.

Fuchs D, Malkovsky M, Reibnegger G, Werner ER, Forni G, Wachter H: Endogenous release of interferon-gamma and diminished response of peripheral blood mononuclear cells to antigenic stimulation. Immunol Lett 1989, December 23: 103-108. 10.1016/0165-2478(89)90120-XCrossRef

35.

Ayala A, Perrin MM, Meldrum DR, Ertel W, Chaudry IH: Hemorrhage induces an increase in serum TNF which is not associated with elevated levels of endotoxin. Cytokine 1990, 2: 170-174.CrossRefPubMed

36.

Ayala A, Wang P, Ba ZF, Perrin MM, Ertel W, Chaudry IH: Differential alterations in plasma IL-6 and TNF levels following trauma and hemorrhage. Am J Physiol 1991, 260: R167-R171.PubMed

37.

Damas P, Reuter A, Gysen P, Demonty J, Lamy M, Franchimont P: Tumor necrosis factor and interleukin-1 serum levels during severe sepsis in humans. Crit Care Med 1989, 17: 975-978.CrossRefPubMed

38.

Damas P, Ledoux D, Nys M, Vrindts Y, De Groote D, Franchimont P, Lamy M: Cytokine serum level during severe sepsis in human IL-6 as a marker of severity. Ann Surg 1992, 215: 356-362.PubMedCentralCrossRefPubMed

39.

Romagnani S: Th1 and Th2 in human diseases. Clin Immunol Immunopathol 1996, 80: 225-235. 10.1006/clin.1996.0118CrossRefPubMed

40.

Martin C, Boisson C, Haccoun M, Thomachot L, Mege JL: Patterns of cytokine evolution (tumor necrosis factor-α and interleukin-6) after septic shock, hemorrhagic shock, and severe trauma. Crit Care Med 1997, 25: 1813-1819. 10.1097/00003246-199711000-00018CrossRefPubMed

41.

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.PubMedCentralPubMed

42.

Porteu F, Nathan C: Shedding of tumor necrosis factor receptors by activated human neutrophils. J Exp Med 1990, 172: 599-607.CrossRefPubMed

43.

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.PubMed

44.

Wong GC, Clark SC: Multiple actions of interleukin 6 within a cytokine network. Immunol Today 1988, 9: 137-139. 10.1016/0167-5699(88)91200-5CrossRefPubMed

45.

Okusawa S, Gelfand JA, Ikejima T, Connolly RJ, Dinarello CA: Interleukin-1 induces a shock like state in rabbits. Synergism with tumor necrosis factor and the effects of cyclooxygenase inhibition. J Clin Invest 1988, 81: 1162-1172.PubMedCentralCrossRefPubMed

46.

Tracey KJ, Lowry SF, Fahey TJI, Albert JD, Fong Y, Hesse D, Beutler B, Manogue KR, Calvano S, Wei H, Cerami A, Shires GT: Cachectin/tumor necrosis factor induces lethal shock and stress hormone responses in the dog. Surg Gynecol Obstet 1987, 164: 415-422.PubMed

47.

Lejeune P, Lagadec P, Onier N, Pinnard D, Ohshima H, Jeannin JF: Nitric oxide involvement in tumor-induced immunosuppression. J Immunol 1994, 152: 5077-5083.PubMed

48.

O'Neill PJ, Ayala A, Wang P, Ba ZF, Morrison MH, Schultze AE, Reich SS, Chaudry IH: Role of Kupffer cells in interleukin-6 release following trauma-hemorrhage and resuscitation. Shock 1988, 1: 43-47.CrossRef

49.

Ayala A, Meldrum DR, Perrin MM, Chaudry IH: The release of transforming growth factor-β following hemorrhage: its role as a mediator of host immunosuppression [abstract]. FASEB J 1992, 6: A1604.

50.

Miller-Graziano CL, Szabo G, Griffey K, Metha B, Kodys K, Catalano D: Role of elevated monocyte transforming growth factor beta (TGF-beta) production in posttrauma immunosuppression. J Clin Immunol 1991, 11: 95-102.CrossRefPubMed

51.

Waal Malefyt R, Abrams J, Bennett B, Figdor CG, Vries JE: Interleukin 10 (IL-10) inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes. J Exp Med 1991, 174: 1209-1220.CrossRefPubMed

52.

