Early elevated HMGB1 level predicting the outcome in exertional heatstroke

Heatstroke is generally considered as a syndrome of hyperthermia associated with systemic inflammation leading to multiorgan dysfunction. High mobility group box-1 protein (HMGB1) has recently been identified as a late mediator of systemic inflammation inducing multiorgan dysfunction. Elevation of plasma HMGB1 in heatstroke has been observed in animals, but there is no data available about its changes in heatstroke patients. The objectives of this study are to observe the time course of plasma HMGB1 changes and assess its prognostic value in patients with exertional heatstroke.

Blood samples were taken from the patients with exertional heatstroke. Plasma HMGB1 level was detected by the enzyme-linked immunosorbent assay. C-reactive protein level was measured using a fully automated IMMAGE Immunochemistry System. Secreted HMGB1 in the culture supernatant of peripheral blood monocyte was assessed by immunoblotting. Acute Physiology and Chronic Health Evaluation II score was evaluated within 24 hours of admission.

HMGB1 released into circulation at early stage, with peak levels occurring within 6 hours to 13 hours postheatstroke. Plasma HMGB1 levels remained markedly elevated in the following 6 days postheatstroke when compared with healthy volunteers (p<0.005). Positive correlation (r=0.798, p<0.001) was found between Acute Physiology and Chronic Health Evaluation II score and HMGB1 level at admission. HMGB1 levels at admission between survivors and nonsurvivors were significantly different (p<0.001). Receiver operating curve analysis showed that at a level of 47 ng/mL, HMGB1 level at admission indicated lethality with 77.4% sensitivity and 84.2% specificity.

HMGB1 level at admission is an indicator of the severity of illness and a useful mortality predictor in exertional heatstroke.