Serum TNF-alpha Levels Research Articles

The impact of different biocompatible coated cardiopulmonary bypass circuits on inflammatory response and oxidative stress

This study was to compare the impact of different biocompatible coated circuits on inflammatory response and oxidative stress induced during cardiopulmonary bypass (CPB). Seventy-eight patients undergoing elective coronary artery bypass grafting (CABG) with CPB were randomly assigned to five groups with different biocompatible coated circuits: Trillium, Bioline, Phosphorylcholine, Polymethoxyethyl acrylate (PMEA), and the uncoated control group. Blood was drawn at three different time points: before CPB, 6 and 72 hours post CPB. Unlike the Trillium group, serum levels of TNF-alpha in the Bioline and Phosphorylcholine groups significantly increased only at 72 hours post CPB (p < 0.05). Serum levels of IL-6 significantly increased at 6 and 72 hours post CPB in all groups (p < 0.01). The Trillium group showed a significant increase of IL-10 compared to the control group at 72 hours post CPB (p < 0.05). Serum levels of NOx in the Phosphorylcholine group significantly decreased at 6 hours post CPB compared to baseline (p < 0.05). Both the Bioline and Phosphorylcholine groups showed statistical decreases in serum NOx levels compared with other groups at 6 hours post CPB (p < 0.05). A significant difference in NOx levels between the Bioline and the control group was also observed at 72 hours post CPB. Myeloperoxidase levels were significantly elevated at 6 and 72 hours post CPB in all groups (p < 0.05). Inflammatory response and oxidative stress are elevated during CABG with CPB. Heparin-coated and the Phosphorylcholine-coated circuits induce less inflammatory responses and oxidative stress compared to other circuits.

TNF-alpha in CRPS and ‘normal’ trauma – Significant differences between tissue and serum

Posttraumatic TNF-alpha signaling may be one of the factors responsible for pain and hyperalgesia in complex regional pain syndromes (CRPS). In order to further specify the role of TNF-alpha we investigated tissue (skin) and serum concentrations in three different patient groups: patients with osteoarthritis and planned surgery, with acute traumatic upper limb bone fracture waiting for surgery, and with CRPS I. Thirty patients (10 in each group) were recruited. Mean CRPS duration was 36.1±8.1weeks (range 8–90weeks). Skin punch biopsies were taken at the beginning of the surgery in osteoarthritis and fracture patients and from the affected side in CRPS patients. Blood samples were taken before the respective procedures. Skin and serum TNF-alpha levels were quantified by ELISA. Compared to patients with osteoarthritis, skin TNF-alpha was significantly elevated in CRPS (p<0.001) and fracture patients (p<0.04). Skin TNF-alpha in CRPS patients was higher than in patients with acute bone fracture (p<0.02). In contrast, serum TNF-alpha values were the same in osteoarthritis and CRPS, and lower in fracture patients (p<0.03). Our results indicate a local but not systemic increase of TNF-alpha in CRPS patients. This increase persists for months after limb trauma and may offer the opportunity for targeted treatment.

Influence of separate components of Yiqi Qingwen Jiedu mixture to serum inflammatory cytokines of mice infected with influenza virus FM1

