Serum Concentrations Of Monocyte Chemoattractant Protein-1 Research Articles

Circulating Monocyte Chemoattractant Protein-1 (MCP-1) in Patients with Primary Biliary Cholangitis.

Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease that leads to the destruction of the intrahepatic bile ducts. While the inflammatory process can be mediated by monocyte chemotactic protein-1 (MCP-1), the importance of circulating MCP-1 as a biomarker is unclear. Our aim was to assess the diagnostic significance of the serum concentrations of MCP-1 in PBC patients. We compared circulating MCP-1 with biochemical, immunological and histological parameters. Serum samples were collected from 120 PBC patients, 60 pathologic controls and 30 healthy donors. MCP-1 levels were determined by using commercial enzyme-linked immunosorbent assay (ELISA). Elevated serum MCP-1 levels were detected in 66% of PBC patients with a specificity of 97%. Significantly higher levels of MCP-1 protein were found in the sera of patients with PBC than in the group of healthy individuals-410.2 pg/mL vs. 176.0 pg/mL, p < 0.01). Patients with higher concentrations of alkaline phosphatase also had higher levels of MCP-1 (r = 0.4, p < 0.01). In accordance with Ludwig's classification, a positive correlation of serum MCP-1 concentration with the degree of fibrosis was observed, OR = 6.1, p = 0.0003. We compared the MCP-1 with procollagen type III, hyaluronic acid (HA), FIB-4 index, APRI and collagen type IV when predicting the advance of liver fibrosis. Circulating MCP-1 is better correlated with liver fibrosis and is also associated with the occurrence of specific antimitochondrial autoantibodies and specific anti-nuclear autoantibodies-anti-gp210. MPC-1 can be considered to be a tool for diagnosing the degree of fibrosis in PBC, and combinations of MCP-1 and other specific biomarkers could support the diagnosis of PBC.

ОЦЕНКА ЗНАЧИМОСТИ ВЗАИМОСВЯЗИ МЕЖДУ ПОКАЗАТЕЛЯМИ РЕМОДЕЛИРОВАНИЯ СОСУДОВ, ВОСПАЛИТЕЛЬНОГО ОТВЕТА И ПОЛИМОРФИЗМА ГЕНОВ ДИСФУНКЦИИ ЭНДОТЕЛИЯ У ПАЦИЕНТОВ МУЖСКОГО ПОЛА С ИНФАРКТОМ МИОКАРДА В ЗАВИСИМОСТИ ОТ НАЛИЧИЯ ИЛИ ОТСУТСТВИЯ ГИПЕРТОНИЧЕСКОГО АНАМНЕЗА

Introduction. Endothelial dysfunction, arterial hypertension and surrogate events of myocardial infarction are interrelated phenomena, while the genetic predisposition in these patients is an independent risk factor for the development of cardiovascular pathology. Aim. The aim of the study was to evaluate the significance of the interaction of associations of polymorphic loci of adhesion molecule genes (immunoglobulin VCAM1), MCP-1 chemokine, vascular endothelial growth factor (VEGFA), nitric oxide control enzyme (DDAH1), markers of the inflammatory response, vascular remodeling and endothelial dysfunction in patients with male myocardial infarction, depending on the presence or absence of arterial hypertension in history in the development of myocardial infarction. Material and methods. 667 male patients and 621 practically healthy individuals in the comparison group were examined. Patients underwent determination of general clinical parameters, serum concentrations of monocyte-chemoattractant protein-1 (MCP-1), vascular endothelial growth factor (VEGFA), cytokines (IL-1,6; TNF-α), molecular genetic study, measurement of media intima thickness of the common carotid artery. Selected in the group of patients with myocardial infarction, individuals with or without a history of arterial hypertension. Results and discussion. As a result of a comparative analysis of groups of patients with and without a history of arterial hypertension with a group of healthy individuals, significant differences in the frequencies of genotypes and alleles for the following polymorphic gene loci were revealed: MCP-1, VEGFA, DDAH1, VCAM1. The serum concentration of cytokines (IL-1,6; TNF-α) in patients, regardless of the presence or absence of a history of hypertension, significantly exceeded the level in the comparison group. The VEGFA index in patients with myocardial infarction with arterial hypertension was significantly increased compared to the serum level in patients with myocardial infarction without arterial hypertension. Conclusion. A higher significance of the interaction between indicators of vascular remodeling, inflammation, endothelial dysfunction gene polymorphism in the development of myocardial infarction in patients with a history of hypertension, in contrast to non-hypertensive patients with myocardial infarction, was revealed, which indicates a powerful contribution of arterial hypertension to the etiology and implementation of myocardial infarction.

