OBJECTIVE: To determine serum levels of TNF-alpha (tumor necrosis factor alpha) as a prediction of endometriosis. DESIGN: Prospective clinical case control study. SETTING: Department of Obstetrics and Gynaecology and Department of Pathology, Jessenius Faculty Hospital, Kollarova 2, Martin, Slovakia. METHODS: The serum TNF-alpha was determined in women who underwent laparoscopy or laparotomy due to pelvic pain, infertility, dysmenorea or pelvic tumor. Endometriosis was confirmed histologically and classified by rAFS. RESULTS: On the basis of entering criteria 65 women were enrolled in this study. In 61 cases serum level of TNF-alpha was evaluated. The average serum level of TNF-alpha in the endometriotic group was 73.847 pg/ml (n=30) and without endometriosis was 21.089 pg/ml (n=31). We have found a significant statistical difference between the above mentioned groups in the medium levels of TNF-alpha (p<0.0001). We did not find statistical significance between TNF-alpha levels and in the group of women with endometriosis in relation to the stage of the disease (I.-II., III.-IV., adenomyosis). At a cut-off level of TNF-alpha 30 pg/ml there was a 63.33% sensitivity, 77.42% specificity, a positive prediction value 73.07%, and 68.57% of negative predictive value. CONCLUSION: TNF-alpha serum levels are good diagnostic markers of endometriosis in the spectrum of noninvasive methods.

• MeSH
• biologické markery krev   MeSH
• dospělí MeSH
• endometrióza krev   diagnóza   MeSH
• lidé MeSH
• senzitivita a specificita MeSH
• TNF-alfa analýza   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• biologické markery MeSH
• TNF-alfa MeSH

Macrophages and lymphocytes of pig fetuses stimulated in vitro with bacterial mitogens such as lipopolysaccharide and Nocardia opaca delipidated cell mitogen showed a high TNF-alpha cytoplasmic expression. TNF-alpha was detected by immunofluorescence in peripheral blood lymphocytes and lymphocytes from the thymic region as early as at 34 d of gestation. Macrophages were the main producers of TNF-alpha at later developmental stages.

• MeSH
• aktivace lymfocytů MeSH
• aktivace makrofágů MeSH
• buněčná stěna imunologie   MeSH
• fetální krev cytologie   MeSH
• gestační stáří MeSH
• játra cytologie   embryologie   imunologie   MeSH
• kultivované buňky MeSH
• lipopolysacharidy farmakologie   MeSH
• lymfocyty účinky léků   metabolismus   MeSH
• makrofágy účinky léků   metabolismus   MeSH
• miniaturní prasata embryologie   metabolismus   MeSH
• mitogeny imunologie   MeSH
• Nocardia chemie   imunologie   MeSH
• organické látky MeSH
• orgánová specificita MeSH
• prasata MeSH
• thymus cytologie   embryologie   imunologie   MeSH
• TNF-alfa biosyntéza   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• lipopolysacharidy MeSH
• mitogeny MeSH
• Nocardia delipidated cell mitogen MeSH Prohlížeč
• organické látky MeSH
• TNF-alfa MeSH

Insulin resistance and obesity are very frequent disorders and are described as the dominant risk factors for cardiovascular disease. The aim of this study was to analyze the interrelations between several metabolic variables (including TNF-alpha) and factors related to insulin resistance in groups of both normal and hyperlipidemic postmenopausal women and men of appropriate age, and to attempt to elucidate the gender differences. The study was carried out on 70 out-patients of the Metabolic Center. From these, 40 patients (20 men and 20 women) were selected with mild hyperlipidemia. Two other groups (10 men and 20 women) with approximately normal serum lipids parameters were taken as "controls". In hyperlipidemic women the mean serum concentration of the TNF-alpha was no different from that in the control group in spite of the fact that values of HOMA IR, insulin, proinsulin and lipid parameters increased significantly. In hyperlipidemic men we have found the decrease in TNF-alpha in comparison with the control group. In all four groups the statistical analysis showed correlations between metabolic parameters (including TNF-alpha) and parameters related to insulin resistance. Also differences in relation to the gender have been found. Multiple regression analysis demonstrated the important role of TNF-alpha in the regulation of both the insulin resistance and in the secretion of insulin in women. In men, BMI and HDL-cholesterol played a dominant role, while the role of TNF-alpha seemed to be minimal.

