Is boosting the immune system in sepsis appropriate?

Critical Care

Volumn 18, Issue 2, 2014, Pages

  Cavaillon, Jean Marc ^a   Eisen, Damon ^b,c   Annane, Djilalli ^d  

^a INSTITUT PASTEUR   (France)

^b ROYAL MELBOURNE HOSPITAL   (Australia)

^c UNIVERSITY OF MELBOURNE   (Australia)

^d RAYMOND POINCARÉ HOSPITAL   (France)

Author keywords

[No Author keywords available]

Indexed keywords

ARACHIDONATE 5 LIPOXYGENASE; B7 ANTIGEN; CD86 ANTIGEN; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4; GAMMA INTERFERON; GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR; INTERLEUKIN 1; INTERLEUKIN 10; INTERLEUKIN 12; INTERLEUKIN 15; INTERLEUKIN 17; INTERLEUKIN 2; INTERLEUKIN 23; INTERLEUKIN 33; INTERLEUKIN 4; INTERLEUKIN 6; INTERLEUKIN 7; LEUKOTRIENE A4; PROSTAGLANDIN E2; SCAVENGER RECEPTOR A; TRANSFORMING GROWTH FACTOR BETA; TUMOR NECROSIS FACTOR RELATED APOPTOSIS INDUCING LIGAND;

ABDOMINAL INFECTION; ADJUVANT THERAPY; APOPTOSIS; BRONCHOPNEUMONIA; CYTOKINE PRODUCTION; DISEASE CLASSIFICATION; ENTEROCOCCUS FAECIUM; FUNGAL CELL WALL; HEART MUSCLE CELL; HUMAN; IMMUNE RESPONSE; IMMUNE STATUS; IMMUNOMODULATION; IMMUNORECEPTOR TYROSINE BASED INHIBITION MOTIF; IMMUNOSUPPRESSIVE TREATMENT; INFLAMMATION; INNATE IMMUNITY; INTENSIVE CARE; LEUKOCYTE; MACROPHAGE; MAST CELL; META ANALYSIS (TOPIC); MULTIPLE ORGAN FAILURE; NEUTROPHIL; NONHUMAN; PERIPHERAL BLOOD MONONUCLEAR CELL; PNEUMONIA; PRIORITY JOURNAL; PSEUDOMONAS AERUGINOSA; REGULATORY T LYMPHOCYTE; REVIEW; SEPSIS; STAPHYLOCOCCUS AUREUS; T LYMPHOCYTE; TH17 CELL; TH2 CELL; TISSUE SPECIFICITY;

EID: 84899044664     PISSN: 13648535     EISSN: 1466609X     Source Type: Journal    
DOI: 10.1186/cc13787     Document Type: Review

References (108)