Faist E, Mewes A, Baker CC, Strasser T, Alkan SS, Rieber P, Heberer G: Prostaglandin E₂ dependent suppression of interleukin-2 production in patients with major trauma. J Trauma 1987, 27: 837-848.CrossRefPubMed

53.

Knapp W, Baumgartner G: Monocyte-mediated suppression of human B lymphocyte differentiation in vitro. J Immunol 1978, 121: 1177-1183.PubMed

54.

Johnston PA, Selkurt EE: Effect of hemorrhagic shock on renal release of prostaglandin E. Am J Physiol 1976, 230: 831-838.PubMed

55.

Bonta IL, Parnham MJ: Immunomodulatory-antiinflammatory functions of E-type prostaglandins. Minireview with emphasis on macrophage mediated effects. Int J Immunopharmacol 1982, 4: 103-109. 10.1016/0192-0561(82)90057-1CrossRefPubMed

56.

Plaut M: The role of cyclic AMP in modulating cytotoxic T lymphocytes. I. In vivo-generated cytotoxic lymphocytes, but not in vitro-generated cytotoxic lymphocytes, are inhibited by cyclic AMP-active agents. J Immunol 1979, 123: 692-701.PubMed

57.

Chaudry IH, Ayala A: Immune consequences of hypovolemic shock and resuscitation. Curr Opin Anaesthesiology 1993, 6: 385-392.CrossRef

58.

Ayala A, Chaudry IH: Dietary n-3 polyunsaturated fatty acid modulation of immune cell function pre- or post-trauma. Nutrition 1995, 11: 1-11.PubMed

59.

Beutler B: Tumor necrosis factor and other cytokines in septic syndrome. In Sepsis. (Edited by: Vincent JL). Berlin: Springer-Verlag 1994, 107-121.CrossRef

60.

Shirakawa T, Tokunaga A, Onda M: Release of immunosuppressive substances after gastric resection is more prolonged than after mastectomy in humans. Int Surg 1998, 83: 210-214.PubMed

61.

Feldbush TL, Hobbs MV, Severson CD, Ballas ZF, Weiler JM: Role of complement in the immune response. Fed Proc 1984, 43: 2548-2552.PubMed

62.

Marks JD, Marks CB, Luce JM, Montgomery B, Turner J, Metz CA, Murray JF: Plasma tumor necrosis factor in patients with septic shock. Am Rev Respir Dis 1990, 141: 94-97.CrossRefPubMed

63.

Marano MA, Fong Y, Moldawer LL, Wei H, Calvano SE, Tracey KJ, Barie PS, Manogue K, Cerami A, Shires GT, Lowry SF: Serum cachectin/tumor necrosis factor in critically ill patients with burns correlates with infection and mortality. Surg Gynecol Obstet 1990, 170: 32-38.PubMed

64.

Waage A, Halstensen A, Espevik T: Association between tumor necrosis factor in serum and fatal outcome in patients with meningococcal disease. Lancet 1987, i: 355-357. 10.1016/S0140-6736(87)91728-4CrossRef

65.

Waage A, Brandtzaeg P, Halstensen A, Kierulf P, Espevik T: 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: 333-338.CrossRefPubMed

66.

Molloy RG, Mannick JA, Rodrick ML: Cytokines, sepsis and immunomodulation. Br J Surg 1993, 80: 289-297.CrossRefPubMed

67.

Angele MK, Wichmann MW, Ayala A, Cioffi WG, Chaudry 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.CrossRefPubMed

68.

Zapata-Sirvent RL, Hansbrough JF, Cox MC, Carter WH: Immunologic alterations in a murine model of hemorrhagic shock. Crit Care Med 1992, 20: 508-517.CrossRefPubMed

69.

Simons RK, Hoyt DB, Winchell RJ, Rose RM, Holbrook T: Elevated selectin levels after severe trauma: a marker for sepsis and organ failure and a potential target for immounomodula-tory therapy. J Trauma 1996, 41: 653-662.CrossRefPubMed

70.

Bone RC: Toward an epidemiology and natural history of SIRS (systemic inflammatory response syndrome). JAMA 1992, 268: 3452-3455. 10.1001/jama.268.24.3452CrossRefPubMed

71.

Center for Disease Control: Mortality Patterns – United States, 1989. MMWR 1992, 41: 121-125.

72.

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: 316-335.CrossRefPubMed

73.

