Serum Levels Of Intercellular Adhesion Molecule-1 Research Articles

Marcadores de ativação endotelial e auto-anticorpos na artrite reumatóide

Rheumatoid arthritis (RA) is an inflammatory chronic disease characterized by the production of antibodies and participation of the vascular endothelium in its pathogenesis. OBJECTIVES: to analyze the correlation of serum levels of the intercellular adhesion molecule 1 (ICAM-1), von Willebrand factor (vWF), Rheumatoid factor (RF), and anti-cyclic citrulinated peptide (anti-CCP) with clinical, laboratory, and radiological parameters of RA. METHODS: Serum levels of ICAM-1, vWF, RF, and anti-CCP were measured in 38 RA patients and 24 controls. Disease activity was measured by the DAS-28 score and functional capa-city was assessed using the HAQ score. The American College of Rheumatism criteria defined the functional class. Hand and fist X-rays were analyzed using the Sharp's score. Statistical analysis utilized the chi-square, Student's t, Kolmogorov-Smirnov, and Mann-Whitney tests, as appropriate, as well as the Spearman's correlation coefficient. RESULTS: Age range was from 52 ± 12.5 and 49 ± 9.4 years-old in RA and controls, respectively. Disease duration range was 68 ± 66.6 months. Serum vWF levels had a positive significant correlation to disease evolution, whereas RF and anti-CCP correlated to the Sharp score. Serum vWF and ICAM-1 levels correlated to DAS-28, while only vWF correlated with HAQ and Sharp scores. CONCLUSION: This study shows that RF and anti-CCP autoantibody levels are correlated to disease prognosis rather than activity. Serum vWF levels are positively correlated to both activity and severity parameters of the disease.

Carotid Atherosclerosis and Endothelial Cell Adhesion Molecules as Predictors of Long-Term Outcome in Chronic Hemodialysis Patients

Background/Aims: Cardiovascular disease (CVD) remains the leading cause of increased morbidity and mortality for hemodialysis (HD) patients. The aim of this study was to investigate the predictive values of carotid artery atherosclerotic lesions and endothelial adhesion molecule levels for long-term outcome in non-diabetic HD patients. Methods: 112 HD patients (60 male, mean age 59 years) consecutively entered the study. Atherosclerotic disease was assessed by measuring the mean and maximum intima-media thickness (IMT and IMT_max respectively) of the common carotid arteries using an ultrasound scanner. Circulating intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) levels were measured by ELISA. Patients were followed for the next 5 years and primary end points on follow-up were all-cause death, death from CVD causes and incidence of a CVD event. Results: Kaplan-Meier analysis showed that survival curves for all-cause mortality, CVD mortality and morbidity differed significantly between the upper and lower tertiles of baseline IMT (p = 0.002, p = 0.01 and p = 0.001 respectively) and IMT_max values (p = 0.0007, p = 0.006 and p = 0.0003 respectively), as well as ICAM-1 (p = 0.008, p = 0.003 and p = 0.02 respectively) and VCAM-1 levels (p = 0.004, p = 0.012 and p = 0.025 respectively). In non-adjusted analysis all-cause mortality and CVD mortality and morbidity were significantly associated with IMT (p = 0.003, p = 0.01 and p = 0.001 respectively) and IMT_max values (p = 0.001, p = 0.007 and p = 0.0007 respectively). After adjusting for other significant covariates, IMT values remained associated only with CVD morbidity (p = 0.03), while IMT_max were associated with both CVD mortality and morbidity (p = 0.03 and p = 0.01 respectively). All-cause mortality and CVD mortality and morbidity were also significantly associated with serum ICAM-1 (p = 0.004, p = 0.005 and p = 0.01 respectively) and VCAM-1 levels (p = 0.008, p = 0.02 and p = 0.03 respectively). After adjusting for the same covariates, the associations between ICAM-1 and all-cause mortality and CVD mortality and morbidity remained significant (p = 0.02, p = 0.01 and p = 0.02 respectively), while serum VCAM-1 levels were independently associated only with all-cause mortality (p = 0.02). Conclusions: In non-diabetic HD patients, carotid atherosclerosis and adhesion molecule levels are independent predictors of long-term clinical outcomes and may be useful surrogate markers for risk stratification in these patients.

