Serum Levels Of Tumor Necrosis Factor-alpha Research Articles

Effect of Streptomyces 23-2B metabolites on hepatic lipid peroxidation and some antioxidant parameters in Wister rats

Streptomyces 23-2B is one of actinomycetes associated with marine clam Donax trunculus and has potential source of bioactive metabolites, which possesses a broad spectrum antibiotic and anticancer activities. This study aims to evaluate the effect of Streptomyces 23-2B metabolites on hepatic lipid peroxidation (LPO), reduced glutathione (GSH) levels, as well as serum uric acid, total cholesterol (TC), triglyceride (TG), nitric oxide (NO) and tumor necrosis factor-alpha (TNF-α) levels of rat. Animals were divided into four groups: the control group, which received 0.1 ml of 10% Tween-80 by intraperitoneally injection, and the other three experimental groups, which received 10% Tween 80 solution of Streptomyces 23-2B metabolites in doses of 0.5, 5 and 50 mg/kg body weight at an interval 2 days for 2 weeks. LPO levels showed significant decrease with the lowest doses. The effect at a dose of 50 mg/kg of Streptomyces 23-2B metabolites on TG was more pronounced than the other two doses (0.5 and 5 mg/kg body weight). Hypocholesterolemia was recorded in the treated rats with 0.5 and 5 mg/kg of Streptomyces 23-2B. However, the highest dose enhanced the elevation of serum TNF-α and NO levels. Thus, the present study reveals that Streptomyces 23-2B metabolite is a newly discovered biomaterial from microorganisms. The novel substance showed inhibitory activity against LPO in rat liver homogenate and improving the immune response by releasing TNF-α and NO in serum.

TLR9 Polymorphisms Are Associated with Altered IFN-γ Levels in Children with Cerebral Malaria

Toll-like receptor (TLR) polymorphisms have been associated with disease severity in malaria infection, but mechanisms for this association have not been characterized. The TLR2, 4, and 9 single nucleotide polymorphism (SNP) frequencies and serum interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) levels were assessed in Ugandan children with cerebral malaria (CM, N = 65) and uncomplicated malaria (UM, N = 52). The TLR9 C allele at -1237 and G allele at 1174 were strongly linked, and among children with CM, those with the C allele at -1237 or the G allele at 1174 had higher levels of IFN-gamma than those without these alleles (P = 0.03 and 0.008, respectively). The TLR9 SNPs were not associated with altered IFN-gamma levels in children with UM or altered TNF-alpha levels in either group. We present the first human data that TLR SNPs are associated with altered cytokine production in parasitic infection.

Kupffer-cell activity is essential for thyroid hormone rat liver preconditioning

We studied the role of Kupffer cell functioning in T3 liver preconditioning against ischemia-reperfusion (IR) injury using the macrophage inactivator gadolinium chloride (GdCl3) previous to T3 treatment. Male Sprague-Dawley rats given a single i.p. dose of 0.1 mg T3/kg were subjected to 1 h ischemia followed by 20 h reperfusion, in groups of animals pretreated with 10 mg GdCl3/kg i.v. 72 h before T(3) or with the respective vehicles. IR resulted in significant enhancement of serum aspartate aminotransferase (3.3-fold increase) and tumor necrosis factor-alpha (93% increase) levels, development of liver damage, and diminished nuclear factor-kappaB DNA binding over control values. These changes, which were suppressed by the T3 administration prior to IR, persisted in animals given GdCl3 before T3 treatment, under conditions of complete elimination of ED2+ Kupffer cells achieved in a time window of 72 h. It is concluded that Kupffer cell functioning is essential for T3 liver preconditioning, assessed in a warm IR injury model by hepatic macrophage inactivation.

Preventive effects of chronic exogenous growth hormone levels on diet-induced hepatic steatosis in rats.

