interleukin-8 and Hypercholesterolemia

To assess whether antioxidant, anti-inflammatory and other cardio-protective effects attributed to cocoa are achieved when regularly consuming moderate amounts of a flavanol-rich soluble cocoa product, a non-randomized, controlled, crossover, free-living study was carried out in healthy (n = 24; 25.9 ± 5.6 years) and moderately hypercholesterolemic (200-240 mg dL(-1); n = 20; 30.0 ± 10.3 years) volunteers. Participants consumed two servings per day (7.5 g per serving) of a soluble cocoa product (providing 45.3 mg flavanols per day) in milk, which was compared with consuming only milk during a 4 week period. The effects on systolic and diastolic blood pressure and heart rate were determined, as well as on serum lipid and lipoprotein profiles, interleukins (IL)-1β, IL-6, IL-8, IL-10, tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), vascular (VCAM-1) and intercellular cell adhesion molecules (ICAM-1), serum malondialdehyde (MDA), carbonyl groups (CG), ferric reducing/antioxidant power (FRAP), oxygen radical absorbance capacity (ORAC), and free radical scavenging capacity (ABTS). During the study, the volunteers' diets and physical activity were also evaluated, as well as any changes in weight, skin folds, circumferences and related anthropometric parameters. Cocoa and certain polyphenol-rich fruits and vegetables and their derivatives were restricted. After consuming the cocoa product positive effects were observed such as an increase in serum HDL-C (p < 0.001) and dietary fiber intake (p = 0.050), whereas IL-10 decreased (p = 0.022). Other cardiovascular-related biomarkers and anthropometric parameters were unaffected. We have therefore concluded that regular consumption of this cocoa product in a Spanish-Mediterranean diet may protect against cardiovascular disease in healthy and hypercholesterolemic subjects without producing any weight gain or other anthropometric changes.

Topics: Adolescent; Adult; Anthropometry; Blood Pressure; Cacao; Cholesterol, HDL; Female; Flavonols; Heart Rate; Humans; Hypercholesterolemia; Interleukin-10; Interleukin-6; Interleukin-8; Male; Middle Aged; Tumor Necrosis Factor-alpha; Vascular Cell Adhesion Molecule-1; Young Adult

Statins are potent lipid-lowering drugs but anti-inflammatory effects have also been suggested. Our aim was to investigate the effects of simvastatin on proinflammatory cytokines and matrix metalloproteinases (MMPs). Eighty hypercholesterolemic men were randomized to simvastatin 40 mg or placebo for 6 weeks. Simvastatin treatment significantly reduced C-reactive protein (CRP) levels while interleukin (IL)-6 levels remained unchanged. The ex vivo release of IL-1β and IL-6 was not altered by simvastatin, whereas the release of TNF-α and IL-8 increased after 6 weeks of simvastatin treatment. Similarly, the circulating levels of MMP-3 and TIMP-1 remained unaffected by simvastatin while MMP-9 increased. However, none of the effects except for the CRP reduction within the simvastatin group reached statistical significance when compared to the placebo group. Our findings are in contrast to previous in vitro and animal data and question the in vivo relevance of some of the pleiotropic effects of simvastatin.

Topics: Adult; Anticholesteremic Agents; C-Reactive Protein; Cholesterol; Cytokines; Humans; Hypercholesterolemia; Interleukin-1beta; Interleukin-6; Interleukin-8; Male; Matrix Metalloproteinases; Middle Aged; Simvastatin; Tissue Inhibitor of Metalloproteinase-1; Triglycerides; Tumor Necrosis Factor-alpha

We have earlier demonstrated that muesli enriched with oat beta-glucan effectively lowered serum LDL cholesterol. Addition of plant stanols further lowered LDL cholesterol. Besides these hypocholesterolemic effects, beta-glucan and plant stanol esters (PSE) may also affect inflammatory processes. Forty-two mildly hypercholesterolemic subjects randomly consumed for 4 wk (crossover design) control muesli (4.8 g control fiber), beta-glucan muesli (4.8 g oat beta-glucan), or combination muesli (4.8 g oat beta-glucan plus 1.4 g stanol as PSE). Changes in cytokine production (IL-6, IL-8, and TNF-alpha) of LPS-stimulated peripheral blood mononuclear cells (PBMC) and whole blood were evaluated, as well as changes in plasma high-sensitivity (hs)-CRP. Additionally, changes in expression profiles of 84 genes involved in atherosclerosis metabolism were assessed in isolated PBMC. IL-6, IL-8, and TNF-alpha production by PBMC and whole blood after LPS stimulation did not differ between the treatments. Also high-sensitivity C-reactive protein (hs-CRP) levels were similar. beta-Glucan consumption did not change gene expression, while only 3 genes (ADFP, CDH5, CSF2) out of the 84 genes from the atherosclerotic risk panel were differentially expressed (p < 0.05) after consumption of PSE. Consumption of beta-glucan with or without PSE did not influence inflammatory parameters in mildly hypercholesterolemic subjects.