Serum Intercellular Adhesion Molecule‐1 in Patients With Nonalcoholic Steatohepatitis: Comparison With Alcoholic Hepatitis

Nonalcoholic fatty liver disease (NAFLD) includes both nonalcoholic fatty liver (FL) and nonalcoholic steatohepatitis (NASH). It has previously been reported that alcoholic hepatitis, which shows morphological findings similar to that of NASH, leads to the onset of endotoxinemia and to an increase in the production of tumor necrosis factor-alpha (TNF-alpha) and/or interleukin-1 (IL-1) from macrophages. Tumor necrosis factor-alpha and IL-1 induce strong expression of intercellular adhesion molecule-1 (ICAM-1) of the cell membranes of hepatocytes and/or sinusoidal endothelial cells, resulting in increased serum ICAM-1 levels in our previous study. In this study, we clarified the significance of serum ICAM-1 levels in patients with NAFLD, and especially in NASH. Thirty-three obese patients of NAFLD (FL: n=14, NASH: n=19) with no habit of drinking, 20 cases of alcoholic liver diseases (alcoholic hepatitis; ASH: n=10, alcoholic hepatic fibrosis; HF: n=10), and 10 healthy individuals were studied. Serum ICAM-1 concentrations were analyzed by enzyme-linked immunoassay in patients with NAFLD and alcoholic liver diseases. Potential factors were assessed for increase in serum ICAM-1 and a diagnostic tool for NASH including ICAM-1 levels, C-reactive protein (CRP), white blood cell count, aspartate aminotransferase, alanine aminotransferase, gamma-gluatmyl transferase, total cholesterol, triglyceride, type-IV collagen, body mass index, homeostasis model assessment (HOMA-IR), and existence of high blood pressure. The serum ICAM-1 level was significantly higher in the patients with NASH than in the patients with FL, and in the normal subjects. The serum ICAM-1 level was also significantly higher in the patients with ASH. The serum ICAM-1 level in the patients with ASH was remarkably high compared with that of the patients with NASH. No significant difference in serum ICAM-1 levels was found between the patients with NASH and those with HF. The serum ICAM-1 level was significantly higher in patients with high blood pressure than in those without high blood pressure in NAFLD. A multivariate analysis using multiple logistic regression showed that high blood pressure and GGTP were the significant factors contributing to high serum ICAM-1 levels, while highly sensitive CRP and ICAM-1 were the significant factors for the diagnosis of NASH. The serum ICAM-1 concentration is increased in patients with NASH. The serum level of ICAM-1 in patients with NAFLD may be a useful marker for the diagnosis of NASH.

Gliclazide treatment lowers serum ICAM-1 levels in poorly controlled type 2 diabetic patients

To investigate the potential effect of gliclazide on serum ICAM-1 (intercellular adhesion molecule-1) and VCAM-1 (vascular cell adhesion molecule-1) levels in poorly controlled type 2 diabetic patients. The study included 104 patients, randomly divided into two groups. Group A comprised 53 patients (26 men) treated with gliclazide with a mean age of 67.5+/-9.9 years, a mean diabetes duration of 13.4+/-5.4 years and a mean HbA1c of 8.6+/-1.1%. Group B comprised 51 patients (25 men) treated with glibenclamide with a mean age of 66.4+/-10.9 years, a mean diabetes duration of 13.2+/-6.1 years and a mean HbA1c of 8.4+/-1.3%. A third group of 30 healthy controls (15 men) with a mean age of 63.3+/-10.4 years was also included. Serum levels of ICAM-1 and VCAM-1 were measured at the beginning of the study and after six months of treatment. Pretreatment serum ICAM-1 and VCAM-1 levels did not differ between groups A and B, while they were significantly higher (P=0.0001) than in healthy controls. No significant difference in HbA1c, body mass index, blood pressure control and lipid profile between the two groups was observed after the sixth month of treatment. In group A, serum ICAM-1 levels after six months of treatment were significantly reduced from 623.12+/-61.17 ng/ml to 370.14+/-49.92 ng/ml (P=0,01), while no reduction was found in VCAM-1 levels. In group B, no reduction was found in serum ICAM-1 and VCAM-1 levels after the end of the study. Our results suggest that gliclazide treatment reduces serum ICAM-1 levels in poorly controlled type 2 diabetic patients. This reduction is independent of the hypoglycaemic action of gliclazide.

Inflammatory and anti-inflammatory variable clusters and risk prediction in acute coronary syndrome patients: A factor analysis approach