1. Hotchkiss RS, Monneret G, Payen D. Immunosuppression in sepsis: a novel understanding of the disorder and a new therapeutic approach. Lancet Infect Dis 2013, 13:260-268. 10.1016/S1473-3099(13)70001-X, 3798159, 23427891.
2. Zakharova M, Ziegler HK. Paradoxical anti-inflammatory actions of TNF-alpha: inhibition of IL-12 and IL-23 via TNF receptor 1 in macrophages and dendritic cells. J Immunol 2005, 175:5024-5033.
3. Noti M, Corazza N, Mueller C, Berger B, Brunner T. TNF suppresses acute intestinal inflammation by inducing local glucocorticoid synthesis. J Exp Med 2010, 207:1057-1066. 10.1084/jem.20090849, 2867273, 20439544.
4. González-Navajas JM, Law J, Nguyen KP, Bhargava M, Corr MP, Varki N, Eckmann L, Hoffman HM, Lee J, Raz E. Interleukin 1 receptor signaling regulates DUBA expression and facilitates toll-like receptor 9-driven antiinflammatory cytokine production. J Exp Med 2010, 207:2799-2807. 10.1084/jem.20101326, 3005235, 21115691.
5. Fukushima A, Ozaki A, Ishida W, Fukata K, Ueno H. Systemic interferon-gamma suppresses the development of endotoxin-induced uveitis in mice. Curr Eye Res 2005, 30:7-12. 10.1080/02713680490522461, 15875359.
6. Lauw FN, Pajkrt D, Hack CE, Kurimoto M, van Deventer SJH, van der Poll T. Proinflammatory effects of IL-10 during human endotoxemia. J Immunol 2000, 165:2783-2789.
7. Petit-Bertron AF, Pedron T, Gross U, Coppée JY, Sansonetti PJ, Cavaillon JM, Adib-Conquy M. Adherence modifies the regulation of gene expression induced by interleukin-10. Cytokine 2005, 29:1-12.
8. Moore KW, De Waal Malefyt R, Coffman RL, O'Garra A. Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol 2001, 19:683-765. 10.1146/annurev.immunol.19.1.683, 11244051.
9. Garcia-Lazaro JF, Thieringer F, Lüth S, Czochra P, Meyer E, Renteria IB, Galle PR, Lohse AW, Herkel J, Kanzler S. Hepatic over-expression of TGF-beta1 promotes LPS-induced inflammatory cytokine secretion by liver cells and endotoxemic shock. Immunol Lett 2005, 101:217-222. 10.1016/j.imlet.2005.06.003, 16054705.
10. Kalinski P. Regulation of immune responses by prostaglandin E2. J Immunol 2012, 188:21-28. 10.4049/jimmunol.1101029, 3249979, 22187483.
11. Abraham E, Wunderink R, Silverman H, Perl TM, Nasraway S, Levy H, Bone R, Wenzel RP, Balk R, Allred R, Pennington JE, Wherry JC, Bellamy P, Cryer H, Busuttil R, Winston D, Perry C, Leeper KV, Jones C, Martin M, Tuma P, Baird I, Brooks J, Baird R, Rangel S, Wagner N, Costigan M, Gutierrez G, Johnson P, et al. Efficacy and safety of monoclonal antibody to human tumor necrosis factor alpha in patients with sepsis syndrome. A randomized, controlled, double-blind, multicenter clinical trial. TNF-alpha MAb sepsis study group. JAMA 1995, 273:934-941. 10.1001/jama.1995.03520360048038, 7884952.
12. Reinhart K, Wiegand-Löhnert C, Grimminger F, Kaul M, Withington S, Treacher D, Eckart J, Willatts S, Bouza C, Krausch D, Stockenhuber F, Eiselstein J, Daum L, Kempeni J. Assessment of the safety and efficacy of the monoclonal anti-tumor necrosis factor antibody-fragment, MAK 195 F, in patients with sepsis and septic shock: a multicenter, randomized, placebo-controlled, dose-ranging study. Crit Care Med 1996, 24:733-742. 10.1097/00003246-199605000-00003, 8706447.
13. Tetta C, Gianotti L, Cavaillon JM, Wratten ML, Fini M, Braga M, Bisagni P, Giavaresi G, Bolzani R, Giardino R. Continuous plasmafiltration coupled with sorbent adsorption in a rabbit model of endotoxic shock. Crit Care Med 2000, 28:1526-1533. 10.1097/00003246-200005000-00045, 10834707.
14. Lorente JA, Marshall JC. Neutralization of tumor necrosis factor in preclinical models of sepsis. Shock 2005, 24:107-119. 10.1097/01.shk.0000191343.21228.78, 16374382.
15. Miles RH, Paxton TP, Dries DJ, Gamelli RL. Interferon-gamma increases mortality following cecal ligation and puncture. J Trauma 1994, 36:607-611. 10.1097/00005373-199405000-00001, 8189458.
