Early biomarker activity in severe sepsis and septic shock and a contemporary review of immunotherapy trials: Not a time to give up, but to give it earlier

Shock

Volumn 39, Issue 2, 2013, Pages 127-137

  Rivers, Emanuel P ^a   Jaehne, Anja Kathrin ^a   Nguyen, H Bryant ^b   Papamatheakis, Demosthenes G ^c   Singer, Daniel ^d   Yang, James J ^a   Brown, Samantha ^a   Klausner, Howard ^a  

^a HENRY FORD HOSPITAL   (United States)

^b LOMA LINDA UNIVERSITY   (United States)

^c UNIVERSITY OF CALIFORNIA   (United States)

^d MOUNT SINAI SCHOOL OF MEDICINE   (United States)

Author keywords

biomarkers; clinical trials; cytokines; early inflammation; immune modulation; immunotherapy; review; Sepsis; septic shock; translational research

Indexed keywords

BIOLOGICAL MARKER; CASPASE 3; D DIMER; GELATINASE B; HIGH MOBILITY GROUP B1 PROTEIN; INTERCELLULAR ADHESION MOLECULE 1; INTERLEUKIN 1 RECEPTOR BLOCKING AGENT; INTERLEUKIN 10; INTERLEUKIN 1BETA; INTERLEUKIN 6; INTERLEUKIN 8; MYELOPEROXIDASE; TUMOR NECROSIS FACTOR ALPHA; VASCULOTROPIN;

APOPTOSIS; DISEASE MARKER; HUMAN; IMMUNOTHERAPY; INFLAMMATION; NONHUMAN; PROTEIN BLOOD LEVEL; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; SEPSIS; SEPTIC SHOCK; SYSTEMATIC REVIEW;

ANIMALS; BIOLOGICAL MARKERS; CASE-CONTROL STUDIES; DISEASE MODELS, ANIMAL; EARLY DIAGNOSIS; FEMALE; HUMANS; IMMUNOLOGIC FACTORS; IMMUNOTHERAPY; MALE; MIDDLE AGED; RANDOMIZED CONTROLLED TRIALS AS TOPIC; SEPSIS; SHOCK, SEPTIC; TIME-TO-TREATMENT;

EID: 84872897812     PISSN: 10732322     EISSN: 15400514     Source Type: Journal    
DOI: 10.1097/SHK.0b013e31827dafa7     Document Type: Review

References (111)