BackgroundNon-alcoholic fatty liver disease (NAFLD), which is characterized by hepatic steatosis, can be reversed by early treatment. Several case reports have indicated that the administration of recombinant growth hormone (GH) could improve fatty liver in GH-deficient patients. Here, we investigated whether chronic exogenous GH levels could improve hepatic steatosis induced by a high-fat diet in rats, and explored the underlying mechanisms.ResultsHigh-fat diet-fed rats developed abdominal obesity, fatty liver and insulin resistance. Chronic exogenous GH improved fatty liver, by reversing dyslipidaemia, fat accumulation and insulin resistance. Exogenous GH also reduced serum tumour necrosis factor-alpha (TNF-alpha) levels, and ameliorated hepatic lipid peroxidation and oxidative stress. Hepatic fat deposition was also reduced by exogenous GH levels, as was the expression of adipocyte-derived adipokines (adiponectin, leptin and resistin), which might improve lipid metabolism and hepatic steatosis. Exogenous GH seems to improve fatty liver by reducing fat weight, improving insulin sensitivity and correcting oxidative stress, which may be achieved through phosphorylation or dephosphorylation of a group of signal transducers and activators of hepatic signal transduction pathways.ConclusionsChronic exogenous GH has positive effects on fatty liver and may be a potential clinical application in the prevention or reversal of fatty liver. However, chronic secretion of exogenous GH, even at a low level, may increase serum glucose and insulin levels in rats fed a standard diet, and thus increase the risk of insulin resistance.

The Efficacy of a Topical Gel Prepared Using Lake Urmia Mud in Patients with Knee Osteoarthritis

Osteoarthritis (OA) is characterized by progressive cartilage degradation and secondary inflammation of the synovial membrane. Studies have shown that mud therapy may influence serum levels of several cytokines involved in the pathogenesis of OA and chondrocyte metabolism. The main targets of our research were to make use of Lake Urmia mud for topical gel formulation, evaluation of the possible therapeutic effects of this gel on symptoms of patients with knee OA and the evaluation of serum tumor necrosis factor-alpha (TNF-alpha) level after mud therapy in comparison with the application of a placebo. Fifty (50) patients suffering from knee OA participated in this study and randomized into two groups: case group and control group. Patients in the case group received mud therapy and the placebo was applied to patients in the control group. Three (3) parameters including pain, morning stiffness, and joint functionality were assessed in all patients. Visual analogue scale and Western Ontario McMaster Osteoarthritis index (WOMAC) were the employed scales for pain assessment. Functional capacity was evaluated by using WOMAC functional capacity and WOMAC global index. All the mentioned steps were done before and after treatment. Blood samples, in both groups, were collected for measuring tumor necrosis factor (TNF)-alpha serum level. All the differences (for three parameters), in the case group, were statistically significant. TNF-alpha serum level reduction in both groups were detected: 19.41% in the case group and 1.76% in the control group. Mud therapy using formulated gel is an effective method in knee OA treatment and pain reduction. Further studies may be needed for the evaluation of possible synergism between pharmacological treatment and mud therapy.

Effect of tocotrienols on iron-induced renal dysfunction and oxidative stress in rats

Ferric nitrilotriacetate (Fe-NTA) is a well-established nephrotoxic agent. This study was designed to investigate the modulatory effect of the subacute administration of tocotrienol-rich fraction (T3), a product from palm oil, and α-tocopherol (T) on Fe-NTA-induced renal injury and oxidative stress. Fe-NTA administration markedly increased blood urea nitrogen (BUN) and serum creatinine level, which was coupled with a marked lipid peroxidation, reduced activity of glutathione levels, and morphological alterations in rat kidney. Pretreatment with T3 (50 mg/kg/day) and T (50 mg/kg/day) for 7 days before Fe-NTA administration significantly reduced the serum creatinine and BUN levels, reduced lipid peroxidation in a significant manner, and restored levels of reduced glutathione and superoxide dismutase. T3 pretreatment also attenuated the serum tumor necrosis factor-alpha levels, as compared to pretreatment with T, and restored normal renal morphology. These findings suggest a strong correlation between iron-induced oxidative stress and renal dysfunction and point toward the protective effects of T3 in Fe-NTA-induced renal injury.