To observe dynamically the influence of 4 parts of forming of YQJM (Yiqi Qingwen Jiedu mixture) (referred to as 4 parts of forming) including the methods of relieving superficies with acrid-warm, relieving superficies with acrid-cold, clearing away heat and poison and replenishing Qi to serum inflammatory cytokines of the model mice infected with influenza virus. And to discuss the mechanism of 4 parts of forming of anti-influenza immune injury and restoration. Made the model with the mice infected by FM1 influenza infection, used ELISA method, observed dynamically the influence of four methods on the level of serum TNF-alpha, IL-6, IL-1, IFN-gamma and IL-10 inflammatory cytokines. The level of serum TNF-alpha, IL-6, IL-1 and IFN-gamma of mice infected by FM1 significantly increased, while the level of serum IL-10 was lower than the control group on the first day of infection, but the levels were much higher than the control group in 3 to 7 days after infection. The method of relieving superficies with acrid-warm significantly decreased the levels of serum TNF-alpha, IL-6, IL-1 on the 5th day after infection, and significantly increased the levels of serum IL-10 on the 3rd and 7th day after infection. The method could inhibit the immune injury to some extent. The method of relieving superficies with acrid-cold decreased the levels of serum TNF-alpha and IL-6 in 5 to 7 days after infection, increased the level of serum IL-1 on the 3rd day after infection, decreased the level of serum IL-1 on the 7th day after infection, significantly increased the levels of serum IL-10 in 1 to 3 days and on the 7th day after infection. The method could be against inflammatory injury. The method of clearing away heat and poison decreased the levels of serum TNF-alpha, IL-6, IL-1 after infection in 3 to 5 days and on the 7th day, and significantly increased IL-10 each time after infection. It exhibited more strong inhibition of inflammatory injury and repair. The method of replenishing Qi significantly decreased the level of serum TNF-alpha and IL-6 in 3 to 7 days after infection, increased the level of serum IL-1 the first 3 days after infection, but decreased the level of serum IL-1 on the 7th day after infection. The method significantly increased the levels of serum IL-10 in 3 to 5 days and on the 7th day. It exhibited inhibition of inflammatory injury. The method of relieving superficies with acrid-cold significantly increased the levels of serum IFN-gamma in 3 days after infection, while the methods of clearing away heat and poison and replenishing Qi significantly increased the levels of serum IFN-gamma in 1 to 3 days and on the 7th day. They exhibited anti-virus and suppression of the immune injury. Chinese medicine could correct the imbalance of inflammatory cytokines and be against injury, promote injury restoration, and protect the body.

The Values of Serum and Ascetic Fluid Tumor Necrosis Factor-Alpha (TNF- alpha), TNF-Receptor 1 and C-Reactive Protein (CRP) in Patients with Cirrhotic Ascites

Spontaneous bacterial peritonitis (SBP) is defined as an infection of initially sterile ascitic fluid (AF) without a detectable, surgically treatable source of infection. It is a frequent and severe complication of cirrhotic ascites. Because of the high morbidity and mortality of SBP, the rapid and accurate diagnosis is required. Aim: The present study aimed to measure the levels of tumor necrosis factor-alpha (TNF-alpha), tumor necrosis factor receptor (TNF-r p55) and C-reactive protein (CRP) in both ascetic fluid and serum of patients with sterile and infected cirrhotic ascites to show their diagnostic values as compared to ascitic fluid culture and polymorphnuclear leukocyte (PMN) count. Patients and methods: TNF-alpha, TNF-r p55 and CRP were measured in both ascetic fluid and serum of 20 patients with spontaneous bacterial peritonitis (SBP), in addition to 22 patients with sterile cirrhotic ascites. Results: The results of clinical examination showed a significant difference as regard abdominal pain, fever jaundice, upper GIT bleedings, encephalopathy and Sclerotherapy among both groups. The serum levels of CRP and TNF-alpha were significantly higher in patients with SBP as comparing to patients have sterile ascites, but TNF-r p55 serum level showed no significant difference. On evaluation of ascetic fluid parameters, total leucocytic count (TLC), plymorphnuclear (PMN) count , CRP, TNF-alpha, TNF-r p55 are significantly higher in SBP patient group than group of sterile ascites. Sensitivity and specificity of ascitic fluid PMN (cut-off value >250 cells/ mm3) in discriminating infected ascites from sterile ascites were 70% and 86.4%, respectively. Sensitivity and specificity of ascitic fluid CRP (cut-off value >1.0 mg/dL) in discriminating infected ascites from sterile ascites were 85% and 72.7%, respectively. Sensitivity and specificity of ascitic fluid TNF-alpha (cut off value >12 pg/ml) in discriminating infected ascites from sterile ascites were 80% and 63.6%, respectively. Sensitivity and specificity of TNF-r p55 (cut-off value >6.2 pg/ml) in discriminating infected ascites from sterile ascites were 75% and 68.2%, respectively. Conclusion: We concluded that, the elevated serum and ascetic fluid levels of CRP, TNF-alpha and TNF-r may suggest their role in the pathogenesis of ascetic fluid infection and their higher sensitivity and specificity make them to be good discriminators in ascetic fluid infection (especially a cheap and easy ascitic fluid CRP levels). Thus may help in rapid diagnosis and early start empirical antibiotic therapy without waiting the culture results.

