Compensatory anti-inflammatory response syndrome

Summary

The concept of ‘Compensatory anti-inflammatory response syndrome’ (CARS) was proposed in 1997 by Roger Bone (1941–1997) to qualify the consequences of the counter-regulatory mechanisms initiated to limit the overzealous inflammatory process in patients with infectious (sepsis) or non-infectious systemic inflammatory response syndrome (SIRS). One major consequence of CARS is the modification of the immune status that could favour the enhanced susceptibility of intensive care patients to nosocomial infections. Indeed, most animal ‘two-hit’ models illustrate an enhanced sensitivity to infection after a first insult. However, this observation is highly dependent on the experimental procedure. Numerous functions of circulating leukocytes are altered in sepsis and SIRS patients, as well as in animal models of sepsis or SIRS. However, this is rather a reprogramming of circulating leukocytes, since there is not a global defect of the immune cells functions. Furthermore, within tissues, leukocytes are rather primed or activated than immunosuppressed. Thus, CARS may be considered as an adapted compartmentalized response with the aim to silence some acute proinflammatory genes, and to maintain the possible expression of certain genes involved in the anti-infectious process.

Keywords

Immunity - monocyte - neutrophil - cytokine - endotoxin - infection - two-hit model

• References

• 1 Angus DC, Linde-Zwirble WT, Lidicker J. et al. The epidemiology of severe sepsis in the United States: Analysis of incidence, outcome, and associated costs of care. Crit Care Med 2001; 29: 1303-1310.
• 2 Annane D, Bellissant E, Cavaillon JM. Septic shock. Lancet 2005; 365: 63-78.
• 3 Bone RC, Balk RA, Cerra FB. et al. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest 1992; 101: 1644-1655.
• 4 Cavaillon J, Annane D. Compartmentalization of the inflammatory response in sepsis and SIRS. J Endotoxin Res 2006; 12: 151-170.
• 5 Frick IM, Bjorck L, Herwald H. The dual role of the contact system in bacterial infectious disease. Thromb Haemost 2007; 98: 497-502.
• 6 Versteeg HH, Peppelenbosch MP, Spek CA. The pleiotropic effects of tissue factor: a possible role for factor VIIa-induced intracellular signalling?. Thromb Haemost 2001; 86: 1353-1359.
• 7 Gando S, Nanzaki S, Sasaki S. et al. Significant correlations between tissue factor and thrombin markers in trauma and septic patients with disseminated intravascular coagulation. Thromb Haemost 1998; 79: 1111-1115.
• 8 Bergmann S, Hammerschmidt S. Fibrinolysis and host response in bacterial infections. Thromb Haemost 2007; 98: 512-520.
• 9 Raaphorst J, Johan Groeneveld AB, Bossink AW. et al. Early inhibition of activated fibrinolysis predicts microbial infection, shock and mortality in febrile medical patients. Thromb Haemost 2001; 86: 543-549.
• 10 Dempfle CE. Coagulopathy of sepsis. Thromb Haemost 2004; 91: 213-224.
• 11 Nold MF, Nold-Petry CA, Fischer D. et al. Activated protein C downregulates p38 mitogen-activated protein kinase and improves clinical parameters in an in-vivo model of septic shock. Thromb Haemost 2007; 98: 1118-1126.
• 12 Girardin E, Roux-Lombard P, Grau GE. et al. Imbalance between tumour necrosis factor-alpha and soluble TNF receptor concentrations in severe meningococcaemia. Immunology 1992; 76: 20-23.
• 13 Marchant A, Devière J, Byl B. et al. Interleukin-10 production during septicaemia. Lancet 1994; 343: 707-708.
• 14 Fischer E, Van Zee KJ, Marano MA. et al. Interleukin-1 receptor antagonist circulates in experimental inflammation and in human disease. Blood 1992; 79: 2196-2200.
• 15 Marie C, Cavaillon J-M, Losser M-R. Elevated levels of circulating transforming growth factor-b1 in patients with the sepsis syndrome. Ann Intern Med 1996; 125: 520-521.
• 16 Munford RS, Pugin J. Normal response to injury prevent systemic inflammation and can be immunosuppressive. Am J Respir Crit Care Med 2001; 163: 316-321.
• 17 Cavaillon J-M. ‘Septic Plasma‘: an immunosuppressive milieu. Am J Respir Crit Care Med 2002; 166: 1417-1418.
• 18 Meakins JL, Pietsch JB, Bubenick O. et al. Delayed hypersensitivity: indicator of acquired failure of host defenses in sepsis and trauma. Ann Surg 1977; 186: 241-250.
• 19 Christou NV. Host defense mechanism in surgical patients : a correlation study of the delayed hypersensitivity skin test response, granulocyte function and sepsis. Can J Surg 1985; 28: 39-49.
• 20 Miller CL, Baker CC. Changes in lymphocyte activity after thermal injury. The role of suppressor cells. J Clin Invest 1979; 63: 202-210.
