Home LiteratureArticle Details
PMID: 12925683 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Review

The enigma of sepsis.

The Journal of clinical investigation ·Vol. 112 ·No. 4 ·2003-08-00 ·Pages 460-7

Riedemann NC, Guo RF, Ward PA

Abstract

Sepsis remains a serious cause of morbidity and mortality, and the pathophysiology of the disease is not clear. The definition of the clinical manifestations of sepsis is ever evolving. This review discusses the search for effective therapeutic interventions, hurdles in translational sepsis research, and new therapies in development in current clinical trials.

MeSH Terms
Animals Antigens, CD/physiology Apoptosis Clinical Trials as Topic Complement C5a/physiology HMGB1 Protein/physiology Humans Macrophage Migration-Inhibitory Factors/physiology Protein C/therapeutic use Receptor, Anaphylatoxin C5a Receptors, Complement/physiology Sepsis/diagnosis,etiology,therapy
Chemicals
Antigens, CD HMGB1 Protein Macrophage Migration-Inhibitory Factors Protein C Receptor, Anaphylatoxin C5a Receptors, Complement Complement C5a
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Riedemann Niels C
Department of Pathology, University of Michigan Medical School, 1301 Catherine Road, Ann Arbor, Michigan 48109-0602, USA.
Guo Ren-Feng
Ward Peter A
References (75)
75 references, click to expand
  1. Efficacy and safety of recombinant human activated protein C for severe sepsis.
    N Engl J Med. 2001 Mar 8;344(10):699-709 PMID: 11236773
  2. Caspase inhibitors improve survival in sepsis: a critical role of the lymphocyte.
    Nat Immunol. 2000 Dec;1(6):496-501 PMID: 11101871
  3. Apoptosis in sepsis: a new target for therapeutic exploration.
    FASEB J. 2001 Apr;15(6):879-92 PMID: 11292647
  4. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care.
    Crit Care Med. 2001 Jul;29(7):1303-10 PMID: 11445675
  5. Anti-tumor necrosis factor therapy in sepsis: update on clinical trials and lessons learned.
    Crit Care Med. 2001 Jul;29(7 Suppl):S121-5 PMID: 11445746
  6. Plasma levels of macrophage migration inhibitory factor are elevated in patients with severe sepsis.
    Intensive Care Med. 2001 Aug;27(8):1412-5 PMID: 11511957
  7. Macrophage migration inhibitory factor is a critical mediator of systemic inflammatory response syndrome.
    Intensive Care Med. 2001 Jul;27(7):1187-93 PMID: 11534567
  8. Caring for the critically ill patient. High-dose antithrombin III in severe sepsis: a randomized controlled trial.
    JAMA. 2001 Oct 17;286(15):1869-78 PMID: 11597289
  9. Intensive insulin therapy in critically ill patients.
    N Engl J Med. 2001 Nov 8;345(19):1359-67 PMID: 11794168
  10. Early goal-directed therapy in the treatment of severe sepsis and septic shock.
    N Engl J Med. 2001 Nov 8;345(19):1368-77 PMID: 11794169
  11. HMGB1 as a late mediator of lethal systemic inflammation.
    Am J Respir Crit Care Med. 2001 Nov 15;164(10 Pt 1):1768-73 PMID: 11734424
  12. Tumor necrosis factor and interleukin-1 in the serum of children with severe infectious purpura.
    N Engl J Med. 1988 Aug 18;319(7):397-400 PMID: 3135497
  13. Tumor necrosis factor and endotoxin induce similar metabolic responses in human beings.
    Surgery. 1988 Aug;104(2):280-6 PMID: 2456628
  14. Whole-body inflammation in trauma patients. An autopsy study.
    Arch Surg. 1988 Dec;123(12):1519-24 PMID: 3056336
  15. Complement levels in septic primates treated with anti-C5a antibodies.
    J Surg Res. 1989 Mar;46(3):195-9 PMID: 2493531
  16. Sepsis syndrome: a valid clinical entity. Methylprednisolone Severe Sepsis Study Group.
    Crit Care Med. 1989 May;17(5):389-93 PMID: 2651003
  17. The anaphylatoxins C3a and C5a are vasodilators in the canine coronary vasculature in vitro and in vivo.
    Agents Actions. 1991 Nov;34(3-4):345-9 PMID: 1810146
  18. Anti-tumor necrosis factor antibody therapy fails to prevent lethality after cecal ligation and puncture or endotoxemia.
    J Immunol. 1992 May 1;148(9):2724-30 PMID: 1315357
  19. Definitions for sepsis and organ failure.
    Crit Care Med. 1992 Jun;20(6):724-6 PMID: 1597021