The Values of Serum and Ascetic Fluid Tumor Necrosis Factor-Alpha (TNF- alpha), TNF-Receptor 1 and C-Reactive Protein (CRP) in Patients with Cirrhotic Ascites

Spontaneous bacterial peritonitis (SBP) is defined as an infection of initially sterile ascitic fluid (AF) without a detectable, surgically treatable source of infection. It is a frequent and severe complication of cirrhotic ascites. Because of the high morbidity and mortality of SBP, the rapid and accurate diagnosis is required. Aim: The present study aimed to measure the levels of tumor necrosis factor-alpha (TNF-alpha), tumor necrosis factor receptor (TNF-r p55) and C-reactive protein (CRP) in both ascetic fluid and serum of patients with sterile and infected cirrhotic ascites to show their diagnostic values as compared to ascitic fluid culture and polymorphnuclear leukocyte (PMN) count. Patients and methods: TNF-alpha, TNF-r p55 and CRP were measured in both ascetic fluid and serum of 20 patients with spontaneous bacterial peritonitis (SBP), in addition to 22 patients with sterile cirrhotic ascites. Results: The results of clinical examination showed a significant difference as regard abdominal pain, fever jaundice, upper GIT bleedings, encephalopathy and Sclerotherapy among both groups. The serum levels of CRP and TNF-alpha were significantly higher in patients with SBP as comparing to patients have sterile ascites, but TNF-r p55 serum level showed no significant difference. On evaluation of ascetic fluid parameters, total leucocytic count (TLC), plymorphnuclear (PMN) count , CRP, TNF-alpha, TNF-r p55 are significantly higher in SBP patient group than group of sterile ascites. Sensitivity and specificity of ascitic fluid PMN (cut-off value >250 cells/ mm3) in discriminating infected ascites from sterile ascites were 70% and 86.4%, respectively. Sensitivity and specificity of ascitic fluid CRP (cut-off value >1.0 mg/dL) in discriminating infected ascites from sterile ascites were 85% and 72.7%, respectively. Sensitivity and specificity of ascitic fluid TNF-alpha (cut off value >12 pg/ml) in discriminating infected ascites from sterile ascites were 80% and 63.6%, respectively. Sensitivity and specificity of TNF-r p55 (cut-off value >6.2 pg/ml) in discriminating infected ascites from sterile ascites were 75% and 68.2%, respectively. Conclusion: We concluded that, the elevated serum and ascetic fluid levels of CRP, TNF-alpha and TNF-r may suggest their role in the pathogenesis of ascetic fluid infection and their higher sensitivity and specificity make them to be good discriminators in ascetic fluid infection (especially a cheap and easy ascitic fluid CRP levels). Thus may help in rapid diagnosis and early start empirical antibiotic therapy without waiting the culture results.

TUMOR NECROSIS FACTOR IS NOT ASSOCIATED WITH INTESTINAL ISCHEMIA/REPERFUSION-INDUCED LUNG INFLAMMATION

Intestinal ischemia-reperfusion (I/R) injury may cause acute systemic and lung inflammation. Here, we revisited the role of TNF-alpha in an intestinal I/R model in mice, showing that this cytokine is not required for the local and remote inflammatory response upon intestinal I/R injury using neutralizing TNF-alpha antibodies and TNF ligand-deficient mice. We demonstrate increased neutrophil recruitment in the lung as assessed by myeloperoxidase activity and augmented IL-6, granulocyte colony-stimulating factor, and KC levels, whereas TNF-alpha levels in serum were not increased and only minimally elevated in intestine and lung upon intestinal I/R injury. Importantly, TNF-alpha antibody neutralization neither diminished neutrophil recruitment nor any of the cytokines and chemokines evaluated. In addition, the inflammatory response was not abrogated in TNF and TNF receptors 1 and 2-deficient mice. However, in view of the damage on the intestinal barrier upon intestinal I/R with systemic bacterial translocation, we asked whether Toll-like receptor (TLR) activation is driving the inflammatory response. In fact, the inflammatory lung response is dramatically reduced in TLR2/4-deficient mice, confirming an important role of TLR receptor signaling causing the inflammatory lung response. In conclusion, endogenous TNF-alpha is not or minimally elevated and plays no role as a mediator for the inflammatory response upon ischemic tissue injury. By contrast, TLR2/4 signaling induces an orchestrated cytokine/chemokine response leading to local and remote pulmonary inflammation, and therefore disruption of TLR signaling may represent an alternative therapeutic target.