Preinfection aerobic treadmill training improves resistance against Trypanosoma cruzi infection in mice

Exercise performed before infections has been linked to improvement of the immune response against infections. The purpose of this study was to evaluate the influence of preinfection moderate-intensity treadmill training on acute Trypanosoma cruzi infection in mice. Ninety-nine female BALB/c mice were divided into 4 groups, as follows: training + infection (T+I) (n = 41); no training + infection (NT+I) (n = 38); training + no infection (T+NI) (n = 10); and no training + no infection (NT+NI) (n = 10). The exercise program for trained groups was carried out on a motorized treadmill for 8 weeks. Infected groups were inoculated with the Y strain of T. cruzi. Infectivity, prepatent period, patent period, parasitemia peak, mortality, survival time, weight, food intake, tumor necrosis factor-alpha serum levels, and peritoneal macrophage hydrogen peroxide production were evaluated. We found that preinfection training induced statistically significant reductions in parasitemia peak (p < 0.03) and weight loss (p < 0.04). However, no statistically significant differences were found for the other parameters evaluated when trained and nontrained infected groups were compared. We conclude that preinfection aerobic training induces some improvement in the immune response to T. cruzi infection in female BALB/c mice.

Tumor necrosis factor receptor‐associated protein 1 regulates cell adhesion and synaptic morphology via modulation of N‐cadherin expression

An increase in serum tumor necrosis factor-alpha (TNF-alpha) levels is closely related to the pathogenesis of major depression. However, the underlying molecular mechanism between this increase and impairment of brain function remains elusive. To better understand TNF-alpha/TNF receptor 1 signaling in the brain, we analyzed the brain distribution and function of tumor necrosis factor receptor-associated protein 1 (TRAP1). Here we show that TRAP1 is broadly expressed in neurons in the mouse brain, including regions that are implicated in the pathogenesis of major depression. We demonstrate that small interfering RNA-mediated knockdown of TRAP1 in a neuronal cell line decreases tyrosine phosphorylation of STAT3, followed by a reduction of the transcription factor E2F1, resulting in a down-regulation of N-cadherin, and affects the adhesive properties of the cells. In addition, in cultured hippocampal neurons, reduced expression of N-cadherin by TRAP1 knockdown influences the morphology of dendritic spines. We also report a significant association between several single nucleotide polymorphisms in the TRAP1 gene and major depression. Our findings indicate that TRAP1 mediates TNF-alpha/TNF receptor 1 signaling to modulate N-cadherin expression and to regulate cell adhesion and synaptic morphology, which may contribute to the pathogenesis of major depression.

High interleukin-6 and tumor necrosis factor-alpha serum levels in hepatitis C infection associated or not with mixed cryoglobulinemia

The objective of this study is to evaluate serum levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-a) in a series of patients with hepatitis C virus (HCV)-related mixed cryoglobulinemia (HCV-MC) and to correlate these parameters with the clinical features of the disease. Serum IL-6 and TNF-a were assayed in 61 patients with HCV-MC, in 61 sex- and age-matched patients with HCV chronic hepatitis without cryoglobulinemia (HCV+), and in 61 sex- and age-matched healthy controls. HCV-MC patients showed significantly higher mean IL-6 levels than controls (p=0.005) or HCV+ patients (p = 0.02). Moreover, IL-6 was increased in cryoglobulinemic patients with active vasculitis, even if the statistical significance was not reached (p=0.056). Serum TNF-a levels were significantly higher in HCV-MC than in HCV+ or in controls (p<0.01). The study demonstrates high IL-6 and TNF-a serum levels in HCV-MC patients; moreover, IL-6 levels tended to be higher in HCV-MC patients in presence of active vasculitis.

Modulation of antigen‐induced chronic fatigue in mouse model of water immersion stress by naringin, a polyphenolic antioxidant

It is believed that physical stress, infection and oxidative stress are involved in the development of chronic fatigue syndrome. There is little evidence stating the beneficial role of nutritional supplements in chronic fatigue syndrome. Based on this, this study was designed to evaluate the effect of naringin, a natural polyphenol, in a mouse model of immunologically-induced fatigue, wherein purified lipopolysaccharide (LPS) as well as Brucella abortus (BA) antigen was used as immunogens. The assessment of chronic fatigue syndrome was based on chronic water-immersion stress test for 10 mins as well as measurement of hyperalgesia for 19 days. Immobility time and tail withdrawal latency as well as oxidative stress were taken as the markers of fatigue. Mice challenged with LPS or BA for 19 days showed significant increase in the immobility time, hyperalgesia and oxidative stress on 19th day. Serum tumor necrosis factor-alpha (TNF-alpha) levels markedly increased with LPS or BA challenge. Concurrent treatment with naringin resulted in the significant decrease in the immobility time as well as hyperalgesia. There was significant attenuation of oxidative stress as well as in TNF-alpha levels. Present findings strongly suggest the role of oxidative stress and immunological activation in the pathophysiology of chronic fatigue syndrome, and treatment with naringin can be a valuable option in chronic fatigue syndrome.

