Objectives: To assess the role of short-term response to first anti-TNF in long-term prediction of disability.Methods: In nationwide registry ATTRA, we identified ankylosing spondylitis patients starting anti-TNF between 01/2003 and 12/2016. Full disability and work impairment (WI; WPAI questionnaire) were predicted via the Cox- and lagged-parameter mixed-effect regression.Results: 2,274 biologicals-naïve patients newly indicated to anti-TNF were prospectively followed (6,333 patient-years; median follow-up 1.9 years). Reaching BASDAI < 4 (77.4%) and ASDAS-CRP < 2.1 (61.1%) after 3 months of anti-TNF both decreased the risk of future disability by ≈2.5-fold. ASDAS-CRP < 2.1 predicted non-disability better than BASDAI < 4 & CRP < 5 mg/L (p = 0.032). BASDAI < 4 & CRP < 5 mg/L was comparable to BASDAI < 4 (p = 0.941) and to BASDAI change by >50% or by >2 points (p = 0.902). ASDAS-CRP change >1.1 and >2.0 both failed to predict non-disability. Once on anti-TNF therapy, the strongest predictor of WI was Pain (SF36). Yearly increase in indirect costs remains below €3,000 in those reaching ASDAS-CRP < 2.1.Conclusions: Low disease activity measured by ASDAS-CRP ≤ 2.1 should be used to measure the outcome of new anti-TNF therapy. Continuous WI could be decreased through pain management.

• MeSH
• absentérství MeSH
• ankylózující spondylitida komplikace   diagnóza   farmakoterapie   epidemiologie   MeSH
• biologické přípravky terapeutické užití   MeSH
• časové faktory MeSH
• dospělí MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• longitudinální studie MeSH
• postižení statistika a číselné údaje   MeSH
• posuzování pracovní neschopnosti MeSH
• prognóza MeSH
• průzkumy a dotazníky MeSH
• registrace statistika a číselné údaje   MeSH
• stupeň závažnosti nemoci MeSH
• TNF-alfa antagonisté a inhibitory   imunologie   MeSH
• výkonnost * účinky léků   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH

The inhalation of metal (including lead) nanoparticles poses a real health issue to people and animals living in polluted and/or industrial areas. In this study, we exposed mice to lead(II) nitrate nanoparticles [Pb(NO3)2 NPs], which represent a highly soluble form of lead, by inhalation. We aimed to uncover the effects of their exposure on individual target organs and to reveal potential variability in the lead clearance. We examined (i) lead biodistribution in target organs using laser ablation and inductively coupled plasma mass spectrometry (LA-ICP-MS) and atomic absorption spectrometry (AAS), (ii) lead effect on histopathological changes and immune cells response in secondary target organs and (iii) the clearance ability of target organs. In the lungs and liver, Pb(NO3)2 NP inhalation induced serious structural changes and their damage was present even after a 5-week clearance period despite the lead having been almost completely eliminated from the tissues. The numbers of macrophages significantly decreased after 11-week Pb(NO3)2 NP inhalation; conversely, abundance of alpha-smooth muscle actin (α-SMA)-positive cells, which are responsible for augmented collagen production, increased in both tissues. Moreover, the expression of nuclear factor κB (NF-κB) and selected cytokines, such as tumor necrosis factor alpha (TNFα), transforming growth factor beta 1 (TGFβ1), interleukin 6(IL-6), IL-1α and IL-1β , displayed a tissue-specific response to lead exposure. In summary, diminished inflammatory response in tissues after Pb(NO3)2 NPs inhalation was associated with prolonged negative effect of lead on tissues, as demonstrated by sustained pathological changes in target organs, even after long clearance period.

