Higher Serum Levels Of TNF-α Research Articles

Association between cytokines and methylation of SOCS-1 in serum of patients with ankylosing spondylitis

In this study, we aim to determine the relationship between methylation level of an inflammatory-related gene, SOCS-1 in serum samples of patients with ankylosing spondylitis (AS) and their degree of inflammation as well as serum cytokine level. Quantitative real time methylation specific PCR was performed to examine the promoter methylation of SOCS-1 in serum samples of 43 HLA-B27+ AS patients and 6 B27+ healthy controls. Degree of inflammation was accessed by spondylopathy, sacroiliitis as well as acute phase reactant, erythrocyte sedimentation rate and C-reactive protein (CRP). Serum IL-6 and TNF-α level was determined by ELISA assay. SOCS-1 methylation can only be found in serums samples from patients but not normal control. Methylation of SOCS-1 significantly associated with severity of patient's spondylopathy (P < 0.005), sacroiliitis (P < 0.005) and acute phase reactant CRP (P = 0.0278). AS patients also exhibited higher serum IL-6 (P < 0.001) and TNF-α level (P < 0.001). Importantly, patients with high serum IL-6 or TNF-α level demonstrated a significantly higher SOCS-1 methylation (P < 0.001). In conclusion, this proof-of-principle study suggested that methylation of SOCS-1 can be detected in serum of HLA-B27+ AS patients but not in B27+ controls. The pathogenic potential of SOCS-1 methylation in AS deserves further investigation.

Genetic endowment of proinflammatory cytokine tumor necrosis factor‐α (–) 308 G &gt; A polymorphism to Parthenium hysterophorus‐induced airborne contact dermatitis in an Indian cohort

Parthenium dermatitis is a common airborne allergic health problem that induces a cell-mediated hypersensitivity immune response involving activated T lymphocytes, which culminates in injury to the skin. The disease is manifested as itchy erythematous papules and plaques and primarily affects the exposed areas and flexures. This study aimed to identify the role of tumor necrosis factor (TNF)-α (-) 308G>A polymorphism in the pathogenesis of parthenium dermatitis. A total of 120 subjects, including 60 patients exclusively diagnosed for parthenium dermatitis and 60 healthy individuals, were included in the study. The genotyping of the TNF-α (-) 308G>A region was carried out by the amplification refractory mutational system. In the present study, we demonstrated that polymorphism of the TNF-α (-) 308 position (A and/or G) was not statistically significant, and there was no difference in the distribution of any alleles of this locus in cases and controls. The present study suggests that there is a lack of association of potent proinflammatory cytokine TNF-α (-) 308G>A polymorphism in parthenium dermatitis in the Indian cohort. It interprets genetically endowed transcriptional capacity due to this particular single nucleotide polymorphism but does not support the prevalence of high serum levels of TNF-α in parthenium-induced skin allergic inflammation.

Can Tumor Necrosis Factor-αand Interleukin-6 Be Used as Prognostic Markers of Infection following Ureteroscopic Lithotripsy?

Introduction. Ureteroscopic lithotripsy (URS) although highly effective for the treatment of ureteral stones is associated with certain complications, the more common of which are postoperative fever and infection. In the present study we aimed to evaluate the levels of serum cytokines in patients undergoing ureteroscopic lithotripsy and investigate any possible correlation between levels of cytokines and infectious complications after URS. Materials and Methods. Thirty patients (19 males, 11 females), with a mean age of 47 (range: 26–68) that underwent URS lithotripsy for ureteral stones, and 10 healthy volunteers serving as the control group were enrolled in this study. Serum samples for TNF-α and IL-6 were obtained before surgical intervention and after 1, 24, and 48 hours and 2 , 24, and 48 hours, respectively. The preoperative and postoperative levels were compared and correlated with the possible complications after URS. Results. Serum TNF-α levels were statistically significant, increased 1 hour (P = 0.0083) and 48 hours (P < 0.001) after operation. IL-6 levels were found statistically significant, elevated after 2 and 24 hours from the URS (P < 0.001). In 2 patients we observed postoperative fever (>38.5°C). These two patients had high preoperative values of TNF-α and IL-6 ( 30 and 50 pg/mL, resp.) and these values increased postoperatively. Conclusion. High preoperative levels of serum TNF-α and IL-6 may indicate a predisposition for postoperative inflammation and infection following URS lithotripsy.