• MeSH
• homeostáza MeSH
• hyperlipidemie krev   MeSH
• inzulinová rezistence * MeSH
• lidé středního věku MeSH
• lidé MeSH
• metabolický syndrom metabolismus   MeSH
• TNF-alfa analýza   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• TNF-alfa MeSH

The effects of tumor necrosis factor-alpha (TNF-alpha; cachectin) and lipopolysaccharide of Salmonella enteritidis (LPS; endotoxin) on leucine metabolism in rats were evaluated in the whole body using intravenous infusion of L-[1-14C]leucine and in isolated perfused liver (IPL) using the single-pass perfusion technique with alpha-keto[1-14C]isocaproate as a tracer for measurement of ketoisocaproic acid (KIC) oxidation, and the recirculation technique for measurement of hepatic amino acid exchanges. The data obtained in TNF-alpha and LPS groups were compared with those obtained in controls. Both TNF-alpha and LPS treatment induced an increase of whole body leucine turnover, oxidation, and clearance. As the result of a higher increase of leucine oxidation than of incorporation into the pool of body proteins, the fractional oxidation of leucine was increased. The fractional rate of protein synthesis increased significantly in the spleen (both in TNF-alpha and LPS rats), in blood plasma, liver, colon, kidneys, gastrocnemius muscle (in LPS rats), and in lungs (TNF-alpha-treated rats), whereas it decreased in the jejunum (LPS rats). In IPL of TNF-alpha- and LPS-treated rats a decrease of KIC oxidation and higher uptake of branched-chain amino acids (BCAA; valine, leucine, and isoleucine) were observed when compared with control animals. We hypothesize that the negative consequences of increased whole body proteolysis and of increased oxidation of BCAA induced by TNF-alpha and/or LPS are reduced by decreased activity of hepatic branched-chain ketoacid dehydrogenase that can help resupply BCAA to the body.

• MeSH
• aminokyseliny krev   metabolismus   MeSH
• biologické modely MeSH
• endotoxiny farmakologie   MeSH
• játra účinky léků   metabolismus   MeSH
• ketokyseliny farmakokinetika   MeSH
• krysa rodu Rattus MeSH
• leucin metabolismus   MeSH
• lidé MeSH
• lipopolysacharidy farmakologie   MeSH
• myši MeSH
• potkani Wistar MeSH
• radioisotopová diluční technika MeSH
• radioizotopy uhlíku MeSH
• rekombinantní proteiny farmakokinetika   farmakologie   MeSH
• Salmonella enteritidis MeSH
• tělesná hmotnost MeSH
• TNF-alfa farmakokinetika   farmakologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• alpha-ketoisocaproic acid MeSH Prohlížeč
• aminokyseliny MeSH
• endotoxiny MeSH
• ketokyseliny MeSH
• leucin MeSH
• lipopolysacharidy MeSH
• radioizotopy uhlíku MeSH
• rekombinantní proteiny MeSH
• TNF-alfa MeSH