• 21 Dawson CW, Ledgerwood AM, Rosenberg JC. et al. Anergy and altered lymphocyte function in the injured patient. Am Surg 1982; 48: 394-401.
• 22 Angele MK, Faist E. Clinical review: immunodepression in the surgical patient and increased susceptibility to infection. Crit Care 2002; 06: 298-305.
• 23 Volk HD, Reinke P, Docke WD. Clinical aspects: from systemic inflammation to ‘immunoparalysis‘. Chem Immunol 2000; 74: 167-177.
• 24 Bone RC, Grodzin CJ, Balk RA. Sepsis: A new hypothesis for pathogenesis of the disease process. Chest 1997; 121: 235-243.
• 25 Cavaillon J-M, Adib-Conquy M, Cloëz-Tayarani I. et al. Immunodepression in sepsis and SIRS assessed by ex vivo cytokine production is not a generalized phenomenon : a review. J Endotoxin Res 2001; 07: 85-93.
• 26 Hotchkiss RS, Karl IE. The pathophysiology and treatment of sepsis. N Engl J Med 2003; 348: 138-150.
• 27 Le Tulzo Y, Pangault C, Gacouin A. et al. Early circulating lymphocyte apoptosis in human septic shock is associated with poor outcome. Shock 2002; 18: 487-494.
• 28 Hotchkiss RS, Tinsley KW, Swanson PE. et al. Sepsis-induced apoptosis causes progressive profound depletion of B and CD4+ T lymphocytes in humans. J Immunol 2001; 166: 6952-6963.
• 29 Messaris E, Kekis P, Memos N. et al. Sepsis: prognostic role of apoptosis regulators in gastrointestinal cells. World J Surg 2007; 31: 787-794.
• 30 Hotchkiss RS, Tinsley KW, Swanson PE. et al. Endothelial cell apoptosis in sepsis. Crit Care Med 2002; 30: S225-228.
• 31 Kuckleburg CJ, Tiwari R, Czuprynski CJ. Endothelial cell apoptosis induced by bacteria-activated platelets requires caspase-8 and –9 and generation of reactive oxygen species. Thromb Haemost 2008; 99: 363-372.
• 32 Adrie C, Bachelet M, Vayssier-Taussat M. et al. Mitochondrial membrane potential and apoptosis peripheral blood monocytes in severe human sepsis. Am J Respir Crit Care Med 2001; 164: 389-395.
• 33 Hotchkiss RS, Tinsley KW, Swanson PE. et al. Depletion of dendritic cells, but not macrophages, in patients with sepsis. J Immunol 2002; 168: 2493-2500.
• 34 Hotchkiss RS, Tinsley KW, Swanson PE. et al. Prevention of lymphocyte cell death in sepsis improves survival in mice. Proc Natl Acad Sci USA 1999; 96: 14541-14546.
• 35 Braun JS, Novak R, Herzog KH. et al. Neuroprotection by a caspase inhibitor in acute bacterial meningitis. Nat Med 1999; 05: 298-302.
• 36 Coopersmith CM, Stromberg PE, Dunne WM. et al. Inhibition of intestinal epithelial apoptosis and survival in a murine model of pneumonia-induced sepsis. JAMA 2002; 287: 1716-1721.
• 37 Hotchkiss RS, Swanson PE, Knudson CM. et al. Overexpression of Bcl-2 in transgenic mice decreases apoptosis and improves survival in sepsis. J Immunol 1999; 162: 4148-4156.
• 38 Qin S, Wang H, Yuan R. et al. Role of HMGB1 in apoptosis-mediated sepsis lethality. J Exp Med 2006; 203: 1637-1642.
• 39 Wang H, Bloom O, Zhang M. et al. HMG-1 as a late mediator of endotoxin lethality in mice. Science 1999; 285: 248-251.
• 40 Hatada T, Wada H, Nobori T. et al. Plasma concentrations and importance of High Mobility Group Box protein in the prognosis of organ failure in patients with disseminated intravascular coagulation. Thromb Haemost 2005; 94: 975-979.
• 41 Keel M, Ungethum U, Steckholzer U. et al. Inter-leukin-10 counterregulates proinflammatory cytokine-induced inhibition of neutrophil apoptosis during severe sepsis. Blood 1997; 90: 3356-3363.
• 42 Jia SH, Li Y, Parodo J. et al. Pre-B cell colony-enhancing factor inhibits neutrophil apoptosis in experimental inflammation and clinical sepsis. J Clin Invest 2004; 113: 1318-1327.
• 43 Conus S, Perozzo R, Reinheckel T. et al. Caspase-8 is activated by cathepsin D initiating neutrophil apoptosis during the resolution of inflammation. J Exp Med 2008; 205: 685-698.
• 44 Selig C, Nothdurft W. Cytokines and progenitor cells of granulocytopoiesis in peripheral blood of patients with bacterial infections. Infect Immun 1995; 63: 104-109.
• 45 Ansari-Lari MA, Kickler TS, Borowitz MJ. Immature granulocyte measurement using the Sysmex XE-2100. Relationship to infection and sepsis. Am J Clin Pathol 2003; 120: 795-799.