Cerebral hemodynamics and endothelial function in patients with Fabry disease

BackgroundCerebral vasculopathy have been described in Fabry disease, in which altered cerebral blood flow, vascular remodelling or impairment of endothelial function could be involved. Our study aims to evaluate these three possibilities in a group of Fabry patients, and compare it to healthy controls.MethodsCerebral hemodynamics, vascular remodelling and systemic endothelial function were investigated in 10 Fabry patients and compared to data from 17 healthy controls. Transcranial Doppler was used to study blood flow velocity of intracranial arteries and cerebral vasomotor reactivity. For the study of vascular remodelling and endothelial function, intima-media thickness of common carotid arteries, flow-mediated dilation in brachial artery and serum levels of soluble VCAM-1, TNF-α, high-sensitive CRP and IL-6 were measured. Differences between groups were evaluated using appropriate tests.ResultsNo relevant differences were observed in cerebral hemodynamic parameters, intima-media thickness or flow-mediated dilation. There was a trend for low serum levels of IL-6 and high serum levels of TNF-α and high-sensitive CRP in Fabry patients; plasma concentrations of soluble VCAM-1 were significantly higher in Fabry disease patients than in healthy volunteers (p = 0.02).ConclusionsIn our sample, we did not find relevant alterations of cerebral hemodynamics in Fabry disease patients. Increased levels of plasmatic endothelial biomarkers seem to be the most important feature indicative of possible vascular dysfunction in Fabry disease patients.

Transforming Growth Factor-β1 and Tumor Necrosis Factor-α are Associated with Clinical Severity and Airflow Limitation of COPD in an Additive Manner

The role of tumor necrosis factor-α (TNF-α) and transforming growth factor-β1 (TGF-β1) in chronic obstructive pulmonary disease (COPD) is controversial. The purpose of this study was to assess the relationships among polymorphisms, clinical phenotypes, and the serum levels of TNF-α and TGF-β1. Polymorphisms of promoters of TNF-α (rs 361525 and rs 1800629) and TGF-β1 (rs 1800469) in 110 COPD patients, 110 nonsmoker health controls without COPD, and 34 smokers were evaluated. Pulmonary functions, chest computed tomography, TGF-β1, and TNF-α were assessed. The genetic polymorphism of TNF-α (rs 361525) was associated with COPD. More severe COPD patients had higher serum levels of TNF-α and TGF-β1; moreover, serum levels of TGF-β1of mild COPD patients were higher than normal controls. All of the studied subjects were divided into four groups by the 95th percentile value of control as cutoff serum value of TGF-β1 (224.35ρg/ml) or TNF-α (17.56ρg/ml) to define the high value of TGF-β1 or TNF-α, which are higher than those cutoff of values (>224.35 or 17.56ρg/ml). The FEV1 of the group with high TGF-β1+low TNF-α or low TGF-β1+high TNF-α or high TNF-α+high TGF-β1 was lower than the group with low TGF-β1+low TNF-α group. Moreover, the lowest value of FEV1 was in the group with high TNF-α+high TGF-β1. The genetic polymorphism of the TNF-α is associated with COPD. Both TGF-β1 and TNF-α modulate clinical severity and airflow limitation in an additive manner.

Research on the Relationship Between Serum Levels of Inflammatory Cytokines and Non-small Cell Lung Cancer