• MeSH
• aktiny agonisté   genetika   imunologie   MeSH
• alveolární makrofágy účinky léků   imunologie   patologie   MeSH
• aplikace inhalační MeSH
• biologická dostupnost MeSH
• dusičnany farmakokinetika   toxicita   MeSH
• exprese genu MeSH
• inhalační expozice analýza   MeSH
• interleukin-1alfa agonisté   genetika   imunologie   MeSH
• interleukin-1beta agonisté   genetika   imunologie   MeSH
• interleukin-6 agonisté   genetika   imunologie   MeSH
• játra účinky léků   imunologie   patologie   MeSH
• kovové nanočástice aplikace a dávkování   toxicita   MeSH
• látky znečišťující vzduch farmakokinetika   toxicita   MeSH
• myši inbrední ICR MeSH
• myši MeSH
• NF-kappa B agonisté   genetika   imunologie   MeSH
• olovo farmakokinetika   toxicita   MeSH
• plíce účinky léků   imunologie   patologie   MeSH
• poločas MeSH
• spektrofotometrie atomová MeSH
• tkáňová distribuce MeSH
• TNF-alfa agonisté   genetika   imunologie   MeSH
• transformující růstový faktor beta1 agonisté   genetika   imunologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Neuroblastoma survivors show signs of immunosenescence early after therapy in CD8+ T cell compartment and elevated plasma TNF-α but in later follow-up immune recovery comes into play. Whether the recovery phenotype is long lasting or transient remains to be elucidated, however, late adverse effects often occur in childhood cancer survivors.

• MeSH
• CD8-pozitivní T-lymfocyty imunologie   MeSH
• imunosenescence imunologie   MeSH
• lidé MeSH
• neuroblastom imunologie   MeSH
• přežívající onkologičtí pacienti MeSH
• přežívající MeSH
• rizikové faktory MeSH
• TNF-alfa imunologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• dopisy MeSH
• práce podpořená grantem MeSH

Hot water extract from biomass of heterotrophic mutant green alga Parachlorella kessleri HY1 (Chlorellaceae) was deproteinised, and three polysaccharidic fractions were obtained by preparative chromatography. The low-molecular fraction (1.5 × 104g mol-1) was defined mainly as branched O-2-β-xylo-(1→3)-β-galactofuranan where xylose is partially methylated at O-4. Two high-molecular fractions (3.05 × 105 and 9.84 × 104g mol-1) were complex polysaccharides containing α-l-rhamnan and xylogalactofuranan parts in different ratios. The polysaccharides were well soluble in hot water and, upon cooling, tended to self-segregate. Immunomodulatory activities of the obtained fractions were preliminary tested using ELISA, FACS and ImmunoSpot kits. The polysaccharides increased the TNF-α production in melanoma bearing mice with much higher intensity than in healthy mice. This was in agreement with the FACS results on T and B cells indicating their possibly secondary activation by innate immunity cells.