• 46 Taneja R, Sharma AP, Hallett MB. et al. Immature circulating neutrophils in sepsis have impaired phagocytosis and calcium signalling. Shock. 2008 [Epub ahead of print].
• 47 Livaditi O, Kotanidou A, Psarra A. et al. Neutrophil CD64 expression and serum IL-8: sensitive early markers of severity and outcome in sepsis. Cytokine 2006; 36: 283-290.
• 48 Cummings CJ, Martin TR, Frevert CW. et al. Expression and function of the chemokine receptor CXCR1 and CXCR2 in sepsis. J Immunol 1999; 162: 2341-2346.
• 49 Stephan F, Yang K, Tankovic J. et al. Impairment of polymorphonuclear neutrophil functions precedes nosocomial infections in critically ill patients. Crit Care Med 2002; 30: 315-322.
• 50 McCall CE, Grosso-Wilmoth LM, LaRue K. et al. Tolerance to endotoxin-induced expression of the inter-leukin-1β gene in blood neutrophils of humans with the sepsis syndrome. J Clin Invest 1993; 91: 853-861.
• 51 Marie C, Muret J, Fitting C. et al. Reduced ex vivo interleukin-8 production by neutrophils in septic and non-septic systemic inflammatory response syndrome. Blood 1998; 91: 3439-3446.
• 52 Marie C, Muret J, Fitting C. et al. IL-1 receptor antagonist production during infectious and noninfectious systemic inflammatory response syndrome. Crit. Care Med 2000; 28: 2277-2283.
• 53 Schultz MJ, Olszyna DP, de Jonge E. et al. Reduced ex vivo chemokine production by polymorphonuclear cells after in vivo exposure of normal humans to endotoxin. J Infect Dis 2000; 182: 1264-1267.
• 54 Wenisch C, Parschalk B, Patruta S. et al. Effect of polyclonal immunoglobulins on neutrophil phagocytic capacity and reactive oxygen production in patients with gram-negative septicemia. Infection 1999; 27: 183-186.
• 55 Kaufmann I, Hoelzl A, Schliephake F. et al. Polymorphonuclear leukocyte dysfunction syndrome in patients with increasing sepsis severity. Shock 2006; 26: 254-261.
• 56 Martins PS, Kallas EG, Neto MC. et al. Upregulation of reactive oxygen species generation and phagocytosis, and increased apoptosis in human neutrophils during severe sepsis and septic shock. Shock 2003; 20: 208-212.
• 57 Botha AJ, Moore FA, Moore EE. et al. Postinjury neutrophil priming and activation states: therapeutic challenges. Shock 1995; 03: 157-166.
• 58 Bass DA, Olbrantz P, Szejda P. et al. Subpopulations of neutrophils with increased oxidative product formation in blood of patients with infection. J Immunol 1986; 136: 860-866.
• 59 Pitman 3^rd JM, Thurman GW, Anderson BO. et al. WEB2170, a specific platelet-activating factor antagonist, attenuates neutrophil priming by human serum after clinical burn injury: the 1991 Moyer Award. J Burn Care Rehabil 1991; 12: 411-419.
• 60 Wenisch C, Graninger W. Are soluble factors relevant for polymorphonuclear leukocyte dysregulation in septicemia?. Clin Diagn Lab Immunol 1995; 02: 241-245.
• 61 Mariano F, Tetta C, Guida G. et al. Hemofiltration reduces the serum priming activity on neutrophil chemiluminescence in septic patients. Kidney Int 2001; 60: 1598-1605.
• 62 Doerfler ME, Danner RL, Shelhamer JH. et al. Bacterial lipopolysaccharides prime human neutrophils for enhanced production of leukotriene B4. J Clin Invest 1989; 83: 970-977.
• 63 Wrann CD, Winter SW, Barkhausen T. et al. Distinct involvement of p38-, ERK1/2 and PKC signalling pathways in C5a-mediated priming of oxidative burst in phagocytic cells. Cell Immunol 2007; 245: 63-69.
• 64 Wewers MD, Rinehart JJ, She ZW. et al. Tumor necrosis factor infusions in humans prime neutrophils for hypochlorous acid production. Am J Physiol 1990; 259: L276-282.
• 65 Wyman TH, Dinarello CA, Banerjee A. et al. Physiological levels of interleukin-18 stimulate multiple neutrophil functions through p38 MAP kinase activation. J Leukoc Biol 2002; 72: 401-409.
• 66 Fortin CF, Lesur O, Fulop Jr. T. Effects of TREM-1 activation in human neutrophils: activation of signalling pathways, recruitment into lipid rafts and association with TLR4. Int Immunol 2007; 19: 41-50.
• 67 Muthu K, He LK, Melstrom K. et al. Perturbed bone marrow monocyte development following burn injury and sepsis promote hyporesponsive monocytes. J Burn Care Res 2008; 29: 12-21.
