Background: Sepsis is associated with systemic inflammation that may impact lipoprotein function. In particular, high-density lipoproteins (HDLs) that display pleiotropic protective roles may be dysfunctional in septic conditions. The aim of this study was to evaluate the HDL profile and the inflammatory context in septic shock patients admitted to our intensive care unit (ICU). Methods: In this study, 20 septic shock patients and 20 controls (ICU patients without septic shock) were included. Plasma samples were collected on days 1, 2 and 7. Total cholesterol and lipoprotein concentrations were determined. HDL profiles were obtained using the Lipoprint ® System (non-denaturing electrophoresis). Quantification of pro-inflammatory cytokines (interleukin 1b, 6 and 8), cell-free DNA and lipopolysaccharide-binding protein was also performed. Results: HDL concentration was statistically lower in septic shock patients than in controls. At days 1 and 2, septic patients had significantly more large-sized HDL than control patients. Patients recovered a normal lipid profile at day 7. Conclusions: Our results emphasize that HDL levels are dramatically decreased in the acute phase of septic shock and that there is a shift toward large HDL particles, which may reflect a major dysfunction of these lipoproteins. Further mechanistic studies are required to explore this shift observed during sepsis.

Background High-density lipoproteins exert pleiotropic effects including antiinflammatory, antiapoptotic, and lipopolysaccharide-neutralizing properties. The authors assessed the effects of reconstituted high-density lipoproteins (CSL-111) intravenous injection in different models of sepsis. Methods Ten-week-old C57BL/6 mice were subjected to sepsis by cecal ligation and puncture or intraperitoneal injection of Escherichia coli or Pseudomonas aeruginosa pneumonia. CSL-111 or saline solution was administrated 2 h after the sepsis. Primary outcome was survival. Secondary outcomes were plasma cell-free DNA and cytokine concentrations, histology, bacterial count, and biodistribution. Results Compared with saline, CSL-111 improved survival in cecal ligation and puncture and intraperitoneal models (13 of 16 [81%] survival rate vs. 6 of 16 [38%] in the cecal ligation and puncture model; P = 0.011; 4 of 10 [40%] vs. 0 of 10 [0%] in the intraperitoneal model; P = 0.011). Cell-free DNA concentration was lower in CSL-111 relative to saline groups (68 [24 to 123] pg/ml vs. 351 [333 to 683] pg/ml; P < 0.001). Mice injected with CSL-111 presented a decreased bacterial count at 24 h after the cecal ligation and puncture model both in plasma (200 [28 to 2,302] vs. 2,500 [953 to 3,636] colony-forming unit/ml; P = 0.021) and in the liver (1,359 [360 to 1,648] vs. 1,808 [1,464 to 2,720] colony-forming unit/ml; P = 0.031). In the pneumonia model, fewer bacteria accumulated in liver and lung of the CSL-111 group. CSL-111–injected mice had also less lung inflammation versus saline mice (CD68+ to total cells ratio: saline, 0.24 [0.22 to 0.27]; CSL-111, 0.07 [0.01 to 0.09]; P < 0.01). In all models, no difference was found for cytokine concentration. 111Indium bacterial labeling underlined a potential hepatic bacterial clearance possibly promoted by high-density lipoprotein uptake. Conclusions CSL-111 infusion improved survival in different experimental mouse models of sepsis. It reduced inflammation in both plasma and organs and decreased bacterial count. These results emphasized the key role for high-density lipoproteins in endothelial and organ protection, but also in lipopolysaccharide/bacteria clearance. This suggests an opportunity to explore the therapeutic potential of high-density lipoproteins in septic conditions. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New