Topics: Adult; Atherosclerosis; Avena; beta-Glucans; C-Reactive Protein; Cross-Over Studies; Dietary Fiber; Double-Blind Method; Female; Gene Expression; Genetic Predisposition to Disease; Humans; Hypercholesterolemia; Inflammation; Interleukin-1; Interleukin-8; Leukocytes, Mononuclear; Lipopolysaccharides; Male; Middle Aged; Sitosterols; Tumor Necrosis Factor-alpha

To explore the effect of compositie salviae dropping pill (CSDP) on hyperlipemia patients with phlegm and blood stasis syndrome.. Hyperlipemia patients were divided randomly into two groups. One group of 40 patients were treated by CSDP, another group of 41 patients were treated by simvastatin. The TC, TG, HDL-C, LDL-C, ApoA and ApoB levels, ALT, r-GT, IL-6, MDA level and SOD activity were determined before and after being treated.. After 3 months treatment, the TC, TG and LDL-C levels were obviously decreased in two groups (P <0.01, P < 0.05), there is no significant difference between the effective rate of two groups. The ALT, r-GT, IL-8 and MDA levels of treatment group were obviously decreased (P < 0.01, P < 0.05), while the ApoA level and SOD activity increased obviously in those patients (P <0.05, P <0.01, respectively). However, the ALT, r-GT, IL-6, MDA, HDL-C, ApoA level and SOD activity had no significant difference after treatment in control group.. Our study suggest that CSDP have the function of falling serum lipid level without damaging liver function, its function of protecting liver function might related to its function of improving of anti-oxidation and decreasing of inflammation, the mechanism of CSDP disparting and removing phlem and blood stasis in the processes lipid metabolism need to be studied further.

Topics: Adult; Alanine Transaminase; Camphanes; Drug Combinations; Drugs, Chinese Herbal; Female; gamma-Glutamyltransferase; Humans; Hypercholesterolemia; Hypertriglyceridemia; Interleukin-8; Male; Middle Aged; Panax notoginseng; Phytotherapy; Plants, Medicinal; Salvia miltiorrhiza; Superoxide Dismutase

Topics: Adult; Cholesterol, HDL; Female; Graft Rejection; Humans; Hypercholesterolemia; Interleukin-8; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged

Foods incorporating plant sterols (PS) consistently decrease serum low-density lipoprotein cholesterol (LDL-C), although results vary depending on the PS form and food matrix. The objective was to study the effect of a novel triglyceride-recrystallized phystosterol (TRP) incorporated into fat-free milk on markers of cardiovascular risk compared to unmodified free sterols alone in the same fat-free milk.. Hypercholesterolemic men and women (n = 13 males/7 females; 56 ± 10 years; body mass index 27.3 ± 5.9 kg/m(2)) participated in 3 sequential 4-week phases of 480 mL milk consumption. During phase 1 (control) all subjects consumed 2% milk containing no PS, followed by phase 2 with fat-free milk containing free PS (2 g/d fPS) and phase 3 with fat-free milk with TRP (2 g/d). After each phase, determinations of lipoprotein cholesterol distribution, particle concentration via nuclear magnetic resonance (NMR), apolipoproteins, inflammatory markers, and fat-soluble dietary antioxidants were made.. Body mass, body composition, dietary energy and macronutrients, and physical activity were unaffected throughout the study. Compared to the control 2% milk, LDL-C was significantly (p < 0.05) decreased by fPS (-9.1%) and was further decreased by TRP (-15.4%); reductions with TRP were significantly greater. Total LDL particle concentration was decreased to a greater extent after TRP (-8.8%) than fPS (-4.8%; p < 0.05). Only TRP significantly decreased serum levels of apolipoprotein B (apoB; -6%), interleukin-8 (IL-8; -11%) and monocyte chemotactic protein-1 (MCP-1; -19%). Plasma α- and γ-tocopherols and carotenoids, normalized to cholesterol, remained unchanged throughout the study with the exception that β-carotene was lowered by 18%.. In summary, TRP in fat-free milk may provide cardiovascular benefits beyond that of fPS by inducing more substantial decreases in LDL cholesterol and particle concentration, associated with declines in markers of vascular inflammation.

