High-mobility group box 1 as a surrogate prognostic marker in dogs with systemic inflammatory response syndrome

Objective To evaluate various surrogate markers associated with the inflammatory and counter-inflammatory responses with respect to mortality in dogs with systemic inflammatory response syndrome (SIRS). Design Prospective observational study. Setting Veterinary Teaching Hospital. Animals Twenty-eight dogs with naturally occurring diseases and SIRS from January 2007 to May 2009. Interventions Upon admission to the veterinary hospital, history and baseline data from the physical examination, including parameters previously defined for meeting SIRS criteria, were documented. Heparinized blood samples were collected and plasma cytokines interleukin-6 (IL-6), IL-10, and high-mobility group box 1 (HMGB1) were measured by sandwich ELISA. Measurements and Main Results In nonsurvivors, median plasma HMGB1 concentrations (0.718 mu g/L, interquartile range [IQR]; 0.300-1.626 mu g/L) and the ratio of HMGB1 to IL-10 (2.236, IQR; 0.972-5.367) were significantly increased as compared with those found in survivors (0.300 mu g/L, IQR; 0.300-0.312 mu g/L for HMGB1; 1.017, IQR; 0.862-1.126 for the ratio of HMGB1 to IL-10, P=0.007 and 0.024, respectively). Plasma IL-6, IL-10, and the ratio of IL-6 to IL-10 were not significantly different between groups. Among the parameters studied, HMGB1 and the ratio of HMGB1 to IL-10 performed the best in discriminating outcome in dogs with SIRS according to receiver operator characteristic curve analysis. Conclusions Increases in plasma HMGB1 concentration and the ratio of HMGB1 to IL-10 may predict poorer outcomes in dogs with SIRS. The approach described may lead to reliable prognostic biomarkers and new therapeutic concepts in the study of SIRS in dogs.