• 68 Pachot A, Cazalis MA, Venet F. et al. Decreased expression of the fractalkine receptor CX3CR1 on circulating monocytes as new feature of sepsis-induced immunosuppression. J Immunol 2008; 180: 6421-6429.
• 69 von Knethen A, Tautenhahn A, Link H. et al. Activation-induced depletion of protein kinase C alpha provokes desensitization of monocytes/macrophages in sepsis. J Immunol 2005; 174: 4960-4965.
• 70 Muñoz C, Carlet J, Fitting C. et al. Dysregulation of in vitro cytokine production by monocytes during sepsis. J Clin Invest 1991; 88: 1747-1754.
• 71 Ertel W, Kremer J, Kenney J. et al. Down-regulation of proinflammatory cytokine release in whole blood from septic patients. Blood 1995; 85: 1341-1347.
• 72 Fumeaux T, Dufour J, Stern S. et al. Immune monitoring of patients with septic shock by measurement of intraleukocyte cytokines. Intensive Care Med 2004; 30: 2028-2037.
• 73 Granowitz EV, Porat R, Mier JW. et al. Intravenous endotoxin suppresses the cytokine response of peripheral blood mononuclear cells of healthy humans. J Immunol 1993; 151: 1637-1645.
• 74 Zhang X, Morrison DC. Lipopolysaccharide structure-function relationship in activation versus reprogramming of mouse peritoneal macrophages. J Leukoc Biol 1993; 54: 444-450.
• 75 Cabié A, Fitting C, Farkas J-C. et al. Influence of surgery on in-vitro cytokine production by human monocytes. Cytokine 1992; 04: 576-580.
• 76 Adib-Conquy M, Asehnoune K, Moine P. et al. Longterm impaired expression of nuclear factor-kB and IkBa in peripheral blood mononuclear cells of patients with major trauma. J Leuk Biol 2001; 70: 30-38.
• 77 Marie C, Fitting C, Muret J. et al. Interleukin-8 production in whole blood assays: is interleukin-10 responsible for the downregulation observed in sepsis ?. Cytokine 2000; 12: 55-61.
• 78 Weiss M, Fischer G, Barth E. et al. Dissociation of LPS-induced monocytic ex vivo production of granulocyte colony-stimulating factor (G-CSF) and TNF-alpha in patients with septic shock. Cytokine 2001; 13: 51-54.
• 79 Maxime V, Fitting C, Annane D. et al. Corticoids normalize leukocyte production of macrophage migration inhibitory factor in septic shock. J Infect Dis 2005; 191: 138-144.
• 80 Adib-Conquy M, Adrie C, Fitting C. et al. Up-regulation of MyD88s and SIGIRR, molecules inhibiting Toll-like receptor signalling, in monocytes from septic patients. Crit Care Med 2006; 34: 2377-2385.
• 81 Adib-Conquy M, Moine P, Asehnoune K. et al. Toll-like receptor-mediated tumor necrosis factor and interleukin-10 production differ during systemic inflammation. Am J Resp Crit Care Med 2003; 168: 158-164.
• 82 Adrie C, Adib-Conquy M, Laurent I. et al. Successful cardiopulmonary resuscitation after cardiac arrest as a ‘sepsis like’ syndrome. Circulation 2002; 106: 562-568.
• 83 Haupt W, Zirngibl H, Riese J. et al. Depression of tumor necrosis factor-alpha, interleukin-6, and inter-leukin-10 production: a reaction to the initial systemic hyperactivation in septic shock. J Invest Surg 1997; 10: 349-355.
• 84 Talwar S, Munson PJ, Barb J. et al. Gene expression profiles of peripheral blood leukocytes after endotoxin challenge in humans. Physiol Genomics 2006; 25: 203-215.
• 85 Fahy RJ, Exline MC, Gavrilin MA. et al. Inflammasome mRNA expression in human monocytes during early septic shock. Am J Respir Crit Care Med 2008; 177: 983-988.
• 86 Biberthaler P, Bogner V, Baker HV. et al. Genome-wide monocytic mRNA expression in polytrauma patients for identification of clinical outcome. Shock 2005; 24: 11-19.
• 87 Adib-Conquy M, Adrie C, Moine P. et al. NF-kB expression in mononuclear cells of septic patients resembles that observed in LPS-tolerance. Am J Respir Crit Care Med 2000; 162: 1877-1883.
• 88 Ziegler-Heitbrock HWL, Wedel A, Schraut W. et al. Tolerance to lipopolysaccharide involves mobilization of nuclear factor kB with predominance of p50 homo-dimers. J Biol Chem 1994; 269: 17001-17004.
• 89 Kobayashi K, Hernandez LD, Galan JE. et al. IRAK-M is a negative regulator of Toll-like receptor signalling. Cell 2002; 110: 191-202.
• 90 Escoll P, del Fresno C, Garcia L. et al. Rapid up-regulation of IRAK-M expression following a second endotoxin challenge in human monocytes and in monocytes isolated from septic patients. Biochem Biophys Res Commun 2003; 311: 465-472.