Background Numerous inflammatory mediators such as C-reactive protein (CRP), fibrinogen, interleukin-18 (IL-18), and inter-cellular adhesion molecule-1 (ICAM-1) have been proposed for risk stratification in acute coronary syndrome (ACS) patients. However, interactions between these markers have made it difficult to assess their true role in risk prediction. Factor analysis is a multivariable statistical technique that reduces a large number of intercorrelated variables to a smaller set of independent clusters, underlining physiological relationships. The aim of this study was to investigate, using factor analysis, a clustering of pro-inflammatory markers, anti-inflammatory cytokines such as interleukin-10 (IL-10) and HDL cholesterol, and to determine their role in prediction of risk of recurrent coronary events in ACS patients. Methods We assessed 320 consecutive patients (236 men; 67 years; IQ 58–74 years) admitted with ACS. The composite of cardiac death and re-hospitalization with non-fatal myocardial infarction, or unstable angina, was the pre-specified study end-point. Serum CRP, fibrinogen, HDL cholesterol, IL-10, IL-18 and ICAM-1 levels were measured at study entry. We assessed independent predictors of the combined end-point during a 1-year follow-up using multiple logistic regression analysis. Results Factor analysis identified three clusters which were arbitrarily interpreted as (1) a “systemic inflammation” cluster with positive loadings of CRP and fibrinogen, (2) a “local inflammation–endothelial dysfunction” cluster with positive loadings of IL-18 and ICAM-1 and (3) an “anti-inflammation” cluster comprising IL-10 and HDL cholesterol. Only the “anti-inflammation” cluster was a significant predictor (OR 0.66, 95% CI: 0.49–0.89) of adverse cardiac events during a 1-year follow-up and remained significant (OR 0.65, 95% CI: 0.48–0.88) in a multivariate model that included all three factors. Conclusions Although inflammatory markers such as CRP predict future cardiovascular events in ACS patients, when all inflammatory mediators are taken into account in a prospective analysis of risk, markers reflecting anti-inflammatory mechanisms are better prognostic markers.

Microvascular Function, Metabolic Syndrome, and Novel Risk Factor Status in Women With Cardiac Syndrome X

To characterize microvascular function, candidate risk pathways, and metabolic syndrome prevalence in women with cardiac syndrome X, 52 nondiabetic women with angiographically normal epicardial arteries but >1 mm of planar ST depression during exercise testing (patients) and 24 healthy controls of similar age were recruited. In addition to fasting blood samples and anthropometric measurements, forearm cutaneous microvascular function after iontophoresis of acetylcholine and sodium nitroprusside was assessed by laser Doppler imaging. Despite body mass index correction and a larger proportion on statin therapy, patients had high levels of insulin (p=0.016), triglycerides (p=0.018), intercellular adhesion molecule-1 (p=0.021), von Willebrand factor (p=0.005), and leptin (p=0.005) and lower levels of high-density lipoprotein cholesterol (p=0.042) compared with controls. Consistent with these data, 30% of patients but only 8% of controls fulfilled criteria for the metabolic syndrome as defined by the National Cholesterol Education Program (p=0.015). Endothelium-dependent and -independent microvascular functions were markedly impaired in patients (p<0.001), and the odds ratio for cardiac syndrome X was 7.38 (95% confidence interval 2.2 to 24.7) if the acetylcholine response was <8,710 flux units. In conclusion, women with cardiac syndrome X more commonly have metabolic syndrome and related adiposity, metabolic, and inflammatory derangements. They also have significantly impaired skin microvascular function as assessed by laser Doppler imaging, consistent with generalized vascular dysfunction, a finding with potential diagnostic implications.

ICAM1 amino-acid variant K469E is associated with paediatric bronchial asthma and elevated sICAM1 levels

Intercellular adhesion molecule-1 (ICAM1) acts as ligand for beta2-integrin molecules and mediates leucocyte trafficking to the site of inflammation. Intercellular adhesion molecule-1-deficient mice show impaired lymphocyte recruitment to the lung, less airway hyper-responsiveness and less lung inflammation than healthy controls. Thus, the aim of the study was to test common ICAM1 polymorphisms for association with paediatric asthma. Furthermore, we were interested in whether soluble ICAM1 (sICAM1) serum levels were in correlation with genotypes. The following polymorphisms in ICAM1 were genotyped on 352 children with asthma and 270 controls: rs5491 (resulting in the amino-acid exchange K56M), rs5493 (G241S), rs5498 (K469E), rs5030400 (R478W) and rs885743 in the 3'-untranslated region. In addition, sICAM1 serum levels were measured. Only K469E and rs885743 were present in our populations. K469E showed association with asthma (P = 0.0037 with Armitage's trend test). Haplotype analysis by FAMHAP using both polymorphisms revealed association with asthma by P < 0.000001. In addition, serum sICAM1 levels were correlated with K469E genotypes (P = 0.009 by Kruskal-Wallis test). We conclude from our data that K469KE is associated with paediatric asthma in the German population. Furthermore, the same polymorphism is correlated with serum levels of sICAM1. Functional analyses have to further clarify the pathophysiological mechanism conferred by the polymorphisms.

Evaluation of soluble adhesion molecules CD44 (CD44st, CD44v5, CD44v6), ICAM-1, and VCAM-1 as tumor markers in head and neck cancer

Purpose Standard CD44 (CD44st), CD44 variant 5 (CD44v5), and CD44 variant 6 (CD44v6), intercellular adhesion molecule 1(ICAM-1), and vascular cell adhesion molecule 1(VCAM-1) are expressed in human malignant cells and tissues. Their mechanism remains unclear but has been reported to be associated with the progression and metastasis of malignancies. Materials and methods In this study, we investigated any correlations between the soluble adhesion molecule CD44 (st, v5, and v6), ICAM-1, and VCAM-1 and the clinicopathologic variables (eg, age, sex, histological grading, tumor size, lymph node status, distant metastasis, and TNM staging) and evaluated the difference between the pretreatment level in the patients with head and neck cancer and that in the control group. Furthermore, we examined the difference between the pretreatment serum levels and the after-treatment serum levels in the group with head and neck cancer. The pretreatment and after-treatment serum levels of soluble CD44st, CD44v5, CD44v6, ICAM-1, and VCAM-1 were measured in 81 patients with head and neck cancer and in 20 healthy volunteers as controls. Results There were no significant differences between the serum levels of sCD44st, sCD44v5, sCD44v6, sICAM-1, and sVCAM-1 and the clinicopathologic variables in cancer patients. However, the higher serum level of sCD44v6 was significantly associated with distant metastasis ( P = .02). Especially, we found that the pretreatment serum levels of sCD44st, sCD44v5, and sCD44v6 were markedly associated with TNM staging (CD44st P = .0017, CD44v5 P = .0005, CD44v6 P = .0046). Furthermore, the median serum levels of sCD44st, sCD44v5, sCD44v6, sICAM-1, and sVCAM-1 before treatment of head and neck cancer were significantly higher than those of the control group (CD44st P = .0067, CD44v5 P = .0048, CD44v6 P = .0007, ICAM-1 P = .0089, VCAM-1 P = .0178). The median serum level of sCD44st after treatment in the group of patients was significantly lower than that of pretreatment (CD44st P = .0001). And, both the median serum levels of sCD44v5 and sCD44v6 after treatment were also lower than those of pretreatment (CD44v5 P = .0004, CD44v6 P = .0025). Conclusions The possible roles of soluble adhesion molecules in the prognosis of head and neck carcinoma deserve further elucidation and evaluation with long-term patient follow-up.

Increased plasma soluble adhesion molecules; ICAM-1, VCAM-1, and E-selectin levels in patients with slow coronary flow

Background Inflammation has been reported to be a major contributing factor to many cardiovascular events. In the present study, we aimed to evaluate plasma soluble adhesion molecules; intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin as possible indicators of endothelial activation or inflammation in patients with slow coronary flow. Method Study population included 17 patients with angiographically proven normal coronary arteries and slow coronary flow in all three coronary vessels (group I, 11 male, 6 female, mean age = 48 ± 9 years), and 20 subjects with angiographically proven normal coronary arteries without associated slow coronary flow (group II, 11 male, 9 female, mean age = 50 ± 8 years). Coronary flow rates of all patients and control subjects were documented by Thrombolysis In Myocardial Infarction frame count (TIMI frame count). All patients in group I had TIMI frame counts greater than two standard deviation above those of control subjects (group II) and, therefore, were accepted as exhibiting slow coronary flow. Serum levels of ICAM-1, VCAM-1, and E-selectin were measured in all patients and control subjects using commercially available ELISA kits. Results Serum ICAM-1, VCAM-1, and E-selectin levels of patients with slow coronary flow were found to be significantly higher than those of control subjects with normal coronary flow (ICAM-1: 545 ± 198 ng/ml vs. 242 ± 113 ng/ml respectively, p < 0.001, VCAM-1: 2040 ± 634 ng/ml vs. 918 ± 336 ng/ml respectively, p < 0.001, E-selectin: 67 ± 9 ng/ml vs. 52 ± 8 ng/ml respectively, p < 0.001). Average TIMI frame count was detected to be significantly correlated with plasma soluble ICAM-1 ( r = 0.550, p < 0.001), VCAM-1 ( r = 0.569, p < 0.001) and E-selectin ( r = 0.443, p = 0.006). Conclusion Increased levels of soluble adhesion molecules in patients with slow coronary flow may be an indicator of endothelial activation and inflammation and are likely to be in the causal pathway leading to slow coronary flow.