1. Kumar G, Kumar N, Taneja A, Kaleekal T, Tarima S, McGinley E, Jimenez E, Mohan A, Khan RA, Whittle J, et al.: Nationwide trends of severe sepsis in the 21st century (2000-2007). Chest 140:1223-31, 2011.
2. Andrews R, Elixhauser A. The national hospital bill: growth trends and 2005 update on the most expensive conditions by payer. Healthcare Cost and Utilization Project. 2007. Available at: http://www.hcup-us.ahrq.gov/reports/ statbriefs/sb42.pdf:1-13. Last accessed May 2012.
3. Bone RC: Immunologic dissonance: a continuing evolution in our understanding of the systemic inflammatory response syndrome (SIRS) and the multiple organ dysfunction syndrome (MODS) [see comments]. Ann Intern Med 125:680-687, 1996.
4. Nasraway SA: The problems and challenges of immunotherapy in sepsis. Chest 123:451S-459S, 2003.
5. Ranieri VM, Thompson BT, Barie PS, Dhainaut JF, Douglas IS, Finfer S, Gardlund B, Marshall JC, Rhodes A, Artigas A, et al.: Drotrecogin alfa (activated) in adults with septic shock. N Engl J Med 366:2055-2064, 2012.
6. Phase III study finds Eisai's eritoran fails to reduce mortality in severe Sepsis. Genetic Engineering & Biotechnology News. 2012. Available at: http://www.genengnews.com/gen-news-highlights/phase-iii-study-finds-eisai-s- eritoran-fails-to-reduce-mortality-in-severe-sepsis/81244581/. Accessed Jan 26, 2011.
7. Agennix stops phase II/III talactoferrin study in sepsis due to higher death rates. 2012. Available at: http://www.genengnews.com/gen-news-highlights/ agennix-stops-phase-ii-iii-talactoferrin-study-in-sepsis-due-to-higher-death- rates/81246312/. Accessed February 04, 2012.
8. Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, Peterson E, Tomlanovich M: Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 345:1368-1377, 2001.
9. Rivers EP, Kruse JA, Jacobsen G, Shah K, Loomba M, Otero R, Childs EW: The influence of early hemodynamic optimization on biomarker patterns of severe sepsis and septic shock. Crit Care Med 35:2016-2024, 2007.
10. Roman-Marchant O, Orellana-Jimenez CE, De Backer D, Melot C, Vincent JL: Septic shock of early or late onset: does it matter? Chest 126:173-178, 2004.
11. Brun-Buisson C, Doyon F, Carlet J, Dellamonica P, Gouin F, Lepoutre A, Mercier JC, Offenstadt G, Regnier B: Incidence, risk factors, and outcome of severe sepsis and septic shock in adults. A multicenter prospective study in intensive care units. French ICU Group for Severe Sepsis. JAMA 274: 968-974, 1995.
12. Estenssoro E, Gonzalez F, Laffaire E, Canales H, Saenz G, Reina R, Dubin A: Shock on admission day is the best predictor of prolonged mechanical ventilation in the ICU. Chest 127:598-603, 2005.
13. Kiers HD, Griesdale DE, Litchfield A, Reynolds S, Gibney RT, Chittock D, Pickkers P, Sweet DD: Effect of early achievement of physiologic resuscitation goals in septic patients admitted from the ward on the kidneys. J Crit Care 25:G563-G569, 2010.
14. Dorresteijn MJ, van Eijk LT, Netea MG, Smits P, van der Hoeven JG, Pickkers P: Iso-osmolar prehydration shifts the cytokine response towards a more anti-inflammatory balance in human endotoxemia. J Endotoxin Res 11:287-293, 2005.
15. Hollenberg SM: Mouse models of resuscitated shock. Shock 24(Suppl 1): 58-63, 2005.
16. Martich GD, Boujoukos AJ, Suffredini AF: Response of man to endotoxin. Immunobiology 187:403-416, 1993.
17. Dyson A, Singer M: Animal models of sepsis: why does preclinical efficacy fail to translate to the clinical setting? Crit Care Med 37:S30-S37, 2009.