This study was conducted to evaluate the levels of TNF-α, IL-6, IL-8 and VEGF in serum of patients with non- small cell lung cancer, for assessing their possible diagnostic and prognostic roles. We enrolled 48 patients newly diagnosed with non-small cell lung cancer and 40 healthy controls. TNF- α, IL-6 and IL-8 levels were measured in the serum of all the subjects with specific radioimmunoassay kits, while EGF was analyzed by sandwich enzyme immunoassay techniques. A statistically significant difference was observed between lung cancer patients and the control group regarding the values of TNF-α, IL-6, IL-8 and VEGF in serum. Moreover, TNF-α, IL-8 and VEGF levels were higher in patients with advanced stages compared to early stages. In addition, higher serum levels of TNF-α, IL-6, IL-8 and VEGF were found in smokers than in non-smokers, both in patients and controls. Serum levels of TNF-α, IL-6, IL-8 and VEGF were all elevated in lung cancer patients, suggesting that inflammatory cytokines could be jointly used as a screening tool. Though TNF-α, IL-8 and VEGF levels were related to advanced disease, long-term survival studies of NSCLC patients should be performed to confirm whether they can act as biomarkers of advanced disease. In addition, smoking would be an important contributor to the processes of inflammation and lung cancer.

Targeting Transmembrane TNF-α Suppresses Breast Cancer Growth

TNF antagonists may offer therapeutic potential in solid tumors, but patients who have high serum levels of TNF-α fail to respond to infliximab, suggesting consumption of the circulating antibody and loss of transmembrane TNF-α (tmTNF-α) on tumors by ectodomain shedding. Addressing this possibility, we developed a monoclonal antibody (mAb) that binds both full-length tmTNF-α and its N-terminal truncated fragment on the membrane after tmTNF-α processing but does not cross-react with soluble TNF-α. We documented high levels of tmTNF-α expression in primary breast cancers, lower levels in atypical hyperplasia or hyperplasia, but undetectable levels in normal breast tissue, consistent with the notion that tmTNF-α is a potential therapeutic target. Evaluations in vitro and in vivo further supported this assertion. tmTNF-α mAb triggered antibody-dependent cell-mediated cytotoxicity against tmTNF-α-expressing cells but not to tmTNF-α-negative cells. In tumor-bearing mice, tmTNF-α mAb delayed tumor growth, eliciting complete tumor regressions in some mice. Moreover, tmTNF-α mAb inhibited metastasis and expression of CD44v6, a prometastatic molecule. However, the antibody did not activate tmTNF-α-mediated reverse signaling, which facilitates tumor survival and resistance to apoptosis, but instead inhibited NF-κB activation and Bcl-2 expression by decreasing tmTNF-α-positive cells. Overall, our results established that tmTNF-α mAb exerts effective antitumor activities and offers a promising candidate to treat tmTNF-α-positive tumors, particularly in patients that are nonresponders to TNF antagonists.

The role of cholinergic anti-inflammatory pathway in acetic acid-induced colonic inflammation in the rat

The “cholinergic anti-inflammatory pathway” provides neurological modulation of cytokine synthesis to limit the magnitude of the immune response. This study aimed to evaluate the impact of the cholinergic anti-inflammatory pathway on the extent of tissue integrity, oxidant-antioxidant status and neutrophil infiltration to the inflamed organ in a rat model of acetic acid-induced colitis. Colitis was induced by intrarectal administration of 5% acetic acid (1ml) to Sprague–Dawley rats (200–250g; n=7–8 per group). Control group received an equal volume of saline intrarectally. The rats were treated with either nicotine (1mg/kg/day) or huperzine A (0.1mg/kg/day) intraperitoneally for 3days. After decapitation, the distal colon was scored macroscopically and microscopically. Tissue samples were used for the measurement of malondialdehyde (MDA) and glutathione (GSH) levels, and myeloperoxidase (MPO) activity. Formation of reactive oxygen species was monitored by using chemiluminescence (CL). Nuclear factor (NF)-κB expression was evaluated in colonic samples via immunohistochemical analysis. Trunk blood was collected for the assessment of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-10, resistin and visfatin levels. Both nicotine and huperzine A reduced the extent of colonic lesions, increased colonic MDA level, high MPO activity and NF-κB expression in the colitis group. Elevation of serum IL-1β level due to colitis was also attenuated by both treatments. Additionally, huperzine A was effective to reverse colitis-induced high lucigenin-enhanced CL values and serum TNF-α levels. Colitis group revealed decreased serum visfatin levels compared to control group which was completely reversed by nicotine. In conclusion, modulation of the cholinergic system either by nicotine or ACh esterase inhibition improved acetic acid-induced colonic inflammation as confirmed by macroscopic and microscopic examination and biochemical assays.

