Plasma Levels Of Monocyte Chemoattractant Protein-1 Research Articles

Plasma and peritoneal fluid cytokine profiles in patient with Essure® implant: Towards a molecular signature?

Objective(s)Many patients with Essure® implant may experience adverse events related to the device. Although local inflammation does not appear to be the pathophysiological mechanism underlying the symptoms, systemic inflammation could play a role. In the present study, as cytokines are involved in the inflammatory process, we proposed to investigate the profile of circulating and peritoneal cytokines. Study designIn this retrospective study, we evaluated the levels of cytokines in peritoneal fluid (PF) as well as in plasma sample from three different groups: Essure® group, endometriosis group (known to be associated with immune dysregulation), and control group. ResultsThere were 60 symptomatic patients with Essure® device, 30 patients with endometriosis and a control group of 30 patients. The PF levels of Interleukin-10 (IL-10), Interleukin-6 (IL-6), and Monocyte chemoattractant protein-1 (MCP-1) were statistically higher in endometriosis group than in Essure® group and control group. The plasma level of MCP-1 was higher in Essure® group than in endometriosis group and control group. The plasma level of TNF-α was higher in Essure® group than in control group. ConclusionsThe chemokine MCP-1 as well as the pro-inflammatory TNF-α, are known to be increased in patients with fibromyalgia and chronic fatigue syndrome. Since patients with Essure® may exhibit symptoms similar to fibromyalgia, MCP-1 and TNF-α may be relevant markers in symptomatic patients with Essure®. Because of the lack of longitudinal data (no evaluation of postoperative cytokine profile and no assessment of the level of clinical improvement), other studies are needed to confirm these preliminary results.

High Levels of Monocyte Chemoattractant Protein-1 Plasma Are A Risk Factor for Neurocognitive Disorders in Human Immunodeficiency Virus Infection with Antiretroviral Therapy

Background: HIV-associated neurocognitive disorder (HAND) is a neurocognitive dysfunction caused by HIV infection. The prevalence of neurocognitive disorders of HIV in Indonesia is about 51%. Despite receiving antiretroviral therapy, HAND is still a common complication that causes morbidity in people with HIV. One of the foundations of HAND pathogenesis is inflammation. Infection of macrophages/microglia and astrocytes leads to excessive production of viral gene products and chemokines, one of them is Monocyte chemoattractant protein 1 (MCP-1). The purpose of this study was to determine plasma MCP-1 levels that increase the risk of neurocognitive disorders in HIV infection with antiretroviral therapy. Methods: This matched case-control study involved 76 subjects with HIV, 38 subjects with neurocognitive disorders, and 38 subjects without neurocognitive disorders. Cognitive status was reviewed based on MoCA-Ina examination criteria. Plasma MCP-1 levels were measured by enzyme-linked immunosorbent assay (ELISA). Results: Of the 76 subjects, the mean age of the case group was 42.08 ± 9.44 years and the control group was 42.16± 8.90 years. The cut point value based on the ROC curve of the plasma MCP-1 level was 82.14 pg/mL. It had an 86.8% sensitivity and 52.6% specificity for the occurrence of neurocognitive disorders in HIV. The risk of neurocognitive disorders in HIV was found in MCP-1 plasma ≥ 82.14 pg/mL (OR 7.33, p < 0.001, CI 95% = 2.35-22.83). Based on multivariate analysis, MCP-1 levels were independently associated with the incidence of neurocognitive disorders in HIV (AOR 11.01, CI 95% = 2.75-44.01, p=0.001). Conclusion: This study showed that high plasma MCP-1 levels were an event risk factor for neurocognitive disorders in HIV with antiretroviral therapy.

Association Between Plasma Levels of Monocyte Chemoattractant Protein-1 (MCP-1) and 28-Day Mortality in Elderly Patients with Sepsis: A Retrospective Single-Center Study.

BACKGROUND Previous studies have identified an association between plasma levels of the inflammatory cytokine, monocyte chemoattractant protein-1 (MCP-1), and outcomes for patients with sepsis. This retrospective single-center study assessed the association between plasma levels of MCP-1 and 28-day mortality in 136 patients ≥65 years diagnosed with sepsis between October 2020 and October 2021. MATERIAL AND METHODS The objective was to compare and analyze the parameters in the survival group (n=35) and the 28-day mortality group (n=101), including Sequential Organ Failure Assessment (SOFA), Acute Physiology and Chronic Health Evaluation II (APACHE II), plasma MCP-1, and laboratory test results. Plasma MCP-1 was quantified by cytokine test kit (LKTM014B, R&D). Statistical analysis was carried out in SPSS 26.0 and MedCalc 92.1.0 software. RESULTS The 28-day mortality group exhibited higher levels of SOFA, APACHEII, and plasma MCP-1 (all P<0.001), as well as lower levels of albumin, compared to the survival group (P<0.05). The logistic regression analysis findings indicated that SOFA, APACHEII, plasma MCP-1, and SBP are all independent risk factors for 28-day mortality. The area under the curve for SOFA, APACHEII, MCP-1, MCP-1+ SOFA, and MCP-1+APACHEII were 0.845, 0.744, 0.712, 0.879, and 0.822, respectively. MCP-1+SOFA exhibited higher sensitivity than SOFA alone. Furthermore, the assessment values of plasma MCP-1 combined with SOFA were superior to those of APACHE II or plasma MCP-1 (Z₁=2.661, Z₂=3.272, both P<0.01). CONCLUSIONS The findings from this study from a single center support those of previous studies that increased plasma levels of MCP-1 are significantly associated with 28-day mortality in patients with sepsis.

