Bench-to-bedside review: Immunoglobulin therapy for sepsis - biological plausibility from a critical care perspective

Critical Care

Volumn 16, Issue 2, 2011, Pages

  Shankar Hari, Manu ^a,b,c   Spencer, Jo ^b   Sewell, William A ^d   Rowan, Kathryn M ^c   Singer, Mervyn ^e  

^a GUY'S AND ST THOMAS' NHS FOUNDATION TRUST   (United Kingdom)

^b KING'S COLLEGE LONDON   (United Kingdom)

^c King's College London   (United Kingdom)

^d SCUNTHORPE GENERAL HOSPITAL   (United Kingdom)

^e UNIVERSITY COLLEGE LONDON   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

CD16 ANTIGEN; CD209 ANTIGEN; COMPLEMENT; COMPLEMENT COMPONENT C1Q; COMPLEMENT COMPONENT C5A; ENDOBULIN SD; FC RECEPTOR; GAMMAVENIN; GAMUMINE; HIGH MOBILITY GROUP B1 PROTEIN; HUMAN IMMUNOGLOBULIN; IMMUNOGLOBULIN; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; IMMUNOGLOBULIN G; IMMUNOGLOBULIN M; INTERLEUKIN 1; INTERLEUKIN 1 RECEPTOR; INTERLEUKIN 6; MAJOR HISTOCOMPATIBILITY ANTIGEN CLASS 1; PENTAGLOBULIN; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG;

ANTIBODY SPECIFICITY; APOPTOSIS; ASEPTIC MENINGITIS; BACTERIAL CLEARANCE; BACTERIAL MENINGITIS; BACTERIAL PNEUMONIA; COMPLEMENT CLASSICAL PATHWAY; DRUG HYPERSENSITIVITY; ENDOTOXEMIA; GENETIC TRANSCRIPTION; GRAM NEGATIVE INFECTION; HUMAN; IMMUNE DEFICIENCY; IMMUNE RESPONSE; IMMUNOMODULATION; IMMUNOTHERAPY; INTENSIVE CARE; KIDNEY DYSFUNCTION; LOADING DRUG DOSE; MONOCYTE; NEUTROPHIL CHEMOTAXIS; PHENOTYPE; POSTOPERATIVE INFECTION; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; SEPSIS; SEPTICEMIA; SIGNAL TRANSDUCTION; SYSTEMATIC REVIEW; T LYMPHOCYTE; THROMBOEMBOLISM; TOXIC SHOCK SYNDROME; PASSIVE IMMUNIZATION; PROCEDURES;

CRITICAL CARE; HUMANS; IMMUNIZATION, PASSIVE; IMMUNOGLOBULINS, INTRAVENOUS; SEPSIS;

EID: 84858394440     PISSN: 13648535     EISSN: 1466609X     Source Type: Journal    
DOI: 10.1186/cc10597     Document Type: Review

References (161)

1. Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, Cohen J, Opal SM, Vincent JL, Ramsay G. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med 2003, 31:1250-1256. 10.1097/01.CCM.0000050454.01978.3B, 12682500.
2. Linde-Zwirble WT, Angus DC. Severe sepsis epidemiology: sampling, selection, and society. Crit Care 2004, 8:222-226. 10.1186/cc2917, 522859, 15312201.
3. Harrison DA, Welch CA, Eddleston JM. The epidemiology of severe sepsis in England, Wales and Northern Ireland, 1996 to 2004: secondary analysis of a high quality clinical database, the ICNARC Case Mix Programme Database. Crit Care 2006, 10:R42. 10.1186/cc4854, 1550902, 16542492.
4. Martin GS, Mannino DM, Eaton S, Moss M. The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med 2003, 348:1546-1554. 10.1056/NEJMoa022139, 12700374.
5. Angus DC, Wax RS. Epidemiology of sepsis: an update. Crit Care Med 2001, 29:S109-116.
6. Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med 2001, 29:1303-1310. 10.1097/00003246-200107000-00002, 11445675.
7. Rittirsch D, Flierl MA, Ward PA. Harmful molecular mechanisms in sepsis. Nat Rev Immunol 2008, 8:776-787. 10.1038/nri2402, 2786961, 18802444.
8. Abraham E, Singer M. Mechanisms of sepsis-induced organ dysfunction. Crit Care Med 2007, 35:2408-2416. 10.1097/01.CCM.0000282072.56245.91, 17948334.
9. Bone RC. Why sepsis trials fail. JAMA 1996, 276:565-566. 10.1001/jama.1996.03540070061032, 8709407.
10. Phillip Dellinger R, Parrillo JE. Mediator modulation therapy of severe sepsis and septic shock: does it work?. Crit Care Med 2004, 32:282-286. 10.1097/01.CCM.0000105423.06091.8E, 14707593.
11. Rittirsch D, Hoesel LM, Ward PA. The disconnect between animal models of sepsis and human sepsis. J Leukoc Biol 2007, 81:137-143.
12. Dyson A, Singer M. Animal models of sepsis: why does preclinical efficacy fail to translate to the clinical setting?. Crit Care Med 2009, 37:S30-37. 10.1097/CCM.0b013e3181922bd3, 19104223.
13. Dellinger RP, Vincent JL, Marshall J, Reinhart K. Important issues in the design and reporting of clinical trials in severe sepsis and acute lung injury. J Crit Care 2008, 23:493-499. 10.1016/j.jcrc.2007.12.022, 19056012.
14. Bianchi ME. DAMPs, PAMPs and alarmins: all we need to know about danger. J Leukoc Biol 2007, 81:1-5.
15. Oberholzer A, Oberholzer C, Moldawer LL. Sepsis syndromes: understanding the role of innate and acquired immunity. Shock 2001, 16:83-96. 10.1097/00024382-200116020-00001, 11508871.
16. Takeuchi O, Akira S. Pattern recognition receptors and inflammation. Cell 2010, 140:805-820. 10.1016/j.cell.2010.01.022, 20303872.
