HDL has been considered to be a protective factor in
sepsis; however, most contributing studies were conducted using the 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 knock-out (KO) and transgenic mice to elucidate the roles of HDL in
sepsis.
ApoA-I-KO mice were more susceptible to CLP-induced septic death as shown by the 47.1% survival of
apoA-I-KO mice versus the 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 displayed less capacity for LPS neutralization compared with serum from B6 mice. In addition,
apoA-I-KO mice had less LPS clearance, reduced
corticosterone generation, and impaired leukocyte recruitment in
sepsis. In contrast to
apoA-I-KO mice,
apoA-I transgenic 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 and leukocyte recruitment. Our study supports efforts to raise HDL levels as a therapeutic approach for
sepsis.