interleukin-8 and Coronary-Disease

Physical activity is effective in primary and secondary prevention of cardiovascular disease. In this study, we tested the hypothesis that exercise training improves glucose and lipid metabolism, the inflammatory/anti-inflammatory balance, and the outcome of elective percutaneous coronary intervention (PCI) in patients with stable coronary disease.. Sixty-two patients scheduled to undergo PCI for stable angina were randomized to intensive physical activity (n=33) consisting of home-based exercise on a bicycle ergometer or maintain their usual sedentary life (n=29). The training program started 2 months before PCI and terminated 6 months afterwards. Clinical examination, blood sampling (fasting glucose, glycated hemoglobin, lipid profile, apolipoprotein B, apolipoprotein A1, C-reactive protein, serum amyloid A, interleukin-6, interleukin-8, and interleukin-10), and maximal exercise tests were performed at inclusion, 1 week before PCI, and 3 and 6 months afterwards.. Fifty-six patients [28 per group, 45 men, mean age 63 (SD 7.8) years] completed the follow-up. According to self-reports, patients in the training group exercised more often and longer [4.9 (SD 1.1) vs. 0.6 (SD 1.3) days/week, 36 (SD 12) vs. 15 (SD 31) min/session, P<0.0001]. Improvement in maximal exercise capacity was significantly better in the training group [27 (SD 27) vs. 9 (SD 27) W, P=0.02]. Exercise had no significant effects on glucose and lipid metabolism, plasma cytokines, or acute-phase reactants.. A home-based training program significantly improved maximal exercise capacity but did not affect glucose or lipid metabolism or markers of inflammation.

Topics: Aged; Angina Pectoris; Angioplasty, Balloon, Coronary; Apolipoprotein A-I; Apolipoproteins B; Biomarkers; Blood Glucose; C-Reactive Protein; Coronary Disease; Energy Metabolism; Exercise Therapy; Exercise Tolerance; Female; Glycated Hemoglobin; Home Care Services; Humans; Inflammation Mediators; Interleukin-10; Interleukin-6; Interleukin-8; Lipids; Male; Middle Aged; Serum Amyloid A Protein; Sweden; Time Factors; Treatment Outcome

Intensive statin therapy has been shown to improve prognosis in patients with coronary heart disease (CHD). It is unknown whether such benefit is mediated through the reduction of atherosclerotic plaque burden.. To examine the efficacy of high-dose atorvastatin in the reduction of carotid intimal-medial thickness (IMT) and inflammatory markers in patients with CHD.. Randomised trial.. Single centre.. 112 patients with angiographic evidence of CHD.. A high dose (80 mg daily) or low dose (10 mg daily) of atorvastatin was given for 26 weeks.. Carotid IMT, C-reactive protein (CRP) and proinflammatory cytokine levels were assessed before and after therapy.. The carotid IMT was reduced significantly in the high-dose group (left: mean (SD), 1.24 (0.48) vs 1.15 (0.35) mm, p = 0.02; right: 1.12 (0.41) vs 1.01 (0.26) mm, p = 0.01), but was unchanged in the low-dose group (left: 1.25 (0.55) vs 1.20 (0.51) mm, p = NS; right: 1.18 (0.54) vs 1.15 (0.41) mm, p = NS). The CRP levels were reduced only in the high-dose group (from 3.92 (6.59) to 1.35 (1.83) mg/l, p = 0.01), but not in the low-dose group (from 2.25 (1.84) to 3.36 (6.15) mg/l, p = NS). A modest correlation was observed between the changes in carotid IMT and CRP (r = 0.21, p = 0.03).. In patients with CHD, intensive atorvastatin therapy results in regression of carotid atherosclerotic disease, which is associated with reduction in CRP levels. On the other hand, a low-dose regimen only prevents progression of the disease.

Topics: Aged; Atorvastatin; C-Reactive Protein; Carotid Arteries; Carotid Artery Diseases; Coronary Disease; Double-Blind Method; Drug Administration Schedule; Female; Follow-Up Studies; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Interleukin-18; Interleukin-6; Interleukin-8; Lipids; Male; Middle Aged; Pyrroles; Tumor Necrosis Factor-alpha; Tunica Intima; Tunica Media

To measure the serum level of secretory type II phospholipase A2 (sPLA2) in patients with coronary heart disease and investigate the possible relationship with IL-8 and LPA.. A total of 110 patients with acute coronary syndrome (ACS), 63 patients with stable coronary heart disease (SCHD) group and 89 non-CHD control patients were studied. Serum levels of sPLA2, IL-8, LPA and hs-CRP were measured and the correlation among these parameters was observed.. The levels of serum sPLA2 [(68 +/- 17) U/ml], IL-8 [(182 +/- 80) pg/ml] and LPA [(2.85 +/- 0.36) micromol/L] were significantly higher in CHD patients than those in controls [sPLA2: (55 +/- 12) U/ml; IL-8: (119 +/- 33) pg/ml; LPA: (2.34 +/- 0.36) micromol/L, all P < 0.01], and sPLA2 and IL-8 were also significantly higher in ACS patients [sPLA2: (71 +/- 18) U/ml; IL-8: (195 +/- 78) pg/ml] than those in SCHD patients [sPLA2: (63 +/- 12) U/ml; IL-8: (159 +/- 79) pg/ml, both P < 0.01]. Serum sPLA2 level was positively correlated with hs-CRP, IL-8 and LPA (r = 0.203, P = 0.007; r = 0.658, P < 0.01; r = 0.231, P = 0.005, respectively). The relative risk of having CHD is 6.248 (P < 0.01) with the sPLA2 level above 63.75 U/ml.. Elevated serum sPLA2 level is a risk factor for CHD.

Topics: Adult; Aged; Aged, 80 and over; C-Reactive Protein; Coronary Angiography; Coronary Disease; Female; Group II Phospholipases A2; Humans; Interleukin-8; Lysophospholipids; Male; Middle Aged; Phospholipases A; Phospholipases A2

Aprotinin is a broad-spectrum serine protease inhibitor that has been shown to attenuate the systemic inflammatory response in patients undergoing cardiac surgery with cardiopulmonary bypass. Although epsilon-aminocaproic acid is similar to aprotinin in its ability to inhibit excessive fibrinolysis (ie, plasmin activity and D-dimer formation), its ability to influence proinflammatory cytokine production remains unclear. This study was designed to compare the effects of epsilon-aminocaproic acid and aprotinin on plasma levels of interleukin-6 and interleukin-8 during and after cardiopulmonary bypass.. Sixty patients were randomized in a double-blind fashion to receive epsilon-aminocaproic acid, aprotinin, or saline (placebo) in similar dosing regimens (loading dose, pump prime, and infusion). Arterial blood samples were collected before, during, and after cardiopulmonary bypass, and plasma levels of D-dimer, interleukin-6, and interleukin-8 were measured. Data were analyzed using repeated measures analysis of variance.. Both epsilon-aminocaproic acid and aprotinin administration resulted in significant (P <.05) reductions in D-dimer and interleukin-8 levels compared with saline. These reductions in D-dimer and interleukin-8 levels did not differ between the 2 drug-treated groups. The effect of these two antifibrinolytic agents on interleukin-6 was qualitatively similar to that noted with interleukin-8 but did not reach statistical significance.. When dosed in a similar manner, epsilon-aminocaproic acid seems to be as effective as aprotinin at reducing interleukin-6 and interleukin-8 levels in patients undergoing primary coronary artery bypass graft surgery. These data indicate that suppression of excessive plasmin activity or D-dimer formation or both may play an important role in the generation of proinflammatory cytokines during and after cardiopulmonary bypass.