• MeSH
• B-lymfocyty účinky léků   imunologie   patologie   MeSH
• CD antigeny genetika   imunologie   MeSH
• Chlorophyta chemie   MeSH
• imunologické faktory chemie   izolace a purifikace   farmakologie   MeSH
• interferon gama genetika   imunologie   MeSH
• interleukin-2 genetika   imunologie   MeSH
• interleukin-4 genetika   imunologie   MeSH
• lipopolysacharidy antagonisté a inhibitory   farmakologie   MeSH
• melanom imunologie   patologie   MeSH
• metylace MeSH
• molekulová hmotnost MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• nádory kůže imunologie   patologie   MeSH
• polysacharidy chemie   izolace a purifikace   farmakologie   MeSH
• primární buněčná kultura MeSH
• regulace genové exprese účinky léků   MeSH
• rostlinné extrakty chemie   MeSH
• rozpustnost MeSH
• sacharidové sekvence MeSH
• T-lymfocyty účinky léků   imunologie   patologie   MeSH
• TNF-alfa genetika   imunologie   MeSH
• voda MeSH
• xylosa chemie   izolace a purifikace   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND & AIMS: We investigated the effects of inducing deep remission in patients with early Crohn's disease (CD). METHODS: We collected follow-up data from 122 patients (mean age, 31.2 ± 11.3 y) with early, moderate to severe CD (median duration, 0.2 years; interquartile range, 0.1-0.5) who participated in the Effect of Tight Control Management on CD (CALM) study, at 31 sites, representing 50% of the original CALM patient population. Fifty percent of patients (n = 61) were randomly assigned to a tight control strategy (increased therapy based on fecal level of calprotectin, serum level of C-reactive protein, and symptoms), and 50% were assigned to conventional management. We categorized patients as those who were vs were not in deep remission (CD endoscopic index of severity scores below 4, with no deep ulcerations or steroid treatment, for 8 or more weeks) at the end of the follow-up period (median, 3.02 years; range, 0.05-6.26 years). The primary outcome was a composite of major adverse outcomes that indicate CD progression during the follow-up period: new internal fistulas or abscesses, strictures, perianal fistulas or abscesses, or hospitalization or surgery for CD. Kaplan-Meier and penalized Cox regression with bootstrapping were used to compare composite rates between patients who achieved or did not achieve remission at the end of the follow-up period. RESULTS: Major adverse outcomes were reported for 34 patients (27.9%) during the follow-up period. Significantly fewer patients in deep remission at the end of the CALM study had major adverse outcomes during the follow-up period (P = .01). When we adjusted for potential confounders, deep remission (adjusted hazard ratio, 0.19; 95% confidence interval, 0.07-0.31) was significantly associated with a lower risk of major adverse outcome. CONCLUSIONS: In an analysis of follow-up data from the CALM study, we associated induction of deep remission in early, moderate to severe CD with decreased risk of disease progression over a median time of 3 years, regardless of tight control or conventional management strategy.

• MeSH
• adalimumab aplikace a dávkování   škodlivé účinky   MeSH
• antiflogistika aplikace a dávkování   škodlivé účinky   MeSH
• azathioprin aplikace a dávkování   škodlivé účinky   MeSH
• časové faktory MeSH
• Crohnova nemoc diagnóza   farmakoterapie   imunologie   patologie   MeSH
• dospělí MeSH
• hospitalizace statistika a číselné údaje   MeSH
• indukce remise metody   MeSH
• kombinovaná farmakoterapie škodlivé účinky   metody   MeSH
• lidé MeSH
• mladý dospělý MeSH
• následné studie MeSH
• prednison aplikace a dávkování   škodlivé účinky   MeSH
• progrese nemoci MeSH
• retrospektivní studie MeSH
• stupeň závažnosti nemoci MeSH
• TNF-alfa antagonisté a inhibitory   imunologie   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Research Support, N.I.H., Extramural MeSH

• MeSH
• adalimumab farmakologie   terapeutické užití   MeSH
• dermatologické látky farmakologie   terapeutické užití   MeSH
• hidradenitis suppurativa diagnóza   farmakoterapie   imunologie   MeSH
• humanizované monoklonální protilátky farmakologie   terapeutické užití   MeSH
• hýždě MeSH
• interleukin-17 imunologie   metabolismus   MeSH
• léková rezistence MeSH
• lidé středního věku MeSH
• lidé MeSH
• receptory interleukinu-17 antagonisté a inhibitory   metabolismus   MeSH
• stupeň závažnosti nemoci MeSH
• TNF-alfa antagonisté a inhibitory   imunologie   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

