TNF-α Levels In Patients Research Articles

Sa1234 RNA-Seq Derived Whole Blood Gene Expression Signature As a Biomarker for Differential Diagnosis and Intestinal Inflammation in Inflammatory Bowel Disease

Introduction: In the last two decades the therapeutic paradigm of Crohn's disease (CD) has changed dramatically thanks to the use of biological drugs. In this scenario, we must consider the pivotal role of tumor necrosis factor-alpha (TNF-α), a pro-inflammatory cytokine, in the pathogenesis and relapse of CD. High levels of TNF-α have been associated with the development of intestinal inflammation in CD and blocking this cytokine with anti-TNF-α molecules may result in mucosal healing. In addition several studies have shown increased TNF-α levels in the serum and in the intestinal mucosa of patients with CD. However, little is known about the course of TNF-α levels and their relationship with disease recurrence in CD patients during maintenance treatment with Adalimumab. Aim: We assessed TNF-α levels in patients with CD who were in maintenance treatment with ADA and correlated them with clinical and endoscopic disease activity. Methods: In this prospective observational cohort study, performed at a single tertiary referral center, 23 [14M/9F; mean age 41 (range 21-66) infliximab-Naive patients with CD in maintenance treatment with ADA were included and followed-up. Blood samples were drawn at standardized time points (i.e. at 6, 12, 18, 24 months and in case of CD relapse) just before ADA injection. Antibodies against ADA (AAA) were measured using an homogenous mobility shift assay (HMSA; Prometheus Lab, San Diego, United States). Blood samples were considered positive for AAA presence if ≥1.7 U/mL. Disease activity was assessed at the same points by means of the Harvey-Bradshaw Index (HBI, remission 16). Moreover, endoscopic activity was assessed at baseline and at the time of relapse by means of CD endoscopic index (CDEIS 5 responder, CDEIS<3 complete endoscopic remission and mucosal healing). Results: We have data from 133 blood samples. AAA were observed in 26/133 (19.5%) samples, and 10/26 (38.5%) had a value of AAA ≥1.7 U/mL. TNF-α levels were present in all samples assessed (Mean 4.4, range 027.2). As shown in the figure, per-patient median TNF-α levels were strongly correlated with median HBI scores (r2=0.702, p<0.0001). Moreover, TNF levels were also correlated with CDEIS (r2=0.350, p=0.001). Conclusion: TNF-α levels strongly correlated with disease activity based on HBI and CDEIS indices in patients with CD in maintenance treatment with ADA. Indeed, moderate to severe patients often have high sustained TNF-α levels.

Sa1235 PKM2 As a Novel Serum Biomarker of IBD Activity, A Early Pilot Study

Introduction: In the last two decades the therapeutic paradigm of Crohn's disease (CD) has changed dramatically thanks to the use of biological drugs. In this scenario, we must consider the pivotal role of tumor necrosis factor-alpha (TNF-α), a pro-inflammatory cytokine, in the pathogenesis and relapse of CD. High levels of TNF-α have been associated with the development of intestinal inflammation in CD and blocking this cytokine with anti-TNF-α molecules may result in mucosal healing. In addition several studies have shown increased TNF-α levels in the serum and in the intestinal mucosa of patients with CD. However, little is known about the course of TNF-α levels and their relationship with disease recurrence in CD patients during maintenance treatment with Adalimumab. Aim: We assessed TNF-α levels in patients with CD who were in maintenance treatment with ADA and correlated them with clinical and endoscopic disease activity. Methods: In this prospective observational cohort study, performed at a single tertiary referral center, 23 [14M/9F; mean age 41 (range 21-66) infliximab-Naive patients with CD in maintenance treatment with ADA were included and followed-up. Blood samples were drawn at standardized time points (i.e. at 6, 12, 18, 24 months and in case of CD relapse) just before ADA injection. Antibodies against ADA (AAA) were measured using an homogenous mobility shift assay (HMSA; Prometheus Lab, San Diego, United States). Blood samples were considered positive for AAA presence if ≥1.7 U/mL. Disease activity was assessed at the same points by means of the Harvey-Bradshaw Index (HBI, remission 16). Moreover, endoscopic activity was assessed at baseline and at the time of relapse by means of CD endoscopic index (CDEIS 5 responder, CDEIS<3 complete endoscopic remission and mucosal healing). Results: We have data from 133 blood samples. AAA were observed in 26/133 (19.5%) samples, and 10/26 (38.5%) had a value of AAA ≥1.7 U/mL. TNF-α levels were present in all samples assessed (Mean 4.4, range 027.2). As shown in the figure, per-patient median TNF-α levels were strongly correlated with median HBI scores (r2=0.702, p<0.0001). Moreover, TNF levels were also correlated with CDEIS (r2=0.350, p=0.001). Conclusion: TNF-α levels strongly correlated with disease activity based on HBI and CDEIS indices in patients with CD in maintenance treatment with ADA. Indeed, moderate to severe patients often have high sustained TNF-α levels.

