INTRODUCTION: Central nervous system (CNS) involvement in diffuse large B-cell lymphoma (DLBCL) is a rare but serious condition requiring accurate diagnostics. Cerebrospinal fluid (CSF) analysis plays a crucial role, particularly in cases where biopsy is not feasible, and imaging is inconclusive. AREAS COVERED: Chemical markers have limitations, particularly in low-cellularity samples. Novel molecular techniques, including circulating tumor DNA (ctDNA) analysis and microRNAs (miRNAs), are gaining prominence for their ability to detect gene mutations at diagnosis and monitor minimal residual disease during follow-up. The sensitivity and specificity of genetic mutations, particularly MYD88 L265P, in combination with interleukin-10 (IL-10) levels, are discussed. The literature search methodology involved reviewing relevant studies and clinical data.This review examines both traditional and emerging methods for CSF analysis in diagnosing CNS involvement in DLBCL. Conventional approaches such as cytomorphology, flow cytometry, and biochemical markers have limitations, particularly in low-cellularity samples. Novel molecular techniques, including ctDNA analysis and miRNAs, are gaining prominence for their ability to detect gene mutations at diagnosis and monitor minimal residual disease during follow-up. The sensitivity and specificity of genetic mutations, particularly MYD88 L265P, in combination with interleukin-10 (IL-10) levels, are discussed. The literature search methodology involved reviewing relevant studies and clinical data. EXPERT OPINION: Advancements in CSF biomarker analysis are improving the diagnosis of CNS lymphoma, aiding early detection and personalized treatment approaches. However, further research and broader clinical validation are necessary for their routine implementation.
- MeSH
- cirkulující nádorová DNA mozkomíšní mok genetika MeSH
- diagnostické techniky molekulární metody MeSH
- difúzní velkobuněčný B-lymfom * diagnóza mozkomíšní mok genetika patologie MeSH
- interleukin-10 genetika mozkomíšní mok MeSH
- lidé MeSH
- meningeální nádory * diagnóza mozkomíšní mok genetika MeSH
- mikro RNA genetika mozkomíšní mok MeSH
- mutace MeSH
- myeloidní diferenciační faktor 88 genetika MeSH
- nádorové biomarkery * mozkomíšní mok genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
INTRODUCTION: A critical step preceding the potential biomedical application of nanoparticles is the evaluation of their immunomodulatory effects. Such nanoparticles are expected to enter the bloodstream where they can be recognized and processed by circulating monocytes. Despite the required biocompatibility, this interaction can affect intracellular homeostasis and modulate physiological functions, particularly inflammation. This study focuses on titanium dioxide (TiO2) as an example of relatively low cytotoxic nanoparticles with potential biomedical use and aims to evaluate their possible modulatory effects on the inflammasome-based response in human primary monocytes. METHODS: Monocyte viability, phenotypic changes, and cytokine production were determined after exposure to TiO2 (diameter, 25 nm; P25) alone. In the case of the modulatory effects, we focused on NLRP3 activation. The production of IL-1β and IL-10 was evaluated after (a) simultaneous activation of monocytes with bacterial stimuli muramyl dipeptide (MDP), or lipopolysaccharide (LPS), and TiO2 (co-exposure model), (b) prior activation with TiO2 alone and subsequent exposure to bacterial stimuli MDP or LPS. The differentiation of TiO2-treated monocytes into macrophages and their polarization were also assessed. RESULTS: The selected TiO2 concentration range (30-120 μg/mL) did not induce any significant cytotoxic effects. The highest dose of TiO2 promoted monocyte survival and differentiation into macrophages, with the M2 subset being the most prevalent. Nanoparticles alone did not induce substantial production of inflammatory cytokines IL-1β, IL-6, or TNF-α. The immunomodulatory effect on NLRP3 depended on the type of costimulant used. While co-exposure of monocytes to MDP and TiO2 boosted NLRP3 activity, co-exposure to LPS and TiO2 inhibited NLRP3 by enhancing IL-10 release. The inhibitory effect of TiO2 on NLRP3 based on the promotion of IL-10 was confirmed in a post-exposure model for both costimulants. CONCLUSION: This study confirmed a non-negligible modulatory effect on primary monocytes in their inflammasome-based response and differentiation ability.