Topics: Aged; Aminocaproic Acid; Antifibrinolytic Agents; Aprotinin; Cardiopulmonary Bypass; Coronary Artery Bypass; Coronary Disease; Cytokines; Double-Blind Method; Female; Fibrin Fibrinogen Degradation Products; Follow-Up Studies; Humans; Inflammation Mediators; Infusions, Intravenous; Interleukin-6; Interleukin-8; Intraoperative Complications; Male; Middle Aged; Postoperative Complications; Probability; Reference Values; Risk Assessment; Treatment Outcome

Cardiac surgery with cardiopulmonary bypass (CPB) results in vascular injury and tissue damage which involves leukocyte-endothelial interactions mediated by cytokines and adhesion molecules. This study was designed to demonstrate the effect of normothermic and hypothermic CPB to cytokine and soluble adhesion molecule levels in adults and to determine whether these levels correlate to the patients postoperative course.. In 25 patients after normothermic and in 25 patients after hypothermic coronary artery bypass grafting with cardiopulmonary bypass (CPB), blood samples for cytokine and soluble adhesion molecule analysis were taken preoperatively, 24, 36, 48 h, and 6 days postoperatively. Soluble adhesion molecules (sE-selectin, sICAM-1) were measured by ELISA and cytokines (TNF-alpha, IL-6, IL-8) by chemilumenscent-immunoassay. Clinical data were collected prospectively.. Postoperatively, adhesion molecule and cytokine levels were significantly elevated after CPB. Mean plasma levels of sICAM-1 was 2.4-fold higher after 6 days. Mean plasma concentration of sE-selectin peaked after 48 h with a 2-fold increase compared to normothermic conditions. In the hypothermia group sICAM-1, sE-selectin, IL-6, and IL-8 showed significantly higher levels (P<0.0057, P<0.0012, P<0.0419, P<0.0145) after 24 h compared to the normothermia group. No clinical differences were seen.. Adhesion molecules and cytokines are elevated after CPB. Patients after hypothermic CPB show significant higher sICAM-1, sE-selectin, IL-6, and IL-8 levels after 24 h compared to normothermic conditions. These results are mainly due to longer CPB and crossclamp times but do not alter the patient's postoperative course.

Topics: Adult; Aged; Analysis of Variance; Biomarkers; Body Temperature; Cardiopulmonary Bypass; Coronary Disease; Cytokines; Enzyme-Linked Immunosorbent Assay; Female; Heart Arrest, Induced; Humans; Hypothermia, Induced; Intercellular Adhesion Molecule-1; Interleukin-6; Interleukin-8; Male; Middle Aged; Postoperative Period; Prognosis; Prospective Studies; Radioimmunoassay; Sensitivity and Specificity; Statistics, Nonparametric; Tumor Necrosis Factor-alpha

The introduction of limited approaches to the heart and the avoidance of cardiopulmonary bypass (CPB) aim to reduce the invasiveness of CABG by decreasing the systemic release of inflammatory cytokines, such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-8, as well as the anti-inflammatory agent IL-10. This study compares the humoral immune response in patients undergoing CABG with standard, minimally invasive, and "off-pump" techniques.. Thirty patients were divided into 3 operative groups: full sternotomy approach plus CPB (group A); full sternotomy approach, off pump (group B); and limited left anterior thoracotomy, off pump (group C). Plasma levels of TNF-alpha receptors p55 and p75, IL 6, IL-8, and IL-10 were taken at baseline, during CPB, and at 4, 24, and 48 hours and 6 days after surgery. A significant increased release of activated complement factors C5a and C3d, IL-8, and IL-10 was observed in patients subjected to CPB (group A) during the initial period and for a short time after perfusion (P:<0.05). TNF-alpha receptors p55 and p75 showed a prolonged elevation (up to 48 hours) in the CPB group compared with the 2 off-pump groups. IL-6 showed no different release among the 3 surgical groups throughout the entire period. There was no significant difference in any parameter measured in relation to the type of operative approach.. There is an inflammatory, as well as an anti-inflammatory, response during CABG that is related to the general surgical trauma. The release of immune mediators is enhanced by the use of CPB during various perioperative and postoperative phases. The type of operative approach did not influence this immune response.

Topics: Aged; Antibody Formation; Cardiopulmonary Bypass; Complement C3d; Complement C5a; Coronary Artery Bypass; Coronary Disease; Female; Heart-Assist Devices; Humans; Interleukin-10; Interleukin-6; Interleukin-8; Intraoperative Period; Male; Middle Aged; Postoperative Complications; Protein Isoforms; Receptors, Tumor Necrosis Factor; Thoracotomy; Treatment Outcome

The inflammatory response to cardiopulmonary bypass is believed to play an important role in end organ dysfunction after open heart surgery and may be more profound after normothermic systemic perfusion. The aim of the present study was to investigate the effects of cardiopulmonary bypass temperature on the production of markers of inflammatory activity after coronary artery surgery.. Forty-five low risk patients undergoing elective coronary artery surgery were prospectively randomized into three groups: hypothermia (28 degrees C, n = 15), moderate hypothermia (32 degrees C, n = 15), and normothermia (37 degrees C, n = 15). All patients received cold antegrade crystalloid cardioplegia and topical myocardial cooling with saline at 4 degrees C. Serum samples were collected for the estimation of neutrophil elastase, interleukin 8, C3d, and IgG under ice preoperatively, 5 min after heparinisation, 30 min following start of CPB, at the end of CPB, 5 min after protamine administration, and 4, 12 and 24 h postoperatively.. Patients were similar with regard to preoperative and intraoperative characteristics (age, sex, severity of symptoms, number of grafts performed, aortic cross clamp time, cardiopulmonary bypass time). Neutrophil elastase concentration increased markedly as early as 30 min after the onset of cardiopulmonary bypass and peaked 5 min after protamine administration. Levels were not significantly different between the three groups. A similar finding was apparent for C3d release. Interleukin 8 concentrations also demonstrated a considerable increase related to cardiopulmonary bypass in all groups, but there was a significantly more rapid decline in interleukin 8 concentrations in the normothermic group in the postoperative period. Eluted IgG fraction showed a much earlier peak concentration than the other markers, occurring within 30 min of the start of cardiopulmonary bypass. Levels reached a plateau, before declining soon after the end of bypass and remained higher than preoperative values at 24 h. There was no difference between the three groups. The cumulative release of all markers was calculated from the concentration-time curves, and was not statistically different between groups.. Normothermic systemic perfusion was not shown to produce a more profound inflammatory response compared to hypothermic and moderately hypothermic cardiopulmonary bypass.

Topics: Aged; Cardiopulmonary Bypass; CD3 Complex; Chi-Square Distribution; Coronary Disease; Elective Surgical Procedures; Enzyme-Linked Immunosorbent Assay; Female; Follow-Up Studies; Humans; Hypothermia, Induced; Immunoglobulin G; Inflammation; Inflammation Mediators; Interleukin-8; Leukocyte Count; Leukocyte Elastase; Male; Middle Aged; Postoperative Care; Prospective Studies; Statistics, Nonparametric; Treatment Outcome

Topics: Adult; Aged; Angina, Unstable; Biomarkers; Coronary Disease; Creatine Kinase; Female; Humans; Interleukin-8; Male; Middle Aged; Myocardial Infarction; Myoglobin; Pilot Projects; Predictive Value of Tests

Brain-derived neurotrophic factor (BDNF) regulates the lipid metabolism, atherosclerosis plaque formation, and inflammatory process, while the study about its clinical role in coronary heart disease (CHD) is few. The present study intended to explore the expression of BDNF and its relationship with stenosis, inflammation, and adhesion molecules in CHD patients.. After serum samples were obtained from 207 CHD patients, BDNF, tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, IL-6, IL-8, IL-17A, vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) levels were determined using ELISA. Then, the BDNF level was also examined in 40 disease controls (DCs) and 40 healthy controls (HCs), separately.. BDNF was lower in CHD patients than in DCs and HCs (median (95% confidential interval) value: 5.6 (3.5-9.6) ng/mL vs. 10.7 (6.1-17.0) ng/mL and 12.6 (9.4-18.2) ng/mL, both p < 0.001). BDNF could well distinguish CHD patients from DCs (area under the curve [AUC]: 0.739) and HCs (AUC: 0.857). BDNF was negatively associated with triglyceride (p = 0.014), total cholesterol (p = 0.037), and low-density lipoprotein cholesterol (p = 0.008). BDNF was negatively associated with CRP (p < 0.001), TNF-α (p < 0.001), IL-1β (p = 0.008), and IL-8 (p < 0.001). BDNF was negatively related to VCAM-1 (p < 0.001) and ICAM-1 (p = 0.003). BDNF was negatively linked with the Gensini score (p < 0.001).. BDNF reflects the lipid dysregulation, inflammatory status, and stenosis degree in CHD patients.