Suppression of tumour necrosis factor-α by Schizonepeta tenuifolia water extract via inhibition of IκBα degradation and Jun N-terminal kinase/stress-activated protein kinase activation

The anti-inflammatory effects of an aqueous extract of Schizonepeta tenuifolia on lipopolysaccharide (LPS)-induced tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in vivo and in vitro have been investigated. C57BL/6 mice were orally administered phosphate-buffered saline (control) or S. tenuifolia water extract (50, 200, 500 or 1000 mg/kg) for 10 days before intraperitoneal administration of LPS (1.3 mg/kg). Blood samples were obtained 1 h after LPS challenge, followed by determination of TNF-alpha and IL-6 levels. Peritoneal macrophages from thioglycollate-injected mice were obtained and stimulated with LPS and S. tenuifolia water extract for viability assay, cytokine analysis, real-time RT PCR and Western blotting. Oral administration of S. tenuifolia water extract to mice significantly reduced LPS-induced serum levels of TNF-alpha, but not IL-6. When peritoneal macrophages were treated in vitro with S. tenuifolia water extract, the inhibition of LPS-induced TNF-alpha was more pronounced than that of IL-6 at the level of secreted protein and mRNA. S. tenuifolia water extract reduced the degradation of IkappaBalpha and the nuclear relocation of p65 NF-kappaB, but the phosphorylation of IkappaBalpha was not affected. Inhibition of c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) by S. tenuifolia water extract led secondarily to the inhibition of phospho-c-Jun and phospho-ATF-2. These results indicated that the downregulation of TNF-alpha by S. tenuifolia water extract may have involved the inhibition of both IkappaBalpha degradation and activation of c-Jun and ATF-2 involving suppression of JNK/SAPK.

Whether co-administration of garlic has negative influence on &lt;i&gt;Scutellaria baicalensis georgi&lt;/i&gt; in treating models rats with pelvic inflammation?

The research was to explore whether co-administration of garlic has negative influence on Scutellaria baicalensis Georgi (Scutellaria baicalensis) in treating models rats with pelvic inflammation. Twelve model rats were randomized into a Scutellaria baicalensis group and a Scutellaria baicalensis+garlic group with six in each group for pharmacokinetic analysis. Twenty-four rats were randomized into a Scutellaria baicalensis group, a Scutellaria baicalensis+garlic group, a model control group and a normal control group with six rats in each group for detecting the serum levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin 6 (IL-6) with enzyme-linked immunosorbent assay (ELISA). The results showed that in the Scutellaria baicalensis group, the maximum concentration (C(max)) of baicalin, area under the plasma concentration-time curve (AUC) and the time to C(max) (T(max)) were significantly higher and apparent clearance (CL/F) were significantly lower than those of Scutellaria baicalensis+garlic group. The serum levels of TNF-alpha and IL-6 in the Scutellaria baicalensis group were both significantly lower than Scutellaria baicalensis+garlic group. It was then concluded that garlic not only had negative influence on the absorption of active compounds in Scutellaria baicalensis, but decreased the curative effects of Scutellaria baicalensis in treating model rats with pelvic inflammation. Garlic should not be co-administered with Scutellaria baicalensis.

Effects of Qingyi Huaji decoction on serum levels of interleukin-6, interleukin-8 and tumor necrosis factor-α in nude mice bearing pancreatic tumors

To investigate the effects of Qingyi Huaji (QYHJ) decoction, a compound traditional Chinese herbal medicine, on tumor inhibition rate and serum levels of interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-alpha) in nude mice with transplanted tumors of human pancreatic cancer. The tumor-bearing mice model was established by subcutaneously inoculating with xenografts of pancreatic cancer into the right armpit of 40 BALB/c nude mice. After successful modeling, the mice were randomly divided into untreated group (Arabic gum), capecitabine group, low-dose QYHJ decoction group (36 g/kg) and high-dose QYHJ decoction group (72 g/kg), with 10 mice in each group. Citrate buffer solution (containing 5% Arabic gum), capecitabine suspension and QYHJ decoction were administered to four groups by gavage respectively. After 5-week treatment, the concentrations of serum IL-6, IL-8 and TNF-alpha were examined by enzyme-linked immunosorbent assay (ELISA) using blood sample from eye socket. Then the mice were euthanized by cervical dislocation. Tumor weight and the tumor inhibition rate were calculated. Tumor weight in the low-dose QYHJ decoction group decreased significantly as compared with the untreated group (P<0.05). Serum levels of IL-6 and TNF-alpha in low- and high-dose QYHJ groups were extremely significantly lower than those in the untreated group (P<0.01). Serum level of IL-8 in the low-dose QYHJ group was significantly lower than that in the untreated group (P<0.05). Correlation analysis showed that transplanted tumor weight of the mice was linearly positively correlated with serum levels of IL-6, IL-8 or TNF-alpha (P<0.01). Conventional dose of QYHJ decoction is effective in suppressing pancreatic carcinoma in nude mice. The mechanism may be related to down-regulation of serum cytokines such as IL-6, IL-8 and TNF-alpha.

