Skip to main content

Advertisement

SpringerLink
Log in

High-mobility group box 1 protein plasma concentrations during septic shock

  • Original
  • Published:
Intensive Care Medicine Aims and scope Submit manuscript

Abstract

Objective

To investigate plasma high-mobility group box 1 protein (HMGB1) concentration and its relationship with organ dysfunction and outcome in septic shock patients.

Design and setting

Prospective, noninterventional study. Medical adult intensive care unit at a university hospital in France.

Patients

42 critically ill patients with septic shock.

Methods

Arterial blood was drawn within 12 h of admission for the measurement of plasma HMGB1 concentration by ELISA. Repeated sampling was performed on days 3, 7, and 14.

Results

Median HMGB1 concentration was 4.4 ng/ml (IQR 1.2–12.5) at admission, with no difference between survivors and nonsurvivors. A positive correlation was observed between HMGB1 and SOFA score and lactate, and procalcitonin concentrations. There was a progressive but statistically nonsignificant decline in HMGB1 concentration among the survivors, while nonsurvivors showed an increase in HMGB1 level between days 1 and 3. SOFA score and lactate and procalcitonin concentrations did not vary significantly between days 1 and 3. When measured on day 3, HMGB1 discriminated survivors from nonsurvivors with 66% sensitivity and 67% specificity, and concentration greater than 4 ng/ml was associated with an odds ratio of death of 5.5 (95% CI 1.3–23.6).

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Bustin M, Hopkins RB, Isenberg I (1978) Immunological relatedness of high mobility group chromosomal proteins from calf thymus. J Biol Chem 253:1694–1699

    PubMed  CAS  Google Scholar 

  2. West KL, Castellini MA, Duncan MK, Bustin M (2004) Chromosomal proteins HMGN3a and HMGN3b regulate the expression of glycine transporter 1. Mol Cell Biol 24:3747–3756

    Article  PubMed  CAS  Google Scholar 

  3. Park JS, Arcaroli J, Yum HK, Yang H, Wang KY, Choe KH, Strassheim D, Pitts TM, Tracey KF, Abraham E (2003) Activation of gene expression in human neutrophils by high mobility group box 1 protein. Am J Physiol Cell Physiol 284:C870–C879

    PubMed  CAS  Google Scholar 

  4. Wang H, Bloom O, Zhang M, Vishnubhakat JM, Ombrellino M, Che J, Frazier A, Yang H, Ivanova S, Borovikova L, Manogue KR, Faist E, Abraham E, Andersson J, Andersson U, Molina PE, Abumrad NN, Sama A, Tracey KJ (1999) HMG-1 as a late mediator of endotoxin lethality in mice. Science 285:248–251

    Article  PubMed  CAS  Google Scholar 

  5. Sansonetti PJ (2006) The innate signalling of dangers and the dangers of innate signalling. Nat Immunol 7:1237–1242

    Article  PubMed  CAS  Google Scholar 

  6. Kalinina N, Agrotis A, Antropova Y, DiVitto G, Kanellakis P, Kostolias G, Ilyinskaia O, Tararak E, Bobik A (2004) Increased expression of the DNA-binding cytokine HMGB1 in human atherosclerotic lesions. Role of activated macrophages and cytokines. Atheroscler Thromb Vasc Biol 24:2320–2325

    Article  CAS  Google Scholar 

  7. Chen G, Li J, Ochani M, Rendon-Mitchell B, Qiang X, Susarla S, Ulloa L, Yang H, Fan S, Goyert SM, Wang P, Tracey KJ, Sama AE, Wang H (2004) Bacterial endotoxin stimulates macrophages to release HMGB1 partly through CD14- and TNF-dependent mechanisms. J Leukoc Biol 76:994–1001

    Article  PubMed  CAS  Google Scholar 

  8. Scaffidi P, Misteli T, Bianchi ME (2002) Release of chromatin protein HMGB1 by necrotic cells triggers inflammation. Nature 418:191–195

    Article  PubMed  CAS  Google Scholar 

  9. Rovere-Querini P, Capobianco A, Scaffidi P, Valentinis B, Catalanotti F, Giazzon M, Dumitriu IE, Muller S, Iannacone M, Traversari C, Bianchi ME, Manfredi AA (2004) HMGB1 is an endogenous immune adjuvant released by necrotic cells. EMBO Rep 5:825–830