Assessment of Monocyte Chemo-Attractant Protein-1 (MCP-1) and Other Biochemical Parameters in Iraqi Pregnant Women

The monocyte chemo-attractant protein-1 (MCP-1) is one of the pro-inflammatory cytokines. It controls the passage and infiltration of monocytes, macrophages, natural killers, and T cells into the sites of inflammation. The aim of this study is to inspect the role of MCP-1 in maternal metabolic, physiological changes and pregnancy complications like gestational diabetes mellitus, dyslipidemia, and hypertension to develop pharmaceutical strategies for these complications. This study included ninety Iraqi women divided into three groups: thirty pregnant women in their first trimester as the P1 group; thirty pregnant women in their third trimester as the P2 group; and thirty healthy non-pregnant women as the control or C group. Serum concentrations of MCP-1 were analyzed by the ELISA technique (sandwich principle). Fasting plasma glucose (FPG), C-reactive protein (CRP), fasting serum insulin (FSI), glycosylated hemoglobin (HbA1c), lipid profile, systolic, diastolic blood pressure, liver function enzymes ALT, AST and anthropometric parameters were measured. Our results revealed that serum MCP-1 significantly declined in the first trimester (P1) compared to the C group (p&lt;0.05) and non-significantly declined in the third trimester (P2) compared to that in the C group, while there was a significant difference in serum MCP-1 between the P1 and P2 groups (p&lt;0.05 ). Serum CRP showed a highly significant increase in the P1 and P2 groups compared to the C group at (p&lt;0.01). There is a highly significant difference between the P1 and P2 groups (p&lt;0.01). Serum MCP-1 had a significant positive correlation with body mass index (BMI), body fat percentage (BF %), systolic blood pressure (SBP) and C-reactive protein (CRP) in the P2 group (p&lt;0.05). No significant differences in FPG or HbA1C were found between all the studied groups. Lipid parameters: TC, TG, LDL, and VLDL showed a highly significant increase in the P2 group compared to the C and P1 groups (p&lt;0.01). HDL showed a highly significant decrease in the P2 group compared to the C group (p&lt;0.01), while it was only significantly decreased in the P2 group compared to the P1 group (p&lt;0.05). Depending on these results, we found that serum MCP-1 declines in pregnancy, the BMI, BF%, and the contractile arterial blood pressure (SBP) have a positive correlation with MCP-1 in late pregnancy, and the inflammation marker (CRP) has an independent association with MCP-1 in early gestation.

Quantile-specific heritability of monocyte chemoattractant protein-1, and relevance to rs1024611-disease interactions.

Monocyte chemoattractant protein-1 (MCP-1) concentrations are 34% to 47% heritable. Larger -2518 G/A (rs1024611) genotypes differences are reported for: 1) MCP-1 production in stimulated vs. basal cells; and 2) MCP-1 concentrations in diseased (sepsis, brain abscess, hepatitis B virus, Alzheimer's disease, Behcet's disease, and systemic lupus erythematosus) vs. healthy patients. Those results suggest that the -2518 G/A effect size may depend on whether the phenotype is high or low relative to its distribution (quantile-dependent expressivity). To test whether quantile-dependent expressivity applies more broadly to genetic influences on MCP-1 concentrations, quantile-specific offspring-parent (βOP) and full-sib regression slopes (βFS) were estimated by applying quantile regression to the age- and sex-adjusted serum MCP-1 concentrations of Framingham Heart Study families. Quantile-specific heritabilities were calculated as h2=2βOP/(1+rspouse) and h2={(1+8rspouseβFS)0.5-1}/(2rspouse)). Heritability (h2±SE) of MCP-1 concentrations increased from 0.15±0.05 at the 10th percentile of the MCP-1 distribution, 0.23±0.04 at the 25th, 0.32±0.05 at the 50th, 0.43±0.07 at the 75th, and 0.44±0.07 at the 90th percentile, or an 0.0041±0.0009 increase for each one-percent increment in the MCP-1 distribution (Plinear trend=2.4×10-5) when estimated from βOP, and (Plinear trend=7.7×10-9) when estimated from βFS. Compared to the 10th percentile, βOP-estimated h2 was 3-fold greater at the 90th percentile (Pdifference=0.0003), and 6.9-fold greater when estimated from βFS (Pdifference=3.3×10-6). Re-analysis of in vivo comparison of MCP-1 concentrations in controls vs. patients with MCP-1-elevating conditions, and in vitro studies of MCP-1 production in basal vs. stimulated cells, show rs1024611 genotypes differences that were consistent with quantile-dependent expressivity. The heritability of circulating MCP-1 concentrations is quantile-dependent.