Predictors of response to extracorporeal photopheresis in advanced mycosis fungoides and Sézary syndrome

Extracorporeal photopheresis (ECP) has been utilized for more than 20 years to treat cutaneous T-cell lymphoma (CTCL), but a clinical response can take up to 9 months to manifest. This study was undertaken to determine whether clinical features, laboratory values, cytokine levels, or gene expression levels of tumor markers are useful to predict the subsequent response to ECP in CTCL patients with blood involvement. Twenty-one patients with CTCL treated with ECP as monotherapy for at least 6 months were retrospectively identified. Laboratory and clinical data and blood obtained at baseline, 3, and 6 months of treatment were used for analysis. In pretreatment blood specimens, a lower percentage of Sézary cells and a higher absolute eosinophil count were associated with a favorable clinical response. Clinical evidence of an early response after 3 months of ECP did not reliably predict a favorable response at 6 months or beyond. Comparison of cytokines, gene transcripts, and other laboratory measures of disease did not correlate with the subsequent clinical response, although lactate dehydrogenase levels tended to decrease progressively in ECP-responsive cases and increase progressively in ECP-non-responsive cases. Additionally, serum levels of TNF-alpha significantly increased from baseline to 6 months of ECP, but was not found to correlate with the clinical response. Although we found that increased eosinophils and decreased percentage of Sézary cells were associated with a favorable clinical response to ECP, we were not able to identify the predictors of ECP response within the first 3 months of treatment.

Tumor necrosis factor-&amp;alpha; serum levels in healthy smokers and nonsmokers

Tobacco smoking is the most important risk factor for chronic obstructive pulmonary disease (COPD) development. Inhaled cigarette smoke can induce tumor necrosis factor-alpha (TNF-alpha) production by alveolar macrophages, which in turn may enhance the production of metalloproteinases (MMPs). MMPs have been involved in mediating airway inflammation and lung destruction. We aimed to measure the TNF-alpha serum levels in healthy heavy smokers and healthy nonsmokers to determine the dose-response relationship based on the cigarette smoke exposure. We included in our study 43 healthy heavy smokers and 19 healthy nonsmokers (the control group). The smokers group was classified as less than one pack, one pack, and more than one pack per day. A clinical and paraclinical evaluation was performed in both groups, without any evidence of infection or COPD. The serum levels of TNF-alpha were assessed by ELISA. The TNF-alpha serum levels were significantly higher for the group of smokers compared to the group of nonsmokers (P < 0.004). We also noticed an increased TNF-alpha concentration in the serum of smokers with more than one pack per day compared with those with less than one pack per day (P < 0.03). There was a positive correlation between the serum level of TNF-alpha and tobacco smoke exposure. The high levels of TNF-alpha in the serum of smokers suggest an imbalance between the proinflammatory and anti-inflammatory factors as a result of tobacco smoke exposure. The concentration of TNF-alpha is elevated in the serum of healthy heavy smokers in a cigarette dose-dependent manner. We speculate that the serum level of TNF-alpha might be a useful biomarker for the selection of heavy smokers with a high risk of developing smoke induced pulmonary diseases.

Change of early serum TNF-alpha and IL-6 levels in acute cerebral infarction and its significances

To investigate the change of early serum TNF-alpha and IL-6 levels in acute cerebral infarction and its significances. Serum TNF-alpha and IL-6 levels in 30 health subjects and 35 patients with acute cerebral infarction (ACI) within 6 hours of onset were measured by enzyme linked immunosorbent assay (ELISA); neurological deficits scores (NDS) in all cases were determined, and Spearman test was used for correlation. The serum levels of TNF-alpha and IL-6 in ACI group were markedly higher than those in health subjects and there was a positive correlation of TNF-alpha and IL-6 levels with 6 h NDS (rs=0.89 and 0.93, P<0.001) and with NDS progression (rs=0.90 and 0.91, P<0.001). Early serum TNF-alpha and IL-6 levels in progressive cerebral infarction (PCI) group were evidently higher than those in stable cerebral infarction (SCI)[(49.56+/-12.12) pg/L compared with (24.30+/-7.4) ng/L and (39.76+/-7.88) ng/L compared with (20.78+/-6.28) ng/L, respectively, P<0.01)]. The early serum levels of TNF-alpha and IL-6 in ACI markedly increase and are closely correlated with disease severity; which may be of value in PCI risk evaluation.

TNFA Gene Promoter Polymorphisms and Susceptibility to Recurrent Pregnancy Loss in Italian Women

The aim of this study was to investigate the relationship between serum tumor necrosis factor alpha (TNF-alpha) levels and single nucleotide polymorphisms (SNPs) of the TNFA gene promoter (-376G/A, -308G/A, and -238G/A) in 100 Italian Caucasian women with reproductive failure and 100 fertile controls. Molecular analysis of TNFA SNPs showed higher frequencies of -238G allele (P = .028) as well as the presence of a 3-loci haplotype (-376G/-308A/-238G; P = .020) in fertile controls compared to women with reproductive failure. Serum TNF-alpha levels were higher in study women compared to controls ( P = .001). Of interest, the TNFA -376G/-308A/-238G haplotype was an independent predictor of low TNF-alpha levels (P = .021) and miscarriage (P = .023) in multivariate analyses. In conclusion, these findings support the concept of an association of TNFA polymorphisms and recurrent pregnancy loss (RPL). In particular, the TNFA -238GG variant and the TNFA -376G/-308A/-238G haplotype might represent protective factors, probably through reduced TNF-alpha production and/or mediated responses.

Increased serum levels of brain-derived neurotropic factor during migraine attacks: a pilot study.

There is a growing body of evidence implicating inflammatory cytokines and brain-derived neurotropic factor (BDNF) in the generation of migraine pain. No previous study evaluated BNDF levels during migraine attacks and there are conflicting results regarding tumor necrosis factor-alpha (TNF-alpha) serum levels. This study compared serum levels of TNF-alpha, soluble TNF receptors 1 and 2 (sTNF-R1 and sTNF-R2), and BDNF during migraine attacks and in headache-free periods. Nine patients with episodic migraine were clinically evaluated during a migraine attack and in a headache-free period. Blood sample of each patient in both occasions was collected and all serum was submitted to TNF-alpha, sTNF-R1, sTNF-R2, and BDNF determination by ELISA. There was no significant difference in the serum levels of TNF-alpha, sTNF-R1 and sTNF-R2 in migraine attack period and headache-free period. BDNF serum levels were significantly higher during migraine attack than in pain-free period. This is the first report showing that BDNF serum levels increase during migraine attack. This reinforces the view that BDNF may be implicated in the physiopathology of migraine.

Experiment study about effect of Yinqiao detoxifcation oral liquid on natural killercells and TNF-α, TGF-β1 of BALB/C nude mouse infected by influenza virus

To explore the effect of Yinqiao detoxifcation oral liquid on activity of natural killer cells (NK) and serum content of TNF-alpha, TGF-beta1 of BALB/C nude mouse infected by influenza virus. To establish infected mice model by FM1 followed by intragastric administration of Yinqiao detoxifcation oral liquid for treatment. LDH method was used to observe NK cells. ELISA method was used to determine the levels of TNF-alpha, TGF-beta1, in serum on 1st, 3rd, 5th, 7th days after infection. Comparing to the normal group, the NK activity of the model group was significantly increased on 1 dpi (day post infection), and significantly decreased on 3, 5, 7 dpi. The NK activity of three dosage groups (5, 10, 20 g x kg(-1)) of Yinqiao detoxifcation oral liquid were respectively higher than that of the model on 3, 5, 7 dpi, especially with high dose (P < 0.01). The serum level of TNF-alpha and TGF-beta1 of model group is higher than that of normal group on 1, 3, 5, 7 d. Compared with model group, the serum level of Yinqiao detoxifcation oral liquid groups (5, 10, 20 g x kg(-1)) were decreased in different degree on every time point, especially the serum level of the higher dose of Yinqiao detoxifcation oral liquid decreased on 3 dpi (P < 0.05), Yinqiao detoxifcation oral liquid inhibit the serum level of TGF-beta1 in a dose-dependent manner. Yinqiao detoxifcation oral liquid could enhance the activity of NK cell and decrease the serum level of TNF-alpha and TGF-beta1 of the mice infected by influenza virus.

