Effects of curcumin on serum cytokine concentrations in subjects with metabolic syndrome: A post-hoc analysis of a randomized controlled trial

BackgroundCytokines are involved in the development of metabolic abnormalities that may result in metabolic syndrome (MetS). Since curcumin has shown anti-inflammatory properties, the aim of this study was to evaluate the effect of curcumin supplementation on serum cytokines concentrations in subjects with MetS.MethodsThis study was a post-hoc analysis of a randomized controlled trial in which males and females with diagnosis of MetS, according to the criteria defined by the National Cholesterol Education Program Adult Treatment Panel III guidelines, were studied. Subjects who met the inclusion criteria were randomly assigned to either curcumin (daily dose of 1 g/day) or a matched placebo for a period of 8 weeks.ResultsOne hundred and seventeen subjects were assigned to either curcumin (n = 59) or placebo (n = 58) groups. Within-group analysis revealed significant reductions in serum concentrations of TNF-α, IL-6, TGF-β and MCP-1 following curcumin supplementation (p < 0.001). In the placebo group, serum levels of TGF-β were decreased (p = 0.003) but those of IL-6 (p = 0.735), TNF-α (p = 0.138) and MCP-1 (p = 0.832) remained unaltered by the end of study. Between-group comparison suggested significantly greater reductions in serum concentrations of TNF-α, IL-6, TGF-β and MCP-1 in the curcumin versus placebo group (p < 0.001). Apart from IL-6, changes in other parameters remained statistically significant after adjustment for potential confounders including changes in serum lipids and glucose levels, and baseline serum concentration of the cytokines.ConclusionResults of the present study suggest that curcumin supplementation significantly decreases serum concentrations of pro-inflammatory cytokines in subjects with MetS.     

Pro-inflammatory and anti-inflammatory cytokines in acute ischemic stroke and their relation to early neurological deficit and stroke outcome

ObjectivesOur aim was to explore (i) the difference in concentration of IL-6, TNF-α and IL-10 between acute ischemic stroke patients and control individuals; (ii) the association of plasma cytokine concentration with stroke severity at admission assessed by NIHSS and stroke outcome in 90 days assessed by Barthel index (BI) and modified Rankin scale (mRS).Materials and methodsStudy included 68 stroke patients admitted within 12 h of symptoms onset and 71 controls.ResultsIL-6 was increased in patients relative to controls (P = 0.035) and this increase was associated with severe stroke (P = 0.007) and worse outcome (P = 0.030 and 0.019; assessed by BI and mRS, respectively), whereas IL-10 was decreased (P = 0.044) and associated with better outcome (P = 0.043). TNF-α did not differ between studied groups (P = 0.302).ConclusionsIncreased IL-6 and reduced IL-10 concentrations are present in early stroke period and are associated with a degree of neurological deficit and/or stroke outcome.     

Pro-inflammatory and atherogenic circulating factors in non-alcoholic fatty liver disease associated to metabolic syndrome

BackgroundIt is not elucidated if liver fat deposits associated to metabolic syndrome (MS) aggravate the atherogenic state. We evaluated, in MS patients, if the presence of non-alcoholic hepatic steatosis (HS) determines differences in inflammatory markers and VLDL characteristics.MethodsSeventy-five patients with MS were divided into 2 groups depending on the presence or absence of HS, assessed by ultrasound. Lipid profile, free fatty acids (FFA), VLDL composition, adiponectin, tumor necrosis factor-alpha (TNF-α), high sensitivity C-reactive protein (hs-CRP), and soluble adhesion molecules (sVCAM-1 and sICAM-1) were measured.ResultsHS patients presented increased triglycerides levels, HOMA-IR and FFA. Patients with HS showed a reduction in adiponectin (p = 0.04) and increase in hs-CRP (p = 0.02), independently of insulin-resistance (IR). FFA correlated positively with TNF-α (p = 0.04) and inversely with adiponectin (p = 0.01). hs-CRP correlated with all inflammatory markers, independently of IR: TNF-α (r = 0.34, p = 0.02), sVCAM-1 (r = 0.29 p = 0.03), sICAM-1 (r = 0.56, p = 0.01), adiponectin (r = ?0.34, p = 0.04). HS patients presented higher VLDL mass and number of particles. Adiponectin correlated with VLDL cholesterol content (r = ?0.47, p = 0.04), independently of IR. VLDL, once secreted, would suffer from changes, becoming more atherogenic.ConclusionsSimple HS would play an important role increasing cardiovascular risk, independently of IR. hs-CRP may represent a useful biomarker of this condition.     