16. Spight D, Trapnell B, Zhao B, Berclaz P, Shanley TP. Granulocyte-macrophage-colony-stimulating factor-dependent peritoneal macrophage responses determine survival in experimentally induced peritonitis and sepsis in mice. Shock 2008, 30:434-442. 10.1097/SHK.0b013e3181673543, 2743401, 18277945.
17. Reim D, Westenfelder K, Kaiser-Moore S, Schlautkotter S, Holzmann B, Weighardt H. Role of T cells for cytokine production and outcome in a model of acute septic peritonitis. Shock 2009, 31:245-250. 10.1097/SHK.0b013e31817fd02c, 18650777.
18. van Schaik SM, Abbas AK. Role of T cells in a murine model of Escherichia coli sepsis. Eur J Immunol 2007, 37:3101-3110. 10.1002/eji.200737295, 17948264.
19. Heuer JG, Zhang T, Zhao J, Ding C, Cramer M, Justen KL, Vonderfecht SL, Na S. 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.
20. Hiraki S, Ono S, Tsujimoto H, Kinoshita M, Takahata R, Miyazaki H, Saitoh D, Hase K. Neutralization of interleukin-10 or transforming growth factor-beta decreases the percentages of CD4+ CD25+ Foxp3+ regulatory T cells in septic mice, thereby leading to an improved survival. Surgery 2012, 151:313-322. 10.1016/j.surg.2011.07.019, 21982068.
21. Souza-Fonseca-Guimaraes F, Adib-Conquy M, Cavaillon JM. Natural killer (NK) cells in antibacterial innate immunity: angels or devils?. Mol Med 2012, 18:270-285. 3324953, 22105606.
22. Scumpia PO, McAuliffe PF, O'Malley KA, Ungaro R, Uchida T, Matsumoto T, Remick DG, Clare-Salzler MJ, Moldawer LL, Efron PA. CD11c + dendritic cells are required for survival in murine polymicrobial sepsis. J Immunol 2005, 175:3282-3286.
23. Maier M, Wutzler S, Bauer M, Trendafilov P, Henrich D, Marzi I. Altered gene expression patterns in dendritic cells after severe trauma: implications for systemic inflammation and organ injury. Shock 2008, 30:344-351. 10.1097/SHK.0b013e3181673eb4, 18323745.
24. Hotchkiss RS, Swanson PE, Knudson CM, Chang KC, Cobb JP, Osborne DF, Zollner KM, Buchman TG, Korsmeyer SJ, Karl IE. Overexpression of Bcl-2 in transgenic mice decreases apoptosis and improves survival in sepsis. J Immunol 1999, 162:4148-4156.
25. Chen W, Frank M, Jin W, Wahl S. TGF-beta released by apoptotic T cells contributes to an immunosuppressive milieu. Immunity 2001, 14:715-725. 10.1016/S1074-7613(01)00147-9, 11420042.
26. Ren Y, Xie Y, Jiang G, Fan J, Yeung J, Li W, Tam PK, Savill J. Apoptotic cells protect mice against lipopolysaccharide-induced shock. J Immunol 2008, 180:4978-4985.
27. Byrne A, Reen DJ. Lipopolysaccharide induces rapid production of IL-10 by monocytes in the presence of apoptotic neutrophils. J Immunol 2002, 168:1968-1977.
28. Perl M, Chung CS, Lomas-Neira J, Rachel TM, Biffl WL, Cioffi WG, Ayala A. Silencing of Fas, but not caspase-8, in lung epithelial cells ameliorates pulmonary apoptosis, inflammation, and neutrophil influx after hemorrhagic shock and sepsis. Am J Pathol 2005, 167:1545-1559. 10.1016/S0002-9440(10)61240-0, 1613198, 16314469.
29. Glynne PA, Evans TJ. Inflammatory cytokines induce apoptotic and necrotic cell shedding from human proximal tubular epithelial cell monolayers. Kidney Int 1999, 55:2573-2597. 10.1046/j.1523-1755.1999.00456.x, 10354308.
30. Husain KD, Stromberg PE, Woolsey CA, Turnbull IR, Dunne WM, Javadi P, Buchman TG, Karl IE, Hotchkiss RS, Coopersmith CM. Mechanisms of decreased intestinal epithelial proliferation and increased apoptosis in murine acute lung injury. Crit Care Med 2005, 33:2350-2357. 10.1097/01.CCM.0000182797.89252.A3, 1317567, 16215392.
31. Buerke U, Carter JM, Schlitt A, Russ M, Schmidt H, Sibelius U, Grandel U, Grimminger F, Seeger W, Mueller-Werdan U, Werdan K, Buerke M. Apoptosis contributes to septic cardiomyopathy and is improved by simvastatin therapy. Shock 2008, 29:497-503. 10.1097/SHK.0b013e318142c434, 18598004.
