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The mHLA-DR System in the Critically Ill

  • A. Gouel
  • A. Lepape
  • B. Allaouchiche
Part of the Annual Update in Intensive Care and Emergency Medicine book series (AUICEM, volume 2012)

Abstract

Nosocomial infections represent a major public health problem, with an incidence of about 12 % in the intensive care unit (ICU) in 2005 [1]. Such infections are responsible for a substantial level of morbidity and mortality, and increased length of stay in the ICU and healthcare-associated costs. A new risk factor for nosocomial infection, immunosuppression, has recently been identified in critically ill patients. It is well accepted that every severe inflammatory stress state is accompanied by a hyper-inflammation state, followed by secondary immunosuppression induced by anti-inflammatory mechanisms dedicated to control the initial inflammatory response. This immunosuppressive mechanism has been found in numerous circumstances, such as sepsis, severe trauma, or invasive surgery. In the absence of clinical signs of immune status, various biological parameters have been evaluated. Among the biomarkers studied, monocyte expression of human leukocyte antigen (HLA-DR), or mHLA-DR, has provided the most satisfactory results in representing immune function. The goal of this review is to present an overview of mHLA-DR in the ICU, in terms of its prognostic value for mortality and secondary infections and its potential in the monitoring of new immune treatments in septic shock.

Keywords

Septic Shock Human Leukocyte Antigen Sequential Organ Failure Assessment Severe Acute Pancreatitis Granulocyte Macrophage Colony Stimulate Factor 
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.

