Serum Concentrations Of Tumor Necrosis Factor-alpha Research Articles

Serum tumor necrosis factor-alpha concentrations are negatively correlated with serum 25(OH)D concentrations in healthy women

BackgroundCirculating 25 hydroxyvitamin D (25 (OH)D), an accurate measure of vitamin D status, is markedly greater in individuals with increased exposure to ultraviolet B (UVB) light via sunlight or the use of artificial UV light. Aside from the known relationship between vitamin D and bone, vitamin D has also been implicated in immune function and inflammation. Furthermore, a mass of evidence is accumulating that vitamin D deficiency could lead to immune malfunction. Our overall objective was to study the relationship between vitamin D status (as determined by serum 25(OH) D concentrations) and inflammatory markers in healthy women.MethodsThis observational study included 69 healthy women, age 25–82 years. Women with high UVB exposure and women with minimal UVB exposure were specifically recruited to obtain a wide-range of serum 25(OH)D concentrations. Health, sun exposure and habitual dietary intake information were obtained from all subjects. Body composition was determined by dual-energy-x-ray absorptiometry. A fasting blood sample was collected in the morning and analyzed for serum 25(OH)D, parathyroid hormone (iPTH), estradiol (E2), cortisol, and inflammatory markers [tumor necrosis factor -alpha (TNF-α), interleukin-6 and -10 (IL-6, IL-10), and C-reactive protein (CRP)].ResultsWomen with regular UVB exposure (Hi-D) had serum 25(OH)D concentrations that were significantly higher (p < 0.0001) and iPTH concentrations that were significantly lower (p < 0.0001) than women without regular UVB exposure (Lo-D). Although IL-6, IL-10, and CRP did not have a statistically significant relationship with 25(OH)D concentrations, linear regression models revealed a significant inverse relationship between serum 25(OH)D and TNF-α concentrations. This relationship remained significant after controlling for potential covariates such as body fat mass, menopausal status, age, or hormonal contraceptive use.ConclusionSerum 25(OH)D status is inversely related to TNF-α concentrations in healthy women, which may in part explain this vitamin's role in the prevention and treatment of inflammatory diseases. Results gleaned from this investigation also support the need to re-examine the biological basis for determining optimal vitamin D status.

Endotoxemia por lipopolissacarídeo de Escherichia coli, em eqüinos: efeitos de antiinflamatórios nas concentrações sérica e peritoneal do fator de necrose tumoral alfa (TNF-alfa)

Avaliou-se a inibição da produção do fator de necrose tumoral alfa (TNF-alfa) devido ao pré-tratamento com antiinflamatório esteroidal (dexametasona) e não esteroidal (diclofenaco sódico) em eqüinos com endotoxemia induzida experimentalmente. Foram utilizados 15 cavalos machos não castrados, distribuídos em três grupos de cinco animais: controle (C), diclofenaco sódico (DS) e dexametasona (DM). A endotoxemia subletal foi induzida pela infusão intravenosa (IV) de 0,1mg/kg/pv de lipopolissacarídeo (LPS) de Escherichia coli 055:B5, administrado em 250ml de solução estéril de cloreto de sódio a 0,9%, durante 15min. Os cavalos do grupo-controle foram tratados com solução de cloreto de sódio a 9% IV. Nos animais do grupo DS, administraram-se, por via oral, 2,2mg/kg de diclofenaco sódico e, nos do grupo DM, 1,1mg/kg de dexametasona IV, respectivamente, 60 e 30min antes da infusão da endotoxina. Mensurou-se, por meio de ensaio de toxicidade com células da linhagem L929, a concentração de TNF-alfa no soro e no líquido peritoneal às 0, 1¼, 3 e 6 horas após injeção do LPS. No grupo-controle, observou-se aumento significativo de TNF-alfa sérico, em relação ao valor basal e aos grupos DS e DM, 1,15 horas após a indução da endotoxemia. No líquido peritoneal, as concentrações observadas estavam abaixo daquelas da curva padrão de TNF-alfa, não havendo diferença entre os grupos (P&gt;0,05).

