Significant Differences In TNF-α Levels Research Articles

Analyzing Substance Levels and Pain Perception in Painless Labor: The Impact of Spinal Epidural Analgesia.

Inflammation affects labor by influencing contractions and dilation. Pain, often linked to tissue ischemia, involves mediators like nitric oxide (NO), TNF-α, and substance P (SP). Neuraxial analgesia, including combined spinal epidural analgesia (SEA) with levobupivacaine, is preferred for its effectiveness and minimal side effects in painless labor. Understanding the impact of painless labor techniques on biomolecular processes such as NO, TNF-α, and substance P levels is crucial for improving pain management strategies. This study investigates these effects in parturients undergoing SEA with levobupivacaine, contributing to the development of novel pain medications and enhancing obstetric care. This experimental study, conducted at a General Hospital in Indonesia, involved 60 expectant mothers in labor or in the third trimester, expected to give birth vaginally at Permata Hati Metro Hospital. Blood serum was used for analysis, and serum NO, TNF-α, and SP levels were assessed using ELISA kit. There's a significant decrease in NO levels before and post-treatment in the SEA group compared to the control group (p < 0.05). However, no significant difference in TNF-α levels was observed between groups before and after treatment (p > 0.05). Additionally, there was no significant difference in SP levels between groups before treatment, but a significant difference was seen after treatment (p < 0.05). SEA significantly reduced labor pain compared to the control group (P < 0.05), with notable improvements in vital signs and APGAR scores, while also shortening labor duration (P < 0.001). In conclusion, SEA with levobupivacaine during painless labor reduces NO levels significantly and shows a trend of decreasing TNF-α and substance P levels, although not statistically significant, with clinical benefits for both patients and babies.

Evaluation of salivary tumor necrosis factor α as a diagnostic biomarker in oral submucosal fibrosis and squamous cell carcinoma of the oral cavity and oropharynx: a cross sectional observational study.

Tumor necrosis factor α (TNF-α) is known to be associated with chronic inflammation, and its expression has been shown to increase in advanced cancers. Chronic inflammation is a characteristic feature of oral submucous fibrosis (OSMF), which is a potentially malignant disorder (PMD). Squamous cell carcinoma (SCC) is associated with considerable mortality and morbidity and an early detection or monitoring would greatly help in achieving an effective cure. TNF-α was thus evaluated for use as a biomarker in the present study according to the stage of OSMF and histological grade of SCC in the oral cavity and oropharynx. This study included 45 patients divided into 3 groups-OSMF group, SCC group and control group-each comprising 15 participants. Saliva samples were collected from each patient, and salivary TNF-α levels were estimated using an ELISA kit. Statistical analysis revealed no significant differences in TNF-α levels among the OSMF, SCC and control groups; however, there was an increase in the salivary TNF-α level in patients with stage 3 disease according to the clinical stage of OSMF, for which the p value was 0.027. An increase in the TNF-α concentration with increasing clinical stage suggested a role for TNF-α in the spread of OSMF involvement in anatomical structures of the oral cavity and oropharynx. No significant difference in salivary TNF-α levels was noted among the OSMF, SCC and control groups. The study showed a positive correlation of TNF-α with increasing stages of OSMF but was not a reliable biomarker in the categorization of the same.

Association of Tumor Necrosis Factor-Alpha with Psychopathology in Patients with Schizophrenia.

We investigated the relationship between serum tumor necrosis factor-alpha (TNF-α) levels and psychopathological symptoms, clinical and socio-demographic characteristics and antipsychotic therapy in individuals with schizophrenia. TNF-α levels were measured in 90 patients with schizophrenia and 90 healthy controls matched by age, gender, smoking status, and body mass index. The Positive and Negative Syndrome Scale (PANSS) was used to assess the severity of psychopathology in patients. No significant differences in TNF-α levels were detected between the patients and controls (p=0.736). TNF-α levels were not correlated with total, positive, negative, general, or composite PANSS scores (all p>0.05). A significant negative correlation was observed between TNF-α levels and the PANSS cognitive factor (ρ=-0.222, p=0.035). A hierarchical regression analysis identified the cognitive factor as a significant predictor of the TNF-α level (beta=-0.258, t=-2.257, p=0.027). There were no significant differences in TNF-α levels among patients treated with different types of antipsychotics (p=0.596). TNF-α levels correlated positively with the age of onset (ρ=0.233, p=0.027) and negatively with illness duration (ρ=-0.247, p=0.019) and antipsychotic treatment duration (ρ=-0.256, p=0.015). These results indicate that TNF-α may be involved in cognitive impairment in schizophrenia, and would be a potential clinical-state marker in schizophrenia.