Salivary and serum concentrations of monocyte chemoattractant protein-1, macrophage inhibitory factor, and fractalkine in relation to rheumatoid arthritis and periodontitis.

Monocyte chemoattractant protein-1 (MCP-1), macrophage migration inhibitory factor (MIF), and fractalkine are chemokines that are expressed by a variety of cell types to regulate macrophage inflammatory response. The aim of the study was to examine the effects of periodontitis and rheumatoid arthritis (RA) on their serum and salivary concentrations. Adults with either periodontitis (P, n=21), or with rheumatoid arthritis (RA, n=23), or with both diseases (RA+P, n=23) were included in the study. Systemically and periodontally healthy individuals (n=22) served as controls. Saliva and serum samples were collected from all participants before the medical and periodontal examinations. Salivary and serum MCP-1, MIF, and fractalkine concentrations were measured by the Luminex technique. Total salivary protein levels were determined by the Bradford assay. Salivary MCP-1, MIF, and fractalkine concentrations were elevated in both RA groups (RA+P and RA) in comparison with systemically healthy controls. As related to total salivary protein levels, higher MCP-1 (P=0.003) and fractalkine (P=0.045) concentrations were found in controls compared with the P group. In serum, MCP-1 concentrations in the RA+P group were higher (P=0.003) than those of group P. Elevated serum fractalkine concentrations were observed in both periodontitis groups (RA+P, P=0.014; and P, P=0.013) compared with controls. In RA, MCP-1, MIF, and fractalkine concentrations are elevated in saliva. These chemokines may disrupt oral macrophage responses and potentially take part in the interaction between periodontitis and RA.

Changes In Cognition During A 24-h Simulated Military Operation. Role Of Classical Monocytes And Beta-alanine.

Cognitive dysfunction during sustained military operations (SUSOP’s) may be related to the recruitment and infiltration of classical monocytes into the brain. Beta-alanine (BA) supplementation may attenuate cognitive dysfunction and improve resilience to stress exposure, which may be relevant during a SUSOP. PURPOSE: To examine the effect of BA on serum monocyte chemoattractant protein-1 (MCP1), C-C chemokine receptor 2 (CCR2), macrophage-1-antigen (CD11b) and cognition (COG), and to examine the relationships between these variables during a SUSOP. METHODS: Nineteen recreationally active men ingested 12g·day-1 BA (n = 10) or placebo (PL; n = 9) for 14-days prior to completing a simulated 24-h SUSOP. MCP1 was assessed via multiplex assay. Classical monocyte CCR2 and CD11b expression were assessed via flow cytometry. Throughput (TP) scores were extracted from seven cognitive subtests administered via Automated Neuropsychological Assessment Metric (ANAM) software. The relative weight of each ANAM subtest was determined by dividing its outer weight by the standard deviation of all TP scores for that subtest. TP scores were multiplied by their relative weights, and the values summed to provide a value for COG. Assessments occurred at baseline (0H), 12-hours (12H), 18-hours (18H) and 24-hours (24H). A two-way mixed ANOVA was used to assess differences between BA and PL. The statistical significance of pathway (β) coefficients derived from partial least squares structural equation modeling were used to evaluate relationships between MCP1, CCR2, CD11b and COG. RESULTS: MCP1 was significantly greater at 12H, 18H and 24H relative to 0H (p’s < 0.001). CCR2 expression was significantly lower at 12H (p = 0.031), 18H and 24H (p’s < 0.001), while CD11b expression was significantly greater at 12H (p = 0.039) and 24H (p = 0.003) relative to 0H. COG was significantly lower at 18H and 24H compared to 0H and 12H (p’s ≤ 0.001). No significant differences were noted between BA and PL for any variable (p’s > 0.05). MCP1 had a direct negative relationship with cognition (β = -0.395, p = 0.002). CCR2 and CD11b were not directly related to cognition (p’s > 0.50). CONCLUSIONS: Greater serum MCP1 concentrations were associated with increased cognitive dysfunction during the SUSOP. BA did not affect MCP1, CCR2, CD11b or COG compared to placebo.

Ratio of IL-8 in CSF versus Serum Is Elevated in Patients with Unruptured Brain Aneurysm.