Changes and curative effect of serum cell cytokine of burning mouth syndrome(BMS) patients before and after medical treatment

Objective To discuss changes and curative effect of serum interleukin-2 and 6 and tumor necrosis factor-α (TNF-α) of burning mouth syndrome (BMS) patients before and after medical treatment.Methods 50 cases of BMS patients were selected as case group,and who were given Clonazepam tablets (2mg) and Fluoxetine capsules (20 mg) one time daily for 4 weeks.Observe and compare the changes of serum IL-2 and 6,and TNF-αof patients in two groups before and after 4 weeks' medical treatment,and proceeded with the clinical curative effect observation.Moreover,30 cases of healthy subjects who just took the physical examination in medical examination center(MEC) at that moment was the control group.Results The serum IL-2 and IL-6,and TNF-αlevels of patients in case group before medical treatment was obviously higher than those in control group (t =4.31,2.97,3.84,all P ＜0.01).After 4 weeks' medical treatment,serum IL-2 and IL-6,and TNF-αlevels of patients had obviously declined than before (t =2.88,2.34,3.21,P ＜ 0.05 or P ＜ 0.01).After 4 weeks' medical treatment,there were 6 cured cases,14 cases with significant effect,and 24 cases with curative effect,and the total clinical efficiency reaches 88.0％ (44/50).Conclusion BMS patients have abnormal elevation of serum IL-2 and 6,and TNF-α,which may be the sensitive serological indicators of the early diagnosis of BMS.The changes of serum IL-2 and IL-6,and TNF-α levels may be the index of follow-up curative effect and prognosis observation. Key words: Burning Mouth Syndrome(BMS) ; Interleukin ; Tumor Necrosis Factor

Expression of tumor necrosis factor α and its correlation with severity of oral submucous fibrosis: a case-control study.

The objective of this case-control study was to evaluate the plasma tumor necrosis factor α (TNF-α) levels in patients with oral submucous fibrosis and to determine the relation of plasma TNF-α levels with the severity of oral submucous fibrosis. Blood samples were collected from 25 patients who were diagnosed with oral submucous fibrosis and from 25 age- and sex-matched control participants. The plasma was isolated by centrifugation of blood samples. The levels of plasma TNF-α were estimated using enzyme-linked immunosorbent assay. A total of 19 out of 25 patients had detectable plasma TNF-α levels ranging from 0.1 to 106.4 pg/mL (mean, 23.46 pg/mL), whereas only 12 out of 25 control participants had detectable plasma TNF-α levels ranging from 0.1 to 33.3 pg/mL (mean, 6.93 pg/mL). The difference between the TNF-α levels of patients and controls was statistically significant (P = .015) according to the Mann-Whitney test. Patients with oral submucous fibrosis had significantly increased TNF-α levels compared with controls.

