Serum Concentrations Of MCP-1 Research Articles

Effect of GLP-1RA Treatment on Adhesion Molecules and Monocyte Chemoattractant Protein-1 in Diabetic Patients with Atherosclerosis.

Cardiovascular disease (CVD) remains a prominent cause of global mortality, primarily driven by atherosclerosis. Diabetes mellitus, as a modifiable risk factor, significantly contributes to atherogenesis. Monocyte recruitment to the intima is a critical step in atherosclerotic plaque formation, involving chemokines and adhesion molecules such as selectins, ICAM-1, and MCP-1. Glucagon-like peptide 1 receptor agonists (GLP-1RAs) are a promising group of drugs for reducing cardiovascular risk in diabetic patients, prompting investigation into their mechanisms of action. This interventional study enrolled 50 diabetes patients with atherosclerotic plaque, administering GLP-1RA for 180 days. Serum concentrations of MCP-1, ICAM-1, and L-selectin were measured before and after treatment. Anthropometric and biochemical parameters were also assessed. GLP-1RA treatment resulted in significant improvements in anthropometric parameters, glycemic control, blood pressure, and biochemical markers of liver steatosis. Biomarker laboratory analysis revealed higher baseline levels of MCP-1, ICAM-1, and L-selectin in diabetic patients with atherosclerotic plaque compared to healthy controls. Following treatment, MCP-1 and L-selectin levels decreased significantly (p < 0.001), while ICAM-1 levels increased (p < 0.001). GLP-1RA treatment in diabetic patients with atherosclerotic plaque leads to favorable changes in serum molecule levels associated with monocyte recruitment to the endothelium. The observed reduction in MCP-1 and L-selectin suggests a potential mechanism underlying GLP-1RA-mediated cardiovascular risk reduction. Further research is warranted to elucidate the precise mechanisms and clinical implications of these findings in diabetic patients with atherosclerosis.

Estimation of blood-based biomarkers of glial activation related to neuroinflammation

BackgroundNeuroinflammation is a well-known feature of Alzheimer’s disease (AD), and a blood-based test for estimating the levels of neuroinflammation would be expected. In this study, we examined and validated a model using blood-based biomarkers to predict the level of glial activation due to neuroinflammation, as estimated by 11C-DPA-713 positron emission tomography (PET) imaging. MethodsWe included 15 patients with AD and 10 cognitively normal (CN) subjects. Stepwise backward deletion multiple regression analysis was used to determine the predictors of the TSPO-binding potential (BPND) estimated by PET imaging. The independent variables were age, sex, diagnosis, apolipoprotein E4 positivity, body mass index and the serum concentration of blood-based biomarkers, including monocyte chemotactic protein 1 (MCP-1), fractalkine, chitinase 3-like protein-1 (CHI3L1), soluble triggering receptor expressed on myeloid cells 2 (sTREM2), and clusterin. ResultsSex, diagnosis, and serum concentrations of MCP1 and sTREM2 were determined as predictors of TSPO-BPND in the Braak1-3 area. The serum concentrations of MCP1 and sTREM2 correlated positively with TSPO-BPND. In a leave one out (LOO) cross-validation (CV) analysis, the model gave a LOO CV R2 of 0.424, which indicated that this model can account for approximately 42.4% of the variance of brain TSPO-BPND. ConclusionsWe found that the model including serum MCP-1 and sTREM2 concentration and covariates of sex and diagnosis was the best for predicting brain TSPO-BPND. The detection of neuroinflammation in AD patients by blood-based biomarkers should be a sensitive and useful tool for making an early diagnosis and monitoring disease progression and treatment effectiveness.

Serum IL-6 and MCP-1 concentrations in dogs with lymphoma before and after doxorubicin treatment as a potential marker of cellular senescence.