Susceptibility and mechanism of sodium salicylate-induced tinnitus model in low estrogen rats

Objective: The susceptibility of tinnitus rats with low estrogen level induced by sodium salicylate and the changes of tumor necrosis factor α (TNF-α) in serum were observed to investigate the relationship between tinnitus occurrence and estrogen level. Methods: Forty-two healthy female Wistar rats were randomly divided into control group(n=6), normal group(n=6), sham operation group(n=6) and ovariectomized group(n=24). Control group was intraperitoneally injected with normal saline 200 mg/kg for 14 consecutive days. Normal group, sham operation group and ovariectomized group were intraperitoneally injected with sodium salicylate 200 mg/kg for 14 consecutive days. Before and after sodium salicylate induction, the tinnitus behavior of rats in each group was detected by prepulse inhibition (PPI) and gap pre-pulse inhibition of the acoustic startle (GPIAS) test. Before and after sodium salicylate induction, blood samples were collected from eyeballs of rats in each group, and serum levels of estradiol and TNF-α were detected by ELISA. SPSS 25.0 software was used to analyze the data. Results: (1) Following 14 days of sodium salicylate intervention, there was no significant difference in PPI inhibition rate between groups or within groups(all P>0.05). (2)There was no significant difference in the inhibition rate of GPIAS in the four groups before sodium salicylate injection(F=0.217, P>0.05). With sodium salicylate injected for 14 days, the inhibition rate of GPIAS in ovariectomized group (30.88%±15.40%) was significantly lower than that in the other three groups (44.11%±21.06%, 38.27%±10.92%, 51.59%±11.34%), and the difference was statistically significant(F=3.533, P<0.05). The inhibition rate of GPIAS in ovariectomized group with sodium salicylate injected for 14 days was significantly lower than that before injection, and the difference was statistically significant(t=2.977, P<0.05).There was no significant difference in GPIAS inhibition rate between the other three groups before and after sodium salicylate injection(P>0.05). (3)The level of TNF-α in ovariectomized rats was significantly higher than that in the other three groups, the difference was statistically significant(all P<0.05). With sodium salicylate injection for 14 days, TNF-α level in the ovariectomized group increased more significantly than that in the other three groups, the difference was statistically significant(F=8.045, P<0.05). TNF-α levels increased following salicylate injection in normal group, sham operation group and ovariectomized group, and the differences were statistically significant(t value was -4.843, -4.932 and -5.965 respectively, each P<0.05). There was no significant difference in TNF-α levels before and after normal saline injection in control group(all P>0.05). Conclusion: Low estrogen levels increase susceptibility to sodium salicylate-induced tinnitus. Decreased estrogen levels may increase susceptibility to tinnitus through the increased expression of pro-inflammatory factor TNF-α.

PB2254: ASSOCIATION BETWEEN TNF-ALPHA LEVELS AND TNF-ALPHA 238 ALLELES POLYMORPHISMS AND SEVERITY OF ANEMIA AMONG SUDANESE CHILDREN WITH FALCIPARUM MALARIA