Topics: Adult; Aged; Animals; Apolipoproteins B; Cardiovascular Diseases; Carotenoids; Chemokine CCL2; Cholesterol, LDL; Dietary Fats; Female; Food Handling; Humans; Hypercholesterolemia; Interleukin-8; Male; Middle Aged; Milk; Phytosterols; Risk Factors; Tocopherols; Triglycerides

The contribution of metabolic factors to the severity of liver disease is not completely understood. In this study, apolipoprotein E-deficient (ApoE-/-) mice were evaluated to define potential effects of hypercholesterolemia on the severity of carbon tetrachloride (CCl4)-induced liver injury. Under baseline conditions, hypercholesterolemic ApoE-/- mice showed increased hepatic oxidative stress (SOD activity/4-hydroxy-2-nonenal immunostaining) and higher hepatic TGF-beta1, MCP-1, and TIMP-1 expression than wild-type control mice. After CCl4 challenge, ApoE-/- mice exhibited exacerbated steatosis (Oil Red O staining), necroinflammation (hematoxylin-eosin staining), macrophage infiltration (F4/80 immunohistochemistry), and fibrosis (Sirius red staining and alpha-smooth muscle actin immunohistochemistry) and more severe liver injury [alanine aminotransferase (ALT) and aspartate aminotransferase] than wild-type controls. Direct correlations were identified between serum cholesterol and hepatic steatosis, fibrosis, and ALT levels. These changes did not reflect the usual progression of the disease in ApoE-/- mice, since exacerbated liver injury was not present in untreated age-paired ApoE-/- mice. Moreover, hepatic cytochrome P-450 expression was unchanged in ApoE-/- mice. To explore potential mechanisms, cell types relevant to liver pathophysiology were exposed to selected cholesterol-oxidized products. Incubation of hepatocytes with a mixture of oxysterols representative of those detected by GC-MS in livers from ApoE-/- mice resulted in a concentration-dependent increase in total lipoperoxides and SOD activity. In hepatic stellate cells, oxysterols increased IL-8 secretion through a NF-kappaB-independent mechanism and upregulated TIMP-1 expression. In macrophages, oxysterols increased TGF-beta1 secretion and MCP-1 expression in a concentration-dependent manner. Oxysterols did not compromise cell viability. Taken together, these findings demonstrate that hypercholesterolemic mice are sensitized to liver injury and that cholesterol-derived products (i.e., oxysterols) are able to induce proinflammatory and profibrogenic mechanisms in liver cells.

Topics: Animals; Apolipoproteins E; Carbon Tetrachloride; Chemical and Drug Induced Liver Injury; Chemokine CCL2; Cholesterol; Genetic Predisposition to Disease; Hepatic Stellate Cells; Hydroxycholesterols; Hypercholesterolemia; Interleukin-8; Liver Diseases; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; NF-kappa B; Oxidative Stress; Superoxide Dismutase; Transforming Growth Factor beta1

Recently, there has been an increasing in the impact of oral health on atherosclerosis and subsequent cardiovascular disease. The aim of this study is to investigate the association between chronic periodontitis and cardiovascular risk markers.. Forty patients with periodontitis and 40 healthy gender-, body mass index-, and age-matched individuals were compared by measuring total cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides, levels of cytokines, antibodies against oxidized low-density lipoprotein, thiobarbituric acid reactive substances, total and differential white blood cell counts, and the non-linear index of refraction.. The levels of triglycerides and high-density lipoprotein in periodontitis patients were significantly higher and lower, respectively (P = 0.002 and P = 0.0126), compared to controls. Total cholesterol, low-density lipoprotein, and lipid peroxide levels were the same in both groups (P = 0.2943, P = 0.1284, and P = 0.067, respectively). Interleukin (IL)-6 and -8, antibodies against oxidized low-density lipoprotein, and leukocyte and neutrophil counts were significantly higher in periodontitis patients (P <0.05). The value of the non-linear index of refraction of low-density lipoprotein solutions was higher in the controls (P = 0.015) compared to individuals with periodontitis.. Our results confirmed and further strengthened the suggested association between coronary artery disease and periodontitis.