Elevation of Serum Soluble E- and P-Selectin in Patients with Hypertension Is Reversed by Benidipine, a Long-Acting Calcium Channel Blocker

Hypertension is a major risk factor for atherosclerotic cardiovascular disease. Selectins, cell-surface adhesion molecules involved in leukocyte rolling and attachment to the vascular endothelium, play a role in the initiation of atherosclerosis. We investigated whether or not serum levels of soluble adhesion molecules are elevated in patients with essential hypertension (EH) and examined whether antihypertensive therapy lowers such levels. Twenty-one patients who had untreated mild to moderate EH without diabetes mellitus, hyperlipidemia, or obesity were recruited at a clinic for hypertensive patients. Blood pressure was measured, and the serum levels of soluble E-selectin, P-selectin, L-selectin, intercellular adhesion molecule 1 (ICAM-1), and vascular-cell adhesion molecule 1 (VCAM-1) were determined by enzyme-linked immunosorbent assays before and after 12, 24, and 53 weeks of antihypertensive treatment with benidipine, a long-acting calcium channel blocker, given at a dose of 6 mg/day for 53 weeks. As a control, 21 age- and sex-matched patients without hypertension were studied. Serum E- and P-selectin levels were significantly higher in the subjects with EH than in the controls (p < 0.01). There were no differences in serum levels of soluble L-selectin, VCAM-1, or ICAM-1 levels between the patients with EH and the controls. Treatment with benidipine decreased the elevated blood pressure over a 53-week study period (mean blood pressure: 119.8 +/- 6.5 mmHg at baseline, 101.0 +/- 5.9 mmHg at 12 weeks, 98.6 +/- 7.3 mmHg at 24 weeks, and 93.9 +/- 5.5 mmHg at 53 weeks). Serum levels of soluble E- and P-selectin decreased after the initiation of benidipine treatment and correlated with diastolic blood pressure. Serum levels of soluble L-selectin, VCAM-1, and ICAM-1 did not change significantly during the period of benidipine treatment. Benidipine treatment reduced the content of P-selectin in the platelets from patients with EH, as determined by Western blot analysis. In conclusion, decreased blood pressure may reduce the rate of progression of atherosclerosis by affecting the expression of E- and P-selectin in the endothelium, the platelets, or both. Benidipine may be protective against vascular damage in people with hypertension, not only by lowering blood pressure, but also by inhibiting the expression of selectins.

The serum levels of ICAM-1, nitric oxide and xanthine oxidase in rheumatoid arthritis

This study was carried out to determine the serum levels of soluble intercellular adhesion molecule 1 (ICAM-1), nitric oxide and xanthine oxidase in patients with rheumatoid arthritis (RA) and to investigate the correlations between ICAM-1 and nitric oxide and xanthine oxidase. Serum samples were obtained from 42 patients with active RA and 30 healthy controls. ICAM-1, nitric oxide and xanthine oxidase levels were determined. ICAM-1, nitric oxide and xanthine oxidase levels were significantly elevated in patients with RA (p < 0.001). We found a significant positive correlation between ICAM-1 and nitric oxide (r = 0.426, p < 0.05). There was also a significant positive correlation between ICAM-1 and xanthine oxidase (r = 0.511, p < 0.01). High serum levels of soluble ICAM-1 may be a consequence of inflammation or tissue damage induced by nitric oxide generated by xanthine oxidase.

The relationship between the serum intercellular adhesion molecule-1 level and the prognosis of the disease in lung cancer.

Background :Adhesion molecules are related to cell-to-cell interaction and inflammatory interaction. In addition, adhesive interactions between tumor cells and adjacent cells and/or extracellular matrix play important roles in the complex process of tumor growth and development. Among these adhesion molecules, expression of intercellular adhesion molecule-1 (ICAM-1) has been identified in colon cancer, bladder cancer, lung cancer, melanoma, pancreatic cancer and hepatocellular carcinoma. In the current study, we analyzed serum ICAM-1 concentrations to investigate the relationship between the serum ICAM-1 level and prognosis in patients with lung cancerMethods :Serum ICAM-1 was measured in 84 patients with lung cancer according to the pathologic type and clinical stage using the ICAM-1 ELISA kit. The Kaplan-Meier method was used to analyse survival time.Results :There was no difference in serum ICAM-1 concentration among the different stages of lung cancer. Furthermore, there was no difference observed between histologic tumor type with regard to serum ICAM-1 concentration. Although the difference was not significant, the overall survival times of patients with a low serum ICAM-1 concentration (<306 ng/mL) was longer than that of patients with a high concentration (≥306 ng/mL) in non-small cell lung cancer patients.Conclusion :These results suggest that high levels of serum ICAM-1 reflect poor prognosis for patients with non-small cell lung cancer.

Changes in plasma levels of adhesion molecules after percutaneous mitral balloon valvuloplasty

Background Adhesion molecules are expressed on vascular endothelium and on immune and inflammatory cells. Recently increased levels of adhesion molecules have been shown in patients with rheumatic mitral stenosis. This study examined the serum levels of the adhesion molecules intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and E-selectin in patients with rheumatic mitral stenosis and the effects of percutaneous mitral balloon valvuloplasty (PMBV) on these adhesion molecules. Materials and methods Thirty five patients (3 men, 32 women, mean age 39±5 years) with severe rheumatic mitral stenosis who underwent percutaneous balloon mitral valvuloplasty, and 35 age and sex matched healthy control subjects were included in the study. Serum levels of ICAM-1, VCAM-1, and E-selectin were measured in all patients who underwent PMBV and in all control subjects. Blood samples were taken for measurement of adhesion molecules immediately before and 24 h after the mitral balloon valvuloplasty. Results The plasma levels of soluble adhesion molecules E-selectin, ICAM-1 and VCAM-1 were significantly elevated in patients with mitral stenosis compared to control subjects: E-selectin, 97±59 vs. 45±24 ng/ml ( P=.001), sICAM-1, 874±301 ng/ml vs. 238±82 ng/ml ( P<.0001); sVCAM-1, 3056±763 ng/ml vs. 985±298 ng/ml ( P<.0001). Plasma levels of VCAM-1 significantly increased 24 h after the valvuloplasty procedure (3056±763 ng/ml vs. 3570±1225 ng/ml P=.013). Plasma levels of E-selectin showed a significant decrease after PMBV (97±59 vs. 70±58 ng/ml, P=.043) and plasma levels of ICAM-1 did not show any change after PMBV (874±301 vs. 944±377 ng/ml, P=.356). Conclusion Cellular adhesion molecules, sICAM-1, E-selectin, sVCAM-1 have shown changes in different directions in response to PMBV. These results necessitate further studies to clarify the mechanism underlying the association between adhesion molecules and PMBV as well as rheumatic mitral stenosis.

Biological determinants of serum ICAM-1, E-selectin, P-selectin and L-selectin levels in healthy subjects: the Stanislas study

Background: Circulating levels of adhesion molecules increase in various inflammation-related diseases, such as atherosclerosis. However, data about factors influencing their concentrations in physiological conditions are scarce. Methods: We have studied the determinants of serum levels of intercellular adhesion molecule-1 (ICAM-1), E-selectin, P-selectin and L-selectin in a sample of healthy individuals: 303 children (4–17 years) and 493 adults (18–55 years). The concentrations of these molecules have been measured by enzyme-linked immunosorbant assay. Results: As far as the children are concerned, a decrease in the levels of ICAM-1, E-selectin, P-selectin and L-selectin has been noticed for both boys and girls aged 4–17 years, without any difference between genders. For the adults, no age-related variation has been found for the ICAM-1, E-selectin and P-selectin levels, while the L-selectin level decreased until 55 years old. In the adult group, no sex-related difference in the concentrations of ICAM-1, E-selectin and L-selectin has been seen. As to the P-selectin level, men had significantly higher levels than women. Multiple regression analysis showed that smoking, homeostasis model assessment (HOMA) index, aspartate aminotransferase (AST), alkaline phosphatase (ALP) and C-reactive protein (CRP) were significant positive determinants of the ICAM-1 concentration, whereas age and apo AI were negative ones. The E-selectin level was positively associated with body mass index (BMI), leukocyte, platelet and erythrocyte counts, glucose, ALP and tumor necrosis factor-alpha (TNF-α), and negatively related to the use of oral contraceptive (OC). Positive determinants of the P-selectin concentration were leukocyte, platelet and erythrocyte counts, whereas sex, the use of oral contraceptive, glucose and TNF-α were negative determinants of P-selectin. Only two determinants have been noticed for the concentration of serum L-selectin: age, which was negatively correlated, and leukocyte count, which was positively associated. Conclusion: Our study contributes to the understanding of the regulation of adhesion molecules in physiological conditions.

Adhesion molecules, endogenous granulocyte colony-stimulating factor levels and replating capacity of progenitors in autoimmune neutropenia of childhood.

To investigate the role of granulocyte colony-stimulating factor (G-CSF) and adhesion molecules and the response of bone marrow to peripheral cytopenia in autoimmune neutropenia of childhood (AIN). Thirty-five children with AIN, 25 with acute leukaemia in remission, 10 of whom developed chemotherapy-associated neutropenia, and 28 non-neutropenic age-matched children were studied. The methods included haemopoietic progenitor cells' colony growth, replating of colony-forming unit-granulocyte macrophage (CFU-GM) of the 7th day and ELISA for the detection of serum levels of cytokines and adhesion molecules. In cases of severe autoimmune neutropenia, haemopoietic progenitors showed increased proliferative capacity compared to the control group (p = 0.03). Intercellular adhesion molecule-1 (ICAM-1), E-selectin, tumour necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) levels inversely correlated with neutrophil counts (r = -0.8, p < 0.001 for ICAM-1, r = -0.5, p = 0.04 for E-selectin, r = -0.58, p = 0.01 for TNF-alpha, r = -0.62, p = 0.04 for IL-1beta). Serum ICAM-1, TNF-alpha and IL-1beta levels correlated positively with G-CSF levels (r = 0.47, p = 0.03 for ICAM-1, r = 0.65, p = 0.01 for TNF-alpha, r = 0.67, p = 0.04 for IL-1beta). Serum G-CSF levels were widely distributed and did not correlate with neutrophil counts (r = -0.44, p = 0.09). In secondary neutropenias the respective levels were lower than those in autoimmune neutropenia. Haemopoietic progenitors show increased proliferative capacity in cases of severe autoimmune neutropenia. G-CSF seems to act as an inducer of endothelium activation. The degree of neutropenia correlates with serum ICAM-1, E-selectin, TNF-alpha and IL-1beta levels, indicating the existence of an activated endothelium and presumably of a latent, low-grade, inflammatory process in severe autoimmune neutropenia.

