Plasma Concentrations Of TNF-α Research Articles

Functional and traditional training improve muscle power and reduce proinflammatory cytokines in older women: A randomized controlled trial

Aging is a natural process that, even in the nonattendance of complex diseases, is associated with a numerous behavioral change that attributes reduced muscle mass, power, strength and function. In addition, aging linked to low-grade inflammatory status, characterized by increased plasma concentrations of inflammatory cytokines such as TNF-α and IL-6. Physical exercise is the main non-pharmacological strategy for improving the physical fitness of the aged individuals. However, it is still controversial whether exercise can reduce aging-mediated inflammation. To analyze the effects of functional (FT) and traditional (TT) training practice on muscle power and inflammatory profile in physically active older women. The study has been performed for twenty-six weeks in which twenty-four weeks utilized for training sessions and two weeks for physical and biochemical assessments. Forty-three older women (age FT: 64.25±4.70, range: 60-75; TT: 64.90±3.03, range: 60-71; Control: 65.91±5.79, range: 60-75) were randomly divided into three groups: Functional (FT; n=16); Traditional (TT; n=16) training groups; and Control Group (CG; n=11) respectively. Muscle power tests were performed by push (Bench press) and squatting (Squat) actions. The jumping ability was performed through Counter Movement Jump (CMJ). In addition, isometric strength were assessed by Hand Grip Test. Plasma cytokine concentration was measured using flow cytometry. Functional and traditional training sessions subjected to aged women demonstrated a significant enhancement in their physical activity and muscle power. The trained individuals from above two groups showed significant improvements in all analyzed parameters excluding hand-grip. Functional and traditional training exercise reduced the plasma concentrations of TNF-α (FT: p=0.0001; TT: p=0.0410) and whereas FT group has reduced IL-6 (p=0.0072), but did not affect the alterations of pre and post measurements of IL-2 (FT: p=0.0651; TT: p=0.2146) and IL-10 values (FT: p=0.2658; TT: p=0.3116). There was no significant difference in any of the test parameters between FT and TT groups. The functional and traditional training practices showed equivalent beneficial outcomes by increasing muscle power and reducing systemic markers associated with inflammation.

ELEVATED PLASMA LEVELS OF TNF-ALPHA, INF-GAMMA, IL-10 AND TGF-BETA IN MALARIA PATIENTS FROM TWO MALARIA NON-ENDEMIC REGIONS IN KARNATAKA, INDIA

Purpose: In India, Plasmodium vivax malaria is endemic and accounts for 50-55% of the total malaria burden in the country. There has been limited sero-epidemiological data available from malaria non-endemic regions in Karnataka state. In this study, we aimed to evaluate the plasma levels of Tumor necrosis factor-α (TNF-α), Interferon- γ (IFN-γ), Interleukin-10 (IL-10), and Transforming growth factor- β (TGF-β) and correlate with malaria parasitaemia and infection type in vivax and falciparum malaria cases reported from two study centres.
 Methods: This hospital-based cross sectional observational study was conducted at BLDEU SHRI B.M. Patil Medical College, Hospital and Research Centre Vijayapur, Karnataka and BGS Global Institute of Medical Sciences, Bengaluru, Karnataka during 2016 to 2019. A total number of 45 microscopy positive and molecularly confirmed malaria cases were included in the study. Plasma samples were analyzed for the concentrations of four cytokines by Enzyme-linked immunosorbent assay (ELISA). 20 uninfected healthy volunteers were used as controls. Correlation of cytokines and parasitemia was done using Pearson correlation analysis.
 Results: The results show an overall significant elevation of plasma TNF-α (p<0.05), IFN-γ (p<0.005), IL-10 (p<0.001), and TGF-β (p<0.001) in malaria patients compared to healthy controls. Except TNF-α (p<0.001), there was no significant difference in infection type specific immune responses. No significant correlation was seen among all the four cytokines with parasite load. A Receiver operating curve (ROC) was generated and showed that TNF-α, IL-10, and IFN-γ were the best individual predictors of malaria.
 Conclusions: We conclude that significantly elevated plasma concentrations of TNF-α-, IL-10, IFN-γ and TGF-β in both P. vivax and P. falciparum cases suggest their active involvement in mounting defensive immune response against malaria infection.
 Keywords: Malaria, Plasmodium vivax malaria, TNF-α, INF-γ, IL-10, TGF-β, Karnataka