18. Levy MM, Dellinger RP, Townsend SR, Linde-Zwirble WT, Marshall JC, Bion J, Schorr C, Artigas A, Ramsay G, Beale R, et al.: The Surviving Sepsis Campaign: results of an international guideline-based performance improvement program targeting severe sepsis. Crit Care Med 38:367-374, 2010.
19. Chalfin DB, Trzeciak S, Likourezos A, Baumann BM, Dellinger RP: Impact of delayed transfer of critically ill patients from the emergency department to the intensive care unit. Crit Care Med 35:1477-1483, 2007.
20. Lundberg JS, Perl TM, Wiblin T, Costigan MD, Dawson J, Nettleman MD, Wenzel RP: Septic shock: an analysis of outcomes for patients with onset on hospital wards versus intensive care units. Crit Care Med 26:1020-1024, 1998.
21. Carr GE, Edelson DP, Yuen TC, McConville JF, Kress JP, VandenHoek TL, Hall JB: In-Hospital cardiac arrest among patients with coexisting pneumonia: a report from the American Heart Association's get with the guidelinesV resuscitation program. Am J Respir Crit Care Med 183:A6339, 2011.
22. Sevransky JE, Nour S, Susla GM, Needham DM, Hollenberg S, Pronovost P: Hemodynamic goals in randomized clinical trials in patients with sepsis: a systematic review of the literature. Crit Care 11:R67, 2007.
23. Holzheimer RG: Antibiotic induced endotoxin release and clinical sepsis: a review. J Chemother 13(Spec. No. 1):159-172, 2001.
24. Mathy-Hartert M, Deby-Dupont G, Deby C, Jadoul L, Vandenberghe A, Lamy M: Cytotoxicity towards human endothelial cells, induced by neutrophil mye-loperoxidase: protection by ceftazidime. Mediators Inflamm 4:437-443, 1995.
25. Milano S, Arcoleo F, D'Agostino P, Cillari E: Intraperitoneal injection of tetracyclines protects mice from lethal endotoxemia downregulating inducible nitric oxide synthase in various organs and cytokine and nitrate secretion in blood. Antimicrob Agents Chemother 41:117-121, 1997.
26. Halter JM, Pavone LA, Steinberg JM, Gatto LA, DiRocco J, Landas S, Nieman GF: Chemically modified tetracycline (COL-3) improves survival if given 12 but not 24 hours after cecal ligation and puncture. Shock 26:587-591, 2006.
27. Kanoh S, Rubin BK: Mechanisms of action and clinical application of macro-lides as immunomodulatory medications. Clin Microbiol Rev 23:590-615, 2010.
28. Kumar A, Roberts D, Wood KE, Light B, Parrillo JE, Sharma S, Suppes R, Feinstein D, Zanotti S, Taiberg L, et al.: Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med 34:1589-1596, 2006.
29. Tsujimoto H, Ono S, Efron PA, Scumpia PO, Moldawer LL, Mochizuki H: Role of Toll-like receptors in the development of sepsis. Shock 29:315-321, 2008.
30. Tidswell M, Tillis W, Larosa SP, Lynn M, Wittek AE, Kao R, Wheeler J, Gogate J, Opal SM: Phase 2 trial of eritoran tetrasodium (E5564), a Toll-like receptor 4 antagonist, in patients with severe sepsis. Crit Care Med 38:72-83, 2010.
31. Rice TW, Wheeler AP, Bernard GR, Vincent JL, Angus DC, Aikawa N, Demeyer I, Sainati S, Amlot N, Cao C, et al.: A randomized, double-blind, placebo-controlled trial of TAK-242 for the treatment of severe sepsis. Crit Care Med 38:1685-1694, 2010.
32. Vincent JL, Sun Q, Dubois MJ: Clinical trials of immunomodulatory therapies in severe sepsis and septic shock. Clin Infect Dis 34:1084-1093, 2002.
33. Effect of high-dose glucocorticoid therapy on mortality in patients with clinical signs of systemic sepsis. The Veterans Administration Systemic Sepsis Cooperative Study Group. N Engl J Med 317:659-665, 1987.
