Inflammation Research

, Volume 61, Issue 4, pp 375–379 | Cite as

Increased plasma levels of heparin-binding protein in patients with shock: a prospective, cohort study

  • Michelle S. Chew
  • Adam Linder
  • Stefan Santen
  • Anders Ersson
  • Heiko Herwald
  • Henrik Thorlacius
Original Research Paper



Heparin-binding protein (HBP) is a potent inducer of increased vascular permeability. The purpose of this study was to examine plasma levels of HBP in patients with shock.


Fifty-three consecutive patients with septic and non-septic shock at a mixed-bed intensive care unit were included, as well as 20 age-matched controls. Patients with local infections but without signs of shock served as infectious controls. Enzyme-linked immunosorbent assay was used to determine plasma levels of HBP.


There were no differences in serum HBP levels between healthy controls and those with local infections, including urinary tract infections, pneumonia and gastroenteritis, without shock. Levels of HBP were higher in patients with non-septic shock and septic shock than healthy controls. However, there was no difference in serum HBP levels between patients with septic shock and those with non-septic shock. Moreover, HBP levels were not different between patients with low and high APACHE II scores. Plasma levels of HBP were similar in surviving and non-surviving patients with shock.


HBP is elevated in patients with shock from septic and non-septic etiologies. Future investigations are required to define the functional role of HBP in patients with shock.


Inflammation Leukocytes Neutrophils Sepsis 



This work was supported by grants from the Swedish Medical Research Council (2007-7480 and 2009-4872), Crafoord foundation, Einar and Inga Nilsson foundation, Harald and Greta Jaensson foundation, Greta and Johan Kock foundation, Fröken Agnes Nilsson foundation, Franke and Margareta Bergqvist foundation, Magnus Bergvall foundation, Mossfelt foundation, Nanna Svartz foundation, Ruth and Richard Julin foundation, Svenska Läkaresällskapet, MAS foundations, Scandinavian Society for Anesthesiology and Intensive Care Acta Foundation, Malmö University Hospital and Lund University. None of these funding bodies were involved in the study design, data collection, analysis, manuscript preparation or submission. We thank Monica Heidenholm for excellent technical assistance.

Conflict of interest

The authors declare that they have no competing interests.