BackgroundChemotherapy can induce cellular senescence and a secretory phenotype characterized by an increased expression of inflammatory cytokines, such as IL‐6 and MCP‐1. Increased IL‐6 and MCP‐1 serum concentrations have been documented in dogs with lymphoma, but no studies have evaluated the effects of chemotherapy on cytokine concentrations.ObjectivesTo measure IL‐6 and MCP‐1 in 16 client‐owned dogs with lymphoma, at baseline and before and after doxorubicin, as a potential marker for senescence and correlate cytokine concentrations with treatment response and toxicities.MethodsSerum IL‐6 and MCP‐1 concentrations at baseline, 0‐h, 3‐h, 6‐h, 24‐h and 1 week post doxorubicin were measured using a canine ELISA. We hypothesized that IL‐6 and MCP‐1 concentrations would increase following doxorubicin as a result of induction of cellular senescence.ResultsIL‐6 concentrations were unchanged from baseline to 0‐h but significantly decreased 1 week post doxorubicin (p = 0.001) compared to 0–6 h (p = 0.045) and 24‐h (p = 0.001) time points. MCP‐1 concentrations significantly decreased from baseline to 0‐h (p = 0.003). Compared to 0–6 h, MCP‐1 concentrations transiently increased at 24‐h (p = 0.001) and decreased at 1 week (p = 0.014) post doxorubicin. Changes in IL‐6 and MCP‐1 concentrations did not correlate with leukocyte count, response to treatment or chemotherapy toxicities.ConclusionsChanges in IL‐6 and MCP‐1 concentrations did not support doxorubicin‐induced cellular senescence or correlate with leukocyte count, response to treatment or chemotherapy toxicity. However, our results suggest that remission status and doxorubicin treatment may influence cytokine concentrations and future studies are warranted to investigate the role of these cytokines as biomarkers.

Longitudinal Analysis of Serum Biochemical Changes following Anterior Cruciate Ligament Injury and Reconstruction: A Matched Comparison-Control Analysis

Objectives:Individuals with an anterior cruciate ligament (ACL) injury are at high risk of developing posttraumatic osteoarthritis (PTOA). A comprehensive study is needed to determine the time course of joint tissue metabolic changes occurring following ACL injury and reconstruction (ACLR). The purpose of this longitudinal nested comparison-control study was to simultaneously evaluate serum biomarkers of inflammation and cartilage matrix damage in ACL injured patients prior to ACLR and 6 and 12 months post-ACLR, as well as in matched uninjured controls.Methods:Serum was collected from 34 ACL injured individuals (53% female, 20.7±2.4 years old, 24.2±4.1 body mass index [BMI]) within 14 days of primary ACL injury (baseline), as well as at 6 and 12 months following bone-patellar-tendon-bone autograft ACLR. Serum was also collected from 34 uninjured matched controls (53% Female, 20.5±2.4 years old, 24.1±3.5 BMI) at a single timepoint. Blood was collected from the antecubital fossa, centrifuged and stored at -80°C prior to batch analysis. Commercial enzyme-linked immunosorbent assays were used to evaluate concentrations of: 1) a pro-inflammatory cytokine [Monocyte Chemoattractant Protein; MCP-1]; 2) a matrix degrading enzyme [matrix metalloproteinase-3; MMP-3]; 3) a cartilage breakdown biomarker [cartilage oligomeric matrix protein; COMP]; and type-II collagen turnover [type-II collagen cleavage: synthesis; C2C:CPII]. Separate Bonferroni-corrected independent t-tests were used to determine differences between the ACL injured group at each timepoint and uninjured controls for each biomarker (P ≤ 0.015). Similarly, separate Bonferroni-corrected dependent t-tests were used to determine differences in biomarker concentrations over time for the ACLR group.Results:Serum concentrations of MCP-1 and COMP were greater in the ACL injured individuals at all timepoints compared to the controls (P ≤ 0.015, Table 1), yet no differences were found over time in the ACL injured group. MMP-3 concentrations increased between baseline and 6 months post-ACLR (P ≤ 0.015, see Table), yet no differences were found between 6 and 12 months post-ACLR, between baseline and 12 months, or between ACLR and controls at any of the time points. C2C:CPII was not different between ACL injured individuals and controls at baseline or 6 months post-ACLR. C2C:CPII was significantly increased between 6 and 12 months-post ACLR, and was found to be greater than baseline and greater than controls at 12 months post-ACLR (P ≤ 0.015, see Table).Conclusion:Our study is critical in demonstrating the time course of multiple joint tissue metabolic changes following ACL injury and ACLR. Elevated serum MCP-1 and COMP concentrations, linked to early deleterious metabolic processes associated with PTOA development, are evident soon after ACL injury and persist at 12 months post-ACLR. Serum MMP-3 concentrations were elevated 6 months post-ACLR compared to the baseline measurements, suggesting factors occurring after ACLR initiate upregulation of matrix degrading enzymes. Furthermore, elevated C2C:CPII occurs within the first 12 months post ACLR but not until after the 6-month post-ACLR timepoint. Further studies are needed to determine how long these joint tissue metabolic changes persist after ACL injury and ACLR, as well as how joint tissue metabolism is affected by the type and timing of different surgical and nonsurgical treatments.