Quercetin attenuates adipose hypertrophy, in part through activation of adipogenesis in rats fed a high-fat diet

An impaired capacity of adipose tissue expansion leads to adipocyte hypertrophy, inflammation and insulin resistance (IR) under positive energy balance. We previously showed that a grape pomace extract, rich in flavonoids including quercetin (Q), attenuates adipose hypertrophy. This study investigated whether dietary Q supplementation promotes adipogenesis in the epididymal white adipose tissue (eWAT) of rats consuming a high-fat diet, characterizing key adipogenic regulators in 3T3-L1 pre-adipocytes. Consumption of a high-fat diet for 6 weeks caused IR, increased plasma TNFα concentrations, eWAT weight, adipocyte size and the eWAT/brown adipose tissue (BAT) ratio. These changes were accompanied by decreased levels of proteins involved in angiogenesis, VEGF-A and its receptor 2 (VEGF-R2), and of two central adipogenic regulators, i.e. PPARγ and C/EBPα, and proteins involved in mature adipocyte formation, i.e. fatty acid synthase (FAS) and adiponectin. Q significantly reduced adipocyte size and enhanced angiogenesis and adipogenesis without changes in eWAT weight and attenuated systemic IR and inflammation. In addition, high-fat diet consumption increased eWAT hypoxia inducible factor-1 alpha (HIF-1α) levels and those of proteins involved in adipose inflammation (TLR-4, CD68, MCP-1, JNK) and activation of endoplasmic reticulum (ER) stress, i.e. ATF-6 and XBP-1. Q mitigated all these events. Q and quercetin 3-glucoronide prevented TNFα-mediated downregulation of adipogenesis during 3T3-L1 pre-adipocytes early differentiation. Together, Q capacity to promote a healthy adipose expansion enhancing angiogenesis and adipogenesis may contribute to reduced adipose hypertrophy, inflammation and IR. Consumption of diets rich in Q could be useful to counteract the adverse effects of high-fat diet-induced adipose dysfunction.

PLASMA INTERLEUKIN-6 LEVELS MAY BE ASSOCIATED WITH THE LENGTH OF STAY TIME OF ADULT HYPERGLYCEMIC PATIENTS IN AN INTENSIVE CARE UNIT.

Estimation of intensive care unit (ICU) length of stay time (LOS) may be challenging, and pro-inflammatory cytokines can be used as a marker for this purpose. The current study aimed to investigate the association between pro-inflammatory cytokine levels and LOS in hyperglycemic patients admitted to adult ICU. This is a prospective observational study. All adult ICU patients with a blood glucose level higher than 250 mg/dL, during the study period were included. Hospitalization day demographics were recorded, and plasma IL-6, IL1-ß, and TNF-α concentrations were measured. A total of 74 patients were enrolled in the study. Diabetic ketoacidosis (DKA) was positive in 31 patients, and the remaining 43 were in the non-DKA (NDKA) group. There was no difference between the two groups in terms of age, gender, LOS, hemoglobin, hematocrit, lactate levels, and platelets count. IL-6, IL-1ß, and TNF-α levels did not show any difference between DKA and NDKA groups (p=0.784, 0.413, and 0.288, respectively). There was a positive correlation between IL-6 levels and LOS (n=74, Pearson correlation=0.330; p=0.004). Among pro-inflammatory cytokines, IL-6 showed a better performance for the prediction of LOS than IL-1ß, TNF-α, and CRP.

Increased circulatory IL-6 during 8-week fluoxetine treatment is a risk factor for suicidal behaviors in youth

ObjectiveSelective serotonin reuptake inhibitors (SSRIs) are commonly used to treat anxiety and/or depression in pediatric populations. However, the response rates are low (approximately 50%). Moreover, SSRI use is frequently associated with adverse events (AE). Currently there are no available biomarkers for treatment response/AE. Identification of biomarkers predicting early response and/or AE could help maximize the benefit-risk ratio for the use of SSRIs, and accelerate matching of treatments to patients. Pro-inflammatory cytokines were proposed as potential biomarkers. MethodNinety-two patients (35 boys and 57 girls) with major depressive disorder and/or anxiety disorders, aged 13.90 ± 2.41 years, were treated with fluoxetine (FLX) for 8 weeks. Plasma concentrations of TNFα, IL-6, and IL-1β were measured by enzyme linked immunosorbent assays before and after FLX treatment. Clinical response and AE were measured using several clinical scales, including the Clinical Global Impression – improvement, Children's Depression Rating Scale–Revised, the Beck Depression Inventory, the Screen for Child Anxiety Related Emotional Disorders, the Columbia suicide severity rating scale, and the Suicide Ideation Questionnaire. ResultsIL-6 levels increased after treatment only in the group of children who developed FLX-associated suicidality. ConclusionAn increase in IL-6 levels during treatment may be a risk factor for the emergence of FLX-associated suicidality (OR = 1.70). Further studies are necessary to clarify the role and mechanism(s) of this cytokine in the pathogenesis of this life-threatening AE.