32. Zhou M, Simms HH, Wang P. Adrenomedullin and adrenomedullin binding protein-1 attenuate vascular endothelial cell apoptosis in sepsis. Ann Surg 2004, 240:321-330. 10.1097/01.sla.0000133253.45591.5b, 1356410, 15273558.
33. Sharshar T, Gray F, Lorin De La Grandmaison G, Hopkinson NS, Ross E, Dorandeu A, Orlikowski D, Raphael JC, Gajdos P, Annane D. Apoptosis of neurons in cardiovascular autonomic centres triggered by inducible nitric oxide synthase after death from septic shock. Lancet 2003, 362:1799-1805. 10.1016/S0140-6736(03)14899-4, 14654318.
34. Benjamim CF, Canetti C, Cunha FQ, Kunkel SL, Peters-Golden M. Opposing and hierarchical roles of leukotrienes in local innate immune versus vascular responses in a model of sepsis. J Immunol 2005, 174:1616-1620.
35. Park SW, Chen SW, Kim M, Brown KM, Kolls JK, D'Agati VD, Lee HT. Cytokines induce small intestine and liver injury after renal ischemia or nephrectomy. Lab Invest 2011, 91:63-84. 10.1038/labinvest.2010.151, 2991383, 20697374.
36. Lee HT, Kim M, Kim JY, Brown KM, Ham A, D'Agati VD, Mori-Akiyama Y. Critical role of interleukin-17A in murine intestinal ischemia-reperfusion injury. Am J Physiol Gastrointest Liver Physiol 2013, 304:G12-G25. 10.1152/ajpgi.00201.2012, 23125155.
37. Bone RC, Grodzin CJ, Balk RA. Sepsis: a new hypothesis for pathogenesis of the disease process. Chest 1997, 121:235-243.
38. Cavaillon J-M, Adib-Conquy M, Cloëz-Tayarani I, Fitting C. Immunodepression in sepsis and SIRS assessed by ex vivo cytokine production is not a generalized phenomenon: a review. J Endotoxin Res 2001, 7:85-93.
39. Tamayo E, Fernández A, Almansa R, Carrasco E, Heredia M, Lajo C, Goncalves L, Gómez-Herreras JI, de Lejarazu RO, Bermejo-Martin JF. Pro- and anti-inflammatory responses are regulated simultaneously from the first moments of septic shock. Eur Cytokine Netw 2011, 22:82-87.
40. Tang BM, Huang SJ, McLean AS. Genome-wide transcription profiling of human sepsis: a systematic review. Crit Care 2010, 14:R237. 10.1186/cc9392, 3219990, 21190579.
41. Muñoz C, Carlet J, Fitting C, Misset B, Bleriot JP, Cavaillon JM. Dysregulation of in vitro cytokine production by monocytes during sepsis. J Clin Invest 1991, 88:1747-1754. 10.1172/JCI115493, 295719, 1939659.
42. Kim OY, Monsel A, Bertrand M, Coriat P, Cavaillon JM, Adib-Conquy M. Differential down-regulation of HLA-DR on monocyte subpopulations during systemic inflammation. Crit Care 2010, 14:R61. 10.1186/cc8959, 2887183, 20385017.
43. Kox M, Timmermans K, Veaneker M, Scheffer G, Pickkers P. Immune paralysis in trauma patients, implications for pre-hospital intervention. Crit Care 2013, 17:9.
44. Adrie C, Adib-Conquy M, Laurent I, Monchi M, Vinsonneau C, Fitting C, Fraisse F, Dinh-Xuan AT, Carli P, Spaulding C, Dhainaut JF, Cavaillon JM. Successful cardiopulmonary resuscitation after cardiac arrest as a 'sepsis like' syndrome. Circulation 2002, 106:562-568. 10.1161/01.CIR.0000023891.80661.AD, 12147537.
45. Gentile LF, Cuenca AG, Efron PA, Ang D, Bihorac A, McKinley BA, Moldawer LL, Moore FA. Persistent inflammation and immunosuppression: a common syndrome and new horizon for surgical intensive care. J Trauma Acute Care Surg 2012, 72:1491-1501. 10.1097/TA.0b013e318256e000, 3705923, 22695412.
46. Danikas DD, Karakantza M, Theodorou GL, Sakellaropoulos GC, Gogos CA. Prognostic value of phagocytic activity of neutrophils and monocytes in sepsis. Correlation to CD64 and CD14 antigen expression. Clin Exp Immunol 2008, 154:87-97. 10.1111/j.1365-2249.2008.03737.x, 2561092, 18727624.
47. Adib-Conquy M, Adrie C, Fitting C, Gattoliat O, Beyaert R, Cavaillon JM. Up-regulation of MyD88s and SIGIRR, molecules inhibiting Toll-like receptor signaling, in monocytes from septic patients. Crit Care Med 2006, 34:2377-2385. 10.1097/01.CCM.0000233875.93866.88, 16850005.
48. Peck OM, Fan H, Tempel GE, Teti G, Halushka PV, Cook JA. Staphylococcus aureus and lipopolysaccharide induce homologous tolerance but heterologous priming: role of interferon-gamma. Shock 2004, 21:254-260. 10.1097/01.shk.0000111662.09279.59, 14770039.
