Résumé
Le polytraumatisme s’accompagne d’un syndrome de réponse inflammatoire systémique (SRIS) causé par la libération de composants intracellulaires nommés danger-associated molecular patterns (DAMP). Ces DAMP vont directement stimuler des récepteurs spécifiques, les pattern recognition receptors, présents sur les cellules de l’immunité, entraînant le relargage de médiateurs de l’inflammation. Pour éviter les complications systémiques d’un SRIS non contrôlé, l’organisme développe précocement une réponse anti-inflammatoire systémique compensatrice (CARS). Le CARS entraîne une immunodépression post-traumatique, de durée et d’amplitude variable. Cette immunodépression est « physiologique » au départ et présente chez tous les patients. L’immunodépression devient pathologique si elle perdure, entraînant alors des infections post-traumatiques (pneumopathies essentiellement) qui sont la première cause de complications en réanimation. Sans que l’on sache exactement pourquoi, certains patients ont une récupération immunologique très rapide qui les protège des complications. Un monitorage immunologique pourrait donc permettre de cibler les patients qui récupèrent plus lentement et qui sont susceptibles de bénéficier d’un traitement immunomodulateur. À l’heure actuelle, la diminution de l’expression membranaire monocytaire de HLA-DR est le meilleur marqueur pour prédire la survenue d’infections secondaires. Différents traitements stimulant l’immunité (GM-CSF, interféron-γ, glucans, immunoglobulines) ont été évalués chez l’homme sans monitorage immunologique, avec des résultats variables. L’hydrocortisone a montré des effets bénéfiques probablement en diminuant l’amplitude du SRIS. L’évaluation de nouveaux traitements immunostimulants, fondés sur les données physiopathologiques et un monitorage immunologique (HLA-DR notamment) maintenant disponible dans la plupart des centres, devrait permettre dans le futur de modifier le devenir des patients traumatisés.
Abstract
Severe multiple trauma is accompanied by a systemic inflammatory response syndrome (SIRS) caused by a massive release of intracellular components called danger-associated molecular patterns (DAMP). These DAMP will directly stimulate specific receptors present at the surface of immune cells, called pattern recognition receptors. The activation of these receptors will induce the release of inflammatory mediators. In an attempt to avoid systemic complications of uncontrolled SIRS, the body develops a systemic compensatory anti-inflammatory response syndrome (CARS). CARS induces a post-traumatic immunodepression with a variable duration and amplitude. This immunodepression is physiological, and present in all patients. When immunodepression lasts too long, it becomes pathological, inducing secondary infections (pneumonia mainly), which are the leading cause of complications in ICU. For unknown reasons, some patients will have a rapid immunological recovery, protecting theme from complications. Adequate immunological monitoring could therefore identify patients who recover more slowly and are likely to benefit from an immunomodulatory treatment. At present, the decreased monocytic membrane expression of HLA-DR is the best marker for predicting the occurrence of secondary infections. Several drugs stimulating immunity (GM-CSF, interferon-γ, glucans, immunoglobulins) have been evaluated in patients without immunological monitoring with varying results. Hydrocortisone showed beneficial effects probably by decreasing the amplitude of SIRS. The evaluation of new immune-stimulating treatment, based on pathophysiological data and immunological monitoring (including HLA-DR) now available in most centers, could deeply modify the outcome of severe trauma patients.
