Related Experiment Video
Updated: Aug 16, 2026
On-Chip Endothelial Inflammatory Phenotyping
Published on: July 21, 2012
High-density lipoproteins attenuate interleukin-6 production in endothelial cells exposed to pro-inflammatory stimuli
Monica Gomaraschi1, Nicoletta Basilico, Francesca Sisto
1Center E. Grossi Paoletti, Department of Pharmacological Sciences, Via Balzaretti 9, 20133 Milano, Italy.
Insights
High-density lipoproteins (HDL) reduce interleukin-6 (IL-6) production in endothelial cells and lower plasma IL-6 levels. Lower HDL cholesterol is linked to higher IL-6, suggesting HDL’s protective role in inflammation.
Area of Science:
- Cardiovascular Science
- Immunology
- Molecular Biology
Background:
- Endothelial dysfunction is a key factor in atherosclerosis.
- Interleukin-6 (IL-6) is a pro-inflammatory cytokine implicated in cardiovascular disease.
- High-density lipoproteins (HDL) are known for their protective cardiovascular effects.
Purpose of the Study:
- To investigate HDL's ability to attenuate endothelial dysfunction.
- To assess HDL's effect on cytokine-induced IL-6 production in endothelial cells.
- To measure plasma IL-6 levels in individuals with varying HDL-cholesterol levels.
Main Methods:
- Assessed TNFalpha-induced IL-6 production in cultured endothelial cells treated with human plasma HDL.
- Measured IL-6 mRNA levels and investigated the role of p38 MAP kinase.
- Quantified plasma IL-6 concentrations in healthy individuals with low, average, and high HDL-cholesterol.
Main Results:
- Human plasma HDL inhibited IL-6 production in a concentration-dependent manner.
- Reconstituted HDL with apoA-I and phosphatidylcholine mimicked this effect; lipid-free apoA-I or liposomes did not.
- Lower HDL-cholesterol levels were significantly associated with higher plasma IL-6 concentrations.
Conclusions:
- HDL attenuates IL-6 production by inhibiting p38 MAP kinase.
- HDL may mitigate the pro-atherogenic effects of inflammatory states by reducing IL-6.
- Lower HDL cholesterol is an independent predictor of elevated IL-6 levels.
Abstract:
The purpose of the present study was to investigate the ability of high-density lipoproteins (HDL) to attenuate endothelial dysfunction, by assessing down-regulation of cytokine-induced interleukin-6 (IL-6) production in cultured endothelial cells, and measuring plasma IL-6 levels in three groups of healthy individuals with low, average, or high plasma HDL-cholesterol. Human plasma HDL caused a concentration-dependent inhibition of TNFalpha-induced IL-6 production in human endothelial cells (by 58.5+/-1.5% at 2 mg of HDL-protein/ml). Reconstituted HDL made with apolipoprotein A-I (apoA-I) and phosphatidylcholine were as effective as plasma HDL, while lipid-free apoA-I or phosphatidylcholine liposomes had no effect. HDL attenuated IL-6 mRNA levels, an effect which occurs through inhibition of p38 MAP kinase. The median plasma IL-6 concentration was significantly higher in subjects with low HDL-cholesterol (2.54 pg/ml) compared with those with average or high HDL-cholesterol (1.31 pg/ml and 1.47 pg/ml, respectively). When all subjects were considered together, a lower HDL-cholesterol was the strongest independent predictor of higher IL-6 (F=25.38, P<0.001). By inhibiting IL-6 production and lowering plasma IL-6 concentration, HDL may limit the pro-atherogenic effects of both acute and chronic inflammatory states, of which IL-6 is a key orchestrator.
Related Concept Videos
01:38Inflammation
01:24T Cell Types and Functions
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
01:28Inflammatory Response
Inflammation can be triggered by various stimuli, such as impact, abrasion, chemical irritation, infections, and extreme hot or cold temperatures. These can damage cells and connective tissue fibers,...