Background: Falciparum malaria is the most leading cause of mortality and morbidity in the world especially in Africa among infants and young children due to severe malaria and malaria anemia. TNF-α is plays a central role in malaria pathogenicity either in the cure or complication of malaria. TNF-α levels overproduction and promoter polymorphisms at TNF-α 238 alleles may play a central role in reduced red cell production and malaria-related anemia through suppression of bone marrow erythropoiesis and dyserythropoiesis. Aims: The purpose of this study was to evaluate the TNF-α 238 alleles polymorphism and its association with TNF-α levels in the severe malaria anemia among Sudanese children in Gezira State. Methods: A cross-sectional hospital-based study was included 200 Sudanese children (mean age 8.43 ± 3.80 years; 53% boys; 47% girls). 100 children with severe falciparum malaria (mean age 8.63 ± 3.40 years; 61% boys; 39% girls) and 100 children with uncomplicated falciparum malaria (mean age 8.83 ± 4.20 years; 45% boys; 55% girls). RBCs parameters were determined using the Sysmex XP 300 N automated hematology analyzer. ELISA was further processed for TNF-α level using Human TNF-α ELISA MAX™ Deluxe Sets. DNA extraction was done using G-DEX™IIb Genomic DNA Extraction Kit. PCR and gel running system were used for detecting TNF-α 238 alleles polymorphism (A allele/ G allele). Obtained data were analyzed by SPSS (V 20.0) and Stat disk (V 13.0). Results: TNF-α 238A allele was a common allele (66.8%) among Sudanese children with falciparum malaria, and the G allele was rare (33.2%). While TNF-α 238 GA, AA, and GG account for (54.5, 39.5, and 6% respectively). Falciparum malaria-related anemia accounted for 32%, commonly in SM (55%) compared to UM (9%) giving highly statistically significant differences in TNF-α levels between falciparum malaria-related anemia and falciparum malaria without anemia (P value 0.000). Otherwise, The average of TNF-α levels in mild, moderate, and severe anemia were (190.75 ± 102.55, 189.70 ± 80.35, and 299.75 ± 82.27 pg/ml respectively) giving highly significant differences and strongly significant positive correlated with the severity of anemia (r + 0.309; P value 0.000). TNF-α 238 GA, AA, and GG account for (58, 36, and 6% respectively) in UM; while (51, 43, and 6% respectively) in SM. The TNF-α 238 A allele accounts for 83.6% of malaria anemia (P value 0.000) and 100% severe anemia (P value 0.000); children who have TNF-α 238 A allele, they have ability to acquire falciparum malaria-related anemia with susceptibility to 3.13 folds risk. Summary/Conclusion: Overproduction of TNF-α is essential for the elimination and clearance of falciparum parasite but may be associated with severity of malaria and malaria anemia. Overproduction of TNF-α in children with TNF-α 238 A allele may result in falciparum malaria-related anemia among children (mainly severe anemia). The findings of this study will assist clinicians in diagnosing and better managing severe malaria cases.

The relationship of tumor necrosis factor alpha levels and neutrophils with skin wound age caused by sharp trauma

Background: Sharp force injuries are the second most common cause of trauma after blunt force injury. TNF- α is a cytokine that triggers the expression of adhesion molecules, other cytokines and chemokines by endothelial cells, stopped and migrated to damaged tissues or infections that trigger inflammation. Furthermore, the initial population of leukocytes leading to the wound comprises mostly neutrophils. This study aimed to assess the correlation between TNF-α levels in the blood and skin tissues and neutrophils number with the wound age of wounds caused by sharp trauma. Methods: This study is an experimental study using animal models. The samples were divided into the control group and the group in which the blood and the skin tissue samples were taken 1-, 3-, 12-, 24-, 48- and 72 hours after being sharp traumatized. The Elisa method examined the samples from the blood, and the skin of the right back of the mice was examined for TNF-α levels. Others from the left-back skin of the mice were microscopically examined to assess the number of neutrophils. Results: The TNF- α level from the skin samples were detected in wound tissue as the peak levels were in the 24 hours post-traumatic group. The TNF-α levels from blood samples indicated a significant difference in TNF-α levels in each group (p &lt; 0.05). However, TNF-α levels from skin samples showed no significant difference between each group. From the microscopic examination, there was a significant difference in the infiltration of neutrophil cells in all groups (p&lt;0,05). The neutrophils peak at 24 hours post-traumatic. Conclusion: There was no significant correlation between the TNF-α levels and the number of neutrophils with the wound age in wounds caused by sharp traumas.

