LPS-induced cytokine production and expression of LPS-receptors by peripheral blood mononuclear cells of patients with familial hypercholesterolemia and the effect of HMG-CoA reductase inhibitors

• Published in: Atherosclerosis 1998-07, Vol.139 (1), p.147-152
• Main Authors: de Bont, Natasja, Netea, Mihai G, Rovers, Chantal, Smilde, Tineke, Demacker, Pierre N.M, van der Meer, Jos W.M, Stalenhoef, Anton F.H
• Format: Article
• Language: English
• Subjects: Animals; Anticholesteremic Agents - therapeutic use; Atorvastatin; Biological and medical sciences; CD11 Antigens - metabolism; Cohort Studies; Cytokines; Cytokines - blood; Disorders of blood lipids. Hyperlipoproteinemia; Double-Blind Method; Familial hypercholesterolemia; Heptanoic Acids - therapeutic use; Heterozygote; HMG-CoA reductase inhibitors; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use; Hyperlipoproteinemia Type II - blood; Hyperlipoproteinemia Type II - drug therapy; Lipids - blood; Lipopolysaccharide Receptors - metabolism; Lipopolysaccharides - pharmacology; LPS-receptors; Medical sciences; Metabolic diseases; Mice; Monocytes - drug effects; Monocytes - metabolism; Pyrroles - therapeutic use; Simvastatin - therapeutic use
• ISSN: 0021-9150; 1879-1484
• DOI: 10.1016/S0021-9150(98)00074-4

Inflammatory processes play an important role in atherogenesis, and proinflammatory cytokines such as interleukin-1 β (IL-1 β), IL-6, and tumour necrosis factor α (TNF α) are thought to be mediators in this phenomenon. We have previously established that peritoneal macrophages of LDL-receptor knock-out mice, which are hypercholesterolemic and are prone to atherosclerosis, have an increased LPS-induced cytokine production capacity, ex vivo. The aim of the present study was to investigate whether the process leading to atherosclerosis in patients with familial hypercholesterolemia (FH) is associated with increased cytokine production capacity of peripheral blood mononuclear cells (PBMC) and/or increased expression of adhesion molecules on monocytes and lymphocytes. Furthermore, we assessed the effect of cholesterol lowering on the production capacity of PBMC, as these drugs are beneficial with regard to cardiovascular diseases. LPS-induced IL-1 β and TNF α production by PBMCs of 21 heterozygous FH patients appeared to be similar to the production by PBMCs of 21 healthy volunteers. In addition, expression of the LPS-receptors CD14 and β2-integrins in nine patients and controls did not differ either. In a second series of experiments, HMG-CoA synthesis inhibitors were ineffective to change the LPS-induced production by PBMC of IL-1 α, IL-1 β, IL-1 receptor antagonist (IL-1ra), IL-6, and TNF α. In conclusion, cytokine production capacity of blood cells or the expression of LPS-receptors on circulating PBMC do not deviate in subjects with FH and also do not change as a result of treatment with cholesterol synthesis inhibitors.