BACKGROUND: Evidence of the impact of in utero exposure to anti-tumor necrosis factor (TNF)-alpha on long-term childhood development is limited. The aim was to assess the impact of in utero exposure to anti-TNF-alpha due to mothers' inflammatory bowel disease (IBD) on long-term postnatal development of exposed children. METHODS: We included consecutive children (≥12 months of age) born to mothers with IBD (2007-2016) treated with anti-TNF-alpha during pregnancy in 3 centers in the Czech Republic. A control group was comprised of unexposed children of non-IBD mothers undergoing mandatory check-ups at general pediatricians' offices. Data on perinatal period, psychomotor development, vaccination, infections, antibiotics, and allergy were collected by treating pediatricians using a predefined questionnaire. RESULTS: Seventy-two exposed and 69 unexposed children were included (median age, 35 and 50 months, respectively). Exposed children had growth and psychomotor development similar to controls. There was no significant difference in infectious complications within the first year of life (23.9% vs 17.4%; P = 0.36) or during the whole follow-up between exposed infants and controls (P = 0.32). Concomitant immunosuppressants during pregnancy and anti-TNF-alpha levels in cord blood were not associated with elevated infection rate within the first year of life (P > 0.05). Over 95% of exposed children had adequate serologic response to vaccination, except for haemophilus and mumps vaccines. Clinically manifested allergy was similar between the groups (P = 0.98). CONCLUSIONS: Anti-TNF-alpha exposure in utero does not seem to have a negative impact on postnatal development of children with regard to infectious complications, allergy, growth, or psychomotor development when compared with unexposed children of non-IBD women.

• Klíčová slova
• anti-TNF-alpha, children, infections, inflammatory bowel disease, vaccination,
• MeSH
• adalimumab aplikace a dávkování   MeSH
• dítě MeSH
• gastrointestinální látky aplikace a dávkování   MeSH
• idiopatické střevní záněty farmakoterapie   imunologie   MeSH
• infliximab aplikace a dávkování   MeSH
• kohortové studie MeSH
• kojenec MeSH
• komplikace těhotenství diagnóza   farmakoterapie   imunologie   MeSH
• lidé MeSH
• matky MeSH
• následné studie MeSH
• předškolní dítě MeSH
• prognóza MeSH
• studie případů a kontrol MeSH
• těhotenství MeSH
• TNF-alfa antagonisté a inhibitory   MeSH
• zpožděný efekt prenatální expozice farmakoterapie   imunologie   MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• pozorovací studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• adalimumab MeSH
• gastrointestinální látky MeSH
• infliximab MeSH
• TNF-alfa MeSH

TNF-alpha is a pleiotropic cytokine that is considered as a primary modifier of inflammatory and immune reaction in response to various inflammatory diseases and tumour. We investigated levels of TNF-alpha in 43 radicular cysts and 15 odontogenic keratocysts, obtained from patients undergoing surgery, under local anaesthesia, and after aspiration of cystic fluid from non-ruptured cysts. TNF-alpha is elevated in both cysts' fluid, but higher values were found in radicular cysts in comparison to keratocysts. The significantly higher concentration of TNF-alpha was associated with smaller radicular cysts, higher protein concentration, higher presence of inflammatory cells in peri cystic tissues, and the degree of vascularisation and cysts wall thickness (Mann-Whitney U-test, p < 0.05). No correlation was found based on these parameters in odontogenic keratocyst, but all cysts have detectable concentrations of TNF-alpha. We here for the first time present that a difference in the concentration of TNF-alpha exists between these two cystic types.

• MeSH
• cystická tekutina chemie   MeSH
• lidé MeSH
• odontogenní cysty chemie   MeSH
• radikulární cysta chemie   MeSH
• TNF-alfa analýza   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• TNF-alfa MeSH

IL-18 is a multifunctional cytokine that augments both innate and acquired immunity and potentiates Th1 and Th2 reactions. We studied the expression of IL-18 receptor (IL-18R) on renal and respiratory epithelial cell lines. Both cell lines upregulated IL-18R mRNA and IL-18R membrane expression in response to TNF alpha and other proinflammatory cytokines. The function of IL-18R was confirmed by induction of IL-8 release from epithelial cells in response to recombinant IL-18. Epithelial cells may represent an important target for IL-18, mainly under inflammatory conditions associated with TNF alpha release.