- MeSH
- acetylmuramyl-alanyl-isoglutamin farmakologie MeSH
- buněčná diferenciace účinky léků MeSH
- cytokiny metabolismus MeSH
- inflamasomy účinky léků MeSH
- interleukin-10 metabolismus MeSH
- interleukin-1beta metabolismus MeSH
- kovové nanočástice chemie toxicita MeSH
- kultivované buňky MeSH
- lidé MeSH
- lipopolysacharidy * farmakologie MeSH
- makrofágy účinky léků MeSH
- monocyty * účinky léků MeSH
- nanočástice chemie toxicita MeSH
- protein NLRP3 * metabolismus MeSH
- titan * chemie farmakologie toxicita MeSH
- viabilita buněk * účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
INTRODUCTION: Inflammation of the placenta is harmful to both the fetus and the mother. Inflammation is strongly associated with diabetes, a common complication of pregnancy. Hofbauer cells (HBCs), unique immune system cells of fetal origin in the placenta, play complex roles, including growth of placental villi and their branching, stromal remodelling, and angiogenesis. METHODS: Our study investigated the expression of IL-1β, IL-10, CYP2C8, CYP2C9, CYP2J2 and sEH in HBCs from patients with type 1 diabetes mellitus (T1DM) and gestational diabetes mellitus (GDM) compared to healthy controls using immunohistochemistry. We also assessed the structure of the villus stroma using Masson ́s trichrome. RESULTS: In T1DM, HBCs showed inflammatory activation characterised by increased IL-1β and decreased CYP epoxygenase expression compared to normal placentas. Conversely, significant inflammation in HBCs appeared less likely in GDM, as levels of IL-1β and CYP epoxygenases remained stable compared to normal placentas. However, GDM showed a significant increase in sEH expression. Both types of diabetes showed delayed placental villous maturation and hypovascularisation, with GDM showing a more pronounced effect. CONCLUSION: The expression profiles of IL-1β, CYP epoxygenases and sEH significantlly differ between controls and diabetic placentas and between T1DM and GDM. These facts suggest an association of the CYP epoxygenase-EETs-sEH axis with IL-1β expression as well as villous stromal hypovascularisation. Given the stable high expression of IL-10 in both controls and both types of diabetes, it appears that immune tolerance is maintained in HBCs.
- MeSH
- diabetes mellitus 1. typu * metabolismus MeSH
- gestační diabetes * MeSH
- interleukin-10 metabolismus MeSH
- lidé MeSH
- placenta metabolismus MeSH
- těhotenství MeSH
- zánět metabolismus MeSH
- Check Tag
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
INTRODUCTION: In pulmonary hypertension (PH), pulmonary arterial remodeling is often accompanied by perivascular inflammation. The inflammation is characterized by the accumulation of activated macrophages and lymphocytes within the adventitial stroma, which is comprised primarily of fibroblasts. The well-known ability of fibroblasts to secrete interleukins and chemokines has previously been implicated as contributing to this tissue-specific inflammation in PH vessels. We were interested if pulmonary fibroblasts from PH arteries contribute to microenvironmental changes that could activate and polarize T-cells in PH. METHODS: We used single-cell RNA sequencing of intact bovine distal pulmonary arteries (dPAs) from PH and control animals and flow cytometry, mRNA expression analysis, and respirometry analysis of blood-derived bovine/human T-cells exposed to conditioned media obtained from pulmonary fibroblasts of PH/control animals and IPAH/control patients (CM-(h)PH Fibs vs CM-(h)CO Fibs). RESULTS: Single-cell RNA sequencing of intact bovine dPAs from PH and control animals revealed a pro-inflammatory phenotype of CD4+ T-cells and simultaneous absence of regulatory T-cells (FoxP3+ Tregs). By exposing T-cells to CM-(h)PH Fibs we stimulated their proinflammatory differentiation documented by increased IFNγ and decreased IL4, IL10, and TGFβ mRNA and protein expression. Interestingly, we demonstrated a reduction in the number of suppressive T-cell subsets, i.e., human/bovine Tregs and bovine γδ T-cells treated with CM-(h)PH-Fibs. We also noted inhibition of anti-inflammatory cytokine expression (IL10, TGFβ, IL4). Pro-inflammatory polarization of bovine T-cells exposed to CM-PH Fibs correlated with metabolic shift to glycolysis and lactate production with increased prooxidant intracellular status as well as increased proliferation of T-cells. To determine whether metabolic reprogramming of PH-Fibs was directly contributing to the effects of PH-Fibs conditioned media on T-cell polarization, we treated PH-Fibs with the HDAC inhibitor SAHA, which was previously shown to normalize metabolic status and examined the effects of the conditioned media. We observed significant suppression of inflammatory polarization associated with decreased T-cell proliferation and recovery of mitochondrial energy metabolism. CONCLUSION: This study demonstrates how the pulmonary fibroblast-derived microenvironment can activate and differentiate T-cells to trigger local inflammation, which is part of the vascular wall remodeling process in PH.