49. Quintin J, Saeed S, Martens JH, Giamarellos-Bourboulis EJ, Ifrim DC, Logie C, Jacobs L, Jansen T, Kullberg BJ, Wijmenga C, Joosten LA, Xavier RJ, van der Meer JW, Stunnenberg HG, Netea MG. Candida albicans infection affords protection against reinfection via functional reprogramming of monocytes. Cell Host Microbe 2012, 12:223-232. 10.1016/j.chom.2012.06.006, 3864037, 22901542.
50. Cavaillon JM, Adrie C, Fitting C, Adib-Conquy M. Reprogramming of circulatory cells in sepsis and SIRS. J Endotoxin Res 2005, 11:311-320. 10.1177/09680519050110050901, 16263005.
51. Suzuki T, Shimizu T, Szalay L, Choudhry MA, Rue LW, Bland KI, Chaudry IH. Androstenediol ameliorates alterations in immune cells cytokine production capacity in a two-hit model of trauma-hemorrhage and sepsis. Cytokine 2006, 34:76-84. 10.1016/j.cyto.2006.04.007, 16737821.
52. Neunaber C, Oestern S, Andruszkow H, Zeckey C, Mommsen P, Kutter D, Stöfen M, Krettek C, Hildebrand F. Cytokine productive capacity of alveolar macrophages and Kupffer cells after femoral fracture and blunt chest trauma in a murine trauma model. Immunol Lett 2013, 152:159-166. 10.1016/j.imlet.2013.05.012, 23735227.
53. Philippart F, Fitting C, Cavaillon JM. Lung microenvironment contributes to the resistance of alveolar macrophages to develop tolerance to endotoxin*. Crit Care Med 2012, 40:2987-2996. 10.1097/CCM.0b013e31825b8d57, 22878679.
54. Hoogerwerf JJ, de Vos AF, van't Veer C, Bresser P, de Boer A, Tanck MW, Draing C, van der Zee JS, van der Poll T. Priming of alveolar macrophages upon instillation of lipopolysaccharide in the human lung. Am J Respir Cell Mol Biol 2010, 42:349-356. 10.1165/rcmb.2008-0362OC, 19448156.
55. Zager RA, Johnson AC, Lund S. 'Endotoxin tolerance': TNF-alpha hyper-reactivity and tubular cytoresistance in a renal cholesterol loading state. Kidney Int 2007, 71:496-503. 10.1038/sj.ki.5002092, 17228359.
56. Zurovsky Y, Eligal Z. Reduction of risk following endotoxin injection in unilaterally nephrectomized rats. Exp Toxicol Pathol 1996, 48:41-46. 10.1016/S0940-2993(96)80092-3, 8919270.
57. Zhang S, Kim CC, Batra S, McKerrow JH, Loke P. Delineation of diverse macrophage activation programs in response to intracellular parasites and cytokines. PLoS Negl Trop Dis 2010, 4:e648. 10.1371/journal.pntd.0000648, 2846935, 20361029.
58. Hacham M, Cristal N, White RM, Segal S, Apte RN. Complementary organ expression of IL-1 vs IL-6 and CSF-1 activities in normal and LPS injected mice. Cytokine 1996, 8:21-31. 10.1006/cyto.1995.0004, 8742063.
59. Raschke RA, Garcia-Orr R. Hemophagocytic lymphohistiocytosis: a potentially underrecognized association with systemic inflammatory response syndrome, severe sepsis, and septic shock in adults. Chest 2011, 140:933-938. 10.1378/chest.11-0619, 21737492.
60. Ding Y, Chung CS, Newton S, Chen Y, Carlton S, Albina JE, Ayala A. Polymicrobial sepsis induces divergent effects on splenic and peritoneal dendritic cell function in mice. Shock 2004, 22:137-144. 10.1097/01.shk.0000131194.80038.3f, 2253681, 15257086.
61. Metzger DW, Salmon SL, Kirimanjeswara G. Differing effects of interleukin-10 on cutaneous and pulmonary Francisella tularensis live vaccine strain infection. Infect Immun 2013, 81:2022-2027. 10.1128/IAI.00024-13, 3676042, 23529615.
62. Blanchet C, Jouvion G, Fitting C, Cavaillon JM, Adib-Conquy M. Protective or deleterious role of scavenger receptors SR-A and CD36 on host resistance to Staphylococcus aureus depends on the site of infection. PloS One 2014, 9:e87927. 10.1371/journal.pone.0087927, 3909292, 24498223.
63. Dorrington MG, Roche AM, Chauvin SE, Tu Z, Mossman KL, Weiser JN, Bowdish DM. MARCO is required for TLR2- and Nod2-mediated responses to Streptococcus pneumoniae and clearance of pneumococcal colonization in the murine nasopharynx. J Immunol 2013, 190:250-258. 10.4049/jimmunol.1202113, 3529821, 23197261.