Docosahexaenoic Acid and Eicosapentaenoic Acid Supplementation Differentially Modulate Pro- and Anti-inflammatory Cytokines in Subjects with Chronic Inflammation (OR29-02-19)

ObjectivesDespite extensive works on the cardioprotective effects of fish oil containing docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), the distinct mechanisms by which DHA and EPA modulate inflammation and plasma lipids are not well characterized. We compared the effects of DHA and EPA supplementation on serum cytokines and blood monocyte inflammatory response and on blood lipids in subjects with chronic inflammation. MethodsTwenty-one subjects (9 men and 12 women, 50–75 y) with chronic inflammation (CRP > 2 μg/mL) were enrolled in a randomized, controlled crossover trial consisting of a 4-week lead-in control phase (high oleic sunflower oil, 3 g/d) followed by two sequential 10-week supplementation phases with pure DHA or EPA (3 g/d each) with a 10-week washout in between. Serum concentrations of cytokines were determined by electrochemiluminescence (ECL) assay. Following lipopolysaccharides (LPS) stimulation of blood monocytes, gene expression and secretion of cytokines were assessed by qPCR and ECL. Plasma lipid concentrations were measured by enzymatic assays. ResultsRelative to the control phase, DHA reduced the LPS-induced gene expression of pro-inflammatory TNFA (median % change: –45%, P < 0.001), IL6 (–51%, P < 0.05), MCP1 (–28%, P < 0.04) as well as anti-inflammatory IL10 (–33%, P < 0.02) and the secretion of TNF-α (–41%, P < 0.02), MCP-1 (–29%, P < 0.01), and IL-10 (–47%, P < 0.05) in monocytes. On the other hand, EPA increased serum concentrations of IL-10 (+14%, P < 0.05) and lowered only TNFAexpression (–20%, P < 0.03) in monocytes. When compared to EPA supplementation, DHA decreased serum concentrations of MCP-1 (P < 0.03), and monocyte MCP-1 secretion (P < 0.05) and IL10 expression (P < 0.04). Regarding plasma concentrations of lipids, relative to the control phase, both DHA (–16%, P < 0.001) and EPA decreased triglycerides (–22%, P < 0.001) while only DHA increased LDL-cholesterol (+7%, P < 0.02). ConclusionsDHA and EPA differently modulate the balance between pro- and anti-inflammatory cytokines in serum and blood monocytes in subjects with chronic inflammation. While DHA inhibits a broad range of pro- and anti-inflammatory cytokines, EPA has a relatively minor role in lowering pro-inflammatory cytokines but preserves the anti-inflammatory IL-10. DHA, but not EPA, increases LDL-cholesterol. Funding SourcesFunded by USDA/NIFA.

New markers of cell migration and inflammation in children with chronic kidney disease

Context: Chronic kidney disease (CKD) is characterized by immunocompetent cell migration and inflammation. Monocyte chemoattractant protein (MCP)-1 and macrophage colony-stimulating factor (MCSF) stimulate monocyte migration and transition into macrophages with subsequent release of neopterin. Objective: The aim of the study was to analyze these parameters in children with various stages of CKD. Material and methods: The study group consisted of 41 CKD children, 19 patients on haemodialysis (HD), 22 children on automated peritoneal dialysis (APD) and 23 controls. Serum concentrations of MCP-1, MCSF and neopterin were assessed by ELISA. Correlations to matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) were analyzed. Results: MCP-1, MCSF and neopterin were significantly elevated in all patients versus controls and the highest values concerned HD children. A single HD session lessened the concentrations of all parameters, yet they rose back before the next HD session. All markers correlated with MMPs and TIMPs in different combinations. Conclusions: Systemic inflammation and cell migration are triggered by CKD and additionally aggravated by chronic dialysis, with the more evident negative impact of HD than APD. Discrepancies in MCP1, MCSF and neopterin serum concentrations suggest they may serve as new markers of cellular and inflammatory responses in children with CKD.

