Severe Stroke Induces Long-Lasting Alterations of High-Mobility Group Box 1

Background and Purpose-The signals that initiate the poststroke inflammatory response are unknown. High-mobility group box (HMGB) 1 protein is a nuclear protein that is passively released from necrotic tissue and is able to activate leukocytes, which in turn secrete HMGB1. HMGB1 is also able to activate antigen-presenting cells and therefore stands at the crossroads of innate and adaptive immunity. Methods-Plasma HMGB1 concentrations were determined at multiple time points after ischemic stroke (N=110) and correlated to stroke severity and biomarkers of inflammation. The relationships between HMGB1, stroke outcome, and autoimmune responses to brain antigens were also assessed. Results-Stroke resulted in an increase in HMGB1 that persisted for 30 days. Plasma HMGB1 was correlated with the number of circulating leukocytes but was not predictive of either stroke outcome or the development of autoimmune responses to brain antigens. Patients with a T(H)1(+) response to myelin basic protein at 90 days after stroke, however, had higher plasma HMGB1. Conclusions-HMGB1 appears to be involved in the postischemic inflammatory response, but it remains unclear whether HMGB1 initiates this response or merely reflects activation of leukocytes by another signal. (Stroke. 2013;44:246-248.)