The relationship between the levels of gonadotropic hormones and OPG,leptin, TGF-β1 and TGF-β2 in Chinese adult women

BackgroundThe relationship between the levels of gonadotropic hormones and bone metabolism-related cytokines in Chinese women is unclear. We investigated the relationship between FSH and LH and OPG, leptin, TGF-β1, and TGF-β2 in Chinese women.MethodsA cross-sectional study of 694 Chinese women, aged 20 to 82 y was conducted. Levels of serum FSH, LH, OPG, leptin, TGF-β1, and TGF-β2 were determined.ResultsIn premenopausal females, serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels seemly showed no correlation with the cytokine levels. In perimenopausal females, serum FSH and LH levels showed significant positive correlation with osteoprotegerin (OPG) and transforming growth factor-β2 (TGF-β2) levels (r = 0.286 to 0.405, all P = 0.000), whereas they showed negative correlation with TGF-β1 levels (r = ? 0.413 and ? 0.354, all P = 0.000). In postmenopausal females, FSH and LH levels showed positive correlation with OPG levels (r = 0.247 and 0.241, all P = 0.000), negative correlation with leptin and TGF-β1 levels (r = ? 0.234 to ? 0.319, all P = 0.000), and no correlation with TGF-β2 levels. Multiple linear regression stepwise analysis revealed the following results. In premenopausal females, 2.0% and 1.5% of the changes in LH could be explained by OPG and leptin, respectively, while 1.9% of the changes in OPG could be explained by LH. In perimenopausal females, the determinants of OPG and TGF-β1 on FSH were 10.9% and 17.0%, respectively, and the determinants of OPG, TGF-β1 and TGF-β2 on LH were 4.5%, 4.9% and 16.4%, respectively. The determinants of FSH and LH on OPG were 14.5% and 2.5%, respectively. The determinant of FSH on TGF-β1 was 4.5%, while the determinant of LH on TGF-β2 was 16.4%. In postmenopausal females, the determinants of leptin and OPG on FSH were 10.2% and 2.8%, respectively, and the determinants of OPG and TGF-β1 on LH were 5.8% and 2.3%, respectively. The determinant of FSH on OPG, leptin and TGF-β1 were 6.1%, 3.4% and 9.2%.ConclusionsThese results indicate that age-related gonadotropic hormone levels are associated with changes in OPG, TGF-β1, TGF-β2 and leptin, and change with menopausal status.     

Association of high sensitivity C-reactive protein (hsCRP) and tumour necrosis factor-alpha (TNF-alpha) with carotid intimal medial thickness in subjects with different grades of glucose intolerance--the Chennai Urban Rural Epidemiology Study (CURES-31)

ObjectiveTo assess the association of high sensitivity C-Reactive Protein [hsCRP] and Tumour Necrosis Factor-α [TNF-α] with IMT in Asian Indians with different grades of glucose intolerance.Design and methodsSubjects with normal glucose tolerance [NGT](n = 150), impaired glucose tolerance [IGT] (n = 150) and type 2 diabetes (DM) (n = 150) were recruited from the Chennai Urban Rural Epidemiology Study [CURES], in south India. hsCRP was estimated by nephelometry and TNF-α by enzyme linked immunosorbent assay. Carotid IMT was assessed by high resolution B-mode ultrasonography.ResultshsCRP and TNF-α levels were higher in those with DM [p < 0.001] and IGT [p < 0.001] compared to NGT. In linear regression analysis, both hsCRP [p = 0.003] and TNF-α [p =0.001] showed an association with IMT among NGT subjects even after adjusting for age and gender. Among IGT subjects, TNF-α was associated with IMT [p < 0.001], while no association was observed either with hsCRP or TNF-α in diabetic subjects. In NGT subjects, mean IMT was highest in those with high values [III tertile] of both TNF-α and hsCRP [0.83 ± 0.1 mm; p < 0.001] followed by those with high TNF-α + low hsCRP [0.74 ± 0.09 mm; p < 0.001], high hsCRP  low TNF-α [0.67 ± 0.09 mm; p < 0.001], and lowest in those with both low TNF-α and hsCRP [I tertile] [0.63 ± 0.05 mm.ConclusionWe conclude that in Asian Indians 1. Levels of hsCRP and TNF-α increase with increasing severity of glucose intolerance 2. Both hsCRP and TNF-α are associated with IMT in NGT subjects while TNF-α alone is associated with IMT in IGT subjects 3. hsCRP and TNF-α have a cumulative effect on mean IMT values in NGT subjects.     

Serum brain-derived neurotrophic factor in patients with type 2 diabetes mellitus: Relationship to glucose metabolism and biomarkers of insulin resistance

ObjectivesThe aims of this study were to measure serum levels of brain-derived neurotrophic factor (BDNF) in patients with type 2 diabetes mellitus (T2DM) and to investigate the association of these BDNF levels with biomarkers of glucose metabolism and insulin resistance.Design and methodsWe studied 112 patients with T2DM and 80 age- and gender-matched control subjects.ResultsSerum BDNF levels were significantly lower in patients with T2DM compared to control subjects (15.5 ± 5.2 ng/mL vs. 20.0 ± 7.3 ng/mL, P < 0.01). In patients with T2DM, BDNF levels were significantly higher in females than in males (P < 0.01). In the female patients, BDNF was positively related to immunoreactive insulin (IRI) (ρ = 0.458, P < 0.05) and HOMA-R (ρ = 0.444, P < 0.05). Stepwise multiple regression analysis showed a significant relationship between BDNF and IRI (F = 5.294, P < 0.05) in female patients with diabetes.ConclusionsThese findings suggest that BDNF may contribute to glucose metabolism.     

A multiplex immunoassay gives different results than singleplex immunoassays which may bias epidemiologic associations

ObjectivesMultiplex immunoassays are increasingly used in epidemiologic studies to measure inflammatory factors, however there are few published evaluations of this technology. Our objective was to compare a common multiplex immunoassay to singleplex immunoassays for measuring inflammatory factors, and to examine how combining data from each affects an epidemiologic association.Design and methodsPlasma IL-1 beta, IFN-gamma, IL-6, and TNF-alpha were measured in 100 samples using a multiplex kit from Mesoscale Discovery (MSD) and singleplex ELISAs from R&;D Systems. Separate samples (n = 80) were collected to compare multiplex and singleplex assays from MSD. We simulated the effect of combining MSD multiplex and R&;D singleplex data on the association between sugar sweetened beverage (SSB) intake and IL-6 in the Health Professionals Follow-up Study (HPFS; n = 1314).ResultsCompared to R&;D ELISAs, the MSD multiplex proportionally and significantly overestimated IL-1 beta (slope = 1.2), and IFN-gamma (slope = 2.9) but underestimated IL-6 (slope = 0.5). Correlations were ≥ 0.81 except for TNF-alpha (r = 0.31). Compared to MSD singleplex, the MSD multiplex proportionally underestimated IFN-gamma (slope = 0.7) and TNF-alpha (slope = 0.5). Correlations were ≥ 0.96. The association between sugar sweetened beverage intake and IL-6 in the HPFS (+ 0.16 pg/mL per serving/day, p = 0.02, all singleplex) was gradually attenuated as multiplex data made an increasing contribution to the data-set. (+ 0.09 pg/mL [? 45%], p = 0.02, all multiplex)ConclusionsA multiplex immunoassay for inflammatory factors yielded significantly different results than singleplex immunoassays—including those from the same company. Correlations were not consistently high, except among assays from the same company. Such differences may distort epidemiologic relationships if data from both methods are merged.     

The association between transforming growth factor β3 polymorphisms and left ventricular structure in hypertensive subjects

BackgroundTransforming growth factor β (TGF-β) may be a crucial regulator of cardiac remodeling. We investigated the association between the TGF-β gene polymorphisms and left ventricular structure.MethodsA total of 658 hypertensive subjects were genotyped for the TGF-β1 T869C and TGF-β3 (rs3917187 and rs4252338) polymorphisms.ResultsTGF-β3 rs3917187 AA homozygotes had, while accounting for covariates, greater left ventricular end-systolic (LVESD, P = 0.004) and end-diastolic dimension (LVEDD, P = 0.007) than G allele carriers. Moreover, left ventricular mass index (LVMI) in AA genotype was 123.0 ± 3.1 g/m² significantly higher than that in AG (114.6 ± 1.6 g/m²) and GG (115.4 ± 2.1 g/m², P = 0.03) genotypes. In multivariate regression analysis, TGF-β3 rs3917187 genotype as an independent predictor had statistically significant effects on LVESD (β = 0.164, P = 0.002), LVEDD (β = 0.172, P = 0.003) and LVMI (β = 0.136, P = 0.016), respectively. In further analyses, we observed a significant interaction between the rs3917187 and alcohol intake in relation to LVESD (P_int = 0.04) and left ventricular fractional shortening (LVFSH, P_int = 0.012). However, no relationship could be found between left ventricular parameters and the T869C or the rs4252338.ConclusionThe present results demonstrated that the TGF-β3 rs3917187 polymorphism was associated with left ventricular structure, and had an interactive influence with alcohol on LVESD and LVFSH in hypertensive subjects.     

Serum heat shock protein 70 levels in relation to circulating cytokines, chemokines, adhesion molecules and angiogenic factors in women with preeclampsia

BackgroundWe have previously reported that serum levels of 70 kDa heat shock protein (Hsp70, HSPA1A) are increased and reflect systemic inflammation, oxidative stress and hepatocellular injury in preeclampsia. The purpose of this study was to determine whether increased serum Hsp70 concentrations in women with preeclampsia are related to circulating levels of cytokines, chemokines, adhesion molecules and angiogenic factors, the key players in the pathogenesis of the disease.MethodsSixty preeclamptic patients and 60 normotensive, healthy pregnant women were involved in this case-control study. Levels of Hsp70 (HSPA1A) and transforming growth factor (TGF)-beta1 in maternal sera were assessed by ELISA. Serum levels of interleukin (IL)-1beta, IL-1 receptor antagonist, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p40, IL-12p70, IL-18, interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, interferon-gamma-inducible protein (IP)-10, monocyte chemotactic protein (MCP)-1, intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 were determined by multiplex suspension array. Serum total soluble fms-like tyrosine kinase-1 (sFlt-1) and biologically active placental growth factor (PlGF) levels were measured by electrochemiluminescence immunoassay. For statistical analyses, the Mann–Whitney U-test, the Fisher exact and Pearson chi-square tests, the Spearman rank order correlation, multiple linear regression and logistic regression were applied.ResultsSerum levels of Hsp70 were significantly higher in preeclamptic patients than in healthy pregnant women. Additionally, most of the measured inflammatory variables differed significantly between the two study groups except for serum IL-1beta and TGF-beta1 levels and IL-18/IL-12p70 and IL-12p70/IL-12p40 ratios, indicating a bias toward a pro-inflammatory status in preeclampsia. Preeclamptic patients had significantly higher sFlt-1 levels and sFlt-1/PlGF ratio and significantly lower PlGF concentrations as compared to healthy pregnant women. In the preeclamptic group, serum Hsp70 concentrations showed significant correlations with serum levels of IL-12p40 (R = 0.59, p < 0.001), MCP-1 (R = 0.43, p < 0.001), ICAM-1 (R = 0.39, p = 0.0020) and VCAM-1 (R = 0.46, p < 0.001). Furthermore, elevated serum Hsp70 level and sFlt-1/PlGF ratio had a synergistic (joint) effect in the risk of preeclampsia, as shown by the substantially higher odds ratios of their combination than of either alone.ConclusionsIncreased serum Hsp70 concentrations in women with preeclampsia were associated with pro-inflammatory changes in circulating cytokine profile, suggesting that circulating Hsp70 might contribute to the development of the excessive systemic inflammatory response characteristic of the maternal syndrome of the disease.     

Association of the TNF-α -308G/A polymorphism with family history of type 2 diabetes mellitus in a Mexican population

AimsWe examined the possible association of the ? 308G/A polymorphism of the TNF-α promoter gene in type 2 diabetes mellitus (DM2) patients and in non-diabetic subjects with and without family history of DM2.MethodsWe studied 87 non-diabetic subjects without DM2 family history in at least one of two generations, 48 non-diabetic subjects with DM2 family history and 95 DM2 patients. Genotyping was carried out by PCR-RFLP.ResultsThe frequency of TNF-α ? 308G/A genotype was significantly lower in non-diabetic subjects without DM2 relatives (6%) as compared to DM2 patients (24%) (odds ratio (OR) = 5.24; 95% confidence interval (CI) = 1.9–15.8, p < 0.0005), but similar to non-diabetic subjects with DM2 relatives (29%) (OR = 0.77; CI = 0.3–1.7, p = 0.4). Logistic regression analysis showed the association of TNF-α ? 308G/A polymorphism with DM2 family history (OR = 5.80; CI = 1.77–18.98, p < 0.0003).ConclusionsOur results suggest that TNF-α ? 308G/A polymorphism is associated with DM2 family history and is a risk factor for DM2.     

Cytokine elevations in acute coronary syndrome and ovarian cancer: a mechanism for the up-regulation of the acute phase proteins in these different disease etiologies

Objectives:To identify if a common set of cytokines is elevated in both ovarian cancer and acute coronary syndrome (ACS).Design and methods:A cytokine array (Randox Ltd) was measured in healthy women (n = 33), women with ACS (n = 21) and ovarian cancer (n = 45).Results:Women with ACS or ovarian cancer had higher concentrations of IL-6, IL-8, VEGF, MCP-1, and EGF as compared to healthy volunteers.Discussion:Common cytokine elevations are present in both ACS and ovarian cancer.     

Plasma high sensitivity C-reactive protein and its relationship with cytokine levels in children with newly diagnosed type 1 diabetes and ketoacidosis

BackgroundHigh-sensitivity C-reactive protein (hs-CRP) and pro-inflammatory cytokines have been suggested as sensitive markers of endothelial dysfunction. Our aim was to monitor plasma hs-CRP levels at different time-points and in different degrees of ketoacidosis severity, its association with cytokine levels and its role as a marker of severe ketoacidosis complications.Patients and methodsWe studied in 38 newly diagnosed children with type 1 diabetes and ketoacidosis, aged 7.7 ± 3.1 years, hs-CRP, white blood cell count (WBC), and plasma levels of cytokines IL-1β (interleukin-1β), IL-2, IL-6, IL-8, IL-10, TNF-α (tumor necrosis factor-α) prior to and during DKA management.ResultsOn admission, the levels of WBC, PMN, IL-6 and IL-10 were elevated, but were all reduced within 120 h after ketoacidosis management. In the group with moderate/severe ketoacidosis, but not in mild ketoacidosis, hs-CRP levels were significantly reduced at 24 h (p = 0.021), WBC and IL-6 at 120 h (p = 0.003), while IL-10 was prematurely reduced at 6–8 h (p = 0.008). Moreover hs-CRP was significantly associated with WBC (p = 0.023) and IL-6 (p = 0.028) on admission, with IL-6 (p = 0.002) and IL-8 (p = 0.014) at 24 h and with IL-10 (p = 0.027) at 120 h. The above were not observed in the group with mild ketoacidosis.ConclusionsIn the children with moderate/severe diabetic ketoacidosis of our study, increased levels of hs-CRP and IL-6 were observed, together with leukocytosis and neutrophilia, without the presence of infection. As hs-CRP was found to be strongly associated with the inflammatory IL-6, the prolonged elevation of hs-CRP levels in children with severe ketoacidosis could serve as a marker for the development of its severe complications.     

Prognostic value of cytokines and chemokines in addition to the GRACE Score in non-ST-elevation acute coronary syndromes

BackgroundIncreased cytokine and chemokine levels are associated with cardiovascular events in patients with non-ST-elevation acute coronary syndromes (ACS), but the incremental prognostic value of these inflammatory markers is not known. We determined if cytokine and chemokine assessment adds prognostic information to the GRACE Score in patients with ACS.MethodsFive cytokines (interleukin (IL)-1β, IL-6, IL-10, IL-12p70, and tumor necrosis factor (TNF)-α soluble receptor I), five chemokines (IL-8, CCL5, CXCL9, CCL2, and CXCL10) and C-reactive protein (CRP) were measured at admission of 87 patients admitted with ACS.ResultsDuring hospitalization, the incidence of cardiovascular events was 13% (7 deaths, 1 nonfatal acute myocardial infarction, and 3 refractory unstable angina). Individuals who developed events had significantly greater levels of CRP, IL-1β, IL-12, TNF-α, IL-8, CXCL9 and CCL2, compared with those free of events. Thus, these markers were used to build an Inflammatory Score, by the input of one point for each of these variables above the 75th percentile. After adjustment for the GRACE Score, the Inflammatory Score independently predicted events (OR = 1.80; 95% CI = 1.12–1.88). Incorporation of the Inflammatory Score into the GRACE Score promoted a C-statistics improvement from 0.77 (95% CI = 0.58–0.96) to 0.85 (95% CI = 0.71–1.0). Net reclassification improvement obtained with GRACE–Inflammatory Score was 13% (P = 0.007), indicating a significant reclassification. When only CRP was incorporated into GRACE, the increase on C-statistics was not relevant (from 0.77 to 0.80).ConclusionCytokines and chemokines measured at admission add prognostic information to the GRACE Score in patients admitted with ACS.     

Decreased serum brain-derived neurotrophic factor concentration in young nonobese subjects with low insulin sensitivity

ObjectiveInsulin resistance and type 2 diabetes are associated with an increased risk of neurodegenerative diseases. Decreased brain-derived neurotrophic factor (BDNF) levels might play a role in the pathogenesis of neuropsychiatric disorders. The aim of our study was to estimate serum BDNF concentration in nonobese women divided into subgroups according to their insulin sensitivity.Design and methodsWe studied 46 young, healthy, nonobese women. Insulin sensitivity was estimated with the euglycemic–hyperinsulinemic clamp technique. Then, participants were divided into subgroups of high (mean, 12.79 ± 2.01 mg/kg fat-free mass/min) and low insulin sensitivity (mean, 7.33 ± 1.66 mg/kg fat-free mass/min).ResultsWe observed decreased serum BDNF concentration in women with low insulin sensitivity in comparison to high insulin sensitivity group (3306.11 ± 603.10 vs 4141.91 ± 755.37 pg/mL, p = 0.001). Serum BDNF was positively related to insulin sensitivity (r = 0.43, p = 0.003). This correlation remained significant after adjustment for other estimated parameters.ConclusionsSerum BDNF is decreased in young nonobese women with low insulin sensitivity. Early detection and prevention of insulin resistance might be useful in the prevention of neurodegenerative disorders.     

Association of hsp70-2 (+1267A/G), hsp70-hom (+2437T/C), HMOX-1 (number of GT repeats) and TNF-alpha (+489G/A) polymorphisms with COPD in Croatian population

ObjectiveTo test for possible association of hsp70-2 (+ 1267A/G), hsp70-hom (+ 2437T/C), HMOX-1 (number of GT repeats) and TNF-α (+ 489G/A) polymorphisms with chronic obstructive pulmonary disease (COPD) in Croatian population.MethodsGenotyping of DNA isolated from whole blood of 130 COPD patients (as defined by spirometry) and 95 healthy controls was performed. Fragment size analysis upon restriction enzyme digestion and/or sequencing was used for genotype/allele definition. Significance of findings was tested using χ² test.Resultshsp70-2 (+ 1267A/G) polymorphism was significantly associated with COPD. Results of genotyping analysis indicated that a genotype carrying G allele was preferentially associated with COPD; odds ratio (OR) = 1.50, 95% confidence interval (CI) = 1.00–2.24 and P = 0.061. OR for the GG genotype was 3.47 with CI = 1.26–9.56 and P = 0.04. No association for hsp70-hom (+ 2437T/C), TNF-α (+ 489G/A) and HMOX-1 (number of GT repeats) polymorphisms were found. In addition, comparison of genotype frequencies among different stages of disease severity (GOLD II-IV) revealed no discrimination for any of the tested polymorphisms.ConclusionThis study is supporting the association of hsp70-2 (+ 1267A/G) polymorphism and COPD. Higher frequency of G allele and GG genotype in Croatian COPD patients was observed. There was no evidence for the association of hsp70-hom (+ 2437T/C), TNF-α (+ 489G/A) SNPs and HMOX-1 (number of GT repeats) polymorphism with COPD. Allele and genotype frequencies for all of the tested polymorphisms show no association with disease severity (GOLD II-IV).     

Synergistic effects of the polymorphisms in the PAI-1 and IL-6 genes with smoking in determining their associated risk with coronary artery disease

ObjectivesTo assess the relationship between IL-6 and PAI-1 polymorphisms and coronary artery disease (CAD) and to observe the interactions between these polymorphic variants and smoking in the CAD risk.Design and methodThe study population consisted of 178 patients with angiographically documented CAD and 202 blood donors. The analyses of genetic polymorphisms were performed using the PCR-RFLP method.ResultsThe frequency of PAI-1 5G allele was higher in the entire CAD group than in control group (p = 0.04, OR = 1.35). Also the 5G allele carriers (4G5G + 5G5G) were more frequent in patients than in controls (p = 0.03, OR = 1.93). The number of women carrying 5G allele was again significantly higher among patients (OR = 10.95 p = 0.0075). The IL-6 C allele frequency was higher only in the CAD male subgroup (p = 0.035, OR = 1.44). We found synergistic and cumulative effects between specific genotype patterns and smoking in determining the risk of CAD, especially between PAI-1(4G5G + 5G5G)+IL-6(CC) and smoking (SIM = 4.18 and p = 0.0005, OR = 9.20, respectively).ConclusionsThere are synergistic and cumulative effects of 5G allele of PAI-1 polymorphism and C allele of IL-6 polymorphism with smoking in determining their associated risk with CAD.     

Relationship between circulating cytokine levels and physical or psychological functioning in patients with advanced cancer

ObjectiveTo investigate the relation between functional impairments of cancer patients and circulating cytokines using a multiplex technique.Design and methods50 patients with cancer were assessed using the quality of life (QOL) questionnaire. 27 plasma cytokine levels were determined by using the Bio-Plex array system. The relation to QOL scores was assessed using Chi-square test for categorical variables and univariate linear regression analysis for cytokine levels.ResultsMultivariate analysis showed that interleukin-6 (IL-6) level is a significant independent determinant of physical (β = ? 0.238, P = 0.0126) and cognitive functioning (β = ? 0.462, P = 0.0006) and that vascular endothelial growth factor (VEGF) level is a significant independent determinant of emotional functioning (β = ? 0.414, P = 0.039).ConclusionThis study, in which 27 cytokines are simultaneously tested with cutting edge technology, demonstrates that plasma IL-6 and VEGF are significant independent determinants of functional impairments in patients with cancer.     

Association between serum retinol-binding protein 4 and small dense low-density lipoprotein cholesterol levels in young adult women