Characterization of neuroinflammation and periphery-to-CNS inflammatory cross-talk in patients with disc herniation and degenerative disc disease

The aim of the study was to identify inflammatory cytokines/chemokines associated with neuroinflammation and periphery-to-CNS inflammatory cross-talk in degenerative disc disease (DDD) and lumbar disc herniation (LDH), common causes of low back pain (LBP). A secondary aim was to investigate the associations between cytokines and symptom severity. MethodsIn total, 40 DDD and 40 LDH patients were recruited from a surgical waiting list, as well as 39 healthy controls (HC) and 40 cerebrospinal fluid (CSF) controls. The subjects completed questionnaires and pressure algometry was performed at the lumbar spine and forearm. The CSF, serum and disc tissues were collected during surgery. Inflammatory mediators TNF, INFg, IL-1b, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13 and MCP1 were analysed by immunoassay (Meso Scale Discovery) and quantitative real-time polymerase chain reaction (qPCR) was used for analysis of IL-6, IL-8, MCP1 and TSPO expression in intervertebral discs (IVDs). ResultsIn the LDH group, we found elevated IL-8 concentrations in CSF indicating neuroinflammation, while IL-8 and MCP1 concentrations in serum were lower compared to HC. The IVD expression of IL-6, IL-8 and TSPO was lower in LDH patients compared to DDD. LDH patients had a positive correlation between IL-8 concentrations in CSF and serum and IL-8 in CSF was associated with higher pain intensity and increased spinal pressure pain sensitivity. The MCP1 concentration in serum was associated with higher global pain ratings and increased spinal pressure pain sensitivity, while IL-6 serum concentration correlated with the intensity of the neuropathic pain component (leg pain) in LDH patients. IVD expression of TSPO in LDH patients was associated with increased intensity of back pain. No differences were found in cytokine CSF concentrations between DDD patients and CSF controls, but DDD patients had lower IL-8 and MCP1 serum concentrations than HC. In female DDD patients, IL-8 and MCP1 concentrations in serum were associated with increased intensity of back pain. ConclusionOur results suggest that neuroinflammation mediated by elevated IL-8 concentrations in CSF and IL-8 mediated periphery-to-CNS inflammatory cross-talk contributes to pain in LDH patients and suggest a link between TSPO expression in discs and low back pain.

Cytokine Response Associated with Hepatitis C Virus Clearance in HIV Coinfected Patients Initiating Peg Interferon-α Based Therapy.

BackgroundTreatment of hepatitis C virus (HCV) infection based on peginterferon-α (pegIFNα) and ribavirin induces important changes in cytokine release and T cell activation.ObjectiveImmune response to pegIFNα-ribavirin therapy was explored in patients coinfected by HCV and HIV.MethodsConcentrations of 25 cytokines and CD8+ T cell activation were monitored in HCV/HIV coinfected patients classified as sustained virological responders (SVR, n=19) and non-responders (NR, n=11).ResultsHigh pretreatment concentrations of IP-10 (CXCL-10) and MCP-1 (CCL-2) were associated with a poor anti-HCV response. PegIFNα-ribavirin therapy increased CD8+ T cell activation and induced significant changes in levels of eleven cytokines related to both Th1 and Th2 responses in SVR (IL-1β, IL-1RA, IL-4, IL-5, IL-6, IL-7, IL-12p40/70, IL-13, IP-10, eotaxin, MCP-1) but of only six cytokines in NR (IL-1β, IL-2, IL-5, IL-12p40/70, IL-13, eotaxin). The highest rise in MIP-1β and MCP-1 levels was observed four weeks after anti-HCV treatment initiation in SVR compared to NR (p=0.002 and p=0.03, respectively), whereas a decrease in IL-8 concentration was associated with treatment failure (p= 0.052).ConclusionsHigher and broader cytokine responses to pegIFNα-ribavirin therapy were observed in SVR patients compared to NR. Changes in IL-8, MIP-1β, and MCP-1 serum concentrations may be associated with efficacy of pegIFNα- and ribavirin-based therapies in patients coinfected by HCV and HIV.

