HMGB1 and Sepsis: In contrast, HMGB1 is a late mediator of lethal systemic inflammation [11], and HMGB1 has a prolonged therapeutic window as compared to those early inflammatory cytokines; circulating TNF-α and IL-6 are elevated for 5 days after the onset of sepsis, and serum HMGB1 levels are increased from day 7 until at least day 28 [12].