The elevated plasma cell-free DNA (cfDNA) concentrations were repeatedly reported in association with the process of inflammation. The qualitative and quantitative characteristics of plasma cfDNA in active (newly diagnosed) celiac disease patients (CD) have not yet been studied despite the fact that cfDNA of healthy individuals is able to regulate immune response. We determined the total cfDNA concentration and relative content of telomeric sequences in plasma cfDNA in CD (n = 10) and healthy age- and sex-matched controls (HC, n = 10) by quantitative PCR. To obtain the evidence that the observed biological effects are caused solely by cfDNA molecules, we applied the treatment of paired plasma samples with DNase. Using paired samples of plasma (non-treated/native and treated by DNase), we analyzed the contribution of cfDNA to the activation of TLR9 and TNF-α mRNA expression in THP1 monocytic cell line. There were no significant differences in the quantities of plasma cfDNA and relative contents of telomeric sequences in their pools. When we compared the levels of TNF-α mRNA expression in THP1 cells achieved after stimulation with native CD and HC plasma samples, we found significantly (p = .031) higher expression after stimulation with CD samples. We documented also the ability of cfDNA contained in CD plasma samples to stimulate the production of TLR9 mRNA. The TLR9 mRNA expression levels were significantly (p = .014) lowered after cfDNA removal from CD plasma samples. The design of our experiments allowed us to study the effects of cfDNA without its isolation from plasma. cfDNA contained in CD plasma samples differs significantly in its immunoregulatory capacity from cfDNA in HC plasma. The differences are caused neither by different concentrations of cfDNA in plasma samples nor by different relative abundance of telomeric sequences. Further studies are needed to elucidate the role of plasma cfDNA in celiac disease pathogenesis.

• MeSH
• celiakie krev   MeSH
• dospělí MeSH
• imunologické faktory * krev   imunologie   farmakologie   MeSH
• kvantitativní polymerázová řetězová reakce MeSH
• lidé MeSH
• pilotní projekty MeSH
• regulace genové exprese * účinky léků   imunologie   MeSH
• THP-1 buňky MeSH
• TNF-alfa * biosyntéza   imunologie   MeSH
• toll-like receptor 9 * biosyntéza   imunologie   MeSH
• volné cirkulující nukleové kyseliny * krev   imunologie   farmakologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Candida albicans can enhance the invasion of oral epithelial cells by Porphyromonas gingivalis, although the fungus is not a periodontal pathogen. In this study, we investigated whether C. albicans augments proinflammatory cytokine production by mouse macrophage-like J774.1 cells incubated with synthetic bacterial components. Mouse macrophage-like J774.1 cells, mouse primary splenocytes, human THP-1 cells, and A549 cells were pretreated with or without heat-killed C. albicans (HKCA) or substitutes for C. albicans cell wall components in 96-well flat-bottomed plates. Cells were then washed and incubated with Pam3CSK4, a Toll-like receptor (TLR) 2 ligand, or lipid A, a TLR4 ligand. Culture supernatants were analyzed by ELISA for secreted IL-6, MCP-1, TNF-α, and IL-8. HKCA augmented TLR ligand-induced proinflammatory cytokine production by J774.1 cells, mouse splenocytes, and THP-1 cells, but not A549 cells. However, IL-6, MCP-1, and TNF-α production induced by Pam3CSK4 or lipid A was not augmented when cells were pretreated with curdlan, a dectin-1 ligand, or mannan, a dectin-2 ligand. In contrast, pretreatment of cells with TLR ligands upregulated the production of IL-6 and TNF-α, but not MCP-1, induced by Pam3CSK4 or lipid A. The results suggest that C. albicans augments synthetic bacterial component-induced cytokine production by J774.1 cells via the TLR pathway, but not the dectin-1 or dectin-2 pathway.