  20. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine.
    Chest. 1992 Jun;101(6):1644-55 PMID: 1303622
  21. MIF is a pituitary-derived cytokine that potentiates lethal endotoxaemia.
    Nature. 1993 Oct 21;365(6448):756-9 PMID: 8413654
  22. The macrophage is an important and previously unrecognized source of macrophage migration inhibitory factor.
    J Exp Med. 1994 Jun 1;179(6):1895-902 PMID: 8195715
  23. Protection from septic shock by neutralization of macrophage migration inhibitory factor.
    Nat Med. 2000 Feb;6(2):164-70 PMID: 10655104
  24. Overexpression of Bcl-2 in the intestinal epithelium improves survival in septic mice.
    Crit Care Med. 2002 Jan;30(1):195-201 PMID: 11902262
  25. New and emerging therapies for sepsis.
    Ann Pharmacother. 2002 Apr;36(4):648-54 PMID: 11918516
  26. Inhibition of intestinal epithelial apoptosis and survival in a murine model of pneumonia-induced sepsis.
    JAMA. 2002 Apr 3;287(13):1716-21 PMID: 11926897
  27. Anti-c5a ameliorates coagulation/fibrinolytic protein changes in a rat model of sepsis.
    Am J Pathol. 2002 May;160(5):1867-75 PMID: 12000738
  28. C5a receptor and thymocyte apoptosis in sepsis.
    FASEB J. 2002 Jun;16(8):887-8 PMID: 12039868
  29. Activation of endothelial cell protease activated receptor 1 by the protein C pathway.
    Science. 2002 Jun 7;296(5574):1880-2 PMID: 12052963
  30. Increased C5a receptor expression in sepsis.
    J Clin Invest. 2002 Jul;110(1):101-8 PMID: 12093893
  31. Release of macrophage migration inhibitory factor and CXCL8/interleukin-8 from lung epithelial cells rendered necrotic by influenza A virus infection.
    J Virol. 2002 Sep;76(18):9298-306 PMID: 12186913
  32. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock.
    JAMA. 2002 Aug 21;288(7):862-71 PMID: 12186604
  33. HMGB1 B box increases the permeability of Caco-2 enterocytic monolayers and impairs intestinal barrier function in mice.
    Gastroenterology. 2002 Sep;123(3):790-802 PMID: 12198705
  34. Complement-induced impairment of innate immunity during sepsis.
    J Immunol. 2002 Sep 15;169(6):3223-31 PMID: 12218141
  35. Ethyl pyruvate prevents lethality in mice with established lethal sepsis and systemic inflammation.
    Proc Natl Acad Sci U S A. 2002 Sep 17;99(19):12351-6 PMID: 12209006
  36. An economic evaluation of activated protein C treatment for severe sepsis.
    N Engl J Med. 2002 Sep 26;347(13):993-1000 PMID: 12324556
  37. Assessing the use of activated protein C in the treatment of severe sepsis.
    N Engl J Med. 2002 Sep 26;347(13):1030-4 PMID: 12324563
  38. Serum complement levels and severity of sepsis.
    Res Commun Chem Pathol Pharmacol. 1994 May;84(2):189-95 PMID: 8091004
  39. MIF as a glucocorticoid-induced modulator of cytokine production.
    Nature. 1995 Sep 7;377(6544):68-71 PMID: 7659164
  40. Treatment of septic shock with the tumor necrosis factor receptor:Fc fusion protein. The Soluble TNF Receptor Sepsis Study Group.
    N Engl J Med. 1996 Jun 27;334(26):1697-702 PMID: 8637514
  41. Chronological changes in the complement system in sepsis.
    Surg Today. 1996;26(4):225-9 PMID: 8727941
  42. Human circulating eosinophils secrete macrophage migration inhibitory factor (MIF). Potential role in asthma.
    J Clin Invest. 1998 Jun 15;101(12):2869-74 PMID: 9637721
  43. Antibiotic treatment influences outcome in murine sepsis: mediators of increased morbidity.
    Shock. 1998 Aug;10(2):110-7 PMID: 9721977
  44. Targeted disruption of migration inhibitory factor gene reveals its critical role in sepsis.
    J Exp Med. 1999 Jan 18;189(2):341-6 PMID: 9892616
  45. Overexpression of Bcl-2 in transgenic mice decreases apoptosis and improves survival in sepsis.
    J Immunol. 1999 Apr 1;162(7):4148-56 PMID: 10201940
  46. Protective effects of C5a blockade in sepsis.
    Nat Med. 1999 Jul;5(7):788-92 PMID: 10395324
  47. HMG-1 as a late mediator of endotoxin lethality in mice.
    Science. 1999 Jul 9;285(5425):248-51 PMID: 10398600
  48. Prevention of lymphocyte cell death in sepsis improves survival in mice.