Pro-inflammatory cytokines in patients with various kinds of acne treated with isotretinoin

IntroductionAcne vulgaris is the most frequently diagnosed dermatosis in patients aged between 11 and 30. It is believed that it affects about 80% of persons in this age group or even, taking into account lesions of low intensity, 100% of young people. The role of cytokines in the pathogenesis of acne is not fully known. The TLR2 receptors play a role in the aetiology of acne. Stimulation of TLR2 by Propionibacterium acnes makes the IL-8 and IL-12 concentrations increase.AimThe aim of this work was to determine IL-1β, IL-1α, IL-8 and TNF-α levels in patients’ sera used to test response to TLR2 stimulation. A decrease in the levels of the above mentioned cytokines together with a decrease in sebum production were defined as an indication of efficient treatment with isotretinoin.Material and methodsThe tests were performed in 155 patients treated for different clinical forms of acne with an oral isotretinoin preparation in the Dermatology Clinic of the Silesian Medical University in Katowice in 2009–2011 – I group and the patients treated with oral isotretinoin 2 and 5 years ago – II group. The control group consisted of 40 healthy individuals.ConclusionsMeasurements of IL-1α, IL-1β and TNF-α sera concentrations could be assessed in parallel to the improvement of the clinical condition and can constitute a good indication of the efficiency of the isotretinoin treatment.

Serum levels of tumor necrosis factor-α in patients with lichen planus

Background Lichen planus (LP) is an inflammatory skin disorder of unknown etiology. Tumor necrosis factor-a (TNF-α) is a multifunctional proinflamatory cytokine, which plays an important role not only in immunity and inflammation but also in the control of cell proliferation, differentiation, and apoptosis. Aims The present study was designed to investigate the serum level of TNF-α in patients with LP of different clinical presentations in comparison with healthy participants to study its possible role in the pathogenesis of LP. Patients and methods A total of 30 patients with different clinical variants of LP (16 male and 14 female patients) and 30 controls matched for age and sex were enrolled in this prospective case-control study after exclusion of those who had received treatment for LP or immunological treatment within the preceding 6 weeks, or those whose serum levels of TNF-α were suspected to be elevated because of other causes or diseases. The serum level of TNF-α was measured by means of the ELISA method in both patients and controls. Results The serum TNF-α level was significantly higher (P Conclusion The findings in our study support the role of TNF-α in the pathogenetical process of LP and suggest that markedly elevated serum TNF-α level might be an important indicator of the risk for developing oral lesions in patients with LP.

Perioperative Levels of Tumor Necrosis Factor-α Correlate With Outcomes in Children and Adults With Tetralogy of Fallot Undergoing Corrective Surgery

Previous studies reporting on tumor necrosis factor-α (TNF-α) as a marker of inflammatory response (IR) in patients with congenital heart disease were limited by small sample size and variability in diagnosis. We report perioperative changes in TNF-α levels and their correlation with preoperative factors and clinical outcomes in a large homogenous group of patients with tetralogy of Fallot (TOF) undergoing definitive repair at a tertiary care center. A total of 167 patients were divided into four groups on the basis of age. Group 1 included infants less than 1 year, group 2 included children between 1 and 12 years, group 3 included adolescents between 12 and 18 years, and group 4 included adults more than 18 years of age. Serum TNF-α levels were measured at three time points and correlated with perioperative variables. The baseline TNF-α level correlated with patients' nutritional status and degree of cyanosis in all four groups. The magnitude of IR in the postcardiopulmonary bypass (post-CPB) period as measured by TNF-α level was much higher and correlated more consistently with adverse clinical outcomes in the younger age group (groups 1 and 2). On multivariable analysis; age at operation, preoperative degree of hypoxemia and TNF-α levels were found to be independent predictors of clinical outcomes. We demonstrated a rise in serum TNF-α levels in patients with TOF undergoing definitive repair on CPB, which correlated with preoperative severity of cyanosis, nutritional status, and adverse clinical outcomes. The TNF-α levels may be monitored to identify cyanotic patients at an increased risk of exhibiting augmented IR to CPB.