Undaria pinnatifida Fucoidan-Rich Extract Recovers Immunity of Immunosuppressed Mice.

We investigated the immune restoration activity of Undaria pinnatifida fucoidan-rich extract in cyclophosphamide-induced immunosuppressed mice. C57BL/6 mice were intraperitoneally injected with 80 mg/kg of cyclophosphamide (CP) and orally administered with either drinking water (DW), red ginseng extract (RG), or one of three different doses of Undaria pinnatifida fucoidan-rich extract (DSU02 50, 100, and 150 mg/kg). After 14 days, liver, spleen, and whole blood were isolated from each animal. The frequencies of NK and CD3+, CD4+, and CD8+ T cells were significantly increased in splenocytes isolated from the DSU02 100 mg/kg and DSU02 150 mg/kg groups (NK1.1+, 5.4% or 4.9% vs 3.8%; CD3+, 39.3% or 37.9% vs 32.3%; CD4+, 22% or 20.2% vs 17.4%; CD8+, 12.7% or 11.6% vs 10.1%). NK cytotoxicity was enhanced in the DSU02-fed groups at all doses (CP-treated DW, 93.4%; RG, 107.2%; DSU02 50, 107.3%; DSU02 100, 107.3%; DSU02 150, 107.1%), and the proliferation of T cells (CD3+, CD4+, and CD8+) was also greater in the DSU02 100 mg/kg and DSU02 150 mg/kg administered groups compared with the unfed group. Plasma concentrations of TNF-α, IgM, and total IgG from the DSU02 150 mg/kg group were also significantly higher compared with the other groups (TNF- α: CP-treated DW - 21.5 pg/ml, DSU02 150 - 47.1 pg/ml; IgM: CP-treated DW - 82.9 ng/ml, DSU02 150 - 110.8 ng/ml; total IgG: CP-treated DW - 114.4 ng/ml, DSU02 150 - 162.7 ng/ml). We suggest that Undaria pinnatifida fucoidan-rich extract could be a promising candidate for a marine natural immune stimulator.

Effect of α-linolenic acid on vascular function and metabolic risk markers during the fasting and postprandial phase: A randomized placebo-controlled trial in untreated (pre-)hypertensive individuals.

Only a limited number of studies have examined the vascular and postprandial effects of α-linolenic acid (ALA, C18:3n-3). Therefore, we performed a well-controlled trial focusing specifically on the effects of ALA on vascular function and metabolic risk markers during the fasting and postprandial phase in untreated (pre-)hypertensive individuals. In a double-blind randomized, placebo-controlled parallel study, 59 overweight and obese adults (40 men and 19 women, aged 60±8 years) with a high-normal blood pressure or mild (stage I) hypertension consumed daily either 10g of refined cold-pressed flaxseed oil, providing 4.7g ALA (n=29), or 10g of high-oleic sunflower (control) oil (n=30) for 12 weeks. As compared with the high-oleic oil control, intake of flaxseed oil did not change brachial artery flow-mediated vasodilation, carotid-to-femoral pulse wave velocity, retinal microvascular calibers and plasma markers of microvascular endothelial function during the fasting and postprandial phase. Fasting plasma concentrations of free fatty acid (FFA) and TNF-α decreased by 58μmol/L (P=0.02) and 0.14pg/mL (P=0.03), respectively. No differences were found in other fasting markers of lipid and glucose metabolism, and low-grade systemic inflammation. In addition, dietary ALA did not affect postprandial changes in glucose, insulin, triacylglycerol, FFA and plasma inflammatory markers after meal intake. A high intake of ALA, about 3-5 times the recommended daily intake, for 12 weeks decreased fasting FFA and TNF-α plasma concentrations. No effects were found on other metabolic risk markers and vascular function during the fasting and postprandial phase in untreated high-normal and stage I hypertensive individuals.

