Interleukin-10 Ratio Research Articles

Psychological stress exerts effects on pathogenesis of hepatitis B via type-1/type-2 cytokines shift toward type-2 cytokine response.

BackgroundPsychological and physical stress has been demonstrated to have an impact on health through modulation of immune function. Despite high prevalence of stress among patients with hepatitis B virus (HBV) infection, little is known about whether and how stress exerts an effect on the course of hepatitis B.MethodsEighty patients with chronic hepatitis B(CHB) completed the Perceived Stress Scale-10(PSS-10) and State-Trait Anxiety Inventory(STAI). Fresh whole blood was subject to flow cytometry for lymphocytes count. Plasma samples frozen at −80°C were thawed for cytokines, alanine aminotransferase (ALT), and virus load. These patients were grouped into high or low perceived stress, state anxiety and trait anxiety groups according to the scale score. Sociodemographic, disease-specific characteristics, lymphocytes count and cytokines were compared.ResultsFirstly, a negative association between ALT and stress (t = −4.308; p = .000), state anxiety (t = −3.085; p = .003) and trait anxiety (t = −4.925; p = .000) were found. As ALT is a surrogate marker of hepatocytes injury, and liver injury is a consequence of immune responses. Next, we tested the relationship between stress/anxiety and lymphocytes. No statistical significance were found with respect to counts of total T cells, CD4+ T cell, CD8+ T cell, NK cell, and B cell count between high and low stress group. Type-2 cytokine interleukin-10 (IL-10) level was significantly higher in high stress group relative to lower counterpart (t = 6.538; p = 0.000), and type-1 cytokine interferon-gamma (IFN-γ) level shown a decreased tendency in high stress group (t = −1.702; p = 0.093). Finally, INF-γ:IL-10 ratio displayed significant decrease in high perceived stress(t = −4.606; p = 0.000), state anxiety(t = −5.126; p = 0.000) and trait anxiety(t = −4.670; p = 0.000) groups relative to low counterparts.ConclusionOur data show stress is not related to the lymphocyte cells count in CHB patients, however, stress induces a shift in the type-1/type-2 cytokine balance towards a type-2 response, which implicated a role of psychological stress in the course of HBV related immune-pathogenesis.

Association of interleukin 1 receptor antagonist (IL1RN) gene polymorphism with recurrent pregnancy loss risk in the North Indian Population and a meta-analysis.

An appropriate ratio of interleukin 1 beta to interleukin 1 receptor antagonist (IL1Ra) is required for successful pregnancy. Our objective was to study the genetic association between IL1RN variable numbers of tandem repeat (VNTR) polymorphism and recurrent pregnancy loss (RPL). To analyze the association between IL1RN VNTR allele and RPL, we investigated the IL1RN VNTR polymorphism in 136 RPL patients and in 200 healthy control women. Meta-analysis on this polymorphism was conducted to support our findings. PCR based approach was used to analyze IL1RN VNTR polymorphism and it was further confirmed by sequencing. Systematic review and meta-analysis was done using electronic database (Pub-Med, Google Scholar and Ovid) up to February 27, 2013. This meta-analysis was assessed by comprehensive meta-analysis software version 2. For meta-analysis 549 cases and 1,450 controls were included. The frequency of IL1RN genotype 2/2 was significantly higher in RPL compared to control group (AORs 3.10, 95 % CI 1.58-6.11, p = 0.001). The presence of rare allele also increased the risk of RPL significantly (ORs 1.63, 95 % CI 1.16-2.29, p = 0.004). The meta-analysis stratified by ethnicity showed that individuals with allele 2 had increased risk of RPL (OR 1.29, 95 % CI 1.04-1.61, p = 0.01), in Asians population by using fixed model. However the data of the present study clearly suggests that IL1RN VNTR polymorphism is a genetic risk factor for pregnancy loss in the study population.

Effects of chronic hepatitis C genotype 1 and 4 on serum activins and follistatin in treatment naïve patients and their correlations with interleukin-6, tumour necrosis factor-α, viral load and liver damage.

The importance of activins and follistatin in liver diseases has recently emerged. The aim of the present study was to measure the influence of chronic infection with viral hepatitis C (CHC) genotype 1 and 4 on serum levels of activin-A, activin-B and follistatin, and to determine their correlations with viral load, liver damage, interleukin-6 (IL-6) and tumour necrosis factor (TNF)-α. Sera samples collected from 20 male and 20 female treatment naïve CHC genotype 1 and 4 Saudi patients (ten males and ten females for each genotype), and 40 gender- and age-matched healthy participants were analysed for activin-A, activin-B and follistatin using enzyme-linked immunosorbent assay and their levels were correlated with IL-6, TNF-α, viral load and AST platelet ratio index (APRI). Serum activin-A, activin-B, IL-6 and TNF-α were significantly increased, while serum follistatin was significantly decreased, in both genders of CHC patients compared with control subjects, In both viral genotypes, activin-A was strongly and positively correlated with the viral load, APRI, IL-6 and TNF-α, and negatively with albumin (P<0.01). Activin-B showed the same correlations of activin-A only in CHC genotype 1 patients, but it was weaker than activin-A. No correlation was detected with follistatin. Serum activins, particularly activin-A, and follistatin are significantly altered by CHC genotype 1 and 4. This dysregulation of activins/follistatin axis may be associated with viral replication, host immune response and liver injury. Further studies are needed to illustrate the definite role(s) and clinical value of activins and follistatin in CHC.

AB0062 IL-6'S Role in Hypertrofic Left Ventricul in Patient with Rheumatoid Arthritis

BackgroundRheumatoid Arthritis (RA) is an inflammatory and systemic disease. Cardiac involvement during the course of the disease is increase with the RA disease activity. All the cytokines that are involved...

Evaluated plasma interleukin-18/interleukin-10 ratio is a risk factor for acute coronary syndromes in patients with stable angina pectoris

Studies suggested that interleukin-18 (IL-18)/interleukin-10 (IL-10) ratio is an independent predictor of adverse cardiovascular events in patients with acute coronary syndromes (ACS). In this study we aimed to evaluate the predictive significance of IL-18/IL-10 for the occurrence of ACS in patients with stable angina pectoris (SAP) over a 40-month follow-up. The IL-18, IL-10 levels of 257 patients with SAP were determined by Enzyme-Linked Immunosorbent Assay (ELISA). Two hundred and fifty-two patients, 42 of whom had ACS and 210 were event-free, were divided into two groups according to the presence or absence of the occurrence of ACS during the 40-month follow-up. Plasma IL-18 and IL-18/IL-10 ratios were both significantly higher (p = 0.001 and p = 0.044, respectively) among patients with ACS, however, IL-10 level was lower (p = 0.046) compared to the patients without ACS. The elevation of plasma IL-18/IL-10 ratio and the number of coronary artery lesions made the advantage ratio of ACS in patients with SAP increase 4.242 times and 1.942 times (p = 0.000 and p = 0.011, respectively). Plasma IL-18 and IL-10 levels in patients with SAP are closely related to the occurrence of ACS, elevated IL-18/IL-10 ratio has a positive predictive value for the occurrence of ACS in patients with SAP.

Spectral-domain optical coherence tomographic and fundus autofluorescence findings in eyes with primary intraocular lymphoma

BackgroundThe purpose of this study was to evaluate the findings on spectral-domain optical coherence tomography (SD-OCT) and fundus autofluorescence (FAF) in three eyes with primary intraocular lymphoma (PIOL).MethodsThe medical records of three eyes from three patients with biopsy-proven PIOL and retinal infiltrations were reviewed. The SD-OCT and fluorescein angiographic findings were evaluated in the three eyes and FAF images in two eyes.ResultsThe PIOL in the three patients was monocular. Vitreous opacities and retinal infiltrations were observed in the three eyes, and iritis was present in two eyes. The cytologic diagnosis was class V in two eyes and class III in one eye. The interleukin-10/interleukin-6 ratio was >1.0 in the vitreous and aqueous humor of the three eyes. The FAF images for two eyes showed abnormal granular hyperautofluorescence and hypoautofluorescence which were the reverse of the pattern in the fluorescein angiographic images. In all three eyes, SD-OCT showed hyper-reflective infiltrations at the level of the retinal pigment epithelium (RPE), a separation of the Bruch membrane from the RPE, damage to the RPE, disruption of the photoreceptor inner segment/outer segment junction, and multiple hyper-reflective signals in the inner retina.ConclusionBecause of the characteristic FAF and SD-OCT findings in these eyes with PIOL, we suggest that these noninvasive methods may be used for a rapid diagnosis of PIOL and also for understanding the pathology of PIOL.

The Role of Different Anesthetic Techniques in Altering the Stress Response During Cardiac Surgery in Children

Our goal was to evaluate the role of three anesthetic techniques in altering the stress response in children undergoing surgery for repair of congenital heart diseases utilizing cardiopulmonary bypass in the setting of fast tracking or early tracheal extubation. Furthermore, we wanted to evaluate the correlation between blunting the stress response and the perioperative clinical outcomes. Prospective, randomized, double-blinded study. Single center from December 2008 to May of 2011. Forty-eight subjects (low-dose fentanyl plus placebo, n = 16; high-dose fentanyl plus placebo, n = 17; low-dose fentanyl plus dexmedetomidine, n = 15) were studied between ages 30 days to 3 years old who were scheduled to undergo repair for a ventricular septal defect, atrioventricular septal defect, or Tetralogy of Fallot. Children undergoing surgical repair of congenital heart disease were randomized to receive low-dose fentanyl (10 mcg/kg; low-dose fentanyl), high-dose fentanyl (25mcg/kg; high-dose fentanyl), or low-dose fentanyl plus dexmedetomidine (as a 1 mcg/kg loading dose followed by infusion at 0.5mcg/kg/hr until separation from cardiopulmonary bypass. In addition, patients received a volatile anesthetic agent as needed to maintain hemodynamic stability. Blood samples were tested for metabolic, hormonal and cytokine markers at baseline, after sternotomy, after the start of cardiopulmonary bypass, at the end of the procedure and at 24 hours postoperatively. Forty-eight subjects (low-dose fentanyl plus placebo, n = 16; high-dose fentanyl plus placebo, n = 17; low-dose fentanyl plus dexmedetomidine, n = 15) were studied. Subjects in the low-dose fentanyl plus placebo group had significantly higher levels of adrenocorticotropic hormone, cortisol, glucose, lactate, and epinephrine during the study period. The lowest levels of stress markers were seen in the high-dose fentanyl plus placebo group both over time (adrenocorticotropic hormone, p= 0.01; glucose, p = 0.007) and at individual time points (cortisol and lactate at the end of surgery, epinephrine poststernotomy; p < 0.05). Subjects in the low-dose fentanyl plus dexmedetomidine group had lower lactate levels at the end of surgery compared with the low-dose fentanyl plus placebo group (p < 0.05). Although there were no statistically significant differences in plasma cytokine levels between the three groups, the low-dose fentanyl plus placebo group had significantly higher interleukin-6:interleukin-10 ratio at 24 hours postoperatively (p < 0.0001). In addition, when compared with the low-dose fentanyl plus placebo group, the low-dose fentanyl plus dexmedetomidine group showed a lower norepinephrine level from baseline at poststernotomy, after the start of cardiopulmonary bypass, and at the end of surgery (p ≤ 0.05). Subjects in the low-dose fentanyl plus placebo group had more postoperative narcotic requirement (p = 0.004), higher prothrombin time (p ≤ 0.03), and more postoperative chest tube output (p < 0.05). Success of fast tracking was not significantly different between groups (low-dose fentanyl plus placebo 75%, high-dose fentanyl plus placebo 82%, low-dose fentanyl plus dexmedetomidine 93%; p = 0.39). The use of low-dose fentanyl was associated with the greatest stress response, most coagulopathy, and highest transfusion requirement among our cohorts. Higher dose fentanyl demonstrated more favorable blunting of the stress response. When compared with low-dose fentanyl alone, the addition of dexmedetomidine improved the blunting of the stress response, while achieving better postoperative pain control.

자폐증 유사증상 발현 마우스의 점액 면역에 대한 연구

Objectives: This study was undertaken in order to evaluate a potential mechanism involved in gastro-intestinal problems observed in autistic subjects and uses an animal model of autism investigation. Methods: BTBR T+tf/J, a mouse strain with typical socio-behavioral characteristics of autistic subjects and FVB mice with highly social behaviors as the control strain were used. Both genders of mice aged three weeks and six months were used from four separate litters for each strain. Serum was prepared following cardiac puncture, and mesenteric lymph nodes were collected for in vitro stimulation and enumeration of major immune cell proportion. Results: The level of serum IgA was significantly enhanced in six-month-old BTBR mice compared with three-week-old BTBR, which was not observed with the FVB control mice. The serum IgE level was also higher among BTBR mice than among age-sex matched FVB mice, respectively. Considering the ratio of interleukin-4 vs interferon-gamma production from mesenteric lymph node T cells, skewedness toward type-2 reactivities was observed. In addition, the proportion of B cells in mesenteric lymph nodes was significantly higher in BTBR mice than in FVB mice. Conclusion: Upregulation of mucosal immunity related with enhanced type-2 immune reactivity observed in BTBR mice could be involved with the etiology of gastro-intestinal abnormalities in autism.

English

The aim of this study was to evaluate the immunomodulatory effect of probiotics, namely the production of interferon &gamma; (IFN-&gamma;) and interleukin-4 (IL-4) cytokines,&nbsp;in vitro&nbsp;and&nbsp;in vivo. Our experimental groups included ten lactic acid bacterial (LAB) strains, complex strains, a LAB cell free fraction and a control group. Our models included human peripheral blood mononuclear cells (PBMCs) as the human model and BALB/c mice as the animal model. The experiment was carried out over a period of 4 weeks during which the food intake and the body weight of our animal model was reported weekly. BALB/ c mice were randomly divided into three groups and injected with 2 &micro;g/ mouse and 6 &micro;g/ mouse ovalbumin (OVA) mixed with complete Freund&rsquo;s adjuvant (CFA) at week zero and two. After week four the serum total immunoglobulin E (IgE) was measured. The results show that probiotic products induced IFN-&gamma;, suppressed IL-4, and increased the IFN-&gamma;/ IL-4 (Th-1/ Th-2) ratio significantly in PBMCs. Probiotic products also decreased significantly the serum total IgE and OVA-specific IgE levels in our animal model. Our study indicates that the multi-species probiotics may therefore have an anti-allergy effect. &nbsp; Key words:&nbsp;Probiotics, human peripheral blood mononuclear cell, cytokines, immunoglobulin E, anti-allergy effect.

P023 Cytokine imbalances in HIV-1 infected patients from North India

Introduction Cytokines have a complex effect on the replication of HIV-1 and conversely in infected individuals HIV-1 directly affects cytokine production. Different studies postulate that the progression of disease in HIV-1 infected individuals may be controlled by the balance between the levels of type 1 (Th 1 ) and type 2 cytokines (Th 2 ). Two important cytokines involved in the Th 1 /Th 2 cross regulation are interferon- γ (IFN- γ ), a product of Th 1 cells and interleukin-10 (IL-10), a product of Th 2 cells. Determining the cytokine profile in HIV-1 infected patients and correlating with their levels in HIV-1 seronegative Injecting Drug Users (IDUs) and HIV-1 seronegative healthy subjects will help in the assessment of cytokine imbalances in HIV-1 infection. Methods The blood from 30 healthy individuals, 30 IDUs and 30 HIV-1 positive patients were collected and informed consent was obtained. The study was approved by the institute ethics committee. The level of Th 1 and Th 2 cytokines in the plasma was determined by ELISA. Results The level of IL-10 was significantly higher and IFN- γ was significantly lower in HIV-1 infected patients compared to IDUs (for IL-10 p = 0.0071 and for IFN- γ p = 0.0062) and seronegative healthy individuals (for IL-10 p = 0.0068 and for IFN- γ p = 0.004). The IFN- γ /IL-10 ratio was significantly lower in HIV-1 infected patients in comparison to IDUs ( p = 0.0001) and seronegative healthy individuals ( p = 0.0002). Conclusion There is a trend towards a shifting of the cytokine profile from Th 1 to Th 2 in HIV-1 infected patients, while no variation was observed in the IDUs and healthy subjects. The Th 1 to Th 2 shift may promote disease progression in the HIV-1 infected patients and needs to be confirmed by conducting longitudinal studies.

Cytokine Responses to Novel Antigens in a Peri-Urban Population in Brazil Exposed to Leishmania infantum chagasi

Visceral leishmaniasis (VL) is fatal if untreated, and there are no vaccines for this disease. High levels of CD4-derived interferon-γ (IFN-γ) in the presence of low levels of interleukin-10 (IL-10) predicts vaccine success. Tumor necrosis factor-α (TNF-α) is also important in this process. We characterized human immune responses in three groups exposed to Leishmania infantum chagasi in Brazil: 1) drug-cured VL patients (recovered VL); 2) asymptomatic persons with positive Leishmania-specific delayed-type hypersensitivity skin reactions (DTH+); and 3) DTH-negative household contacts. Magnitude of DTH correlated with crude Leishmania antigen-driven IFN-γ, TNF-α, and IL-5, but not IL-10. DTH+ persons showed equivalent levels of IFN-γ, but higher levels of IL-10, to tryparedoxin peroxidase and Leishmania homolog of receptor for activated C kinase compared with recovered VL patients. The IFN-γ:IL-10 and TNF-α:IL-10 ratios were higher in recovered VL patients than in DTH+ persons. Seven of 11 novel candidates (R71, L37, N52, L302.06, M18, J41, and M22) elicited cytokine responses (36-71% of responders) in recovered VL patients and DTH+ persons. This result confirmed their putative status as cross-species vaccine/immunotherapeutic candidates.

Prediction of response to bacillus Calmette-Guérin treatment in non-muscle invasive bladder cancer patients through interleukin-6 and interleukin-10 ratio

This study aimed to evaluate whether the interleukin-6 (IL-6) and interleukin-10 (IL-10) ratio (IL-6/IL-10) can be used as a prognostic marker of recurrence following bacillus Calmette-Guérin (BCG) therapy in patients with high-risk non-muscle invasive bladder cancer (NMIBC). One hundred and twenty-one consecutive urological patients (72 affected by high-risk NMIBC and 49 controls) were selected for this prospective study. Urine samples for dipstick and interleukin analyses were collected from each subject before surgery. All patients underwent transurethral resection of bladder tumours (TUR-BT), followed by six weekly BCG instillations. IL-6 and IL-10 concentrations in urine were determined by solid phase ELISA Quantikine IL-6 and IL-10 Immunoassay. Patients with NMIBC were stratified in accordance with IL-6/IL-10: group A ≤0.09 and group B >0.10. The main outcome measures were time to first recurrence and recurrence rate following BCG therapy. At enrolment, IL-6/IL-10 was not statistically different between patients and controls (p=0.763, degrees of freedom (df)=1, F-test result (F)=0.092). Of the 72 patients with NMIBC, 38 (52.7%) had an IL-6/IL-10 of ≤0.09 (group A), while 34 (47.3%) had an IL-6/IL-10 of >0.10 (group B). A significant difference between IL-6/IL-10 and status at follow-up was found (p=0.016, df=1, χ2=5.800). The Kaplan-Meier curves demonstrated that group B patients had a significantly higher probability of being recurrence-free than group A patients [p=0.003; recurrence rate (RR)=3.1]. At multivariate analysis, IL-6/IL-10 (p<0.003) and the number of lesions (p<0.001) were identified as independent predictors of BCG response probability. In conclusion, this study highlights the feasible role of IL-6/IL-10 in predicting recurrence following BCG therapy in high-risk NMIBC.

Effect of Clarithromycin in Inflammatory Markers of Patients with Ventilator-Associated Pneumonia and Sepsis Caused by Gram-Negative Bacteria: Results from a Randomized Clinical Study

One recent, double-blind, randomized clinical trial with 200 patients showed that clarithromycin administered intravenously for 3 days in patients with ventilator-associated pneumonia (VAP) accelerated the resolution of pneumonia and decreased the risk of death from septic shock and multiple organ dysfunctions (MODS). The present study focused on the effect of clarithromycin on markers of inflammation in these patients. Blood was drawn immediately before the administration of the allocated treatment and on six consecutive days after the start of treatment. The concentrations of circulating markers were measured. Monocytes and neutrophils were isolated for immunophenotyping analysis and for cytokine stimulation. The ratio of serum interleukin-10 (IL-10) to serum tumor necrosis factor alpha (TNF-α) was decreased in the clarithromycin group compared with the results in the placebo group. Apoptosis of monocytes was significantly increased on day 4 in the clarithromycin group compared with the rate of apoptosis in the placebo group. On the same day, the expression of CD86 was increased and the ratio of soluble CD40 ligand (sCD40L) to CD86 in serum was unchanged. The release of TNF-α, IL-6, and soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) by circulating monocytes after stimulation was greater in the clarithromycin group than in the placebo group. The expression of TREM-1 on monocytes was also increased in the former group. These effects were pronounced in patients with septic shock and MODS. These results suggest that the administration of clarithromycin restored the balance between proinflammatory versus anti-inflammatory mediators in patients with sepsis; this was accompanied by more efficient antigen presentation and increased apoptosis. These effects render new perspectives for the immunotherapy of sepsis.

High Sensitivity C-Reactive Protein to Interleukin 6 Ratio and Ischemic Stroke Risk in a Multi-Ethnic Cohort: The Northern Manhattan Study (IN3-1.001)

Objective: We hypothesized that stroke-free individuals with elevated hs-CRP but low IL6 would have an increased risk of ischemic stroke in the population-based Northern Manhattan Study. Background Individuals with elevated high sensitivity C-reactive protein (hsCRP) are at increased risk of stroke in some populations. Interleukin-6 (IL6) is a pro-inflammatory cytokine with auto-inhibitory regulatory mechanisms. Studies have shown that the hsCRP to IL6 ratio is lower among statin users and may reflect decreased inflammation. Design/Methods: Stroke-free participants age >40 years had serum samples drawn at enrollment into the prospective, population-based northern Manhattan Study. Hs-CRP was measured using nephelometry and IL6 was measured using ELISA. Quartiles (values from 1-4) were calculated for each marker independently. We created a trichotomized variable with categorization dependent on which component is dominant in terms of quartiles: hs-CRP-dominant if hs-CRP-quartile>IL6-quartile; IL6-dominant if hs-CRP-quartile. Results: Both hsCRP and IL6 were available in 1656 participants (mean age 69.1±10.3 years; 21% white, 24% black, and 54% Hispanic; median follow-up 10.1 years, with 113 incident ischemic strokes). Independently, IL6 was protective against stroke risk, and HsCRP was not associated with stroke risk, in fully adjusted models. The hsCRP-dominant group was associated with increased risk of IS (adjusted HR 2.37, 95%CI 1.50-3.67) and the IL6 dominant group was associated with decreased risk (adjusted HR 0.45, 95%CI 0.24-0.82), compared to the referent group. Conclusions: In this multi-ethnic cohort, hsCRP and IL6 dominant categories were associated with stroke risk. Combined measures of inflammatory biomarkers may be a measure of chronic inflammation and predict ischemic events, even when individual measures do not. Disclosure: Dr. Luna has nothing to disclose. Dr. Moon has nothing to disclose. Dr. Liu has nothing to disclose. Dr. Cespedes has nothing to disclose. Dr. Spitalnik has nothing to disclose. Dr. Paik has nothing to disclose. Dr. Sacco has nothing to disclose. Dr. Elkind has received personal compensation for activities with Jarvik Heart, Bristol-Myers Squibb/Sanofi Pharmaceuticals, GlaxoSmithKline, Organon. Dr. Elkind has received personal compensation in an editorial capacity for the journal Neurology. Dr. Elkind has received research support from diaDexus, Inc., Bristol-Myers Squibb Company, Sanofi-Aventis Pharmaceuticals Inc., and the National Institute of Health.

One-Year Consumption of a Grape Nutraceutical Containing Resveratrol Improves the Inflammatory and Fibrinolytic Status of Patients in Primary Prevention of Cardiovascular Disease

The search for complementary treatments in primary prevention of cardiovascular disease (CVD) is a high-priority challenge. Grape and wine polyphenol resveratrol confers CV benefits, in part by exerting anti-inflammatory effects. However, the evidence in human long-term clinical trials has yet to be established. We aimed to investigate the effects of a dietary resveratrol-rich grape supplement on the inflammatory and fibrinolytic status of subjects at high risk of CVD and treated according to current guidelines for primary prevention of CVD. Seventy-five patients undergoing primary prevention of CVD participated in this triple-blinded, randomized, parallel, dose-response, placebo-controlled, 1-year follow-up trial. Patients, allocated in 3 groups, consumed placebo (maltodextrin), a resveratrol-rich grape supplement (resveratrol 8 mg), or a conventional grape supplement lacking resveratrol, for the first 6 months and a double dose for the next 6 months. In contrast to placebo and conventional grape supplement, the resveratrol-rich grape supplement significantly decreased high-sensitivity C-reactive protein (-26%, p = 0.03), tumor necrosis factor-α (-19.8%, p = 0.01), plasminogen activator inhibitor type 1 (-16.8%, p = 0.03), and interleukin-6/interleukin-10 ratio (-24%, p = 0.04) and increased anti-inflammatory interleukin-10 (19.8%, p = 0.00). Adiponectin (6.5%, p = 0.07) and soluble intercellular adhesion molecule-1 (-5.7%, p = 0.06) tended to increase and decrease, respectively. No adverse effects were observed in any patient. In conclusion, 1-year consumption of a resveratrol-rich grape supplement improved the inflammatory and fibrinolytic status in patients who were on statins for primary prevention of CVD and at high CVD risk (i.e., with diabetes or hypercholesterolemia plus ≥1 other CV risk factor). Our results show for the first time that a dietary intervention with grape resveratrol could complement the gold standard therapy in the primary prevention of CVD.