Topics: Brain-Derived Neurotrophic Factor; Cholesterol, LDL; Constriction, Pathologic; Coronary Disease; Cytokines; Humans; Intercellular Adhesion Molecule-1; Interleukin-8; Tumor Necrosis Factor-alpha; Vascular Cell Adhesion Molecule-1

What is this article about? This study aimed to find the clinical value of measuring the protein ITIH4 in patients with coronary heart disease (CHD). What was done? A total of 300 CHD patients and 30 non-CHD people (with chest pain or suspected CHD symptoms) were enrolled in this study. Blood ITIH4 levels of all people were detected. What were the results? Blood ITIH4 levels were lower in CHD patients compared with non-CHD people. In CHD patients, a high level of ITIH4 was associated with low inflammation, reduced vessel narrowness and a good prognosis. What do the results mean? Blood ITIH4 serves as an anti-inflammatory biomarker, whose high level represents better conditions in CHD patients.

Topics: Anti-Inflammatory Agents; Biomarkers; Constriction, Pathologic; Coronary Disease; Humans; Interleukin-17; Interleukin-6; Interleukin-8; Proteinase Inhibitory Proteins, Secretory; Tumor Necrosis Factor-alpha

BACKGROUND Diabetes is a risk factor for coronary atherosclerosis and coronary heart disease. Resveratrol (RESV) is a natural compound with anti-inflammatory effects. The objective of this study is to evaluate the cardio protective effects of RESV in a diabetic rat model with coronary heart disease. MATERIAL AND METHODS Diabetic rat model with coronary heart disease was constructed by feeding high-fat and high-calorie diet, followed by injection of streptozotocin. The diabetic rats received RESV or DMSO as treatment. Insulin, total cholesterol, and total triglyceride levels in serum were measured using enzyme-linked immunosorbent assay (ELISA) to evaluate the effect of RESV in alleviating diabetic symptoms. Inflammatory factors, including tumor necrotic factor α, interleukin-6, interleukin-8, intracellular adhesion molecule 1, vascular-cell adhesion molecule 1, and monocyte chemoattractant protein-1 were assayed using ELISA. Real-time polymerase chain reaction and western blot analysis were performed to evaluate the impact of RESV treatment on the TLR4/MyD88/NF-κB signaling pathway (toll-like receptor 4/myeloid differentiation factor 88/nuclear factor kappa B signaling pathway). Hematoxylin and eosin staining was used to document pathological changes in cardiovascular muscles. RESULTS RESV preserved pancreatic tissue, which therefore reduced levels of glucose and triglycerides glyceride in serum. Inflammatory factors were also suppressed by RESV. TLR4/MyD88/NF-κB signaling pathway was downregulated after RESV treatment. CONCLUSIONS RESV offers protective effects of cardiovascular tissues in the diabetic rat model with coronary heart disease. Those effects are mediated by downregulating the TLR4/MyD88/NF-κB signaling pathway.

Topics: Animals; Blotting, Western; China; Cholesterol; Coronary Disease; Diabetes Mellitus, Experimental; Disease Models, Animal; Down-Regulation; Enzyme-Linked Immunosorbent Assay; Insulin; Intercellular Adhesion Molecule-1; Interleukin-6; Interleukin-8; Male; Myeloid Differentiation Factor 88; NF-kappa B; Rats; Rats, Sprague-Dawley; Resveratrol; Signal Transduction; Toll-Like Receptor 4; Tumor Necrosis Factor-alpha

BACKGROUND Vitamin D (VD) deficiency and local inflammation of plaque are potential new risk factors and prevention goals for coronary heart disease (CHD). MATERIAL AND METHODS This study included 135 CHD patients and 45 chest tightness or chest pain patients (control group). Basic clinical data and serum 25-OH-VD, TNF-α, IL-6, IL-8, and IL-1β of the 2 groups were compared by SPSS 25.0. A CHD rat model was used to explore the potential molecular mechanisms. RESULTS The serum 25-OH-VD level in the control group was significantly higher compared to the CHD group, and decreased with the worsening of the CHD condition. Logistic regression found that serum 25-OH-VD was a protective factor in the occurrence of CHD. In CHD patients, the level of serum 25-OH-VD had a negative correlation with serum TNF-α (r=-0.651, P<0.001), IL-6 (r=-0.457, P<0.001), IL-8 (r=-0.755, P<0.001), and IL-1β (r=-0.628, P<0.001). In animal experiments, VD deficiency enhanced the level of serum TC, TG, and LDL-C. VD deficiency could increase the inflammatory response by upregulating the expression of p65 protein and reducing SIRT1 protein expression in heart tissue, thereby inducing or aggravating the state of CHD. CONCLUSIONS Serum 25-OH-VD was a protective factor in the occurrence of CHD, and VD deficiency could induce or aggravate the state of CHD by enhancing inflammation through the NF-κB pathway.

Topics: Aged; Animals; China; Coronary Disease; Disease Models, Animal; Female; Humans; Inflammation; Interleukin-1beta; Interleukin-6; Interleukin-8; Male; Middle Aged; NF-kappa B; Rats; Rats, Sprague-Dawley; Risk Factors; Sirtuin 1; Tumor Necrosis Factor-alpha; Vitamin D; Vitamin D Deficiency

A major goal of biomedicine is to understand the function of every gene in the human genome. Loss-of-function mutations can disrupt both copies of a given gene in humans and phenotypic analysis of such 'human knockouts' can provide insight into gene function. Consanguineous unions are more likely to result in offspring carrying homozygous loss-of-function mutations. In Pakistan, consanguinity rates are notably high. Here we sequence the protein-coding regions of 10,503 adult participants in the Pakistan Risk of Myocardial Infarction Study (PROMIS), designed to understand the determinants of cardiometabolic diseases in individuals from South Asia. We identified individuals carrying homozygous predicted loss-of-function (pLoF) mutations, and performed phenotypic analysis involving more than 200 biochemical and disease traits. We enumerated 49,138 rare (<1% minor allele frequency) pLoF mutations. These pLoF mutations are estimated to knock out 1,317 genes, each in at least one participant. Homozygosity for pLoF mutations at PLA2G7 was associated with absent enzymatic activity of soluble lipoprotein-associated phospholipase A2; at CYP2F1, with higher plasma interleukin-8 concentrations; at TREH, with lower concentrations of apoB-containing lipoprotein subfractions; at either A3GALT2 or NRG4, with markedly reduced plasma insulin C-peptide concentrations; and at SLC9A3R1, with mediators of calcium and phosphate signalling. Heterozygous deficiency of APOC3 has been shown to protect against coronary heart disease; we identified APOC3 homozygous pLoF carriers in our cohort. We recruited these human knockouts and challenged them with an oral fat load. Compared with family members lacking the mutation, individuals with APOC3 knocked out displayed marked blunting of the usual post-prandial rise in plasma triglycerides. Overall, these observations provide a roadmap for a 'human knockout project', a systematic effort to understand the phenotypic consequences of complete disruption of genes in humans.

