Bopp et al. documented that septic patients have elevated circulating sRAGE levels and that non-survivors show higher plasma sRAGE concentrations than survivors, suggesting that sRAGE is related to severity and clinical outcome in sepsis [49] . Knowledge on the role of endogenous sRAGE in sepsis is scarce. Hudson et al. demonstrated that sRAGE levels might represent an early marker of microvascular dysfunction, a pheno me non also present in sepsis [50] . Furthermore, increased sRAGE concentrations in sepsis might represent the acute infl ammatory status as splice variants of RAGE or as split off variants of the cell surface RAGE, the latter analogous to ICAM-1, another member of the immunoglobulin superfamily, which is a marker of cellular damage during sepsis. Another possibility is that systemic sRAGE levels might be elevated in parallel with HMGB1/ S100A12 levels as a counter-system against HMGB1/ S100A12 elicited tissue eff ects. More research is needed to clarify the functional role of sRAGE in sepsis and its putative role as a new sepsis marker.