Evaluating the Serum Levels of Inflammatory Cytokines in Women with Various Causes of Infertility during Controlled Ovarian Stimulation Cycles

Introduction: Concentration of inflammatory cytokines in serum levels and their role in the success of reproductive cycles with female infertility factors is unknown, so the aim of this study was to evaluate the serum levels of inflammatory cytokines in women with different causes of female infertility during controlled ovarian stimulation cycles.&#x0D; Methods: In this case-control study, 25 infertile women with female infertility or unknown causes (case group) and 24 infertile women with male infertility causes (control group) participated in controlled ovarian stimulation cycles. 5 cc of blood was taken from them on the day of ovulation and after serum isolation, serum IL6 and TNFα levels were measured by ELISA.&#x0D; Results: In this study, there was no significant difference in TNFα and IL6 levels between case and control groups (P&gt; 0.05). There was also no significant difference in TNFα levels in terms of causes of infertility (P&gt; 0.05). However, there was a significant difference in IL6 level in terms of various causes of infertility (P = 0.02). There was a significant difference between polycystic ovarian as well as unknown group and male factor group considering serum levels of interleukin-6 (P = 0.008, P = 0.02, respectively). Furthermore, the highest level of IL6 (28.3 ±20.36) belonged to the infertility group with unknown cause and a significant relationship was found between IL6 level and the number of oocytes and embryos (P &lt;0.01).&#x0D; Conclusion: Higher serum IL6 levels in the infertility group with unknown cause could be considered as a factor in the pathogenesis of infertility in the patients with unknown causes and a parameter affecting the number of oocytes and embryos in this group. However, studies with a larger target population are needed to explain this potential indicator.

Protective effects of hydroalcoholic extract of Stachys pilifera on paracetamol-induced nephrotoxicity in female rats.

Background and purpose:Stachys pilifera is used in traditional medicine due to its antioxidant, anti-inflammatory, and antimicrobial effects. The goal of this study was to examine the renoprotective activity of the hydroalcoholic extract of aerial parts of S. pilifera on paracetamol (PCM)-induced nephrotoxicity.Experimental approach:The Wistar female rats were randomly divided into four groups including control, PCM, S. pilifera hydroalcoholic extract (SPE), and PCM + SPE. The animals received SPE (500 mg/kg) for one week and PCM (3 g/kg) on the 6th day orally. Kidney function tests and oxidant/antioxidant markers were determined in serum and tissue homogenate, respectively. Protein and mRNA levels of TNF-α, as well as hematoxylin and eosin staining, were assessed in the kidney tissue.Findings/Results:Treatment with SPE in the PCM group significantly decreased blood urea nitrogen and creatinine against the merely PCM rats (P < 0.05). The amount of nitric oxide metabolite and superoxide dismutase activity in the group receiving SPE showed a significant increase compared to PCM rats (P < 0.05). A significant difference in TNF-α levels between the groups was not observed. Histological changes were improved in the rats treated with SPE.Conclusion and implications:Totally, our findings showed that SPE can inhibit PCM nephrotoxicity by enhancing kidney function markers, antioxidant status, and histological changes. Though, more researches are required to estimate the possible mechanism of SPE.

Differences between Tumor Necrosis Factor-Alpha Levels and Interleukin-2 Levels in people with schizophrenia who get risperidone drugs in the acute phase of treatment in the Prof. DR. M. Ildrem Psychiatric Hospital, Medan

Background: We looked for differences between Tumor Necrosis Factor – Alpha and Interleukin-2 levels in people with schizophrenia who got risperidone medication in the acute phase of treatment at Prof.DR.M.Ildrem psychiatric hospital Medan.&#x0D; Methods: We conducted a cross-sectional study that included 40 subjects. This study is a numerical comparative analytical study not paired with a single measurement with subject retrieval performed in a non-probability sampling method of consecutive sampling type.&#x0D; Results: The analysis test results showed Median levels of TNF-α in the group of people with schizophrenia were obtained at 3.40 with a minimum score of 0.65 and with a maximum score of 43.8 while in the healthy control group the median score of TNF-α levels was 14.75 with a minimum score of 5.18 and a maximum score of 31.1. The average IL-2 level in people with schizophrenia was found at 5.26 with a standard deviation of ±0.987 and at the control was obtained at 3.43 with a standard deviation ± 0.665.&#x0D; Conclusions: There is a significant difference in TNF-α levels between groups of people with schizophrenia who get risperidone 4 mg in the acute phase of treatment and control. There was a significant difference between IL-2 levels between people with schizophrenia who got risperidone 4 mg in the acute phase of treatment and control.