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References
Mathers CD, Loncar D (2006) Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med 3:e442
Myburgh JA, Cooper DJ, Finfer SR, et al (2008) Epidemiology and 12-month outcomes from traumatic brain injury in australia and new zealand. J Trauma 64:854–62
Seguin P, Laviolle B, Dahyot-Fizelier C, et al (2014) Effect of oropharyngeal povidone-iodine preventive oral care on ventilator-associated pneumonia in severely brain-injured or cerebral hemorrhage patients: a multicenter, randomized controlled trial. Crit Care Med 42:1–8
Meisel C, Schwab JM, Prass K, et al (2005) Central nervous system injury-induced immune deficiency syndrome. Nat Rev Neurosci 6:775–86
Asehnoune K, Roquilly A, Abraham E (2012) Innate immune dysfunction in trauma patients: from pathophysiology to treatment. Anesthesiology 117:411–6
Roquilly A, Marret E, Abraham E, Asehnoune K (2014) Pneumonia Prevention to Decrease Mortality in Intensive Care Unit: A Systematic Review and Meta-analysis. Clin Infect Dis 60:64–75
Zhang Q, Raoof M, Chen Y, et al (2010) Circulating mitochondrial DAMPs cause inflammatory responses to injury. Nature 464:104–7
Wilson NS, Behrens GM, Lundie RJ, et al (2006) Systemic activation of dendritic cells by Toll-like receptor ligands or malaria infection impairs cross-presentation and antiviral immunity. Nat Immunol 7:165–72
Bochicchio GV, Napolitano LM, Joshi M, et al (2001) Systemic inflammatory response syndrome score at admission independently predicts infection in blunt trauma patients. J Trauma 50:817–20
Woiciechowsky C, Schöning B, Cobanov J, et al (2002) Early IL-6 plasma concentrations correlate with severity of brain injury and pneumonia in brain-injured patients. J Trauma 52:339–45
Bornstein SR, Chrousos GP (1999) Clinical review 104: Adrenocorticotropin (ACTH)- and non-ACTH-mediated regulation of the adrenal cortex: neural and immune inputs. J Clin Endocrinol Metab 84:1729–36
Chrousos GP (1995) The hypothalamic-pituitary-adrenal axis and immune-mediated inflammation. N Engl J Med 332:1351–62
Jamieson AM, Yu S, Annicelli CH, Medzhitov R (2010) Influenza virus-induced glucocorticoids compromise innate host defense against a secondary bacterial infection. Cell Host Microbe 7:103–14
Imhoff M, Gahr RH, Hoffmann P (1990) Delayed cutaneous hypersensitivity after multiple injury and severe burn. Ann Ital Chir 61:525–8
Deknuydt F, Roquilly A, Cinotti R, et al (2013) An in vitro model of mycobacterial granuloma to investigate the immune response in brain-injured patients. Crit Care Med 41:245–54
Adib-Conquy M, Adrie C, Moine P, et al (2000) NF- κ B Expression in Mononuclear Cells of Patients with Sepsis Resembles That Observed in Lipopolysaccharide Tolerance. Am J Respir Crit Care Med 162:1877–83
Adib-Conquy M, Adrie C, Moine P, et al (2000) NF-kappaB expression in mononuclear cells of patients with sepsis resembles that observed in lipopolysaccharide tolerance. Am J Respir Crit Care Med 162:1877–83
Göebel A, Kavanagh E, Lyons A, et al (2000) Injury induces deficient interleukin-12 production, but interleukin-12 therapy after injury restores resistance to infection. Ann Surg 231:253–61
Spolarics Z, Siddiqi M, Siegel JH, et al (2003) Depressed interleukin-12-producing activity by monocytes correlates with adverse clinical course and a shift toward Th2-type lymphocyte pattern in severely injured male trauma patients. Crit Care Med 31:1722–9
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:R208
Segura E, Villadangos JA (2009) Antigen presentation by dendritic cells in vivo. Curr Opin Immunol 21:105–10
Wolk K, Höflich C, Zuckermann-Becker H, et al (2007) Reduced monocyte CD86 expression in postinflammatory immunodeficiency. Crit Care Med 35:458–67
Wolk K, Döcke WD, Baehr von V, et al (2000) Impaired antigen presentation by human monocytes during endotoxin tolerance. Blood 96:218–23
Roquilly A, Broquet A, Jacqueline C, et al (2014) Hydrocortisone Prevents Immunosuppression by Interleukin-10+ Natural Killer Cells After Trauma-Hemorrhage. Crit Care Med 42:e752–61