- MeSH
- interleukin-10 MeSH
- interleukin-4 MeSH
- kultivační média speciální metabolismus MeSH
- lidé MeSH
- plicní hypertenze * metabolismus MeSH
- skot MeSH
- T-lymfocyty - podskupiny metabolismus MeSH
- transformující růstový faktor beta MeSH
- zánět metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- skot MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
PURPOSE: To investigate the ocular surface inflammation in patients with primary open angle glaucoma and ocular hypertension by analyzing tears and to compare findings with healthy controls. METHODS: Observational case-control study. Tear samples were collected by 5 μl microcapillary tube from 24 patients with glaucoma treated by antiglaucoma drops, 9 non-treated patients with ocular hypertension and 45 healthy controls. Tears were analyzed from right eye by multiplex Bio-Plex system for the presence of 6 cytokines: IL1β, IL10, IL4, IFNγ, MIF and VEGF. RESULTS: Significantly higher concentrations of IL1β and IL10 (glaucoma or ocular hypertension vs. healthy controls, p < 0.0001), VEGF (glaucoma vs. ocular hypertension, p < 0.05; ocular hypertension vs. healthy controls, p < 0.02) and MIF (glaucoma vs. healthy controls, p < 0.03) were detected in patients' tears. Both patient groups have activated to a significantly lower extent the Th1 pathway represented by IFNγ than Th2 pathway represented by IL10 (p < 0.001) and, at the same time, the IFNγ/IL4 ratio was significantly increased in healthy controls (p < 0.001) and patients with ocular hypertension (p < 0.02) compared to glaucoma individuals. CONCLUSION: This study shows that secretion of inflammation-related cytokines by conjunctival cells is increased in both, glaucoma and ocular hypertension patients and can be detected in their tears. Nevertheless, data indicates stronger ocular surface inflammation in non-treated follow-up patients diagnosed with ocular hypertension than in glaucoma subjects treated by antiglaucoma drops.
- MeSH
- antihypertenziva terapeutické užití MeSH
- cytokiny metabolismus MeSH
- glaukom s otevřeným úhlem * MeSH
- glaukom * farmakoterapie MeSH
- interleukin-10 metabolismus MeSH
- interleukin-4 metabolismus MeSH
- lidé MeSH
- nitrooční tlak MeSH
- oční hypertenze * MeSH
- oční roztoky MeSH
- slzy metabolismus MeSH
- studie případů a kontrol MeSH
- vaskulární endoteliální růstový faktor A metabolismus MeSH
- zánět metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
The use of herbal medicinal products and supplements in amateur and professional sports has increased in the last decades. This is because most of these products and supplements contain bioactive compounds with a variety of biological properties that exert a physiological effect on the human body. The aim of this study was to analyze the effect of dietary supplementation with lyophilized black chokeberry extract on the levels of pro-inflammatory cytokines, hepcidin, and selected markers of iron metabolism in a group of young football players. This double-blind study included 22 male football players (mean = 19.96 ± 0.56), divided into two groups: supplemented and placebo. Before and after a 90-day period of training combined with supplementation (6 g of lyophilized black chokeberry extract), participants performed maximal multistage 20-m shuttle run tests at the beginning and at the end of the supplementation period, with blood sampled for analysis at different times before and after exercise. The levels of IL-6, IL-10, ferritin, myoglobin, hepcidin, 8-OHdG, albumin, and TAC were analyzed. The analysis of variance revealed a significant effect of 90-day supplementation with the lyophilized extract on changes in the IL-6 and IL-10 levels, and TAC induced by maximal aerobic effort. In conclusion, supplementation with lyophilized black chokeberry extract improves the performance and antioxidant status of serum in humans and induces protective changes in inflammatory markers.
- MeSH
- dvojitá slepá metoda MeSH
- fotbal MeSH
- hepcidiny MeSH
- interleukin-10 MeSH
- interleukin-6 MeSH
- lidé MeSH
- mladý dospělý MeSH
- Photinia * MeSH
- potravní doplňky * MeSH
- rostlinné extrakty * farmakologie MeSH
- sportovci MeSH
- zánět MeSH
- železo * metabolismus MeSH
- Check Tag
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- randomizované kontrolované studie MeSH
Inflammation and immunity belong to the main factors influencing tumor growth. In this study, we attempted to identify a profile of biomarkers associated with gliomas. We found decreased serum levels of sTREM-1 (soluble triggering receptor expressed on myelocytes) and increased levels of IL-10 in all grades of glioma patients in comparison with healthy controls (sTREM-1: grade II: p=0.0051, grade III: p=0.02, grade IV: p=0.01; IL-10: grade II: p=0.0017, grade III: p=0.03, grade IV: p=0.007). However, we did not find any combination of tested markers with good sensitivity and specificity in grades II and III of glioma patients to discriminate them from healthy controls. In grade IV glioma patients, two sets of markers showed promising results in distinguishing patients from healthy people. For the first set consisting of four selected markers, sTREM-1, sHLA-G, BDNF, and IL-13, the ROC curves indicate a good discriminatory capability for glioblastoma patients (AUC=0.9510). The best discriminatory capability for glioblastoma patients (AUC=0.9534) was found for the second set consisting of three selected markers sTREM-1, sHLA-G, and BDNF with 79.2% sensitivity and 94.1% specificity.
- MeSH
- biologické markery MeSH
- glioblastom * MeSH
- gliom * MeSH
- interleukin-10 MeSH
- lidé MeSH
- mozkový neurotrofický faktor MeSH
- receptor TREM-1 MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
OBJECTIVE: To investigate the physiological profile of pro-inflammatory and anti-inflammatory cytokines in tears produced by epithelial cells under the effect of endogenous and exogenous biological factors. Knowing the physiological cytokine profile in tears with its biological characteristics including sex- and age-specific effects is fundamental when tears are analyzed for diagnostic or prognostic purposes in eye diseases. METHODS: Tear samples were collected from right eye of 45 healthy volunteers (24 males, 21 females) by 5 μl microcapillary tube. Cytokines interleukin 1β, interleukin 10, interleukin 4, interferon gamma, macrophage migration inhibitory factor, and vascular endothelial growth factor were quantified by multiplex Bio-Plex system. RESULTS: The production of macrophage migration inhibitory factor cytokine by epithelial cells on the ocular surface is higher in males compared to females (p = 0.05); actually, most of female tear samples present with undetectable macrophage migration inhibitory factor levels. Our results show the negative correlations between the age and concentrations of interleukin 4 (p < 0.01) and interferon gamma (p < 0.01) in tears, respectively, and positive associations of vascular endothelial growth factor levels with the age above 45 years (p < 0.05). CONCLUSIONS: Data in this study indicate that age and sex may affect the physiological levels of cytokines in tears. Consequently, the impacts of biological factors need to be recognized and taken into consideration before the levels of cytokines in patients' tears are analyzed for medical reasons. Concentrations of interleukin 1β and interleukin 10 cytokines, however, are very low in healthy tears and do not seem to be influenced by studied biological factors; therefore, they meet the requirements for analytes suitable for medical diagnostic and prognostic purposes.