34. Annane D, Sebille V, Charpentier C, Bollaert PE, Francois B, Korach JM, Capellier G, Cohen Y, Azoulay E, Troche G, et al.: Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA 288:862-871, 2002.
35. Sprung CL, Annane D, Keh D, Moreno R, Singer M, Freivogel K, Weiss YG, Benbenishty J, Kalenka A, Forst H, et al.: Hydrocortisone therapy for patients with septic shock. N Engl J Med 358:111-124, 2008.
36. Arons MM, Wheeler AP, Bernard GR, Christman BW, Russell JA, Schein R, Summer WR, Steinberg KP, Fulkerson W, Wright P, et al.: Effects of ibu-profen on the physiology and survival of hypothermic sepsis. Ibuprofen in Sepsis Study Group. Crit Care Med 27:699-707, 1999.
37. Memis D, Karamanlioglu B, Turan A, Koyuncu O, Pamukcu Z: Effects of lornoxicam on the physiology of severe sepsis. Crit Care 8:R474-R482, 2004.
38. Malik R. Agennix AG halts phase II/III OASIS trial in severe sepsis. 2012. Available at: http://agennix.com/index.php?option=com-content&view= article& id=205%3Aagennix-ag-halts-phase-iiiii-oasis-trial-in-severe- sepsis&catid= 23%3Apress-releases-2012&Itemid=56&lang=en.
39. Shimizu T, Hanasawa K, Sato K, Umeki M, Koga N, Naganuma T, Sato S, Shimonishi T, Ikeda T, Matsuno N, et al.: Direct hemoperfusion with polymyxin-BYimmobilized fiber columns improves septic hypotension and reduces inflammatory mediators in septic patients with colorectal perforation. Langenbecks Arch Surg 394:303-311, 2009.
40. Meisel C, Schefold JC, Pschowski R, Baumann T, Hetzger K, Gregor J, Weber-Carstens S, Hasper D, Keh D, Zuckermann H, et al.: Granulocyte-macrophage colony-stimulating factor to reverse sepsis-associated immuno-suppression: a double-blind, randomized, placebo-controlled multicenter trial. Am J Respir Crit Care Med 180:640-648, 2009.
41. Dinarello CA: The role of interleukin-1 in host responses to infectious diseases. Infect Agents Dis 1:227-236, 1992.
42. Boermeester MA, van Leeuwen PA, Coyle SM, Wolbink GJ, Hack CE, Lowry SF: Interleukin-1 blockade attenuates mediator release and dysregulation of the hemostatic mechanism during human sepsis. Arch Surg 130:739-748, 1995.
43. Fisher CJ, Jr., Dhainaut JF, Opal SM, Pribble JP, Balk RA, Slotman GJ, Iberti TJ, Rackow EC, Shapiro MJ, Greenman RL, et al.: Recombinant human interleukin 1 receptor antagonist in the treatment of patients with sepsis syndrome. Results from a randomized, double-blind, placebo-controlled trial. Phase III rhIL-1ra Sepsis Syndrome Study Group. JAMA 271:1836-1843, 1994.
44. Opal SM, Fisher CJ, Jr., Dhainaut JF, Vincent JL, Brase R, Lowry SF, Sadoff JC, Slotman GJ, Levy H, Balk RA, et al.: Confirmatory interleukin-1 receptor antagonist trial in severe sepsis: a phase III, randomized, double-blind, placebo-controlled, multicenter trial. The Interleukin-1 Receptor Antagonist Sepsis Investigator Group. Crit Care Med 25:1115-1124, 1997.
45. Hein OV, Misterek K, Tessmann JP, van Dossow V, Krimphove M, Spies C: Time course of endothelial damage in septic shock: prediction of outcome. Crit Care 9:R323-R330, 2005.
46. Abraham E, Anzueto A, Gutierrez G, Tessler S, San Pedro G, Wunderink R, Dal Nogare A, Nasraway S, Berman S, Cooney R, et al.: Double-blind randomised controlled trial of monoclonal antibody to human tumour necrosis factor in treatment of septic shock. NORASEPT II Study Group. Lancet 351:929-933, 1998.
