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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.

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