Early Excision of a Full-Thickness Burn Prevents Peripheral Nerve Conduction Deficits in Mice

A full-thickness 20 percent body surface area burn in mice produces a significant decrease in tibial motor nerve conduction velocity within 6 hours of the burn and in sensory conduction velocity within 7 days. This suggests that cutaneous burn injury produces a systemic response that affects peripheral motor and sensory nerve function at a distance from the burn site. The authors tested the hypothesis that burn wound excision either 30 minutes or 3 hours after burn would prevent neuropathy. A 20 percent body surface area third-degree burn was applied to the backs of anesthetized mice using procedures that followed National Institutes of Health guidelines. Motor nerve conduction velocity and sensory conduction velocity were determined in intact, anesthetized mice by percutaneous nerve stimulation. Burn wounds were excised and closed at 30 minutes or 3 hours after burn. Motor nerve conduction velocity and sensory conduction velocity were measured before burn and 1, 3, 7, 14, and 21 days after a burn or sham procedure. The number of circulating neutrophils and serum concentrations of tumor necrosis factor-alpha, nitrite, and electrolytes were also determined in each group. Motor nerve conduction velocity and sensory conduction velocity in the 30-minute excision (n = 10) and sham group (n = 5) were not significantly different. Motor nerve conduction velocity and sensory conduction velocity in the nonexcised group (n = 10) and 3-hour excision group (n = 10) were significantly decreased. Serum tumor necrosis factor-alpha concentration was elevated 6 hours after burn in nonexcised animals (n = 9) and in 3-hour excision mice (n = 8) but was not significantly different in the sham (n = 8) and the 30-minute excision group (n = 7). The authors conclude that burn wound excision at 30 minutes but not at 3 hours prevents the nerve conduction deficits measured in mice with 20 percent body surface area burns. The cellular basis of burn-induced neuropathy is unknown, but nitric oxide and tumor necrosis factor alpha-alpha appear to play a role.

Liquid ventilation

Liquid ventilation

Proinflammatory cytokines in early assessment of the prognosis of acute pancreatitis.

Proinflammatory cytokines are involved in the pathogenesis of acute pancreatitis. The value of serum levels of tumor necrosis factor-alpha, interleukin-1-beta, interleukin-6, and interleukin-8 in predicting the outcome of acute pancreatitis was evaluated. In 50 patients with acute pancreatitis, the serum concentrations of tumor necrosis factor-alpha, interleukin-1-beta, interleukin-6, interleukin-8, and C-reactive protein were determined on days 1, 2, 3, 4, and 7 after admission. Acute Physiology and Chronic Health Evaluation (APACHE II) scores were recorded on days 1, 2, and 3. Serum concentrations of interleukin-1-beta, interleukin-6, interleukin-8, and C-reactive protein on days 1-7 were significantly higher in patients with severe pancreatitis than in patients with mild pancreatitis. Patients with severe attacks had significantly elevated serum tumor necrosis factor-alpha concentrations on days 1-3 compared with those with mild attacks, but not on days 4 and 7. The median peak value of tumor necrosis factor-alpha, interleukin-1-beta, interleukin-6, and interleukin-8 was reached on day 1, in contrast to the median peak of C-reactive protein, which was reached on day 2. Using cutoff levels of 12 pg/ml for tumor necrosis factor-alpha, 1 pg/ml for interleukin-1-beta, 400 pg/ml for interleukin-6, 100 pg/ml for interleukin-8, 12 mg/dl for C-reactive protein, and 10 for the Acute Physiology and Chronic Health Evaluation (APACHE II) score, the accuracy rates for detecting severe pancreatitis were 72%, 82%, 88%, 74%, 80%, and 72%, respectively, on day 1 and 78%, 74%, 80%, 76%, 80%, and 78%, respectively, on day 2. Among the proinflammatory cytokines, interleukin-6 is the most useful parameter for early prediction of the prognosis of acute pancreatitis.

Elevated serum tumor necrosis factor-alpha concentrations and bioactivity in Type 2 diabetics and patients with android type obesity

The role of tumor necrosis factor-alpha in insulin resistance has been studied in 59 patients with Type 2 diabetes, 28 with android type obesity and 35 healthy lean controls. Immunoreactive concentrations and bioactivity of serum tumor necrosis factor-alpha have repeatedly been determined in 8 weeks intervals for 12 months, five times per patients, by using ELISA and L929 cell cytotoxicity bioassay. Significantly higher immunoreactive tumor necrosis factor-alpha concentrations and bioactivity have been found in both, the Type 2 diabetic and obese groups as compared to the healthy persons. Tumor necrosis factor-alpha concentrations and bioactivity have showed a significant positive linear correlation with the elevated basal serum C-peptide levels and body mass indexes in both groups of patients. According to these data the cytokine might play a role in insulin resistance in obesity as well in Type 2 diabetes.