Only scarce data pertaining to interleukin 8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) chemokines in human aneurysm can be found in the current literature. Therefore, the aim of this study was the evaluation of cerebrospinal fluid (CSF) and serum IL-8 and MCP-1 concentration in unruptured intracranial aneurysm (UIA) patients (n = 25) compared to the control group (n = 20). IL-8 and MCP-1 concentrations were measured with ELISA method. We demonstrated that CSF IL-8 concentration of UIA patients is significantly higher (p < 0.001) than that presented in the serum, which can indicate its local synthesis within central nervous system. CSF IL-8 concentration was also significantly related to aneurysm size, which may reflect the participation of IL-8 in the formation and development of brain aneurysms. IL-8 Quotient (CSF IL-8 divided by serum IL-8) in UIA patients was statistically higher compared to control individuals (p = 0.045). However, the diagnostic utility analysis did not equivocally indicate the diagnostic usefulness of the IL-8 Quotient evaluation in brain aneurysm patients. Nevertheless, this aspect requires further study.

Is there a Correlation between Monocyte Chemoattractant Protein-1 with Autotaxin, Azurocidin-1, Apolipoprotein C-III and Elastase-2 in Male Iraqi Acute Myocardial Infraction Patients?

Acute Myocardial infarction (AMI) is one of the important reasons of loss of life and bodily incapacity global prompt via cardiovascular diseases (CVD). AMI stimulates the innate immune system that is required to employee leukocytes to remove necrotic cells and recruit myocardial healing. To evaluate serum concentrations of Monocyte Chemoattractant Protein-1 (MCP-1), Autotaxin (ATX), Azurocidin-1 (AZU-1), Apolipoprotein C-III (APOC3) and Elastase-2 (ELA-2) in male Iraqi AMI patients and healthy controls (HCs), and explain the association of MCP-1with ATX, AZU-1, APOC3 and ELA-2 in male Iraqi AMI patients, also explore the best parameter which can use to differentiate between AMI patients. This case-control study included 84 men aged 40–68 years. Waist circumference (WC), hip circumference (HC), thoracic circumference (TC), neck circumference (NC), height, weight, age, and further covariates were obtained via an inquiry form. They were separated into two equivalent groups: the patients group and the healthy group, serum concentrations of MCP-1, ATX, AZU-1, APOC3 and ELA-2 were estimated via ELISA. Serum of MCP-1, ATX, AZU-1, APOC3 and ELA-2 concentrations were importantly greater in patients with AMI than in HCs (p&lt; 0.001). MCP-1 concentrations were importantly linked with ATX, AZU-1, APOC3 and ELA-2 in AMI cases (p&lt; 0.001). The greater value of MPC-1 association was with ELA-2 (r=0.592). MCP-1 exhibited the maximum value for área under curve (AUC=1) in comparison to other studied biomarkers. The present data explained the role of MCP-1, ATX, AZU-1, APOC3 and ELA-2 in AMI disease; we found they have central functions in this disease, mainly obese patients. Attention must be taken to avoid confusion among risk markers and risk factors. Great serum concentrations of MCP-1 offered important correlations between risk markers and risk factors of AMI disease.

Monocyte chemoattractant protein-1 (MCP-1) and fibroblast growth factor-21 (FGF-21) as biomarkers of subclinical atherosclerosis in women

Atherosclerosis is a primary risk factor for cardiovascular disease (CVD). Proinflammatory biochemical factors can influence vascular health; monocyte chemoattractant protein-1 (MCP-1) is elevated in patients with CVD while fibroblast growth factor-21 (FGF-21) acts directly on cardiac tissue to reduce infarction damage. However, the relationship between plasma concentrations of MCP-1, FGF-21 and subclinical CVD indices remains equivocal. To determine the association between MCP-1, FGF-21 and subclinical atherosclerosis [i.e., carotid intima-media thickness (cIMT)] in women without clinical evidence of CVD. A cross-sectional analysis of 140 women without history of CVD was performed. Anthropometrics were collected, serum concentrations of MCP-1 and FGF-21 were determined by enzyme-linked immunosorbent assay, and cIMT was quantified (B-mode ultrasonography). The correlations between MCP-1, FGF-21 and the presence of clinical and laboratory of subclinical atherosclerosis (i.e., cIMT ≥0.70 mm), comparison intergroup and odd ratio with multiple logistic regression were analyzed. MCP-1, but not FGF-21 correlated with some obesity indicators. In median comparison among groups, subclinical atherosclerosis showed higher serum concentrations of MCP-1and lower serum concentrations of FGF-21. In postmenopausal women, there were significant differences MCP-1 (p = 0.001), and FGF-21 (p = 0.010). Multiple logistic regression analysis in postmenopausal women with subclinical atherosclerosis, between MCP-1 (p = 0.001) and FGF-21 (p = 0.037) showed association with cIMT, along with age. MCP-1 and FGF-21 levels are associated with subclinical atherosclerosis disease severity (i.e., cIMT) in postmenopausal women without CVD. Further efforts focused on characterizing the relationship between novel blood-borne markers of early CVD pathology are warranted and should be pursued.