• 91 Zhang G, Ghosh S. Negative regulation of toll-like receptor-mediated signalling by Tollip. J Biol Chem 2002; 277: 7059-7065.
• 92 Nakagawa R, Naka T, Tsutsui H. et al. SOCS-1 participates in negative regulation of LPS responses. Immunity 2002; 17: 677-687.
• 93 Janssens S, Burns K, Tschopp J. et al. Regulation of interleukin-1– and lipopolysaccharide-induced NFkappaB activation by alternative splicing of MyD88. Curr Biol 2002; 12: 467-471.
• 94 Wald D, Qin J, Zhao Z. et al. SIGIRR, a negative regulator of Toll-like receptor-interleukin 1 receptor signalling. Nat Immunol 2003; 04: 920-927.
• 95 Wullaert A, Verstrepen L, Van Huffel S. et al. LIND/ABIN-3 is a novel LPS-inducible inhibitor of NF-kB activation. J Biol Chem 2007; 282: 81-90.
• 96 Verstrepen L, Adib-Conquy M, Kreike M. et al. Expression of the NF-kappaB inhibitor ABIN-3 in response to TNF and toll-like receptor 4 stimulation is itself regulated by NF-kappaB. J Cell Mol Med 2008; 12: 316-329.
• 97 West MA, Koons A, Crandall M. et al. Whole blood leukocyte mitogen activated protein kinases activation differentiates intensive care unit patients with systemic inflammatory response syndrome and sepsis. J Trauma 2007; 62: 805-811.
• 98 Hershman MJ, Cheadle WG, Wellhausen SR. et al. Monocyte HLA-DR antigen expression characterizes clinical outcome in the trauma patients. Br J Surg 1990; 77: 204-207.
• 99 Tschaikowsky K, Hedwig-Geissing M, Schiele A. et al. 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 2002; 30: 1015-1023.
• 100 Weijer S, Lauw FN, Branger J. et al. Diminished interferon-γ production and responsiveness after endotoxin administration to healhy humans. J Infec Dis 2002; 186: 1748-1753.
• 101 Monneret G, Lepape A, Voirin N. et al. Persisting low monocyte human leukocyte antigen-DR expression predicts mortality in septic shock. Intensive Care Med 2006; 32: 1175-1183.
• 102 Caille V, Chiche JD, Nciri N. et al. Histocompatibility leukocyte antigen-D related expression is specifically altered and predicts mortality in septic shock but not in other causes of shock. Shock 2004; 22: 521-526.
• 103 Ayala A, Ertel W, Chaudry IH. Trauma-induced suppression of antigen presentation and expression of major histocompatibility class II antigen complex in leukocytes. Shock 1996; 05: 79-90.
• 104 van den Berk JMM, Oldenburger RHJ, van den Berg AP. et al. Low HLA DR expression on monocytes as a prognostic marker for bacterial sespsis after liver transplantation. Transplantation 1997; 63: 1846-1848.
• 105 Ayala A, Deol ZK, Lehman DL. et al. Polymicrobial sepsis but not low-dose endotoxin infusion causes decreased splenocyte IL-2/IFN-gamma release while increasing IL-4/IL-10 production. J Surg Res 1994; 56: 579-585.
• 106 Muret J, Marie C, Fitting C. et al. Ex vivo T-lymphocyte derived cytokine production in SIRS patients is influenced by experimental procedures. Shock 2000; 13: 169-174.
• 107 Puyana JC, Pellegrini JD, De AK. et al. Both T-helper-1– and T-helper-2-type lymphokines are depressed in posttrauma anergy. J Trauma 1998; 44: 1037-1045.
• 108 Venet F, Pachot A, Debard AL. et al. Increased percentage of CD4+CD25+ regulatory T cells during septic shock is due to the decrease of CD4+CD25– lymphocytes. Crit Care Med 2004; 32: 2329-2331.
• 109 Ayala A, Chung CS, Lomas JL. et al. Shock-induced neutrophil mediated priming for acute lung injury in mice: divergent effects of TLR-4 and TLR-4/FasL deficiency. Am J Pathol 2002; 161: 2283-2294.
• 110 Shenkar R, Abraham E. Mechanisms of lung neutrophil activation after hemorrhage or endotoxemia: roles of reactive oxygen intermediates, NF-κB and cyclic AMP response element binding protein. J Immunol 1999; 163: 954-962.
• 111 Abraham E, Arcaroli J, Shenkar R. Activation of extracellular signal-regulated kinases, NF-κB, and cyclic adenosine 5‘-monophosphate response element binding protein in lung neutrophils occurs by differing mechanisms after hemorrhage or endotoxemia. J Immunol 2001; 166: 522-530.
• 112 Coldren CD, Nick JA, Poch KR. et al. Functional and genomic changes induced by alveolar trans-migration in human neutrophils. Am J Physiol Lung Cell Mol Physiol 2006; 291: L1267-1276.