Yi JS, Cox MA, Zajac AJ (2010) T-cell exhaustion: characteristics, causes and conversion. Immunology 129:474–81
Boomer JS, To K, Chang KC, et al (2011) Immunosuppression in patients who die of sepsis and multiple organ failure. JAMA 306:2594–605
Heffernan DS, Monaghan SF, Thakkar RK, et al (2012) Failure to normalize lymphopenia following trauma is associated with increased mortality, independent of the leukocytosis pattern. Crit Care 16:R12
Ni Choileain N, MacConmara M, Zang Y, et al (2006) Enhanced regulatory T cell activity is an element of the host response to injury. J Immunol 176:225–36
Xiao W, Mindrinos MN, Seok J, et al (2011) A genomic storm in critically injured humans. J Exp Med 208:2581–90
Burchard K (2001) A review of the adrenal cortex and severe inflammation: quest of the “eucorticoid” state. The Journal of Trauma: Injury, Infection, and Critical Care 51:800–14
Webster JI, Tonelli L, Sternberg EM (2002) Neuroendocrine regulation of immunity. Ann Rev Immunol 20:125–63
Kaufmann I, Briegel J, Schliephake F, et al (2008) Stress doses of hydrocortisone in septic shock: beneficial effects on opsonization-dependent neutrophil functions. Intensive Care Med 34:344–9
Keh D, Boehnke T, Weber-Cartens S, et al (2003) Immunologic and hemodynamic effects of “low-dose” hydrocortisone in septic shock: a double-blind, randomized, placebo-controlled, crossover study. Am J Respir Crit Care Med 167:512–20
Annane D, Bellissant E, Bollaert PE, et al (2009) Corticosteroids in the treatment of severe sepsis and septic shock in adults: a systematic review. JAMA 301:2362–75
Asehnoune K, Seguin P, Allary J, et al (2014) Hydrocortisone and fludrocortisone for prevention of hospital-acquired pneumonia in patients with severe traumatic brain injury (Corti-TC): a double-blind, multicentre phase 3, randomised placebocontrolled trial. Lancet Respir Med 2:706–16
Roquilly A, Mahe PJ, Seguin P, et al (2011) Hydrocortisone therapy for patients with multiple trauma: the randomized controlled HYPOLYTE study. JAMA 305:1201–9
Lepelletier Y, Zollinger R, Ghirelli C, et al (2010) Toll-like receptor control of glucocorticoid-induced apoptosis in human plasmacytoid predendritic cells (pDCs). Blood 116:3389–97
Kajino K, Nakamura I, Bamba H, et al (2007) Involvement of IL-10 in exhaustion of myeloid dendritic cells and rescue by CD40 stimulation. Immunology 120:28–37
Spruijt NE, Visser T, Leenen LP (2010) A systematic review of randomized controlled trials exploring the effect of immunomodulative interventions on infection, organ failure, and mortality in trauma patients. Crit Care. BioMed Central Ltd 14:R150
de Felippe Júnior J, da Rocha e Silva Júnior M, Maciel FM, et al (1993) Infection prevention in patients with severe multiple trauma with the immunomodulator beta 1-3 polyglucose (glucan). Surg Gynecol Obstet 177:383–8
Leentjens J, Kox M, Koch RM, et al (2012) Reversal of immunoparalysis in humans in vivo: a double-blind, placebocontrolled, randomized pilot study. Am J Respir Crit Care Med 186:838–45
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. Critical Care Medicine 37:2746–52
Döcke WD, Randow F, Syrbe U, et al (1997) Monocyte deactivation in septic patients: restoration by IFN-gamma treatment. Nat Med 3:678–81
Meisel C, Schefold JC, Pschowski R, et al (2009) Granulocytemacrophage colony-stimulating factor to reverse sepsisassociated immunosuppression: a double-blind, randomized, placebo-controlled multicenter trial. Am J Respir Crit Care Med 180:640–8
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Cet article correspond à la conférence faite par l’auteur au congrès de la SRLF 2015 dans la session : Prise en charge du polytraumatisé.
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Roquilly, A., Vourc’h, M. & Asehnoune, K. L’immunodépression post-traumatique : de la physiopathologie au traitement. Réanimation 24 (Suppl 2), 285–290 (2015). https://doi.org/10.1007/s13546-015-1032-z
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DOI: https://doi.org/10.1007/s13546-015-1032-z