Repeated Fractions of X-Radiation to the Breast Fat Pads of Mice Augment Activation of the Autotaxin-Lysophosphatidate-Inflammatory Cycle.

Breast cancer patients are usually treated with multiple fractions of radiotherapy (RT) to the whole breast after lumpectomy. We hypothesized that repeated fractions of RT would progressively activate the autotaxin–lysophosphatidate-inflammatory cycle. To test this, a normal breast fat pad and a fat pad containing a mouse 4T1 tumor were irradiated with X-rays using a small-animal “image-guided” RT platform. A single RT dose of 7.5 Gy and three daily doses of 7.5 Gy increased ATX activity and decreased plasma adiponectin concentrations. The concentrations of IL-6 and TNFα in plasma and of VEGF, G-CSF, CCL11 and CXCL10 in the irradiated fat pad were increased, but only after three fractions of RT. In 4T1 breast tumor-bearing mice, three fractions of 7.5 Gy augmented tumor-induced increases in plasma ATX activity and decreased adiponectin levels in the tumor-associated mammary fat pad. There were also increased expressions of multiple inflammatory mediators in the tumor-associated mammary fat pad and in tumors, which was accompanied by increased infiltration of CD45+ leukocytes into tumor-associated adipose tissue. This work provides novel evidence that increased ATX production is an early response to RT and that repeated fractions of RT activate the autotaxin–lysophosphatidate-inflammatory cycle. This wound healing response to RT-induced damage could decrease the efficacy of further fractions of RT.

Dietary administration of resistant starch improved caecal barrier function by enhancing intestinal morphology and modulating microbiota composition in meat duck.

Resistant starch (RS) was recently approved to exert a powerful influence on gut health, but the effect of RS on the caecal barrier function in meat ducks has not been well defined. Thus, the effect of raw potato starch (RPS), a widely adopted RS material, on microbial composition and barrier function of caecum for meat ducks was determined. A total of 360 Cherry Valley male ducks of 1-d-old were randomly divided and fed diets with 0 (control), 12, or 24 % RPS for 35d. Diets supplemented with RPS significantly elevated villus height and villus height:crypt depth ratio in the caecum. The 16S rRNA sequence analysis indicated that the diet with 12 % RPS had a higher relative abundance of Firmicutes and the butyrate-producing bacteria Faecalibacterium, Subdoligranulum, and Erysipelatoclostridium were enriched in all diets. Lactobacillus and Bifidobacterium were significantly increased in the 24 % RPS diet v. the control diet. When compared with the control diet, the diet with 12 % RPS was also found to notably increase acetate, propionate and butyrate contents and up-regulated barrier-related genes including claudin-1, zonula occludens-1, mucin-2 and proglucagon in the caecum. Furthermore, the addition of 12 % RPS significantly reduced plasma TNF-α, IL-1β and endotoxin concentrations. These data revealed that diets supplemented with 12 % RPS partially improved caecal barrier function in meat ducks by enhancing intestinal morphology and barrier markers expression, modulating the microbiota composition and attenuating inflammatory markers.

Effects of autologous platelet-rich plasma on postoperative outcomes in patients undergoing Sun′s procedure

Objective To evaluate the effect of autologous platelet-rich plasma (aPRP) on postoperative outcomes in the patients undergoing Sun′s procedure. Methods One hundred and sixteen patients with acute Stanford type A aortic dissection of both sexes, aged 18-64 yr, with body mass index of 19-34 kg/m2, of American Society of Anesthesiologist physical status Ⅳ, were divided into aPRP group (group A) and control group (group C) by a random number table method, with 58 cases in each group.After anesthesia induction and intubation, aPRP preparation was completed before surgery in group A, and surgery began in group C. After heparin neutralization, group A received retransfusion of platelet-rich plasma, while group C received conventional fluid management.Thromboelastography was performed on all patients, and the results were recorded.The intraoperative amount of allogeneic blood products and blood loss were recorded in two groups.Plasma concentrations of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) were recorded after anesthesia induction (T0), immediately after completion of aPRP preparation (T1), 3 h after heparin neutralization (T2), and at 24 and 48 h after surgery (T3, 4). The volume of postoperative chest drainage and amount of allogeneic blood products, mechanical ventilation time, lengths of intensive care unit and hospital stay, incidence of important complications and fatality rate within 30 days after surgery were also collected. Results Compared with group C, the intraoperative amount of allogeneic blood products and blood loss were significantly reduced, α angle and MA values of thromboelastograph were larger, plasma concentrations of TNF-α and IL-6 were reduced at T2, 3, postoperative chest drainage volume and allogeneic blood transfusion were reduced, the postoperative mechanical ventilation time and length of hospital stay were shortened, and the incidence of pulmonary complications was reduced in group A(P 0.05). Conclusion aPRP can improve postoperative outcomes in the patients undergoing Sun′s procedure. Key words: Platelet-rich plasma; Aneurysm, dissecting; Prognosis