- MeSH
- inhibiční faktory migrace makrofágů * metabolismus MeSH
- interferon gama * metabolismus MeSH
- interleukin-10 metabolismus MeSH
- interleukin-1beta * metabolismus MeSH
- interleukin-4 * metabolismus MeSH
- lidé MeSH
- sexuální faktory MeSH
- slzy * metabolismus MeSH
- vaskulární endoteliální růstový faktor A * metabolismus MeSH
- věkové faktory MeSH
- zdraví dobrovolníci pro lékařské studie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: According to the biodiversity hypothesis of immune-mediated diseases, lack of microbiological diversity in the everyday living environment is a core reason for dysregulation of immune tolerance and - eventually - the epidemic of immune-mediated diseases in western urban populations. Despite years of intense research, the hypothesis was never tested in a double-blinded and placebo-controlled intervention trial. OBJECTIVE: We aimed to perform the first placebo-controlled double-blinded test that investigates the effect of biodiversity on immune tolerance. METHODS: In the intervention group, children aged 3-5 years were exposed to playground sand enriched with microbially diverse soil, or in the placebo group, visually similar, but microbially poor sand colored with peat (13 participants per treatment group). Children played twice a day for 20 min in the sandbox for 14 days. Sand, skin and gut bacterial, and blood samples were taken at baseline and after 14 days. Bacterial changes were followed for 28 days. Sand, skin and gut metagenome was determined by high throughput sequencing of bacterial 16 S rRNA gene. Cytokines were measured from plasma and the frequency of blood regulatory T cells was defined as a percentage of total CD3 +CD4 + T cells. RESULTS: Bacterial richness (P < 0.001) and diversity (P < 0.05) were higher in the intervention than placebo sand. Skin bacterial community, including Gammaproteobacteria, shifted only in the intervention treatment to resemble the bacterial community in the enriched sand (P < 0.01). Mean change in plasma interleukin-10 (IL-10) concentration and IL-10 to IL-17A ratio supported immunoregulation in the intervention treatment compared to the placebo treatment (P = 0.02). IL-10 levels (P = 0.001) and IL-10 to IL-17A ratio (P = 0.02) were associated with Gammaproteobacterial community on the skin. The change in Treg frequencies was associated with the relative abundance of skin Thermoactinomycetaceae 1 (P = 0.002) and unclassified Alphaproteobacteria (P < 0.001). After 28 days, skin bacterial community still differed in the intervention treatment compared to baseline (P < 0.02). CONCLUSIONS: This is the first double-blinded placebo-controlled study to show that daily exposure to microbial biodiversity is associated with immune modulation in humans. The findings support the biodiversity hypothesis of immune-mediated diseases. We conclude that environmental microbiota may contribute to child health, and that adding microbiological diversity to everyday living environment may support immunoregulation.
- MeSH
- Bacteria genetika MeSH
- biodiverzita MeSH
- cytokiny MeSH
- dvojitá slepá metoda MeSH
- interleukin-10 * MeSH
- interleukin-17 * MeSH
- lidé MeSH
- písek MeSH
- předškolní dítě MeSH
- regulační T-lymfocyty MeSH
- Check Tag
- lidé MeSH
- předškolní dítě MeSH
- Publikační typ
- časopisecké články MeSH
- randomizované kontrolované studie MeSH
PURPOSE: Common variable immunodeficiency (CVID) is the most frequent symptomatic primary immunodeficiency, with heterogeneous clinical presentation. Our goal was to analyze CD8 T cell homeostasis in patients with infection only CVID, compared to those additionally affected by dysregulatory and autoimmune phenomena. METHODS: We used flow and mass cytometry evaluation of peripheral blood of 40 patients with CVID and 17 healthy donors. RESULTS: CD8 T cells are skewed in patients with CVID, with loss of naïve and increase of effector memory stages, expansion of cell clusters with high functional exhaustion scores, and a highly activated population of cells with immunoregulatory features, producing IL-10. These findings correlate to clinically widely used B cell-based EURO classification. Features of exhaustion, including loss of CD127 and CD28, and expression of TIGIT and PD-1 in CD8 T cells are strongly associated with interstitial lung disease and autoimmune cytopenias, whereas CD8 T cell activation with elevated HLA-DR and CD38 expression predict non-infectious diarrhea. CONCLUSION: We demonstrate features of advanced differentiation, exhaustion, activation, and immunoregulatory capabilities within CD8 T cells of CVID patients. Assessment of CD8 T cell phenotype may allow risk assessment of CVID patients and provide new insights into CVID pathogenesis, including a better understanding of mechanisms underlying T cell exhaustion and regulation.