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References

  1. 1.
    REA-RAISIN (2006) Surveillance des infections nosocomiales en réanimation adulte en France — Résultats 2005. Available at: http://www.ladocumentationfrancaise.fr/var/storage/rapports-publics//064000852/0000.pdf Accessed Jan 2012Google Scholar
  2. 2.
    Moalic V, Ferec C (2005) HLA typing, analysis methods, and clinical applications. Presse Med 34: 1101–1108PubMedCrossRefGoogle Scholar
  3. 3.
    Döcke WD, Hoflich C, Davis KA, et al (2005) Monitoring temporary immunodepression by flow cytometric measurement of monocytic HLA-DR expression: a multicenter standardized study. Clin Chem 51: 2341–2347PubMedCrossRefGoogle Scholar
  4. 4.
    Cheadle WG, Hershman MJ, Wellhausen SR, Polk HC Jr (1991) HLA-DR antigen expression on peripheral blood monocytes correlates with surgical infection. Am J Surg 161: 639–645PubMedCrossRefGoogle Scholar
  5. 5.
    Nierhaus A, Montag B, Timmler N, et al (2003) Reversal of immunoparalysis by recombinant human granulocyte-macrophage colony-stimulating factor in patients with severe sepsis. Intensive Care Med 29: 646–651PubMedGoogle Scholar
  6. 6.
    Fumeaux T, Pugin J (2002) Role of interleukin-10 in the intracellular sequestration of human leukocyte antigen-DR in monocytes during septic shock. Am J Respir Crit Care Med 166: 1475–1482PubMedCrossRefGoogle Scholar
  7. 7.
    Döcke WD, Randow F, Syrbe U, et al (1997) Monocyte deactivation in septic patients: restoration by IFN-gamma treatment. Nat Med 3: 678–681PubMedCrossRefGoogle Scholar
  8. 8.
    Volk HD, Reinke P, Krausch D, et al (1996) Monocyte deactivation—rationale for a new therapeutic strategy in sepsis. Intensive Care Med 22 (Suppl 4): 474–481CrossRefGoogle Scholar
  9. 9.
    Schinkel C, Sendtner R, Zimmer S, Faist E (1998) Functional analysis of monocyte subsets in surgical sepsis. J Trauma 44: 743–748PubMedCrossRefGoogle Scholar
  10. 10.
    Tschaikowsky K, Hedwig-Geissing M, Schiele A, Bremer F, Schywalsky M, Schuttler J (2002) Coincidence of pro-and anti-inflammatory responses in the early phase of severe sepsis: Longitudinal study of mononuclear histocompatibility leukocyte antigen-DR expression, procalcitonin, C-reactive protein, and changes in T-cell subsets in septic and postoperative patients. Crit Care Med 30: 1015–1023PubMedCrossRefGoogle Scholar
  11. 11.
    Monneret G, Lepape A, Voirin N, et al (2006) Persisting low monocyte human leukocyte antigen-DR expression predicts mortality in septic shock. Intensive Care Med 32: 1175–1183PubMedCrossRefGoogle Scholar
  12. 12.
    Landelle C, Lepape A, Voirin N, et al (2010) Low monocyte human leukocyte antigen-DR is independently associated with nosocomial infections after septic shock. Intensive Care Med 36: 1859–1866PubMedCrossRefGoogle Scholar
  13. 13.
    Lukaszewicz AC, Grienay M, Resche-Rigon M, et al (2009) Monocytic HLA-DR expression in intensive care patients: interest for prognosis and secondary infection prediction. Crit Care Med 37: 2746–2752PubMedCrossRefGoogle Scholar
  14. 14.
    Caille V, Chiche JD, Nciri N, et al (2004) Histocompatibility leukocyte antigen-D related expression is specifically altered and predicts mortality in septic shock but not in other causes of shock. Shock 22: 521–526PubMedCrossRefGoogle Scholar
  15. 15.
    Monneret G, Debard AL, Venet F, et al (2003) Marked elevation of human circulating CD4+CD25+ regulatory T cells in sepsis-induced immunoparalysis. Crit Care Med 31: 2068–2071PubMedCrossRefGoogle Scholar
  16. 16.
    Saenz JJ, Izura JJ, Manrique A, Sala F, Gaminde I (2001) Early prognosis in severe sepsis via analyzing the monocyte immunophenotype. Intensive Care Med 27: 970–977PubMedCrossRefGoogle Scholar
  17. 17.
    Perry SE, Mostafa SM, Wenstone R, Shenkin A, McLaughlin PJ (2003) Is low monocyte HLA-DR expression helpful to predict outcome in severe sepsis? Intensive Care Med 29: 1245–1252PubMedCrossRefGoogle Scholar
  18. 18.
    Ploder M, Pelinka L, Schmuckenschlager C, et al (2006) Lipopolysaccharide-induced tumor necrosis factor alpha production and not monocyte human leukocyte antigen-DR expression is correlated with survival in septic trauma patients. Shock 25: 129–134PubMedGoogle Scholar
  19. 19.
    Hynninen M, Pettila V, Takkunen O, et al (2003) Predictive value of monocyte histocompatibility leukocyte antigen-DR expression and plasma interleukin-4 and-10 levels in critically ill patients with sepsis. Shock 20: 1–4PubMedCrossRefGoogle Scholar
  20. 20.
    Hotchkiss RS, Opal S (2010) Immunotherapy for sepsis—a new approach against an ancient foe. N Engl J Med 363: 87–89PubMedCrossRefGoogle Scholar
  21. 21.