Evaluation of neurovascular function in mouse cortex using multispectral optical imaging after ischemic stroke

Objective: To acquire the signal of neuron excitability and blood oxygen in mouse cortex after ischemic stroke, and to clarify the relationship between the change of neurovascular function and the degree of cerebral infarction. Methods: The male C57BL/6 mouse(n=20) about 6-8 weeks and 20 g weight were produced the embolic stroke modal by photochemical injury. The mouse cortex was scanned by the multispectral optical imaging while using electric stimulation in 1, 3 and 7 d after operation. Then several data around the infarction were acquired including neuron excitability, the total hemoglobin concentration and deoxygenated hemoglobin concentration. The ischemic cerebral infarction size was analyzed by TTC staining. Plasma TNF-α concentration was measured by enzyme-linked immunosorbent assay(ELISA). And modified neurological severity score (mNSS) was recorded after ischemic stroke(n=30). Then correlativity analysis was used between the optical signals and three indicators of cerebral infarction degree. Results: The changes of neuron excitability signals were 1.15%±0.28%, 2.84%±1.06%, 2.21%±0.55%. The total hemoglobin concentration signals were 3.71%±2.76%,3.19%±2.70%,4.27%±3.05%. The deoxygenated hemoglobin concentration signals were 2.93%±2.33%, 3.60%±1.74%, 2.08%±1.28%. The neural signal was correlated to cerebral infarction size, plasma TNF-α concentration and mNSS(r=-0.441, -0.449,-0.404, all P<0.05), and mNSS had a great effect on neuron excitability(β=-0.169,P<0.05). Meanwhile, the total hemoglobin concentration was correlated to cerebral infarction size(r=0.440,P<0.05). Conclusion: The signal of neuron and blood oxygen is able to represent the change of neurovascular function and evaluate the progression of ischemic stroke.

Effect of flaxseed oil on muscle protein loss and carbohydrate oxidation impairment in a pig model after lipopolysaccharide challenge.

Flaxseed oil is rich in α-linolenic acid (ALA), which is the metabolic precursor of EPA and DHA. The present study investigated the effect of flaxseed oil supplementation on lipopolysaccharide (LPS)-induced muscle atrophy and carbohydrate oxidation impairment in a piglet model. Twenty-four weaned pigs were used in a 2 × 2 factorial experiment including dietary treatment (5 % maize oil v. 5 % flaxseed oil) and LPS challenge (saline v. LPS). On day 21 of treatment, the pigs were injected intraperitoneally with 100 μg/kg body weight LPS or sterile saline. At 4 h after injection, blood, gastrocnemius muscle and longissimus dorsi muscle were collected. Flaxseed oil supplementation increased ALA, EPA, total n-3 PUFA contents, protein:DNA ratio and pyruvate dehydrogenase complex quantity in muscles (P < 0·05). In addition, flaxseed oil reduced mRNA expression of toll-like receptor (TLR) 4 and nucleotide-binding oligomerisation domain protein (NOD) 2 and their downstream signalling molecules in muscles and decreased plasma concentrations of TNF-α, IL-6 and IL-8, and mRNA expression of TNF-α, IL-1β and IL-6 (P < 0·05). Moreover, flaxseed oil inclusion increased the ratios of phosphorylated protein kinase B (Akt) 1:total Akt1 and phosphorylated Forkhead box O (FOXO) 1:total FOXO1 and reduced mRNA expression of FOXO1, muscle RING finger (MuRF) 1 and pyruvate dehydrogenase kinase 4 in muscles (P < 0·05). These results suggest that flaxseed oil might have a positive effect on alleviating muscle protein loss and carbohydrates oxidation impairment induced by LPS challenge through regulation of the TLR4/NOD and Akt/FOXO signalling pathways.

Partner HIV Serostatus Impacts Viral Load, Genital HIV Shedding, and Immune Activation in HIV-Infected Individuals.