Topics: Adult; Age Factors; Antibodies; Body Mass Index; Case-Control Studies; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Chronic Periodontitis; Coronary Artery Disease; Female; Humans; Hypercholesterolemia; Hypertriglyceridemia; Interleukin-6; Interleukin-8; Leukocyte Count; Lipid Peroxides; Lipoproteins, LDL; Male; Middle Aged; Neutrophils; Oxidation-Reduction; Refractometry; Risk Factors; Sex Factors; Thiobarbituric Acid Reactive Substances

Statins are known to have pleiotropic effects. We examined the effect and mechanism of simvastatin therapy on EPC differentiation and pro-angiogenic cytokines in patients with hypercholesterolemia.. Twenty-two hypercholesterolemia patients without any other modifiable cardiovascular risk factors or history of previous lipid-lowering therapy were given simvastatin 20 mg/day for 4 weeks. Blood were drawn pre- and post-therapy. The in vitro effects of simvastatin were studied in a separate set of experiments.. Simvastatin treatment significantly increased the number of DiI-acLDL, UEA-1 lectin double-positive EPCs and facilitated its appearance. By FACS analysis of freshly isolated PBMNCs, KDR (+) cells increased after simvastatin treatment while there were no differences in CD34, AC133, and VE-cadherin. Also, serum concentration of IL-8 was markedly increased, while VEGF was only slightly increased. In vitro, PBMNCs co-cultured with simvastatin showed increased cluster formation at day 7, and simvastatin facilitated the appearance and networking of EPCs compared with vehicle. Simvastatin-co-cultured PBMNCs showed significantly increased KDR (+) cells, in contrast to CD34, CD31, and VE-Cadherin (+) cells. In response to simvastatin, IL-8 was mainly increased in monocyte culture supernatants while VEGF increased in smooth muscle cell culture supernatants. These cytokines were associated with increased EPC migratory function. The increase in IL-8 secretion from monocytes by statin treatment was associated with phosphorylation and inactivation of GSK3beta, which was reversed by constitutive activation of GSK-3beta.. Simvastatin enhances endothelial differentiation of peripheral blood mononuclear cells in patients with hypercholesterolemia and increases pro-angiogenic cytokine IL-8 secretion from monocytes. Our results may explain the pro-angiogenic effects associated with statin therapy and offer further evidence of statin pleiotropism.

Topics: Animals; Cell Differentiation; Cells, Cultured; Endothelial Cells; Humans; Hypercholesterolemia; Interleukin-8; Mice; Monocytes; Simvastatin; Vascular Endothelial Growth Factor A

A number of studies have shown that statins decrease morbidity and mortality in patients with cardiovascular diseases. The anti-inflammatory effects of statins have recently been implicated in the clinical benefit that can be obtained in the treatment of atherosclerosis. Little is known about the mechanisms by which statins counteract inflammation.. In this study, we asked whether simvastatin can influence in vitro and in vivo production of the proinflammatory cytokines interleukin (IL)-6, IL-8, and monocyte chemoattractant protein-1. A total of 107 hypercholesterolemic patients were treated with simvastatin. As measured by ELISA, serum levels of cytokines significantly decreased after 6 weeks of treatment (P<0.05). Furthermore, simvastatin decreased the expression of IL-6, IL-8, and monocyte chemoattractant protein-1 mRNA in peripheral blood mononuclear cells. Similar results were obtained in vitro by using cultured human umbilical vein endothelial cells and peripheral blood mononuclear cells from healthy normolipemic donors. Exposure to simvastatin, atorvastatin, or cerivastatin caused downregulation of the expression of cytokine mRNA in a time- and dose-dependent manner. Furthermore, all statins tested were able to reduce the concentrations of cytokines in cellular and extracellular fractions of human umbilical vein endothelial cells (P<0.05).. Our data show that simvastatin is anti-inflammatory through the downregulation of cytokines in the endothelium and leukocytes. These effects may explain some of the clinical benefits of these drugs in the treatment of atherosclerosis.

