The class
Landmark hypothesis proposes CETP as an immunological gatekeeper that could be repurposed to treat sepsis (Trends Endocrinol Metab 2020)
Original title: A Novel Role for CETP as Immunological Gatekeeper: Raising HDL to Cure Sepsis?
Since raising HDL with CETP inhibitors failed to reduce cardiovascular disease risk in clinical trials, this review proposes a novel physiological role for CETP: modulating HDL to help resolve bacterial infections. Drawing on evidence from isolated macrophages, rodents, and humans, the authors argue that when Gram-negative bacteria invade the blood, as in sepsis, Kupffer cells lose CETP expression to raise HDL levels, which then binds lipopolysaccharide to prevent systemic endotoxemia and induces a proinflammatory macrophage response that mediates bacterial clearance. The authors propose repurposing CETP inhibitors as a treatment for sepsis, a hypothesis that launched a subsequent line of CETP-sepsis research.
Original abstract
Raising HDL using cholesteryl ester transfer protein (CETP) inhibitors failed to show a clinically relevant risk reduction of cardiovascular disease in clinical trials, inviting reconsideration of the role of CETP and HDL in human physiology. Based on solid evidence from studies with isolated macrophages, rodents, and humans, we propose that a major function of CETP may be to modulate HDL in order to help resolve bacterial infections. When gram-negative bacteria invade the blood, as occurs in sepsis, Kupffer cells lose their expression of CETP to increase HDL levels. This rise in HDL prevents systemic endotoxemia by binding lipopolysaccharide and induces a systemic proinflammatory response in macrophages to mediate bacterial clearance. This raises the interesting possibility to repurpose CETP inhibitors for the treatment of sepsis.
the classinfectioninflammation
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.