• 113 Pang G, Ortega M, Zighang R. et al. Autocrine modulation of IL-8 production by sputum neutrophils in chronic bronchial sepsis. Am J Respir Crit Care Med 1997; 155: 726-731.
• 114 Petit-Bertron AF, Tabary O, Corvol H. et al. Circulating and airway neutrophils in cystic fibrosis display different TLR expression and responsiveness to inter-leukin-10. Cytokine 2008; 41: 54-60.
• 115 Corvol H, Fitting C, Chadelat K. et al. Distinct cytokine production by lung and blood neutrophils from children with cystic fibrosis. Am J Physiol Lung Cell Mol Physiol 2003; 284: L997-1003.
• 116 Fan J, Marshall JC, Jimenez M. et al. Hemorrhagic shock primes for increased expression of cytokine-induced neutrophil chemoattractant in the lung : role in pulmonary inflammation following lipopolysaccharide. J Immunol 1998; 161: 440-447.
• 117 Jarrar D, Kuebler JF, Rue LW. 3^rd, et al. Alveolar macrophage activation after trauma-hemorrhage and sepsis is dependent on NF-kappaB and MAPK/ERK mechanisms. Am J Physiol Lung Cell Mol Physiol 2002; 283: L799-805.
• 118 Fitting C, Dhawan S, Cavaillon JM. Compartmentalisation of endotoxin tolerance. J Infect Dis 2004; 189: 1295-1303.
• 119 Jacobs RF, Tabor DR, Burks AW. et al. Elevated interleukin-1 release by human alveolar macrophages during adult respiratory distress syndrome. Am Rev Respir Dis 1989; 140: 1686-1692.
• 120 Tran Van Nhieu J, Misset B, Lebargy F. et al. Expression of tumor necrosis factor-a gene in alveolar macrophages from patients with the adult respiratory distress syndrome. Am Rev Respir Dis 1993; 147: 1585-1589.
• 121 Schwartz MD, Moore E, Moore FA. et al. Nuclear factor-kappa B is activated in alveolar macrophages from patients with acute respiratory distress syndrome. Crit Care Med 1996; 24: 1285-1292.
• 122 Tsuchida K, Takemoto Y, Yamagami S. et al. Detection of peptidoglycan and endotoxin in dialysate, using silkworm larvae plasma and limulus amebocyte lysate methods. Nephron 1997; 75: 438-443.
• 123 Kobayashi M, Yoshida T, Takeuchi D. et al. Gr-1+CD11b+ cells as an accelerator of sepsis stemming from Pseudomonas aeruginosa wound infection in thermally injured mice. J Leukoc Biol 2008; 83: 1354-1362.
• 124 Ronco C, Brendolan A, Lonnemann G. et al. A pilot study of coupled plasma filtration with adsorption in septic shock. Crit Care Med 2002; 30: 1250-1255.
• 125 Constantian M. Association of sepsis with an immunosuppressive polypeptide in the serum of burn patients. Ann Surg 1978; 188: 209-215.
• 126 Prins JM, Kuijper EJ, Mevissen ML. et al. Release of tumor necrosis factor alpha and interleukin 6 during antibiotic killing of Escherichia coli in whole blood: influence of antibiotic class, antibiotic concentration, and presence of septic serum. Infect Immun 1995; 63: 2236-2242.
• 127 Majetschak M, Flach R, Heukamp T. et al. Regulation of whole blood tumor necrosis factor production upon endotoxin stimulation after severe blunt trauma. J Trauma 1997; 43: 880-887.
• 128 Grundmann U, Rensing H, Adams HA. et al. Endotoxin desensitization of human mononuclear cells after cadiopulmonary bypass: role of humoral factors. Anesthesiology 2000; 93: 359-369.
• 129 Cavaillon JM, Adrie C, Fitting C. et al. Endotoxin tolerance: is there a clinical relevance?. J Endotoxin Res 2003; 09: 101-107.
• 130 Spinas G, Bloesch D, Kaufmann M. et al. Induction of plasma inhibitors of interleukin 1 and TNF-alpha activity by endotoxin administration to normal humans. Am J Physiol 1990; 259: R993-R997.
• 131 Kitchens RL, Thompson PA, Viriyakosol S. et al. Plasma CD14 decreases monocyte responses to LPS by transferring cell-bound LPS to plasma lipoproteins. J Clin Invest 2001; 108: 485-493.
• 132 Vreugdenhil ACE, Snoeck AMP, van’t Veer C. et al. LPS-binding protein circulates in association with apoB-containing lipoproteins and enhances endotoxin-LDL/ VLDL interaction. J Clin Invest 2001; 107: 225-234.
• 133 Cavaillon JM, Fitting C, Haeffner-Cavaillon N. et al. Cytokine response by monocytes and macrophages to free and lipoprotein-bound lipopolysaccharide. Infect Immun 1990; 58: 2375-2382.
• 134 Munford RS, Hall CL, Lipton JM. et al. Biological activity, lipoprotein-binding behavior, and in vivo disposition of extracted and native forms of Salmonella typhimurium lipopolysaccharides. J Clin Invest 1982; 70: 877-888.