BackgroundSerum retinol-binding protein 4 (RBP4) and small dense low-density lipoprotein (sdLDL) have been suggested to be associated with insulin resistance, but no information is available on the relationship between RBP4 and sdLDL.MethodsWe determined serum RBP4, sdLDL-cholesterol, and other metabolic variables on 38 young women, aged 19–29 years. The homeostatic model assessment of insulin resistance (HOMA-IR) was used for the estimation of insulin resistance.ResultsIn simple regression analyses, RBP4 levels had significant correlations with total cholesterol (r = 0.354, P = 0.029), LDL-cholesterol (r = 0.396, P = 0.014), and sdLDL-cholesterol (r = 0.510, P = 0.001) levels. The sdLDL-cholesterol levels also correlated significantly with total cholesterol (r = 0.402, P = 0.012), LDL-cholesterol (r = 0.627, P < 0.001) and triglycerides (r = 0.449, P = 0.005). Stepwise multiple regression analyses showed only sdLDL-cholesterol (β coefficient (ß) = 0.510, P = 0.001) level was a significant independent predictor of RBP4 levels (adjusted R² = 0.240), whereas RBP4 (ß = 0.289, P = 0.026) level was one of major factors affecting sdLDL-cholesterol levels (adjusted R² = 0.519). There was no significant association of HOMA-IR with RBP4 or sdLDL levels.ConclusionsWe showed an independent linkage between serum RBP4 and sdLDL-cholesterol levels in young adult women. These findings may contribute to understanding of lipoprotein metabolisms involved in diabetes and cardiovascular disease.     

Effects of a single dose of oral iron on hepcidin concentrations in human urine and serum analyzed by a robust LC-MS/MS method

BackgroundThe measurement of serum hepcidin, a peptide hormone that regulates iron metabolism, is clinically important to the understanding of iron homeostasis in health and disease. To date, the quantification of serum hepcidin levels by conventional immunological detection methods has proven problematic due to challenges in obtaining high quality antibodies which demonstrate good reproducibility. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF) has been employed recently for more sensitive quantification of hepcidin; however, this method has high background levels and therefore less than optimal specificity.MethodsIn order to increase the specificity of the mass spectrometry based assay, we developed a robust, ultra-performance liquid-chromatography-tandem mass spectrometry (UPLC-MS/MS) protocol using multiple selected reaction monitoring (mSRM) for quantification of hepcidin levels in urine and serum of human subjects. With this assay, we assessed levels of hepcidin before and for up to 8 h after oral ingestion of ferrous sulfate in ten adult human subjects without known disease.ResultsThe linear response of hepcidin quantitation on each instrument was measured, and the correlation coefficients of these calibrations were r² = 0.9512 ± 0.0202 (n = 5) for urine and r² = 0.9709 ± 0.0291 (n = 5) for serum [r² = mean ± SD]. Compared to baseline, the levels of urinary hepcidin between 2–4 h and 4–8 h of both women and men showed significant increases with p < 0.05 and p < 0.001, respectively. The levels of serum hepcidin between 4 h and 8 h in both women and men showed significant increases, compared with baseline values, with both p < 0.01. Interestingly, we also observed some degree of oscillation of levels, occurring at later time points.ConclusionsWe have developed and validated a new method for measuring hepcidin concentrations in human serum and urine and used it to demonstrate early increases with iron supplement in both urinary and serum levels of hepcidin, which return to baseline levels, except in urine samples from men.     

Changes of serum adhesion molecules and cytokines in post-ERCP pancreatitis: Adhesion molecules and cytokines in acute pancreatitis

ObjectivesTo assess the early changes of soluble IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, TNF-α, TNF-β, IL-17A, IL-22, soluble (s) P-Selectin, sE-Selectin and sICAM-1 in post-ERCP pancreatitis (PEP).MethodsSingle center, prospective study of 318 ERCP procedures. Serum samples were acquired from all patients prior to ERCP, 6 hours and 24 hours after the procedure. For every PEP case, another patient was chosen as a control, matched for gender, age and time period in which ERCP took place.ResultsTotally, 28 cases and 28 controls were studied. Except for significantly higher IL-1b levels in cases at baseline, no significant differences were observed between cases and controls after Bonferroni corrections. An increase in IL-6 was noted between baseline and 6 h in cases alone (p = 0.016). There was a significant fall in sP-selectin levels at 6 and 24 hours compared to baseline in all patients (corrected p = 0.008 and 0.016 for cases and 0.016 and 0.048 for controls respectively). An increase of sE-selectin in cases was observed between 6 and 24 hours post-ERCP (corrected p = 0.03).ConclusionsSoluble forms of cytokines and adhesion molecules studied seem not to play a major role in PEP.