Topics: 1-Alkyl-2-acetylglycerophosphocholine Esterase; Apolipoprotein C-III; Cohort Studies; Consanguinity; Coronary Disease; Cytochrome P450 Family 2; Dietary Fats; DNA Mutational Analysis; Exome; Fasting; Female; Gene Deletion; Gene Frequency; Genes; Genetic Association Studies; Homozygote; Humans; Interleukin-8; Male; Middle Aged; Myocardial Infarction; Neuregulins; Pakistan; Pedigree; Phenotype; Phosphoproteins; Postprandial Period; Reverse Genetics; RNA Splice Sites; Sodium-Hydrogen Exchangers; Triglycerides

Variants at the interleukin 6 receptor (IL6R) gene regulate inflammation and are associated with risk of coronary heart disease (CHD). The aim of the present study was to investigate the effects of IL6R haplotypes on circulating levels of inflammatory biomarkers and risk of CHD. We performed a discovery analysis in SHEEP, a myocardial infarction (MI) case control study (n = 2,774) and replicated our results in two large, independent European populations, PROCARDIS, a CHD case control study (n = 7,998), and IMPROVE (n = 3,711) a prospective cardiovascular cohort study. Two major haplotype blocks (rs12083537A/G and rs4075015A/T--block 1; and rs8192282G/A, rs4553185T/C, rs8192284A/C, rs4240872T/C and rs7514452T/C--block 2) were identified in the IL6R gene. IL6R haplotype associations with C-reactive protein (CRP), fibrinogen, IL6, soluble IL6R (sIL6R), IL6, IL8 and TNF-α in SHEEP, CRP and fibrinogen in PROCARDIS and CRP in IMPROVE as well as association with risk of MI and CHD, were analyzed by THESIAS. Haplotypes in block 1 were associated neither with circulating inflammatory biomarkers nor with the MI/CHD risk. Haplotypes in block 2 were associated with circulating levels of CRP, in all three study populations, with fibrinogen in SHEEP and PROCARDIS, with IL8 and sIL6Rin SHEEP and with a modest, non significant, increase (7%) in MI/CHD risk in the three populations studied. Our results indicate that IL6R haplotypes regulate the circulating levels of inflammatory biomarkers. Lack of association with the risk of CHD may be explained by the combined effect of SNPs with opposite effect on the CHD risk, the sample size as well as by structural changes affecting sIL6R stability in the circulation.

Topics: Aged; Biomarkers; C-Reactive Protein; Case-Control Studies; Coronary Disease; Female; Fibrinogen; Haplotypes; Humans; Interleukin-8; Male; Middle Aged; Polymorphism, Single Nucleotide; Receptors, Interleukin-6; Tumor Necrosis Factor-alpha

Inflammation is now believed to be responsible for coronary heart disease (CHD). This belief has stimulated the evaluation of various inflammatory markers for predicting CHD. This study was designed to investigate the association between four inflammatory cytokines (CD121a, interleukin [IL]-1β, IL-8, and IL-11) and CHD. Here, we evaluated 443 patients with CHD and 160 CHD-free controls who underwent coronary angiography. Cytokines were evaluated using flow cytometry, and statistical analyses were performed to investigate the association between cytokine levels and the risk of CHD. Patients with CHD had significantly higher levels of CD121a. The odds ratios for CHD according to increasing CD121a quartiles were 1.00, 1.47 [95% confidence interval (CI): 0.79-2.72], 2.67 (95% CI: 1.47-4.84), and 4.71 (95% CI: 2.65-8.37) in an age- and sex-adjusted model, compared to 1.00, 1.48 (95% CI: 0.70-3.14), 2.25 (95% CI: 1.10-4.62), and 4.39 (95% CI: 2.19-8.79) in a model that was adjusted for multiple covariates. A comparison of the stable angina, unstable angina, and acute myocardial infarction (AMI) subgroups revealed that patients with AMI had the highest CD121a levels, although IL-1β levels were similar across all groups. IL-8 levels were also increased in AMI patients, and IL-11 levels were higher in CHD patients than in non-CHD patients. Correlation analysis revealed a positive association between CD121a, IL-8, and the Gensini score. Together, the significant increase in CD121a levels among CHD patients suggests that it may be a novel inflammatory marker for predicting CHD.

Topics: Adult; Aged; Aged, 80 and over; Angina, Stable; Angina, Unstable; Biomarkers; Case-Control Studies; Coronary Disease; Female; Humans; Inflammation Mediators; Interleukin-11; Interleukin-1beta; Interleukin-8; Male; Middle Aged; Myocardial Infarction; Predictive Value of Tests; Receptors, Interleukin-1 Type I

To detect the level of interleukin-8 (IL-8) and interleukin-10 (IL-10) in serum and gingival crevicular fluid in patients with chronic severe periodontitis (CP) and coronary heart disease (CHD) and investigate the relationship between CP and CHD.. Thirty patients with CHD and CP(group A), twenty-five patients with only CP(group B) and thirty healthy controls (group C) were included in this study. Gingival crevicular fluid and serum IL-8, IL-10 levels were detected by ELISA. SPSS 11.5 software package was used for statistical analysis.. The periodontal indexes including bleeding on probing and probing depth were significantly different among the 3 groups. In group A and B, the level of IL-8 in gingival crevicular fluid and serum were significantly lower, whereas the IL-10 level was significantly higher, in comparison to those in group C (P<0.05).. IL-8 and IL-10 may be associated with the pathogenesis of periodontitis and CHD. There may be a relationship between CHD and CP.

Topics: China; Chronic Periodontitis; Coronary Disease; Enzyme-Linked Immunosorbent Assay; Gingival Crevicular Fluid; Humans; Interleukin-10; Interleukin-8; Periodontal Index

Topics: Adult; Aged; Asian People; Biomarkers; Cohort Studies; Coronary Disease; Cross-Sectional Studies; Eating; Follow-Up Studies; Humans; Interleukin-8; Male; Middle Aged; Plasminogen Activator Inhibitor 1; Prospective Studies; Risk Factors; Soy Foods

The objective of this study was to investigate inflammatory markers of the postpericardiotomy syndrome (PPS) and to determine individuals prone to develop the PPS.. The study included 75 patients with a stable coronary disease that had underwent coronary artery bypass surgery. Serum samples were collected prior to the surgery and on the 5th day after the operation, to measure the concentration of IL-8, IL-6, IL-1β, IL-10, TNF, IL-12p70. All included patients were screened for the PPS before discharge from the hospital and 6 months after the surgery. The 49 patients developed the PPS (65.4%), among them 42 (56%) patients had pleural effusion, and 23 (31%) had pericardial effusion. The cytokine analysis has shown an inverse correlation between IL-8 concentration before the surgery, and the occurrence of the PPS (p = 0.026). There were also positive correlations between the magnitude of increase of IL-8 and IL-1β concentrations on the 5th day after the surgery and the occurrence of the PPS (p = 0.006 and p = 0.049 respectively). Multivariate analysis revealed IL-8 concentration before surgery as an independent risk factor of the PPS development (HR = 0.976; 95%CI: 0.956-0.996, p = 0.02). Cut-off point was established to assess the predictive value of IL-8 concentration (21.1 pg/ml). The test parameters were: sensitivity: 62.5%, specificity: 75%, positive predictive value: 83% and negative predictive value: 50%. Clinical evaluation showed the relationship between the hemoglobin concentration before the surgery and the PPS occurrence (p = 0.01).. The IL-8 and IL-1β may participate in the postpericardiotomy syndrome pathogenesis, and the IL-8 concentration measurement may select patients with the risk of the PPS development.

Topics: Aged; Area Under Curve; Coronary Artery Bypass; Coronary Disease; Cytokines; Female; Hemoglobins; Humans; Interleukin-1beta; Interleukin-8; Male; Middle Aged; Multivariate Analysis; Pericardial Effusion; Pleural Effusion; Postoperative Period; Postpericardiotomy Syndrome; Risk Factors; ROC Curve

We examined the association between job strain and coronary heart disease (CHD) and investigated the role of markers of inflammation and endothelial dysfunction as possible mediators of job strain-associated CHD risk.. The sample (n = 1027) included employed participants (35-64 years old, 68% male) from the population-based MONICA/KORA (Monitoring of Trends and Determinants in Cardiovascular Disease/Kooperative Gesundheitsforschung in der Region Augsburg) studies. At baseline Karasek's Job Strain Index was assessed during standardized personal interviews, and nine biological markers were measured (1984-1995). Participants were followed (average, 12 years) to assess incident events (sudden cardiac death or fatal and nonfatal myocardial infarction). In this case-cohort design, the final sample contained 114 cases and 913 noncases.. Baseline distributions of cardiometabolic risk factors were significantly different between cases and noncases, with no detectable job strain-specific differences. However, cases with high job strain had higher monocyte chemoattractant protein-1, interleukin (IL)-8, and IL-18 compared with noncases with high job strain. High-sensitivity C-reactive protein, IL-6, and soluble intercellular adhesion molecule-1 were increased in cases versus noncases, regardless of work stress. Job strain was associated with incident coronary events in Cox proportional hazards models adjusted for age, sex, and survey (hazard ratio = 2.57, 95% confidence interval = 1.09-6.07) and after adjustment for CHD risk factors (2.35, 1.003-5.49). Adjustment for monocyte chemoattractant protein-1 or IL-8 increased this risk estimate by 14.5% or 9.4%, respectively, whereas adjustment for C-reactive protein and soluble intercellular adhesion molecule-1 led to decreased hazard ratios (-9.9% and -5.5%, respectively).. Job strain increased CHD risk in healthy workers; the associated inflammatory burden may contribute to stress-related coronary pathogenesis.

