Article thumbnail

High-Mobility Group Box-1 Protein Serum Levels Do Not Reflect Monocytic Function in Patients with Sepsis-Induced Immunosuppression

By Nadine Unterwalder, Christian Meisel, Konstantinos Savvatis, Ben Hammoud, Christina Fotopoulou, Hans-Dieter Volk, Petra Reinke and Joerg C. Schefold


Background. High-mobility group box-1 (HMGB-1) protein is released during “late sepsis” by activated monocytes. We investigated whether systemic HMGB-1 levels are associated with indices of monocytic activation/function in patients with sepsis-induced immunosuppression. Methodology. 36 patients (31 male, 64 ± 14 years) with severe sepsis/septic shock and monocytic deactivation (reduced mHLA-DR expression and TNF-α release) were assessed in a subanalysis of a placebo-controlled immunostimulatory trial using GM-CSF. HMGB-1 levels were assessed over a 9-day treatment interval. Data were compared to standardized biomarkers of monocytic immunity (mHLA-DR expression, TNF-α release). Principle findings. HMGB-1 levels were enhanced in sepsis but did not differ between treatment and placebo groups at baseline (14.6 ± 13.5 versus 12.5 ± 11.5 ng/ml, P = .62). When compared to controls, HMGB-1 level increased transiently in treated patients at day 5 (27.8 ± 21.7 versus 11.0 ± 14.9, P = .01). Between group differences were not noted at any other point of assessment. HMGB-1 levels were not associated with markers of monocytic function or clinical disease severity. Conclusions. GM-CSF treatment for sepsis-induced immunosuppression induces a moderate but only transient increase in systemic HMGB-1 levels. HMGB-1 levels should not be used for monitoring of monocytic function in immunostimulatory trials as they do not adequately portray contemporary changes in monocytic immunity

Topics: Research Article
Publisher: Hindawi Publishing Corporation
OAI identifier:
Provided by: PubMed Central

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.

Suggested articles


  1. (2009). A novel biomarker-guided immunomodulatory approach for the therapy of sepsis,”
  2. (2007). A novel role for HMGB1 in TLR9-mediated inflammatory responses to
  3. (2003). Am Esch, “Reversal of immunoparalysis by recombinant human granulocyte-macrophage colony-stimulating factor in patients with severe sepsis,”
  4. (2006). Anti-high-mobility group box chromosomal protein 1 antibodies improve survival of rats with sepsis,”
  5. (2008). Consider delayed immunosuppression into the concept of sepsis,”
  6. (2009). e i s e l ,J .C .S c h e f o l d ,R .P s c h o w s k i ,T .B a u m a n n
  7. (2007). Factors masking HMGB1 in human serum and plasma,”
  8. (2003). H .Y a n g ,K .J .T r a c e y ,J .A n d e r s s o n ,a n dJ
  9. (2008). High mobility group protein-1 inhibits phagocytosis of apoptotic neutrophils through binding to phosphatidylserine,”
  10. (2006). HMGB-1 as a therapeutic target for infectious and inflammatory disorders,”
  11. (2007). i a n ,A .M .A v a l o s ,S . - Y .M a o ,B .C h e n ,K .S e n t h i l ,H .W u ,P . P a r r o c h e ,S .D r a b i c ,D .G o l e n b o c k ,C .S i r o i s
  12. i l v a ,J .A r c a r o l i ,Q .H e ,D .S v e t k a u s k a i t e ,C .C o l d r e n
  13. (1985). II: a severity of disease classification system,”
  14. Kruschke,H.Zuckermann,H.-D.Volk,andP.Reinke,“Anovel selective extracorporeal intervention in sepsis: immunoadsorption of endotoxin, interleukin 6, and complementactivatingproduct5a,”Shock,vol.28,no.4,pp.418–425,2007.
  15. (2006). l l o aa n dD .M e s s m e r ,“ H i g h - m o b i l i t yg r o u pb o x1 (HMGB1) protein: friend and foe,” Cytokine and Growth Factor Reviews,
  16. (2005). L o t z ea n dK .J .T r a c e y ,“ H i g h - m o b i l i t yg r o u pb o x1 protein (HMGB1): nuclear weapon in the immune arsenal,”
  17. (2008). Monitoring immune dysfunctions in the septic patient: a new skin for the old ceremony,”
  18. (1997). Monocyte deactivation in septic patients: restoration by IFN-γ treatment,”
  19. (2008). Nosocomial infection after septic shock among intensive care unit patients,” Infection Control and Hospital Epidemiology,
  20. o n a l d i ,F .T a l a m o ,P .S c a ffidi,
  21. (2005). P .K i e f e r ,S .U .W e b e r ,M .H e d w i g - G e i s s i n g ,E .K r e u z f e l d e r
  22. (2002). Release ofchromatin protein HMGB1 by necrotic cells triggers inflammation,”
  23. (2002). The immunopathogenesis of sepsis,”
  24. (2006). The role of high mobility group box-1 protein in severe sepsis,”
  25. (1996). The SOFA (Sepsis-Related Organ Failure Assessment) score to describe organ dysfunction/failure,”
  26. (2008). Therapeutic potential of HMGB1-targeting agents in sepsis,”
  27. (2004). Y .A l - A b e d ,H .W a n g