47. Abraham E, Wunderink R, Silverman H, Perl TM, Nasraway S, Levy H, Bone R, Wenzel RP, Balk R, Allred R, 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 273:934-941, 1995.
48. Cohen J, Carlet J: INTERSEPT: an international, multicenter, placebo-controlled trial of monoclonal antibody to human tumor necrosis factor-alpha in patients with sepsis. International Sepsis Trial Study Group. Crit Care Med 24:1431-1440, 1996.
49. Fisher CJ, Jr., Opal SM, Dhainaut JF, Stephens S, Zimmerman JL, Nightingale P, Harris SJ, Schein RM, Panacek EA, Vincent JL, et al.: Influence of an anti-tumor necrosis factor monoclonal antibody on cytokine levels in patients with sepsis. The CB0006 Sepsis Syndrome Study Group. Crit Care Med 21:318-327, 1993.
50. Panacek EA, Marshall JC, Albertson TE, Johnson DH, Johnson S, MacArthur RD, Miller M, Barchuk WT, Fischkoff S, Kaul M, et al.: Efficacy and safety of the monoclonal anti-tumor necrosis factor antibody F(ab¶)2 fragment afe-limomab in patients with severe sepsis and elevated interleukin-6 levels. Crit Care Med 32:2173-2182, 2004.
51. Reinhart K, Karzai W: Anti-tumor necrosis factor therapy in sepsis: update on clinical trials and lessons learned. Crit Care Med 29:S121-S125, 2001.
52. Rice TW, Wheeler AP, Morris PE, Paz HL, Russell JA, Edens TR, Bernard R: Safety and efficacy of affinity-purified, anti-tumor necrosis factor-alpha, ovine Fab for injection (CytoFab) in severe sepsis. Crit Care Med 34:2271-2281, 2006.
53. Staubach KH, Schroder J, Stuber F, Gehrke K, Traumann E, Zabel P: Effect of pentoxifylline in severe sepsis: results of a randomized, double-blind, placebo-controlled study. Arch Surg 133:94-100, 1998.
54. Kirschenbaum L, Astiz M, Rackow EC: Antibodies to TNF-alpha: too little, too late? Crit Care Med 26:1625-1626, 1998.
55. Suffredini AF, Fantuzzi G, Badolato R, Oppenheim JJ, O'Grady NP: New insights into the biology of the acute phase response. J Clin Immunol 19:203-214, 1999.
56. Mees ST, Toellner S, Marx K, Faendrich F, Kallen KJ, Schroeder J, Haier J, Kahlke V: Inhibition of interleukin-6Ytranssignaling via gp130-Fc in hemor-rhagic shock and sepsis. J Surg Res 157:235-242, 2009.
57. Dandona P, Nix D, Wilson MF, Aljada A, Love J, Assicot M, Bohuon C: Procalcitonin increase after endotoxin injection in normal subjects. J Clin Endocrinol Metab 79:1605-1608, 1994.
58. Hein O, Misterek K, Tessmann J-P, van Dossow V, Krimphove M, Spies C: Time course of endothelial damage in septic shock: prediction of outcome. Critical Care 9:R323-R330, 2005.
59. Abraham E, Naum C, Bandi V, Gervich D, Lowry SF, Wunderink R, Schein RM, Macias W, Skerjanec S, Dmitrienko A, et al.: Efficacy and safety of L-315920Na/S-5920, a selective inhibitor of 14-kDa group IIA secretory phospholipase A2, in patients with suspected sepsis and organ failure. Crit Care Med 31:718-728, 2003.
60. Zeiher BG, Steingrub J, Laterre PF, Dmitrienko A, Fukiishi Y, Abraham E: L-315920NA/S-5920, a selective inhibitor of group IIA secretory phospho-lipase A2, fails to improve clinical outcome for patients with severe sepsis. Crit Care Med 33:1741-1748, 2005.
61. Jenkins JK, Carey PD, Byrne K, Sugerman HJ, Fowler AA 3rd: Sepsis-induced lung injury and the effects of ibuprofen pretreatment. Analysis of early alveolar events via repetitive bronchoalveolar lavage. Am Rev Respir Dis 143:155-161, 1991.
62. Ikuta N, Taniguchi H, Kondoh Y, Takagi K, Hayakawa T: Sustained high levels of circulatory interleukin-8 are associated with a poor outcome in patients with adult respiratory distress syndrome. Intern Med 35:855-860, 1996.
