Kinetics of HMGB1 level changes in a canine endotoxemia model

In this study, we investigated the kinetics of tumor necrosis factor (TNF)-α, interleukin (IL)-6 and high mobility group box 1 (HMGB1) concentrations in a 48-h model of canine endotoxemia by lipopolysaccharide (LPS) injection. Four healthy beagles were slowly administered 1 mg/kg of LPS diluted in normal saline, while two others were administered normal saline as controls. Blood collection was performed at 0 h (baseline), 1 h and 3 h (for TNF-α), 6 h, 12 h, 24 h and 48 h of the experiment, and cytokine levels were determined using the sandwich ELISA method. Early increments of TNF-α and IL-6 were observed (< 3 h), but HMGB1 levels increased the most at 12 h of the experiment and gradually decreased until 48 h. During the whole experiment, IL-6 and HMGB1 were sustained over 12 h of LPS injection, whereas TNF-α decreased within 6 h of LPS injection. Taken together, canine HMGB1 levels increase relatively late (< 12 h) and sustained longer than TNF-α and IL-6 in response to endotoxin. This is the first study to evaluate canine HMGB1 cytokine from endotoxemia in dogs.