Studies of seronegative individuals in HIV discordant relationships provide important insights into the effects of HIV exposure on the seronegative partner, but few have examined the impact of partner serostatus on disease progression in seropositive individuals. We investigated the impact of HIV serostatus on clinical and biological factors influencing HIV disease progression in 337 HIV-infected heterosexual individuals in stable long-term HIV-seroconcordant or HIV-serodiscordant relationships. Seroconcordant individuals had significantly higher plasma viral loads (pVLs) than HIV-infected partners in serodiscordant partnerships [4.4 log10 copies RNA/mL (interquartile range 3.7-5.0) versus 3.9 (3.3-4.5), P < 0.0001], irrespective of gender. pVLs correlated inversely with CD4 T-cell counts, although CD4 counts did not differ significantly between seroconcordant and serodiscordant individuals. HIV+ seroconcordant individuals had higher frequencies of CCR5 CD4 and CD8 T cells (P = 0.03 and P = 0.02, respectively) than HIV+ individuals in serodiscordant relationships and higher concentrations of plasma IL-1β (P = 0.04), TNF-α (P = 0.02), and IL-10 (P = 0.02). Activated CD4 T-cell frequencies and TNF-α were the most influential in determining variation in pVLs, independently of CD4 counts. In addition, HIV+ seroconcordant women had significantly higher genital VLs (gVLs) than HIV+ women in serodiscordant relationships (P < 0.001), with pVLs correlating significantly with gVLs (Rho = 0.65, P < 0.0001). Cervical and blood T-cell activation tended to correlate positively, although partner seroconcordance did not influence genital T-cell activation. We conclude that HIV+ seroconcordant individuals have higher frequencies of activated, CCR5-expressing T cells in blood and higher pVLs and gVLs than their HIV+ counterparts in discordant relationships, which could translate to faster disease progression or larger viral reservoir.

Clinical and paraclinical changes in experimental colisepticemia in neonatal calves

The present study aim was to assess changes in clinical signs and plasma cytokines in calves experimentally infected with Escherchia coli and use them as a tool to diagnose colisepticemia. Ten healthy Holstein-Frisian bull calves were used for this experimental study. Experimental colisepticemia was induced in calves with intravenous injection of 1.5 × 109 CFU of O111:H8 strain of E.coli. Clinical scores were recorded before induction of septicemia, every 30 minutes for 8 hours, every hour from 8 till 12 h, every 3 hours from 12 till 24 hours after bacterial challenge. Blood samples were collected to determine plasma concentration of tumor necrosis factor-α (TNF-α) and gamma interferon gamma (IFN-γ) before and after E.coli IV injection. Blood culture was performed before and after bacterial challenge to confirm colisepticemia. The present study showed that total clinical score of the calves increased with a simultaneous significant rise in plasma concentration of TNF-α and INF-γ during septicemia period (P&amp;lt; 0.05). Changes in the heart and respiratory rate during septicemia and using clinical scoring are not enough to assess the magnitude of infection and disease progress; therefore, it is recommended some laboratory tests be used for better evaluation of clinical status of the septic calves

Effect of preoperative recombinant human erythropoietin administration on inflammatory lung injury due to cardiopulmonary bypass

Objective To discuss the effects of preoperative use of recombinant human erythropoietin (rHuEPO) on inflammatory lung injury patients after cardiopulmonary bypass (CPB) under extracorporeal circulation. Methods A total of 54 patients who were scheduled to receive elective open cardiac operations under CPB were enrolled. They were divided into two groups(n=27). rHuEPO group: patients were titrated intravenously with rHuEPO (100 IU/kg, diluted into 50 ml normal saline) for consecutive three days at the same time period before operation. Control group: equivalent normal saline in place of rHuEPO was given to patients via venous injection. Peak airway pressure (Ppeak), plateau pressure (Pplat), and pulmonary dynamic compliance (Cdyn) were well monitored and recorded before CPB (T1), immediately after chest closure (T2), and 2, 4 h and 6 h after surgery (T3, T4, and T5). At T1, T2, T5, and 12, 24, 48 h, and 72 h after surgery (T6, T7, T8, and T9), arterial oxygenation indices (OI) were also recorded. Furthermore, at pre-rHuEPO treatment (T0), T1, T2, T5, T6, T7, T8, and T9, the plasma levels of the tumor necrosis factor (TNF)-α and interleukin (IL)-1β and IL-10 were measured. The time of mechanical ventilation and stay in intense care unit (ICU), discharge time and hospitalization stay were also recorded. Results Compared with the control group, Cdyn in the rHuEPO group at T2-T5 were significantly increased (P<0.05), whereas Ppeak and Pplat were decreased (P<0.05). OI values of rHuEPO group at T2 and T5-T9 were significantly higher than that of control group(P<0.05). It was demonstrated that at any time point after closing chest, the plasma concentrations of TNF-α, IL-1β, and IL-10 in both groups were relatively elevated compared with those before, while the concentrations of TNF-α and IL-1β in the rHuEPO group were lower than those in control group (P<0.05). Compared with the control group, patients receiving rHuEPO treatment underwent an apparent reduction in both mechanical ventilation and staying time in ICU (P<0.05). Conclusions Preoperative rHuEPO administration can attenuate the inflammatory lung injury after CPB via the anti-inflammation pathway and ameliorate pulmonary functions. Key words: Recombinant human erythropoietin; Cardiopulmonary bypass; Lung injury; Inflammatory response