• MeSH
• buněčné linie MeSH
• Candida albicans chemie   fyziologie   MeSH
• cytokiny genetika   imunologie   MeSH
• infekce bakteriemi čeledi Bacteroidaceae genetika   imunologie   mikrobiologie   MeSH
• interleukin-6 genetika   imunologie   MeSH
• lektiny typu C genetika   imunologie   MeSH
• lidé MeSH
• makrofágy imunologie   mikrobiologie   MeSH
• myši MeSH
• Porphyromonas gingivalis chemie   fyziologie   MeSH
• TNF-alfa genetika   imunologie   MeSH
• toll-like receptor 2 genetika   imunologie   MeSH
• vysoká teplota MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Coronary artery disease (CAD) is a clinical manifestation of atherosclerosis in the arteries supplying myocardium. Inflammation is the cornerstone in the development and progression of atherosclerosis. Amongst the various biomolecules tumour necrosis factor-α (TNF-α), interleukin-18 (IL-18) and interleukin-1β (IL-1β) build an inflammatory bionetwork in developing the disease. In this study we investigated the association of TNF-α SNPs [–308G/A (rs1800629), −1031T/C (rs1799964), −863C/A (rs1800630)]; IL-18 [–137G/C (rs187238)] and IL-1β SNPs [+3954C/T (rs1143634), −31C/T (rs1143627), and −511C/T (rs16944)] with coronary artery disease risk in Kashmiri population. A total of 200 cases and 260 controls were recruited in the study. Logistic regression analysis was done to investigate the association between SNPs and CAD risk. In case of TNF-α, the −308G/A-A/A and −863A/A showed an association with disease while −1031T/C was found to have an inverse relation. The IL-18–137G/C showed no statistically significant difference between controls and cases. For IL-1β the +3954C/T and −31C/T SNP variants showed no disease association while −511T/T showed significant association. Haplotypic analysis revealed the haplotype ATCGCC and GTACCTC to be associated with CAD risk and GTCGTTT, in particular, showing a profound association. Overall, our study suggests that TNF-α and IL-1β promoter polymorphisms may act as genetic risk factors in developing the coronary artery disease.

• MeSH
• ateroskleróza genetika   patofyziologie   MeSH
• biologické markery MeSH
• interleukin-18 genetika   imunologie   MeSH
• interleukin-1beta genetika   imunologie   MeSH
• koronární nemoc genetika   MeSH
• lidé MeSH
• polymorfismus genetický MeSH
• studie případů a kontrol MeSH
• TNF-alfa genetika   imunologie   MeSH
• zánět * krev   patofyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH

Kyasanur Forest disease virus (KFDV) is a highly pathogenic tick-borne flavivirus enzootic to India. In humans, KFDV causes a severe febrile disease. In some infected individuals, hemorrhagic manifestations, such as bleeding from the nose and gums and gastrointestinal bleeding with hematemesis and/or blood in the stool, have been reported. However, the mechanisms underlying these hemorrhagic complications remain unknown, and there is no information about the specific target cells for KFDV. We investigated the interaction of KFDV with vascular endothelial cells (ECs) and monocyte-derived dendritic cells (moDCs), which are key targets for several other hemorrhagic viruses. Here, we report that ECs are permissive to KFDV infection, which leads to their activation, as demonstrated by the upregulation of E-selectin, intercellular adhesion molecule 1, and vascular cell adhesion molecule 1 at the mRNA and protein levels. Increased expression of these adhesive molecules correlated with increased leukocyte adhesion. Infected ECs upregulated the expression of interleukin (IL)-6 but not IL-8. Additionally, moDCs were permissive to KFDV infection, leading to increased release of IL-6 and tumor necrosis factor-α. Supernatants from KFDV-infected moDCs caused EC activation, as measured by leukocyte adhesion. The results indicate that ECs and moDCs can be targets for KFDV and that both direct and indirect mechanisms can contribute to EC activation.

• MeSH
• CD antigeny genetika   imunologie   MeSH
• cévní buněčněadhezivní molekula-1 genetika   imunologie   MeSH
• dendritické buňky imunologie   virologie   MeSH
• endoteliální buňky imunologie   virologie   MeSH
• interleukin-6 genetika   imunologie   MeSH
• interleukin-8 genetika   imunologie   MeSH
• kadheriny genetika   imunologie   MeSH
• kultivované buňky MeSH
• lidé MeSH
• messenger RNA MeSH
• mezibuněčná adhezivní molekula-1 genetika   imunologie   MeSH
• nemoc kyasanurského lesa imunologie   MeSH
• TNF-alfa genetika   imunologie   MeSH
• viry klíšťové encefalitidy imunologie   patogenita   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH