Background: Chronic hepatitis C (CHC) is associated with altered cell-mediated immune response. Objective: The aim of the study was to characterize functional alterations in CD4+ T cell subsets and myeloid-derived suppressor cells (MDSCs) during chronic hepatitis C virus (HCV) infection. Methodology. The expression levels of the lineage-defining transcriptional factors (TFs) T-bet, Gata3, Rorγt, and Foxp3 in circulating CD4+ T cells and percentages of MDSCs in peripheral blood were evaluated in 33 patients with CHC, 31 persons, who had spontaneously cleared the HCV infection, and 30 healthy subjects. Analysis. The CD4+ T cells TFs T-bet (T-box expressed in T cells), Foxp3 (Forkhead box P3 transcription factor), Gata3 (Gata-binding protein 3), and Rorγt (retinoic-acid-related orphan receptor gamma) and activation of CD8+ T cells, as well as percentages of MDSCs, were measured by multicolor flow cytometry after intracellular and surface staining of peripheral blood mononuclear cells with fluorescent monoclonal antibodies. Result: The patients with CHC had significantly lower percentages of CD4+ T cells expressing Rorγt and Gata3 and higher percentages of Foxp3-expressing CD4+ T cells than healthy controls and persons who spontaneously cleared HCV infection. The ratios of T-bet+/Gata3+ and Foxp3+/Rorγt+ CD4+ T cells were the highest in the patients with CHC. In the patients with CHC, the percentages of Gata3+ and Rorγt+ CD4+ T cells and the percentages of T-bet+ CD4+ T cells and CD38+/HLA-DR+ CD8+ T cells demonstrated significant positive correlations. In addition, the percentage of CD38+/HLA-DR+ CD8+ T cells correlated negatively with the percentage of MDSCs. Conclusion: Chronic HCV infection is associated with downregulation of TFs Gata3 and Rorγt polarizing CD4+ T cells into Th2 and Th17 phenotypes together with upregulation of Foxp3 responsible for induction of regulatory T cells suppressing immune response.
- Publikační typ
- časopisecké články MeSH
The aim was to analyze T-regulatory cells (Tregs), activated CD8(+) T cells, and transforming growth factor-beta (TGF)-β in hepatitis C patients. We enrolled 31 patients with chronic genotype 1 hepatitis C virus (HCV) infection, 30 seropositive persons with spontaneous HCV elimination, and 23 healthy volunteers. The patients were examined at the beginning of the interferon-alpha (IFN-α)-based therapy (baseline) and at weeks 4 (W4) and 12 (W12) of the therapy. The percentage of Tregs and the expression of activation markers CD38 and HLA-DR on CD8(+) T cells were analyzed in the peripheral blood by flow cytometry. Serum levels of TGF-β were measured in a multiplex assay using flow cytometry. The percentage of Tregs in patients was higher than in controls and seropositive persons. Similarly, the percentage of CD8(+) T cells expressing CD38 and HLA-DR was higher in patients compared with controls and seropositive persons. Chronic HCV infection is associated with elevated circulating Tregs and activated CD8(+) T cells. During IFN-α-based therapy these cells gradually increase, whereas TGF-β serum levels decrease.
- MeSH
- aktivace lymfocytů * MeSH
- antigeny CD38 analýza MeSH
- antivirové látky terapeutické užití MeSH
- CD8-pozitivní T-lymfocyty chemie imunologie MeSH
- chronická hepatitida C farmakoterapie patologie virologie MeSH
- dospělí MeSH
- genotyp MeSH
- Hepacivirus klasifikace genetika MeSH
- HLA-DR antigeny analýza MeSH
- imunofenotypizace MeSH
- inhibitory proteas terapeutické užití MeSH
- interferon alfa terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- membránové glykoproteiny analýza MeSH
- mladý dospělý MeSH
- průtoková cytometrie MeSH
- regulační T-lymfocyty imunologie MeSH
- ribavirin terapeutické užití MeSH
- senioři MeSH
- sérum chemie MeSH
- transformující růstový faktor beta krev MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Psoriasis is associated with metabolic activity of adipose tissue which produces pro- and anti-inflammatory adipokines. Goeckerman therapy (GT) represents an effective treatment of psoriasis. This study evaluated variation of selected inflammatory and metabolic markers during GT and the relationships between the markers, severity of the disease (PASI score), body mass, and the basic characteristics of the therapy. The study was conducted on a group of patients (n = 32) and on a control group (n = 24). Before GT, we found significantly elevated levels of proinflammatory CRP (p < 0.001) and leptin (p < 0.05) in psoriatic patients (compared to the controls). The therapy significantly decreased the levels of CRP and adiponectin. We found positive correlations between CRP and total duration of GT (p < 0.05) and CRP and the time of UV exposure (p < 0.01) and negative correlations between adiponectin and the total duration of GT (p < 0.05) and adiponectin and the application of CCT ointment (p < 0.001). From our results, we can conclude that GT causes partial reduction of both proinflammatory and anti-inflammatory markers. However, the levels of proinflammatory CRP and leptin remained significantly higher in the patients than in the control group.
- MeSH
- adiponektin krev MeSH
- biologické markery MeSH
- C-reaktivní protein analýza MeSH
- dospělí MeSH
- index tělesné hmotnosti MeSH
- leptin krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- masti MeSH
- psoriáza krev farmakoterapie MeSH
- senioři MeSH
- stupeň závažnosti nemoci MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: Toll-like receptor (TLR) 2 belongs to the large TLR receptor family comprised of at least 10 members with different roles in innate immunity. Psoriasis is recognized as a T-cell driven immune-mediated systemic inflammatory disease with a skin manifestation. An effective therapeutic approach to treat psoriasis is Goeckerman therapy (GT). The aim of this study was to assess both the kinetics of the expression of TLR2 on blood cells and the concentration of soluble (s)TLR2 in serum of patients with psoriasis and to examine the effect of GT on both TLR2 expression and sTLR2 level. METHODS: Both membrane and sTLR2 were determined in 20 patients and 20 healthy controls. sTLR2 was evaluated by enzyme-linked immunosorbent assay. Flow cytometry method was used to determine the expression of membrane TLR2 of monocytes and granulocytes. RESULTS: The serum level of sTLR2 was significantly lower (P < 0.0001) in patients both before and after GT compared to the control group. Compared to the membrane expression of TLR2 on monocytes of healthy blood donors, TLR2 expression was significantly higher in patients both before and after GT (P = 0.0001). Similarly, TLR2 expression on granulocytes was significantly higher in patients both before (P = 0.0061) and after (P < 0.0001) therapy than in control. CONCLUSIONS: Membrane and soluble TLR2 may be involved in the pathogenesis of psoriasis. Both remained unchanged by GT.
- MeSH
- buněčná membrána chemie MeSH
- dehet uhelný terapeutické užití MeSH
- dospělí MeSH
- fotochemoterapie * MeSH
- granulocyty chemie MeSH
- keratolytika terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- monocyty chemie MeSH
- psoriáza krev farmakoterapie MeSH
- studie případů a kontrol MeSH
- terapie ultrafialovými paprsky * MeSH
- toll-like receptor 2 analýza krev MeSH
- zdraví dobrovolníci pro lékařské studie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Kontinuální tvorba výpotků jakékoliv etiologie zásadním způsobem ovlivňuje kvalitu života nemocných. Akumulace tekutiny v pleurální dutině postupně komprimuje plicní parenchym. Prvním příznakem bývá progrese námahové dušnosti, později se přidává i klidová dušnost. S nárůstem výpotku dochází ke kompresi plicního parenchymu s rozvojem plicní atelektázy. Nemocný je ohrožen vznikem zánětového onemocnění plic v nevzdušném plicním parenchymu. U diagnózy maligního onemocnění je riziko zánětových komplikací výrazně vyšší vzhledem k předchozí chemoterapii či radioterapii, která zásadním způsobem snižuje imunitu. Opakovaná tvorba výpotku se výrazně podílí na rozvoji terminálního stavu nádorové kachexie. Efektivní metodou léčby je chemická pleurodéza, která se užívá u vybraného spektra nemocných. Principem je navození aseptické pleuritidy. Nejefektivnější cestou aplikace léčiva je videotorakoskopie. V souboru bylo 47 nemocných, 29 (61,7 %) mužů a 18 (38,3 %) žen, s cytologicky prokázaným recidivujícím maligním pleurálním výpotkem. Věkové rozmezí 42–80 let, Ø věk 65 let. Cílem práce bylo objektivizovat průběh celkových a lokálních zánětových změn po talkáži. Efekt léčby nebyl ovlivněn základním typem nádorového onemocnění. U obou skupin nebyly významně odlišné pooperační komplikace, což dokládá bezpečnost zvolené metody a podporuje správně zvolený algoritmus léčby.