17. Cinel I, Opal SM. Molecular biology of inflammation and sepsis: a primer. Crit Care Med 2009, 37:291-304. 10.1097/CCM.0b013e31819267fb, 19050640.
18. Hoffman HM, Brydges SD. The genetic and molecular basis of inflammasome-mediated disease. J Biol Chem 2011, 286:10889-10896. 10.1074/jbc.R110.135491, 21296874.
19. Latz E. The inflammasomes: mechanisms of activation and function. Curr Opin Immunol 2010, 22:28-33. 10.1016/j.coi.2009.12.004, 2844336, 20060699.
20. Orel L, Neumeier H, Hochrainer K, Binder BR, Schmid JA. Crosstalk between the NF-kappaB activating IKK-complex and the CSN signalosome. J Cell Mol Med 2010, 14:1555-1568.
21. Abraham E. Nuclear factor-kappaB and its role in sepsis-associated organ failure. J Infect Dis 2003, 187:S364-369. 10.1086/374750, 12792853.
22. Wei N, Serino G, Deng XW. The COP9 signalosome: more than a protease. Trends Biochem Sci 2008, 33:592-600. 10.1016/j.tibs.2008.09.004, 18926707.
23. Corda S, Laplace C, Vicaut E, Duranteau J. Rapid reactive oxygen species production by mitochondria in endothelial cells exposed to tumor necrosis factor-alpha is mediated by ceramide. Am J Respir Cell Mol Biol 2001, 24:762-768.
24. Samavati L, Lee I, Mathes I, Lottspeich F, Huttemann M. Tumor necrosis factor alpha inhibits oxidative phosphorylation through tyrosine phosphorylation at subunit I of cytochrome c oxidase. J Biol Chem 2008, 283:21134-21144. 10.1074/jbc.M801954200, 3258931, 18534980.
25. Singer M. Mitochondrial function in sepsis: acute phase versus multiple organ failure. Crit Care Med 2007, 35:S441-448. 10.1097/01.CCM.0000278049.48333.78, 17713391.
26. Conway Morris A, Kefala K, Wilkinson TS, Dhaliwal K, Farrell L, Walsh T, Mackenzie SJ, Reid H, Davidson DJ, Haslett C, Rossi AG, Sallenave JM, Simpson AJ. C5a mediates peripheral blood neutrophil dysfunction in critically ill patients. Am J Respir Crit Care Med 2009, 180:19-28. 10.1164/rccm.200812-1928OC, 2948533, 19324972.
27. 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 USA 2009, 106:6303-6308. 10.1073/pnas.0809422106, 2669369, 19332785.
28. Ward NS, Casserly B, Ayala A. The compensatory anti-inflamatory response syndrome (CARS) in critically ill patients. Clin Chest Med 2008, 29:617-625. viii, 10.1016/j.ccm.2008.06.010, 2786900, 18954697.
29. Osuchowski MF, Welch K, Siddiqui J, Remick DG. Circulating cytokine/inhibitor profiles reshape the understanding of the SIRS/CARS continuum in sepsis and predict mortality. J Immunol 2006, 177:1967-1974.
30. Limaye AP, Kirby KA, Rubenfeld GD, Leisenring WM, Bulger EM, Neff MJ, Gibran NS, Huang ML, Santo Hayes TK, Corey L, Boeckh M. Cytomegalovirus reactivation in critically ill immunocompetent patients. JAMA 2008, 300:413-422. 10.1001/jama.300.4.413, 2774501, 18647984.
31. Luyt C-E, Combes A, Deback C, Aubriot-Lorton M-H, Nieszkowska A, Trouillet J-L, 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.
32. Ni Choileain N, MacConmara M, Zang Y, Murphy TJ, Mannick JA, Lederer JA. Enhanced regulatory T cell activity is an element of the host response to injury. J Immunol 2006, 176:225-236.
33. Hotchkiss RS, Coopersmith CM, McDunn JE, Ferguson TA. The sepsis seesaw: tilting toward immunosuppression. Nat Med 2009, 15:496-497. 10.1038/nm0509-496, 19424209.
34. Hotchkiss RS, Nicholson DW. Apoptosis and caspases regulate death and inflammation in sepsis. Nat Rev Immunol 2006, 6:813-822. 10.1038/nri1943, 17039247.
35. Durandy A, Kaveri SV, Kuijpers TW, Basta M, Miescher S, Ravetch JV, Rieben R. Intravenous immunoglobulins - understanding properties and mechanisms. Clin Exp Immunol 2009, 158:2-13. 2801035, 19883419.
36. Späth PJ. Structure and function of immunoglobulins. Sepsis 1999, 3:197-218.
37. Kazatchkine MD, Kaveri SV. Immunomodulation of autoimmune and inflammatory diseases with intravenous immune globulin. N Engl J Med 2001, 345:747-755. 10.1056/NEJMra993360, 11547745.
38. Smith KG, Clatworthy MR. FcgammaRIIB in autoimmunity and infection: evolutionary and therapeutic implications. Nat Rev Immunol 2010, 10:328-343. 10.1038/nri2762, 20414206.
39. Lu J, Marnell LL, Marjon KD, Mold C, Du Clos TW, Sun PD. Structural recognition and functional activation of FcgammaR by innate pentraxins. Nature 2008, 456:989-992. 10.1038/nature07468, 2688732, 19011614.
40. Espeli M, Niederer HA, Traherne JA, Trowsdale J, Smith KGC. Genetic variation, Fc [gamma] receptors, KIRs and infection: the evolution of autoimmunity. Curr Opin Immunol 2010, 22:715-722. 10.1016/j.coi.2010.10.003, 21050737.
41. Aschermann S, Lux A, Baerenwaldt A, Biburger M, Nimmerjahn F. The other side of immunoglobulin G: suppressor of inflammation. Clin Exp Immunol 2010, 160:161-167. 2857938, 20041883.
42. Willcocks LC, Smith KG, Clatworthy MR. Low-affinity Fcgamma receptors, autoimmunity and infection. Expert Rev Mol Med 2009, 11:e24.
43. Nimmerjahn F, Ravetch JV. Antibody-mediated modulation of immune responses. Immunol Rev 2010, 236:265-275. 10.1111/j.1600-065X.2010.00910.x, 20636822.
44. Chiamolera M, Launay P, Montenegro V, Rivero MC, Velasco IT, Monteiro RC. Enhanced expression of Fc alpha receptor I on blood phagocytes of patients with gram-negative bacteremia is associated with tyrosine phosphorylation of the FcR-gamma subunit. Shock 2001, 16:344-348. 10.1097/00024382-200116050-00004, 11699071.
45. Leino L, Sorvajarvi K, Katajisto J, Laine M, Lilius EM, Pelliniemi TT, Rajamaki A, Silvoniemi P, Nikoskelainen J. Febrile infection changes the expression of IgG Fc receptors and complement receptors in human neutrophils in vivo. Clin Exp Immunol 1997, 107:37-43. 10.1046/j.1365-2249.1997.d01-899.x, 1904561, 9010254.
46. Waterman PM, Cambier JC. The conundrum of inhibitory signaling by ITAM-containing immunoreceptors: potential molecular mechanisms. FEBS Lett 2010, 584:4878-4882. 10.1016/j.febslet.2010.09.029, 2998577, 20875413.
47. Pinheiro-da-Silva F, Chiamolera M, Charles N, Kanamaru Y, Velasco IT, Benhamou M, Monteiro RC. B lymphocytes undergo apoptosis because of FcgammaRIIb stress response to infection: a novel mechanism of cell death in sepsis. Shock 2006, 25:61-65.
48. Nimmerjahn F, Ravetch JV. The antiinflammatory activity of IgG: the intravenous IgG paradox. J Exp Med 2007, 204:11-15. 10.1084/jem.20061788, 2118416, 17227911.
49. McNab FW, Rajsbaum R, Stoye JP, O'Garra A. Tripartite-motif proteins and innate immune regulation. Curr Opin Immunol 2011, 23:46-56. 10.1016/j.coi.2010.10.021, 21131187.
50. Sjoberg AP, Trouw LA, Blom AM. Complement activation and inhibition: a delicate balance. Trends Immunol 2009, 30:83-90. 10.1016/j.it.2008.11.003, 19144569.
51. Roumenina LT, Ruseva MM, Zlatarova A, Ghai R, Kolev M, Olova N, Gadjeva M, Agrawal A, Bottazzi B, Mantovani A, Reid KB, Kishore U, Kojouharova MS. Interaction of C1q with IgG1, C-reactive protein and pentraxin 3: mutational studies using recombinant globular head modules of human C1q A, B, and C chains. Biochemistry 2006, 45:4093-4104. 10.1021/bi052646f, 16566583.
52. Frank MM, Basta M, Fries LF. The effects of intravenous immune globulin on complement-dependent immune damage of cells and tissues. Clin Immunol Immunopathol 1992, 62:S82-86. 10.1016/0090-1229(92)90045-P, 1728991.
53. Garcia-Garcia E, Nieto-Castaneda G, Ruiz-Saldana M, Mora N, Rosales C. FcgammaRIIA and FcgammaRIIIB mediate nuclear factor activation through separate signaling pathways in human neutrophils. J Immunol 2009, 182:4547-4556. 10.4049/jimmunol.0801468, 19342628.
54. Seely AJ, Pascual JL, Christou NV. Science review: Cell membrane expression (connectivity) regulates neutrophil delivery, function and clearance. Crit Care 2003, 7:291-307. 10.1186/cc1853, 270693, 12930553.
55. Seely AJ, Naud JF, Campisi G, Giannias B, Liu S, DiCarlo A, Ferri LE, Pascual JL, Tchervenkov J, Christou NV. Alteration of chemoattractant receptor expression regulates human neutrophil chemotaxis in vivo. Ann Surg 2002, 235:550-559. 10.1097/00000658-200204000-00014, 1422471, 11923612.
56. Ferri LE, Pascual J, Seely AJ, Chaudhury P, Christou NV. Soluble L-selectin attenuates tumor necrosis factor-alpha-mediated leukocyte adherence and vascular permeability: a protective role for elevated soluble L-selectin in sepsis. Crit Care Med 2002, 30:1842-1847. 10.1097/00003246-200208000-00028, 12163803.
57. Swartz DE, Seely AJ, Ferri L, Giannias B, Christou NV. Decreased systemic polymorphonuclear neutrophil (PMN) rolling without increased PMN adhesion in peritonitis at remote sites. Arch Surg 2000, 135:959-966. 10.1001/archsurg.135.8.959, 10922259.
58. Schaub A, von Gunten S, Vogel M, Wymann S, Ruegsegger M, Stadler BM, Spycher M, Simon HU, Miescher S. Dimeric IVIG contains natural anti-Siglec-9 autoantibodies and their anti-idiotypes. Allergy 2011, 66:1030-1037. 10.1111/j.1398-9995.2011.02579.x, 21385183.
59. von Gunten S, Schaub A, Vogel M, Stadler BM, Miescher S, Simon HU. Immunologic and functional evidence for anti-Siglec-9 autoantibodies in intravenous immunoglobulin preparations. Blood 2006, 108:4255-4259. 10.1182/blood-2006-05-021568, 16902148.
60. von Gunten S, Simon HU. Natural anti-Siglec autoantibodies mediate potential immunoregulatory mechanisms: implications for the clinical use of intravenous immunoglobulins (IVIg). Autoimmun Rev 2008, 7:453-456. 10.1016/j.autrev.2008.03.015, 18558361.
61. Taccone FS, Stordeur P, De Backer D, Creteur J, Vincent JL. Gamma-globulin levels in patients with community-acquired septic shock. Shock 2009, 32:379-385. 10.1097/SHK.0b013e3181a2c0b2, 19295479.
62. Dietz S, Lautenschlaeger C, Mueller-Werdan U, Werdan K. Low levels of immunoglobulin G in patients with sepsis or septic shock: a signum mali ominis?. Crit Care 2010, 14:P26.
63. Werdan K, Pilz G, Bujdoso O, Fraunberger P, Neeser G, Schmieder RE, Viell B, Marget W, Seewald M, Walger P, Stuttmann R, Speichermann N, Peckelsen C, Kurowski V, Osterhues HH, Verner L, Neumann R, Müller-Werdan U, . Score-Based Immunoglobulin Therapy of Sepsis (SBITS) Study Group Score-based immunoglobulin G therapy of patients with sepsis: the SBITS study. Crit Care Med 2007, 35:2693-2701. 10.1097/01.CCM.0000295426.37471.79, 18074471, Score-Based Immunoglobulin Therapy of Sepsis (SBITS) Study Group.
64. Venet F, Gebeile R, Bancel J, Guignant C, Poitevin-Later F, Malcus C, Lepape A, Monneret G. Assessment of plasmatic immunoglobulin G, A and M levels in septic shock patients. Int Immunopharmacol 2011, 11:2086-2090. 10.1016/j.intimp.2011.08.024, 21924385.
65. Krakauer T. Chemotherapeutics targeting immune activation by staphylococcal superantigens. Med Sci Monit 2005, 11:RA290-295.
66. Bueno C, Criado G, McCormick JK, Madrenas J. T cell signalling induced by bacterial superantigens. Chem Immunol Allergy 2007, 93:161-180.
67. Darville T, Milligan LB, Laff oon KK. Intravenous immunoglobulin inhibits staphylococcal toxin-induced human mononuclear phagocyte tumor necrosis factor alpha production. Infect Immun 1997, 65:366-372. 174604, 9009284.
68. Takei S, Arora YK, Walker SM. Intravenous immunoglobulin contains specific antibodies inhibitory to activation of T cells by staphylococcal toxin superantigens [see comment]. J Clin Invest 1993, 91:602-607. 10.1172/JCI116240, 287991, 8432865.
69. Kato K, Sakamoto T, Ito K. Gamma-globulin inhibits superantigen-induced lymphocyte proliferation and cytokine production. Allergol Int 2007, 56:439-444. 10.2332/allergolint.O-06-462, 17965583.
70. Abboud N, Chow SK, Saylor C, Janda A, Ravetch JV, Scharff MD, Casadevall A. A requirement for FcgammaR in antibody-mediated bacterial toxin neutralization. J Exp Med 2010, 207:2395-2405. 10.1084/jem.20100995, 2964574, 20921285.
71. Darenberg J, Ihendyane N, Sjolin J, Aufwerber E, Haidl S, Follin P, Andersson J, Norrby-Teglund A. Intravenous immunoglobulin G therapy in streptococcal toxic shock syndrome: a European randomized, double-blind, placebocontrolled trial. Clin Infect Dis 2003, 37:333-340. 10.1086/376630, 12884156.
72. O'Horo J, Safdar N. The role of immunoglobulin for the treatment of Clostridium difficile infection: a systematic review. Int J Infect Dis 2009, 13:663-667. 10.1016/j.ijid.2008.11.012, 19186089.
73. Shah SS, Hall M, Srivastava R, Subramony A, Levin JE. Intravenous immunoglobulin in children with streptococcal toxic shock syndrome. Clin Infect Dis 2009, 49:1369-1376. 10.1086/606048, 2761980, 19788359.
74. Trautmann M, Held TK, Susa M, Karajan MA, Wulf A, Cross AS, Marre R. Bacterial lipopolysaccharide (LPS)-specific antibodies in commercial human immunoglobulin preparations: superior antibody content of an IgM-enriched product. Clin Exp Immunol 1998, 111:81-90. 10.1046/j.1365-2249.1998.00445.x, 1904862, 9472665.
75. Rivers EP. Point: adherence to early goal-directed therapy: does it really matter? Yes. After a decade, the scientific proof speaks for itself. Chest 2010, 138:476-480. 10.1378/chest.10-1405, 20822986.
76. Tesar DB, Bjorkman PJ. An intracellular traffic jam: Fc receptor-mediated transport of immunoglobulin G. Curr Opin Struct Biol 2010, 20:226-233. 10.1016/j.sbi.2010.01.010, 2865255, 20171874.
77. Aukrust P, Muller F, Svenson M, Nordoy I, Bendtzen K, Froland SS. Administration of intravenous immunoglobulin (IVIG) in vivo - down regulatory effects on the IL-1 system. Clin Exp Immunol 1999, 115:136-143. 10.1046/j.1365-2249.1999.00757.x, 1905185, 9933433.
78. Ichiyama T, Yoshitomi T, Nishikawa M, Fujiwara M, Matsubara T, Hayashi T, Furukawa S. NF-kappaB activation in peripheral blood monocytes/macrophages and T cells during acute Kawasaki disease. Clin Immunol 2001, 99:373-377. 10.1006/clim.2001.5026, 11358434.
79. Ichiyama T, Ueno Y, Hasegawa M, Niimi A, Matsubara T, Furukawa S. Intravenous immunoglobulin inhibits NF-kappaB activation and affects Fcgamma receptor expression in monocytes/macrophages. Naunyn Schmiedebergs Arch Pharmacol 2004, 369:428-433. 10.1007/s00210-004-0877-x, 14985941.
80. Ichiyama T, Ueno Y, Isumi H, Niimi A, Matsubara T, Furukawa S. An immunoglobulin agent (IVIG) inhibits NF-kappaB activation in cultured endothelial cells of coronary arteries in vitro. Inflamm Res 2004, 53:253-256. 10.1007/s00011-004-1255-3, 15167972.
81. Macmillan HF, Rowter D, Lee T, Issekutz AC. Intravenous immunoglobulin G selectively inhibits IL-1alpha-induced neutrophil-endothelial cell adhesion. Autoimmunity 2010, 43:619-627. 10.3109/08916931003599062, 20380586.
82. Sewell WA, Jolles S. Immunomodulatory action of intravenous immunoglobulin. Immunology 2002, 107:387-393. 10.1046/j.1365-2567.2002.01545.x, 1782817, 12460182.
83. Li X, Li Y, Shan L, Shen E, Chen R, Peng T. Over-expression of calpastatin inhibits calpain activation and attenuates myocardial dysfunction during endotoxaemia. Cardiovasc Res 2009, 83:72-79. 10.1093/cvr/cvp100, 19318376.
84. Hu H, Li X, Li Y, Wang L, Mehta S, Feng Q, Chen R, Peng T. Calpain-1 induces apoptosis in pulmonary microvascular endothelial cells under septic conditions. Microvasc Res 2009, 78:33-39. 10.1016/j.mvr.2009.04.005, 19379762.
85. Fareed MU, Evenson AR, Wei W, Menconi M, Poylin V, Petkova V, Pignol B, Hasselgren PO. Treatment of rats with calpain inhibitors prevents sepsis induced muscle proteolysis independent of atrogin-1/MAFbx and MuRF1 expression. Am J Physiol Regul Integr Comp Physiol 2006, 290:R1589-1597. 10.1152/ajpregu.00668.2005, 16455766.
86. Wei W, Fareed MU, Evenson A, Menconi MJ, Yang H, Petkova V, Hasselgren PO. Sepsis stimulates calpain activity in skeletal muscle by decreasing calpastatin activity but does not activate caspase-3. Am J Physiol Regul Integr Comp Physiol 2005, 288:R580-590.
87. Arredondo J, Chernyavsky AI, Karaouni A, Grando SA. Novel mechanisms of target cell death and survival and of therapeutic action of IVIg in Pemphigus. Am J Pathol 2005, 167:1531-1544. 10.1016/S0002-9440(10)61239-4, 1613205, 16314468.
88. Ross C, Svenson M, Nielsen H, Lundsgaard C, Hansen MB, Bendtzen K. Increased in vivo antibody activity against interferon alpha, interleukin-1alpha, and interleukin-6 after high-dose Ig therapy. Blood 1997, 90:2376-2380.
89. Menezes MC, Benard G, Sato MN, Hong MA, Duarte AJ. In vitro inhibitory activity of tumor necrosis factor alpha and interleukin-2 of human immunoglobulin preparations. Int Arch Allergy Immunol 1997, 114:323-328. 10.1159/000237689, 9414134.
90. Bendtzen K, Hansen MB, Ross C, Svenson M. Detection of autoantibodies to cytokines. Mol Biotechnol 2000, 14:251-261. 10.1385/MB:14:3:251, 10890016.
91. Ueno T, Ikeda T, Ikeda K, Taniuchi H, Suda S, Yeung MY, Matsuno N. HMGB-1 as a useful prognostic biomarker in sepsis-induced organ failure in patients undergoing PMX-DHP. J Surg Res 2011, 171:183-190. 10.1016/j.jss.2009.11.708, 20338589.
92. Mantell LL, Parrish WR, Ulloa L. Hmgb-1 as a therapeutic target for infectious and inflammatory disorders. Shock 2006, 25:4-11.
93. Hagiwara S, Iwasaka H, Hasegawa A, Asai N, Noguchi T. High-dose intravenous immunoglobulin G improves systemic inflammation in a rat model of CLP-induced sepsis. Intensive Care Med 2008, 34:1812-1819. 10.1007/s00134-008-1161-1, 18500418.
94. Urbonaviciute V, Furnrohr BG, Weber C, Haslbeck M, Wilhelm S, Herrmann M, Voll RE. Factors masking HMGB1 in human serum and plasma. J Leukoc Biol 2007, 81:67-74.
95. Ait-Oufella H, Maury E, Lehoux S, Guidet B, Off enstadt G. The endothelium: physiological functions and role in microcirculatory failure during severe sepsis. Intensive Care Med 2010, 36:1286-1298. 10.1007/s00134-010-1893-6, 20443110.
96. Xu C, Poirier B, Duong Van Huyen JP, Lucchiari N, Michel O, Chevalier J, Kaveri S. Modulation of endothelial cell function by normal polyspecific human intravenous immunoglobulins: a possible mechanism of action in vascular diseases. Am J Pathol 1998, 153:1257-1266. 10.1016/S0002-9440(10)65670-2, 1853054, 9777957.
97. Rittirsch D, Flierl MA, Nadeau BA, Day DE, Huber-Lang M, Mackay CR, Zetoune FS, Gerard NP, Cianflone K, Köhl J, Gerard C, Sarma JV, Ward PA. Functional roles for C5a receptors in sepsis. Nat Med 2008, 14:551-557. 10.1038/nm1753, 2753858, 18454156.
98. Liu B, Zhang J, Tan PY, Hsu D, Blom AM, Leong B, Sethi S, Ho B, Ding JL, Thiagarajan PS. A computational and experimental study of the regulatory mechanisms of the complement system. PLoS Comput Biol 2011, 7:e1001059. 10.1371/journal.pcbi.1001059, 3024260, 21283780.
99. Singer M, Jones AM. Bench-to-bedside review: The role of C1-esterase inhibitor in sepsis and other critical illnesses. Crit Care 2011, 15:203. 3222011, 21345278.
100. Thrane AS, Skehan JD, Thrane PS. A novel interpretation of immune redundancy and duality in reperfusion injury with important implications for intervention in ischaemic disease. Med Hypotheses 2007, 68:1363-1370. 10.1016/j.mehy.2006.10.044, 17169498.
101. Niederbichler AD, Hoesel LM, Westfall MV, Gao H, Ipaktchi KR, Sun L, Zetoune FS, Su GL, Arbabi S, Sarma JV, Wang SC, Hemmila MR, Ward PA. An essential role for complement C5a in the pathogenesis of septic cardiac dysfunction. J Exp Med 2006, 203:53-61. 10.1084/jem.20051207, 2118072, 16380509.
102. Amara U, Flierl MA, Rittirsch D, Klos A, Chen H, Acker B, Brückner UB, Nilsson B, Gebhard F, Lambris JD, Huber-Lang M. Molecular intercommunication between the complement and coagulation systems. J Immunol 2010, 185:5628-5636. 10.4049/jimmunol.0903678, 3123139, 20870944.
103. Tanaka J, Nakae T, Onoe T, Horiuchi Y, Miyamoto H, Adan-Kubo J, Adachi H, Ono Y. Complement-mediated bacteriolysis after binding of specific antibodies to drug-resistant Pseudomonas aeruginosa: morphological changes observed by using a field emission scanning electron microscope. J Infect Chemother 2010, 16:383-387. 10.1007/s10156-010-0074-4, 20532941.
104. Basta M, Van Goor F, Luccioli S, Billings EM, Vortmeyer AO, Baranyi L, Szebeni J, Alving CR, Carroll MC, Berkower I, Stojilkovic SS, Metcalfe DD. F(ab)'2-mediated neutralization of C3a and C5a anaphylatoxins: a novel effector function of immunoglobulins. Nat Med 2003, 9:431-438. 10.1038/nm836, 12612546.
105. Konrad S, Baumann U, Schmidt RE, Gessner JE. Intravenous immunoglobulin (IVIG)-mediated neutralisation of C5a: a direct mechanism of IVIG in the maintenance of a high Fc gammaRIIB to Fc gammaRIII expression ratio on macrophages. Br J Haematol 2006, 134:345-347. 10.1111/j.1365-2141.2006.06185.x, 16848778.
106. Rittirsch D, Flierl MA, Ward PA. Harmful molecular mechanisms in sepsis. Nat Rev Immunol 2008, 8:776-787. 10.1038/nri2402, 2786961, 18802444.
107. Ward PA. Sepsis, apoptosis and complement. Biochem Pharmacol 2008, 76:1383-1388. 10.1016/j.bcp.2008.09.017, 2656915, 18848819.
108. Tha-In T, Metselaar HJ, Tilanus HW, Groothuismink ZM, Kuipers EJ, de Man RA, Kwekkeboom J. Intravenous immunoglobulins suppress T-cell priming by modulating the bidirectional interaction between dendritic cells and natural killer cells. Blood 2007, 110:3253-3262. 10.1182/blood-2007-03-077057, 17673603.
109. Parrino J, Hotchkiss RS, Bray M. Prevention of immune cell apoptosis as potential therapeutic strategy for severe infections. Emerg Infect Dis 2007, 13:191-198. 10.3201/eid1302.060963, 2725847, 17479879.
110. Turina M, Fry DE, Polk HC. Acute hyperglycemia and the innate immune system: clinical, cellular, and molecular aspects. Crit Care Med 2005, 33:1624-1633. 10.1097/01.CCM.0000170106.61978.D8, 16003073.
111. Anthony RM, Wermeling F, Karlsson MC, Ravetch JV. Identification of a receptor required for the anti-inflammatory activity of IVIG. Proc Natl Acad Sci USA 2008, 105:19571-19578. 10.1073/pnas.0810163105, 2604916, 19036920.
112. Crow AR, Brinc D, Lazarus AH. New insight into the mechanism of action of IVIg: the role of dendritic cells. J Thromb Haemost 2009, 7:245-248.
113. Tawfik DS, Cowan KR, Walsh AM, Hamilton WS, Goldman FD. Exogenous immunoglobulin downregulates T-cell receptor signaling and cytokine production. Pediatr Allergy Immunol 2012, 23(1):88-95. 10.1111/j.1399-3038.2010.01129.x, 21265884.
114. Araujo LM, Chauvineau A, Zhu R, Diem S, Bourgeois EA, Levescot A, Huerre M, Gombert JM, Bayry J, Daëron M, Bruhns P, Kaveri SV, Herbelin A. Cutting edge: intravenous Ig inhibits invariant NKT cell-mediated allergic airway inflammation through FcgammaRIIIA-dependent mechanisms. J Immunol 2011, 186:3289-3293. 10.4049/jimmunol.1003076, 21317388.
115. Smed-Sorensen A, Moll M, Cheng TY, Lore K, Norlin AC, Perbeck L, Moody DB, Spetz AL, Sandberg JK. IgG regulates the CD1 expression profile and lipid antigen-presenting function in human dendritic cells via FcgammaRIIa. Blood 2008, 111:5037-5046. 10.1182/blood-2007-07-099549, 2384132, 18337560.
116. MacMillan HF, Lee T, Issekutz AC. Intravenous immunoglobulin G-mediated inhibition of T-cell proliferation reflects an endogenous mechanism by which IgG modulates T-cell activation. Clin Immunol 2009, 132:222-233. 10.1016/j.clim.2009.04.002, 19447680.
117. De Groot AS, Moise L, McMurry JA, Wambre E, Van Overtvelt L, Moingeon P, Scott DW, Martin W. Activation of natural regulatory T cells by IgG Fc-derived peptide "Tregitopes". Blood 2008, 112:3303-3311. 10.1182/blood-2008-02-138073, 2569179, 18660382.
118. Kessel A, Ammuri H, Peri R, Pavlotzky ER, Blank M, Shoenfeld Y, Toubi E. Intravenous immunoglobulin therapy affects T regulatory cells by increasing their suppressive function. J Immunol 2007, 179:5571-5575.
119. Bayry J, Fournier EM, Maddur MS, Vani J, Wootla B, Sibéril S, Dimitrov JD, Lacroix-Desmazes S, Berdah M, Crabol Y, Oksenhendler E, Lévy Y, Mouthon L, Sautès-Fridman C, Hermine O, Kaveri SV. Intravenous immunoglobulin induces proliferation and immunoglobulin synthesis from B cells of patients with common variable immunodeficiency: A mechanism underlying the beneficial effect of IVIg in primary immunodeficiencies. J Autoimmun 2011, 36:9-15. 10.1016/j.jaut.2010.09.006, 20970960.
120. Wesche-Soldato DE, Swan RZ, Chung CS, Ayala A. The apoptotic pathway as a therapeutic target in sepsis. Curr Drug Targets 2007, 8:493-500. 10.2174/138945007780362764, 1852483, 17430119.
121. von Gunten S, Yousefi S, Seitz M, Jakob SM, Schaffner T, Seger R, Takala J, Villiger PM, Simon HU. Siglec-9 transduces apoptotic and nonapoptotic death signals into neutrophils depending on the proinflamatory cytokine environment. Blood 2005, 106:1423-1431. 10.1182/blood-2004-10-4112, 15827126.
122. Pène F, Courtine E, Ouaaz F, Zuber B, Sauneuf B, Sirgo G, Rousseau C, Toubiana J, Balloy V, Chignard M, Mira JP, Chiche JD. Toll-like receptors 2 and 4 contribute to sepsis-induced depletion of spleen dendritic cells. Infect Immun 2009, 77:5651-5658. 10.1128/IAI.00238-09, 2786456, 19805530.
123. Unsinger J, McDonough JS, Shultz LD, Ferguson TA, Hotchkiss RS. Sepsis induced human lymphocyte apoptosis and cytokine production in "humanized" mice. J Leukoc Biol 2009, 86:219-227. 10.1189/jlb.1008615, 2726769, 19369639.
124. Wang SD, Huang KJ, Lin YS, Lei HY. Sepsis-induced apoptosis of the thymocytes in mice. J Immunol 1994, 152:5014-5021.
125. Schroeder S, Lindemann C, Decker D, Klaschik S, Hering R, Putensen C, Hoeft A, von Ruecker A, Stuber F. Increased susceptibility to apoptosis in circulating lymphocytes of critically ill patients. Langenbecks Arch Surg 2001, 386:42-46. 10.1007/s004230000181, 11405088.
126. Hotchkiss RS, Swanson PE, Freeman BD, Tinsley KW, Cobb JP, Matuschak GM, Buchman TG, Karl IE. Apoptotic cell death in patients with sepsis, shock, and multiple organ dysfunction. Crit Care Med 1999, 27:1230-1251. 10.1097/00003246-199907000-00002, 10446814.
127. Le Tulzo Y, Pangault C, Gacouin A, Guilloux V, Tribut O, Amiot L, Tattevin P, Thomas R, Fauchet R, Drenou B. Early circulating lymphocyte apoptosis in human septic shock is associated with poor outcome. Shock 2002, 18:487-494. 10.1097/00024382-200212000-00001, 12462554.
128. Wheeler D. Death to sepsis: targeting apoptosis pathways in sepsis. Crit Care 2009, 13:1010. 10.1186/cc8162, 2811923, 20053298.
129. Savill J, Fadok V. Corpse clearance defines the meaning of cell death. Nature 2000, 407:784-788. 10.1038/35037722, 11048729.
130. Nakatani K, Takeshita S, Tsujimoto H, Sekine I. Intravenous immunoglobulin (IVIG) preparations induce apoptosis in TNF-alpha-stimulated endothelial cells via a mitochondria-dependent pathway. Clin Exp Immunol 2002, 127:445-454. 10.1046/j.1365-2249.2002.01769.x, 1906310, 11966760.
131. Prasad NK, Papoff G, Zeuner A, Bonnin E, Kazatchkine MD, Ruberti G, Kaveri SV. Therapeutic preparations of normal polyspecific IgG (IVIg) induce apoptosis in human lymphocytes and monocytes: a novel mechanism of action of IVIg involving the Fas apoptotic pathway. J Immunol 1998, 161:3781-3790.
132. Radosevich M, Burnouf T. Intravenous immunoglobulin G: trends in production methods, quality control and quality assurance. Vox Sang 2010, 98:12-28. 10.1111/j.1423-0410.2009.01226.x, 19660029.
133. St-Amour I, Laroche A, Bazin R, Lemieux R. Activation of cryptic IgG reactive with BAFF, amyloid beta peptide and GM-CSF during the industrial fractionation of human plasma into therapeutic intravenous immunoglobulins. Clin Immunol 2009, 133:52-60. 10.1016/j.clim.2009.06.005, 19604724.
134. Beck OE, Kaiser PE. Distribution of human IgG subclasses in commercial intravenous immunoglobulin preparations: a rate nephelometric method. Vox Sanguinis 1981, 41:79-84. 10.1111/j.1423-0410.1981.tb01018.x, 7331283.
135. Ravetch J. In vivo veritas: the surprising roles of Fc receptors in immunity. Nat Immunol 2010, 11:183-185. 10.1038/ni0310-183, 20157296.
136. von Gunten S, Simon HU. Cell death modulation by intravenous immunoglobulin. J Clin Immunol 2010, 30:S24-30.
137. Reipert BM, Stellamor MT, Poell M, Ilas J, Sasgary M, Reipert S, Zimmermann K, Ehrlich H, Schwarz HP. Variation of anti-Fas antibodies in different lots of intravenous immunoglobulin. Vox Sanguinis 2008, 94:334-341. 10.1111/j.1423-0410.2008.001036.x, 18266779.
138. Hentrich M, Fehnle K, Ostermann H, Kienast J, Cornely O, Salat C, Ubelacker R, Buchheidt D, Behre G, Hiddemann W, Schiel X. IgMA-enriched immunoglobulin in neutropenic patients with sepsis syndrome and septic shock: a randomized, controlled, multiple-center trial. Crit Care Med 2006, 34:1319-1325. 10.1097/01.CCM.0000215452.84291.C6, 16540956.
139. Rodriguez A, Rello J, Neira J, Maskin B, Ceraso D, Vasta L, Palizas F. Eff ects of high-dose of intravenous immunoglobulin and antibiotics on survival for severe sepsis undergoing surgery. Shock 2005, 23:298-304. 10.1097/01.shk.0000157302.69125.f8, 15803051.