Genetic polymorphisms in TNFgenes and tuberculosis in North Indians

BackgroundPulmonary tuberculosis, the most common clinical form of mycobacterial diseases, is a granulomatous disease of the lungs caused by Mycobaterium tuberculosis. A number of genes have been identified in studies of diverse origins to be important in tuberculosis. Of these, both tumor necrosis factor α (TNF-α) and lymphotoxin α (LT-α) play important immunoregulatory roles.MethodsTo investigate the association of TNF polymorphisms with tuberculosis in the Asian Indians, we genotyped five potentially functional promoter polymorphisms in the TNFA gene and a LTA_NcoI polymorphism (+252 position) of the LTA gene in a clinically well-defined cohort of North-Indian patients with tuberculosis (N = 185) and their regional controls (N = 155). Serum TNF-α (sTNF-α) levels were measured and correlated with genotypes and haplotypes.ResultsThe comparison of the allele frequencies for the various loci investigated revealed no significant differences between the tuberculosis patients and controls. Also, when the patients were sub-grouped into minimal, moderately advanced and far advanced disease on the basis of chest radiographs, TST and the presence/absence of cavitary lesions, none of the polymorphisms showed a significant association with any of the patient sub-groups. Although a significant difference was observed in the serum TNF-α levels in the patients and the controls, none of the investigated polymorphisms were found to affect the sTNF-α levels. Interestingly, it was observed that patients with minimal severity were associated with lower log sTNF-α levels when compared to the patients with moderately advanced and far advanced severity. However, none of these differences were found to be statistically significant. Furthermore, when haplotypes were analyzed, no significant difference was observed.ConclusionsThus, our findings exclude the TNF genes as major risk factor for tuberculosis in the North Indians.

Eicosapentanoic acid prolongs survival and attenuates inflammatory response in an experimental model of lethal trauma

In an attempt to define the efficacy of intravenously administered n-3 polyunsaturated fatty acids (PUFAs) in an animal model of lethal trauma following femur fracture, an intravenous solution of eicosapentanoic acid (EPA) - one n-3 PUFA - was administered in 25 rabbits; 13 were controls and 12 were treated with EPA 30 min after fracture. Vital signs were recorded and serum concentrations of tumor necrosis factor-alpha (TNFalpha) and respiratory burst of neutrophils were assessed. Survival of controls was 7.7% and of animals treated with EPA 50% (log-rank: 5.162; p: 0.023). Vital signs of both groups did not differ. Oxidative burst of neutrophils was greater among EPA-treated animals compared with controls at 48 h (p: 0.010). Serum levels of TNFalpha of the former group were decreased compared with the latter at 48 h (p: 0.019). Bacterial growth of enterobacteriaceae from liver and spleen after death or euthanasia was lower among EPA-treated rabbits than controls. These results suggest that EPA possesses considerable immunomodulatory activities improving survival in a model of lethal trauma. Restoration of oxidative burst conferring efficient phagocytosis of evading bacteria seems the most probable mechanism of action.

Proinflammatory cytokine levels in fibromyalgia patients are independent of body mass index

BackgroundFibromyalgia (FM) is characterized by chronic, widespread muscular pain and tenderness and is generally associated with other somatic and psychological symptoms. Further, circulatory levels of proinflammatory cytokines (IL-1β, TNF-α, and IL-6) may be altered in FM patients, possibly in association with their symptoms. Recently, rises in BMI have been suggested to contribute to increased circulating levels of proinflammatory cytokines in FM patients. Our aim was to measure the circulatory levels of proinflammatory cytokines to determine the influence of BMI on these levels in FM patients and healthy volunteers (HVs). In Spanish FM patients (n = 64) and HVs (n = 25), we measured BMI and serum concentrations of proinflammatory cytokines by capture ELISA.FindingsThere were significant differences in BMI levels between FM patients (26.40 ± 4.46) and HVs (23.64 ± 3.45) and significant increase in IL-6 in FM patients (16.28 ± 8.13 vs 0.92 ± 0.32 pg/ml) (P < 0.001). IL-1β and TNF-α decreased in FM patients compared with HVs. By ANCOVA, there was no significant association between BMI and TNF-α (F = 0.098, p = 0.75) or IL-6 (F = 0.221, p = 0.63) levels in FM patients.ConclusionsOur analysis in FM patients of BMI as a covariate of proinflammatory cytokines levels showed that serum TNF-α and IL-6 levels are independent of BMI. Further studies are necessary to dissect these findings and their implication in future therapeutic approaches for FM patients.