Schroder J, Kahlke V, Staubach KH, Zabel P, Stuber F: Gender differences in human sepsis. Arch Surg 1998, 133: 1200-1205. 10.1001/archsurg.133.11.1200CrossRefPubMed

74.

Zellweger R, Ayala A, Stein S, DeMaso CM, Chaudry IH: Females in proestrus state tolerate sepsis better than males. Crit Care Med 1997, 25: 106-110. 10.1097/00003246-199701000-00021CrossRefPubMed

75.

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. Cytokine 1996, 8: 853-863. 10.1006/cyto.1996.0114CrossRefPubMed

76.

Angele MK, Knoferl MW, Ayala A, Cioffi WG, Bland K, Chaudry IH: Male and female sex steroids: do they produce deleterious or beneficial effects on immune responses following trauma-hemorrhage? Surg Forum 1998, 49: 43-45.

77.

Knoferl MW, Diodato MD, Angele MK, Ayala A, Cioffi WG, Bland KI, Chaudry IH: Do female sex steroids adversely or beneficially affect the depressed immune responses in males after trauma-hemorrhage? Arch Surg 2000, 135: 425-433. 10.1001/archsurg.135.4.425CrossRefPubMed

78.

Mannucci PM: Venous thromboembolism and hormone replacement therapy. Eur J Intern Med 2001, 12: 478-483. 10.1016/S0953-6205(01)00169-8CrossRefPubMed

79.

Catania RA, Angele MK, Ayala A, Cioffi WG, Bland K, Chaudry IH: Dehydroepiandrosterone (DHEA) restores immune function following trauma-hemorrhage by a direct effect on T-lymphocytes. Cytokine 1998, 11: 443-450. 10.1006/cyto.1998.0458CrossRef

80.

Angele MK, Catania RA, Ayala A, Cioffi WG, Bland K, Chaudry IH: Dehydroepiandrosterone (DHEA): an inexpensive steroid hormone which decreases the mortality from sepsis. Arch Surg 1998, 133: 1281-1288. 10.1001/archsurg.133.12.1281CrossRefPubMed

81.

Wichmann MW, Ayala A, Chaudry I: Male sex steroids are responsible for depressing macrophage immune function after trauma-hemorrhage. Am J Physiol 1997, 273: C1335-C1340.PubMed

82.

Angele MK, Ayala A, Monfils BA, Cioffi WG, Bland KI, Chaudry IH: Testosterone and/or low estradiol: normally required but harmful immunologically for males after trauma-hemorrhage. J Trauma 1998, 44: 78-85.CrossRefPubMed

83.

Angele MK, Xu YX, Ayala A, Catania RA, Cioffi WG, Bland KI, Chaudry IH: Gender differences in immune responses: increased thymocyte apoptosis occurs only in males but not in females after trauma-hemorrhage. Surg Forum 1997, 48: 95-97.

84.

Gannon CJ, Napolitano LM, Pasquale M, Tracy K, McCarter RJ: Male gender increases risk of postinjury pneumonia. Surg Forum 2001, 52: 468-469.

85.

Offner PJ, Moore EE, Biffl WL: Male gender is a risk factor for post-injury major infections [abstract]. In Proceedings of the 19th Meeting of the Surgical Infection Society 1999, 20.

86.

Oberholzer A, Keel M, Trentz O, Ertel W: Die inzidenz von septischen komplikationen nach polytrauma ist geschlechts-spezifisch [abstract]. Hefte zu Der Unfallchirurg 63. Jahrestagung der Deutschen Gesellschaft fuer Unfallchirurgie: 1999, 231-232.

Title: Clinical review: Immunodepression in the surgical patient and increased susceptibility to infection
Authors: Martin K Angele
Eugen Faist
Publication date: 01-08-2002
Publisher: BioMed Central
Published in: Critical Care / Issue 4/2002
Electronic ISSN: 1364-8535
DOI: https://doi.org/10.1186/cc1514

At a glance: The STEP trials

Springer Medicine

Clinical review: Immunodepression in the surgical patient and increased susceptibility to infection

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 4/2002

Bench-to-bedside review: Lactate and the lung

Bench-to-bedside review: A possible resolution of the glucose paradox of cerebral ischemia

Lactate: A key metabolite in the intercellular metabolic interplay

ICU Cornerstone: Changing our view of blood transfusions

The effects of IgM-enriched immunoglobulin preparations in patients with severe sepsis [ISRCTN28863830]

Clinical review: Splanchnic ischaemia