Altered overnight levels of pro-inflammatory cytokines in men and women with posttraumatic stress disorder

BackgroundPosttraumatic stress disorder (PTSD) is associated with disturbed sleep and elevated levels of pro-inflammatory cytokines, including interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Studies in animals and healthy humans have also shown that disrupted sleep elevates pro-inflammatory cytokines, including IL-6 and TNF-α. A better understanding of overnight cytokine levels and sleep might shed light on possible mechanisms for elevated inflammation in PTSD. Thus, we investigated overnight levels of IL-6 and TNF-α in individuals with and without PTSD while recording sleep polysomnography (PSG). MethodSerum samples were collected from otherwise healthy, medication-free participants with chronic PTSD (n = 44; 50% female; M age = 30.34 ± 8.11) and matched controls (n = 49; 53% female; M age = 30.53 ± 6.57) during laboratory PSG. Levels of IL-6 and TNF-α were measured at hours 0, 2, 4, 6, and 8 after typical sleep onset time using serial serum samples. Plasma IL-6 and TNF-α levels were quantified using enzyme-linked immunosorbent assays. ResultsGrowth model analysis indicated a significantgroup by time interaction for IL-6 (t[247] = -2.92, p = .005) and a significant group by sex by time interaction for TNF-α (t[275] = 2.02, p = .04). PTSD positive men and women initially had higher IL-6 and TNF-α at sleep onset, but not at the end of their sleep cycle. Men with PTSD showed a peak of TNF-α at the end of the sleep cycle, whereas male control subjects demonstrated an inverted U-shaped profile. There were no significant differences in TNF-α levels overnight between women with and without PTSD. ConclusionTo our knowledge, this is the largest study to examine IL-6 overnight in a PTSD sample and the first study to examine overnight TNF-α in PTSD. Overnight IL-6 and TNF-α levels may be altered in individuals with PTSD compared to those without PTSD, and TNF-α trajectories also differed by sex. The current findings highlight the need to consider sex, sleep, time of day, and circadian variation when examining inflammation in PTSD. Additional research in broader study samples will be necessary to clarify associations between disrupted sleep, cytokines, and increased risk for disease in PTSD.

Effect of Circuit Training on TNF Alpha Levels and Six Minutes Walk Test in Patients with Chronic Heart Failure

Abstract: Physical exercise in patients with heart failure can decrease the level of proinflammatory biomarkers andincrease functional capacity. Circuit training is one of the most advantageous exercise models because it improves cardiorespiratory fitness and muscle strength.This study aimed to investigate the effect of circuit training on TNF alphaandsix minutes walk test in patients with chronic heart failure in RSUP Dr. Kariadi. Twenty-six stable chronic heart failure with reduced ejection fraction patients were randomized into exercise group that received circuit training in the rehabilitation center of Kariadi Hospital for a month and control group. TNF- α levels as a inflammatory biomarker and distance of six minute walk test as a functional capacity parameter were taken before and after the exercise period.Nine-teensubjects completed the study without any significant side effects.There was no significant difference in TNF-α levels before and after treatment between treatment groups and control groups (p=0,513). The treatment group with circuit training showed a greater increase in distance of six minute walk test than the control group (p=0,034).It was concluded that circuit training in patients with chronic heart failure can increase distance of six minute walk test, but no changes in TNF alpha levels. Keywords: Circuit training, TNF-a, six minute walk test

Effects of acupoint catgut embedding therapy paired with dietary intervention on tumour necrosis factor-α levels and abdominal circumference in patients with obesity

Obesity is associated with a decreased quality of life and is a risk factor for the development of other diseases. Furthermore, obesity is associated with a chronic inflammatory status that contributes to the development of metabolic dysfunction and metabolic syndrome. Acupuncture assists weight loss through the suppression of appetite and the reduction of the risk of metabolic syndrome. The aim of this study was to determine the effectiveness of acupoint catgut embedding therapy combined with dietary intervention on serum tumour necrosis factor-α (TNF-α) levels and abdominal circumference. This study was a randomised, double-blind, controlled clinical trial involving 36 patients with obesity who were randomly divided into the following groups: catgut embedding method combined with dietary intervention (case group) and sham acupuncture combined with dietary intervention (control group). The results showed a significant difference in TNF-α levels before and after treatment within the case group and a significant difference in abdominal circumference change between the two groups. Acupoint catgut embedding combined with dietary intervention has significant effects on serum TNF-α levels and abdominal circumference in patients with obesity.

Elevation in liver enzymes is associated with increased IL-2 and predicts severe outcomes in clinically apparent dengue virus infection

The objective of the present study was to assess the circulating TNF-α and IL-2 levels in dengue virus (DENV) infected patients and to correlate these with clinical severity of DENV infections. A single analyte quantitative immunoassay was used to detect TNF-α and IL-2 in 24 dengue fever (DF) and 43 dengue haemorrhagic fever (DHF) patients, 15 healthy adults and 6 typhoid patients. The mean TNF-α and IL-2 levels of DENV- infected patients were higher than that of healthy adults and typhoid patients. No significant difference in TNF-α levels was noted between DF and DHF patients (p=0.5) but a significant increase in IL-2 levels was observed in DHF compared with DF patients (mean of DF=59.7pg/mL, mean of DHF=166.9pg/mL; p=0.02). No significant association of TNF-α or IL-2 levels was noted with packed cell volume (>45), thrombocytopenia, leucopenia or the presence of viraemia. The liver function tests measuring AST (aspartate aminotransferase) (p=0.01) and ALT (alanine aminotransferase) (p=0.02) levels were significantly elevated in DENV-infected patients. AST:ALT was significantly elevated in DHF/DSS (dengue shock syndrome) compared with DF patients. A significant positive linear correlation was noted between AST and IL-2 (r=0.31; p=0.01) and ALT and IL-2 elevations (r=0.2; p=0.02). Thus, AST and ALT levels correlate with both disease severity and circulating IL-2 levels. We suggest a role for circulating IL-2 in liver dysfunction and propose that a combined assessment of AST/ALT in conjunction with IL-2 at the early stages of symptomatic DENV infection may be useful to predict the severe forms of dengue.

Seminal plasma leptin and spermatozoon apoptosis in patients with varicocele and leucocytospermia.

Excessive apoptotic spermatozoon death is associated with male infertility. Leptin regulates apoptosis in several cell types. We prospectively investigated if seminal plasma leptin mediates spermatozoon apoptosis in 74 varicocele (VC) patients and 70 leucocytospermia patients. Spermatozoa from 40 normospermic men were used as controls. Routine semen analysis, spermatozoon apoptosis rate, seminal plasma leptin, reactive oxygen species (ROS) and tumour necrosis factor-alpha (TNF-α) levels were measured. In VC and leucocytospermia patients, seminal plasma leptin levels and spermatozoon apoptosis rates were significantly higher compared with controls. In the VC group, seminal plasma ROS levels were significantly higher compared with controls; there were no significant differences in TNF-α levels. In the leucocytospermia group, both ROS and TNF-α levels were significantly higher compared with controls. In both the VC and leucocytospermia groups, there was a significant positive correlation between the spermatozoon apoptosis rate and leptin levels and ROS and leptin levels. There was a significant correlation between leptin and TNF-α levels in the leucocytospermia group. Seminal plasma leptin levels correlate significantly with spermatozoon apoptosis rate, and leptin may be a spermatozoon pro-apoptotic factors. The generation of ROS is a possible mechanism. Leptin may induce apoptosis via TNF-α in leucocytospermia patients.

P165 Altered blood plasma levels of cytokine in schizophrenia

One of the severe mental diseases, schizophrenia, is characterized with multifactorial nature and atrong genetic background [1]. Low-grade inflammatory processes have been shown to contribute to the pathogenesis of schizophrenia [2]. However, recent findings on the role of several cytokines and their genetic variants in schizophrenia are still controversial [3], [4], [5], [6]. In this study, we evaluated the association of proinflammatory and chemotactic cytokine levels with schizophrenia. Enzyme-linked immunsorbent assay (ELISA) was used to measure levels of tumor necrosis factor-α (TNF-α) and interleukin (IL)-8 cytokines in the blood plasma of patients with schizophrenia (neuroleptic-treated patients n = 120, neuroleptic-free patients n = 10) and healthy subjects (controls, n = 120). We found 1.16 times higher TNF-α plasma levels in neuroleptic-treated patients compared to healthy subjects (p < 0.0001). Further, TNF-α levels were higher in neuroleptic-free patients when compared to controls (1.22 times in average, p = 0.025). However, no significant difference in TNF-α levels between neuroleptic-treated and neuroleptic-free subjects was found. Concerning IL-8, the increased levels of this chemokine in neuroleptic-free and neuroleptic-treated patients compared to healthy subjects were found (in average 3.85 and 5.66 times, respectively, p < 0.0001). Importantly, no significant difference in IL-8 plasma levels between neuroleptic-treated and neuroleptic-free patients was detected. Our results indicated altered IL-8 and TNF-α plasma levels in schizophrenia suggesting that these cytokines might be involved in the pathogenesis of schizophrenia.

