As HMGB1 has multiple downstream signaling responses due to activation of different receptors, it also induces cell specific responses when it stimulates cells of the immune system ( Figure 1 ). HMGB1 induces DC maturation as measured by the increased expression of many cell surface markers as well as the secretion of inflammatory cytokines (23, (51) (52) (53) . Monocytes stimulated with HMGB1 have an increased capacity for adhesion (38) and release numerous cytokines and inflammatory mediators (61, (68) (69) (70) . This effect is augmented when administered concomitantly with other cytokines (67, 71) . Neutrophil stimulation with HMGB1 increases the interaction of MAC-1 and RAGE, thus activating the adhesive and migratory function of these cells (56) . Furthermore, HMGB1 stimulates the production of reactive oxygen species by neutrophils through a TLR4 dependent activation of NAD(P)H oxidase (72) , as well as increases the activation of NF-κB which results in increased production and release of cytokines (50, 62) . T cells stimulated with HMGB1 release cytokines and appear to have increased proliferation, survival, and Th1 functional polarization (23, 51) .