Potential Value of Soluble Intercellular Adhesion Molecule-1 in the Serum of Patients with Bladder Cancer

Introduction: The potential value of serum levels of intercellular adhesion molecule-1 (ICAM-1) in the staging and pathological nature of bladder cancer was investigated in this study. Materials and Methods: A total of 90 patients (mean age 64.5 ± 7.1) having transitional cell carcinoma of the bladder and 30 control patients (mean age 64.0 ± 5.5) were enrolled in the study. The serum samples of the patients were obtained on the day before surgery, at the same hour of the day. Results: The preoperative sICAM-1 levels were found to be 46.2 ± 14.7 and 28.0 ± 7.8 ng/ml in the tumor group and the control group respectively, which is significantly higher (p = 0.00). The ICAM-1 levels were not different in the invasive tumor group (36 patients) and the superficial tumor group (54 patients; 47.3 ± 13.8 ng/ml in the invasive group and 45.5 ± 15.3 ng/ml in the superficial tumor group; p = 0.520). The serum levels of sICAM-1 were significantly higher in grade III tumors than grade I and II tumors (62.0 ± 8.7, 38.4 ± 11.9 and 42.2 ± 8.2 ng/ml respectively; p = 0.000). The mean serum sICAM-1 levels in tumors >3 cm and <3 cm were found to be 52.6 ± 15.8 and 40.7 ± 11.0 ng/ml respectively which is statistically significant (p = 0.000). Conclusions: In this study, serum ICAM-1 levels were found to be related to tumor presence, grade and size. Larger series are needed for the thorough understanding of the role of ICAM-1 in bladder cancer.

Clinical significance of serum levels of E-selectin, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 in gastric cancer patients.

This study evaluated serum concentrations of soluble cell adhesion molecules in patients with gastric cancer and in healthy control subjects. Our objectives were to correlate these levels with clinicopathological features, established tumor markers, and patient survival, and to assess changes in serum levels of cell adhesion molecules after tumor surgery. The serum concentrations of the adhesion molecules E-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) were investigated by ELISA in 57 gastric cancer patients, both before and 7 days after surgery, and in 47 healthy control subjects. Preoperative serum concentrations of ICAM-1 and VCAM-1 in gastric cancer patients were significantly higher when compared with those of healthy controls, whereas there were no differences regarding serum E-selectin levels. Serum levels of E-selectin, ICAM-1, and VCAM-1 correlated significantly with each other. There was a significant association between preoperative levels of all three adhesion molecules and disease stage, gastric wall invasion, lymph node involvement, and presence of distant metastases. Their concentrations decreased significantly after radical resection of the tumor, whereas they remained almost unchanged in patients with unresectable disease. Elevated preoperative serum levels of E-selectin, ICAM-1, and VCAM-1 levels were found in 24.6%, 33.3%, and 28.1% of patients, respectively. Elevated levels of all three molecules were significant prognostic factors for patient survival but not independent of disease stage. These findings suggest that serum concentrations of E-selectin, ICAM-1, and VCAM-1 may reflect tumor progression and metastasis, and may be clinically useful.

Clinical significance of serum levels of E-selectin, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 in gastric cancer patients

Objectives This study evaluated serum concentrations of soluble cell adhesion molecules in patients with gastric cancer and in healthy control subjects. Our objectives were to correlate these levels with clinicopathological features, established tumor markers, and patient survival, and to assess changes in serum levels of cell adhesion molecules after tumor surgery. Methods The serum concentrations of the adhesion molecules E-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) were investigated by ELISA in 57 gastric cancer patients, both before and 7 days after surgery, and in 47 healthy control subjects. Results Preoperative serum concentrations of ICAM-1 and VCAM-1 in gastric cancer patients were significantly higher when compared with those of healthy controls, whereas there were no differences regarding serum E-selectin levels. Serum levels of E-selectin, ICAM-1, and VCAM-1 correlated significantly with each other. There was a significant association between preoperative levels of all three adhesion molecules and disease stage, gastric wall invasion, lymph node involvement, and presence of distant metastases. Their concentrations decreased significantly after radical resection of the tumor, whereas they remained almost unchanged in patients with unresectable disease. Elevated preoperative serum levels of E-selectin, ICAM-1, and VCAM-1 levels were found in 24.6%, 33.3%, and 28.1% of patients, respectively. Elevated levels of all three molecules were significant prognostic factors for patient survival but not independent of disease stage. Conclusions These findings suggest that serum concentrations of E-selectin, ICAM-1, and VCAM-1 may reflect tumor progression and metastasis, and may be clinically useful.

