Critical role for CCR2 and HMGB1 in induction of experimental endotoxic shock

•Lipopolysaccharide (LPS) is a toxic endotoxin that elicit strong immune response.•Here we shown CCR2 KO mice with delayed mortality after endotoxemia (LPS).•The use of glycyrrhizic acid, a HMGB1 inhibitor, provided survival benefit. Our aim was to investigate CCR2 and HMGB1 involvement in a murine model of endotoxic shock. We used C57BL/6 CCR2 knockout (KO) mice and wild-type (WT) littermates to establish an optimal dose of LPS. CCR2 KO mice survived more frequently than WT mice after 80, 40 and 20mg/kg of LPS i.p. Inflammation and redox markers were high in WT mice than in CCR2 KO mice. HMGB1 expression was reduced in CCR2 KO mice in parallel to ERK 1/2 activation. Therefore, we used glycyrrhizic acid (50mg/kg), an HMGB1 inhibitor in WT mice injected with LPS, and mortality was fully abolished. Thus, drugs targeting CCR2 and HMGB1 could represent future resources for sepsis treatment.