Topics: Adult; Biomarkers; C-Reactive Protein; Cohort Studies; Coronary Disease; Employment; Female; Germany; Humans; Inflammation; Intercellular Adhesion Molecule-1; Interleukin-18; Interleukin-6; Interleukin-8; Male; Middle Aged; Proportional Hazards Models; Risk Factors; Stress, Psychological

To study the relationship between serum inflammation factors interleukin-8 (IL-8), high-sensitivity C-reaction protein, tumor necrosis factor-α and coronary lesions in coronary heart disease (CHD) patients,. One hundred and six CHD patients were enrolled, 100 healthy subjects served as control group. The levels of serum IL-8, hsCRP (by) and TNF-α were determined. Coronary lesions were calculated by Gensini method.. The levels of Serum IL-8, hsCRP and TNF-α in CHD group were significantly higher than those in control group were significantly higher than those in control group (P < 0.05), and serum IL-8, hsCRP and TNF-α in CHD group increased gradually with the increase of Gensini score (P < 0.05). Pearson correlation analysis showed that Gensini score was positively correlated to IL-8 (P < 0.05), hsCRP (P < 0.05) and TNF-α (P < 0.05) in CHD group.. Severity of coronary lesions in CHD patients may be related to the levels of serum IL-8, hsCRP and TNF-α.

Topics: Aged; C-Reactive Protein; Coronary Disease; Coronary Vessels; Female; Humans; Interleukin-8; Male; Middle Aged; Tumor Necrosis Factor-alpha

Accumulating evidence suggests that inflammation plays an essential role in the pathogenesis of atherosclerosis and that circulating inflammatory markers predict future cardiovascular events. However, previous studies evaluated the predictive value of only a single cytokine at a time.. This study was designed to simultaneously measure plasma levels of multiple cytokines in patients with coronary artery disease and to evaluate their ability to predict long-term prognosis.. The study enrolled 158 consecutive patients with angiographically identified stable coronary artery disease. Using the Luminex micro-beads array system, we simultaneously measured plasma levels of the following 10 cytokines: interleukin (IL)-1beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, tumor necrosis factor (TNF)-alpha, granulocyte-macrophage colony stimulating factor (GM-CSF) and gamma-interferon (IFN-gamma).. None of the 10 cytokine levels as well as high-sensitive C reactive protein (hs-CRP) was correlated with the severity of coronary artery disease. During a 7-year follow-up period, cardiovascular events occurred in 56 patients (35%). Multi-vessel disease, diabetes, and high levels of all of the 10 measured cytokines and hs-CRP were significant predictors of cardiovascular events in univariate analysis. However, multivariate analysis using multi-vessel disease, diabetes and the levels of all of 10 cytokines and hs-CRP showed that the only independent predictor was IL-8 (RR, 2.98; 95%CI, 1.64-7.24; P=0.0001).. IL-8 was the only cytokine that predicted cardiovascular events independent of the other 9 cytokines and hs-CRP. Since IL-8 is a neutrophil chemokine, these results suggest that neutrophil activation may be related to the occurrence of cardiovascular events.

Topics: Biomarkers; C-Reactive Protein; Coronary Angiography; Coronary Disease; Enzyme-Linked Immunosorbent Assay; Female; Follow-Up Studies; Humans; Interleukin-8; Male; Middle Aged; Multivariate Analysis; Nephelometry and Turbidimetry; Prognosis; Retrospective Studies; Risk Factors; Severity of Illness Index; Survival Rate; Time Factors

In this article, we consider comparing the areas under correlated receiver operating characteristic (ROC) curves of diagnostic biomarkers whose measurements are subject to a limit of detection (LOD), a source of measurement error from instruments' sensitivity in epidemiological studies. We propose and examine the likelihood ratio tests with operating characteristics that are easily obtained by classical maximum likelihood methodology.

Topics: Biomarkers; Biometry; Cholesterol; Cholesterol, HDL; Coronary Disease; Humans; Intelligence; Interleukin-8; Likelihood Functions; Models, Statistical; Monte Carlo Method; ROC Curve

Oxidized low density lipoproteins (oxLDLs) may exert several pro-inflammatory effects that can contribute to the development of coronary artery disease (CAD). Evaluating a possible correlation between oxLDLs and clinical expression of CAD, we measured specific lipid peroxidation indices in healthy subjects and in patients at different clinical stages of CAD. We observed a slight, but not significant, increase in plasma content of cholesterol oxidation products, i.e. oxysterols, in all CAD patients, and a slight, but not significant, increase of 4-hydroxynonenal-protein adducts only in subjects with acute CAD. Moreover, CAD patients showed a plasma rise of specific inflammatory proteins, i.e. C-reactive protein, intercellular adhesion molecule-1, and interleukin-8, but not of monocyte chemotactic protein-1. These preliminary data, without excluding an involvement of oxidative stress and inflammation in CAD, do not show a strict correlation between relevant plasma markers, other than C-reactive protein, and acute phase of the disease.

Topics: Aged; Aged, 80 and over; Aldehydes; Antigens, CD; Biomarkers; Blood Proteins; C-Reactive Protein; Cell Adhesion Molecules; Chemokine CCL2; Coronary Disease; Female; Humans; Inflammation; Interleukin-8; Lipid Peroxidation; Male; Middle Aged; Reference Values

We investigated the association of several chemokines with the risk of stable coronary heart disease (CHD) in a large case-control study after adjustment for other established risk factors. Furthermore, we analyzed their correlation with various acute-phase proteins, inflammation-associated cytokines, and an adhesion molecule.. We included 312 patients aged 40 to 68 years with angiographically confirmed and stable CHD and 472 age- and gender-matched controls in this study. The main outcome measure was the odds ratio (OR) for CHD associated with increased levels of interferon (INF)-inducible protein of 10 kd (IP-10), interleukin (IL)-8, regulated on activation normal T-cell expressed and secreted (RANTES), monocyte chemoattractant protein 1 (MCP-1), macrophage inflammation protein 1alpha (MIP-1alpha), or eotaxin determined by rigidly evaluated sandwich ELISAs. Serum levels of IP-10 and IL-8 were higher, and serum levels of RANTES were lower in CHD patients when compared with age- and gender-matched controls. In addition, values in the second and top tertile of IP-10 and IL-8 were associated with an increased OR for CHD when compared with values in the bottom tertile [OR for IP-10 (top tertile) was 2.62 (95% CI, 1.79 to 3.85) in the age- and gender-adjusted model and 1.93 (95% CI, 1.23 to 3.04) in the fully adjusted model, and for IL-8, the OR was 1.77 (95% CI, 1.20 to 2.59) and 1.53 (95% CI, 0.98 to 2.39), respectively]; increased RANTES values were associated with a lower OR for CHD [OR, 0.67 (95% CI, 0.47 to 0.96) and 0.61 (95% CI, 0.40 to 0.94)]. Furthermore, positive correlations of IP-10 and IL-8 with several acute-phase proteins or inflammation-associated cytokines were evident, and positive correlations for IP-10 plasma viscosity and intercellular adhesion molecule 1 were also present.. The current study suggests that there may be no universal upregulation of chemokines in CHD-associated inflammation but different upregulation of IP-10 and IL-8 versus downregulation of RANTES; there was no clear disease association for MCP-1, MIP-1alpha, or eotaxin.