Relationship between IL-18 and sICAM-1 serum levels in patients affected by coeliac disease: preliminary considerations

Objectives: Cytokine production from activated T cells play a pathogenetic role in mucosal lesions of coeliac disease (CD). Active interleukin (IL)-18 is expressed in the small intestinal mucosa in CD but not in healthy controls. IL-18 enhances intercellular adhesion molecule-1 (ICAM-1) expression. We analyzed IL-18 serum levels in CD patients before and after gluten-free diet and the possible correlation with soluble ICAM-1 (sICAM-1) serum levels. Methods: The study comprises ten CD patients before and after gluten free diet and ten healthy controls. Serum IL-18 and sICAM-1 levels were assayed by immunoenzymatic methods. Results: Serum IL-18 and sICAM-1 levels were significantly higher in patients with CD before diet with respect to healthy controls ( P<0.05), with a highly significant correlation between the two parameters (Rho=0.800, P=0.0167). Gluten free diet significantly reduces IL-18 and sICAM-1. Conclusion: Our findings show that IL-18 serum concentrations correlated with the clinical status of CD patients suggesting a role for this cytokine in the pathophysiology of this disease.

Circulating levels of ICAM-1, VCAM-1, and MCP-1 are increased in haemodialysis patients: association with inflammation, dyslipidaemia, and vascular events.

Increased levels of circulating adhesion molecules and chemokines have been reported in haemodialysis (HD) patients but the influence of the HD membranes on their secretion, as well as their pathophysiological implications, remains largely unknown. Circulating levels of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and monocyte chemoattractant protein-1 (MCP-1) were measured by immunosorbent assay (ELISA) in 81 HD patients (45 male, mean age 57+/-13 years) and 35 normal subjects. All patients had been stabilized on renal replacement therapy for >3 months and were free of active infection. Thirty-three patients (40.7%) were routinely dialysed with modified cellulose membranes and 48 patients (59.3%) were dialysed with polysulfone membranes. Blood samples were taken directly from the arteriovenous fistula immediately before and at the end of a routine HD session. Pre-dialysis levels were significantly elevated in HD patients compared with controls (ICAM-1 515+/-177 vs 238+/-664 ng/ml, P<0.0001; VCAM-1 2107+/-648 vs 1012+/-115 ng/ml, P<0.0001; MCP-1 427+/-148 vs 125+/-42 pg/ml, P<0.0001). The HD session resulted in a significant increase in the levels of all three molecules measured (515+/-177 vs 679+/-187 ng/ml, P<0.0001; 2107+/-648 vs 2662+/-800 ng/ml, P<0.0001; 427+/-148 vs 567+/-153 pg/ml, P<0.0001, respectively). There was no difference in pre- or post-dialysis levels of the above molecules between patients routinely dialysed with either modified cellulose or polysulfone membranes. MCP-1 levels had a positive correlation with ICAM-1 levels (r=0.41, P<0.0005). VCAM-1 levels had a negative correlation with HDL levels (r=-0.30, P<0.01) and were significantly elevated in patients with HDL <35 mg/dl compared with patients with HDL > or = 35 mg/dl (2300+/-606 vs 1890+/-633 ng/ml, P<0.005). Log-transformed exact C-reactive protein (CRP) values were significantly correlated with ICAM-1 and VCAM-1 levels (r=0.41, P<0.005 and r=0.43, P<0.005, respectively). In addition, compared with patients with normal CRP values, patients with elevated CRP had significantly increased levels of ICAM-1 (466+/-166 vs 580+/-172 ng/ml, P<0.005). Patients with cardiovascular, cerebrovascular, or peripheral vascular diseases had significantly increased serum CRP and ICAM-1 levels compared with patients with no evidence of vascular disease (19.2+/-12.9 vs 7.9+/-11.8 mg/l, P<0.001 and 608+/-189 vs 474+/-155 ng/ml, P<0.005 respectively). Serum levels of ICAM-1, VCAM-1, and MCP-1 are increased in HD patients and probably result from either inadequate clearance or enhanced synthesis and release. HD session resulted in a significant increase of the above molecule levels but the exact mechanism(s) responsible for these alterations are yet to be fully elucidated. Increased levels of adhesion molecules are associated with inflammation, dyslipidaemia, and cardiovascular events. However, the potential link between these processes and its clinical significance warrants further investigation.