140. Tugrul S, Ozcan PE, Akinci O, Seyhun Y, Cagatay A, Cakar N, Esen F. The effects of IgM-enriched immunoglobulin preparations in patients with severe sepsis [ISRCTN28863830]. Crit Care 2002, 6:357-362. 10.1186/cc1523, 125317, 12225613.
141. Karatzas S, Boutzouka E, Venetsanou K, Myrianthefs P, Fildisis G, Baltopoulos G. The effects of IgM-enriched immunoglobulin preparations in patients with severe sepsis: another point of view. Crit Care 2002, 6:543-544. author reply 545, 10.1186/cc1837, 153443, 12512504.
142. Masaoka T. [Combination therapy of antibiotics and intravenous immunoglobulin]. Nippon Rinsho 2001, 59:781-784.
143. Dominioni L, Bianchi V, Imperatori A, Minoia G, Dionigi R. High-dose intravenous IgG for treatment of severe surgical infections. Digestive Surg 1996, 13:430-434.
144. Schedel I, Dreikhausen U, Nentwig B, Hockenschnieder M, Rauthmann D, Balikcioglu S, Coldewey R, Deicher H. Treatment of gram-negative septic shock with an immunoglobulin preparation: a prospective, randomized clinical trial. Crit Care Med 1991, 19:1104-1113. 10.1097/00003246-199109000-00003, 1884609.
145. Burns ER, Lee V, Rubinstein A. Treatment of septic thrombocytopenia with immune globulin. J Clin Immunol 1991, 11:363-368. 10.1007/BF00918802, 1761642.
146. Wesoly C, Kipping N, Grundmann R. Immunoglobulin therapy of postoperative sepsis. Zeitschrift fur experimentelle Chirurgie, Transplantation, und kunstliche Organe: Organ der Sektion Experimentelle Chirurgie der Gesellschaft fur Chirurgie der DDR 1990, 23:213-216.
147. Grundmann R, Hornung M. Immunoglobulin therapy in patients with endotoxemia and postoperative sepsis--a prospective randomized study. Prog Clin Biol Res 1988, 272:339-349.
148. De Simone C, Delogu G, Corbetta G. Intravenous immunoglobulins in association with antibiotics: a therapeutictrial in septic intensive care unit patients. Crit Care Med 1988, 16:23-26. 10.1097/00003246-198801000-00005, 3276446.
149. Lindquist L, Lundbergh P, Maasing R. Pepsin-treated human gamma globulin in bacterial infections. A randomized study in patients with septicaemia and pneumonia. Vox Sang 1981, 40:329-337. 10.1111/j.1423-0410.1981.tb00717.x, 6166128.
150. Yakut M, Cetiner S, Akin A, Tan A, Kaymakcioglu N, Simsek A, Sen D. Sepsisdeki hastalarda immunglobulin G (IgG) kullaniminin mortalite oranina etkisi. GATA Bulteni 1998, 40:76-81.
151. Behre G, Ostermann H, Schedel I, Helmerking M, Schiel X, Rothenburger M, Geiger S, Dedroogh M, Bockelmann D, Wormann B, Kienast J, Hiddemann W, Abakumov MM. Endotoxin concentrations and therapy with polyclonal IgM-enriched immunoglobulins in neutropenic cancer patients with sepsis syndrome: pilot study and interim analysis of a randomized trial. Antiinfective Drugs Chemother 1995, 13:129-134.
152. Spannbrucker N, Munch HG, Kunze R, Vogel F. Auswirkungen von immunglobulinsubstitution bei sepsis. Intensivmedizin 1987, 6:314.
153. Turgeon AF, Hutton B, Fergusson DA, McIntyre L, Tinmouth AA, Cameron DW, Hebert PC. Meta-analysis: intravenous immunoglobulin in critically ill adult patients with sepsis. Ann Intern Med 2007, 146:193-203.
154. Laupland KB, Kirkpatrick AW, Delaney A. Polyclonal intravenous immunoglobulin for the treatment of severe sepsis and septic shock in critically ill adults: a systematic review and meta-analysis. Crit Care Med 2007, 35:2686-2692. 10.1097/01.CCM.0000295312.13466.1C, 18074465.
155. Kreymann KG, de Heer G, Nierhaus A, Kluge S. Use of polyclonal immunoglobulins as adjunctive therapy for sepsis or septic shock. Crit Care Med 2007, 35:2677-2685. 10.1097/01.CCM.0000295263.12774.97, 18074464.
156. Pildal J, Gotzsche PC. Polyclonal immunoglobulin for treatment of bacterial sepsis: a systematic review. Clin Infect Dis 2004, 39:38-46. 10.1086/421089, 15206051.
157. Norrby-Teglund A, Haque KN, Hammarstrom L. Intravenous polyclonal IgMenriched immunoglobulin therapy in sepsis: a review of clinical efficacy in relation to microbiological aetiology and severity of sepsis. J Intern Med 2006, 260:509-516. 10.1111/j.1365-2796.2006.01726.x, 17116001.
158. Alejandria MM, Lansang MA, Dans LF, Mantaring JB. Intravenous immunoglobulin for treating sepsis and septic shock. Cochrane Database Syst Rev 2002, (1):CD001090.
159. Alejandria MM, Lansang MA, Dans LF, Mantaring JB. Intravenous immunoglobulin for treating sepsis and septic shock. Cochrane Database Syst Rev 2001, (2):CD001090.
160. Khan S, Abuzakouk M, Dore PC, Sewell WA. Administering intravenous immunoglobulin during infection is associated with infusion reactions in selected patients. Ir J Med Sci 2011, 180:125-128. 10.1007/s11845-010-0654-4, 21136195.
161. Koleba T, Ensom MH. Pharmacokinetics of intravenous immunoglobulin: a systematic review. Pharmacotherapy 2006, 26:813-827. 10.1592/phco.26.6.813, 16716135.