Factors related to peripheral arterial disease in patients undergoing hemodialysis: the potential role of monocyte chemoattractant protein-1.

Peripheral arterial disease (PAD) is substantially prevalent among patients in the end stage of renal disease (ESRD). We considered factors related to peripheral arterial disease in patients undergoing hemodialysis including the important role of monocyte chemoattractant protein-1 (MCP-1) serum concentrations. We studied 150 patients in on-line-predilution hemodiafiltration. Dialysis sufficiency was defined by Kt/V for urea. PAD was defined using clinical criteria, ankle-brachial index and Doppler ultrasound in the lower limbs. MCP-1 serum concentrations were measured using enzyme-linked immunoabsorbed assay (ΕLISA). We performed chi-square tests and logistic regression analysis to investigate risk factors for the prevalence of PAD in these patients including MCP-1 serum concentrations. The patients with manifested PAD had elevated MCP-1, higher BP, higher arterial stiffness markers, higher markers of malnutrition, uncontrolled metabolic acidosis, bone disease and lower obtained dialysis adequacy than the patients without PAD. The association between PAD manifestation and high MCP-1 was found significant (x2 = 9.6, p = 0.001). The built logistic regression analysis showed that the high MCP-1 increased the risk for PAD 3.2 (95% C.I 1.3-8.2) folds after adjustment for confounders. PAD was also significantly associated with non-administration of vitamin D agents during dialysis (x2 = 3.5, p = 0.04).Malnutrition, low-grade inflammation mainly defined by high MCP-1 serum concentrations, metabolic acidosis and bone disease were included in significant predictors for peripheral arterial disease in patients undergoing hemodiafiltration. The obtained dialysis sufficiency and the therapy during dialysis sessions seem to play an additional role in the demonstration of peripheral vascular disease in these patients.

Effect of vitamin D supplementation along with weight loss diet on meta-inflammation and fat mass in obese subjects with vitamin D deficiency: A double-blind placebo-controlled randomized clinical trial.

Low serum 25-hydroxyvitamin D (25OHD) is common in obese people. Obesity is associated with a state of low-grade inflammation (meta-inflammation). There is an increasing evidence indicating that vitamin D has anti-adipogenic activity and immunoregulatory effect. This study aimed to assess the effect of vitamin D supplementation on meta-inflammation and fat mass in obese subjects with vitamin D deficiency. In this double-blind placebo-controlled randomized clinical trial, 44 obese subjects with vitamin D deficiency (25OHD<50nmol/L) were assigned into vitamin D (a weight reduction diet+bolus weekly dose of 50000IU vitamin D) or placebo group (weight reduction diet+edible paraffin weekly) for 12weeks. Weight, fat mass and serum levels of 25OHD, calcium, parathyroid hormone (PTH), monocyte chemoattractant protein-1 (MCP-1), interleukin-1β (IL-1β) and Toll-like receptor 4 (TLR4) were assessed before and after the intervention. Vitamin D supplementation resulted in significant increase of serum 25OHD level (P<0.001), and significant decrease in PTH (P<0.001), MCP-1 (P<0.05), IL-1β (P<0.05) and TLR-4 (P<0.05); compared to the baseline values in vitamin D group. Weight, BMI and fat mass decreased in both groups (P<0.05). Between the groups, there were significant decrease in weight, fat mass, serum MCP-1 and PTH concentrations and significant increase in serum 25OHD concentrations after intervention with vitamin D supplementation compared to placebo (P<0.05). Improvement in vitamin D status in obese subjects with vitamin D deficiency in combination with weight loss diet resulted in weight, fat mass and MCP-1 decrease. Weight loss and vitamin D supplementation may act synergistically to reduce levels of meta-inflammation.

Short-term insulin intensive therapy decreases MCP-1 and NF-κB expression of peripheral blood monocyte and the serum MCP-1 concentration in newlydiagnosed type 2 diabetics.

To observe the effect of short-term insulin intensive treatment on the monocyte chemoattractant protein-1 (MCP-1) as well as on the nuclear factor-kappa B (NF-κB) expression of peripheral blood monocyte. This is also in addition to observing the serum MCP-1 level in newlydiagnosed type 2 diabetic patients and probing its anti-inflammation effects. Twenty newly-diagnosed type 2 diabetic patients were treated with an insulin intensive treatment for 2 weeks. MCP-1 and NF-κB expression on the monocyte surface were measured with flow cytometry, the serum MCP-1 level was measured by enzyme linked immunosorbent assay (ELISA) during pretreatment and post-treatment. After 2 weeks of the treatment, MCP-1 and NF-κB protein expression of peripheral blood monocyte and serum MCP-1 levels decreased significantly compared with those of pre-treatment, which were (0.50 ± 0.18)% vs (0.89 ± 0.26)% (12.22 ± 2.80)% vs (15.53 ± 2.49)% and (44.53 ± 3.97) pg/mL vs (49.53 ± 3.47) pg/mL, respectively (P < 0.01). The MCP-1 expression on monocyte surface had a significant positive relationship with serum MCP-1 levels (r = 0.47, P < 0.01). Short-term insulin intensive therapy plays a role in alleviating the increased inflammation reaction in type 2 diabetics.

The Relationship of Residual Renal Function with Cardiovascular Morbidity in Hemodialysis Patients and the Potential Role of Monocyte Chemoattractant Protein-1

Background: Residual renal function (RRF) provides several benefits to patients on dialysis. Monocyte chemoattractant protein-1 (MCP-1) plays an important role in atherosclerotic lesions. We considered the relationship between RRF and cardiovascular morbidity and the significant role of MCP-1 serum concentrations in hemodiafiltration (HDF) patients. Methods: We enrolled 76 patients on on-line HDF. RRF was defined by interdialytic urine output, and we studied the patients in two groups according to the preservation or not of urine output. MCP-1 levels were measured using enzyme-linked immunosorbent assay. χ² tests were applied for the association between RRF and left ventricular hypertrophy (LVH), coronary artery disease (CAD), peripheral artery disease (PAD), and systolic and diastolic cardiac dysfunction. We built an adjusted model using logistic regression analysis for the factors which might impact on the loss of urine output. Results: χ² tests showed a significant association between the loss of urine output and LVH, diastolic dysfunction, and PAD (χ² = 7.4, p = 0.007; χ² = 14.3, p = 0.001; χ² = 4.2, p = 0.03, respectively), although the association with CAD and systolic dysfunction was found to be nonsignificant. The patients without RRF had significantly higher MCP-1, and the urine volume was inversely associated with MCP-1 (r = -465, p = 0.03). In the built adjusted model, the elevated MCP-1 was found to be a significant predictor for the loss of RRF. Conclusion: The loss of RRF was significantly associated with LVH, diastolic dysfunction, and PAD in HDF patients. The increased MCP-1, affected by the lack of urine, may act as an additional underlying factor on this relationship, reflecting a progressive inflammation/oxidative stress condition.

Association between monocyte chemoattractant protein-1 and blood pressure in smokers.

ObjectiveThe expression level of monocyte chemoattractant protein-1 (MCP-1) is increased in atherosclerotic regions, inducing monocyte migration to the blood vessel wall. Although the serum MCP-1 concentration is higher in patients with than without cardiovascular disease, the precise correlations between the serum MCP-1 concentration and factors associated with smoking and atherosclerosis are unknown.MethodsThe serum MCP-1 concentration was measured using an enzyme-linked immunosorbent assay in 207 consecutive smokers who visited our smoking cessation clinic.ResultsSex-adjusted analysis of smokers revealed that the MCP-1 concentration was positively correlated with age (β = 0.311), smoking duration (β = 0.342), systolic blood pressure (β = 0.225), and diastolic blood pressure (β = 0.137) but not with the body mass index. Multivariate regression analysis showed that smoking duration and systolic blood pressure were independent determinants of the MCP-1 concentration.ConclusionsThe MCP-1 concentration was positively correlated with blood pressure among smokers. Long-term smokers with high blood pressure may be more susceptible to plaque rupture at atherosclerotic lesion sites.

Depletion of alveolar macrophages attenuates hypoxic pulmonary hypertension but not hypoxia-induced increase in serum concentration of MCP-1.