63. Sheu CC, Gong MN, Zhai R, Chen F, Bajwa EK, Clardy PF, Gallagher DC, Thompson BT, Christiani DC: Clinical characteristics and outcomes of sepsis-related vs nonYsepsis-related ARDS. Chest 138:559-567, 2010.
64. Folkesson HG, Matthay MA, Hebert CA, Broaddus VC: Acid aspiration-induced lung injury in rabbits is mediated by interleukin-8Ydependent mechanisms. J Clin Invest 96:107-116, 1995.
65. Walkey AJ, Summer R, Ho V, Alkana P: Acute respiratory distress syndrome: epidemiology and management approaches. Clin Epidemiol 4:159-169, 2012.
66. Afshari A, Brok J, Moller AM, Wetterslev J: Inhaled nitric oxide for acute respiratory distress syndrome (ARDS) and acute lung injury in children and adults. Cochrane Database Syst Rev CD002787, 2010.
67. Cepkova M, Matthay MA: Pharmacotherapy of acute lung injury and the acute respiratory distress syndrome. J Intensive Care Med 21:119-143, 2006.
68. Carney DE, McCann UG, Schiller HJ, Gatto LA, Steinberg J, Picone AL, Nieman GF: Metalloproteinase inhibition prevents acute respiratory distress syndrome. J Surg Res 99:245-252, 2001.
69. Parsons PE, Eisner MD, Thompson BT, Matthay MA, Ancukiewicz M, Bernard GR, Wheeler AP: Lower tidal volume ventilation and plasma cytokine markers of inflammation in patients with acute lung injury. Crit Care Med 33:1-6; discussion 230-232, 2005.
70. Paterson RL, Galley HF, Webster NR: The effect of N-acetylcysteine on nuclear factor-kappa B activation, interleukin-6, interleukin-8, and intercellular adhesion molecule-1 expression in patients with sepsis. Crit Care Med 31:2574-2578, 2003.
71. Poeze M, Froon AH, Ramsay G, Buurman WA, Greve JW: Decreased organ failure in patients with severe SIRS and septic shock treated with the platelet-activating factor antagonist TCV-309: a prospective, multicenter, double-blind, randomized phase II trial. TCV-309 Septic Shock Study Group. Shock 14:421-428, 2000.
72. Bartlett RH: Extracorporeal life support in the management of severe respiratory failure. Clin Chest Med 21:555-561, 2000.
73. Singer P, Shapiro H: Enteral omega-3 in acute respiratory distress syndrome. Curr Opin Clin Nutr Metab Care 12:123-128, 2009.
74. Kacmarek RM, Wiedemann HP, Lavin PT, Wedel MK, Tutuncu AS, Slutsky AS: Partial liquid ventilation in adult patients with acute respiratory distress syndrome. Am J Respir Crit Care Med 173:882-889, 2006.
75. Kesecioglu J, Beale R, Stewart TE, Findlay GP, Rouby JJ, Holzapfel L, Bruins P, Steenken EJ, Jeppesen OK, Lachmann B: Exogenous natural surfactant for treatment of acute lung injury and the acute respiratory distress syndrome. Am J Respir Crit Care Med 180:989-994, 2009.
76. Shorr AF, Thomas SJ, Alkins SA, Fitzpatrick TM, Ling GS: D-Dimer correlates with proinflammatory cytokine levels and outcomes in critically ill patients. Chest 121:1262-1268, 2002.
77. Riewald M, Petrovan RJ, Donner A, Mueller BM, Ruf W: Activation of endothelial cell protease activated receptor 1 by the protein C pathway. Science 296:1880-1882, 2002.
78. Bernard GR, Vincent JL, Laterre PF, LaRosa SP, Dhainaut JF, Lopez-Rodriguez A, Steingrub JS, Garber GE, Helterbrand JD, Ely EW, et al.: Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med 344:699-709, 2001.
79. Warren BL, Eid A, Singer P, Pillay SS, Carl P, Novak I, Chalupa P, Atherstone A, Penzes I, Kubler A, et al.: Caring for the critically ill patient. High-dose antithrombin III in severe sepsis: a randomized controlled trial. JAMA 286: 1869-1878, 2001.
