A specific CETP isoform tracks disease severity and may help neutralize bacterial toxin in Gram-negative sepsis (Mol Med 2022)

Original title: The cholesteryl-ester transfer protein isoform (CETPI) and derived peptides: new targets in the study of Gram-negative sepsis

Mol Med · 19 December 2022 · 7

Pérez-Hernández EG, De la Puente-Díaz de León V, Luna-Reyes I, Delgado-Coello B, Sifuentes-Osornio J, Mas-Oliva J

Researchers studied the cholesteryl-ester transfer protein isoform (CETPI), synthesised in the small intestine and able to bind and deactivate bacterial lipopolysaccharide (LPS), in 47 healthy subjects, 50 patients with infection, and 55 patients with sepsis or septic shock from Gram-negative bacteraemia. Plasma CETPI levels were higher in patients with positive blood cultures than in controls and correlated directly with SOFA organ-failure scores. In septic shock patients, high CETPI levels correlated negatively with the cytokines IL-8, IL-1beta, and IL-10, and in patients with liver dysfunction, higher CETPI levels correlated with higher plasma LPS concentration. The authors conclude elevated plasma CETPI is associated with disease severity and organ failure in Gram-negative sepsis, implicating it in the systemic response to LPS and suggesting LPS neutralisation by CETPI as a physiological response worth further study.

Original abstract

Background: Sepsis is a syndrome where the dysregulated host response to infection threatens the life of the patient. The isoform of the cholesteryl-ester transfer protein (CETPI) is synthesized in the small intestine, and it is present in human plasma. CETPI and peptides derived from its C-terminal sequence present the ability to bind and deactivate bacterial lipopolysaccharides (LPS). The present study establishes the relationship between the plasma levels of CETPI and disease severity of sepsis due to Gram-negative bacteria.

Methods: Plasma samples from healthy subjects and patients with positive blood culture for Gram-negative bacteria were collected at the Intensive Care Unit (ICU) of INCMNSZ (Mexico City). 47 healthy subjects, 50 patients with infection, and 55 patients with sepsis and septic shock, were enrolled in this study. CETPI plasma levels were measured by an enzyme-linked immunosorbent assay and its expression confirmed by Western Blot analysis. Plasma cytokines (IL-1β, TNFα, IL-6, IL-8, IL-12p70, IFNγ, and IL-10) were measured in both, healthy subjects, and patients, and directly correlated with their CETPI plasma levels and severity of clinical parameters. Sequential Organ Failure Assessment (SOFA) scores were evaluated at ICU admission and within 24 h of admission. Plasma LPS and CETPI levels were also measured and studied in patients with liver dysfunction.

Results: The level of CETPI in plasma was found to be higher in patients with positive blood culture for Gram-negative bacteria that in control subjects, showing a direct correlation with their SOFA values. Accordingly, septic shock patients showing a high CETPI plasma concentration, presented a negative correlation with cytokines IL-8, IL-1β, and IL-10. Also, in patients with liver dysfunction, since higher CETPI levels correlated with a high plasma LPS concentration, LPS neutralization carried out by CETPI might be considered a physiological response that will have to be studied in detail.

Conclusions: Elevated levels of plasma CETPI were associated with disease severity and organ failure in patients with Gram-negative bacteraemia, defining CETPI as a protein implicated in the systemic response to LPS.

Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.