• MeSH
• ELISA MeSH
• epitelové buňky účinky léků   MeSH
• interleukin-18 genetika   farmakologie   MeSH
• interleukin-8 metabolismus   MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• průtoková cytometrie MeSH
• receptor interleukinu-18 - alfa-podjednotka MeSH
• receptory interleukinu-18 MeSH
• receptory interleukinů metabolismus   MeSH
• rekombinantní proteiny farmakologie   MeSH
• TNF-alfa farmakologie   MeSH
• upregulace účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• IL18R1 protein, human MeSH Prohlížeč
• interleukin-18 MeSH
• interleukin-8 MeSH
• receptor interleukinu-18 - alfa-podjednotka MeSH
• receptory interleukinu-18 MeSH
• receptory interleukinů MeSH
• rekombinantní proteiny MeSH
• TNF-alfa MeSH

The aim of this study was to determine whether and how tumour necrosis factor alpha (TNF-alpha) modulates butyrate effects. After the treatment of human colon adenocarcinoma HT-29 cells with sodium butyrate (NaBt), TNF-alpha or with their combinations we detected cell cycle (flow cytometry), cell proliferation (amidoblack and MTT assays), the amount of dead (floating) and apoptotic cells (flow cytometry and fluorescence microscopy), and the level of differentiation by alkaline phosphatase (ALP) activity (spectrophotometry), relative F-actin content (confocal laser scanning microscopy analysis) and E-cadherin expression (Western blot analysis). Both TNF-alpha and NaBt decreased cell growth in a dose-dependent manner. After combined treatment of the cells with both agents used, either none or additive effects were observed as compared with NaBt treatment alone. The level of dead and apoptotic cells was dose-dependently increased after this combined treatment. In contrast, TNF-alpha suppressed ALP activity and F-actin accumulation induced by NaBt. The results suggest that TNF-alpha does not influence significantly the antiproliferative effects of NaBt but, contrary to its potentiation of apoptosis, it markedly reduces NaBt-induced differentiation of HT-29 colon adenocarcinoma cells.

• MeSH
• alkalická fosfatasa metabolismus   MeSH
• apoptóza MeSH
• buňky HT-29 účinky léků   metabolismus   patologie   MeSH
• butyráty terapeutické užití   MeSH
• kadheriny metabolismus   MeSH
• lidé MeSH
• nádorová transformace buněk MeSH
• nádorové proteiny metabolismus   MeSH
• TNF-alfa terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• alkalická fosfatasa MeSH
• butyráty MeSH
• kadheriny MeSH
• nádorové proteiny MeSH
• TNF-alfa MeSH

The aim was to explore factors associated with intestinal tissue levels of anti-TNF alpha (anti-TNF), anti-TNF antibodies, and cytokines in pediatric patients with Crohn Disease (CD). In a prospective exploratory study of CD patients undergoing ileocecal resection or colonoscopy between 6/2020 and 1/2023, we analysed tissue levels of anti-TNF, anti-TNF antibodies, and cytokines (TNF-α, IL-17, IL-1β, IFN-γ) from intestinal biopsies. Mixed-effects regression models, adjusted for potential confounders, were used. Data from 27 CD patients (18 females, 66.7%) were analysed. Fourteen (52%) received adalimumab (ADA) and thirteen received infliximab (IFX), with a median therapy duration of 17 (IQR 4.5-41.5) months. Higher levels of free anti-TNF were found in macroscopically inflamed tissue compared to non-inflamed tissue (β = 3.42, 95% CI 1.05-6.10). No significant association was found between serum and tissue anti-TNF levels (β= -0.06, 95% CI - 0.70-0.58). Patients treated longer with anti-TNF had increased IL-17 levels (β = 0.19, 95% CI 0.05-0.33), independent of disease duration and age. IFN-γ levels were linked with both follow-up duration and anti-TNF length. Our study shows significantly higher free drug levels in inflamed tissue. Long-term anti-TNF treatment has been linked to increased IL-17 levels, suggesting a possible impact on the cytokine response pathway. We did not observe a relationship between serum and tissue anti-TNF levels.

