Relationship among IL-6, LDL cholesterol and lipid peroxidation

Abstract

Previous studies evidenced a significant reduction in serum cholesterol levels during an episode of acute inflammation. The aim of the present study was to verify the hypothesis of a regulatory role of cytokines through an in vitro model that simulates a situation of vascular inflammation and high levels of LDL or lipoperoxides. Human microvascular endothelial cells-1 were used in all experiments. The cells were exposed for 24 h to increasing doses of LDL, oxidized lipoprotein, and 8-isoprostane (in the absence or presence of SQ29.548, a TXA2 receptor antagonist). Moreover, LDL receptor and oxidized lipoprotein receptor expression analyzed after endothelial cells' incubation with increasing doses of interleukin-6. The ELISA test and quantitative real-time PCR were performed. Endothelial cells showed a significant increase in interleukin-6 medium levels associated with LDL, oxidized LDL and with the degree of oxidation (absence or presence of SQ29.548), while 8-isoprostane did not. Treatment of human microvascular endothelial cells-1 for 24 h with increasing doses of interleukin-6 significantly enhanced LDL receptor and oxidized lipoprotein receptor-1 mRNA expression. Our data suggest the presence of a compensatory mechanism. The induction of a significant increase of IL-6 does not seem to be caused by the presence of the biological activity of 8-isoprostane.

Exploring the Lipid Paradox Theory in Rheumatoid Arthritis: Associations of Low Circulating Low‐Density Lipoprotein Concentration With Subclinical Coronary Atherosclerosis

“…Mechanistically, it is unclear what factor(s) may mediate the disconnect between circulating LDL concentration and atherogenesis in this subgroup of RA patients. Inflammatory cytokines associated with RA, such as interleukin-6, up-regulate LDL receptors and scavenger receptors for modified LDL particles on hepatocytes and macrophages, potentially leading to lower circulating LDL levels while also being proatherogenic (24,25). However, we did not observe an association of higher CRP levels or Disease Activity Scores with low LDL concentration, making these unlikely to be mediators of the associations we observed.…”

Circulating Ceramide: A New Cardiometabolic Biomarker in Patients With Comorbid Acute Coronary Syndrome and Type 2 Diabetes Mellitus

“…They confirmed that interleukin-6 (IL-6) enhances LDL receptor activity in the liver during the inflammatory response, subsequently increasing the elimination of circulating LDL-C. Thus, the acute inflammatory response in patients with ACS may increase the clearance of LDL-C, leading to a decrease in the circulating LDL-C concentration and affecting the accuracy of risk prediction (Lubrano et al, 2015). Determination of ceramide levels using a high-throughput methodology such as LC-MS/MS is efficient and convenient.…”

Modulation of Nitric Oxide Synthases by Oxidized LDLs: Role in Vascular Inflammation and Atherosclerosis Development

“…Overall, these mechanisms represent the basis for the correlation between dysregulation of eNOS/iNOS enzymes induced by high levels of oxLDLs internalization, LOX-1 overexpression, and inflammation of vascular tissues, leading to atherosclerosis development and progression (Figure 1). In accordance with this hypothesis, it has been demonstrated that the increased expression of LOX-1 represents a consequence of increasing concentrations of interleukin 6 (IL-6) indicative of the development of inflammation in microvasculature [22].…”