A randomized controlled dose-escalation study of SSS07, a humanized rabbit anti-human TNF alpha antibody, in healthy Chinese adults

AimsSSS07 is a rabbit derived humanized anti-human TNF-α antibody. This study aimed to explore the pharmacokinetics, safety, and immunogenicity of SSS07 when administrated subcutaneously in healthy adults. MethodsThis was a double-blind, dose-escalation study of SSS07 in 71 adults. Dose cohorts were set to 5 mg, 15 mg, 30 mg, 50 mg, 75 mg, and 100 mg. In each dosage group, other than 100 mg, twelve healthy participants were randomly assigned to receive a single dose of SSS07 (n = 10) or placebo (n = 2). Blood samples were taken for pharmacokinetics and immunogenicity analysis. ResultsNo deaths, serious adverse events or drug-related withdrawals occurred in this trial. No drug limited toxicity appeared. After subcutaneous injection, SSS07 was absorbed slowly with Tmax ranging from 60 to 264 h but eliminated quickly with a short half-life ranging from 21.69 to 78.4 h (1–3 days). From 5 mg to 100 mg, dose-exposure proportionality analysis found a 90% confidence interval (CI) of β of Cmax (1.015–1.193), AUC0-t (1.096–1.263) and AUC0-∞ (0.999–1.174) partially within the range 0.926–1.074. The plasma concentration of TNF-α decreased significantly post-dose, but a few days later, levels of TNF-α elevated rapidly and exceeded its baseline value. All participants receiving SSS07 were found to be anti-drug antibody positive during the study. ConclusionsA single-dose injection of SSS07 was safe and well-tolerated in healthy adults. Doses of SSS07 from 5 mg to 100 mg could not be regarded as nonlinear, based on dose-exposure proportionality analysis. A high incidence of anti-drug antibodies indicated strong immunogenicity, which may influence the pharmacokinetics profile and interfere with the TNF-α inhibition capability of SSS07.

Undaria pinnatifida Fucoidan-Rich Extract Induces Both Innate and Adaptive Immune Responses

Fucoidans are widely used as an ingredient of dietary supplements. We investigated the immune stimulatory activities of Undaria pinnatifida ( Alariaceae) fucoidan-rich extract (UPF-RE) in vitro as well as in vivo . In vitro, the extract stimulated Raw 264.7 cells to produce significant nitric oxide (NO) metabolites and cytokines (TNF-α, IL-1α, IL-1β, and IL-6). It also induced the proliferation of primary mouse splenocytes and the secretion of IL-4, which correlated with the phosphorylation of Extracellular-signal-regulated kinase (ERK) protein. In in vivo experiments, first, 50 mg/kg of 3 different types of UPF-RE, DSU02, DSU02L (low molecular weight, &lt;3 kDa), and DSU02H (high molecular weight, &gt;10 kDa), were orally administered to C57BL/6 mice. After 14 days, the frequencies of CD3+, CD4+, and CD8+ T cells and NK cells from each group were analyzed. Plasma concentrations of TNF-α and IFN-γ were determined. The frequencies of CD3+ and CD4+ showed a statistically significant increase in splenocytes isolated from the DSU02 and DSU02H groups. Also, there was significant production of TNF-α and IFN-γ from the DSU02 group. Second, 3 different concentrations of DSU02 (50, 100, and 150 mg/kg) were orally administered. After 14 days, the proliferative capacity of CD3+, CD4+, and CD8+ T cells was investigated, and the plasma concentrations of IgM and total IgG were determined. Plasma concentration of IgM from the DSU02 150 mg/kg group was statistically significantly higher compared with that from the other groups. We suggest that UPF-RE could be a good candidate for a natural immune stimulator to induce innate as well as adaptive immune responses.