Tumor Necrosis Factor-α Levels Early in Severe Acute Pancreatitis

One of the most important cytokines in pathogenesis of acute pancreatitis is tumor necrosis factor (TNF)-α. The aim of our study was to determine whether the plasma levels of TNF-α in patients with severe acute pancreatitis (SAP) on admission correlate with severity and outcome of SAP. Blood samples were obtained from 100 patients with SAP. Patients were divided into 2 groups according to severity: SAP group (n=69) and SAP-induced multiple organ dysfunction syndrome (MODS) group (n=31). Survivors were patients who were alive 90 days after taking the blood sample for cytokine measurement (53/100). Blood sample for cytokine measurement was drawn immediately after admission. TNF-α was measured by commercial ELISA test in plasma. When comparing SAP group with SAP-induced MODS group, we found that mean values of TNF-α on admission were 191.5-fold lower in group with SAP-induced MODS (P<0.01). When comparing nonsurvivors with survivors, we found that mean values of TNF-α on admission were 63-fold higher in survivors (P<0.01). At cut-off level of 7.95 pg/mL sensitivity was 83.9% and specificity was 72.5%. Patients with TNF-α level lower than 7.95 pg/mL had 3.2-fold higher probability to develop SAP with MODS. At cut-off level of 10.5 pg/mL sensitivity was 83% and specificity was 77.4%. Patients with TNF-α level higher than 10.5 pg/mL had 4.8-fold higher probability to survive. TNF-α is good predictor of severity and outcome. Low TNF-α concentration in patients with SAP predicts development of MODS and fatal outcome.

FRI0365 Metabolic syndrome and tumor necrosis factor in childhood-onset systemic lupus erythematosus

BackgroundPatients with systemic lupus erythematosus (SLE) have a higher incidence of metabolic syndrome (MetS). Among the possible causes we may mention the inflammation associated with increased levels of triglycerides and...

Serum levels of TNF-α in peripheral neuropathy patients and its correlation with nerve conduction velocity in type 2 diabetes mellitus

ObjectiveTo compare serum levels of TNF-α in patients of peripheral neuropathy and patients without neuropathy in type 2 diabetes mellitus. Material and methodsThis cross sectional study was conducted in diagnosed type 2 diabetes mellitus patients. They were divided in groups, Group I (n=37) with clinically detectable diabetic peripheral neuropathy of shorter duration and Group II (n=27) with clinically detectable diabetic peripheral neuropathy of longer duration. They were compared with patients without clinical neuropathy (n=22), clinical diagnosis was based on neuropathy symptom score (NSS) and neuropathy disability score (NDS) for signs. Blood samples were collected for baseline investigations and estimation of serum TNF-α. Nerve conduction velocity was measured in both upper and lower limbs. Median, Ulnar, Common Peroneal and Posterior Tibial nerves were selected for motor nerve conduction study and Median and Sural nerves were selected for sensory nerve conduction study. ResultsThe comparisons were done between various clinical and biochemical parameters in clinically detectable and undetectable peripheral neuropathy groups of type 2 diabetes mellitus. The study showed raised serum levels of TNF-α in peripheral neuropathy patients and significant correlation with nerve conduction velocity. ConclusionHigh level of TNF-α in serum of T2DM patients with neuropathy shows possible contribution in development of neuropathy. Due to its independent association this cytokine might be used as biomarker for diabetic peripheral neuropathy.

The influence of various regimens of treatment on the level of proinflammatory cytokine TNF-alpha in induced sputum in case of an exacerbation of chronic obstructive pulmonary disease (copd) in persons, who suffered from pulmonary tuberculosis

The influence of various regimens of treatment of the regional (in induced sputum) level of proinflammatory cytokine TNF-α in patients with chronic obstructive pulmonary disease (COPD), who have suffered from pulmonary tuberculosis (PT), has been studied. An advantage of using a combined treatment of COPD exacerbation by means of β2agonist and an anticholinergic preparation (berodual), and also doxofillin (aerofillin) for the purpose of correcting regional (endobronchial) imbalance of cytokine homeostasis is proved.