Exposure to hypoxia, leading to hypoxic pulmonary hypertension (HPH), is associated with activation of alveolar macrophages (AM). However, it remains unclear how AM participate in this process. There are studies which imply that the AM product monocyte chemoattractant protein-1 (MCP-1) plays an important role. Thus we tested: 1. if the selective elimination of AM attenuates HPH in rats, 2. the correlation of MCP-1 plasmatic concentrations with the presence and absence of AM during exposure to hypoxia, 3. the direct influence of hypoxia on MCP-1 production in isolated AM. We found that experimental depletion of AM attenuated the chronic hypoxia-induced increase in mean pulmonary arterial pressure, but did not affect the serum MCP-1 concentrations. Furthermore, the MCP-1 production by AM in vitro was unaffected by hypoxia. Thus we conclude that AM play a significant role in the mechanism of HPH, but MCP-1 release from these cells is most likely not involved in this process. The increase of MCP-1 accompanying the development of HPH probably originates from other sources than AM.

Role of monocyte chemoattractant protein-1, stromal derived factor-1 and retinoic acid in pathophysiology of neuropathic pain in rats.

Chemokines have been recently recognized to play a role in chronic pain syndromes' pathophysiology. This study investigated the role of monocyte chemoattractant protein-1 (MCP-1), stromal cell derived factor-1 (SDF-1), and retinoic acid (RA) as targets for the therapeutic approach of neuropathic pain. A chronic constriction injury (CCI) model of neuropathic pain by unilateral ligation of left sciatic nerve was performed in adult female Wistar rats. The effects of doxycycline (Dox, 50 mg/kg/day i.p. for 7 days), single dose of bicyclam (5 mg/kg i.p.), RA (15 mg/kg/day i.p. for 7 days), and their combination(s) on behavioral tests of nociception (Von Frey filaments; paw pressure test) on days 0, 1, 3, 5, and 7 of operation were studied. Serum concentrations of MCP-1 and SDF-1 were measured by ELISA. Histological examination of the sciatic nerve was investigated. CCI of sciatic nerve significantly induced mechanical allodynia and hyperalgesia and an increase of MCP-1 and SDF-1 serum levels. Dox-treated groups (Dox, Dox+bicyclam, Dox+RA, Dox+bicyclam+RA) and bicyclam-treated groups (bicyclam, Dox+bicyclam, bicyclam+RA, Dox+bicyclam+RA) attenuated CCI-induced behavioral and biochemical changes. RA inhibited CCI-induced mechanical hyperalgesia but produced a time-dependent reversal of allodynia. Histological findings showed degenerative changes of sciatic nerve after CCI that were partially recovered in Dox-treated groups. These findings demonstrate an association between serum MCP-1 and SDF-1 concentrations and behavioral manifestations of neuropathic pain. RA administration decreased neuropathic pain (antihyperalgesic effect) but did not cause any improvement in sciatic nerve tissues, either alone or in combination with chemokine antagonists. Thus, chemokines may serve as potential targets for drug development in neuropathic pain treatment.

Iron Deficiency Anaemia is Associated with Decreased Levels of Macrophage Migration Inhibitory Factor and Monocyte Chemoattractant Protein-1

Many bodily systems are affected by iron deficiency anaemia (IDA), including the immune system. However, the pathophysiological mechanisms whereby this anaemia promotes deterioration in immunity remain largely unexplained. In order to enlighten this pathophysiological link , serum levels of macrophage migration inhibitory factor (MIF) and monocyte chemoattractant protein-1 (MCP-1), which play an important roles in a healthy functioning immune system, were examined in patients with IDA and healthy volunteers. A total of 30 patients with IDA (mean age 33.6±7.8 years, 30% male) and 30 healthy individuals (mean age 30.1 ± 8.8 years, 27 % male) were included. Serum MIF and MCP-1 levels were measured in a sandwich-assay format, using commercial enzyme-linked immunosorbent assay kits. There was no statistically significant difference in age and gender distribution between participants with IDA and controls (p>0.05). Serum MIF and MCP-1 concentrations were lower in the IDA group than in the control group (p < 0.005, and p < 0.01, respectively). When considering the role of MIF and MCP-1 in maintaining the normal immune response of the organism, a decrease in production in patients with IDA may contribute to immune dysfunction in these individuals.

Pentoxifylline decreases serum level of adhesion molecules in atherosclerosis patients.