• 135 Grunfeld C, Marshall M, Shigenaga JK. et al. Lipoproteins inhibit macrophage activation by lipoteichoic acid. J Lipid Res 1999; 40: 245-252.
• 136 Pugin J, Stern-Voeffray S, Daubeuf B. et al. Soluble MD-2 activity in plasma from patients with severe sepsis and septic shock. Blood 2004; 104: 4071-4079.
• 137 Brandtzaeg P, Osnes L, Øvstebø R. et al. Net inflammatory capacity of human septic shock plasma evaluated by a monocyte-based target cell assay: identification of interleukin-10 as a major functional deactivator of human monocytes. J Exp Med 1996; 184: 51-60.
• 138 Ayala A, Knotts JB, Ertel W. et al. Role of interleukin 6 and transforming growth factor-beta in the induction of depressed splenocyte responses following sepsis. Arch Surg 1993; 128: 89-94.
• 139 Chen W, Frank M, Jin W. et al. TGF-beta released by apoptotic T cells contributes to an immunosuppressive milieu. Immunity 2001; 14: 715-725.
• 140 Fumeaux T, Pugin J. Role of interleukin-10 in the intracellular sequestration of human leukocyte antigen-DR in monocytes during septic shock. Am J Respir Crit Care Med 2002; 166: 1475-1482.
• 141 Reddy RC, Chen GH, Newstead MW. et al. Alveolar macrophage deactivation in murine septic peritonitis: role of interleukin 10. Infect Immun 2001; 69: 1394-1401.
• 142 Wisnoski N, Chung CS, Chen Y. et al. The contribution of CD4+ CD25+ T-regulatory-cells to immune suppression in sepsis. Shock 2007; 27: 251-257.
• 143 Heuer JG, Zhang T, Zhao J. et al. Adoptive transfer of in vitro-stimulated CD4+CD25+ regulatory T cells increases bacterial clearance and improves survival in polymicrobial sepsis. J Immunol 2005; 174: 7141-7146.
• 144 Delano MJ, Scumpia PO, Weinstein JS. et al. MyD88-dependent expansion of an immature GR-1(+)CD11b(+) population induces T cell suppression and Th2 polarization in sepsis. J Exp Med 2007; 204: 1463-1474.
• 145 Yoshizawa K, Naruto M, Ida N. Injection time of interleukin-6 determines fatal outcome in experimental endotoxin shock. J Interferon Cytokine Res 1996; 16: 995-1000.
• 146 Inoue K, Takano H, Yanagisawa R. et al. Protective role of interleukin-6 in coagulatory and hemostatic disturbance induced by lipopolysaccharide in mice. Thromb Haemost 2004; 91: 1194-1201.
• 147 Steeber DA, Tang ML, Green NE. et al. Leukocyte entry into sites of inflammation requires overlapping interactions between the L-selectin and ICAM-1 pathways. J Immunol 1999; 163: 2176-2186.
• 148 Tilg H, Trehu E, Atkins MB. et al. Interleukin-6 (IL-6) as an anti-inflammatory cytokine: induction of circulating IL-1 receptor antagonist and soluble tumor necrosis factor receptor p55. Blood 1994; 83: 113-118.
• 149 Asehnoune K, Fitting C, Edouard AR. et al. beta2-Adrenoceptor blockade partially restores ex vivo TNF production following hemorrhagic shock. Cytokine 2006; 34: 212-218.
• 150 Prass K, Meisel C, Hoflich C. et al. Stroke-induced immunodeficiency promotes spontaneous bacterial infections and is mediated by sympathetic activation reversal by poststroke T helper cell type 1-like immunostimulation. J Exp Med 2003; 198: 725-736.
• 151 Salicru AN, Sams CF, Marshall GD. Cooperative effects of corticosteroids and catecholamines upon immune deviation of the type-1/type-2 cytokine balance in favor of type-2 expression in human peripheral blood mononuclear cells. Brain Behav Immun 2007; 21: 913-920.
• 152 Panina-Bordignon P, Mazzeo D, Lucia PD. et al. Beta2-agonists prevent Th1 development by selective inhibition of interleukin 12. J Clin Invest 1997; 100: 1513-1519.
• 153 Ramer-Quinn DS, Baker RA, Sanders VM. Activated T helper 1 and T helper 2 cells differentially express the beta-2-adrenergic receptor: a mechanism for selective modulation of T helper 1 cell cytokine production. J Immunol 1997; 159: 4857-4867.
• 154 Gonzalez-Rey E, Chorny A, Delgado M. Regulation of immune tolerance by anti-inflammatory neuropeptides. Nat Rev Immunol 2007; 07: 52-63.
• 155 Tracey KJ. Physiology and immunology of the cholinergic antiinflammatory pathway. J Clin Invest 2007; 117: 289-296.
• 156 Majetschak M, Krehmeier U, Bardenheuer M. et al. Extracellular ubiquitin inhibits the TNF-alpha response to endotoxin in peripheral blood mononuclear cells and regulates endotoxin hyporesponsiveness in critical illness. Blood 2003; 101: 1882-1890.