The relationship between adiponectin, NT-pro-BNP and left ventricular ejection fraction in non-cachectic patients with systolic heart failure: an observational study

NT-pro-brain natriuretic peptide (NT-proBNP) has been shown to be an accurate diagnostic marker in patients with heart failure (HF). Adiponectin (Adp) levels are increased in HF but its diagnostic value is still uncertain in these patients. The study was designed to investigate the possible association of these markers in non-cachectic patients with newly diagnosed systolic heart failure. Fifty-seven systolic HF patients and 20 matched controls were enrolled in an observational cross-sectional study. Physical and echocardiographic examinations were performed and serum Adp, NT-proBNP, tumor necrosis factor-alpha (TNF-α) levels were measured. Study variables were compared between the groups. Correlation analyses were done and the diagnostic validity of the markers was compared with ROC analysis. Adp and NT-proBNP levels were significantly higher in HF group (20.19±12.9 vs. 7.65±4.6 μg/mL; p<0.001 and 1051.74±606.2 vs. 222.53±65.6 pg/mL; p=0.002; respectively). TNF-α levels were similar between the groups (2.83±1.8 vs. 2.08±1.2 pg/mL; p=0.582). Correlation analysis showed significant association among Adp and NT-proBNP levels, (r=0.448; p<0.001), and left ventricular ejection fraction (LVEF) values (r=-0.466; p<0.001). The Adp and NT-proBNP showed comparable diagnostic performances with mean [95% confidence interval] areas under the curves of 0.857 (0.771-0.944) and 0.888 (0.815-0.960), respectively. There were significant correlation between Adp levels with NT-proBNP levels and LVEF values but no any association between Adp levels with body mass index values and TNF-α levels in patients with newly diagnosed systolic heart failure. The result may arouse suspicion about the hypothesis, which proposes that Adp levels simply reflects disease severity or cardiac cachexia in patients with HF.

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.

Selenium and Psoriasis

Psoriasis is a chronic, immune-mediated skin disease characterized by production of reactive oxygen species due to the activation of tumor necrosis factor alpha (TNF-α), which is thought to be an important factor in inducing and maintaining psoriatic lesions. As an external factor, ultraviolet B (UVB) radiation stimulates TNF-α production and secretion by human keratinocytes in vitro and can also reach the upper dermis and suppress endothelial cells in vitro. The selenium level in psoriatic patients has been found to be lower than expected, but studies on its role in the pathogenesis of the disease are scarce. Selenium can influence immune response by changing the expression of cytokines and their receptors or by making immune cells more resistant to oxidative stress. It was reported that selenium supplementation had inhibitory effects on TNF-α levels in patients with psoriasis, but the details are not completely elucidated. Selenium compounds are also known to prevent the in vitro release of UVB-induced proinflammatory cytokines by inhibition of mRNA in human keratinocytes. In the present review, the protective role of selenium in oxidative stress, lesions, and immune system regulation in patients with psoriasis is summarized.

Evidence for an association between tumor necrosis factor-alpha levels and lithium response

The role of inflammation in bipolar disorder has recently emerged as a potential pathophysiological mechanism. Tumor necrosis factor-alpha (TNF-α) modulation may represent a pathogenic molecular target and a biomarker for staging bipolar disorder. In this context, the possible association between lithium response and TNF-α level was examined. Sixty euthymic bipolar patients receiving lithium therapy were recruited for assessment of TNF-α level. The ALDA lithium response scale (LRS) was used to evaluate longitudinal lithium response in bipolar patients, using cut-offs of poor response, partial response and good response. TNF-α level was assessed using enzyme-linked immunosorbent assay. There was a significant increase in TNF-α level in patients with poor lithium response compared to those with good response, also after controlling for a range of potential confounders (adjusted effect size: 0.47, p=0.011). Partial response showed a directionally similar, but attenuated and statistically inconclusive association (adjusted effect size: 0.16, p=0.326). Assessment of response was retrospective and natural course cannot be separated easily from treatment response in an observational design. Selection of additional inflammatory markers could provide for a better understanding of underlying immune changes. This study strengthens the hypothesis that TNF-α level may mark or mediate lithium response, and that continuous immune imbalance in poor lithium responders may occasion treatment resistance. Further investigation of immune alterations in treatment-resistant bipolar patients may be productive.