64. Pang G, Ortega M, Zighang R, Reeves G, Clancy R. Autocrine modulation of IL-8 production by sputum neutrophils in chronic bronchial sepsis. Am J Respir Crit Care Med 1997, 155:726-371. 10.1164/ajrccm.155.2.9032219, 9032219.
65. Muenzer JT, Davis CG, Chang K, Schmidt RE, Dunne WM, Coopersmith CM, Hotchkiss RS. Characterization and modulation of the immunosuppressive phase of sepsis. Infect Immun 2010, 78:1582-15492. 10.1128/IAI.01213-09, 2849407, 20100863.
66. Warren HS, Fitting C, Hoff E, Adib-Conquy M, Beasley-Topliffe L, Tesini B, Liang X, Valentine C, Hellman J, Hayden D, Cavaillon JM. Resilience to bacterial infection: difference between species could be due to proteins in serum. J Infect Dis 2010, 201:223-232. 10.1086/649557, 2798011, 20001600.
67. Seok J, Warren HS, Cuenca AG, Mindrinos MN, Baker HV, Xu W, Richards DR, McDonald-Smith GP, Gao H, Hennessy L, Finnerty CC, López CM, Honari S, Moore EE, Minei JP, Cuschieri J, Bankey PE, Johnson JL, Sperry J, Nathens AB, Billiar TR, West MA, Jeschke MG, Klein MB, Gamelli RL, Gibran NS, Brownstein BH, Miller-Graziano C, Calvano SE, Mason PH, et al. Genomic responses in mouse models poorly mimic human inflammatory diseases. Proc Natl Acad Sci U S A 2013, 110:3507-3512. 10.1073/pnas.1222878110, 3587220, 23401516.
68. Kapetanovic R, Fairbairn L, Beraldi D, Sester DP, Archibald AL, Tuggle CK, Hume DA. Pig bone marrow-derived macrophages resemble human macrophages in their response to bacterial lipopolysaccharide. J Immunol 2012, 188:3382-3394. 10.4049/jimmunol.1102649, 22393154.
69. Takahashi H, Tsuda Y, Takeuchi D, Kobayashi M, Herndon DN, Suzuki F. Influence of systemic inflammatory response syndrome on host resistance against bacterial infections. Crit Care Med 2004, 32:1879-1885. 10.1097/01.CCM.0000139606.34631.61, 15343016.
70. Otto GP, Sossdorf M, Claus RA, Rödel J, Menge K, Reinhart K, Bauer M, Riedemann NC. The late phase of sepsis is characterized by an increased microbiological burden and death rate. Crit Care 2011, 15:R183. 10.1186/cc10332, 3387626, 21798063.
71. Osawa R, Singh N. Cytomegalovirus infection in critically ill patients: a systematic review. Crit Care 2009, 13:R68. 10.1186/cc7875, 2717427, 19442306.
72. Luyt CE, Combes A, Deback C, Aubriot-Lorton MH, Nieszkowska A, Trouillet JL, Capron F, Agut H, Gibert C, Chastre J. Herpes simplex virus lung infection in patients undergoing prolonged mechanical ventilation. Am J Respir Crit Care Med 2007, 175:935-942. 10.1164/rccm.200609-1322OC, 17234903.
73. Torgersen C, Moser P, Luckner G, Mayr V, Jochberger S, Hasibeder WR, Dünser MW. Macroscopic postmortem findings in 235 surgical intensive care patients with sepsis. Anesth Analg 2009, 108:1841-1847. 10.1213/ane.0b013e318195e11d, 19448210.
74. Döcke WD, Randow F, Syrbe U, Krausch D, Asadullah K, Reinke P, Volk HD, Kox W. Monocyte deactivation in septic patients: restoration by IFNg treatment. Nature Med 1997, 3:678-681. 10.1038/nm0697-678, 9176497.
75. Wasserman D, Ioannovich JD, Hinzmann RD, Deichsel G, Steinmann GG. Interferon-gamma in the prevention of severe burn-related infections: a European phase III multicenter trial. The Severe Burns Study Group. Crit Care Med 1998, 26:434-439. 10.1097/00003246-199803000-00010, 9504568.
76. Bo L, Wang F, Zhu J, Li J, Deng X. Granulocyte-colony stimulating factor (G-CSF) and granulocyte-macrophage colony stimulating factor (GM-CSF) for sepsis: a meta-analysis. Crit Care 2011, 15:R58. 10.1186/cc10031, 3221991, 21310070.
77. Verhoef G, Boogaerts M. Treatment with granulocyte-macrophage colony stimulating factor and the adult respiratory distress syndrome. Am J Hematol 1991, 36:285-287. 10.1002/ajh.2830360413, 1672790.