The effect of calcitonin gene-related peptide on healing of intestinal anastomosis in rats with experimental obstructive jaundice

Intestinal anastomotic healing is a complex procedure in which several mediators and cytokines play roles. Calcitonin gene-related peptide is an important neuropeptide in inflammation. In this study we aimed to investigate the effect of calcitonin gene-related peptide on healing of intestinal anastomosis in rats with obstructive jaundice. Obstructive jaundice was induced in rats by the ligation and division of the common bile duct. Four days after the operation, intestinal anastomosis was performed, and either calcitonin gene-related peptide or 0.9% NaCl was administered intraperitoneally to these jaundiced rats and controls. The concentrations of serum tumor necrosis factor-alpha (TNF-alpha) and triglyceride levels of all rats were measured, and healing of the anastomosis was evaluated by measuring the bursting pressure and hydroxyproline content on the 7th postoperative day. Calcitonin gene-related peptide was found to have positive effects on healing of the anastomosis by inhibiting the effects of TNF-alpha and increasing the bursting pressure and hydroxyproline content of the anastomosis. Calcitonin gene-related peptide increases anastomotic wound healing in experimental anastomosis in the presence of obstructive jaundice in rats.

Effects of atorvastatin serum levels of interleukin-6 and tumor necrosis factor-alpha in patients with acute coronary syndromes

Objective To study the effect of atorvastatin on the serum levels of intedeukin-6(IL-6)and tumor necrosis factor-alpha(TNF-α)in patients with acute coronary syndromes(ACS),so as to find out the correlation between the changes of IL-6 and TNF-α levels and ACS.Methods 48 ACS patiems who were in accordance with the inclusion criteria.Were randomly divided into atorvastatin group(n=25)and routine treatment group(n=23).The serum levels of IL-6 and TNF-α were measured with radioimmunoassay before and three weeks after treatment respectively.20 healthy physical examines in the same hospitals at the same period were taken as controls.Who did not take any medicine within the two weeks before blood sampling and their serum levels of IL-6 and TNF-α were detectod during physical examination.Results The serum levels of IL.6 and INF-α were obviously higher in the ACS patients than in the control group(P＜0.05).The serum levels of IL-6 and TNF-α in the atorvastatin group after treatment were markedly lower than those before treatment(P＜0.05)which were still higher than those in the comrol group(P＜0.05).There were no obvious changes of the serum IL-6 and INF-α levels in the routine treatment group (P＞0.05).Conclusion The higher the levels of IL-6 and TNF-α the greater the occurrence rate of ACS.Atorvastatin Can reduce the srtum levels of IL-6 and TNF-α in ACS patients,and it has the effects of inhibiting the inflammarion of the site of lesion and improving the endothelial function. Key words: Atorvastatin; Intedeukin-6; Tumor necrosis factor-alpha; Coronary disease

Renoprotective Effects of Sesamol in Ferric Nitrilotriacetate‐Induced Oxidative Renal Injury in Rats

The present study was designed to investigate the renoprotective effect of 3,4-methylenedioxyphenol (sesamol) on ferric nitrilotriacetate-induced renal toxicity. Rats were pretreated with sesamol (2, 4 and 8 mg/kg, p.o.) 30 min. prior to administration of ferric nitrilotriacetate (8 mg iron/kg, i.p.) to determine the blood urea nitrogen and serum creatinine levels along with renal oxidative stress. Challenge with ferric nitrilotriacetate markedly increased the blood urea nitrogen and serum creatinine levels, which was coupled with a marked lipid peroxidation, reduced activity of glutathione and decreased total nitric oxide levels in rat kidneys. It also produced significant renal morphological alterations and increased serum tumour necrosis factor-alpha levels. Pretreatment with sesamol significantly reduced the serum creatinine and blood urea nitrogen levels, lipid peroxidation, restored levels of reduced glutathione and increased total renal nitric oxide levels. It also attenuated the increased tumour necrosis factor-alpha levels and restored the normal morphology of the kidneys. Present findings strongly suggest the pivotal role of oxidative stress in the ferric nitrilotriacetate-induced renal dysfunction and points towards the renoprotective potential of sesamol in oxidative renal pathologies.

