LPS-Induced Release of IL-1 β,IL-1Ra,IL-6,and TNF- α in Whole Blood from Patients with Familial Hypercholesterolemia: No Effect of Cholesterol-Lowering Treatment

Abstract

Proinflammatory cytokines, such as interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α), are suggested to have an important role in the process of atherosclerosis. Patients with heterozygous familial hypercholesterolemia(FH) have a marked elevation in the plasma level of low-density lipoproteins (LDL), and they show early development of atherosclerosis. The aim of the present study was to test with a whole blood culture system if hyperlipoproteinemia is associated with increased cytokine production capacity in these patients and if treatment with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors influences this production capacity of blood cells, at both the protein and mRNA levels. The capacity of blood cells in a whole blood culture to produce IL-1β, IL-6, TNF-α, IL-12, IL-18, and IL-1 receptor antagonist (IL-1Ra) in response to lipopolysaccharide (LPS) appeared to be similar for heterozygous FH patients and healthy volunteers. Furthermore, the capacity to produce IL-1β, IL-6, and TNF-α in response to LPS was not modified by cholesterol synthesis inhibitors at the level of mRNA expression or at the level of release. On the other hand, the release of IL-1Ra was significantly increased after treatment with HMG-CoA reductase inhibitors, although only at the protein level. This suggests a possible beneficial anti-inflammatory role for this therapy.