78. Bozinovski S, Jones J, Vlahos R, Hamilton J, Anderson G. Granulocyte/macrophage-colony-stimulating factor (GM-CSF) regulates lung innate immunity to lipopolysaccharide through Akt/Erk activation of NFkappa B and AP-1 in vivo. J Biol Chem 2002, 277:42808-42814. 10.1074/jbc.M207840200, 12208854.
79. Khameneh HJ, Isa SA, Min L, Nih FW, Ruedl C. GM-CSF signalling boosts dramatically IL-1 production. PLoS One 2011, 6:e23025. 10.1371/journal.pone.0023025, 3145786, 21829580.
80. Venet F, Foray AP, Villars-Méchin A, Malcus C, Poitevin-Later F, Lepape A, Monneret G. IL-7 restores lymphocyte functions in septic patients. J Immunol 2012, 189:5073-5081. 10.4049/jimmunol.1202062, 23053510.
81. Sinha ML, Fry TJ, Fowler DH, Miller G, Mackall CL. Interleukin 7 worsens graft-versus-host disease. Blood 2002, 100:2642-2649. 10.1182/blood-2002-04-1082, 12239180.
82. Willis CR, Seamons A, Maxwell J, Treuting PM, Nelson L, Chen G, Phelps S, Smith CL, Brabb T, Iritani BM, Maggio-Price L. Interleukin-7 receptor blockade suppresses adaptive and innate inflammatory responses in experimental colitis. J Inflamm (Lond) 2012, 9:39.
83. Hartgring SA, Willis CR, Alcorn D, Nelson LJ, Bijlsma JW, Lafeber FP, van Roon JA. Blockade of the interleukin-7 receptor inhibits collagen-induced arthritis and is associated with reduction of T cell activity and proinflammatory mediators. Arthritis Rheum 2010, 62:2716-2725. 10.1002/art.27578, 20499386.
84. Jin JO, Yu Q. Systemic administration of TLR3 agonist induces IL-7 expression and IL-7-dependent CXCR3 ligand production in the lung. J Leukoc Biol 2013, 93:413-425. 10.1189/jlb.0712360, 23271706.
85. Alderson MR, Tough TW, Ziegler SF, Grabstein KH. Interleukin 7 induces cytokine secretion and tumoricidal activity by human peripheral blood monocytes. J Exp Med 1991, 173:923-930. 10.1084/jem.173.4.923, 2190815, 2007858.
86. Ostatin A, Paltsev A, Leplina O, Shevela Y, Chernykh H. The experience of surgical infections treatment with extracorporal immunotherapy. Medicinskaya Immunol 2000, 2:43-51.
87. Ertel W, Morrison MH, Ayala A, Chaudry IH. Chloroquine attenuates hemorrhagic shock-induced immunosuppression and decreases susceptibility to sepsis. Arch Surg 1992, 127:70-75. 10.1001/archsurg.1992.01420010084012, 1734852.
88. Suzuki T, Shimizu T, Yu HP, Hsieh YC, Choudhry MA, Schwacha MG, Chaudry IH. Tissue compartment-specific role of estrogen receptor subtypes in immune cell cytokine production following trauma-hemorrhage. J Appl Physiol 2007, 102:163-168.
89. Chiang N, Fredman G, Bäckhed F, Oh SF, Vickery T, Schmidt BA, Serhan CN. Infection regulates pro-resolving mediators that lower antibiotic requirements. Nature 2012, 484:524-528. 10.1038/nature11042, 3340015, 22538616.
90. Eisen DP, Reid D, McBryde ES. Acetyl salicylic acid usage and mortality in critically ill patients with the systemic inflammatory response syndrome and sepsis. Crit Care Med 2012, 40:1761-1767. 10.1097/CCM.0b013e318246b9df, 22610182.
91. Wu J, Zhou L, Liu J, Ma G, Kou Q, He Z, Chen J, Ou-Yang B, Chen M, Li Y, Wu X, Gu B, Chen L, Zou Z, Qiang X, Chen Y, Lin A, Zhang G, Guan X. The efficacy of thymosin alpha 1 for severe sepsis (ETASS): a multicenter, single-blind, randomized and controlled trial. Crit Care 2013, 17:R8. 10.1186/cc11932, 23327199.
92. Zhang Y, Chen H, Li YM, Zheng SS, Chen YG, Li LJ, Zhou L, Xie HY, Praseedom RK. Thymosin alpha1- and ulinastatin-based immunomodulatory strategy for sepsis arising from intra-abdominal infection due to carbapenem-resistant bacteria. J Infect Dis 2008, 198:723-730. 10.1086/590500, 18613793.
93. Sodhi A, Paul S. Involvement of mitogen-activated protein kinases in the signal transduction pathway of bone marrow-derived macrophage activation in response to in vitro treatment with thymosin alpha 1. Int Immunopharmacol 2002, 2:47-58. 10.1016/S1567-5769(01)00139-4, 11789669.
