High-mobility group box-1 protein serum levels do not reflect monocytic function in patients with sepsis-induced immunosuppression

Mediators Inflamm. 2010;2010:745724. doi: 10.1155/2010/745724. Epub 2010 Jun 21.


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-alpha 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-alpha 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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Cytokines / blood
  • Female
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
  • HMGB1 Protein / blood*
  • Humans
  • Immune Tolerance*
  • Male
  • Middle Aged
  • Monocytes / physiology*
  • Sepsis / immunology*


  • Cytokines
  • HMGB1 Protein
  • Granulocyte-Macrophage Colony-Stimulating Factor