Myeloablative radioimmunotherapy with 188Re-CD66mAb before stem cell transplantation

Tumour necrosis factor-alpha (TNF-alpha) serum levels may increase due to intensive conditioning regimes with high-dose-chemotherapy and total body irradiation (TBI) before stem cell transplantation. This increases the risk for developing acute graft versus host disease (aGvHD) after stem cell transplantation. In this prospective study we investigated the influence of radioimmunotherapy with 188Re-CD-66-mAb on changes on TNF-alpha serum levels. In 18 patients we measured TNF-alpha before and up to 96 hours after radioimmunotherapy, in 2 patients in addition following TBI, in 9 patients also following chemotherapy. For measuring TNF-alpha we used an automated immunochemiluminescence assay (Immulite 1000 DPC Biermann, Bad Nauheim). The mean follow up period to record incidence of aGVHD was 100 days after stem cell transplantation. Compared to the basal levels before, the levels of TNF-alpha after conditioning with 188Re-CD-66-mAb did not increase significantly and remained in the physiological range. In contrast, these initial physiological cytokine levels increased and became pathological following 48 h after total body irradiation (13.2+/-6.6 pg/ml) and chemotherapy (10.8+/-15.7 pg/ml). In our study we found a low incidence of aGvHD (22.2%, n=4/18). These results demonstrate that additional conditioning therapy with 188Re-CD-66-mAb does not increase proinflammatory cytokine levels of TNF-alpha. This finding may indicate that additive radioimmunotherapy may not be a significant factor for increasing the rate of conditioning-associated aGvHD.

Inflammatory processes enhance cAMP-mediated uterus relaxation in the pregnant rat: the role of TNF-α

The objective of this study was to assess the in vitro uterus relaxing potency of beta(2)-adrenergic receptor (beta(2)-AR) agonists in pregnant rats after in utero administration of the bacterial lipopolysaccharide, Escherichia coli endotoxin (LPS). The LPS (100 microg/kg) was injected into the uterine lumen on day 16 of pregnancy. The effects of beta(2)-AR agonist terbutaline was tested in vitro, in isolated uterine rings precontracted by electric field stimulation. Uterine beta(2)-AR densities were detected by radioligand binding assay, the activated G-protein levels were investigated by a radiolabelled GTP binding assay. Uterine cAMP accumulation and the serum tumor necrosis factor-alpha (TNF-alpha) levels were measured by enzyme immunoassay. The endotoxin-evoked preterm delivery occurred on day 21. Higher pD(2) values of terbutaline (p < 0.001) were detected in endotoxin-treated rats: 9.14 +/- 0.36 vs. 7.71 +/- 0.12 compared with sham-operated rats. The densities or the equilibrium dissociation constants of beta(2)-ARs were not different (p > 0.05) in LPS-treated vs. control animals. Serum TNF-alpha level rose threefold after LPS treatment, but this rise was abolished by thalidomide. In LPS + thalidomide-treated rats, the effect of terbutaline became similar to that in sham-operated controls. By the measurement of myometrial cAMP levels, we documented that the concentration-response curve of terbutaline on cAMP accumulation was shifted to the left in the LPS-treated rats, with a significant rise in the pD(2). We concluded that in the case of uterine inflammation, the in vitro uterus-relaxing potency of beta(2)-agonists enhances, which is possibly mediated by TNF-alpha and uterine cAMP levels and that may serve as a rationale for the use of beta(2)-AR agonists in the attenuation of preterm uterine contractions on an inflammatory basis.

Anti-Ccl2 Spiegelmer Permits 75% Dose Reduction of Cyclophosphamide to Control Diffuse Proliferative Lupus Nephritis and Pneumonitis in MRL-Fas(lpr) Mice

Cyclophosphamide (CYC) can control diffuse proliferative lupus nephritis (DPLN) by potent immunosuppression but remains associated with serious and life-threatening complications. Drugs that specifically target mediators of DPLN may help to reduce CYC dose and side effects. Monocyte chemoattractant protein (MCP-1)/CCL2 mediates monocyte and T cell recruitment in DPLN and Ccl2-specific l-enantiomeric RNA Spiegelmer mNOX-E36 neutralizes the biological effects of murine Ccl2 in vitro and in vivo. We injected MRL(lpr/lpr) mice with DPLN from 14 weeks of age with vehicle, weekly 30 mg/kg CYC (full dose), monthly 30 mg/kg CYC (one-fourth full dose), pegylated control Spiegelmer, pegylated anti-Ccl2 Spiegelmer (3/week), pegylated anti-Ccl2 Spiegelmer plus CYC one-fourth full dose and mycophenolate mofetil. At week 24, DPLN and autoimmune lung injury were virtually abolished with CYC full dose but not with CYC one-fourth full dose. The CYC one-fourth full dose/Spiegelmer combination was equipotent to CYC full dose on kidney and lung injury. CD3(+)CD4(-)CD8(-) and CD3(+)CD4(+)CD25(+) T cells and serum interleukin-12p40 and tumor necrosis factor-alpha levels were all markedly affected by CYC full dose but not by CYC one-fourth full dose. No additive effects of anti-Ccl2 Spiegelmer were noted on bone marrow colony-forming unit-granulocyte macrophage counts and 7/4(high) monocyte counts, lymphoproliferation, and spleen T cell depletion. In summary, anti-Ccl2 Spiegelmer permits 75% dose reduction of CYC for controlling DPLN and pneumonitis in MRL-Fas(lpr) mice, sparing suppressive effects of full-dose CYC on myelosuppression and T cell depletion. We propose anti-Ccl2 Spiegelmer therapy as a novel strategy to reduce CYC toxicity in the treatment of severe lupus.

Nrf2- and PPARα-Mediated Regulation of Hepatic Mrp Transporters after Exposure to Perfluorooctanoic Acid and Perfluorodecanoic Acid

Perfluorooctanoic acid and perfluorodecanoic acid (PFDA) are commonly used as emulsifiers and surfactants in fluoropolymer manufacturing and are known peroxisome proliferator-activated receptor alpha (PPAR alpha) agonists. PPAR alpha activation induces beta- and omega-oxidation enzymes such as Cyp4a14 and acyl-CoA oxidase, which are a likely cause of subsequent oxidative stress and peroxisome proliferation. Conversely, NF-E2-related factor-2 (Nrf2) is a transcription factor that protects against oxidative stress and inflammation by regulating several detoxification and xenobiotic transporter genes. Because PFDA markedly induces hepatic metabolism and oxidative stress, we hypothesized that PFDA exposure would increase expression of hepatic efflux multidrug resistance-associated protein (Mrp) transporters. A single PFDA dose (80 mg/kg) administered to mice increased hepatic Mrp3 (fourfold) and Mrp4 (31-fold) mRNA expression. Upregulation of Mrp3 and Mrp4 correlated with elevated serum-conjugated bilirubin and bile acids, respectively. To determine the mechanism of Mrp3 and Mrp4 induction, PFDA was administered to Nrf2-null mice, PPAR alpha-null mice, and mice pretreated with gadolinium chloride, a Kupffer cell-depleting chemical capable of inhibiting the inflammatory cytokine response. In both PPAR alpha- and Nrf2-null mice, maximal induction of Mrp3 and Mrp4 mRNA after PFDA administration was attenuated. Gadolinium chloride pretreatment reduced serum and hepatic tumor necrosis factor-alpha levels after PFDA treatment, as well as Mrp4 mRNA expression by 30%, suggesting that Kupffer cell-derived mediators may contribute to Mrp induction. Thus, after PFDA administration, the liver mounts a compensatory hepatoprotective response via PPAR alpha and Nrf2, markedly increasing Mrp3 and Mrp4 expression, with corresponding increases in serum of known Mrp3 and Mrp4 substrates.

Protective Effect of Pinitol againstD-Galactosamine-Induced Hepatotoxicity in Rats Fed on a High-Fat Diet

The protective effect of pinitol against D-galactosamine (GalN)-induced liver damage was examined. Forty male Sprague-Dawley rats were divided into normal control, GalN control, and pinitol groups (0.5%, 1%, and 2%). After 8 weeks of feeding, a single dose of GalN (650 mg/kg) was administered 24 h before their sacrifice. The serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and tumor necrosis factor-alpha (TNF-alpha) levels were significantly increased after an injection with GalN (P<0.05), but pinitol supplementation at the level of 0.5% reversed these changes to normal levels. Significant decreases in serum triglyceride and cholesterol and increases in hepatic cholesterol were observed in GalN-intoxicated rats. However, supplementation with pinitol significantly attenuated these trends. In addition, pinitol elevated the Mn-superoxide dismutase, glutathione reductase, and catalase activities, prevented hepatic lipid peroxidation, and restored the hepatic GSH levels and cytochrome P450 2E1 function. Thus, 0.5% pinitol supplementation protected the rats from the hepatotoxicity induced by GalN, at least part of its effect being attributable to attenuation of the oxidative stress and inflammatory process promoted by GalN.

P. gingivalis and E. coli Lipopolysaccharides Exhibit Different Systemic but Similar Local Induction of Inflammatory Markers

Porphyromonas gingivalis is a Gram-negative bacterium that is an important etiologic agent of human adult periodontitis. The goal of the study was to test the hypothesis that two isoforms of P. gingivalis lipopolysaccharide (PgLPS), PgLPS(1435)(/1449) and PgLPS(1690), exhibit differences in their capacity to stimulate systemic versus local responses compared to Escherichia coli lipopolysaccharide (LPS). LPS was inoculated into the scalp of mice, and the response was measured locally at the site of inoculation and systemically in the heart/aorta. Vascular cell adhesion molecule (VCAM)-1 was assessed at the protein level by enzyme-linked immunosorbent assay, and VCAM-1, E-selectin, and intercellular adhesion molecule (ICAM)-1 were assessed at the RNA level of the RNase protection assay. Serum tumor necrosis factor-alpha (TNF-alpha) levels were also measured. E. coli LPS and both isoforms of P. gingivalis LPS were relatively potent in stimulating the expression of inflammatory markers, with E. coli LPS being more potent. In contrast, when the systemic response was measured in the heart/aorta, E. coli LPS, but not P. gingivalis LPS, significantly induced inflammatory markers. At moderate to low doses (1 and 10 microg per injection), serum TNF-alpha levels were minimally induced by P. gingivalis LPS compared to E. coli LPS. Both forms of P. gingivalis LPS stimulated an inflammatory response when injected into connective tissue but were minimally stimulatory when a systemic response was measured. In contrast, E. coli LPS was a potent stimulus at the systemic and local levels.

Elevation of serum soluble intercellular adhesion molecule-1 (sICAM-1) and sE-selectin levels in bronchial asthma.

Adhesion molecules such as ICAM-1 and E-selectin have been shown to play important roles in the production of allergic inflammation. In the present study, we measured serum soluble ICAM-1 (sICAM-1) and soluble E-selectin (sE-selectin) levels by ELISA in 42 patients with bronchial asthma (22 atopic and 20 non-atopic) during asthma attacks and in stable conditions in order to assess the state of ICAM-1 and E-selectin in allergic inflammation. Both serum sICAM-1 levels and serum sE-selectin levels in sera obtained during bronchial asthma attacks were higher than those in sera obtained in stable conditions. These findings were observed regardless of atopic status. To examine the regulatory mechanism in the elevation of serum sICAM-1 and sE-selectin levels, serum tumour necrosis factor-alpha (TNF-alpha) levels were measured by ELISA. TNF-alpha levels in sera obtained during bronchial asthma attacks were higher than those in sera obtained in stable conditions. There was a correlation between the nature of change in serum TNF-alpha levels and the nature of change in serum sICAM-1 levels or serum sE-selectin levels, though serum TNF-alpha levels did not correlate with serum sICAM-1 levels or serum sE-selectin levels. These results suggest that higher levels of sICAM-1 and sE-selectin during asthma attacks may reflect the up-regulation of ICAM-1 and E-selectin expression in allergic inflammation, and that the soluble form of these adhesion molecules may be useful markers for the presence of allergic inflammation. TNF-alpha is shown to enhance the expression and release of ICAM-1 and E-selectin in vitro, however; the regulatory mechanism in the elevation of serum sICAM-1 and sE-selectin levels remains to be clarified.