Serum lipocalin-2 levels are increased in patients with psoriasis

The protein lipocalin (LCN)-2 is known to be related to insulin resistance, obesity and atherosclerotic diseases. Psoriasis is an inflammatory skin disease related to metabolic syndrome. The aim of this study was to examine the relationship between serum LCN2 levels and indicators for metabolic syndrome and inflammatory cytokine levels in patients with psoriasis. Serum LCN2 levels were measured in patients with psoriasis, atopic dermatitis (AD) or bullous pemphigoid (BP), and compared with those of healthy controls. Serum LCN2 levels were also compared with several indicators for metabolic syndrome, and with serum levels of interleukin (IL)-6 and tumour necrosis factor (TNF)-α, two markers of inflammation. Serum LCN2 levels in patients with psoriasis were significantly higher than those of healthy controls, but there was no significant correlation between serum LCN2 and body mass index. Serum LCN2 levels also correlated with serum IL-6 and TNF-α levels in patients with psoriasis. Serum LCN2 levels are a general indicator for increased inflammation in the patients with psoriasis.

Evaluation of Serum TNF-α and TGF-β in Patients with Oral Lichen Planus.

Background and aims The role of cytokines in the immunopathogenesis of oral lichen planus (OLP) has received much attention. The aim of this study was to evaluate the serum levels of TNF-α and TGF-β in patients with OLP in an Iranian population. Materials and methods Thirty-two patients with OLP and 32 age-matched healthy volunteers as a control group were included in this study. Serum tests including TNF-α and TGF-β was performed in both groups. Data analysis was performed using descriptive statistics and Mann–Whitney U test using SPSS software version 16.0. Results The mean of TNF-α in study and control groups were 157 ± 115 pg/ml and 14 ± 10 pg/ml, respectively. The difference between the two means was statistically significant (P < 0.001). Moreover, the mean of TGF-β in study and control groups were 155 ± 26 pg/ml and 175 ± 57 pg/ml, respectively. The difference between the two means was statistically significant (P = 0.03). Conclusion According to the results of the present study, there was a significant decrease in the serum levels of TGF-β and a significant increase in the serum levels of TNF-α in patients with oral lichen planus. The increase in TNF-α serum levels in patients with OLP explains the inflammatory process in the course of the disease.

Single molecule measurements of tumor necrosis factor α and interleukin-6 in the plasma of patients with Crohn's disease

The quantitative measurement of inflammatory cytokines in blood has been limited by insufficient sensitivity of conventional immunoassays. This limitation has prevented the widespread clinical monitoring of cytokine concentrations in chronic inflammatory diseases. We applied a sensitive, single molecule detection technology to measure TNF-α and IL-6 in the plasma of patients with Crohn's disease (CD), before and after treatment with anti-TNF-α therapy. Plasma from 17 patients with CD was collected prior to initiation of anti-TNF-α therapy, and the Crohn's disease activity index (CDAI) was determined for each patient. A sub-set of these patients returned for follow up 12 weeks after treatment started. Plasma from age- and gender-matched controls was also collected. Digital ELISAs were developed for TNF-α and IL-6, and the plasma concentrations of these cytokines were determined using digital ELISA. The limits of detection of the TNF-α and IL-6 digital ELISAs were 0.008 pg/mL and 0.006 pg/mL, respectively. Both cytokines were detected in all samples using digital ELISA and the concentrations of TNF-α and IL-6 in the plasma of patients with CD were (3.6 ± 0.9) pg/mL and (10.9 ± 11.2) pg/mL, respectively. TNF-α levels in patients and healthy controls were not significantly different, but the IL-6 levels in plasma were significantly elevated in patients compared to controls. After therapy, the mean reduction of the concentrations of free TNF-α and IL-6 were 46% and 58%, respectively. Digital ELISA provided the first quantitative measurements of TNF-α and IL-6 concentrations in the plasma of all patients in a population with CD. The changes in cytokine concentrations after therapy—which could be quantified because of the high sensitivity of digital ELISA—could be used for monitoring therapeutic efficacy.