80. Mantell LL, Parrish WR, Ulloa L: HMGB-1 as a therapeutic target for infectious and inflammatory disorders. Shock 25:4-11, 2006.
81. Yang H, Ochani M, Li J, Qiang X, Tanovic M, Harris HE, Susarla SM, Ulloa L, Wang H, DiRaimo R, et al.: Reversing established sepsis with antagonists of endogenous high-mobility group box 1. Proc Natl Acad Sci USA 101:296-301, 2004.
82. Tang Y, Lv B, Wang H, Xiao X, Zuo X: PACAP inhibit the release and cytokine activity of HMGB1 and improve the survival during lethal endo-toxemia. Int Immunopharmacol 8:1646-1651, 2008.
83. Sunden-Cullberg J, Norrby-Teglund A, Rouhiainen A, Rauvala H, Herman G, Tracey KJ, Lee ML, Andersson J, Tokics L, Treutiger CJ: Persistent elevation of high mobility group box-1 protein (HMGB1) in patients with severe sepsis and septic shock. Crit Care Med 33:564-573, 2005.
84. Vanlaere I, Libert C: Matrix metalloproteinases as drug targets in infections caused by gram-negative bacteria and in septic shock. Clin Microbiol Rev 22:224-239, Table of contents, 2009.
85. Albert J, Radomski A, Soop A, Sollevi A, Frostell C, Radomski MW: Differential release of matrix metalloproteinase-9 and nitric oxide following infusion of endotoxin to human volunteers. Acta Anaesthesiol Scand 47: 407-410, 2003.
86. Lalu MM, Csont T, Schulz R: Matrix metalloproteinase activities are altered in the heart and plasma during endotoxemia. Crit Care Med 32:1332-1337, 2004.
87. Shapira L, Soskolne WA, Houri Y, Barak V, Halabi A, Stabholz A: Protection against endotoxic shock and lipopolysaccharide-induced local inflammation by tetracycline: correlation with inhibition of cytokine secretion. Infect Immun 64:825-828, 1996.
88. Nakamura T, Ebihara I, Shimada N, Shoji H, Koide H: Modulation of plasma metalloproteinase-9 concentrations and peripheral blood monocyte mRNA levels in patients with septic shock: effect of fiber-immobilized polymyxin B treatment. Am J Med Sci 316:355-360, 1998.
89. Cruz DN, Antonelli M, Fumagalli R, Foltran F, Brienza N, Donati A, Malcangi V, Petrini F, Volta G, Bobbio Pallavicini FM, et al.: Early use of polymyxin B hemoperfusion in abdominal septic shock: the EUPHAS randomized controlled trial. JAMA 301:2445-2452, 2009.
90. Hao Q, Wang L, Tang H: Vascular endothelial growth factor induces protein kinase DYdependent production of proinflammatory cytokines in endothelial cells. Am J Physiol Cell Physiol 296:C821-C827, 2009.
91. Pickkers P, Sprong T, Eijk L, Hoeven H, Smits P, Deuren M: Vascular endothelial growth factor is increased during the first 48 hours of human septic shock and correlates with vascular permeability. Shock 24:508-512, 2005.
92. Shapiro NI, Yano K, Okada H, Fischer C, Howell M, Spokes KC, Ngo L, Angus DC, Aird WC, et al.: A prospective, observational study of soluble FLT-1 and vascular endothelial growth factor in sepsis. Shock 29:452-457, 2008.
93. van der Flier M, van Leeuwen HJ, van Kessel KP, Kimpen JL, Hoepelman AI, Geelen SP: Plasma vascular endothelial growth factor in severe sepsis. Shock 23:35-38, 2005.
94. Yano K, Liaw PC, Mullington JM, Shih SC, Okada H, Bodyak N, Kang PM, Toltl L, Belikoff B, Buras J, et al.: Vascular endothelial growth factor is an important determinant of sepsis morbidity and mortality. J Exp Med 203: 1447-1458, 2006.
95. Karlsson S, Pettila V, Tenhunen J, Lund V, Hovilehto S, Ruokonen E: Vascular endothelial growth factor in severe sepsis and septic shock. Anesth Analg 106:1820-1826, 2008.