    Article  PubMed  CAS  Google Scholar 

  10. Hori O, Brett J, Slattery T, Cao R, Zhang J, Chen JX, Nagashima M, Lundh ER, Vijay S, ovitechi D (1995) The receptor for advanced glycation end products (RAGE) is a cellular binding site for amphoterin. J Biol Chem 270:25752–25761

    Article  PubMed  CAS  Google Scholar 

  11. Park JS, Svetkauskaite D, He Q, Kim JY, Strassheim D, Ishizaka A, Abraham E (2004) Involvement of Toll-like receptors 2 and 4 in cellular activation by high mobility group box 1 protein. J Biol Chem 279:7370–7377

    Article  PubMed  CAS  Google Scholar 

  12. Ombrellino M, Wang H, Ajemian MS, Talhouk A, Scher LA, Friedman SG, Tracey KJ (1999) Increased serum concentrations of high-mobility-group protein 1 in hemorrhagic shock. Lancet 354:1446–1447

    Article  PubMed  CAS  Google Scholar 

  13. Taniguchi N, Kawahara K, Yone K, Hashiguchi T, Yamakuchi M, Goto M, Inoue K, Yamada S, Ijiri K, Matsunaga S, Nakajima T, Komiya S, Maruyama I (2003) High mobility group box chromosomal protein 1 plays a role in the pathogenesis of rheumatoid arthritis as a novel cytokine. Arthritis Rheum 48:971–981

    Article  PubMed  CAS  Google Scholar 

  14. Yang H, Ochani M, Li J, Qiang X, Tanovic M, Harris HE, Susarla SM, Ulloa L, Wang H, DiRaimo R, Czura CJ, Wang H, Roth J, Warren HS, Fink MP, Fenton MJ, Andersson U, Tracey KJ (2004) Reversing established sepsis with antagonists of endogenous HMGB1. Proc Natl Acad Sci USA 101:296–301

    Article  PubMed  CAS  Google Scholar 

  15. Ulloa L, Ochani M, Yang H, Tanovic M, Halperin D, Yang R, Czura CJ, Fink MP, Tracey KJ (2002) Ethyl pyruvate prevents lethality in mice with established lethal sepsis and systemic inflammation. Proc Natl Acad Sci USA 99:12351–12356

    Article  PubMed  CAS  Google Scholar 

  16. Chen G, Li J, Qiang X, Czura CJ, Ochani M, Ochani K, Ulloa L, Yang H, Tracey KJ, Wang P, Sama AE, Wang H (2005) Suppression of HMGB-1 release by stearoyl lysophosphatidylcholine: an additional mechanism for its therapeutic effects in experimental sepsis. J Lipid Res 46:623–627

    Article  PubMed  CAS  Google Scholar 

  17. Sunden-Cullberg J, Norrby-Teglund A, Rouhiainen A, Rauvala H, Herman G, Tracey KJ, Lee ML, Andersson J, Tokics L, Treutiger CJ (2005) Persistent elevation of high mobility group box-1 protein (HMGB1) in patients with severe sepsis and septic shock. Crit Care Med 33:564–573

    Article  PubMed  CAS  Google Scholar 

  18. Janeway CA Jr (1989) Approaching the asymptote? Evolution and revolution in immunology. Cold Spring Harb Symp Quant Biol 54:1–13

    PubMed  CAS  Google Scholar 

  19. Medzhitov R, Janeway CA Jr (1997) Innate immunity: the virtues of a nonclonal system of recognition. Cell 91:295–298

    Article  PubMed  CAS  Google Scholar 

  20. Poltorak A, He X, Smirnova I, Liu MY, Van Huffel C, Du X, Birdwell D, Alejos E, Silva M, Galanos C, Freudenberg M, Ricciardi-Castagnoli P, Layton B, Beutler B (1998) Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science 282:2085–2088