Topics: Acute-Phase Proteins; Adult; Aged; Biomarkers; Case-Control Studies; Chemokine CCL11; Chemokine CCL2; Chemokine CCL3; Chemokine CCL4; Chemokine CCL5; Chemokine CXCL10; Chemokines; Chemokines, CC; Chemokines, CXC; Coronary Artery Disease; Coronary Disease; Female; Humans; Intercellular Adhesion Molecule-1; Interleukin-8; Macrophage Inflammatory Proteins; Male; Middle Aged; Risk Factors; Up-Regulation; Vasculitis

The chemokines monocyte chemoattractant protein-1 (MCP-1/CCL2), interleukin-8 (IL-8/CXCL8), and interferon-gamma-inducible protein-10 (IP-10/CXCL10) have been reported to be involved in the development of atherosclerosis and type 2 diabetes. The aim of this study was to assess whether elevated systemic levels of these chemokines precede coronary events.. We investigated MCP-1, IL-8, and IP-10 serum levels in a case-cohort design based on data from 381 individuals (294 men, 87 women) with and 1977 individuals (1006 men, 971 women) without incident coronary heart disease (CHD) from the prospective, population-based MONICA/KORA Augsburg study (1984 to 2002). The mean follow-up time was 11.0 years. Baseline concentrations were significantly higher in cases compared with noncases (P < or = 0.001 for all chemokines). MCP-1 and IL-8 remained associated with CHD risk after adjustment for age, sex, and survey with hazard ratios (95% confidence intervals) comparing extreme tertiles of 1.39 (1.05 to 1.84) for MCP-1 and 1.48 (1.10 to 1.99) for IL-8. However, adjustment for further cardiovascular and immunologic risk factors attenuated the observed associations, and they became nonsignificant.. Elevated systemic levels of the chemokines MCP-1, IL-8, and IP-10 precede CHD but do not represent independent risk factors. Thus, the associations are less pronounced than previously shown for type 2 diabetes.

Topics: Case-Control Studies; Chemokine CCL2; Chemokine CXCL10; Chemokines, CXC; Cohort Studies; Coronary Disease; Female; Humans; Interleukin-8; Male; Prospective Studies

To study the role of IL-8 in predicting future coronary artery disease (CAD) in apparently healthy men and women.. A nested case-control study was performed in the prospective EPIC-Norfolk population study. We measured baseline IL-8 concentrations among 785 apparently healthy individuals in whom fatal or nonfatal CAD developed during follow-up and 1570 matched controls. Baseline IL-8 concentrations were higher in cases than in matched controls (3.5 pg/mL versus 3.1 pg/mL, P=0.001). The risk of future CAD increased with increasing quartiles of IL-8 (P linearity <0.0001). Among individuals in the highest IL-8 quartile, the unadjusted odds ratio for future CAD was 1.72 (95% CI, 1.34 to 2.21; P<0.0001). The odds ratio for future CAD was still significant after adjustment for traditional risk factors (OR, 1.58; 95%CI, 1.19 to 2.09; P=0.002) and after additional adjustment for C-reactive protein and white cell count (OR, 1.77; 95% CI, 1.21 to 2.60; P=0.001).. We conclude that among apparently healthy men and women, elevated levels of IL-8 are associated with an increased risk of future CAD. These prospective data support a role for IL-8 in the development of CAD events.

Topics: Aged; Biomarkers; C-Reactive Protein; Case-Control Studies; Cohort Studies; Comorbidity; Coronary Disease; England; Female; Humans; Hypertension; Interleukin-8; Interleukins; Leukocyte Count; Lipids; Lipoproteins; Male; Middle Aged; Obesity; Odds Ratio; Predictive Value of Tests; Prospective Studies; Risk; Risk Factors; Smoking; Tumor Necrosis Factor-alpha

The aim of the present study was to investigate the prognostic value of plasma interleukin-8 (IL-8) for early complications after percutaneous coronary intervention (PCI). The pre- and postprocedural plasma levels of IL-8 and serum C-reactive protein (CRP) were examined by immunoassay, and the expression of CD11b/CD18 on neutrophils was assessed by flow cytometry. Early complications (abrupt occlusion, threatened abrupt occlusion, early recurrence of ischemia, myocardial infarction, cardiac sudden death, and target vessel revascularization) occurred intra-procedure and 30 days after PCI and were observed in 121 consecutive patients with coronary heart disease. Sixteen patients with early complications had high preprocedural levels and high postprocedural differentials of IL-8, CRP, and CD11b/CD18 compared to those without complications (all P < 0.05). The occurrence of complications showed a significant increase in the patients according to the tertiles of IL-8, CRP, and CD11b/CD18. Preprocedural levels of IL-8 (RR = 5.864, CI = 1.658-20.734, P = 0.006) and diabetes (RR = 1.587, CI = 1.246-2.132, P = 0.038) were independent predictors of early complications. There were significant correlations in the postprocedural differential between IL-8 and CD11b/CD18 (r = 0.776, P = 0.002) in patients with complications. The results reveal that the early complications after PCI contribute to preprocedural inflammatory responses. Normal levels of IL-8 may be powerful negative predictors of early complications in patients with CHD following PCI.

Topics: Aged; Angioplasty, Balloon, Coronary; C-Reactive Protein; CD11b Antigen; CD18 Antigens; Coronary Disease; Coronary Restenosis; Female; Forecasting; Humans; Interleukin-8; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia

The objective of the present study was to investigate the prognostic value of plasma interleukin-8 (IL-8) for adverse cardiac events and restenosis in patients with percutaneous coronary intervention (PCI). The pre- and post-procedural peak plasma levels of IL-8 and serum C-reactive protein (CRP) were examined by immunoassay, while adverse cardiae events and restenosis within one year follow-up were observed in 134 consecutive patients who underwent PCI. Angiography revealed that 23.88% (32/134) of the patients had adverse cardiac events and 29.41% (35/119) of the patients had restenosis. Preprocedural levels of IL-8 and CRP and post-procedural peak levels of IL-8 in patients with adverse cardiac events were higher than those without adverse cardiac events (all P < 0.05). The incidence of adverse cardiac events increased from 6.67% in the bottom tertile to 31.82% in the top tertile of IL-8 levels (P = 0.001): a similar trend was observed for restenosis from 10% in low tertile to 51.28% in high tertile of IL-8 levels to 51.8% (P = 0.012). The preprocedural levels of IL-8 (RR = 5.539, CI = 1.720-17.887, P = 0.001) and CRP (RR = 2.031, CI = 1.132-2.049, P = 0.003) were the only independent predictors of adverse cardiac events. The post-procedure peak level of IL-8 (RR = 3.766, CI = 2.990-5.904, P = 0.002) and stent length (RR = 1.468, CI = 1.161-2.022. P = 0.021) were the independent predictors of restenosis. The results demonstrate that the release of IL-8 after PCI is a powerful prognostic factor for cardiac events and restenosis. The higher the peak level of post-procedure IL-8, the lower the event-free survival observed.

Topics: Aged; C-Reactive Protein; Coronary Angiography; Coronary Disease; Coronary Restenosis; Female; Humans; Interleukin-8; Male; Middle Aged; Predictive Value of Tests; Prognosis; Regression Analysis; Stents

The effect of patient age on circulating endothelial progenitor cells (EPCs) and their mobilization during coronary artery bypass grafting (CABG) was assessed.. The EPCs are able to contribute to reparative neovascularization after tissue ischemia. In experimental models, reparative neovascularization is impaired in senescent animals, but the role of EPCs in this impairment, especially in humans, is unknown.. In 50 consecutive patients (43 to 80 years old) with stable coronary artery disease undergoing CABG, the numbers of EPCs and the plasma levels of interleukin (IL)-6, IL-8, IL-10, and IL-18, as well as vascular endothelial growth factor (VEGF) and placental growth factor, were determined preoperatively, after coming off bypass, and 6, 12, 24, and 72 h postoperatively.. Preoperative values of EPCs were lowered with increasing age, similar to the lowering of plasma VEGF levels. These age-associated decreases could not be explained by differences in atherosclerotic risk factors or cardiac function. Bypass surgery induced a rapid mobilization in EPCs, IL-6, IL-8, IL-10, and VEGF, with a peak 6 h postoperatively. Persistently lower levels of EPCs and VEGF throughout the observation period were observed in patients >69 years old, which could not be explained by differences in the operative procedure or inflammatory IL activation.. Despite a significant increase in EPCs and release of cytochemokines during CABG, age is a major limiting factor for mobilization of EPCs. Further studies are necessary to improve the strategies for mobilization, ex vivo expansion, and re-transplantation of EPCs in aging patients.