96. Parent C, Eichacker PQ: Neutrophil and endothelial cell interactions in sepsis. The role of adhesion molecules. Infect Dis Clin North Am 13:427-447, 1999.
97. van Griensven M, Probst C, Muller K, Hoevel P, Pape HC: Leukocyte-endothelial interactions via ICAM-1 are detrimental in polymicrobial sepsis. Shock 25:254-259, 2006.
98. Kumasaka T, Quinlan WM, Doyle NA, Condon TP, Sligh J, Takei F, Beaudet A, Bennett CF, Doerschuk CM: Role of the intercellular adhesion molecule-1 (ICAM-1) in endotoxin-induced pneumonia evaluated using ICAM-1 antisense oligonucleotides, antiYICAM-1 monoclonal antibodies, and ICAM-1 mutant mice. J Clin Invest 97:2362-2369, 1996.
99. Welty-Wolf KE, Carraway MS, Huang YC, Simonson SG, Kantrow SP, Kishimoto TK, Piantadosi CA: Antibody to intercellular adhesion molecule 1 (CD54) decreases survival and not lung injury in baboons with sepsis. Am J Respir Crit Care Med 163:665-673, 2001.
100. Endo S, Inada K, Kasai T, Takakuwa T, Yamada Y, Koike S, Wakabayashi G, Niimi M, Taniguchi S, Yoshida M: Levels of soluble adhesion molecules and cytokines in patients with septic multiple organ failure. J Inflamm 46:212-219, 1995.
101. Kayal S, Jais JP, Aguini N, Chaudiere J, Labrousse J: Elevated circulating E-selectin, intercellular adhesion molecule 1, and von Willebrand factor in patients with severe infection. Am J Respir Crit Care Med 157:776-784, 1998.
102. Sessler CN, Windsor AC, Schwartz M, Watson L, Fisher BJ, Sugerman HJ, Fowler AA 3rd: Circulating ICAM-1 is increased in septic shock. Am J Respir Crit Care Med 151:1420-1427, 1995.
103. Friedman G, Jankowski S, Shahla M, Goldman M, Rose RM, Kahn RJ, et al.: Administration of an antibody to E-selectin in patients with septic shock. Crit Care Med 24:229-233, 1996.
104. Eiserich JP, Baldus S, Brennan ML, Ma W, Zhang C, Tousson A, Castro L, Lusis AJ, Nauseef WM, White CR, et al.: Myeloperoxidase, a leukocyte-derived vascular NO oxidase. Science 296:2391-2394, 2002.
105. Jepsen S, Herlevsen P, Knudsen P, Bud MI, Klausen NO: Antioxidant treatment with N-acetylcysteine during adult respiratory distress syndrome: a prospective, randomized, placebo-controlled study. Crit Care Med 20:918-923, 1992.
106. Angstwurm MW, Engelmann L, Zimmermann T, Lehmann C, Spes CH, Abel P, Strauss R, Meier-Hellmann A, Insel R, Radke J, et al.: Selenium in Intensive Care (SIC): results of a prospective randomized, placebo-controlled, multiple-center study in patients with severe systemic inflammatory response syndrome, sepsis, and septic shock. Crit Care Med 35:118-126, 2007.
107. Wesche-Soldato DE, Swan RZ, Chung CS, Ayala A: The apoptotic pathway as a therapeutic target in sepsis. Curr Drug Targets 8:493-500, 2007.
108. Sfeir T, Saha DC, Astiz M, Rackow EC: Role of interleukin-10 in mono-cyte hyporesponsiveness associated with septic shock. Crit Care Med 29: 129-133, 2001.
109. 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 155:5397-5401, 1995.
110. Kumar A, Zanotti S, Bunnell G, Habet K, Anel R, Neumann A, Cheang M, Dinarello CA, Cutler D, Parrillo JE: Interleukin-10 blunts the human inflammatory response to lipopolysaccharide without affecting the cardiovascular response. Crit Care Med 33:331-340, 2005.
111. Gogos CA, Drosou E, Bassaris HP, Skoutelis A: Pro-versus anti-inflammatory cytokine profile in patients with severe sepsis: a marker for prognosis and future therapeutic options. J Infect Dis 181:176-180, 2000.