Inflammation is involved in development, progression, and complications of atherosclerotic disease. Clinical studies have indicated that the level of monocyte chemoattractant protein 1 (MCP-1), IL-18, and adhesion molecules correlates with the severity of atherosclerosis and can predict future cardiovascular events. Experimental studies have shown pentoxifylline (PTX) reduces these factors in animal models. The purpose of the present pilot study was to evaluate effect of PTX on a group of inflammatory biomarkers in patients with coronary artery disease (CAD). Forty patients with angiographically documented CAD, who fulfilled inclusion and exclusion criteria, were entered in the double-blind, randomized, pilot clinical study. The patients were randomly given PTX (400 mg three times daily) or placebo (3 tab/day) for 2 months. Serum concentrations of MCP-1, IL-18, intercellular adhesion Molecule 1 (ICAM-1), and vascular cell adhesion molecule 1 (VCAM-1) were measured before and at the end of intervention by enzyme-linked immunosorbant assay. Our study showed that the serum levels of ICAM-1 and VCAM-1 was decreased in the study population after two-month treatment (P<0.05). Based on the results of our pilot study, administration of PTX in CAD patients significantly decreases adhesion molecules levels.

Serum monocyte chemoattractant protein-1 is a biomarker in patients with diabetes and periodontitis.

Introduction:The role of serum Monocyte Chemoattractant Protein-1 (MCP-1) as a biomarker of periodontitis is well documented; however, its role in diabetic patients with periodontitis is unknown.Aim:This study was conducted to determine the presence and concentration of serum MCP-1 in diabetic patients with and without periodontitis and correlate it glycemic status with periodontitis.Materials and Methods:Adult diabetic patients were enrolled and grouped into group I, II, and III based on their glycemic status and serum MCP-1 estimated by ELISA. Linear regression and correlation tests were performed using R statistical software, Medcalc software to observe correlation between the serum MCP-1 and glycated hemoglobin level among different groups.Results:Serum samples obtained from 37 patients tested positive for MCP-1. Mean serum MCP-1 concentration was highest (482.3 pg/ml) in group III, lowest (149.3 pg/ml) in group I, and intermediate 398.8 pg/ml in group II. Correlation and regression analysis was done between HbA1c and serum MCP-1. A significant positive correlation (P < 0.001) was observed. Serum MCP-1 increased by 37.278 pg/ml for every 1% rise in HbA1c, and the levels were raised in group II and group III than in group I irrespective of their glycemic status. With an HbA1c range of 6.5-6.9% (group II), the serum MCP-1 values cluster around 380-410 pg/ml. Elevated levels of serum MCP-1 (>500 pg/ml) in three subjects corresponded to HbA1c values more than 12.2% (group III).Conclusion:To our knowledge, this is the first study to document serum MCP-1 levels in diabetic patients with periodontitis. Glycemic status influences serum MCP-1, and lack of glycemic control contributes to increased serum MCP-1 levels. Serum MCP-1 may thus serve as a biomarker of inflammation and disease progression in diabetes with periodontitis.

Associations of matrix metalloproteinase-9 and monocyte chemoattractant protein-1 concentrations with carotid atherosclerosis, based on measurements of plaque and intima–media thickness

PurposeTo examine associations of matrix metalloproteinase-9 (MMP-9) and monocyte chemoattractant protein-1 (MCP-1) concentrations with the severity of carotid atherosclerosis, based on measurements of carotid plaque and intima–media thickness (IMT). MethodsThis cross-sectional study included 116 stroke-free participants (45.7% males, 54.3% females; mean age, 64.73 ± 14.53 years). Serum MMP-9 and MCP-1 concentrations were measured, and plaque morphology, including total plaque score (PS), plaque stability, and IMT, was assessed ultrasonographically. Participants were grouped according to total PS (0, 1–2, ≥3), plaque stability (no plaque, stable, unstable) and IMT tertiles (<0.8 mm, 0.8–1 mm, >1 mm). Multinomial logistic regression models were used to assess the associations of MMP-9 and MCP-1 concentrations with plaque and IMT values after adjusting for vascular risk factors. ResultsMMP-9 quartiles (vs. quartile 1) were significantly associated with a greater prevalence of plaque instability [Q2: odds ratio (OR) = 5.13, 95% confidence interval (CI) = 1.01–24.9, p = 0.042; Q3: OR = 15.5, 95% CI = 3.1–78.1, p = 0.001; Q4: OR = 13.2, 95% CI = 2.7–64.97, p = 0.001] and high total PS (Q3: OR = 10.02, 95% CI = 1.5–65.33, p = 0.016; Q4: OR = 21.5, 95% CI = 3.5–132.1, p = 0.001). MCP-1 concentration was significantly associated with IMT (OR = 22.94, 95% CI = 2.14–245.66, p = 0.01). ConclusionsElevated serum MMP-9 concentration was independently associated with high total carotid artery PS, plaque instability, and large IMT value. MCP-1 concentration was independently associated with IMT, but not with plaque morphology.