Obesity increases eosinophil activity in asthmatic children and adolescents

BackgroundA clear relationship between asthma and obesity has been reported, but the mechanisms remain unclear. The aim of this study was to evaluate the influence of obesity on eosinophil activity (chemotaxis and adhesion) in asthmatic children and adolescents compared with cells from healthy volunteers.MethodsAsthmatic obese (AO), asthmatic non-obese (ANO), non-asthmatic obese (NAO) and non-asthmatic non-obese (NANO) individuals were included in the present study. The chemotaxis of eosinophils after stimulation with eotaxin (300 ng/ml), platelet-activating factor (10 μM; PAF) and RANTES (100 ng/ml) was performed using a microchemotaxis chamber. The eosinophil peroxidase activity was measured to determine the adhesion activity of eosinophils cultivated on fibronectin-coated plates. The serum leptin, adiponectin, TNF-α and IgE levels were quantified using ELISA assays.ResultsThe serum IgE levels and eosinophil counts were significantly higher in asthmatic (obese and non-obese) individuals compared with non-asthmatic individuals (obese and non-obese). Spontaneous eosinophil chemotaxis was greater in the AO group compared with either the ANO or NANO groups. The activation of eosinophils using eotaxin and PAF increased eosinophil chemotaxis in the AO group. RANTES treatment increased eosinophil chemotaxis in the NAO group compared with the NANO or ANO groups. The activation of eosinophils using eotaxin significantly increased eosinophil adhesion in the AO group compared with other groups. The serum leptin and TNF-α levels were higher in obese subjects (asthmatic and non-asthmatic), whereas the levels of adiponectin did not significantly differ among these groups.ConclusionThis study is the first to show increased eosinophilic activity (chemotaxis and adhesion) associated with high serum leptin and TNF-α levels in atopic asthmatic obese children and adolescents compared with non-obese healthy volunteers.

Impact of single nucleotide polymorphism in tumor necrosis factor-α gene 308G/A in Egyptian asthmatic children and wheezing infants

Bronchial asthma is a common disease with multiple determinants that include genetic variation. Although tumor necrosis factor alpha (TNF-α) is a major pro-inflammatory cytokine, the functions of genetic polymorphisms in this cytokine has not been thoroughly examined in the context of asthma pathology. Therefore, we aimed to investigate whether single nucleotide polymorphism (SNP) in TNF-α is associated with asthma and wheezing and whether the association is related to the severity of the disease and other epidemiological factors. Frequencies of TNF-α-308G/A polymorphism were compared in 100 asthmatic children, 100 wheezy infants and 100 age and gender matched controls. Genotype frequencies for TNF-α-308G/A were significantly higher in asthmatic children (60%) and wheezy infants (68%) than the control group (30%). Higher serum levels of TNF-α were observed in genotypes G/A and G/G of asthmatic children and wheezy infants than in controls. No association was found between the G/A polymorphism and the severity of the disease, the total eosinophil count and IgE levels in both groups. We can conclude that genetic variation in TNF-α-308G/A may contribute to childhood asthma and wheezing. These findings could be helpful for future early intervention studies which may have a potential impact on family counseling and management.

Tumor necrosis factor (TNF)-α gene +489 polymorphisms: association with psoriatic arthritis