Continuous pleural effusion production of any aetiology can significantly affect the quality of patients life. Chronic effusion accumulation in the pleural cavity can lead to lung parenchyma compression. The first symptom of this entity is a progressive exertional dyspnea, which can later turn in dyspnea at rest. With the increase of the pleural effusion volume, pulmonary atelectasis can develop due to chronic parenchycha compression. The patient is at risk of inflamatory complications from the territory of non-ventilated parenchyma. Patients with a diagnosis of malignant disease have this risk considerably higher due to their previous chemotherapy or radiation, which substantially affect the immunity system. Repeated pleural effusion formation can significantly take part in the development of the terminal status of cancer cachexia. An effective method of palliative treatment is a chemical pleurodesis, which is used in selected patients. The principle is inducing aseptic inflammation. The most effective way of application is via videothoracoscopy. In a group of 47 patients, there were 29 (61.7 %) men and 18 (38.3 %) women with cytologically diagnosed recurrent malignant pleural. The age ranged between 42 and 80 with average age of 65 years. The aim was to assess the course of local and systemic inflammatory changes after talc application. The effect of treatment was not influenced by the type of malignancy . In both groups there was no significant difference in postoperative complications. This proves the safety of the selected procedure and also supports the correctness of the chosen algorithm of treatment.
- Klíčová slova
- sCD-163, talkáž,
- MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- maligní pleurální výpotek * etiologie farmakoterapie chirurgie MeSH
- mastek terapeutické užití MeSH
- pleurodéza * metody statistika a číselné údaje MeSH
- senioři MeSH
- torakoskopie MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- hodnotící studie MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
BACKGROUND: Malignant pleural effusions accumulate in the space between the visceral (inner) layer covering the lungs and the parietal (outer) layer covering the chest wall. Larger effusions compress the pulmonary parenchyma resulting in increasing dyspnoea. Treatment is always local and palliative. Among others, chemical pleurodesis using talc can be performed in selected patients. Talc is hydrated magnesium silicate (chemically H₂Mg₃(SiO₃)₄) and has been used for pleurodesis since 1935. Videothoracoscopic talc powder insufflation (talc poudrage) is the most effective.However, markers of inflammatory reactions to extraneous substances like talc are not fully understood. The aim of this study was to assess the course of local inflammatory changes in the pleural cavity after talc insufflation. METHODS: The Department of Cardiac Surgery of the Faculty of Medicine and University Hospital in Hradec Kralove, treated 47 patients aged 65 on average; 29 males and 18 females with proven recurrent malignant pleural effusion of various aetiologies from January 2009 to December 2010. They were retrospectively divided into group A (40 patients) without recurring effusion, and group B (7 patients) with recurring effusion and the need for thoracentesis or chest drainage during the 9-month monitoring. RESULTS: Major findings were made in soluble forms of cell receptors. Group B showed statistically higher levels of the anti-inflammatory form of sCD-163 receptor in pleural fluid before the talc poudrage. This showed limited ability to create an adequate inflammatory response to external stimuli. This group also showed lower levels of the inflammatory form of sTLR-2 receptor immediately after the talc insufflation. This revealed low local reactivity to external stimuli. The effect of the treatment was not influenced by morphologic tumour type. No statistically significant differences in postoperative complications were found. This confirmed the safety of both videothoracoscopy and treatment. CONCLUSIONS: There was no correlation between the type of malignant affection and the outcome of the chemical pleurodesis. Patients with relapsing effusion have higher values of concentration of anti-inflammatory sCD-163 in pleural fluid even before the application of talc, and lower levels of concentration of inflammatory sTLR-2 immediately after application of talc.
- MeSH
- antigeny diferenciační myelomonocytární analýza MeSH
- biologické markery analýza MeSH
- CD antigeny analýza MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- maligní pleurální výpotek imunologie terapie MeSH
- mastek imunologie terapeutické užití MeSH
- pleurodéza * MeSH
- receptory buněčného povrchu analýza MeSH
- retrospektivní studie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- toll-like receptor 2 analýza MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
CD200 and its receptor were recognized as having the multiple immunoregulatory functions. Their immunoregulatory, suppressive, and tolerogenic potentials could be very effectively exploited in the treatment of many diseases, e.g. Alzheimer disease, rheumatoid arthritis, and allergy to name only some. Many research projects are aimed to develop clinically valuable methods being based on the structure and function of these paired molecules. In this review, we would like to introduce CD200/CD200R functions in a clinical context.
