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


METHODS
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).


RESULTS
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.
Unterwalder
Nadine
N
Department of Medical Immunology, Charité University Medicine, Campus Mitte, 10117 Berlin, Germany.
Meisel
Christian
C
Savvatis
Konstantinos
K
Hammoud
Ben
B
Fotopoulou
Christina
C
Volk
Hans-Dieter
HD
Reinke
Petra
P
Schefold
Joerg C
JC
D000328:Adult; D000368:Aged; D016207:Cytokines / Q000097:blood; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D024243:HMGB1 Protein / Q000097:blood*; D006801:Humans; D007108:Immune Tolerance; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000502:physiology*; D018805:Sepsis / Q000276:immunology*
D016207:Cytokines; D024243:HMGB1 Protein; D016178:Granulocyte-Macrophage Colony-Stimulating Factor