Objective of this work was to investigate the role of single nucleotide polymorphisms (SNPs) at position +489 of the tumor necrosis factor (TNF)-α gene in generic susceptibility and severity of psoriatic arthritis (PsA). Fifty-seven Caucasian PsA patients diagnosed according to CASPAR criteria and 155 healthy matched controls were studied. PASI score, DAS28 and Disability INdex HAQ were calculated. Genomic DNA was extracted from peripheral blood samples and SNPs +489 G&amp;gt;A (rs 80267959) were amplified by PCR. The SNP +489 genotype was significantly associated with PsA susceptibility (p=0.0136) and severity of clinical and laboratory parameters (p values ranging from 0.016 to 2.908 x 10-12). The difference in severity was accounted for by the difference between the AA and GA genotypes with respect to the GG genotype. These findings suggest that TNF-α gene polymorphisms may influence PsA susceptibility and severity. Psoriatics arthritis (PsA) is a complex immunemediated disease that results from the interplay between multiple genetic and environmental factor [1]. Although the pathogenesis of PsA remains elusive, there is evidence that genetic factors may contribute to the etiology of the disease [2]. Is has been estimated that at least one third of the genetic contribution to PsA resides in the major histocompatibility complex (MHC) region [2]. The tumor necrosis factor (TNF)-α gene, which is located in the short arm of chromosome 6 in the MHC class III region between the HLA-B and HLA-DR genes, has been proposed as a major candidate gene in PsA [3]. This hypothesis is supported by studies which have found high serum, synovial fluid and synovial membrane TNF-α levels in patients with PsA [4,5]. Several single nucleotide polymorphisms (PNPs) have been identified in the TNF-α gene promoter [6]. In particular, two common polymorphisms, namely G to A substitutions at positions -238 and -308 have been studied in patients with PsA. However, association studies of these two TNF-α polymorphisms and genetic susceptibility to PsA have lead to conflicting results [7-12]. Previous studies have indicated the potential role of the SNP at +489 position in the first intron of the TNF-α gene in the susceptibility to some rheumatic autoimmune diseases like rheumatoid arthritis [13], systemic lupus erythematosus [14] and systemic sclerosis [15]. However, to our present knowledge, studies on the association of +489 polymorphism with PsA susceptibility and response to TNF-α inhibitors are not reported in the literature. Is this study we investigated the role of SNPs at +489 within the TNF-α gene in PsA susceptibility and severity.

Changes in serum levels of TNF-α and IL-8 in acute exacerbation of COPD

Objective To explore the significance of changes in levels of TNF-α and IL-8 in acute exacerbation of COPD.Methods The data on 80 patients with acute exacerbation of COPD who had been hospitalized during the period of 2009 to 2011 were retrospectively analyzed.The patients were divided into two groups.The control group included 40 patients with respiratory failure; and the study group included 40 patients without respiratory failure.RIA was used to measure serum levels of TNF-α and IL-8; respiratory function was detected.The association of serum levels of TNF-α and IL-8 with respiratory function was determined.Results Levels of TNF-α and IL-8 were significantly higher in the study group than in the control group (P＜0.05).FEV1％ was significantly lower in the study group than in the control group (P＜0.05).Levels of TNF-α and IL-8 had a negative correlation with FEV1％,with a correlation coefficient of-0.72 and-0.65 (P＜0.05).Conclusions Patients with acute exacerbation of COPD complicated by respiratory failure have higher serum levels of TNF-α and IL-8 than those without respiratory failure.Increased levels of TNF-α and IL-8 may aggravate airway obstruction in COPD patients.TNF-α and IL-8 can help monitor disease severity and prognosis. Key words: COPD; TNF-α; IL-8; Changes

Tumor necrosis factor-alfa and monocyte chemoattractant protein-1 gene polymorphisms in kidney transplant recipients

Tumor necrosis factor-alfa (TNF-α) gene polymorphism is supposed to have a significant influence on the incidence of acute rejection in renal transplantation. The monocyte chemoattractant protein-1 (MCP-1) is another factor supposed to modulate graft rejection. We studied TNF-α and MCP-1 gene polymorphisms in 84 kidney allograft recipients with polymerase chain reaction and restriction fragment length polymorphism and their serum levels by enzyme-linked immunosorbent assay. The patients were classified into two groups based on their outcomes: Group I (n = 47) recipients with stable graft function as the control group and group II (n=37) recipients who experienced acute graft rejection episodes in the first 30 days post-transplantation. A significantly higher incidence of TNF 2 /TNF 2 genotype was observed among patients with acute graft rejection in comparison with the control group (40.5% and 19.2% respectively, P <0.05), while no statistically significant differences were observed in the TNF 1 /TNF 1 genotype between the groups (59.4% and 80.8%, respectively, P >0.05). A significant elevation of serum TNF-α levels was found in group II than group I and between TNF 2 genotype compared with that of TNF1 genotype within group II recipients. Distribution of MCP-1 genotypes in patients with and without acute rejection episodes was not significantly different (70.2% and 76.6% for MCP-1 A/A and 29.7% and 23.4% for MCP-1 G/G, respectively, P >0.05). The serum MCP-1 levels were not significantly different between the groups and between MCP-1 G/G genotype and MCP-1 A/A genotype in group II recipients. In conclusion, TNF-α gene polymorphism or its serum levels may identify patients at risk of acute rejection, where patients with TNF 2 /TNF 2 genotype or high serum TNF-α levels are more likely to have acute rejection episodes, while there was no relation between MCP-1 genotype or its serum levels and acute rejection.