    Article  PubMed  CAS  Google Scholar 

  21. Matzinger P (2002) The danger model: a renewed sense of self. Science 296:301–305

    Article  PubMed  CAS  Google Scholar 

  22. Krzeslak A, Lipinska A (2004) Galectin-3 as a multifunctional protein. Cell Miol Biol Lett 9:305–328

    CAS  Google Scholar 

  23. Mariathasan S, Weiss DS, Newton K, McBride J, O'Rourke K, Roose-Girma M, Lee WP, Weinrauch Y, Monach DM, Dixit VM (2006) Cryopyrin activates the inflammasome in response to toxins and ATP. Nature 440:228–232

    Article  PubMed  CAS  Google Scholar 

  24. Shi Y, Evans JE, Rock KL (2003) Molecular identification of a danger signal that alerts the immune system to dying cells. Nature 425:516–521

    Article  PubMed  CAS  Google Scholar 

  25. Yamada S, Maruyami I (2007) HMGB1, a novel inflammatory cytokine. Clin Chim Acta 375:36–42

    Article  PubMed  CAS  Google Scholar 

  26. Urbonaviciute V, Furnrohr BG, Weber C, Haslbeck M, Wilhelm S, Herrmann M, Voll RE (2007) Factors masking HMGB1 in human serum and plasma. J Leukoc Biol 81:67–74

    Article  PubMed  CAS  Google Scholar 

  27. Yamada S, Inoue K, Yakabe K, Imaizumi H, Maruyama I (2003) High mobility group protein 1 (HMGB1) quantified by ELISA with a monoclonal antibody that does not cross-react with HMGB2. Clin Chem 49:1535–1537

    Article  PubMed  CAS  Google Scholar 

  28. Yamada S, Yakabe K, Ishii J, Imaizumi H, Maruyama I (2006) New high mobility group box 1 assay system. Clin Chim Acta 372:173–178

    Article  PubMed  CAS  Google Scholar 

  29. Gaini S, Pedersen SS, Pedersen C, Koldkjaer OG, Moller HJ (2007) High mobility group box-1 protein (HMGB1) in patients with suspected community-acquired infections and sepsis: a prospective study. Crit Care 11:R32

    Article  PubMed  Google Scholar 

  30. Hatada T, Wada H, Nobori T, Okabayashi K, Maruyama K, Abe Y, Uemoto S, Yamada S, Maruyama I (2005) Plasma concentrations and importance of high mobility group box protein in the prognosis of organ failure in patients with disseminated intravascular coagulation. Thromb Haemost 94:975–979

    PubMed  CAS  Google Scholar 

  31. Eriksson M (2005) Should high mobility group box-1 protein (HMGB1) be measured in patients with severe sepsis and septic shock? If so, when, where, and how? Crit Care Med 33:682–683

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

S.G. designed the study, enrolled patients, performed measurements, and drafted the manuscript; F.M. performed measurements; A.C., D.B., and L.N. enrolled patients; P.E.B. designed the study and drafted the manuscript. All authors approved the final version of the manuscript

Author information

Authors and Affiliations

  1. Service de Réanimation Médicale, Hôpital Central, 29 avenue du Maréchal de Lattre de Tassigny, 54000, Nancy, France

    Sébastien Gibot, Aurélie Cravoisy, Damien Barraud, Lionel Nace, Brune Levy & Pierre-Edouard Bollaert

  2. Groupe Choc, Contrat AVENIR INSERM, U684, Faculté de Médecine, Université Nancy 1, 54500 Vandœuvre lès Nancy, 54000, Nancy, France

    Sébastien Gibot & Brune Levy

  3. Laboratoire d’Immunologie, Faculté de Médecine, Université Nancy 1, 54500 Vandœuvre lès Nancy, 54000, Nancy, France

    Frédéric Massin

Authors
  1. Sébastien Gibot
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Frédéric Massin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Aurélie Cravoisy
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Damien Barraud
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Lionel Nace
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Brune Levy
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Pierre-Edouard Bollaert
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sébastien Gibot.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gibot, S., Massin, F., Cravoisy, A. et al. High-mobility group box 1 protein plasma concentrations during septic shock . Intensive Care Med 33, 1347–1353 (2007). https://doi.org/10.1007/s00134-007-0691-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00134-007-0691-2

Keywords

Search

Navigation