Topics: Adult; Age Factors; Aged; Coronary Artery Bypass; Coronary Disease; Endothelium, Vascular; Female; Humans; Interleukin-10; Interleukin-18; Interleukin-6; Interleukin-8; Male; Middle Aged; Placenta Growth Factor; Pregnancy Proteins; Stem Cells; Vascular Endothelial Growth Factor A

Inflammation is an important phenomenon in atherosclerotic plaque growth and in plaque instability. Cytokines are nuclear mediators in the inflammatory response; some have proinflammatory and others anti-inflammatory roles. Proinflammatory cytokines have been associated with worse outcomes in unstable angina. The aims of this study were to determine the role of the anti-inflammatory cytokine interleukin (IL)-10 and the proinflammatory to anti-inflammatory ratios in the short-term prognosis of patients with unstable angina.. Serum levels of proinflammatory cytokines IL-1beta, IL-6, and IL-8, and of the anti-inflammatory cytokine IL-10 were determined on admission in 127 consecutive patients with severe unstable angina, and comparisons were made between patients who had cardiovascular events (death, nonfatal myocardial infarction, readmission for refractory angina) (n = 20) and patients without coronary events (n = 107) during a follow-up period of 3 months.. IL-10 levels were lower (0.67 +/- 1.13 vs 1.33 +/- 1.67 pg/mL, P =.04) and IL-8 levels were higher (3.6 +/- 2.41 vs 2.23 +/- 2.47 pg/mL, P =.029) in patients in whom cardiovascular events subsequently developed compared with those without events, with resulting higher proinflammatory to anti-inflammatory cytokine ratios in the former group, whereas no significant differences were seen in IL-1beta or IL-6 levels between the groups, except for the subgroup of patients with prolonged rest angina and persistent electrocardiographic changes. A greater ratio of IL-8 to IL-10 serum levels was observed in patients who had coronary events (28 +/- 25 vs 12 +/- 21, P =.007). The risk of subsequent coronary events increased in patients in the highest quartile of proinflammatory to anti-inflammatory cytokine ratio (IL-8/IL-10). Patients in the highest quartile had a relative risk 3.8 times higher than those in the lowest quartile (P =.01).. Lower levels of IL-10, with higher proinflammatory to anti-inflammatory cytokine ratios, were observed on admission in patients with unstable angina who subsequently had cardiovascular events. Higher levels of the anti-inflammatory cytokine IL-10 may be needed to provide protection in unstable angina.

Topics: Adult; Aged; Aged, 80 and over; Angina, Unstable; Biomarkers; Coronary Disease; Female; Follow-Up Studies; Humans; Interleukin-1; Interleukin-10; Interleukin-6; Interleukin-8; Male; Middle Aged; Prognosis; Time Factors

Alterations of the immune system are now believed to play crucial role in the pathogenesis of atherosclerosis. The aim of this study was analysis of soluble forms of selectin-P and interleukin-8 levels in patients with different form of coronary heart disease.. In the study took part 18 patients with stable coronary heart disease, 20 patients with unstable coronary heart disease and 15 healthy persons from control group. Soluble selectin-P and interleukin-8 levels were measured in EDTA plasma with the use of enzyme immunoassay ELISA.. The level of soluble selectin-P was significantly higher in unstable coronary heart disease patients in comparison to the stable coronary heart disease patients (P < or = 0.01) and nonsignificantly higher in comparison to the control group. The level of interleukin-8 were significantly higher in unstable coronary heart disease patients in comparison to the stable coronary heart disease patients (P < or = 0.01) and in comparison to the control group (P < or = 0.02).. Our findings suggest that soluble form of selectin-P and interleukin-8 may be useful clinical predictors of unstable coronary heart disease. The assessment of the risk for the development of coronary heart disease requires further serial investigation.

Topics: Aged; Angina, Unstable; Biomarkers; Case-Control Studies; Coronary Disease; Enzyme-Linked Immunosorbent Assay; Humans; Interleukin-8; Male; Middle Aged; P-Selectin

Topics: Angioplasty, Balloon, Coronary; Chemokine CCL2; Chemokine CCL5; Coronary Disease; Humans; Interleukin-8; Models, Biological; Recurrence

Inflammation plays a pathogenic role in the development of restenosis after percutaneous transluminal coronary angioplasty (PTCA). Monocyte chemoattractant protein-1 (MCP-1) is a potent chemoattractant of monocytes; however, its role in the pathophysiology of restenosis is still unclear. We set out to investigate the role of MCP-1 in restenosis after PTCA. In addition, we tested the hypothesis that MCP-1 exerts its effect, at least in part, by inducing O(2)(-) generation in circulating monocytes. Plasma levels of MCP-1 were measured before and 1, 5, 15, and 180 days after PTCA in 50 patients (30 males and 20 females, aged 62+/-5 years) who underwent PTCA and who had repeated angiograms at 6-month follow-up. Restenosis occurred in 14 (28%) patients. The MCP-1 level was no different at baseline between patients with or without restenosis. However, after the procedure, restenotic patients, compared with nonrestenotic patients, had statistically significant (P<0.0001) elevated levels of MCP-1. In contrast, plasma levels of other chemokines, such as RANTES and interleukin-8, did not differ between the 2 groups after PTCA. Higher MCP-1 throughout the study was correlated with restenosis. Moreover, increased MCP-1 was significantly correlated with increased monocyte activity, as reflected by enhanced O(2)(-) generation. Finally, multivariate regression analysis showed that the MCP-1 plasma level measured 15 days after PTCA was the only statistically significant independent predictor of restenosis (beta=0.688, P<0.0001). This study suggests that MCP-1 production and macrophage accumulation in the balloon-injured vessel may play a pivotal role in restenosis after PTCA. MCP-1 may induce luminal renarrowing, at least in part, by inducing O(2)(-) release in monocytes. Further understanding of the mechanism(s) by which MCP-1 is produced and acts after arterial injury may provide insight into therapies to limit the progression of atherosclerosis and restenosis after balloon angioplasty.

Topics: Aged; Analysis of Variance; Angioplasty, Balloon, Coronary; Chemokine CCL2; Chemokine CCL5; Coronary Disease; Female; Humans; Interleukin-8; Male; Middle Aged; Monocytes; Reactive Oxygen Species; Recurrence; Tetradecanoylphorbol Acetate; Time Factors

The role of Helicobacter pylori (HP) as the main etiological factor in gastritis and peptic ulcer disease is undisputable. Gastric mucosal damage caused by HP involves various bacterial and host-dependent toxic substances that have been recently associated with an increased risk of coronary artery disease (CAD), possibly through the activation acute phase response and of procoagulant hemostatic factors. Recent studies showed a close and strong correlation between plasma increments of some cytokines such as IL-6 or TNFalpha and cardiovascular diseases. HP infection induces platelet activation and aggregation that could be the pathogenic explanation of the association between HP infection and CAD. The aim of this study was to determine the seroprevalence of HP infection and antibodies to CagA, an antigen that is expressed by the most virulent HP strains inducing an enhanced gastric inflammatory response, in patients undergoing routine coronary artery examination. We studied 76 patients with CAD and 81 healthy controls patients without significant change in coronary circulation. Angiograms were read by two independent experienced cardiologists blinded to the results of HP status. The presence of serum IgG antibodies to HP and to CagA and plasma interleukin-8 (IL-8) levels was measured by ELISA. In addition plasma C-reactive protein fibrinogen, total cholesterol and lipids levels were measured in all studied patients. Seropositivity to HP was found in 81.5 % of cases and in 51% of controls and the difference in prevalence was statistically significant, the odds ratio being 4.3 for Hp patients. Antibody to CagA protein was detected in 47.3% of CAD but only in 28% of healthy controls (OR = 2.3 vs OR = 10). C-reactive protein, plasma fibrinogen and total cholesterol were, respectively higher in patients with CAD than in controls. Present data show that there is significant link between CAD and HP infection. The HP infection significantly increases the risk of CAD, especially when both the anti-HP IgG and anti-CagA IgG are considered. Higher prevalence of cytotoxic HP strains might enhance the atherosclerotic process by inducing a persistent, low grade inflammatory response in arterial wall with enhanced synthesis of acute phase reactants.