The Roles of Aerobic Exercise and Folate Supplementation in Hyperhomocysteinemia-Accelerated Atherosclerosis.

Hyperhomocysteinemia (HHcy) is an independent risk factor for atherosclerosis. Effective interventions to reduce HHcy-accelerated atherosclerosis are required. This study aimed to investigate the effects of aerobic exercise (AE) and folate (FA) supplementation on plasma homocysteine (Hcy) level and atherosclerosis development in a mouse model. Six-week-old female apoE-/- mice were grouped into five groups (N = 6-8): HHcy (1.8 g/L DL-homocysteine (DL-Hcy) in drinking water), HHcy + AE (1.8 g/L DL-Hcy and aerobic exercise training on a treadmill), HHcy + FA (1.8 g/L DL-Hcy and 0.006% folate in diet), HHcy + AE + FA (1.8 g/L DL-Hcy, 0.006% folate, and aerobic exercise training on a treadmill), and a control group (regular water and diet). All treatment was sustained for 8 weeks. Triglyceride, cholesterol, lipoprotein, and Hcy levels were determined enzymatically. Plaque and monocyte chemoattractant protein-1 (MCP-1) expression levels in mouse aortic roots were evaluated by immunohistochemistry. Compared to the HHcy group (18.88 ± 6.13 μmol/L), plasma Hcy concentration was significantly reduced in the HHcy + AE (14.79 ± 3.05 μmol/L, p = 0.04), HHcy + FA (9.4 ± 3.85 μmol/L, p < 0.001), and HHcy + AE + FA (9.33 ± 2.21 μmol/L, p < 0.001) groups. Significantly decreased aortic root plaque area and plaque burden were found in the HHcy + AE and HHcy + AE + FA groups compared to those in the HHcy group (both p < 0.05). Plasma MCP-1 level and MCP-1 expression in atherosclerotic lesions were significantly decreased in the HHcy + AE and HHcy + AE + FA groups compared to the HHcy group (all p < 0.05). AE reduced atherosclerosis development in HHcy apoE-/- mice independently of reducing Hcy levels. FA supplementation decreased plasma Hcy levels without attenuating HHcy-accelerated atherosclerosis. AE and FA supplementation have distinct mechanisms in benefiting atherosclerosis.

Diagnostic accuracy of muscle ultrasound and plasma monocyte chemoattractant protein-1 for ICU-acquired weakness in patients with sepsis