Endotoxin and Tumor Necrosis Factor-α in the Pathogenesis of Hepatic Encephalopathy

Hepatic encephalopathy (HE) is a complex neuropsychiatric syndrome characterized predominantly by augmented neuronal inhibition and probably neuronal damage. Several theories concerning the pathogenesis of HE have been proposed; none of these theories is necessarily exclusive. Furthermore, the validity of none of them has been definitively proved experimentally. In this review article an important role of endotoxin and tumor necrosis factor-alpha (TNF) in the pathogenesis of HE is suggested. The involvement of endotoxin and TNF in the pathogenesis of HE seems to be very convincing; it may explain many of the derangements seen in HE. It also seems to be in strong relation to the main theories about HE, the ammonia theory, the GABAergic theory, the benzodiazepine theory, and the AAA/false neurotransmitter theory, where these theories may represent some of the mechanisms whereby TNF may cause inhibition and damage to the CNS in HE, or may represent accompanying features to elevated levels of endotoxin and TNF, with no important role in the pathogenesis of HE. The possible involvement of endotoxin and TNF in the pathogenesis of HE may possess an important clinical application, for serum LPS and TNF concentrations may be of important diagnostic and prognostic value in HE, and treatment with antibodies against endotoxin and against TNF may have potentially beneficial therapeutic effects in this serious and potentially fatal disease.

The role of tumor necrosis factor-α in acute endotoxin-induced hepatotoxicity in ethanol-fed rats

An in vivo model of ethanol ingestion in rats was used to examine tumor necrosis factor-alpha production after intravenous injection with lipopolysaccharide or saline solution. Four groups of 125-gm male Sprague-Dawley rats were given one of the following four diets: liquid ethanol diet (ethanol, 36% of calories), liquid control diet, chow ad libitum or control liquid diet pair-fed to match calories consumed by ethanol-fed rats. After 6 wk of diet, all rats were injected with 1 mg/kg lipopolysaccharide or 0.9% saline. AST concentrations in the ethanol-lipopolysaccharide group (388 +/- 54 U/ml) were significantly increased compared with those in control-saline, ethanol-saline and control-lipopolysaccharide groups (166 +/- 23, 166 +/- 18, 219 +/- 47; p < 0.01). Serum tumor necrosis factor-alpha concentrations for the ethanol-LPS group (3,990 +/- 624 pg/ml) were increased compared with those in control-saline (87 +/- 18), ethanol-saline (68 +/- 24) and control-LPS (695 +/- 165) groups (p < 0.001). A strong correlation was seen between serum tumor necrosis factor-alpha and AST concentrations (r = 0.91, p < 0.001). Treatment with lipopolysaccharide also increased transcriptional levels of tumor necrosis factor-alpha-specific mRNA from hepatic Kupffer cells isolated from rats fed the long-term ethanol diet by a factor of 3 compared with control rats. From these data, we conclude that long-term ethanol administration sensitized hepatic Kupffer cells to secrete high levels of tumor necrosis factor-alpha after lipopolysaccharide injection. Increased serum tumor necrosis factor-alpha concentrations correlated directly with increased levels of serum transaminase, which may have reflected hepatic injury.

Lyophilized liposome encapsulated hemoglobin

To characterize the hemodynamic, biochemical, and hematologic responses to the administration of the oxygen-carrying fluid lyophilized liposome-encapsulated hemoglobin in the conscious, normovolemic rat. Prospective, randomized trial. Animal laboratory, Jefferson Medical College. Eighty-four male Sprague-Dawley rats. Catheters were introduced into the right atrium (through the jugular vein) and both femoral arteries of test animals, and a thermistor was placed in the ascending aorta through the left common carotid artery for infusion of lyophilized liposome-encapsulated hemoglobin, blood collection, and blood pressure (BP) and cardiac output determinations. Lyophilized liposome-encapsulated hemoglobin (n = 8) infusion (1 mL/min iv) at 1 or 6 mL/kg (10% of estimated blood volume) had no detectable effect on BP, cardiac output, total peripheral resistance, and heart rate during the 5-hr observation period. The infusion also had no effect on hematocrit, leukocyte count, and serum tumor necrosis factor-alpha concentrations. Survival at 7 days was 100% (n = 20). Lyophilized liposome-encapsulated hemoglobin caused transient (2-hr) thrombocytopenia (-24 +/- 9% vs. a Ringer's lactate control group, p < .01), and marginally increased serum thromboxane B2 concentrations (14.6 +/- 6 pg/100 microL, p < .01). These data suggest that lyophilized liposome-encapsulated hemoglobin can be safely administered to conscious rats, supporting the development of this substance as a potential blood substitute.

