HMGB1 and infection: In the presence of infection, extracellular hemoglobin and heme amplify inflammation by synergizing with microbial Toll-like receptor (TLR) agonists and non-microbial endogenous ligands, such as high-mobility group box 1 protein (HMGB1), to induce high levels of proinflammatory cytokines including tumor necrosis factor (TNF) and interleukin 6 (IL-6) [3-5].