• 157 Hensler T, Heidecke CD, Hecker H. et al. Increased susceptibility to postoperative sepsis in patients with impaired monocyte IL-12 production. J Immunol 1998; 161: 2655-2659.
• 158 Hebert CA, Luscinskas FW, Kiely JM. et al. Endothelial and leukocyte forms of IL-8. Conversion by thrombin and interactions with neutrophils. J Immunol 1990; 145: 3033-3040.
• 159 Spolarics Z, Siddiqi M, Siegel JH. et al. 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 2003; 31: 1722-1729.
• 160 Suzuki T, Shimizu T, Szalay L. et al. Androstenediol ameliorates alterations in immune cells cytokine production capacity in a two-hit model of trauma-hemorrhage and sepsis. Cytokine 2006; 34: 76-84.
• 161 van Westerloo DJ, Weijer S, Bruno MJ. et al. Toll-like receptor 4 deficiency and acute pancreatitis act similarly in reducing host defense during murine Escherichia coli peritonitis. Crit Care Med 2005; 33: 1036-1043.
• 162 Renckens R, van Westerloo DJ, Roelofs JJ. et al. Acute phase response impairs host defense against Pseudomonas aeruginosa pneumonia in mice. Crit Care Med 2008; 36: 580-587.
• 163 Olszewski MA, Falkowski NR, Surana R. et al. Effect of laparotomy on clearance and cytokine induction in Staphylococcus aureus infected lungs. Am J Respir Crit Care Med 2007; 176: 921-929.
• 164 White JC, Nelson S, Winkelstein JA. et al. Impairment of antibacterial defense mechanisms of the lung by extrapulmonary infection. J Infect Dis 1986; 153: 202-208.
• 165 Chen GH, Reddy RC, Newstead MW. et al. Intra-pulmonary TNF gene therapy reverses sepsis-induced suppression of lung antibacterial host defense. J Immunol 2000; 165: 6496-6503.
• 166 Benjamim CF, Hogaboam CM, Lukacs NW. et al. Sepic mice are susceptible to pulmonary aspergillosis. Am J Pathol 2003; 163: 2605-2617.
• 167 Lyons A, Kelly JL, Rodrick ML. et al. Major injury induces increased production of interleukin-10 by cells of the immune system with a negative impact on resistance to infection. Ann Surg 1997; 226: 450-458.
• 168 Tsuda Y, Takahashi H, Kobayashi M. et al. CCL2, a product of mice early after systemic inflammatory response syndrome (SIRS), induces alternatively activated macrophages capable of impairing antibacterial resistance of SIRS mice. J Leukoc Biol 2004; 76: 368-373.
• 169 Takahashi H, Tsuda Y, Kobayashi M. et al. CCL2 as a trigger of manifestations of compensatory anti-inflammatory response syndrome in mice with severe systemic inflammatory response syndrome. J Leukoc Biol 2006; 79: 789-796.
• 170 Tsuda Y, Kobayashi M, Herndon DN. et al. Impairment of the host’s antibacterial resistance by norepinephrine activated neutrophils. Burns 2008; 34: 460-466.
• 171 Rayhane N, Fitting C, Lortholary O. et al. Administration of endotoxin associated with lipopolysaccharide tolerance protects mice against fungal infection. Infect Immun 2000; 68: 3748-3753.
• 172 Lehner MD, Ittner J, Bundschuh DS. et al. Improved innate immunity of endotoxin-tolerant mice increases resistance to Salmonella enterica serovar typhimurium infection despite attenuated cytokine response. Infect Immun 2001; 69: 463-471.
• 173 Echtenacher B, Mannel DN. Requirement of TNF and TNF receptor type 2 for LPS-induced protection from lethal septic peritonitis. J Endotoxin Res 2002; 08: 365-369.
• 174 Takahashi H, Tsuda Y, Takeuchi D. et al. Influence of systemic inflammatory response syndrome on host resistance against bacterial infections. Crit Care Med 2004; 32: 1879-1885.
• 175 Maung AA, Fujimi S, MacConmara MP. et al. Injury enhances resistance to Escherichia coli infection by boosting innate immune system function. J Immunol 2008; 180: 2450-2458.
• 176 Sterns T, Pollak N, Echtenacher B. et al. Divergence of protection induced by bacterial products and sepsis-induced immune suppression. Infect Immun 2005; 73: 4905-4912.
• 177 Cavaillon JM, Adrie C, Fitting C. et al. Reprogramming of circulatory cells in sepsis and SIRS. J Endotoxin Res 2005; 11: 311-320.
• 178 McCall CE, Yoza BK. Gene silencing in severe systemic inflammation. Am J Respir Crit Care Med 2007; 175: 763-767.
• 179 Foster SL, Hargreaves DC, Medzhitov R. Gene-specific control of inflammation by TLR-induced chromatin modifications. Nature 2007; 447: 972-978.