Abstract 429: HDL Protects Against Polymicrobial-induced Sepsis in Mice

Abstract

HDL has been considered a protective factor in sepsis, however, most contributing studies were conducted using endotoxic animal model; and evidence from clinically relevant septic animal models remains limited and controversial. Furthermore, little is known about the roles of HDL in sepsis other than LPS neutralization. In this study, we employed cecal ligation and puncture (CLP), a clinically relevant septic animal model and utilized ApoA-I knockout (ApoA-I KO) mice and ApoA-I transgenic (ApoA-I-tg) mice to elucidate the roles of HDL in sepsis. ApoA-I KO mice were more susceptible to CLP-induced septic death as shown by 47.1% survival of ApoA-I KO mice versus 76.7% survival of C57BL/6J (B6) mice (p = 0.038). ApoA-I KO mice had exacerbated inflammatory cytokine production during sepsis compared with B6 mice. Further study indicated that serum from ApoA-I KO mice displays less capacity for LPS neutralization compared with serum from B6 mice. In addition, ApoA-I KO mice had moderately impaired LPS clearance and a significant reduction in corticosterone generation in sepsis. In contrast to ApoA-I KO mice, ApoA-I-tg mice were moderately resistant to CLP-induced septic death compared with B6 mice. In conclusion, our findings reveal multiple protective roles of HDL in CLP-induced sepsis. In addition to its well-established role in neutralization of LPS, HDL exerts its protection against sepsis through promoting LPS clearance and modulating corticosterone production. Our study supports efforts to raise HDL levels as a therapeutic approach for sepsis.