    Turina M, Dickinson A, Gardner S, Polk HC Jr (2006) Monocyte HLA-DR and interferongamma treatment in severely injured patients—a critical reappraisal more than a decade later. J Am Coll Surg 203: 73–81PubMedCrossRefGoogle Scholar
  22. 22.
    Hershman MJ, Appel SH, Wellhausen SR, Sonnenfeld G, Polk HC Jr (1989) Interferongamma treatment increases HLA-DR expression on monocytes in severely injured patients. Clin Exp Immunol 77: 67–70PubMedGoogle Scholar
  23. 23.
    Wasserman D, Ioannovich JD, Hinzmann RD, Deichsel G, Steinmann GG (1998) Interferon-gamma in the prevention of severe burn-related infections: a European phase III multicenter trial. The Severe Burns Study Group. Crit Care Med 26: 434–439PubMedCrossRefGoogle Scholar
  24. 24.
    Dries DJ, Perry JF Jr (2002) Interferon-gamma: titration of inflammation. Crit Care Med 30: 1663–1664PubMedCrossRefGoogle Scholar
  25. 25.
    Meisel C, Schefold JC, Pschowski R, et al (2009) Granulocyte-macrophage colony-stimulating factor to reverse sepsis-associated immunosuppression: a double-blind, randomized, placebo-controlled multicenter trial. Am J Respir Crit Care Med 180: 640–648PubMedCrossRefGoogle Scholar
  26. 26.
    Bo L, Wang F, Zhu J, Li J, Deng X (2011) Granulocyte-colony stimulating factor (G-CSF) and granulocyte-macrophage colony stimulating factor (GM-CSF) for sepsis: a meta-analysis. Crit Care 15: R58PubMedCrossRefGoogle Scholar
  27. 27.
    Giannoudis PV, Smith RM, Windsor AC, Bellamy MC, Guillou PJ (1999) Monocyte human leukocyte antigen-DR expression correlates with intrapulmonary shunting after major trauma. Am J Surg 177: 454–459PubMedCrossRefGoogle Scholar
  28. 28.
    Cheron A, Floccard B, Allaouchiche B, et al (2010) Lack of recovery in monocyte human leukocyte antigen-DR expression is independently associated with the development of sepsis after major trauma. Crit Care 14: R208PubMedCrossRefGoogle Scholar
  29. 29.
    Giannoudis PV, Smith RM, Perry SL, Windsor AJ, Dickson RA, Bellamy MC (2000) Immediate IL-10 expression following major orthopaedic trauma: relationship to anti-inflammatory response and subsequent development of sepsis. Intensive Care Med 26: 1076–1081PubMedCrossRefGoogle Scholar
  30. 30.
    Walsh DS, Thavichaigarn P, Pattanapanyasat K, et al (2005) Characterization of circulating monocytes expressing HLA-DR or CD71 and related soluble factors for 2 weeks after severe, non-thermal injury. J Surg Res 129: 221–230PubMedCrossRefGoogle Scholar
  31. 31.
    Allen ML, Peters MJ, Goldman A, et al (2002) Early postoperative monocyte deactivation predicts systemic inflammation and prolonged stay in pediatric cardiac intensive care. Crit Care Med 30: 1140–1145PubMedCrossRefGoogle Scholar
  32. 32.
    Gotzinger P, Sautner T, Spittler A, et al (2000) Severe acute pancreatitis causes alterations in HLA-DR and CD14 expression on peripheral blood monocytes independently of surgical treatment. Eur J Surg 166: 628–632PubMedCrossRefGoogle Scholar
  33. 33.
    Satoh A, Miura T, Satoh K, et al (2002) Human leukocyte antigen-DR expression on peripheral monocytes as a predictive marker of sepsis during acute pancreatitis. Pancreas 25: 245–250PubMedCrossRefGoogle Scholar
  34. 34.
    Yu WK, Li WQ, Li N, Li JS (2004) Mononuclear histocompatibility leukocyte antigen-DR expression in the early phase of acute pancreatitis. Pancreatology 4: 233–243PubMedCrossRefGoogle Scholar
  35. 35.
    Richter A, Nebe T, Wendl K, et al (1999) HLA-DR expression in acute pancreatitis. Eur J Surg 165: 947–951PubMedCrossRefGoogle Scholar
  36. 36.
    Sachse C, Prigge M, Cramer G, Pallua N, Henkel E (1999) Association between reduced human leukocyte antigen (HLA)-DR expression on blood monocytes and increased plasma level of interleukin-10 in patients with severe burns. Clin Chem Lab Med 37: 193–198PubMedCrossRefGoogle Scholar
  37. 37.
    Venet F, Tissot S, Debard AL, et al (2007) Decreased monocyte human leukocyte antigen-DR expression after severe burn injury: Correlation with severity and secondary septic shock. Crit Care Med 35: 1910–1917PubMedCrossRefGoogle Scholar
  38. 38.
    Zhang DP, Yan FL, Xu HQ, Zhu YX, Yin Y, Lu HQ (2009) A decrease of human leucocyte antigen-DR expression on monocytes in peripheral blood predicts stroke-associated infection in critically-ill patients with acute stroke. Eur J Neurol 16: 498–505PubMedCrossRefGoogle Scholar
  39. 39.
    Harms H, Prass K, Meisel C, et al (2008) Preventive antibacterial therapy in acute ischemic stroke: a randomized controlled trial. PLoS ONE 3: e2158CrossRefGoogle Scholar
  40. 40.
    Kox WJ, Volk T, Kox SN, Volk HD (2000) Immunomodulatory therapies in sepsis. Intensive Care Med 26 (Suppl 1): 124–128CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • A. Gouel
  • A. Lepape
  • B. Allaouchiche

There are no affiliations available

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