Tumor Necrosis Factor-α as a Predictor for the Development of Nonalcoholic Fatty Liver Disease: A 4-Year Follow-Up Study

BackgroundTumor necrosis factor (TNF)-α is associated with insulin resistance and systemic inflammatory responses. The aim of this study was to investigate the relationship between TNF-α and the development of nonalcoholic fatty liver disease (NAFLD) in a longitudinal study.MethodsThree hundred and sixty-three apparently healthy subjects (mean age, 40.5±6.1 years; male, 57.6%) without NAFLD were enrolled in 2003. Anthropometric and laboratory measurements were performed. The participants were grouped into tertiles according to their serum TNF-α levels from samples taken in 2003. At a 4-year follow-up, we compared the odds ratios (ORs) of the development of NAFLD according to the tertiles of TNF-α levels measured in 2003.ResultsAt the 4-year follow-up, the cumulative incidence of NAFLD was 29.2% (106/363). The group that developed NAFLD had higher levels of TNF-α than those in the group without NAFLD (3.65±1.79 pg/mL vs. 3.15±1.78 pg/mL; P=0.016). When the 2003 serum TNF-α levels were categorized into tertiles: incidence of NAFLD observed in 2007 was significantly higher with increasing tertiles (22.6%, 35.8%, and 41.5%, respectively; P<0.05). The risk of developing NAFLD was significantly greater in the highest tertile of TNF-α than in the lowest tertile after adjusting for age, smoking, and BMI (OR, 2.20; 95% confidence interval, 1.12 to 4.01; P<0.05).ConclusionHigher serum TNF-α levels in subjects without NAFLD were associated with the development of NAFLD. The results of study might suggest a pathologic role of inflammation in NAFLD.

Polymorphism of tumor necrosis factor alpha (TNF-alpha) gene promoter, circulating TNF-alpha level, and cardiovascular risk factor for ischemic stroke

BackgroundTumor necrosis factor-α (TNF-α) is one of the most typical pro-inflammatory cytokines with both beneficial and destructive properties for the central nervous system. Increasing evidences have demonstrated the important role of TNF-α in the development of ischemic stroke, but studies examining the possible association with stroke or direct functional effects of polymorphisms in TNF-α have been contradictory.FindingsIn this study, a 2-kb length of the proximal promoter of the TNF-α was screened and four polymorphisms were investigated in the case–control study. Our data confirmed the association between -308G/A variant with stroke in 1,388 stroke patients and 1,027 controls and replicated in an independent population of 961 stroke patients and 821 controls (odds ratio (OR) = 1.34, 95% confidence interval (CI) =1.02 to 1.77 and OR = 1.56, 95% CI = 1.09 to 2.23, respectively). To reconcile the association between polymorphisms and stroke and to give a comprehensive picture of the genetic architecture of this important gene, we performed a meta-analysis of 15 published studies in an Asian population. Our results demonstrated an association between rs1800629 and ischemic stroke (OR = 1.43, 95% CI = 1.21 to 1.69). Another meta-analysis results of 14 studies demonstrated that ischemic stroke patients have higher serum TNF-α level than the control subjects (standardized mean difference (SMD) = 2.33, 95% CI = 1.85 to 2.81). In vitro evaluation of potential interaction between variants of the TNF-α gene (−308G/A, -857C/T, and -1031T/C) demonstrated that these three polymorphisms could interact together to determine the overall activity of the TNF-α gene.ConclusionsThese findings strongly implicate the involvement of TNF-α in the pathogenesis of stroke.