Serum TNF-α levels reflect the clinical severity of envenomation following a Hemiscorpius lepturus sting

Hemiscorpius lepturus (H. lepturus), found in south-western areas of Iran and south of Iraq, is considered to be the most dangerous scorpion in the region, and poses a significant risk to the health of the indigenous population due to the unique, clinical manifestations associated with its sting.. In the present study, 36 patients from the Khuzestan province in the southwest of Iran, displaying varying degrees of envenomation following an H. lepturus scorpion sting, were admitted to hospital. Serum levels of interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-8 (IL-8) and tumour necrosis factor-α (TNF-α) were measured using double-ligand, enzyme-linked, immunosorbent assay (ELISA) kits, and were compared with 30 healthy controls and ten age-matched patients stung by the Mesobuthus eupeus (M. eupeus) scorpion, a less dangerous species that produces primarily neurotoxic manifestations. Blood samples from M. eupeus and H. lepturus victims were taken on admission, and from H. lepturus-stung patients six hours after serotherapy with multivalent anti-venom. When compared to healthy volunteers, with the exception of TNF-α, significantly higher serum cytokine levels were measured in patients following M. eupeus envenomation. However, all three groups of H. lepturus-stung patients showed significantly, and in a severity-related manner, higher mean values for all the interleukins that were measured, including TNF-α, when compared with M. eupeus-stung cases. Six hours after serotherapy, there was a greater reduction in cytokine and TNF-α levels in patients classed as having mild symptoms, in comparison with patients classed as having moderate to severe symptoms. The results of the present study suggest that, unlike M. eupeus, the toxic manifestations observed following being stung by H. lepturus are associated with increased serum TNF-α levels and correlate positively with the clinical severity of the symptoms. Furthermore, serotherapy is only effective when administered to mild cases of H. lepturus scorpion envenomation.

TNFα promoter polymorphism is a risk factor for susceptibility in hepatocellular carcinoma in Korean population

Background The underlying genetic factors for the development and progression of hepatocellular carcinoma (HCC) are largely unknown. TNFα is a well characterized inflammatory mediator and is implicated in the development of HCC. We investigated TNFα polymorphisms for association with HCC. Methods The study population consisted of 227 HCC patients and 365 age and sex matched Korean controls. TNFα polymorphisms (G-238A, C-857T, and C-863A) were genotyped using pyrosequencing analysis. TNFα levels in patients with HCC were determined by enzyme linked immunosorbent assay (ELISA). Logistic regression analysis was used to determine the association with HCC and haplotype was calculated using EH program. Results Of three TNFα polymorphisms investigated in our study, C-863A did not correlate with HCC. However, both G-238A and C-857T were found to be significantly associated with HCC. TNFα −238A allele was more frequent in HCC patients than in control [ P = 0.012; odds ratio (OR), 1.89; 95% confidence interval (CI), 1.14–3.13]. TNFα −857T was significantly associated with HCC patients ( P = 0.001; OR, 1.63; 95% CI, 1.21–2.19). Haplotype analysis revealed that the GTC haplotype (G-238A, C-857T, C-863A) was a risk marker for HCC ( P = 0.0021). Serum TNFα level was significantly increased in HCC patients with CT + TT genotype for TNFα −857 ( P = 0.018). Conclusion Our data imply that TNFα G-238A and C-857T, not C-863A, polymorphisms may confer different susceptibilities to the development of HCC with TNFα −238A and −857T alleles playing as risk factors.