Tumor necrosis factor alpha as a marker of systemic and local inflammation in &amp;ldquo;healthy&amp;rdquo; smokers

Tobacco smoking induces a local and systemic inflammatory reaction and also a decline in pulmonary function. There are some novel noninvasive methods to measure the degree of inflammatory bronchial reaction, including the exhaled breath condensate (EBC) in which several inflammatory markers can be measured, including tumor necrosis factor alpha (TNF-alpha). There is a clear clinical need to develop methods that allow early detection of smokers at risk of losing pulmonary function. THE AIMS OF THE PRESENT STUDY ARE: 1) to show that smokers show higher levels of TNF-alpha both in serum and EBC; 2) to analyze the possible influence of gender, age, and weight on this parameter; and 3) to determine a possible association between smoking and pulmonary function parameters and TNF-alpha levels. We have prospectively analyzed two cohorts of smokers and non-smokers subjects without any chronic or acute disease (within eight weeks of study initiation). We have performed pulmonary function tests with bronchodilators and also collected EBC and blood samples before smoking cessation. Statistical analysis was performed with SPSS 11.0 for Windows Statistical Package. The study has enrolled 17 patients (8 smokers), 50% of whom were females. Mean age was 38.59 years old (standard deviation, 7.4). The mean number of cigarettes smoked in the smoker group was 26.14 (11.29) cigarettes/day and the mean age when tobacco first began was 15.14 (2.04) years. We have not been able to show any significant differences in TNF-alpha levels according to age or weight. For the whole series we have not found any significant influence of gender in TNF-alpha levels, but after dividing the series in smokers and nonsmokers, we have shown higher levels of TNF-alpha in serum (5.59 [0.26] pg/mL vs 5.56 [0.37] pg/mL; nonsignificant [NS]) and EBC (4.94 [0.41] pg/mL vs 4.22 [0.36] pg/mL; p = 0.031) in male smokers. On the other hand, nonsmoking females showed slightly higher TNF-alpha levels in serum (5.70 [0.50] pg/mL vs 5.42 [0.29] pg/mL; NS) and EBC (4.54 [0.92] vs 4.11 [0.41 pg/mL]; NS). Smokers had higher TNF-alpha levels in EBC (4.46 [0.58] pg/mL vs 4.34 [0.62] pg/mL; NS), while serum TNF-alpha levels were slightly higher in nonsmokers (5.52 [0.56] pg/mL vs 5.50 [0.27] pg/mL; NS). We have not demonstrated any association between tobacco consumption and TNF-alpha levels. We have not shown any significant relation between pulmonary function and the studied parameters, with only a modest association between forced expiratory volume at one second and forced vital capacity and TNF-alpha levels in EBC. Smokers show higher TNF-alpha levels in EBC. Among smokers, males show higher levels of TNF in serum and EBC. We have not confirmed any significant influence of age or weight on TNF-alpha levels. These levels do not seem to be influenced either by the amount of tobacco or the time since habit began. We have shown a modest relation between pulmonary function and TNF-alpha levels in EBC.