Alpha-lipoic acid modifies circulating angiogenic factors in patients with type 2 diabetes mellitus

AimsIn recent years interest has been focused on angiogenesis as a process involved in coronary artery disease (CAD) and diabetic distal sensorimotor polyneuropathy (DSPN). Recent studies have demonstrated the possible angiogenesis-modulating potential of alpha-lipoic acid (ALA) for DSPN and CAD. The aim of our study was to investigate the influence of ALA on serum angiogenic factors in patients with DM-2 (type 2 diabetes) with CAD and DSPN. MethodsSixty patients with type 2 DM (T2DM) and CAD and 25 non-diabetic subjects were studied. Thirty patients with T2DM, CAD and DSPN were given 600mg of ALA a day for 90 days. VEGF, bFGF, MCP-1, angiogenin, IL-12 and IL-10 concentrations in the sera were measured by flow cytometry. ResultsALA significantly increased VEGF, bFGF and IL-10 and decreased MCP-1 serum concentrations in patients with T2DM and CAD and DSPN. VEGF and IL-10 serum levels, both before and after ALA-treatment, were higher in this group than in T2DM and CAD patients, while circulating bFGF was higher and MCP-1 serum level lower in patients with T2DM and CAD and DSPN only in the post-ALA-treatment, compared to the T2DM and CAD group. ConclusionsALA may influence angiogenesis in type 2 diabetic patients through an effect on some circulating factors including VEGF, bFGF, MCP-1 and IL-10.

Loss of TIMP3 exacerbates atherosclerosis in ApoE null mice

BackgroundTissue inhibitor of metalloproteinase 3 (TIMP3) is a stromal protein that inhibits the activity of various proteases and receptors. We have previously shown TIMP3 to be downregulated in metabolic and inflammatory disorders, such as type 2 diabetes mellitus.We have now generated an ApoE−/−Timp3−/− mouse model in which, through the use of genetics, metabolomics and in-vivo phenotypical analysis we investigated the role of TIMP3 in the development of atherosclerosis. Methods and resultsEn face aorta analysis and aortic root examination showed that ApoE−/−Timp3−/− mice show increased atherosclerosis with increased infiltration of macrophages into the plaque. Serum concentration of MCP-1 were elevated in the serum of ApoE−/−Timp3−/− mice coupled with an expansion of the inflammatory (M1) Gr1+ macrophages, both in the circulation and within the aortic tissue. Targeted analysis of metabolites revealed a trend to reduced short chain acylcarnitines. ConclusionsOur study shows that lack of TIMP3 increases inflammation and polarizes macrophages towards a more inflammatory phenotype resulting in increased atherosclerosis.

Associations among MCP-1 gene -2518 G/A polymorphism, the serum MCP-1 level and acute coronary syndrome

ObjectiveTo investigate the associations among MCP-1-2518 G/A polymorphism, MCP-1 serum levels and ACS in Chinese Han population of Sunan region.MethodsAfter obtaining informed consent, 166 patients with ACS including 94 cases...

Serum Monocyte Chemoattractant Protein-1 and Monocyte Adhesion Molecules in Type 1 Diabetic Patients with Nephropathy

