Th e role of RAGE in abdominal sepsis has been investigated in a limited number of studies so far. RAGEdefi cient mice showed decreased mortality after induction of polymicrobial sepsis induced by CLP in two reports [9, 41] . Moreover, anti-RAGE antibody yielded a better survival even when the anti-RAGE therapy was delayed up to 24 hours after CLP in mice receiving antibiotics [41] . Th e protective eff ect provided by the absence of RAGE was related to a fi rm inhibition of NF-κB activation, suggesting that the lack of excessive NF-κB activation in RAGE -/mice might have contributed to their reduced mortality [9] . In addition, RAGE defi ciency resulted in fewer infl ammatory cells in the peritoneum [9] , which parallels the results of an earlier investigation by the same group of authors identifying RAGE as a counter-receptor for the β2 integrin, Mac-1 (CD11b/CD18), and thereby as a mediator of leukocyte recruitment and adhesion [8] . Furthermore, the protective eff ect of RAGE inhibition in this CLP model could at least in part be the consequence of the inhibition of one of its ligands, HMGB1. Indeed, HMGB1 is secreted into the circulation after CLP and anti-HMGB1 antibody led to increased survival after CLP-induced peritonitis [18] .