Tumor necrosis factor: status in reactions in leprosy before and after treatment.

Tumor necrosis factor-alpha (TNF) is an important mediator of immunologic responses to chronic infections. Sera from 25 patients with acute reactions (6 with type 1 upgrading, 8 with type 1 downgrading, and 11 with type 2 reaction) were assayed for TNF before treatment and after clinical remission of the acute episode. The results were compared with serum TNF levels in healthy controls and fresh pauci- and multibacillary leprosy patients. TNF levels in acute reactions were higher than in the control groups (significant only in upgrading reaction). In type 1 reaction, serum TNF concentrations fell to approximately the levels of the control patients following treatment and clinical remission. In type 2 reaction, however, levels of TNF were seen to rise further (became statistically significant) as a result of therapy induced clinical remission. The rise in TNF-alpha level in reactions in leprosy is significant and indicates its active role in immunopathogenesis. The corresponding decline in TNF-alpha levels seen following regression of type 1 (lepra) reactions was not observed in the case of type 2 (ENL) reaction. This probably reflects the enhancement of cellular immunity in such cases and/or an attempt by the immunologic process to overcome specific inhibitors.

Cachexia and tumour necrosis factor-alpha in cytomegalovirus infection.

Although cachexia is a common feature of cytomegalovirus infection, little is known about its cause. To explore any contributory role that tumour necrosis factor-alpha (TNF) might have the serum concentrations of TNF in eight patients who developed CMV disease after liver transplantation were investigated. All patients exhibited pronounced and long lasting increases in TNF serum concentrations. Increased endogenous TNF concentrations were associated with weight loss and anorexia. In contrast, liver transplant recipients without CMV disease showed no weight loss.

Decreased Serum Triiodothyronine Is Associated with Increased Concentrations of Tumor Necrosis Factor

Previous studies in laboratory animals have shown that tumor necrosis factor-alpha (TNF) may alter thyroid function tests. To determine whether elevated serum TNF levels are associated with altered serum concentrations of T4, T3, free T4, rT3, and TSH, we measured these parameters in 29 nursing home residents with detectable serum TNF levels and compared the levels to those found in 36 patients with undetectable serum TNF levels. The 2 groups were matched for age, sex, clinical problems, use of medications, and nutritional status. Patients with detectable serum TNF levels had significantly lower serum T3 concentrations compared to those with undetectable levels [1.072 +/- 0.588 vs. 1.621 +/- 0.594 nmol/L (mean +/- SD); P less than 0.01]. Differences in other tests did not achieve statistical significance. Thyroid function tests were not significantly different when patients with detectable interleukin-1 alpha levels, another cytokine secreted during endotoxemia, were compared to those with undetectable levels. These observations taken together with the previous findings in laboratory animals suggest that some of the alterations in thyroid hormone levels seen in nonthyroidal illness are associated with elevated serum concentrations of TNF.

Serum tumor necrosis factor-alpha levels in allogeneic bone marrow transplant recipients with acute leukemia.

We determined the serum levels of tumor necrosis factor-alpha (TNF) in allogeneic bone marrow transplant recipients in order to evaluate the relationship between TNF and graft-versus-host disease (GVHD). Eight patients with acute leukemia receiving an HLA-identical marrow graft were studied. Samples from healthy subjects and pretransplant recipients were all negative for TNF. Six of eight patients had detectable levels of TNF in serum after transplantation. All three patients with acute GVHD, and three of five patients without acute GVHD had elevated TNF levels in serum. Among the patients with increased TNF levels, documented infection was demonstrated in only one patient, with a clinical diagnosis of B19 parvovirus infection. Serum TNF levels were elevated when the WBC counts were more than 2,000/microliters. However, serum concentrations of TNF significantly correlated with body temperature. Although we could not conclude definitely that serum TNF levels correlated with severity of GVHD, it was suggested that TNF may be produced as a result of latent infections or immunological reaction against non-HLA allogeneic antigens.