Monocyte chemoattractant protein (MCP)-1 is suggested to be implicated in the pathogenesis of diabetic nephropathy by activating and recruiting monocytes to the glomerulus via regulation of adhesion molecule expressions. The aim of this study was to test potential associations between serum concentrations of MCP-1, monocyte expression of Mac-1 and LFA-1 and nephropathy in type 1 diabetes mellitus. Serum MCP-1 levels and expression of monocyte adhesion molecules in 51 type 1 diabetic patients with and without diabetic nephropathy were compared with matched 15 healthy control subjects. Concentrations of serum MCP-1 were determined by enzyme-linked immunosorbent assays whereas monocyte expression of adhesion molecules Mac-1 and LFA-1 was measured by flow cytometry. Serum MCP-1 levels and expression of Mac-1, but not LFA-1, were significantly higher in diabetic patients compared with controls. The mean serum MCP-1 level was 137.2 +/- 71.4 pg/mL in control patients, whereas it was 246.2 +/- 114.9 pg/ml in diabetic patients (p = 0.002). Serum MCP-1 levels were positively correlated with HbA1c and plasma fasting glucose levels. There was no difference in serum levels of MCP-1 and expression of monocyte adhesion molecules between type 1 diabetic patients with and without diabetic nephropathy. In type 1 diabetic patients, the levels of circulating MCP-1 concentration and expression of Mac-1 is mostly influenced by glycemic control rather than the existence of diabetic nephropathy.

Systemic monocyte chemoattractant protein-1 concentrations are independent of type 2 diabetes or parameters of obesity: results from the Cooperative Health Research in the Region of Augsburg Survey S4 (KORA S4)

Data on the relevance of monocyte chemoattractant protein (MCP)-1 in the pathophysiology of type 2 diabetes (T2D) and obesity are inconsistent. Since MCP-1 is produced by adipocytes and has been postulated to be involved in macrophage infiltration into adipose tissue, we wanted to test whether serum MCP-1 levels were correlated with T2D or obesity. Out of 1653 individuals aged 55 to 74 years participating in the population-based KORA Survey S4 (KORA/Cooperative Health Research in the Region of Augsburg) in Southern Germany, 236 patients with T2D, 242 subjects with impaired glucose tolerance and 244 normoglycaemic controls matched for age and sex were analysed for circulating MCP-1 concentrations. MCP-1 serum concentrations were not associated with impaired glucose tolerance, type 2 diabetes or several parameters of obesity. Moreover, systemic MCP-1 levels were not significantly correlated with all but one (fasting triglycerides) of the biochemical markers tested. Our data indicate that MCP-1 levels are not associated with T2D and that the contribution of fat mass to systemic MCP-1 protein might be low, suggesting that the possible local pathogenic role of MCP-1 may not be reflected by increased systemic levels of MCP-1.

Monocyte-Related Determinants of Inflammation in Patients on Peritoneal Dialysis

Aims: We studied markers of monocyte activation, i.e., the cell surface expression of CD11b and CD62L, and the serum concentrations of monocyte chemotactic protein 1 (MCP-1; a monocyte-specific chemoattractant) and soluble vascular cell adhesion molecule 1 (sVCAM-1; an adhesion molecule involved in monocyte recruitment) in 20 patients on peritoneal dialysis (PD), in 25 patients with chronic renal insufficiency, and in 27 healthy subjects. Results: Monocytes obtained from the peripheral blood of PD patients had a significantly higher expression of CD62L (p = 0.02) as compared with monocytes from healthy subjects and a lower CD11b/CD18 expression as compared with monocytes collected from healthy subjects (p < 0.001) and from patients with renal insufficiency (p < 0.001). Monocytes from PD patients had, however, the capacity to increase the expression of CD11b following stimulation with a potent chemotactic factor. The serum concentrations of MCP-1 and sVCAM-1 were higher in PD patients (575 ± 51 and 1,517 ± 89 ng/ml) than in healthy subjects (225 ± 17 and 668 ± 64 ng/ml, respectively; p < 0.001 for both comparisons). There was a correlation between the levels of sVCAM-1 and MCP-1 (r = 0.48, p < 0.05) in patients on PD, but neither correlated with the monocyte expression of CD11b/CD18 or CD62L. The concentration of C-reactive protein was higher in patients on PD as compared with healthy subjects and correlated significantly with the concentration of sVCAM-1 (r = 0.63, p < 0.01). Conclusions: Monocytes in the peripheral circulation of patients on PD have a CD62L^high/CD11b^low phenotype, indicating that they have not undergone complete differentiation. Patients also have an increase in the systemic chemotactic activity for monocytes in combination with increased levels of sVCAM-1 and C-reactive protein. These inflammatory aberrations may play a pathophysiological role in the response to inflammatory and infectious diseases in patients on PD.