  1. 1.
    Cohen J. The immunopathogenesis of sepsis. Nature. 2002;420:885–91.PubMedCrossRefGoogle Scholar
  2. 2.
    Asaduzzaman M, Zhang S, Lavasani S, Wang Y, Thorlacius H. LFA-1 and Mac-1 mediate pulmonary recruitment of neutrophils and tissue damage in abdominal sepsis. Shock. 2008;30:254–9.PubMedGoogle Scholar
  3. 3.
    Rahman M, Zhang S, Chew M, Ersson A, Jeppsson B, Thorlacius H. Platelet-derived CD40L (CD154) mediates neutrophil upregulation of Mac-1 and recruitment in septic lung injury. Ann Surg. 2009;250:783–90.PubMedCrossRefGoogle Scholar
  4. 4.
    Tapper H, Karlsson A, Mörgelin M, Flodgaard H, Herwald H. Secretion of heparin-binding protein from human neutrophils is determined by its localization in azurophilic granules and secretory vesicles. Blood. 2002;99:1785–93.PubMedCrossRefGoogle Scholar
  5. 5.
    Gautam N, Olofsson AM, Herwald H, Iversen LF, Lundgren-Akerlund E, Hedqvist P, Arfors KE, Flodgaard H, Lindbom L. Heparin-binding protein (HBP/CAP37): a missing link in neutrophil-evoked alteration of vascular permeability. Nat Med. 2001;7:1123–7.PubMedCrossRefGoogle Scholar
  6. 6.
    Soehnlein O, Zernecke A, Eriksson EE, Rothfuchs AG, Pham CT, Herwald H, Bidzhekov K, Rottenberg ME, Weber C, Lindbom L. Neutrophil secretion products pave the way for inflammatory monocytes. Blood. 2008;112:1461–71.PubMedCrossRefGoogle Scholar
  7. 7.
    Chertov O, Michiel DF, Xu L, Wang JM, Tani K, Murphy WJ, Longo DL, Taub DD, Oppenheim JJ. Identification of defensin-1, defensin-2, and CAP37/azurocidin as T-cell chemoattractant proteins released from interleukin-8-stimulated neutrophils. J Biol Chem. 1996;271:2935–40.PubMedCrossRefGoogle Scholar
  8. 8.
    Linder A, Christensson B, Herwald H, Björck L, Akesson P. Heparin-binding protein: an early marker of circulatory failure in sepsis. Clin Infect Dis. 2009;49:1044–50.PubMedCrossRefGoogle Scholar
  9. 9.
    Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, Schein RM, Sibbald WJ. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM consensus conference committee. Chest. 1992;101:1644–55.PubMedCrossRefGoogle Scholar
  10. 10.
    Dellinger RP, Carlet JM, Masur H, Gerlach H, Calandra T, Cohen J, Gea-Banacloche J, Keh D, Marshall JC, Parker MM, Ramsay G, Zimmerman JL, Vincent JL, Levy MM. Surviving sepsis campaign guidelines for management of severe sepsis and septic shock. Crit Care Med. 2004;32:858–73.PubMedCrossRefGoogle Scholar
  11. 11.
    Bernard GR, Vincent JL, Laterre PF, LaRosa SP, Dhainaut JF, Lopez-Rodriguez A, Steingrub JS, Garber GE, Helterbrand JD, Ely EW, Fisher CJ Jr. Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med. 2001;344:699–709.PubMedCrossRefGoogle Scholar
  12. 12.
    Knaus WA, Draper EA, Wagner DP, Zimmerman JE. Prognosis in acute organ system failure. Ann Surg. 1985;202:685–93.PubMedCrossRefGoogle Scholar
  13. 13.
    Påhlman LI, Mörgelin M, Eckert J, Johansson L, Russell W, Riesbeck K, Soehnlein O, Lindbom L, Norrby-Teglund A, Schumann RR, Björck L, Herwald H. Streptococcal M protein: a multipotent and powerful inducer of inflammation. J Immunol. 2006;177:1221–8.PubMedGoogle Scholar
  14. 14.
    Nakae H, Endo S, Inada K, Takakuwa T, Kasai T. Changes in adhesion molecule levels in sepsis. Res Commun Mol Pathol Pharmacol. 1996;91:329–38.PubMedGoogle Scholar
  15. 15.
    Silvestre J, Povoa P, Coelho L, Almeida E, Moreira P, Fernandes A, Mealha R, Sabino H. Is CRP a good prognostic marker in septic patients? Int Care Med. 2009;35:909–13.CrossRefGoogle Scholar
  16. 16.
    Johansson J, Lindbom L, Herwald H, Sjöberg F. Neutrophil-derived heparin binding protein––a mediator of increased vascular permeability after burns? Burns. 2009;35:1185–7.PubMedCrossRefGoogle Scholar
  17. 17.
    Berkestedt I, Herwald H, Ljunggren L, Nelson A, Bodelsson M. Elevated plasma levels of antimicrobial polypeptides in patients with severe sepsis. J Innate Immun. 2010;2:478–82.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Basel AG 2011

Authors and Affiliations

  • Michelle S. Chew
    • 2
  • Adam Linder
    • 3
  • Stefan Santen
    • 1
  • Anders Ersson
    • 2
  • Heiko Herwald
    • 3
  • Henrik Thorlacius
    • 1
  1. 1.Section of Surgery, Department of Clinical Sciences, MalmöSkåne University Hospital, Lund UniversityMalmöSweden
  2. 2.Section of Intensive Care, Department of Clinical Sciences, MalmöSkåne University Hospital, Lund UniversityMalmöSweden
  3. 3.Section of Clinical and Experimental Infection Medicine, Department of Clinical Sciences, LundLund UniversityLundSweden

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