Septic shock induced by lipopolysaccharide (LPS) is characterized by serious systemic inflammatory response and robust production of pro-inflammatory cytokines from activated macrophages. Damage-associated molecular patterns (DAMPs) secreted by activated macrophages are key contributors to septic shock. However, the current knowledge on those DAMPs that promote inflammatory response under LPS-induced septic shock remains poorly understood. Here, we report that Peroxiredoxin 1 (Prdx1) plays a detrimental role in LPS-induced septic shock. Intraperitoneal injection of LPS elicited a progressive course of septic shock in mice, which was characterized by significant lethality along with robust production of cytokines (IL-1 beta, IL-6 and TNF-alpha). Removal of Prdx1 strongly protected mice from LPS-induced death, and decreased IL-1 beta, IL-6 and TNF-alpha productions. Additionally, primary macrophages deficient in Prdx1 are less able to produce much more IL-1 beta, IL-6 and TNF-alpha. Collectively, we provide a demonstration for Prdx1 contributing to LPS-induced septic shock likely via promoting inflammation. (C) 2020 Elsevier Inc. All rights reserved.