    Proc Natl Acad Sci U S A. 1999 Dec 7;96(25):14541-6 PMID: 10588741
  49. Protection of innate immunity by C5aR antagonist in septic mice.
    FASEB J. 2002 Oct;16(12):1567-74 PMID: 12374779
  50. Risk and the efficacy of antiinflammatory agents: retrospective and confirmatory studies of sepsis.
    Am J Respir Crit Care Med. 2002 Nov 1;166(9):1197-205 PMID: 12403688
  51. The pathophysiology and treatment of sepsis.
    N Engl J Med. 2003 Jan 9;348(2):138-50 PMID: 12519925
  52. Induction of MIF synthesis and secretion by tubular epithelial cells: a novel action of angiotensin II.
    Kidney Int. 2003 Apr;63(4):1265-75 PMID: 12631343
  53. Inflammation-promoting activity of HMGB1 on human microvascular endothelial cells.
    Blood. 2003 Apr 1;101(7):2652-60 PMID: 12456506
  54. Anti-inflammatory strategies for the treatment of sepsis.
    Expert Opin Biol Ther. 2003 Apr;3(2):339-50 PMID: 12662146
  55. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference.
    Crit Care Med. 2003 Apr;31(4):1250-6 PMID: 12682500
  56. The epidemiology of sepsis in the United States from 1979 through 2000.
    N Engl J Med. 2003 Apr 17;348(16):1546-54 PMID: 12700374
  57. Novel strategies for the treatment of sepsis.
    Nat Med. 2003 May;9(5):517-24 PMID: 12724763
  58. Adoptive transfer of apoptotic splenocytes worsens survival, whereas adoptive transfer of necrotic splenocytes improves survival in sepsis.
    Proc Natl Acad Sci U S A. 2003 May 27;100(11):6724-9 PMID: 12736377
  59. Regulation by C5a of neutrophil activation during sepsis.
    Immunity. 2003 Aug;19(2):193-202 PMID: 12932353
  60. Neutrophil C5a receptor and the outcome in a rat model of sepsis.
    FASEB J. 2003 Oct;17(13):1889-91 PMID: 12897064
  61. Chemotactic and anaphylatoxic fragment cleaved from the fifth component of guinea pig complement.
    Science. 1968 Oct 18;162(3851):361-3 PMID: 4175690
  62. Prevention of death from endotoxin with antisera. I. The risk of fatal anaphylaxis to endotoxin.
    J Immunol. 1969 Mar;102(3):563-72 PMID: 4180046
  63. Germs.
    N Engl J Med. 1972 Sep 14;287(11):553-5 PMID: 5050429
  64. Generation of C5-derived lysosomal enzyme-releasing activity (C5a) by lysates of leukocyte lysosomes.
    J Immunol. 1974 Nov;113(5):1583-8 PMID: 4473046
  65. Oxygen radicals mediate endothelial cell damage by complement-stimulated granulocytes. An in vitro model of immune vascular damage.
    J Clin Invest. 1978 May;61(5):1161-7 PMID: 207729
  66. Passive immunization against cachectin/tumor necrosis factor protects mice from lethal effect of endotoxin.
    Science. 1985 Aug 30;229(4716):869-71 PMID: 3895437
  67. Multiple-organ failure. Generalized autodestructive inflammation?
    Arch Surg. 1985 Oct;120(10):1109-15 PMID: 4038052
  68. Effects of anti-C5a antibodies on the adult respiratory distress syndrome in septic primates.
    J Clin Invest. 1986 Jun;77(6):1812-6 PMID: 3711336
  69. Shock and tissue injury induced by recombinant human cachectin.
    Science. 1986 Oct 24;234(4775):470-4 PMID: 3764421
  70. Anti-cachectin/TNF monoclonal antibodies prevent septic shock during lethal bacteraemia.
    Nature. 1987 Dec 17-23;330(6149):662-4 PMID: 3317066
  71. Anaphylatoxin formation in sepsis.
    Arch Surg. 1988 May;123(5):645-9 PMID: 3282496
  72. Detection of circulating tumor necrosis factor after endotoxin administration.
    N Engl J Med. 1988 Jun 9;318(23):1481-6 PMID: 2835680
  73. Adjunctive therapy in sepsis: a critical analysis of the clinical trial programme.
    Br Med Bull. 1999;55(1):212-25 PMID: 10695088
  74. Protective effects of anti-C5a in sepsis-induced thymocyte apoptosis.
    J Clin Invest. 2000 Nov;106(10):1271-80 PMID: 11086028
  75. High mobility group 1 protein (HMG-1) stimulates proinflammatory cytokine synthesis in human monocytes.
    J Exp Med. 2000 Aug 21;192(4):565-70 PMID: 10952726
Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI19523
Published
2003-08-00
Pages
460-7
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC171398
Subset
IM
External Links
PubMed source DOI: 10.1172/JCI19523 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2