LPS-induced release of IL-1 beta, IL-1Ra, IL-6, and TNF-alpha in whole blood from patients with familial hypercholesterolemia: no effect of cholesterol-lowering treatment

• Published in: Journal of interferon & cytokine research Vol. 26; no. 2; p. 101
• Main Authors: de Bont, Natasja, Netea, Mihai G, Rovers, Chantal, Smilde, Tineke, Hijmans, Anneke, Demacker, Pierre N M, van der Meer, Jos W M, Stalenhoef, Anton F H
• Format: Journal Article
• Language: English
• Published: United States 01-02-2006
• Subjects: Adult; Anticholesteremic Agents - pharmacology; Atorvastatin Calcium; Female; Genetic Carrier Screening; Heptanoic Acids - pharmacology; Humans; Hyperlipoproteinemia Type II - blood; Hyperlipoproteinemia Type II - drug therapy; Hyperlipoproteinemia Type II - genetics; Interleukin 1 Receptor Antagonist Protein - blood; Interleukin 1 Receptor Antagonist Protein - genetics; Interleukin 1 Receptor Antagonist Protein - secretion; Interleukin-1beta - blood; Interleukin-1beta - genetics; Interleukin-1beta - secretion; Interleukin-6 - blood; Interleukin-6 - genetics; Interleukin-6 - secretion; Lipopolysaccharides - pharmacology; Male; Middle Aged; Pyrroles - pharmacology; Simvastatin - pharmacology; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - secretion
• ISSN: 1079-9907
• DOI: 10.1089/jir.2006.26.101

Proinflammatory cytokines, such as interleukin-1beta (IL-1beta), IL-6, and tumor necrosis factor-alpha (TNF-alpha), 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-1beta, IL-6, TNF-alpha, 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-1beta, IL-6, and TNF-alpha 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.