Pancreatic HB9 protein level is affected by early life stress in young adult rats: possible involvement of TNF-α and corticosterone

This study examined foot shock stress effects, during weaning, on pancreatic HB9 protein expression in young adult male rats in the presence or absence of adulthood stress. The pups were divided into Control, Early life stress, Young adult stress, and Early + young adult stress groups. Plasma corticosterone, insulin, glucose, and TNF-α concentrations, and pancreatic HB9 protein expression were assessed. At 2 weeks of age, stress increased plasma corticosterone level. During young adulthood, plasma TNF-α and glucose concentrations increased, whereas plasma insulin and pancreatic HB9 protein levels decreased in Early life stress group. Whereas, Early + young adulthood stress group showed no change in the study parameters, except for plasma corticosterone and insulin concentrations. Overall, early life stress reduced pancreatic HB9 protein expression possibly by elevating plasma corticosterone and TNF-α levels in early life and adulthood, respectively. However, combined with adulthood stress, HB9 protein expression increased to the level of Control.

Role of Inflammation in the Pathogenesis of Diabetic Peripheral Neuropathy.

BACKGROUND:Diabetic peripheral neuropathy (DPN) means the presence of symptoms and/or signs of peripheral nerve damage that occur to people with diabetes, excluding all other causes of neuropathy. Chronic hyperglycaemia leads to increased secretion of tumour necrotic factor-alpha (TNF-α), with the development of micro and macroangiopathy, damage to nerve fibres and local demyelination.AIM:To determine the role of inflammation in the peripheral nerve damage process concerning people suffering from type II diabetes mellitus.MATERIAL AND METHODS:The study included a total of 80 subjects, men and women, divided into two groups: an examined group (n = 50) consisting of subjects with DPN at the age from 30 to 80 years and a control group (n = 30) of healthy subjects aged from 18 to 45. In the investigated group, a neurological examination was performed using the Diabetic Neuropathy Symptoms (DNS) Score and Electroneurography. All the subjects had the blood plasma concentration of TNF-α by ELISA technique.RESULTS:The average value of TNF-α in the test group was 8.24 ± 2.899 pg/ml, while the control group was 4.36 ± 2.622 pg/ml (p < 0.0001). The average value of TNF-α was correlated with the achieved DNS score in the investigated group (p = 0.005). Concerning the linear association of the concentration of TNF-α with the peripheral nerve velocity in the investigated group, no statistical significance was detected.CONCLUSION:Inflammation can play a role in the pathogenesis of diabetic autonomic neuropathy and cranial neuritis.

Active immune system and dry matter intake during the transition period are associated with postpartum fertility in lactating Zebu cows

The aim of the present study was to assess if the metabolic adaptation and immune status during transition period influence the postpartum reproductive performance in dairy cattle. We assessed the levels of innate immune molecules (Haptoglobin: Hp, Serum Amyloid A: SAA, IL-6, TNF-α, IL-1β, and IL-8) and energy balance indicators [NEFA and Dry Matter Intake (DMI)] in transition Zebu (Deoni breed) cows that became pregnant within breeding period (n = 7) and remained non-pregnant (n = 10) even after the breeding period (i.e. from 45 to 180 days postpartum). Blood samples were collected at weekly intervals during transition period (−21 d before to 21 d after calving) and plasma variables were estimated using commercially available bovine specific ELISA kits. Plasma Hp concentration was significantly (P < 0.01) higher in cows that became pregnant during breeding period as compared to those that remained non-pregnant. While plasma TNF-α concentrations differed significantly (P = 0.05) between groups, such difference was not observed with SAA concentrations. Group x time interaction had a significant effect on plasma IL-6 (P < 0.01), IL-1β (P = 0.05), IL-8 (P = 0.05) concentrations and DMI (P = 0.001). Plasma NEFA concentrations differed significantly (P = 0.03) between groups, although all the experimental cows had NEFA concentrations within the physiological limits. Days in milk had a significant effect on milk yield (P = 0.001) and fat percentage (P = 0.03). It is concluded that active functioning of immune system, stable dry matter intake, and limited fat mobilization during transition period enabled the cows to conceive early during postpartum period.