Relation between insulin resistance and serum concentrations of IL-6 and TNF-α in overweight or obese women with early stage breast cancer

Insulin resistance (IR) and obesity may be risk factors for breast cancer. The mechanism of IR in patients with cancer has not been fully clarified yet. This study was conducted to evaluate the possible role of circulating cytokines; tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6) in inducing IR in 20 overweight or obese patients with early stage breast cancer and to compare their levels with that of body mass index matched 20 healthy controls. IR was calculated by homeostasis model assessment (HOMA) method. Four groups were formed according to a 2.7 HOMA-IR cut-off value as breast cancer with or without IR and controls with or without IR. IL-6 and HOMA-IR values were found to be higher in breast cancer patients with IR compared to other groups. There was no significant difference in TNF-α levels between groups. HOMA-IR values correlated with estradiol and IL-6 levels in all breast cancer patients but not TNF-α. HOMA-IR values, serum insulin, estradiol and IL-6 levels in the receptor positive group were significantly higher than those of the receptor negative group. These results suggested a possible contribution of endogenous IL-6 production and hyperinsulinemia to the development of breast cancer in overweight or obese patients with prominent IR.

IL-1β in bronchial lavage fluid is a non-invasive marker that predicts the viability of the pulmonary graft from the non-heart-beating donor

Background Viability testing of the pulmonary graft retrieved from the non-heart-beating donor (NHBD) is mandatory for successful outcome after lung transplantation. Functional assessment by ex vivo reperfusion, however, remains a cumbersome procedure. In this study, therefore, we wanted to investigate the possible value of the proinflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) measured in bronchial lavage fluid (BLF) in predicting functional outcome of the pulmonary graft after reperfusion. Methods Domestic pigs (29.9 ± 0.56 kg) were sacrificed and divided in 5 groups ( n = 5/group). In the non-ischemic group (NHBD-0), the heart-lung block was explanted immediately. In the other groups the animals were left untouched with increasing time intervals (1 hour = NHBD-1; 2 hours = NHBD-2; 3 hours = NHBD-3). Thereafter both lungs were cooled topically via chest drains up to a total ischemic interval of 4 hours. Finally, in the heart-beating donor group lungs were flushed and stored for 4 hours (4°C) [HBD]. BLF samples were taken from the right lung in all groups after explantation for measurement of IL-1β and TNF-α and the left lung was prepared for evaluation in an isolated reperfusion circuit. Haemodynamic, aerodynamic and oxygenation parameters were measured. Wet-to-dry weight ratio (W/D) was calculated after reperfusion. Results Graft function deteriorated with increasing time intervals after death. A strong correlation was found between the increase of IL-1β concentration measured in BLF and the increase in pulmonary vascular resistance (r = 0.80), mean airway pressure (r = 0.74) and wet-to dry weight ratio (r = 0.78); ( p < 0.0001, for all parameters). No significant differences in TNF-α levels in BLF were observed amongst groups ( p = 0.933). Conclusions IL-1β in BLF prior to reperfusion correlated well with graft function and may therefore be a useful, non-invasive marker that can predict the viability of the pulmonary graft from the NHBD.

Targeted deletion of the lipopolysaccharide (LPS)-binding protein gene leads to profound suppression of LPS responses ex vivo, whereas in vivo responses remain intact.

Gram-negative bacterial lipopolysaccharide (LPS) stimulates phagocytic leukocytes by interacting with the cell surface protein CD14. Cellular responses to LPS are markedly potentiated by the LPS-binding protein (LBP), a lipid-transfer protein that binds LPS aggregates and transfers LPS monomers to CD14. LBP also transfers LPS to lipoproteins, thereby promoting the neutralization of LPS. LBP present in normal plasma has been shown to enhance the LPS responsiveness of cells in vitro. The role of LBP in promoting LPS responsiveness in vivo was tested in LBP-deficient mice produced by gene targeting in embryonic stem cells. Whole blood from LBP-deficient animals was 1,000-fold less responsive to LPS as assessed by the release of tumor necrosis factor (TNF)-alpha. Blood from gene-targeted mice was devoid of immunoreactive LBP, essentially incapable of transferring LPS to CD14 in vitro, and failed to support cellular responses to LPS. These activities were restored by the addition of exogenous recombinant murine LBP to the plasma. Despite these striking in vitro findings, no significant differences in TNF-alpha levels were observed in plasma from wild-type and LBP-deficient mice injected with LPS. These data suggest the presence of an LBP-independent mechanism for responding to LPS. These LBP knockout mice may provide a tool for discovering the nature of the presumed second mechanism for transferring LPS to responsive cells.