Brief Report: Large‐scale analysis of tumor necrosis factor α levels in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) disease manifestations are highly variable among patients, and the prevalence of individual clinical features differs significantly by ancestry. Serum tumor necrosis factor α (TNFα) levels are elevated in some SLE patients and may play a role in disease pathogenesis. The aim of this study was to look for associations between serum TNFα levels, clinical manifestations of SLE, autoantibodies, and serum interferon-α (IFNα) levels in a large multiancestral SLE cohort. We studied serum TNFα levels in 653 SLE patients (214 African Americans, 298 European Americans, and 141 Hispanic Americans). TNFα was measured using an enzyme-linked immunosorbent assay, and IFNα was measured with a functional reporter cell assay. Stratified and multivariate analyses were used to detect associations in each ancestral background separately, with meta-analysis when appropriate. Serum TNFα levels were significantly higher in SLE patients than in non-autoimmune disease controls (P < 5.0 × 10(-3) for each ancestral background). High serum TNFα levels were positively correlated with high serum IFNα levels when tested in the same sample across all ancestral backgrounds (odds ratio range 1.76-1.86, P = 4.8 × 10(-3) by Fisher's combined probability test). While serum TNFα levels alone did not differ significantly among SLE patients of different ancestral backgrounds, the proportion of patients with concurrently high levels of TNFα and IFNα was highest in African Americans and lowest in European Americans (P = 5.0 × 10(-3) ). Serum TNFα levels were not associated with autoantibodies, clinical criteria for the diagnosis of SLE, or age at the time of sampling. Serum TNFα levels are high in many SLE patients, and we observed a positive correlation between serum TNFα and IFNα levels. These data support a role for TNFα in the pathogenesis of SLE across all ancestral backgrounds and suggest important cytokine subgroups within the disease.

Role of some biomarkers in chronic pelvic pain for early detection of endometriosis in infertile women

Abstract Objective Diagnosis of endometriosis in infertile women with chronic pelvic pain depends mainly on laparoscopy, but it has many risks. The aim of this study was to evaluate the value of some biomarkers as a reliable non-invasive method for the diagnosis of early stages of endometriosis in infertile women with chronic pelvic pain. Materials and methods A total of 95 women who underwent laparoscopy were divided into two groups: control cases (30 cases) with no pathologic findings; and endometriosis patients (65 cases) {subdivided into stages 1–2 or minimal–mild (MM) and stages 3–4 or moderate–severe (MS) cases}. Blood was drawn on cycle days 6–10 and stored at −70 °C for subsequent analysis of IL-6, CA-125, TNF-α, HsCRP and VEGF levels. Results High levels of serum IL-6 and serum TNF-α were observed in MM endometriosis as compared to controls ( P P P P P Conclusion Serum IL-6 and TNF-α levels are reliable non-invasive biomarkers for the diagnosis of early stages of endometriosis because they increased significantly in early cases than in late cases. CA125, Hs-CRP & VEGF are significantly increased in late cases, so they cannot be used for early diagnosis.

Serum and gene expression profile of cytokines in first-episode psychosis.

An inflammatory syndrome has been previously reported in chronic schizophrenia. The aims of this study were to investigate: (1) serum levels and leukocyte gene expression of cytokines in patients with first-episode psychosis and controls; and (2) possible causes of abnormal cytokine levels in first-episode psychosis, testing their association with psychosocial stressors, current nicotine and cannabis use, and duration of antipsychotic treatment. We recruited 24 first-episode psychosis patients and 24 healthy controls matched for age, gender, ethnicity and body mass index. Serum interleukin(IL)-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, Tumour Necrosis Factor- α (TNF-α), Interferon- γ (IFN-γ), vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), and monocyte chemotactic protein-1 (MCP-1) were analysed in all subjects. Leukocyte gene expression analyses were conducted only for those cytokines that were different between-groups in the serum analyses. Patients had significantly higher serum levels of IL-1α (effect size d=0.6, p=0.03), IL-1β (d=0.4, p=0.01), IL-8 (d=0.6, p=0.01) and TNF-α (d=0.7, p=0.05) and a trend for higher IL-6 serum levels (d=0.3, p=0.09) when compared with controls. Leukocyte m-RNA levels of IL-1α (d=0.6, p=0.04), IL-6 (d=0.7, p=0.01) and TNF-α (d=1.6, p<0.001), but not IL-1β and IL-8, were also significantly higher in patients. A history of childhood trauma was associated with higher TNF-α serum levels (p=0.01), while more recent stressful life-events were associated with higher TNF-α mRNA levels in leukocytes (p=0.002). In conclusion, first-episode psychosis is characterised by a pro-inflammatory state supported, at least in part, by activation of leukocytes. Past and recent stressors contribute to this pro-inflammatory state.