• Klíčová slova
• Biologics, Crohn disease, Inflammatory bowel disease, Paediatrics,
• MeSH
• adalimumab * terapeutické užití   MeSH
• Crohnova nemoc * farmakoterapie   metabolismus   krev   patologie   MeSH
• cytokiny * metabolismus   krev   MeSH
• dítě MeSH
• infliximab * terapeutické užití   MeSH
• lidé MeSH
• mladiství MeSH
• prospektivní studie MeSH
• střeva patologie   účinky léků   MeSH
• střevní sliznice metabolismus   patologie   MeSH
• TNF-alfa * antagonisté a inhibitory   metabolismus   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• adalimumab * MeSH
• cytokiny * MeSH
• infliximab * MeSH
• TNF-alfa * MeSH

Macrolide antibiotics such as azithromycin or clarithromycin are known to have potent anti-inflammatory and immunomodulatory effects but these properties cannot be widely used due to a risk of bacterial resistance. We studied another polyketide antibiotic, structurally related manumycin A known as a streptomycete derived farnesyltransferase inhibitor with limited antibacterial effects, with respect to its potential regulation of mRNA expression of several genes associated with proinflammatory responses. Downregulation of mRNA for IL-6, TLR-8, IL-1 beta and IL-10 was found in THP-1 cells after 4h stimulation with TNF alpha in the presence of manumycin A and downregulated TLR-8 and EGR-1 genes were observed after 8h. Among the genes upregulated in response to manumycin were HMOX-1, TNFRSF10A, IL-1R1, TICAM2, NLRP12 after 4h and only IL-1R1 after 8h. Furthermore, manumycin A was found to inhibit IL-1beta, IL-6, and IL-8 production in TNF alpha stimulated THP-1 cells and peripheral blood monocytes in a dose dependent manner (0.25-1 μM of manumycin A) without affecting cell viability. Cell viability of blood monocytes decreased by about 30% at manumycin A doses of 2-5 μM. Manumycin A also inhibited IL-18 release from THP-1 cells, while in cultures of blood monocytes, this cytokine was not detectable. That manumycin A mediated downregulation of proinflammatory genes in human monocytes confirmed by a measurement of cytokine levels in culture supernatants, together with a very limited effect on cell viability, might suggest potential anti-inflammatory properties of this polyketide antibiotic.

• Klíčová slova
• Cytokines, Immunomodulation, Manumycin A, Monocytes, THP-1 cells,
• MeSH
• antibakteriální látky farmakologie   MeSH
• antiflogistika farmakologie   MeSH
• buněčné linie MeSH
• cytokiny genetika   metabolismus   MeSH
• imunomodulace MeSH
• lidé MeSH
• messenger RNA genetika   MeSH
• monocyty účinky léků   imunologie   MeSH
• polyeny farmakologie   MeSH
• polynenasycené alkamidy farmakologie   MeSH
• protein 1 časné růstové odpovědi genetika   metabolismus   MeSH
• receptory interleukinu-1 genetika   metabolismus   MeSH
• regulace genové exprese účinky léků   MeSH
• TNF-alfa metabolismus   MeSH
• toll-like receptor 8 genetika   metabolismus   MeSH
• zánět farmakoterapie   imunologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antibakteriální látky MeSH
• antiflogistika MeSH
• cytokiny MeSH
• EGR1 protein, human MeSH Prohlížeč
• manumycin MeSH Prohlížeč
• messenger RNA MeSH
• polyeny MeSH
• polynenasycené alkamidy MeSH
• protein 1 časné růstové odpovědi MeSH
• receptory interleukinu-1 MeSH
• TNF-alfa MeSH
• toll-like receptor 8 MeSH