94. Yang X, Qian F, He HY, Liu KJ, Lan YZ, Ni B, Tian Y, Fu XL, Zhang J, Shen ZG, Li J, Yin Y, Li JT, Wu YZ. Effect of thymosin alpha-1 on subpopulations of Th1, Th2, Th17, and regulatory T cells (Tregs) in vitro. Braz J Med Biol Res 2012, 45:25-32. 10.1590/S0100-879X2011007500159, 3854146, 22245858.
95. Monaghan SF, Thakkar RK, Tran ML, Huang X, Cioffi WG, Ayala A, Heffernan DS. Programmed death 1 expression as a marker for immune and physiological dysfunction in the critically ill surgical patient. Shock 2012, 38:117-122. 10.1097/SHK.0b013e31825de6a3, 22683728.
96. Zhang Y, Li J, Lou J, Zhou Y, Bo L, Zhu J, Zhu K, Wan X, Cai Z, Deng X. Upregulation of programmed death-1 on T cells and programmed death ligand-1 on monocytes in septic shock patients. Crit Care 2011, 15:R70. 10.1186/cc10059, 3222003, 21349174.
97. Guignant C, Lepape A, Huang X, Kherouf H, Denis L, Poitevin F, Malcus C, Chéron A, Allaouchiche B, Gueyffier F, Ayala A, Monneret G, Venet F. Programmed death-1 levels correlate with increased mortality, nosocomial infection and immune dysfunctions in septic shock patients. Crit Care 2011, 15:R99. 10.1186/cc10112, 3219369, 21418617.
98. Huang X, Venet F, Wang YL, Lepape A, Yuan Z, Chen Y, Swan R, Kherouf H, Monneret G, Chung CS, Ayala A. PD-1 expression by macrophages plays a pathologic role in altering microbial clearance and the innate inflammatory response to sepsis. Proc Natl Acad Sci U S A 2009, 106:6303-6308. 10.1073/pnas.0809422106, 2669369, 19332785.
99. Brahmamdam P, Inoue S, Unsinger J, Chang KC, McDunn JE, Hotchkiss RS. Delayed administration of anti-PD-1 antibody reverses immune dysfunction and improves survival during sepsis. J Leukoc Biol 2010, 88:233-240. 10.1189/jlb.0110037, 20483923.
100. Zhang Y, Zhou Y, Lou J, Li J, Bo L, Zhu K, Wan X, Deng X, Cai Z. PD-L1 blockade improves survival in experimental sepsis by inhibiting lymphocyte apoptosis and reversing monocyte dysfunction. Crit Care 2010, 14:R220. 10.1186/cc9354, 3220038, 21118528.
101. Zhu W, Bao R, Fan X, Tao T, Zhu J, Wang J, Li J, Bo L, Deng X. PD-L1 blockade attenuated sepsis-induced liver injury in a mouse cecal ligation and puncture model. Mediators Inflamm 2013, 2013:361501. 3844221, 24324295.
102. Manjuck J, Saha DC, Astiz M, Eales LJ, Rackow EC. Decreased response to recall antigens is associated with depressed costimulatory receptor expression in septic critically ill patients. J Lab Clin Med 2000, 135:153-160. 10.1067/mlc.2000.104306, 10695660.
103. Inoue S, Bo L, Bian J, Unsinger J, Chang K, Hotchkiss RS. Dose-dependent effect of anti-CTLA-4 on survival in sepsis. Shock 2011, 36:38-44. 10.1097/SHK.0b013e3182168cce, 3412306, 21368717.
104. Chang KC, Burnham CA, Compton SM, Rasche DP, Mazuski R, Smcdonough J, Unsinger J, Korman AJ, Green JM, Hotchkiss RS. Blockade of the negative co-stimulatory molecules PD-1 and CTLA-4 improves survival in primary and secondary fungal sepsis. Crit Care 2013, 17:R85. 10.1186/cc12711, 3706819, 23663657.
105. LeMessurier K, Häcker H, Tuomanen E, Redecke V. Inhibition of T cells provides protection against early invasive pneumococcal disease. Infect Immun 2010, 78:5287-5294. 10.1128/IAI.00431-10, 2981332, 20855509.
106. Shubin NJ, Monaghan SF, Heffernan DS, Chung CS, Ayala A. B and T lymphocyte attenuator expression on CD4+ T-cells associates with sepsis and subsequent infections in ICU patients. Crit Care 2013, 17:R276. 10.1186/cc13131, 24289156.
107. Shubin NJ, Chung CS, Heffernan DS, Irwin LR, Monaghan SF, Ayala A. BTLA expression contributes to septic morbidity and mortality by inducing innate inflammatory cell dysfunction. J Leukoc Biol 2012, 92:593-603. 10.1189/jlb.1211641, 3427605, 22459947.
108. Kobayashi Y, Iwata A, Suzuki K, Suto A, Kawashima S, Saito Y, Owada T, Kobayashi M, Watanabe N, Nakajima H. B and T lymphocyte attenuator inhibits LPS-induced endotoxic shock by suppressing Toll-like receptor 4 signaling in innate immune cells. Proc Natl Acad Sci U S A 2013, 110:5121-5126. 10.1073/pnas.1222093110, 3612598, 23479601.