Bacterial Superantigens Enhance the In Vitro Proinflammatory Response and In Vivo Lethality of the TLR2 Agonist Bacterial Lipoprotein

Bacterial superantigens are Gram-positive exotoxins that induce proinflammatory cytokine release in vitro, cause lethal shock in vivo, and can be detected in the bloodstream of critically ill patients. They also have a powerful priming effect on the TLR4 agonist LPS. The aim of this study was to investigate the relationship between superantigens and the TLR2 agonist bacterial lipoprotein (BLP). Priming of human monocytes or PBMCs with superantigens significantly enhanced proinflammatory cytokine TNF-α and IL-6 release in response to BLP stimulation. The priming effect of superantigens could be blocked by inhibiting p38 MAPK during the priming phase as opposed to NF-κB or ERK inhibition. This was consistent with higher expression of the phosphorylated p38 after superantigen priming and BLP or LPS stimulation. C57BL/6 mice with superantigen priming (10 μg/mouse) when challenged with BLP (600 μg/mouse) exhibited substantially higher mortality (100%) compared with mice without superantigen priming (zero). Mice given superantigen alone did not demonstrate any signs of illness. Mice challenged with both superantigen and BLP had significantly higher levels of serum TNF-α and IL-6 compared with those of mice challenged with either agent alone. Depletion of the monocyte/macrophage subpopulation significantly reduced the mortality rate from 100 to 20% in superantigen-primed, BLP-challenged C57BL/6 mice, with a 5- to 10-fold decrease in serum TNF-α and IL-6. Our results demonstrate that bacterial superantigens enhance the in vitro proinflammatory cytokine release and in vivo lethality of BLP. This novel finding may help to explain the massive proinflammatory cytokine release seen in superantigen-mediated septic shock.

Effects of magnetic induction hyperthermia and radiotherapy alone or combined on a murine 4T1 metastatic breast cancer model

Purpose: The purpose of this study was to explore the effects of MIH and radiotherapy alone or combined on metastatic breast cancer and the underlying mechanisms.Materials and methods: A murine 4T1 metastatic breast cancer model was established and randomly assigned into four treatment groups: C (control), R (radiotherapy), MIH, and MIH + R. Tumour volume, lung metastasis, the expression of Bax and MMP-9, T cell subsets, serum cytokine levels, and mouse survival were evaluated.Results: Group MIH + R showed significantly reduced tumour volume, lung metastasis, improved survival and increased Bax expression compared to group R or MIH (P < 0.05). MMP-9 expression in the primary tumour tissue was significantly increased in group R compared to the other groups (P < 0.05), which could be brought down by combined MIH treatment. Group MIH + R showed significantly higher CD4+ T cell percentage as well as CD4+/CD8+ cell ratio than group R (P < 0.05). Group MIH + R showed significantly higher serum levels of TNF-α, IFN-γ and IL-2 than group R (P < 0.05).Conclusions: MIH not only promotes the tumour-cell killing effect of radiotherapy through Bax-mediated cell death, but also improves cellular immunity in mice under radiotherapy and decreases the potential of radiotherapy to enhance MMP-9 expression, which leads to significant improvement in lung metastasis and overall survival of mice under combined treatment of MIH and R. This study is the first to have explored the effect of combined hyperthermia and radiotherapy on tumour metastasis and the underlying mechanisms. It provides insights into the application of MIH as an adjuvant to radiotherapy for metastatic breast cancer.