Association between Metabolic Syndrome Components and Serum High-Sensitivity C-Reactive Protein or Interleukin-6 Levels among Congolese Adults

Metabolic syndrome (MetS) and its components have been linked to elevated serum levels of inflammatory biomarkers such as C-reactive protein, interleukin-6, interleukin-1β and tumor necrosis factor alpha. The aim of our study was to address the association between MetS components with serum hs-CRP and IL-6 levels among Congolese adults. A total of 357 participants (aged 30 - 87 years) were included in this cross-sectional study. Anthropometrics were collected and fasting blood sampled for assessment of fasting blood glycaemia (FBG), lipids and inflammatory parameters using commercially available assays. NCEP-ATPIII criteria were used to define MetS. The Median (IQR) hs-CRP and IL-6 levels were higher in participants with MetS than in those without ([7 (4, 14) versus 6 (4, 8)] mg/L;p = 0.092 and [23.8 (20.9, 27.6) versus 22.3 (19.5, 25.0)] pg/mL;p = 0.002). hs-CRP and IL-6 levels were significantly higher in females with MetS than in those without, but not in males. Among participants, only TG was correlated with hs-CRP (r = 0.149, p = 0.007), and a significant correlation was observed between TG (r = 0.116, p = 0.037), FBG (r = 0.208, p = 0.000), HDL-C (r = −0.119, p = 0.034) and SBP (r = 0.143, p = 0.010) and IL-6. In males, hs-CRP levels were positively correlated with TG (0.316;p = 0.000), negatively with HDL-C (r = −0.290, p = 0.0022), without such correlations in females. In Ames, IL-6 levels were positively correlated with FBG (r = 0.202;p = 0.035), and negatively with HDL-C (r = −0.249, p = 0.009). Significant correlations between IL-6 levels and FBG (r = 0.214;p = 0.000) or SBP (r = 0.227, p = 0.000) were observed in females. Logistic regression analysis was carried out to identify the relationship between MetS components and hs-CRP or IL-6. Values of area under receiver-operating characteristic (ROC) curves suggest potential use of serum hs-CRP (AUC = 0.675) and IL-6 (AUC = 0.656) as diagnostic biomarkers of MetS. Combination of hs-CRP and IL-6 improved diagnosis accuracy, yielding a 0.698 ROC curve area. MetS components are associated with hs-CRP and IL-6 levels among adults Congolese. Combining the two biomarkers hs-CRP and IL-6 improves Mets diagnostic accuracy compared to hs-CRP or IL-6 alone.

The Role of High-sensitivity C-reactive Protein, Interleukin-6 and Cystatin C in Ischemic Stroke Complicating Atrial Fibrillation

This study examined the role of high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6) and cystatin C in ischemic stroke complicating atrial fibrillation (AF) and the relationship of systemic inflammation with this disease in order to identify AF patients who are at high risk of stroke and need optimal anticoagulant therapy.A total of 103 AF patients, simple (n=75) or complicated by ischemic stroke (n=28), and 112 control subjects were recruited.IL-6 level was detected by using enzyme linked immunosorbent assay.Cystatin C and hsCRP levels were measured by means of a particle-enhanced immunonephelometric assay.The results showed that the AF patients had higher levels of hsCRP (P=0.004), IL-6 (P=0.000), and cystatin C (P=0.000) than control subjects.Plasma hsCRP level was increased in the AF patients with ischemic stroke as compared to the patients with simple AF (P=0.036).The AF patients who had the level of hsCRP exceeding 3.83 mg/L were at a higher risk than those with hsCRP level lower than 3.83 mg/L (P=0.030).After adjusting for other factors, cystatin C remained positively associated with IL-6 (r=0.613) and hsCRP (r=0.488).It was concluded that hsCRP is positively correlated with ischemic stroke complicating AF and may be a risk factor independent of other risk factors for AF.Elevated cystatin C level is also indicative of the increased risk of AF.

C-reactive protein,procalcitonin,interleukin-6,vascular endothelial growth factor and oxidative metabolites in diagnosis of infection and staging in patients with gastric cancer

AIM:The current study was to determine the serum/pLasma levels of VEGF,IL-6,malondialdehyde (MDA),nitric oxide (NO),PCT and CRP in gastric carcinoma and correlation with the stages of the disease and accompanying infection. METHODS:We examined the levels of serum VEGF,IL-6, PCT,CRP and plasma MDA,NO in 42 preoperative gastric cancer patients and 23 healthy subjects.There were infection anamneses that had no definite origin in 19 cancer patients. RESULTS:The VEGF levels (mean±SD; pg/mL) were 478.05±178.29 and 473.85±131.24 in gastric cancer patients with and without infection,respectively,and these values were not significantly different (P>0.05).The levels of VEGF, CRP,PCT,It-6,MDA and NO in cancer patients were significantly higher than those in healthy controls and the levels of CRP,PCT,It-6,MDA and NO were statistically increased in infection group when compared with non- infection group (P<0.001). CONCLUSION:Although serum VEGF concentrations were increased in gastric cancer,this increase might not be related to infection.CRP,PCT,IL-6,MDA and NO have obvious drawbacks in the diagnosis of infections in cancer patients. These markers may not help to identify infections in the primary evaluation of cancer patients and hence to avoid unnecessary antibiotic treatments as well as hospitalization. According to the results of this study,IL-6,MDA,NO and especially VEGF can be used as useful parameters to diagnose and grade gastric cancer.

Mechanisms of C-reactive protein, interleukin-6 and soluble CD40L blood concentration changes after coronary stent implantation

Background: The pathway linking inflammation and thrombosis has been extensively studied. Experimental data support that arterial thrombosis also induces a detectable inflammatory response, which in turn, activates prothrombotic pathways closing a vicious circle that interconnects inflammation and thrombosis. Aim: We designed this study to investigate the causes of inflammatory markers increase after coronary angioplasty. Methods: We analyzed the interrelationship of thrombotic and inflammatory markers and the effect of blocking thrombus formation on the inflammatory response in 50 patients undergoing high thrombotic risk coronary angioplasty. The relationship of platelet number to soluble CD40 Ligand, Interleukin-6 and C-reactive protein blood levels was studied. Half of the study population was treated with standard antithrombotic drugs and the other half with the standard therapy plus platelet GP IIb-IIIa receptor inhibitor Eptifibatide. Results: There was a clear correlation between basal platelet count and sCD40L basal levels, post-angioplasty sCD40L increase and post-angioplasty IL-6 levels and post-angioplasty IL-6 levels with post-angioplasty CRP levels. Postangioplasty CRP, IL-6 and sCD40L blood levels were influenced by GP IIb-IIIa treatment in patients with angiographic thrombus. Conclusion: Platelet aggregation induces a proinflammatory response which is blocked by a GP IIb-IIIa inhibitor agent, particularly in patients with patent angiographic thrombus.

Diagnostic value of serum Interleukin-6 combined with synovial IL-6 and C-reactive protein for prosthesis joint infection in patients after joint arthroplasty

Objective:To explore the diagnostic value of serum Interleukin-6(IL-6)combined with synovial IL-6 and C-reactive protein for prosthesis joint infection(PJI)in patients after joint arthroplasty.Methods:A total of 253 patients undergoing revision surgery after the first total hip and total knee arthroplasty in the Second Affiliated Hospital of Hainan Medical College from January 2018 to April 2020 were recruited as the study object.The patients were divided into the PJI group(n=85)and non-PJI group(n=168)according to whether there was PJI,and the baseline characteristics and the laboratory indexe were collected and compared between the two groups.the factors associated with PJI in patients after joint arthroplasty were analyzed by multivariate logistic regression model.And the diagnostic value of each marker for PJI in patients after joint arthroplasty was evaluated by Receiver Operating Characteristic(ROC)curve.Results:The incidence of PJI in this study was 33.6%.Compared with the non-PJI group,the patients in the PJI group had more diabetes mellitus and shorter prosthesis duration(P<0.05).The levels of serum C-reactive protein(CRP),serum interleukin-6(IL-6),synovial IL-6,synovial CRP,synovial leukocyte,synovial neutrophil and ESR in the PJI group were higher than those in non-PJI group,and the level of synovial lymphocyte was lower,with statistically significant differences(P<0.05).Multivariate logistic regression analysis showed that diabetes mellitus(OR=1.706,95%CI:1.02~2.376,P=0.037),prosthesis duration(OR=0.781,95%CI:0.690~0.884,P<0.001),serum IL-6(OR=1.008,95%CI:1.004~1.012,P=0.046),synovial IL-6(OR=1.004,95%CI:1.002~1.006,P=0.011)and synovial CRP(OR=1.481,95%CI:1.010~2.170,P=0.044)were independently related to PJI in patients after joint arthroplasty.ROC curve analysis showed that the area under ROC curve(AUC)of serum IL-6 combined with synovial IL-6 and CRP for diagnose PJI in patients after joint arthroplasty was significantly greater than each marker(0.941 vs 0.760,Z=6.333,P<0.001;0.941 vs 0.743,Z=7.189,P<0.001;0.941 vs 0.785,Z=4.999,P=0.006).Conclusion:Serum IL-6,synovial IL-6 and CRP were independently related to PJI in patients after joint arthroplasty.They all had some diagnostic value,and serum IL-6 combined with synovial IL-6 and CRP had higher capability to diagnose PJI in patients after joint arthroplasty than each marker alone.

Effect of flurbiprofen combined with prednisolone on interleukin-6 in elderly surgery patients

Objective: To determine the effect of flurbiprofen combined with prednisolone on interleukin-6 in elderly surgery patients. Methods: In this double-blind randomized controlled study, patients aged 65 to 80 who were undergoing spinal fusion surgery for disc herniation were administered flurbiprofen 100 mg (P group, flurbiprofen group), prednisolone 0.6 mg/kg (D group, prednisolone group), prednisolone 0.6 mg/kg plus flurbiprofen 100 mg (P + D group, flurbiprofen + prednisolone group) or normal saline (S group, saline group) 15 minutes before the induction of anesthesia. Plasma samples were collected before surgery (T0) and on day 1 (T1), day 2 (T2) and day 3 (T3) following surgery. At the same time, systemic inflammatory response syndrome (SIRS) was assessed by SIRS criteria. The levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP) for collected samples were measured. Results: Other groups had significantly lower levels of IL-6, CRP and occurrence of SIRS than S group (p < 0.05). Compared to groups P and D, the levels of IL-6 and CRP in P + D group were significantly lower on T1 (p < 0.05). Peak levels of IL-6 in all groups were presented on T1 (p 0.05). The levels of CRP within three days were significantly different but did not show peak levels (p > 0.05). Conclusion: Compared to prednisolone or flurbiprofen, combining flurbiprofen with prednisolone in elderly surgery patients led to an increased suppression of IL-6.

Prognostic value of C-reactive protein levels within 6 hours after the onset of acute anterior myocardial infarction with primary PCI

Background Increased levels of inflammatory markers have been documented in various settings of coronary artery disease. The vulnerability of coronary lesions in acute myocardial infarction(AMI) at the time of onset may be related to serum levels of C reactive protein(CRP) on admission, before CRP levels are affected by myocardial damage.Objective This study assessed the predictive value of CRP levels within six hours after the onset of acute anterior myocardial infarction with primary percutaneous coronary intervention(PCI).Methods The plasma CRP of 76 patients with first acute anterior myocardial infarction was measured within 6 hours after onset. They were divided into 2 groups: group 1( n =20) with elevated CRP( ≥0.3mg/dl ) on admission within 6 hours after onset and group 2( n =56) with normal CRP( <0.3mg/dl ) within 6 hours after onset. All patients were treated by primary PCI. The primary combined end points, including death due to cardiac causes, re MI related to the infarction artery(RIA) and repeat intervention of the RIA, and the restenosis rate were assessed in relation to CRP levels within 6 hours after onset. Left ventricular end diastolic volume index(EDVI),end systolic volume index(ESVI),and ejection fraction(EF) on admission and 6 month after the onset were assessed by left ventriculography. Changes in EDVI(ΔEDVI),ESVI(ΔESVI), and EF(ΔEF) were obtained by subtracting respective on admission values from corresponding 6 month follow up values. Results There were no significant differences in baseline characteristics between the two groups. The primary combined end points were significantly more frequent in group 1(20%) than those in group 2( 1.79% , P <0.01 ).In addition, restenosis rates were significantly higher in group 1 than in group 2(41.18% vs 16.07%, P<0.05). Group 1 showed greater increases in left ventricular volume and less improvement in EF compared with group 2(ΔEDVI 6.31 ±2.17 vs 3.29 ±9.46ml/m 2 , ΔESVI 5.92 ±2.31 vs 3.86 ±1.08ml/m 2 , ΔEF 1.92 ±0.47 vs 4.79 ±1.73% , P <0.05 , respectively).Conclusions CRP levels within 6 hours after the onset of AMI might predict adverse outcome after primary PCI and progressive ventricular remodeling within 6 month of AMI.

Serum Concentrations of Angiotensin, C-Reactive Protein, Interleukin-8, and Tumor Necrosis Factor-α in Train Driver Population

Train drivers are engaged in high-stress job. It may induce sleep, fatigue, and alertness loss at work, and endanger public safety. It’s unclear that cytokines of train driver would be influenced by their job. The research considers the hypothesis that stressful professions, such as train driver, influence the body’s immune system through the long-time and high-pressure working, and change production of neuro-immune factors. Using enzyme linked immunosorbent assay (ELISA), several neuro-immune factors were assayed among train drivers (N = 82) and health blood donors (N = 80) enrolled in the Yunnan Collaborative Innovation Center for Public Health and Disease Control. The concentrations of angiotensin, C-reactive protein (CRP), interleukin-8 (IL-8), and tumor necrosis factor-alpha (TNF-α) were determined. Kruskal-Wallis test and Dunn’s multiple comparisons test were performed for overall comparison between groups and for pairwise comparison, respectively. Statistical significance level was set at P < 0.05. The profession of train driving was not associated with significant increases or decreases in the systemic levels of inflammatory (CRP, IL-8, and TNF-α), but it was associated with the high expression of angiotensin in vivo. These findings suggest that the job of train driving may not be associated with significant alterations in systemic immune condition, but arouse the level of angiotensin.

Elevated levels of inflammatory cytokines and high-sensitivity C-reactive protein in periodontitis patients in Kosovo: A pilot study

The following article has been retracted due to the investigation of complaints received against it. The Editorial Board found that the same contents have been published in another journal at the same time. The scientific community takes a very strong view on this matter, and the Open Journal of Stomatology treats all unethical behavior such as plagiarism seriously. This paper published in Vol.3 No.1 32-38, 2013 has been removed from this site. Title: Elevated levels of inflammatory cytokines and high-sensitivity C-reactive protein in periodontitis patients in Kosovo: A pilot study Authors: Zana Sllamniku-Dalipi, Hasan Mehmeti, Fatmir Dragidella, Ferit Kocani, Metush Disha, Kastriot Meqa, Luljeta Begolli, Gramos

Up-regulation interleukin-6 and interleukin-8 by activated protein C in lipopolysaccharide-treated human umbilical vein endothelial cells

Objective: To investigate the effect of activated protein C (APC) on inflammatory responses in human umbilical vein endothelial cells (HUVEC) stimulated with lipopolysaccharide (LPS). Methods: The second passage of collagenase digested HUVEC was divided into the following groups: serum free medium control group (SFM control), phosphate buffer solution control group (PBS control), LPS group with final concentration of 1 μg/ml (LPS group), APC group with final concentration of 7 μg/ml, Pre-APC group (APC pretreatment for 30 min prior to LPS challenge), and Post-APC group (APC administration 30 min after LPS challenge). Supernatant was harvested at 0, 4, 8, 12 and 24 h after LPS challenge. Interleukin-6 (IL-6) and Interleukin-8 (IL-8) levels were analyzed with ELISA. Cells were harvested at 24 h after LPS challenge, and total RNA was extracted. Mes-senger RNA levels for IL-6 and IL-8 were semi-quantitatively determined by RT-PCR. Results: Compared with control group, IL-6 and IL-8 levels steadily increased 4 to 24 h after LPS stimulation. APC treatment could increase LPS-induced IL-6 and IL-8 production. The mRNA levels of IL-6 and IL-8 exhibited a similar change. Conclusion: APC can further increase the level of IL-6 and IL-8 induced by LPS. The effect of these elevated cytokines is still under investigation.

Heparin-binding proteins from boar seminal plasma affecting the release of prostaglandins and interleukin-6 by porcine endometrial and cervical cells and bovine endometrial cells

The objectives of this study were to explore whether heparin-binding proteins, separated by fast protein liquid chromatography from boar seminal plasma influence the release of prostaglandins F2α, (PGF2α), E2 (PGE2) and interleukin-6 (IL-6) by porcine endometrial and cervical cells and even bovine endometrial cells. In Experiment I, we showed that release of PGF2α by endometrial epithelial, endometrial stromal and cervical stromal cells to the medium was inhibited (p α (TNFα) stimulated release of IL-6 by endometrial and cervical stromal cells after 24 h incubation, but in the presence of heparin-binding proteins, this stimulation was attenuated. Release of PGF2α by cryopreserved (Experiment II) and primary (Experiment III) cervical stromal cells was significantly inhibited after 3 h incubation with 66 - 95.4 μg of heparin- binding proteins. A significant inhibition of PGE2 release by cryopreserved and primary cervical stromal cells was already achieved after incubation with 16.5 - 23.9 μg of heparin-binding proteins. The release of IL-6 by cryopreserved cells was stimulated after 3 h incubation with heparin- binding proteins in a dose dependent manner in contrast to the release of IL-6 by freshly isolated cervical stromal cells. We also found (Experiment IV) that porcine heparin-binding seminal plasma proteins inhibited release of PGF2α and stimulated release of IL-6 by bovine endometrial epithelial cells. In conclusion, a group of heparin-binding proteins separated by fast protein liquid chromatography from boar seminal plasma inhibit PGF2α, PGE2 and stimulate IL-6 release by porcine endometrial and cervical cells and even by bovine endometrial cells. Thus, these proteins have a similar effect as the entire seminal plasma.

Interleukin-6 and ratio of plasma interleukin-6/interleukin-10 as risk factors of symptomatic lumbar osteoarthritis

AIM To determine the role of cartilage oligomeric matrix protein(COMP), interleukin(IL)-6, IL-10 and ratio of IL-6/IL-10 as risk factors of symptomatic lumbar osteoarthritis(OA) in postmenopausal women with estrogen deficiency.METHODS Case-control study had been conducted in Sanglah General Hospital from October 2015 until March 2016. The blood samples were obtained and analyzed by enzyme-linked immunosorbent assay(ELISA).RESULTS From 44 pairs of samples which divided into 44 samples as case group and 44 samples as control group showed that high level of COMP in estrogen deficiency postmenopausal women were not at risk(OR = 0.7; 95%CI: 0.261-1.751; P = 0.393) for symptomatic lumbar OA(cut-off point 0.946). Estrogen deficiency in postmenopausal women with the high level of IL-6 had 2.7 times risk(OR = 2.7; 95%CI: 0.991-8.320; P = 0.033) for symptomatic lumbar OA from the low level of IL-6(cut-off point 2.264). At lower level of IL-10, there was no risk for symptomatic lumbar OA(OR = 0.6; 95%CI: 0.209-1.798; P = 0.345) than with the higher level of IL-10(cut-off point 6.049). While the high ratio of IL-6/IL-10 level in estrogen deficiency postmenopausal women gave 3.4 times risk(OR = 3.4; 95%CI: 1.204-11.787; P = 0.011)for symptomatic lumbar OA than the low ratio of IL-6/IL-10 level(cut-off point 0.364).CONCLUSION High ratio of IL-6/IL-10 plasma level was the highest risk factor for causing symptomatic lumbar OA in postmenopausal women with estrogen deficiency.

CHANGES OF INTERLEUKIN-6 AND RELATED FACTORS AS WELL AS GASTRIC INTRAMUCOSAL pH DURING COLORECTAL AND ORTHOPAEDIC SURGICAL PROCEDURES

Objective To investigate the changes of perioperative serum levels of interleukin-6(IL-6), C-reactive protein (CRP), and cortisol, as well as gastric intramucosal pH (pHi) and plasma lactate, aiming to compare systemic changes and tissue perfusion during colorectal and orthopaedic surgical procedures. Methods Twenty patients were randomly assigned to two groups, 10 cases of operation on vertebral canal, 10 cases of colorectal radical operation.Venous blood was drawn at 1 day before operation, 2, 4, and 6 hours following skin incision, and 1 day after operation, in order to measure serum IL-6, CRP, and cortisol.pHi and plasma lactate were also measured at the same time points.Results Serum concentrations of IL-6 and cortisol increased gradually following operation, reaching the peak value at 6 hours from the beginning of operation.CRP was not detectable until the first day after operation.Peak concentration of IL-6 had positive relationship with CRP.These variables changed more significantly in colorectal group than that in orthopaedic group (P<0.05).pHi decreased gradually, reaching the lowest level at 4 hours from the beginning of operation, and to more extent in colorectal group than that in orthopaedic group (P<0.05).Conclusion IL-6 may reflect tissue damage more sensitively than CRP.Colorectal surgery might induce systemic disorder to more extent, in terms of immuno-endocrinal aspect as well as tissue perfusion, reflected with pHi.

MEK AND p38 MAPK-DEPENDANT PATHWAYS ARE INVOLOVED IN THE POSITIVE EFFECT OF INTERLEUKIN-6 ON HUMAN GROWTH HORMONE GENE EXPRESSION IN RAT MtT/S SOMATOTROPH CELLS

Objective To investigate the effect of interleukin-6(IL-6)on the human growth hormone(hGH)gene expression in a rat somatotropic pituitary cell line MtT/S.Methods The plasmids containing various lengths of hGH gene 5'-promoter fragments were constructed.Stably transfected MtT/S cells were created by cotransfecting the above plasmids and pcDNA3.1(+)with DMRIE-C transfection reagent.After the administration of these cells with IL-6 and/or various inhibitors of signaling transduction pathways,the luciferase activities in MtT/S cells lysis were assayed to demonstrate the effects of IL-6 on hGH gene promoter activity and possibly involved mechanism.Results The 103 U/mL IL-6 stimulated GH secretion and synthesis,and promoted the 5'-promoter activity of GH gene in stably transfected MtT/SGL cells with the action of 1.69 times above the control.Among inhibitors of signaling transduction pathways,mitogen-activated protein kinase kinase(MAPKK/MEK)inhibitor PD98059(40 μmol/L)and p38 mitogen-activated protein kinase(MAPK)inhibitor SB203580(5 μmol/L)completely blocked the stimulatory effect of IL-6.Western blot analysis further confirmed the activation of phosphorylated MEK and p38 MAPK in MtT/SGL cells.Neither over-expression of Pit-1 nor inhibition of Pit-1 expression affected IL-6 induction of hGH promoter activity.A series of deletion constructs of hGH promoter were created to identify the DNA sequence that mediated the effect of IL-6.The results showed that the stimulatory effect of IL-6 was abolished following deletion of the-196 to-132 bp fragment.Conclusions IL-6 promotes GH secretion and synthesis by rat MtT/S somatotroph cells.The stimulatory effect of IL-6 on hGH gene promoter appears to require the activation of MEK and p38 MAPK,and a fragment of promoter sequence that spans the-196 to-132 bp of the gene,but may be unlinked with Pit-1 protein.

Serum Y-Box Binding Protein 1 (YBX-1) and Interleukin 6 (IL-6) Are Associated with Metastasis in Breast Cancer Patients

Objectives: The aim of this study was to assess the levels of Y-box binding protein 1 (YBX-1) and interleukin 6 (IL-6) in the sera of metastatic and non-metastatic breast cancer patients (BC), investigate their clinicopathological significance and to analyze their potential use as biomarkers of breast cancer metastasis. Methods: The study included ninety subjects sub-grouped equally into metastatic BC, non-metastatic BC and healthy volunteers. Serum YBX-1 and IL-6 were quantified using ELISA technique while CA 15-3 was quantified using IRMA kit. Clinical data were collected from patients’ records. Results: YBX-1 (p < 0.001), IL-6 (p < 0.001) and CA15-3 (p = 0.017, 0.001) were significantly elevated in metastatic and non-metastatic BC patients compared to healthy controls, however, only YBX-1 (p 0.001) showed a significant difference with cancer metastasis. Generally, YBX-1 and IL-6 were correlated with worse histological grade and late clinical stage in breast cancer patients and they were also associated with axillary lymph nodes involvement and positive vascular invasion in metastatic BC patients. Serum YBX-1 and IL-6 levels were positively correlated to each other (rs = 0.615, p < 0.001) and they showed high sensitivity and specificity compared to CA 15-3 (p < 0.001 and p = 0.004 for YBX-1 and IL-6 respectively) for predicting cancer metastasis. Conclusions: Serum YBX-1 and IL-6 are potential biomarkers of breast cancer patients with significant correlation with bad clinicopathological characteristics. Serum YBX-1 and IL-6 have superior sensitivity and specificity compared to CA15-3 and can serve as potential follow up and prognostic markers.

Relationship between coronary atherosclerosis plaque characteristics and high sensitivity C-reactive proteins, interleukin-6

Background The relationship between inflammatory markers and the characteristics of coronary atherosclerosis plaques is uncertain. The aim of the present study was to evaluate the relationship between the characteristics of coronary atherosclerosis plaques and inflammatory markers such as high sensitivity C-reactive proteins （Hs-CRP） and interleukin-6 （IL-6）. Methods All patients suspected of having coronary heart disease （CHD） underwent Siemens 64-slice CT angiography （64-SCTA） to distinguish the quality of plaque of coronary artery lesions. Blood samples were taken to measure levels of serum Hs-CRP and IL-6 in different plaque groups and the control group and compared with the value of 64-SCTA for detection of coronary artery plaque. Results The sensitivity of detecting coronary artery plaque by 64-SCTA was 87.4%, the specificity was 87.1%, the positive predictive value was 82.2%, and the negative predictive value was 91.0%. Comparing the levels of serum Hs-CRP and IL-6 among plaque groups, the mean levels of serum Hs-CRP and IL-6 in three plaque groups were significantly higher than those in the control group （P 〈0.01）. The mean levels of serum Hs-CRP and IL-6 in the soft plaque group and mixed plaque group were significantly higher than those in hard plaque group （P〈0.01）. Plaque burden in the soft plaque group and mixed plaque group was significantly higher than in the hard plaque group （P 〈0.01）, but there was no statistical difference between the soft plaque group and mixed plaque group （P=-0.246）. There was a negative correlation between the CT scale and Hs-CRP and IL-6 levels in the soft plaque group （r= -0.621, P〈0.01, and r= -0.593, P 〈0.01 respectively）. There was a positive correlation between the plaque burden and Hs-CRP and IL-6 levels in the soft plaque group （r=0.579, P〈0.05 and r=0.429, P〈0.05 respectively）. Conclusions 64-SCTA is an effective way to distinguish the different quality of coronary atherosclerosis plaque. Serum Hs-CRP and IL-6 levels can be considered as the indexes to judge the degree of CHD and may reflect the activity of plaque in CHD patients. Thus it is important for clinical diagnosis and risk evaluation of acute coronary syndrome （ACS） patients.

Association of interleukin-6 and C-reactive protein genetic polymorphisms levels with venous thromboembolism

Background Increased levels of interleukin-6 （IL-6） and C-reactive protein （CRP） have been reported in patients with venous thromboembolisms （VTE）. However, prospective studies did not confirm an association between IL-6, CRP and their polymorphism with the risk of VTE. Methods One hundred and forty patients （including 66 males and 74 females, mean age （55.55±17.11） years） and one hundred and sixty controls （including 74 males and 86 females, mean age （56.58±12.24） years） were involved. An enzyme linked immunosorbent assay （ELISA） method was used for detecting the serum levels of inflammatory factors IL-6 and CRP in both groups. Polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） was used for analyzing the distribution of polymorphisms at the -572C/G and -597G/A sites of the promoter of the IL-6 gene and at 1059G/C of the CRP gene. Results Serum levels of IL-6 and CRP were significantly higher in the VTE group than in the control group （P 〈0.05）. The frequencies of-572C/G promoter polymorphisms CC, CG, and GG in the IL-6 gene were found to be 34%, 48%, and 18%, respectively, and the derived allele frequencies for the C and G alleles were 58% and 42%. There was a significant difference in the -572C/G promoter polymorphisms between the VTE group and control group （P 〈0.05）. For the -597G/A polymorphism, individuals all carried the GG and GA type; AA genotypes were not detected. The frequency of the GG, GC, and CC genotypes at the CRP1059G/C promoter was 87.57%, 7.86% and 3.57% in V-rE group, while 86.25%, 10%, and 3.75% in control group, respectively. The frequency of G and C alleles at CRP 1059G/C was 91.43% and 8.57% in VTE group and 91.56% and 8.44% in the control group. The results showed that there was no statistically significant difference of 1059G/C genotype and mutation frequency of the allele between the VTE group and control group （P 〉0.05）. Multiple Logistic regression analysis showed CC homozygotes of the IL-6 -572G/C, body mass index （BMI）, and CRP, IL-6, and high-density lipoprotein cholesterol （HDL-C） were independent risk factors for VTE （P 〈0.05）. Conclusions We found that V-rE was associated with IL-6 and CRP levels, and there was an association of IL-6 and its promoter polymorphism at -572G/C with the risk of VTE. Thus far, a causal relationship between inflammation and VTE remains to be clarified and more prospective data are required.

The role of endotoxin,TNF-α,and IL-6 in inducing the state of growth hormone insensitivity

AIM: Critical illnesses such as sepsis, trauma, and burns cause a growth hormone insensitivity, which leads to an increased negative nitrogen balance. Endotoxin is generously released into blood under these conditions and stimulates the production of proinflammatory cytokines such as TNF-alpha, IL-6, and IL-1, which may play a very important role in inducing the growth hormone insensitivity. The objective of this current study was to investigate the role of endotoxin, TNF-alpha and IL-6 in inducing the growth hormone insensitivity at the receptor and post-receptor levels. METHODS: Spague-Dawley rats were injected with endotoxin, TNF-alpha, and IL-6, respectively and part of rats injected with endotoxin was treated with exogenous somatotropin simultaneously. All rats were killed at different time points. The expression of IGF-I, GHR, SOCS-3 and beta-actin mRNA in the liver was detected by RT-PCR and the GH levels were measured by radioimmunoassay, the levels of TNF-alpha and IL-6 were detected by ELISA. RESULTS: There was no significant difference in serous GH levels between experimental group and control rats after endotoxin injection, however, liver IGF-I mRNA expression had been obviously down-regulated in endotoxemic rats. Liver GHR mRNA expression also had a predominant down-regulation after endotoxin injection. The lowest regulation of liver IGF-I mRNA expression occurred at 12h after LPS injection, being decreased by 53% compared with control rats. For GHR mRNA expression, the lowest expression occurred at 8h and had a 81% decrease. Although SOCS-3 mRNA was weakly expressed in control rats, it was strongly up-regulated after LPS injection and had a 7.84 times increase compared with control rats. Exogenous GH could enhance IGF-I mRNA expression in control rats, but it did fail to prevent the decline in IGF-I mRNA expression in endotoxemic rats. Endotoxin stimulated the production of TNF-alpha and IL-6, and the elevated IL-6 levels was shown a positive correlation with increased SOCS-3 mRNA expression. The liver GHR mRNA expression was obviously down-regulated after TNF-alpha iv injection and had a 40% decrease at 8h, but the liver SOCS-3 mRNA expression was the 4.94 times up-regulation occurred at 40 min after IL-6 injection. CONCLUSION: The growth hormone insensitivity could be induced by LPS injection, which was associated with down-regulated GHR mRNA expression at receptor level and with up-regulated SOCS-3 mRNA expression at post-receptor level. The in vivo biological activities of LPS were mediated by TNF-alpha and IL-6 indirectly, and TNF-alpha and IL-6 may exert their effects on the receptor and post-receptor levels respectively.

C-reactive protein decreases interleukin-8 production in human endothelial progenitor cells by inhibition of p38 MAPK pathway

Background C-reactive protein （CRP） has been reported to damage the vascular wall by inducing endothelial dysfunction and inflammation, and it is also speculated to have a role in attenuating angiogenic functions of human endothelial progenitor cells （EPCs）. Interleukin-8 （IL-8） is an important mediator of the paracrine mitogenic effect of EPCs which has direct angiogenic effects on mature endothelial cells. We, herein, investigated the direct effect of CRP on IL-8 production and gene expression in cultured human EPCs. Methods EPCs were isolated from the peripheral venous blood of healthy male volunteers. Cells were cultured in EndoCultTM liquid medium in the absence and presence of CRP at clinically relevant concentrations （5 to 25 μg/ml） for different durations （3 to 48 hours）. IL-8 protein and mRNA of cultured EPCs were evaluated using ELISA and real-time PCR. Results The results showed that CRP at a concentration of 10 μg/ml significantly reduced IL-8 secretion of cultured EPCs with a peak at 25 μg/ml, and also decreased mRNA expression in EPCs with a peak at 12 hours. In addition, preincubation of EPCs with SB203580, an inhibitor of p38 mitogen-activated protein kinase （MAPK） decreased CRP inhibition of IL-8 mRNA expression at 12 hours in EPCs. Conclusions Our study, for the first time, demonstrates that CRP directly inhibits EPCs IL-8 secretion, a key cytokine player of angiogenesis induced by EPCs. Inhibition occurred in part via an effect of CRP to active the p38 MAPK signal transduction pathway in EPC. The ability of CRP to inhibit EPCs IL-8 secretion may represent an important mechanism that further links inflammation to cardiovascular disease.

二甲双胍联合补虚活血方治疗2型糖尿病的疗效及对血清CRP、IL-6、血清尿酸影响的研究

目的探究二甲双胍联合补虚活血方治疗2型糖尿病的疗效及对血清C反应蛋白(CRP)、白细胞介素-6(IL-6)、血清尿酸的影响。方法选择2014年8月-2016年8月收治的120例2型糖尿病患者,随机分为两组,每组60例。对照组采用二甲双胍治疗,治疗组在对照组治疗的基础上联合补虚活血方治疗,1个月后对比两组疗效及对血清CRP、IL-6、血清尿酸的影响。结果与治疗前比较,两组空腹血糖(FPG)、糖化血红蛋白(Hb Alc)及餐后2 h血糖(2 h PG)均降低(P<0.05);与对照组比较,治疗组治疗后FPG及Hb Alc水平降低更显著(P<0.05)。与治疗前比较,两组血清CRP、IL-6及血清尿酸水平均降低(P<0.05);与对照组比较,治疗组治疗后血清CRP、IL-6及血清尿酸水平降低更显著(P<0.05)。与对照组比较,治疗组不良反应发生率并未增加,差异无统计学意义(P>0.05)。结论二甲双胍联合补虚活血方治疗2型糖尿病患者能很好地控制血糖水平,改善相关代谢指标及炎症反应,且不良反应少,临床应用安全、有效。