Effects of berberine on serum levels of inflammatory factors and inflammatory signaling pathway in obese mice induced by high fat diet

To investigate the effect of berberine on serum levels of TNF-alpha, IL-6 and adiponectin in obese mice induced by high fat diet and its potential molecular mechanisms. Normal male Kunming mice were randomly divided into two groups taking normal chow (NC, n = 10) and high fat diet (HF, n = 30), respectively. After 13 weeks, HF mice were continuously given high fat diet and divided into three groups, model group (BM), low-dosage of berberine group (BL) and high-dosage of berberine group (BH). Mice in BL and BH were administered berberine by gavage at the dosage of 50 mg x kg(-1) and 150 mg x kg(-1), respectively. Two weeks later, oral glucose tolerance test was performed. At the end of the experiment, the mice were killed and blood samples were collected. The epididymal fat tissue and liver were removed promptly and weighed. The serum cytokine was measured by ELISA. The levels of IkappaB kinase beta (IKK-beta) and IKK-beta (ser181) were detected by Western blotting. Serum levels of TNF-alpha, IL-6 in mice of BM were significantly higher than those in NC (P < 0.05). After two-week treatment of berberine, serum levels of TNF-alpha, IL-6 in BL and BH were lower than those in BM (P < 0.05, respectively). However, there were no significant difference of adiponectin among four groups. The degrees of phosphorylation of IKK-beta (ser181) were decreased in liver and adipose tissue in BH in comparison to that in BM, although the expression of total IKK-beta did not change. Furthermore, the glucose tolerance was improved, while the body weight and epididymal fat were reduced in mice treated with berebrine. 9: Berberine is able to reduce inflammatory cytokines expression and inhibit activation of IKK-beta (ser181) in obese mice, which may partly explain the therapeutic effect of berberine on insulin resistance and abnormal glucose metabolism.

Physical activity reduces circulating TNF-alpha but not pro-thrombotic factors levels in patients with metabolic syndrome

Aims The metabolic syndrome (MS) creates a pro-inflammatory state. Some cytokines increase their levels in patients with MS, among them tumor necrosis factor-alpha (TNF-alpha). On the other hand, MS is associated with a pro-thrombotic state in which increased levels of fibrinogen and plasminogen activator inhibitor type-1 (PAI-1) have been described. We tested the hypothesis that an intervention based on physical activity in adults with MS would reduce TNF-alpha, and the thrombogenic factors fibrinogen and PAI-1. Materials and Methods We studied 51 non-smoking subjects, both genders, between 39 and 62 years old. All of them presented MS and were randomly separated into two groups: Intervened-MS group (I-MS, n = 27), who participated in an 18-week intervention based on exercise and dietary counseling, and non-intervened MS group (NI-MS, n = 24), as control. Biochemical and anthropometric parameters were determined at baseline and at final time (18 weeks). Results The intervention decreased the TNF-alpha serum levels (expressed as median and interquartile range IQR) from basal 3.6 (IQR = 2.1) to a final level of 1.7 (IQR = 1.8) pg/ml, in comparison to the NI-MS group: basal 4.0 (IQR = 1.8) to final 4.7 (IQR = 10.5) pg/ml ( p < 0.0001). On the contrary, this treatment did not produce changes in the pro-thrombotic factors fibrinogen and PAI-1, although variations in PAI-1 were associated with changes in waist circumference ( p = 0.026) and high-density lipoprotein cholesterol ( p = 0.04). Conclusion Our results suggest that a non-pharmacological intervention program based on physical exercise is effective in reducing TNF-alpha levels in patients with MS, but had no effect regarding the levels of the pro-thrombotic factors PAI-1 and fibrinogen.