To explore the diagnostic accuracy of muscle ultrasound and plasma monocyte chemoattractant protein-1 (MCP-1) for ICU-acquired weakness (ICU-AW) in patients with sepsis. A prospective observational study was conducted. Patients with sepsis admitted to the intensive care unit (ICU) of Henan Provincial People's Hospital from April 2021 to October 2021 were enrolled. The demographic data were collected. The enrolled patients were evaluated with Medical Research Council (MRC) score every day until discharged from ICU. During this period, patients with total MRC score < 48 (for two consecutive times and a time interval of 24 hours) were divided into ICU-AW group, those with total MRC score ≥ 48 were served as non-ICU-AW group. On the 1st, 4th and 7th day following admission into ICU, ultrasound was used to measure the muscle linear thickness of the rectus femoris (RF-MLT), the cross sectional area of the rectus femoris (RF-CSA) and the muscle linear thickness of the vastus intermedius muscle (VI-MLT). And meanwhile, the plasmas samples of patients were collected to measure MCP-1 concentration by enzyme-linked immunosorbent assay (ELISA). The difference of each index was compared between the ICU-AW group and the non-ICU-AW group. The risk factors of ICU-AW in patients with sepsis were analyzed by binary Logistic regression. Besides, receiver operator characteristic curve (ROC curve) was plotted, the diagnostic value of ultrasound parameters and plasma MCP-1 level for ICU-AW in patients with sepsis was analyzed. A total of 99 septic patients were enrolled, with 68 patients in the ICU-AW group and 31 patients in the non-ICU-AW group. Compared with the patients in the ICU-AW group, the patients in the non-ICU-AW group tended to be older, and had higher sequential organ failure assessment (SOFA) score, higher acute physiology and chronic health evaluation II (APACHE II) score, higher rates of septic shock, higher blood lactic acid and lower Glasgow coma score (GCS). Binary Logistic regression analysis showed that APACHE II score and septic shock were the risk factors of ICU-AW for septic patients [odds ratio (OR) and 95% confidence interval (95%CI) were 1.310 (1.138-1.509) and 0.232 (0.072-0.746), respectively, both P < 0.05]. The RF-MLT, RF-CSA and VI-MLT on the 1st, 4th and 7th ICU day was falling over time. Compared with the patients in the ICU-AW group, the patients in the non-ICU-AW group had smaller RF-MLT on the 7th day [cm: 0.32 (0.22, 0.47) vs. 0.45 (0.34, 0.63), P < 0.05] and higher 7-day RF-CSA atrophy rate [25.85% (10.37%, 34.28%) vs. 11.65% (2.28%, 22.41%), P < 0.05]. According to ROC curve analysis, 7-day RF-MLT had diagnostic value for ICU-AW of septic patients. Area under ROC curve (AUC) was 0.688 (95%CI was 0.526-0.849); when the cut-off value was 0.41 cm, the sensitivity and the specificity were 66.7% and 68.4%. The levels of plasma MCP-1 in the ICU-AW group were significantly higher than those in the non-ICU-AW group on the 1st, 4th and 7th day. ROC curve analysis showed that the plasma MCP-1 levels on the 1st, 4th and 7th day played a significant role to diagnose ICU-AW for septic patients, the AUC and 95%CI were 0.732 (0.629-0.836), 0.865 (0.777-0.953), 0.891 (0.795-0.986), respectively. When the cut-off values were 206.3, 410.9, 239.5 ng/L, the sensitivity was 87.1%, 64.0%, 82.4%, and the specificity was 54.4%, 96.1%, 86.2%, respectively. The muscle mass parameters on the 7th day of bedside ultrasound and plasma MCP-1 levels had certain diagnostic values for ICU-AW in patients with sepsis.

Protective effects of rosmarinic acid against azoxymethane-induced colorectal cancer in rats.

Colorectal cancer (CRC) incidence is increasing gradually and has been become one of the most common cancers worldwide. Hence, it is important to discover cheap, naturally occurring compounds to be effective in suppressing the devastating effect of colon-related tumors. Rosmarinic acid (RA), one of the compounds of plant origin, possesses attractive features for use as an agent for cancer prevention and treatment. This study investigated the ability of RA to prevent azoxymethane (AOM)-induced rat colon carcinogenesis by evaluating the effect of RA on tumor formation and circulatory oxidant-antioxidant status. Moreover, plasma levels of adiponectin (APN) monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6) were detected by enzyme linked immunosorbent assay. The animals were divided into three groups: Control, AOM, and AOM + RA. Rats were fed a modified pellet diet (15.8% peanut oil was added to the standard diet) during the experimental period. Colon cancer was formed by applying 15 mg/kg AOM intraperitoneal once a week for 4 weeks in both the CRC group and AOM + RA group. Besides AOM, AOM + RA group received 5 mg/kg body weight RA orally every day during the study. The results showed that adenocarcinoma rates formed87.5% ofthe AOM group. With treatment of RA, a reduction in the incidence of adenocarcinoma was observed in the AOM + RA group. The plasma MCP-1, IL-6, and TO levels were significantly higher, APN and TAS levels were significantly lower in the AOM group with respect tocontrols. In addition, there was a significant increase in TAS levels in the RA treatment group compared to the AOM group. These findings suggested that RA may be beneficial in preventing AOM-induced colon carcinogenesis formation.

A Hypomethylating Ketogenic Diet in Apolipoprotein E-Deficient Mice: A Pilot Study on Vascular Effects and Specific Epigenetic Changes.

Hyperhomocysteneinemia (HHcy) is common in the general population and is a risk factor for atherosclerosis by mechanisms that are still elusive. A hypomethylated status of epigenetically relevant targets may contribute to the vascular toxicity associated with HHcy. Ketogenic diets (KD) are diets with a severely restricted amount of carbohydrates that are being widely used, mainly for weight-loss purposes. However, studies associating nutritional ketosis and HHcy are lacking. This pilot study investigates the effects of mild HHcy induced by nutritional manipulation of the methionine metabolism in the absence of dietary carbohydrates on disease progression and specific epigenetic changes in the apolipoprotein-E deficient (apoE–/–) mouse model. ApoE–/– mice were either fed a KD, a diet with the same macronutrient composition but low in methyl donors (low methyl KD, LMKD), or control diet. After 4, 8 or 12 weeks plasma was collected for the quantification of: (1) nutritional ketosis, (i.e., the ketone body beta-hydroxybutyrate using a colorimetric assay); (2) homocysteine by HPLC; (3) the methylating potential S-adenosylmethionine to S-adenosylhomocysteine ratio (AdoHcy/AdoMet) by LC-MS/MS; and (4) the inflammatory cytokine monocyte chemoattractant protein 1 (MCP1) by ELISA. After 12 weeks, aortas were collected to assess: (1) the vascular AdoHcy/AdoMet ratio; (2) the volume of atherosclerotic lesions by high-field magnetic resonance imaging (14T-MRI); and (3) the content of specific epigenetic tags (H3K27me3 and H3K27ac) by immunofluorescence. The results confirmed the presence of nutritional ketosis in KD and LMKD mice but not in the control mice. As expected, mild HHcy was only detected in the LMKD-fed mice. Significantly decreased MCP1 plasma levels and plaque burden were observed in control mice versus the other two groups, together with an increased content of one of the investigated epigenetic tags (H3K27me3) but not of the other (H3K27ac). Moreover, we are unable to detect any significant differences at the p < 0.05 level for MCP1 plasma levels, vascular AdoMet:AdoHcy ratio levels, plaque burden, and specific epigenetic content between the latter two groups. Nevertheless, the systemic methylating index was significantly decreased in LMKD mice versus the other two groups, reinforcing the possibility that the levels of accumulated homocysteine were insufficient to affect vascular transmethylation reactions. Further studies addressing nutritional ketosis in the presence of mild HHcy should use a higher number of animals and are warranted to confirm these preliminary observations.

Involvement of chronic inflammation via monocyte chemoattractant protein-1 in uraemic cardiomyopathy: a human biopsy study.

AimsPatients undergoing dialysis, even those without coronary artery disease or valvular abnormalities, sometimes present with reduced heart function, which resembles dilated cardiomyopathy (DCM). This condition is known as uraemic cardiomyopathy (UCM). The mechanisms of UCM development are not fully understood. Previous studies demonstrated that the balance between placental growth factor (PlGF) and fms‐like tyrosine kinase‐1 (Flt‐1) is correlated with renal function, and PlGF/Flt‐1 signalling is involved in the development of cardiovascular diseases in patients with chronic kidney disease. This study was conducted to evaluate the pathogenesis of UCM and clarify the differences in the mechanisms of UCM and DCM by using human endomyocardial biopsy and blood samples.Methods and resultsThe clinical and pathological features of 30 patients on dialysis with reduced cardiac function [left ventricular ejection fraction (LVEF) ≤50%] (UCM group; mean age: 58.5 ± 9.4 years and LVEF: 39.1 ± 7.2%), 196 DCM patients (DCM group; mean age: 62.7 ± 14.0 years and LVEF: 33.5 ± 8.8%) as controls with reduced cardiac function (LVEF ≤ 45%), and 21 patients as controls with normal cardiac function (control group; mean age: 56.2 ± 19.3 years and LVEF: 67.5 ± 6.7%) were analysed. The percentage of the interstitial fibrosis area in the UCM group was greater than that in the DCM group (P = 0.045). In UCM patients, the percentage of the interstitial fibrosis area was positively correlated with the duration of renal replacement therapy (P < 0.001). The number of infiltrated CD68‐positive macrophages in the myocardium and expression of monocyte chemoattractant protein‐1 (MCP‐1) in cardiomyocytes were significantly greater in the UCM group than in the other groups (P < 0.001, respectively). Furthermore, while the serum level of soluble form of Flt‐1, an endogenous inhibitor of PlGF, in the UCM group was lower compared with that in the DCM group (P < 0.001), the serum levels of PlGF and PlGF/soluble form of Flt‐1 ratio and plasma level of MCP‐1 in the UCM group were higher than those in the DCM group (P < 0.001, respectively).ConclusionsThese results suggest that activated PlGF/Flt‐1 signalling and subsequent macrophage‐mediated chronic non‐infectious inflammation via MCP‐1 in the myocardium are involved in the pathogenesis of UCM.

MCP-1 Predicts Recurrent Cardiovascular Events in Patients with Persistent Inflammation.

Clinical data indicate that patients with C-reactive protein (CRP) levels higher than 2 mg per liter suffer from persistent inflammation, which is associated with high risk of cardiovascular disease (CVD). We determined whether a panel of biomarkers associated with CVD could predict recurrent events in patients with low or persistent inflammation and coronary artery disease (CAD). We followed 917 patients with CAD (median 4.59 ± 2.39 years), assessing CRP, galectin-3, monocyte chemoattractant protein-1 (MCP-1), N-terminal fragment of brain natriuretic peptide (NT-proBNP) and troponin-I plasma levels. The primary outcome was the combination of cardiovascular events (acute coronary syndrome, stroke or transient ischemic event, heart failure or death). Patients with persistent inflammation (n = 343) showed higher NT-proBNP and MCP-1 plasma levels compared to patients with CRP < 2 mg/L. Neither MCP-1 nor NT-proBNP was associated with primary outcome in patients with CRP < 2 mg/L. However, NT-proBNP and MCP-1 plasma levels were associated with increased risk of the primary outcome in patients with persistent inflammation. When patients were divided by type of event, MCP-1 was associated with an increased risk of acute ischemic events. A significant interaction between MCP-1 and persistent inflammation was found (synergy index: 6.17 (4.39–7.95)). In conclusion, MCP-1 plasma concentration is associated with recurrent cardiovascular events in patients with persistent inflammation.

Plasma Inflammatory Biomarkers Associated with Advanced Liver Fibrosis in HIV-HCV-Coinfected Individuals.

Background: HIV and HCV coinfection leads to accelerated liver fibrosis, in which microbial translocation and systemic inflammation might play important roles. Objective: This study aimed to provide an extensive profile of the plasma microbial translocation and inflammation biomarkers associated with advanced liver fibrosis among HIV–HCV-coinfected patients. Methods: This cross-sectional study recruited 343 HIV–HCV-coinfected patients on combination antiretroviral therapy (cART) from a rural prefecture of Yunnan province in Southwest China. The plasma concentrations of sCD14 and 27 cytokines and chemokines were assayed and compared against advanced or mild levels of liver fibrosis. Results: Of the 343 HIV–HCV-coinfected patients, 188 (54.8%) had severe or advanced liver fibrosis (FIB-4 > 3.25). The patients with advanced liver fibrosis (FIB-4 > 3.25 vs. FIB-4 ≤ 3.25) had higher plasma levels of interleukin (IL)-1β, IL-6, IL-7, IL-9, IL-12, IL-15, IL-17, granulocyte macrophage colony stimulating factor (GM-CSF), Interferon-γ (IFN-γ), tumor necrosis factor (TNF-α), IL-4, IL-10, IL-13, fibroblast growth factor 2 (FGF-basic), and Monocyte chemoattractant protein-1 (MCP-1). Multivariable logistic regression models showed that advanced liver fibrosis was associated with an increased plasma level of IL-1β, IL-6, IL-7, IL-12, IL-17, GM-CSF, IFN-γ, IL-4, IL-10, MCP-1, Eotaxin, and FGF-basic, with FGF-basic continuing to be positively and significantly associated with advanced liver fibrosis, after Bonferroni correction for multiple comparisons (adjusted odds ratio (aOR) = 1.92; 95%CI: 1.32–2.81; p = 0.001). Plasma sCD14 was also significantly associated with advanced liver fibrosis (aOR = 1.13; 95%CI: 1.01–1.30; p = 0.049). Conclusions: HIV–HCV-coinfected patients are living with a high prevalence of advanced liver fibrosis which coexists with a mixture of elevated plasma inflammation and microbial translocation biomarkers. The significant associations of advanced liver fibrosis with FGF-basic and sCD14 may reveal pathogenic mechanisms and potential clinical intervention targets for liver fibrosis in HCV–HIV coinfection.

Elevated Plasma Levels of sCD14 and MCP-1 Are Associated With HIV Associated Neurocognitive Disorders Among Antiretroviral-Naive Individuals in Nigeria.

Mononuclear cells play key roles in the pathogenesis of HIV-associated neurocognitive disorders (HAND). Limited studies have looked at the association of markers of monocyte activation with HAND in Africa. We examined this association among HIV-1-infected patients in Nigeria. A total of 190 HIV-infected treatment-naive participants with immune marker data were included in this cross-sectional study. Plasma levels of soluble CD14 (sCD14), soluble CD163, monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-α), and neopterin were measured. Demographically adjusted T scores obtained from a 7-domain neuropsychological test battery were generated, and functional status was assessed using activities of daily living questionnaire. Participants were classified as unimpaired, having asymptomatic neurocognitive impairment (ANI), mild neurocognitive disorder (MND), or HIV-associated dementia (HAD) in line with the "Frascati" criteria. Thirty-two participants (16.8%) had ANI, 14 (7.4%) had MND, whereas none had HAD. In multivariable linear regression analyses, after adjusting for age, gender, education, CD4 count, and viral load, mean levels of sCD14 were higher among those with ANI and MND as compared with the unimpaired (P = 0.033 and 0.023, respectively). Similarly, the mean level of MCP-1 was greater among those with HAND as compared with the unimpaired (P = 0.047). There were also trends for higher levels of sCD163 and TNF-α among females with MND in univariable analyses. Levels of monocyte activation markers correlate with the severity of impairment among individuals with HAND. The mechanisms that underlie these effects and the potential role of gender require further study.

Plasma cytokine profile in synucleinophaties with dementia

Immune response may play a pivotal role in the pathogenesis of the common synucleinopathy as Parkinson’s disease (PD) and could be mediated with the accumulation of neurotoxic alpha-synuclein. There is limited evidence for immune response in another synucleinopathy as dementia with Lewy bodies (DLB). Recent data suggest that immune response may contribute to cognitive impairment. We aimed to estimate plasma cytokine profile in patients with synucleinopathies with dementia (PD dementia (PDD), DLB). Plasma cytokine levels (interferon-gamma (IFN-gamma), interleukin (IL)-4 (IL-4), IL-6, IL-10, tumor necrosis factor alpha (TNF-alpha), monocyte chemoattractant protein-1 (MCP-1)). were estimated in 16 patients with DLB, 19 patients with PDD, 28 patients with PD without dementia (PD) and 19 individuals without neurological disorders (controls) using Luminex array system. Cognitive status was assessed with the Mini–Mental State Examination (MMSE). TNF-alpha and IL-6 plasma levels were elevated in patients with synucleinopathies with dementia (DLB, PDD) compared to controls and IL-10 plasma level was increased in PDD compared to controls (p < 0.05). IFN-gamma levels were decreased in PD and PDD patients compared to controls (p < 0.001, p = 0.026, respectively) and in PD patients than in DLB patients (p = 0.032). Patients with PD, PDD, and DLB were characterized by increased plasma levels of MCP-1 compared to controls (p < 0.001). At the same time, no differences in TNF-alpha, IL-10, IL-6 plasma levels in PD patients compared to controls were found. Our study demonstrated more pronounced immune response in synucleinopathies associated with dementia compared to PD without demetia.

Increased number of monocytes and plasma levels of MCP-1 and YKL-40 in first-episode psychosis.

Accumulating evidence implicates immune activation in the development of schizophrenia. Here, monocyte numbers, monocyte chemoattractant protein-1 (MCP-1) and chitinase-3-like protein 1 (YKL-40) were investigated in plasma and cerebrospinal fluid (CSF) in first-episode psychosis (FEP) patients. CSF and blood were sampled from 42 first-episode psychosis (FEP) patients and 22 healthy controls. The levels of YKL-40 and MCP-1 were measured using electrochemiluminescence assay, and blood monocytes were counted using an XN-9000-hematology analyzer. We found higher plasma levels of MCP-1 and YKL-40 in FEP patients compared with healthy controls, a condition that was unrelated to antipsychotic and/or anxiolytic medication. This was combined with an increased number of blood monocytes and a borderline significant increase in YKL-40 levels in the CSF of tobacco-free FEP patients. Plasma or CSF chemokines or blood monocytes did not correlate with the severity of symptoms or the level of functioning. These data demonstrate activation of monocytes in FEP and strengthens the idea of an immune dysfunction of psychotic disorders. Further studies are required to perceive a role of YKL-40 and MCP-1 in the initiation and progression of schizophrenia.

Monocyte Chemoattractant Protein-1 as a Predictor of Coronary Atherosclerosis in Patients Receiving Coronary Angiography.

Animal studies suggest that monocyte chemoattractant protein-1 (MCP-1) is a promising biomarker for coronary artery atherosclerosis (CAA), but human studies have been inconclusive. To determine potential relationships between plasma MCP-1 and CAA in patients with acute chest pain. A secondary analysis of 150 patients enrolled in emergency department chest pain risk stratification clinical investigations was conducted. Participants with stored blood and known coronary phenotypes (determined by coronary angiography) were selected using stratified randomization such that 50 patients were included into 3 groups: (1) no angiographic evidence of CAA, (2) nonobstructive CAA, and (3) obstructive CAA (stenosis ≥ 70%). Plasma MCP-1 levels were determined by enzyme-linked immunosorbent assay. The association between MCP-1 and obstructive CAA or any CAA was modeled using logistic regression. Variables in the unreduced model included age, sex, race, prior diagnosis of CAA or acute coronary syndrome, hyperlipidemia, hypertension, diabetes, smoking, and cardiac troponin I measurement. Among the 150 participants, 65.3% (98/150) had invasive coronary angiography and 34.7% (52/150) had coronary computed tomographic angiography. Myocardial infarction occurred in 27.3% (41/150) and coronary revascularization occurred in 26% (39/150) of the participants. Each 10 pg/mL increase in MCP-1 measurement was associated with an odds ratio of 1.12 (95% confidence interval, 1.06-1.19) for obstructive CAA. MCP-1 remained a significant predictor of obstructive CAA and any CAA after adjustment for age, sex, race, traditional cardiac risk factors, and cardiac troponin I. MCP-1 is independently associated with CAA among emergency department patients with chest pain.

Early plasma monocyte chemoattractant protein 1 predicts the development of sepsis in trauma patients: A prospective observational study.

Monocyte chemoattractant protein 1 (MCP-1) is an initiating cytokine of the inflammatory cascade. Extracellular MCP-1 exhibits pro-inflammatory characteristic and plays a central pathogenic role in critical illness. The purpose of the study was to identify the association between plasma MCP-1 levels and the development of sepsis after severe trauma.The plasma levels of MCP-1 in severe trauma patients were measured by a quantitative enzyme-linked immune sorbent assay and the dynamic release patterns were recorded at three time points during seven days post-trauma. The related factors of prognosis were compared between sepsis and non-sepsis groups and analyzed using multivariate logistic regression analysis. We also used receiver operating characteristic (ROC) curves to assess the values of different variables in predicting sepsis.A total of 72 patients who met criteria indicative of severe trauma (72.22% of male; mean age, 49.40 ± 14.29 years) were enrolled. Plasma MCP-1 concentrations significantly increased on post-trauma day 1 and that this increase was significantly correlated with the Injury Severity Score (ISS) and interleukin-6 (IL-6). Multivariate logistic regression analysis showed that early MCP-1, ISS, and IL-6 were independent risk factors for sepsis in severe trauma patients. Incorporation of the early MCP-1 into the ISS can increase the discriminative performance for predicting development of sepsis.Early plasma MCP-1 concentrations can be used to assess the severity of trauma and is correlated with the development of sepsis after severe trauma. The addition of the early MCP-1 levels to the ISS significantly improves its ability to predict development of sepsis.

Deletion of the Duffy antigen receptor for chemokines (DARC) promotes insulin resistance and adipose tissue inflammation during high fat feeding.

ObjectiveInflammation in adipose tissues in obesity promotes insulin resistance and metabolic disease. The Duffy antigen receptor for chemokines (DARC) is a promiscuous non-signaling receptor expressed on erythrocytes and other cell types that modulates tissue inflammation by binding chemokines such as monocyte chemoattractant protein-1 (MCP-1) and by acting as a chemokine reservoir. DARC allelic variants are common in humans, but the role of DARC in modulating obesity-related metabolic disease is unknown.MethodsWe examined body weight gain, tissue adiposity, metabolic parameters and inflammatory marker expression in wild-type and DARC knockout mice fed a chow diet (CD) and high fat diet (HFD).ResultsCompared to wild-type mice, HFD-fed DARC knockout mice developed glucose intolerance and insulin resistance independent of increases in body weight or adiposity. Interestingly, insulin sensitivity was also diminished in lean male DARC knockout mice fed a chow diet. Insulin production was not reduced by DARC gene deletion, and plasma leptin levels were similar in HFD fed wild-type and DARC knockout mice. MCP-1 levels in plasma rose significantly in the HFD fed wild-type mice, but not in the DARC knockout mice. Conversely, adipose tissue MCP-1 levels were higher, and more macrophage crown-like structures were detected, in the HFD fed DARC knockout mice as compared with the wild-type mice, consistent with augmented adipose tissue inflammation that is not accurately reflected by plasma levels of DARC-bound MCP-1 in these mice.

Unexpected and striking effect of heparin-free dialysis on cytokine release

Heparin (both unfractionated and low molecular weight) is not only a potent anticoagulant but also has many pleiotropic effects, some of which are mediated by cytokine release. We compared the effect of hemodialysis (HD) with enoxaparin as an anticoagulant and without systemic anticoagulation (heparin-grafted membrane—Evodial) on the release of monocyte chemoattractant protein 1 (MCP-1), endostatin (ES) and activin A (Act-A). Nineteen stable HD patients were dialyzed with or without heparin, and plasma levels of MCP-1, ES and Act-A were measured after such a dialysis. During HD with Evodial, the intradialytic levels of all three cytokines were 2–3 folds lower. The between-anticoagulant differences were significant over time for all three cytokines: MCP-1 (P < 0.001), ES (P < 0.001) and Act-A (P < 0.001). This striking effect of heparin-free dialysis with Evodial membrane may be beneficial not only because it reduces the possibility of bleeding complications but also because it might reduce proinflammatory cytokine concentration and therefore contribute to the improvement in endothelial function. Further studies are needed to determine whether it has a positive effect on morbidity and mortality of maintenance HD patients.

Renal Denervation Reduces Monocyte Activation and Monocyte-Platelet Aggregate Formation: An Anti-Inflammatory Effect Relevant for Cardiovascular Risk.

Overactivation of renal sympathetic nervous system and low-grade systemic inflammation are common features of hypertension. Renal denervation (RDN) reduces sympathetic activity in patients with resistant hypertension. However, its effect on systemic inflammation has not been examined. We prospectively investigated the effect of RDN on monocyte activation and inflammation in patients with uncontrolled hypertension scheduled for RDN. Ambulatory blood pressure, monocyte, and monocyte subset activation and inflammatory markers were assessed at baseline, 3 months, and 6 months after procedure in 42 patients. RDN significantly lowered blood pressure at 3 months (150.5±11.2/81.0±11.2 mm Hg to 144.7±11.8/77.9±11.0 mm Hg), which was sustained at 6 months (144.7±13.8/78.6±11.0 mm Hg). Activation status of monocytes significantly decreased at 3 months (P<0.01) and 6 months (P<0.01) after the procedure. In particular, classical monocyte activation was reduced at 6 months (P<0.05). Similarly, we observed a reduction of several inflammatory markers, including monocyte-platelet aggregates (3 months, P<0.01), plasma monocyte chemoattractant protein-1 levels (3 months, P<0.0001; 6 months, P<0.05), interleukin-1β (3 months, P<0.05; 6 months, P<0.05), tumor necrosis factor-α (3 months, P<0.01; 6 months, P<0.05), and interleukin-12 (3 months, P<0.01; 6 months, P<0.05). A positive correlation was observed between muscle sympathetic nerve activity and monocyte activation before and after the procedure. These results indicate that inhibition of sympathetic activity via RDN is associated with a reduction of monocyte activation and other inflammatory markers in hypertensive patients. These findings point to a direct interaction between the inflammatory and sympathetic nervous system, which is of central relevance for the understanding of beneficial cardiovascular effects of RDN.

MCP-1 Levels are Associated with Cardiac Remodeling but not with Resistant Hypertension.

BackgroundHypertension is a chronic, low-grade inflammation process associated with the release of cytokines and development of target organ damage. Deregulated monocyte chemoattractant protein-1 (MCP-1) levels have been associated with high blood pressure and cardiovascular complications; however, the mechanisms involved are complex and not fully understood.ObjectiveThis study aimed to compare the levels of MCP-1 in patients with resistant (RH) versus mild-to-moderate (HTN) hypertension and their association with the presence or absence of left ventricular hypertrophy (LVH) in all hypertensive subjects.MethodsWe enrolled 256 hypertensive subjects: 120 RH and 136 HTN, investigating the relationship between circulating MCP-1 levels and blood pressure, biochemical data, hematologic profile, and cardiac damage within the RH and HTN groups. Plasma MCP-1 levels were measured by ELISA and LVH was assessed by echocardiography.ResultsWe found no difference in MCP-1 levels between RH and HTN subjects. On the other hand, we encountered lower MCP-1 levels in patients with LVH (105 pg/mL [100 - 260 pg/mL] versus 136 pg/mL (100 - 200 pg/mL), p = 0.005, respectively] compared with those without LVH. A logistic regression model adjusted for body mass index (BMI), age, race, aldosterone levels, and presence of diabetes and RH demonstrated that median levels of MCP-1 (2.55 pg/mL [1.22 - 5.2 pg/mL], p = 0.01) were independently associated with LVH in the entire hypertensive population.ConclusionSince MCP-1 levels were similar in both RH and HTN subjects and decreased in hypertensive patients with existing LVH, our study suggests a possible downregulation in MCP-1 levels in hypertensive individuals with LVH, regardless of hypertension strata.

Monocyte chemoattractant protein-1 is not required for liver regeneration after partial hepatectomy.

BackgroundLiver regeneration following 70 % partial hepatectomy (PH) requires the coordinated expression of soluble mediators produced by macrophages. Monocyte chemoattractant protein-1 (MCP-1) is a potent stimulus of monocyte recruitment and macrophage activation. The goal of this study was to determine how MCP-1 contributes to liver regeneration.MethodsPH was performed on anesthetized C57Bl/6 (wild type) and MCP-1 knockout mice, and macrophage-produced cytokines and hepatocyte proliferation were measured.ResultsIn wild type mice, hepatic MCP-1 protein levels increased 4–6 h after PH, and elevated plasma MCP-1 levels were detected 12 h after PH. Hepatocyte proliferation was comparable in MCP-1 knockout and wild type mice, as was the expression of macrophage-derived cytokines, TNFα and IL-6, and levels of phosphorylated STAT3. The number of CCR2+ cells in the liver was similar in MCP-1 knockout and wild type mice, which suggests that other chemokines may recruit CCR2+ cells in the absence of MCP-1. Studies with CCR2 knockout mice revealed that hepatocyte proliferation was suppressed ~40 % compared to wild type mice 36 h after PH, but proliferation and liver-body-weight ratios were similar at 48 h.ConclusionThese findings suggest that MCP-1 is not required for PH-induced liver regeneration, yet the role of CCR2 warrants further study.