Topics: Adult; Aged; Antibodies, Bacterial; Antigens, Bacterial; Bacterial Proteins; C-Reactive Protein; Cholesterol; Coronary Disease; Female; Helicobacter Infections; Helicobacter pylori; Humans; Interleukin-8; Male; Middle Aged; Triglycerides

We studied the plasma levels of TNF-alpha, IL-6, IL-8 and soluble adhesion molecules (sE-Selectin, sL-Selectin, sVCAM-1) immediately before and during mechanical circulatory support with a Biventricular Assist Device System (BVAD-"Berlin Heart") in comparison to patients with chronic heart failure (NYHA classes II/III) and patients with coronary artery disease with normal ventricular function. Additionally, the biocompatibility of the membranes used in the "Berlin Heart" was tested in vitro. IL-6 and IL-8 but not TNF-alpha could only be detected in patients with cardiogenic shock immediately before starting circulatory support. Furthermore, plasma concentrations of soluble adhesion molecules were statistically significantly elevated in patients with cardiogenic shock compared to patients with coronary artery disease. This picture of a systemic inflammatory response syndrome without significant level of TNF-alpha looks quite similar to that seen in patients following trauma and severe operations. During mechanical circulatory support plasma levels of cytokines and soluble adhesion molecules dropped to low levels in patients, who were successfully maintained on BVAD. By contrast, we have found persistently elevated levels of these mediators in patients with fatal outcome. This seems not to be the result of individual distinct response of blood cells to contact with the artificial surfaces of the device. In summary, our data suggest the development of a systemic inflammatory response syndrome may be due to hypoxia during cardiogenic shock. Persistence of systemic inflammation suggests failing of the mechanical support. Therefore, the monitoring of inflammatory mediators may be relevant as a prognostic marker in these patients (disappearance of peripheral hypoxia).

Topics: Adult; Aged; Cell Adhesion Molecules; Coronary Disease; Female; Heart Failure; Heart-Assist Devices; Humans; Inflammation Mediators; Interleukin-6; Interleukin-8; Male; Materials Testing; Membranes, Artificial; Middle Aged; Prognosis; Shock, Cardiogenic; Systemic Inflammatory Response Syndrome; Tumor Necrosis Factor-alpha

Neutrophil adhesion and direct cytotoxicity for cardiac myocytes require chemotactic stimulation and are dependent upon CD18-ICAM-1 binding. To characterize the potential role of IL-8 in this interaction, canine IL-8 cDNA was cloned and the mature recombinant protein expressed in Escherichia coli BL21 cells. Recombinant canine IL-8 markedly increased adhesion of neutrophils to isolated canine cardiac myocytes. This adhesion resulted in direct cytotoxicity for cardiac myocytes. Both processes were specifically blocked by antibodies directed against CD18 and IL-8. In vivo, after 1 h of coronary occlusion, IL-8 mRNA was markedly and consistently induced in reperfused segments of myocardium. IL-8 mRNA was not induced in control (normally perfused) myocardial segments. Minimal amounts of IL-8 mRNA were detected after 3 or 4 h of ischemia without reperfusion. Highest levels of induction were evident in the most ischemic myocardial segments. IL-8 mRNA peaked in the first 3 h of reperfusion and persisted at high levels beyond 24 h. IL-8 staining was present in the inflammatory infiltrate near the border between necrotic and viable myocardium, as well as in small veins in the same area. These findings provide the first direct evidence for regulation of IL-8 in ischemic and reperfused canine myocardium and support the hypothesis that IL-8 participates in neutrophil-mediated myocardial injury.

Topics: Amino Acid Sequence; Animals; Base Sequence; Cell Adhesion; Cell Movement; Coronary Disease; Dogs; Endothelium, Vascular; Female; Gene Expression Regulation; Inflammation; Interleukin-8; Male; Molecular Sequence Data; Myocardial Reperfusion Injury; Neutrophil Activation; Recombinant Proteins; Time Factors; Tissue Distribution; Transcriptional Activation

1. Reocclusion is still a significant complication after percutaneous transluminal coronary angioplasty. The injury of coronary arteries resulting from PTCA plays an important role in the pathophysiology of both abrupt closure and late restenosis after an initially successful procedure. Cytokines play a pivotal role in the accumulation of circulating blood cells at the endothelium and are known to regulate their interaction with the vessel wall. 2. To obtain further information about this interaction, serum concentrations of soluble endothelial leukocyte adhesion molecule 1 (sELAM-1), leucocyte endothelial cell adhesion molecule 1 (sL-selectin), intercellular adhesion molecule 1 (sICAM-1), interleukin 2 receptor (sIL-2R) and interleukin 8 (IL-8) detected by enzyme-linked immunosorbent assay were monitored in 30 consecutive patients referred for elective PTCA. Fifteen patients who underwent elective coronary angiography without PTCA served as controls. 3. All patients underwent successful first PTCA. Within 24 h the serum concentrations of sELAM-1 increased gradually from 21.7 (SD 7.1) to 48.2 (SD 8.6) ng/ml (P < 0.01); levels of sL-selectin rose from 982.1 (SD 128.7) to 1541.3 (SD 104.6) ng/ml after 48 h (P < 0.01). Serum levels of IL-8 remained stable initially, but peaked at the end of the observation time of 72 h (9.4, SD 3.8, versus 16.1, SD 4.9 ng/ml; P < 0.05). A positive correlation was found between the number of dilatations and the rise in these parameters (P < 0.01). No significant changes were found in the serum concentrations of sICAM-1 and sIL-2R after PTCA or in any of the parameters in patients after coronary angiography. 4. We conclude that PTCA induces a significant rise in the concentration of certain adhesion molecules in serum. Thus, we provide preliminary data on the potential role of cytokines for blood cell-endothelium interaction after PTCA.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Angioplasty, Balloon, Coronary; Cell Adhesion Molecules; Coronary Disease; E-Selectin; Female; Humans; Intercellular Adhesion Molecule-1; Interleukin-8; L-Selectin; Male; Middle Aged; Postoperative Period; Receptors, Interleukin-2; Recurrence

1 We studied the effects of a form of interleukin-8 (i.e., [Ala-IL8]77) on endothelial dysfunction and myocardial injury in rabbits. Pentobarbitone-anaesthetized rabbits were subjected to 1.5 h occlusion of the marginal coronary artery and 3.5 h reperfusion. [Ala-IL8]77 (50 micrograms or its vehicle) was given i.v. as a bolus 10 min prior to reperfusion. [Ala-IL8]77 was also studied in isolated perfused hearts of rabbits. 2 Myocardial ischaemia plus reperfusion in untreated rabbits produced severe endothelial dysfunction and myocardial injury, including marked myocardial necrosis, elevated cardiac myeloperoxidase (MPO) activity in ischaemic cardiac tissue, and loss of response of marginal coronary rings to the endothelium-dependent vasodilators, acetylcholine (ACh) and A23187. 3 Administration of [Ala-IL8]77 10 min prior to reperfusion resulted in significant protective effects in post-ischaemic reperfusion. Compared with untreated rabbits, [Ala-IL8]77 caused a reduced necrotic zone (P less than 0.01), lower MPO activity in the necrotic zone (P less than 0.05), and significantly preserved vasorelaxant responses of marginal coronary artery rings to endothelium-dependent vasodilators, ACh (P less than 0.001) and A23187 (P less than 0.001). 4 These results indicate that myocardial ischaemia and reperfusion result in a severe endothelial dysfunction and myocardial injury which involved the interaction of neutrophils and endothelial cells. However, [Ala-IL8]77 did not appear to exert a direct endothelial protective effect in the absence of neutrophils in rabbit isolated perfused hearts. 5 Inhibition of neutrophil accumulation in the myocardium, perhaps by prevention of endothelial dysfunction resulting from [Ala-IL8]77, leads to significant protective effects in ischaemia and reperfusion in rabbits.

Topics: Acetylcholine; Animals; Blood Pressure; Calcimycin; Coronary Disease; Endothelium, Vascular; Heart Diseases; Heart Rate; In Vitro Techniques; Interleukin-8; Male; Myocardial Reperfusion Injury; Myocardium; Neutrophils; Nitric Oxide; Peroxidase; Rabbits; Superoxides