Topics: Aged; Anticholesteremic Agents; Cells, Cultured; Chemokine CCL2; Down-Regulation; Endothelium, Vascular; Female; Humans; Hypercholesterolemia; Interleukin-6; Interleukin-8; Leukocytes; Lipid Metabolism; Lipids; Male; Monocytes; RNA, Messenger; Simvastatin; Umbilical Veins

Beneficial effects of statins in preventing cardiovascular events may depend, at least in part, on their anti-inflammatory action. The aim of the study was to assess the influence of simvastatin and aspirin on serum levels of C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in hypercholesterolemic subjects.. In 33 asymptomatic men with total cholesterol (TC) >6.5 mmol l(-1) and in 25 men with coronary heart disease and borderline-high cholesterol levels (between 5.2 and 6.5 mmol l(-1)) chronically treated with low-dose aspirin (75 mg/d), serum levels of CRP, TNF-alpha, IL-6, and IL-8 were determined before and after a 3-month simvastatin therapy (20-40 mg daily). In the former group, these markers of inflammation were also measured before and after a 2-week treatment with aspirin (300 mg/d), implemented prior to and in combination with simvastatin. A distinct reduction of CRP and TNF-alpha was found in both groups; IL-6 levels were decreased only in subjects with marked hypercholesterolemia. Aspirin had no effect on the anti-inflammatory action of simvastatin.. In men with hypercholesterolemia simvastatin treatment lowers serum levels of CRP and proinflammatory cytokines. Low-dose aspirin does not add to the anti-inflammatory action of simvastatin.

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Anticholesteremic Agents; Aspirin; C-Reactive Protein; Humans; Hypercholesterolemia; Inflammation; Interleukin-6; Interleukin-8; Male; Middle Aged; Simvastatin; Tumor Necrosis Factor-alpha

Topics: Antibodies, Monoclonal; Arteriosclerosis; Biomarkers; Blood Vessels; Cell Division; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Interleukin-8; Mevalonic Acid; Muscle, Smooth, Vascular; Up-Regulation

Topics: Aged; Aged, 80 and over; Anticholesteremic Agents; Cholesterol; Cytokines; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Inflammation Mediators; Interleukin-1; Interleukin-6; Interleukin-8; Male; Middle Aged; Pravastatin; Receptors, Interleukin-1; Tumor Necrosis Factor-alpha

Interleukin-8 is a cytokine produced by mononuclear cells that is involved in polymorphonuclear neutrophil leukocyte (PMN) recruitment and activation. Several studies have previously demonstrated a leukocyte activation during hypercholesterolemia and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have been found to play a role in the prevention of atherothrombotic disease. The purpose of this study was to determine interleukin-8 (IL-8) mRNA expression and ex vivo production from peripheral blood mononuclear cells (PBMCs) and IL-8-dependent PMN activation of hypercholesterolemic (HC) patients with respect to normocholesterolemic (NC) subjects. Using Northern blot analysis, we found a four- and threefold increase in the amount of IL-8 transcript in PBMC from HC patients, in unstimulated and LPS stimulated cultures, respectively. A specific immunoassay showed a correspondingly significant increase of IL-8 immunoactivity in the conditioned medium of PBMC from HC subjects as compared with controls (unstimulated PBMC: 15 +/- 4 vs. 4.2 +/- 3 ng/ml; P < 0.0001; LPS stimulated PBMC: 65.3 +/- 8 vs. 36.6 +/- 9 ng/ml; P < 0.0001). PMN of HC patients stimulated with IL-8 showed a reduced elastase release with respect to NC subjects before physiological granule release after f-Met-Leu-Phe (fMLP) treatment. These results indicate an upregulation of the IL-8 system in dyslipidemic patients and provide evidence for ongoing in vivo IL-8-dependent PMN activation during hypercholesterolemia.

Topics: Adult; Blotting, Northern; Cells, Cultured; Cholesterol; Female; Gene Expression; Humans; Hypercholesterolemia; Interleukin-8; Leukocyte Elastase; Leukocytes, Mononuclear; Male; Middle Aged; N-Formylmethionine Leucyl-Phenylalanine; Neutrophil Activation; Neutrophils; RNA, Messenger