Cytokine imbalance in systemic lupus erythematosus: a study on northern Indian subjects

The phenotype of systemic lupus erythematosus (SLE) in Asian Indians is more severe as compared with that in Caucasians. The reason is not clear. In this context, we studied serum levels of interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), interleukin-4 (IL-4) and interlekin-10 (IL-10). Their interrelations and correlation with SLEDAI scores were evaluated. Forty patients with active SLE and 40 controls were studied. The mean SLEDAI score and anti-ds DNA level of the patients were 21.45 ± 8.61 and 176.68 ± 81.31 (IU/ml), respectively. Cytokines were estimated by enzyme-linked immunosorbent assay. In controls, the levels of IFN-γ were highest, followed by TNF-α, IL-10 & IL-4. In patients, however, the levels of TNF-α were highest, followed by IFN-γ, IL-10 & IL-4. IL-10 and IL-4 correlated negatively, and IFN-γ and TNF-α correlated positively with the SLEDAI scores. As compared with controls, in patients, the mean values of TNF-α, IL-10 and TNF-α/IL-10 ratio were higher by 6.9, 2.9 and 2.3 times, respectively (p < 0.001). Significant positive correlation was found between these two cytokines in patients (r = 0.327, p < 0.05) but not in controls. The levels and ratio of IL-4 and IFN-γ were comparable between patients and controls. These two cytokines correlated negatively both in controls (r = -0.358, p < 0.05) and patients (r = -0.990, p < 0.001). The ratio of TNF-α/IL-4 was 4.2 times higher, and those of IFN-γ/IL-4 and IFN-γ/IL-10 were 1.89 and 3.40 times lower in patients as compared with controls. A positive correlation between IL-10 and IL-4 (r = 0.345, p < 0.05) and a negative correlation between IL-10 and IFN-γ (r = -0.382, p < 0.05) were observed only in patients. This study showed a distinct profile of cytokine imbalance in patients with SLE from the northern plains of India. The levels, ratios and correlations of cytokines in patients suggested significant deviation from normal. Correlations of cytokines with SLEDAI scores indicated that TNF-α contributes significantly to the pathological manifestations of SLE in patients from the region. A detailed study is warranted.

The effects of abdominal wall-lifting technique, pneumoperitoneum and different anesthesia methods on serum cytokines levels in gynecological patients underwent laparoscopic operation

Objective To study the variation of serum interleukin-6 (IL-6),interleukin-10 (IL-10),tumor necrosis factor alpha(TNF-α) and heat shock protein 70(HSP70) in patients underwent gynecological laparoscopic operations using abdominal walllifting(a gasless technique) or pneumoperitoneum methods under different anesthesia.Methods Fifty-seven patients scheduled for gynecological laparoscopy,with operation time less than 100 min,were randomly divided into three groups ( Ⅰ,Ⅱ,Ⅲ ) with 19cases in each group respectively.Group Ⅰ patients were operated with CO2 pneuioperitoneum laparoscopy under general anesthesia.Group Ⅱ patients were operated under general anesthesia and abdominal wall-lifting technique.Group Ⅲ patients went through the same operative procedures as group Ⅱ,but under epidural anesthesia.Serum levels of IL-6,IL-10,TNF-α and HSP70 of all patients were monitored at four points:before anesthesia (Tt),30 min after the establishment of pneumoperitoneum or wall-lifting (T2),10min after it's removal (T3),and at 8 am on the following day (T4).Results There were no significant difference among serum levels of IL-6,IL-10,TNF-α and HSP70 of the three groups at T1(P＞0.05).The serum levels of all these indexes increased after the beginning of the operations,and reaching its peak at T3 in group Ⅰ and peak values at T4 in group Ⅱ and Ⅲ.The level of serum T NF-α[(31±I4) pg/L] was higher in group Ⅰ than that in group Ⅱ [(24±10) pg/L] at T2(P＜0.05).At point T3,serum levels of IL-6[(46±8)pg/L],TNF-α[(54±18) pg/L and HSP70[(3.18±0.58) μg/L] were significantly higher in group Ⅰ than those[ (39±6) pg/L,(36±17) pg/L,(2.30±0.29) μg/L] in group Ⅱ (P＜0.01),and so was the ratio of IL-6/IL-10(P＜0.05 ).Meanwhile,the serum concentrations of IL-6[(27±10) pg/L] and TNF-α [(24±7) pg/L] were significantly lower in group Ⅲ than those in group Ⅱ[ (P＜0.05).Conclusion Gynecological laparoscopic operation using abdominal wall-lifting method can avoid the effect of CO2 pneumoperitoneum and reduce the stress response during operation.Compared to general anesthesia,less stress response was seen in patients under epidural anesthesia. Key words: Anesthesia,general; Anesthesia,epidural; Laparoscopic surgery; CO2 insufflation; Stress

Inhibition of Classic Signaling Is a Novel Function of Soluble Glycoprotein 130 (sgp130), Which Is Controlled by the Ratio of Interleukin 6 and Soluble Interleukin 6 Receptor

IL-6 trans-signaling via the soluble IL-6 receptor (sIL-6R) plays a critical role in chronic inflammation and cancer. Soluble gp130 (sgp130) specifically inhibits IL-6 trans-signaling but was described to not interfere with classic signaling via the membrane-bound IL-6R. Physiological and most pathophysiological conditions are characterized by a molar excess of serum sIL-6R over IL-6 characterized by free IL-6 and IL-6 found in IL-6·sIL-6R complexes allowing both classic and trans-signaling. Surprisingly, under these conditions, sgp130 was able to trap all free IL-6 molecules in IL-6·sIL-6R·sgp130 complexes, resulting in inhibition of classic signaling. Because a significant fraction of IL-6 molecules did not form complexes with sIL-6R, our results demonstrate that compared with the anti-IL-6R antibody tocilizumab or the anti-trans-signaling monoclonal antibody 25F10, much lower concentrations of the dimeric sgp130Fc were sufficient to block trans-signaling. In vivo, sgp130Fc blocked IL-6 signaling in the colon but not in liver and lung, indicating that the colon is a prominent target of IL-6 trans-signaling. Our results point to a so far unanticipated role of sgp130 in the blockade of classic signaling and indicate that in vivo only low therapeutic concentrations of sgp130Fc guarantee blockade of IL-6 trans-signaling without affecting IL-6 classic signaling.

CS11-5. Inhibition of Interleukin 6 classic signaling is a novel function of soluble gp130 which is controlled by the ratio of Interleukin 6 and soluble Interleukin 6 receptor

CS11-5. Inhibition of Interleukin 6 classic signaling is a novel function of soluble gp130 which is controlled by the ratio of Interleukin 6 and soluble Interleukin 6 receptor

Asymmetric Dimethylarginine: Relationship with Circulating Biomarkers of Inflammation and Cardiovascular Disease Risk in Uncomplicated Obese Women

In recent years, the link between obesity, inflammation and atherosclerosis has attracted increasing interest. Recently, besides the classical inflammatory markers, the competitive nitric oxide synthase antagonist asymmetric dimethylarginine (ADMA) has been shown to be involved in the pathogenesis of atherosclerosis and cardiovascular diseases. Since obese people present a condition of chronic low-grade inflammation and endothelial dysfunction, in the present study we quantified ADMA levels in uncomplicated obese women (with no clinical, cardiac or metabolic complications) and normal-weight control subjects. We investigated the relationship of ADMA with some anthropometric measurements, abdominal visceral and subcutaneous adipose tissue accumulation, and biochemical and proinflammatory factors of the subjects [interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6R), IL6-R/IL-6 ratio, tumor necrosis factor alpha (TNFα), homocysteine (Hey) and plasminogen activator inhibitor-1 (PAI-1)]. ADMA and all the other pro-inflammatory parameters resulted higher in obese patients than in healthy subjects. ADMA significantly correlated with Hey, PAI-1, TNFα and with sIL-6R/IL-6 ratio but not with other anthropometric and biochemical parameters. In a stepwise regression analysis ADMA correlated most closely with Hey and TNFα. In conclusion, in our obese uncomplicated patients TNFα and Hey emerged as strong predictors of ADMA which might be a potential mediator of the effects of different risk factors affecting the cardiovascular system.