- MeSH
- autoimunitní nemoci imunologie MeSH
- CD antigeny imunologie terapeutické užití MeSH
- imunita MeSH
- lidé MeSH
- nádory imunologie terapie MeSH
- nemoci centrálního nervového systému imunologie MeSH
- transplantační imunologie MeSH
- virové nemoci imunologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
Regulatory T cells (Treg) are a specialized subpopulation of T cells that act to suppress inadequate immune response. Psoriasis is recognized as a T -cell driven immune-mediated systemic inflammatory disease with skin manifestation. Effective therapeutical approach to treat psoriasis is Goeckerman therapy (GT ). The aim of this study was to compare the number of Treg in the peripheral blood of 27 psoriatic patients and 19 controls and to evaluate the influence of GT on Treg population in peripheral blood of patients with psoriasis. There was no significant difference in the relative number of Treg cells in the peripheral blood of healthy blood donors and patients with psoriasis before initiation of GT (P = 0.2668). In contrary, the relative number of Treg cells in peripheral blood of patients with psoriasis after GT was significantly higher than those found in healthy blood donors (P = 0.0019). Moreover, the relative number of Treg is significantly increased in psoriatic patients after Goeckerman therapy compared to the pre-treatment level (P = 0.0042). In conclusion, this significant increase in Treg count after GT is probably associated with amelioration of inflammation by GT , as disease activity expressed as PASI decreased in our patients by GT (P = 0.0001).
- MeSH
- dehet uhelný terapeutické užití MeSH
- dermatologické látky terapeutické užití MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- počet lymfocytů MeSH
- psoriáza imunologie terapie MeSH
- regulační T-lymfocyty imunologie MeSH
- terapie ultrafialovými paprsky MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- práce podpořená grantem MeSH
The aim of this study was to examine the role of TLR2 molecule in pleural space during thoracoscopic talc pleurodesis period in patients with malignant pleural effusion. We analyzed TLR2 molecule in soluble form as well as on membrane of granulocytes in pleural fluid. Pleural fluid examination was done at three intervals during pleurodesis procedure: 1st-before the thoracoscopic procedure, 2nd-2 hours after the terminating thoracoscopic procedure with talc insufflation, 3rd-24 hours after the thoracoscopic procedure. We reported significant increase of soluble TLR2 molecule in pleural fluid effusion during talc pleurodesis from preoperative value. This increase was approximately 8-fold in the interval of 24 hours. The changes on granulocyte population were quite different. The mean fluorescent intensity of membrane TLR2 molecule examined by flow cytometry on granulocyte population significantly decreased after talc exposure with comparison to prethoracoscopic density. To estimate the prognostic value of TLR2 expression in pleural fluid patients were retrospectively classified into either prognostically favourable or unfavourable groups. Our results proved that patients with favourable prognosis had more than 3-fold higher soluble TLR2 level in pleural fluid early, 2 hours after talc pleurodesis intervention.
- MeSH
- granulocyty účinky léků metabolismus MeSH
- insuflace metody MeSH
- lidé MeSH
- maligní pleurální výpotek metabolismus terapie MeSH
- mastek aplikace a dávkování MeSH
- pleura účinky léků metabolismus MeSH
- pleurodéza metody MeSH
- prognóza MeSH
- retrospektivní studie MeSH
- senioři MeSH
- toll-like receptor 2 metabolismus MeSH
- torakoskopie metody MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky MeSH
- práce podpořená grantem MeSH
CD200/CD200R are highly conserved type I paired membrane glycoproteins that belong to the Ig superfamily containing a two immunoglobulin‑like domain (V, C). CD200 is broadly distributed in a variety of cell types, whereas CD200R is primarily expressed in myeloid and lymphoid cells. They fulfill multiple functions in regulating inflammation. The interaction between CD200/CD200R results in activation of the intracellular inhibitory pathway with RasGAP recruitment and thus contributes to effector cell inhibition. It was confirmed that the CD200R activation stimulates the differentiation of T cells to the Treg subset, upregulates indoleamine 2,3‑dioxygenase activity, modulates cytokine environment from a Th1 to a Th2 pattern, and facilitates an antiinflammatory IL‑10 and TGF‑β synthesis. CD200/CD200R are required for maintaining self‑tolerance. Many studies have demonstrated the importance of CD200 in controlling autoimmunity, inflammation, the development and spread of cancer, hypersensitivity, and spontaneous fetal loss.
- MeSH
- antigeny povrchové fyziologie MeSH
- CD antigeny fyziologie MeSH
- imunita fyziologie MeSH
- lidé MeSH
- receptory buněčného povrchu fyziologie MeSH
- signální transdukce MeSH
- zánět patofyziologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH