BACKGROUND: Idiopathic bleeding in the second trimester of pregnancy complicates <1% of all pregnancies. This pregnancy complication can be caused by alterations in local hemostasis in the decidua due to infection/inflammation in the choriodecidual niche. This condition is associated with intraamniotic inflammatory complications. Antibiotic therapy effectively reduces the intensity of intraamniotic inflammation in certain pregnancy pathologies. However, whether antibiotic administration can reduce the intensity of the intraamniotic inflammatory response or eradicate microorganisms in patients with idiopathic bleeding during the second trimester of pregnancy remains unclear. OBJECTIVE: This study primarily aimed to determine whether antimicrobial agents can reduce the magnitude of intraamniotic inflammation in patients with idiopathic bleeding in the second trimester of pregnancy by assessing the concentration of interleukin-6 in the amniotic fluid before and after 7 days of antibiotic treatment. The secondary aim was to determine whether treatment with a combination of antibiotics altered the microbial load of Ureaplasma species DNA in amniotic fluid. STUDY DESIGN: This retrospective cohort study included singleton-gestation patients with idiopathic bleeding between 15+0 and 27+6 weeks who underwent transabdominal amniocentesis at the time of admission. Follow-up amniocentesis was performed in a subset of patients unless abortion or delivery occurred earlier. Concentrations of interleukin-6 were measured in the amniotic fluid samples, and the presence of microbial invasion of the amniotic cavity was assessed using culture and molecular microbiological methods. Intraamniotic inflammation was defined as an interleukin-6 concentration ≥3000 pg/mL in the amniotic fluid samples. RESULTS: A total of 36 patients with idiopathic bleeding in the second trimester of pregnancy were included. All the patients underwent initial amniocentesis. Patients with intraamniotic inflammation (n=25) were treated using a combination of antibiotics consisting of intravenous ceftriaxone, intravenous metronidazole, and peroral clarithromycin. The patients without intraamniotic inflammation (n=11) were treated expectantly. In total, 25 patients delivered 7 days after admission. All patients with intraamniotic inflammation at the initial amniocentesis who delivered after 7 days underwent follow-up amniocentesis. Treatment with antibiotics decreased the interleukin-6 concentration in the amniotic fluid at follow-up amniocentesis compared with that at the initial amniocentesis in patients with intraamniotic inflammation (median [interquartile range]: 3457 pg/mL [2493-13,203] vs 19,812 pg/mL [11,973-34,518]; P=.0001). Amniotic fluid samples with Ureaplasma species DNA had a lower microbial load at the time of follow-up amniocentesis compared with the initial amniocentesis (median [interquartile range]: 1.5×105 copies DNA/mL [1.3×105-1.7×105] vs 8.0×107 copies DNA/mL [6.7×106-1.6×108]; P=.02). CONCLUSION: Antibiotic therapy was associated with reduced intraamniotic inflammation in patients with idiopathic bleeding in the second trimester complicated by intraamniotic inflammation. Moreover, antibiotic treatment has been associated with a reduction in the microbial load of Ureaplasma species DNA in the amniotic fluid.
- MeSH
- amniocentéza škodlivé účinky MeSH
- antibakteriální látky terapeutické užití MeSH
- chorioamnionitida * mikrobiologie MeSH
- děložní krvácení MeSH
- DNA MeSH
- druhý trimestr těhotenství MeSH
- interleukin-6 MeSH
- lidé MeSH
- plodová voda mikrobiologie MeSH
- předčasný odtok plodové vody * farmakoterapie MeSH
- retrospektivní studie MeSH
- těhotenství MeSH
- Ureaplasma MeSH
- zánět komplikace MeSH
- Check Tag
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
OBJECTIVE: The aim of this study was to: (1) evaluate the anti-inflammatory effects of cannabidiol (CBD) on primary cultures of human gingival fibroblasts (HGFs) and (2) to clinically monitor the effect of CBD in subjects with periodontitis. BACKGROUND: The use of phytocannabinoids is a new approach in the treatment of widely prevalent periodontal disease. MATERIALS AND METHODS: Cannabinoid receptors were analyzed by western blot and interleukin production detected using enzyme immunoassay. Activation of the Nrf2 pathway was studied via monitoring the mRNA level of heme oxygenase-1. Antimicrobial effects were determined by standard microdilution and 16S rRNA screening. In the clinical part, a placebo-control double-blind randomized study was conducted (56 days) in three groups (n = 90) using dental gel without CBD (group A) and with 1% (w/w) CBD (group B) and corresponding toothpaste (group A - no CBD, group B - with CBD) for home use to maintain oral health. Group C used dental gel containing 1% chlorhexidine digluconate (active comparator) and toothpaste without CBD. RESULTS: Human gingival fibroblasts were confirmed to express the cannabinoid receptor CB2. Lipopolysaccharide-induced cells exhibited increased production of pro-inflammatory IL-6 and IL-8, with deceasing levels upon exposure to CBD. CBD also exhibited antimicrobial activities against Porphyromonas gingivalis, with an MIC of 1.5 μg/mL. Activation of the Nrf2 pathway was also demonstrated. In the clinical part, statistically significant improvement was found for the gingival, gingival bleeding, and modified gingival indices between placebo group A and CBD group B after 56 days. CONCLUSIONS: Cannabidiol reduced inflammation and the growth of selected periodontal pathogenic bacteria. The clinical trial demonstrated a statistically significant improvement after CBD application. No adverse effects of CBD were reported by patients or observed upon clinical examination during the study. The results are a promising basis for a more comprehensive investigation of the application of non-psychotropic cannabinoids in dentistry.
- MeSH
- antiflogistika terapeutické užití farmakologie MeSH
- chlorhexidin terapeutické užití farmakologie analogy a deriváty MeSH
- dospělí MeSH
- dvojitá slepá metoda MeSH
- faktor 2 související s NF-E2 MeSH
- fibroblasty * účinky léků MeSH
- gingiva * účinky léků MeSH
- gingivitida * farmakoterapie MeSH
- hemoxygenasa-1 MeSH
- interleukin-6 analýza MeSH
- interleukin-8 účinky léků MeSH
- kanabidiol * farmakologie terapeutické užití MeSH
- kultivované buňky MeSH
- lidé středního věku MeSH
- lidé MeSH
- parodontitida farmakoterapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- randomizované kontrolované studie MeSH
BACKGROUND: The aim of this prospective study was to evaluate the role of serum IL-6 as a potential predictive biomarker of postoperative complications (POC) in elective colorectal surgery. METHOD: A total of 115 patients underwent colorectal surgery for malignancy. IL-6 was measured on the first and third postoperative days (POD1, POD3), and C-reactive protein (CRP) was measured on the POD3. POC was analysed in subgroups according to Clavien‒Dindo (CD), antibiotic (ATB) treatment, intensive care unit (ICU) and hospital length of stay. The predictive power of variables for evaluated endpoints was analysed using receiver-operating characteristic (ROC) analysis and described by area under the curve (AUC). ROC analysis was adopted for the identification of optimal cut-offs. Histological analysis was performed to verify IL-6 production by the tumour. RESULTS: Out of 115 patients who were analysed, 42% had POC. Patients with POC had significantly higher serum levels of IL-6 on POD1 (p < 0.001) and POD3 (p < 0.001). IL-6 early on POD1 as a predictor of antibiotic treatment, ICU stay and hospital stay (AUC 0.818; 0.811; 0.771) did not significantly differ from the AUC of CRP late on POD3 (0.879; 0.838, 0.752). A cut-off IL-6 value of 113 pg/ml on POD1 and 180.5 pg/ml on POD3 in severe complications (CD > 3a) resulted in 75% and 72% sensitivity, 78.6% and 99% specificity, negative predictive value 96.4% and 97% and positive predictive value 29% and 88.9%. CONCLUSION: The serum level of interleukin-6 can predict severe (CD > 3a) POC early on POD1. On POD3, IL-6 is superior to CRP in terms of high positive predictive power of severe POC. Interestingly, the advantage of IL-6 on POD1 is early prediction of the need for antibiotic treatment, ICU stay and hospital stay, which is comparable to the CRP serum level late on the third POD.
BACKGROUND: Chronic venous disease (CVD) is a common disorder of lower extremities. OBJECTIVES: The study was scheduled to investigate the relationship between polymorphisms in major proinflammatory genes TNF α (-238 A/G; -308 A/G), TNF β (NcoI), IL-1β (+3953 T/C); IL-6 (-174 G/C; -596 G/C) and ADAM17 (3'TACE) and CVD risk. Genotype-phenotype study was calculated to test possible association between examined genotypes and phenotypes of CVD. METHODS: Finally, 150 CVD patients and 227 control subjects were enrolled to the study. Genotypes in proinflammatory gene polymorphisms were identified from isolated DNA by PCR method and restriction analysis. RESULTS: Significant differences in genotype distribution/allelic frequencies in TNF β gene, IL-1 β gene and in ADAM17 gene polymorphisms were found between CVD women and control ones. In the genotype-phenotype study, identified genotypes were associated with arterial hypertension (ADAM17, IL-6-men), ischaemic heart disease (TNF α and β genes), diabetes mellitus (ADAM17-women, TNF β-men), age of CVD onset (TNF α and IL-6), ulceration (ADAM17), duration of ulceration (ADAM17), ulceration recurrence (ADAM17-women), home care necessity (TNF α), varices surgery (TNF α), erysipelas development (ADAM17-men) and tumour development (TNF α). CONCLUSION: Studying of these polymorphisms associations can help us better identify patients at higher risk of developing severe CVD.
- MeSH
- chronická nemoc MeSH
- frekvence genu MeSH
- genetická predispozice k nemoci MeSH
- genotyp MeSH
- interleukin-1beta genetika MeSH
- interleukin-6 genetika MeSH
- jednonukleotidový polymorfismus MeSH
- kardiovaskulární nemoci * genetika MeSH
- lidé MeSH
- lymfotoxin-alfa genetika MeSH
- protein ADAM17 genetika MeSH
- TNF-alfa * genetika MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Úvod: Cílem této studie bylo porovnat hodnoty interleukinu-6 v pupečníkové a periferní krvi novorozence. Klinickým cílem bylo zjistit, zda lze vyšetřením krve z pupečníku nahradit brzký postnatální odběr periferní krve. Pacienti a metody: Do studie byli zahrnuti novorozenci (< 35. týden gestace) narození v roce 2016–2018 ve Fakultní nemocnici Olomouc. U těchto novorozenců se zároveň podařilo odebrat dostatečné množství krve z pupečníku. Výsledky: Párový odběr se zdařil u 73 novorozenců. Mezi pupečníkovou a periferní hodnotou interleukinu-6 byl zjištěn významný rozdíl (p < 0,001). Medián prvního měření (pupečníková krev) byl 6,5 ng/l, medián druhého měření (periferní krev) 56 ng/l. Nárůst je téměř desetinásobný. Závěr: Hodnoty interleukinu-6 z pupečníkové krve a z časného postnatálního odběru se podstatně liší. Na tuto skutečnost je nutné myslet při jeho klinickém využití.
Introduction: The aim of this study was to compare interleukin-6 values in umbilical cord and peripheral blood of newborns. The clinical goal was to determine whether the examination of cord blood can replace early postnatal peripheral blood collection. Patients and methods: Study included premature newborns (< 35th week of gestation) born in 2016-2018 at Olomouc University Hospital. At the same time, it was possible to collect a sufficient amount of blood from the umbilical cord in these newborns. Results: Paired sampling was successful in 73 of these newborns. A significant difference (p < 0,001) was found between the umbilical cord and peripheral interleukin-6 values. The median of the first measurement (cord blood) was 6,5 ng/l, the median of the second measurement (peripheral blood) was 56 ng/l. The increase is almost ten times bigger. Conclusion: The difference of values between interleukin-6 from umbilical cord blood and from early postnatal collection are significantly different and it is necessary to keep it in mind during its clinical use.
- MeSH
- fetální krev imunologie MeSH
- interleukin-6 * analýza izolace a purifikace krev MeSH
- krev imunologie MeSH
- lidé MeSH
- novorozenec nedonošený imunologie krev MeSH
- novorozenec MeSH
- novorozenecká sepse diagnóza etiologie imunologie prevence a kontrola MeSH
- prospektivní studie MeSH
- pupečník imunologie krevní zásobení MeSH
- Check Tag
- lidé MeSH
- novorozenec MeSH
- Publikační typ
- práce podpořená grantem MeSH
Chronic inflammation represents a major threat to human health since long-term systemic inflammation is known to affect distinct tissues and organs. Recently, solid evidence demonstrated that chronic inflammation affects hematopoiesis; however, how chronic inflammation affects hematopoietic stem cells (HSCs) on the mechanistic level is poorly understood. Here, we employ a mouse model of chronic multifocal osteomyelitis (CMO) to assess the effects of a spontaneously developed inflammatory condition on HSCs. We demonstrate that hematopoietic and nonhematopoietic compartments in CMO BM contribute to HSC expansion and impair their function. Remarkably, our results suggest that the typical features of murine multifocal osteomyelitis and the HSC phenotype are mechanistically decoupled. We show that the CMO environment imprints a myeloid gene signature and imposes a pro-inflammatory profile on HSCs. We identify IL-6 and the Jak/Stat3 signaling pathway as critical mediators. However, while IL-6 and Stat3 blockage reduce HSC numbers in CMO mice, only inhibition of Stat3 activity significantly rescues their fitness. Our data emphasize the detrimental effects of chronic inflammation on stem cell function, opening new venues for treatment.
- MeSH
- hematopoetické kmenové buňky metabolismus MeSH
- hematopoéza MeSH
- interleukin-6 * genetika metabolismus MeSH
- lidé MeSH
- myši MeSH
- signální transdukce MeSH
- transkripční faktor STAT3 genetika metabolismus MeSH
- zánět * metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
AIMS: The effect of polyphenolic fraction of Lonicera caerulea (PFLC) and alkaloid fraction of Macleaya cordata (AFMC) mix on the production of inflammatory mediators in human gingival fibroblasts pretreated with lipopolysaccharide (LPS) was investigated. In addition, protective effects of mucoadhesive paste containing combination of PFLC and AFMC (0.05% and 0.01%, respectively; n=15, Group A) and placebo (n=15, Group B) were evaluated in patients after surgical extraction of lower third molars. METHODS: Gingival fibroblasts were pre-treated with LPS (10 μg/mL; 24 h) and PFLC/AFMC (25/0.25; 50/0.25; 100/0.25; 25/0.5; 50/0.5; 100/0.5 μg/mL) in serum-free medium was applied for 4 h. Then the interleukin-6 (IL-6), reactive oxygen species (ROS) generation, level of intracellular glutathione (GSH) and expression of cyclooxygenase-2 (COX-2) were evaluated. The study was a 6-day, single-center, randomized, double-blind and placebo-controlled trial consisting of two parallel treatment arms. A modified Oral health impact profile questionnaire including both general oral condition and extraction related questions, was used to evaluate the oral condition and other changes before (day 0) and on the days 1, 3 and 6 after surgical extraction. RESULTS AND CONCLUSION: The combination of PFLC with AFMC caused a reduction of ROS generation, reduced IL-6 production and suppressed the expression of COX-2. In group A the paste treatment contributed to improvement of oral health-related quality of life. Topical application of PFLC and AFMC into the extraction wound improved post-extraction site wound healing probably by antioxidant and anti-inflammatory mechanisms.
- MeSH
- alkaloidy * farmakologie MeSH
- cyklooxygenasa 2 farmakologie MeSH
- fenoly farmakologie MeSH
- fibroblasty metabolismus MeSH
- hojení ran MeSH
- interleukin-6 MeSH
- kvalita života MeSH
- lidé MeSH
- lipopolysacharidy farmakologie MeSH
- molár třetí * chirurgie metabolismus MeSH
- reaktivní formy kyslíku metabolismus farmakologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- randomizované kontrolované studie MeSH
The aim of this retrospective study was to evaluate the reliability of peak interleukin-6 (IL-6) level within 24 hours after delivery as a predictor for early-onset sepsis (EOS) in very preterm neonates. Interleukin-6 was assessed at 2 hours and at 12 to 24 hours after delivery. The highest level was considered a peak value. The definition of EOS was based on positive blood culture and clinical signs of infection or negative blood culture, clinical signs of infection, and C-reactive protein >10 mg/L. Among 445 enrolled infants, 53 developed EOS. A peak IL-6 level of more than 200 ng/L had a sensitivity of 89% and specificity of 77% for the presence of EOS. The negative predictive value was 98%. Receiver operating characteristics curve had area under the curve of 0.92. Peak IL-6 is a reliable marker of systemic inflammatory response and might be useful to exclude EOS within the first 24 hours.
- MeSH
- biologické markery MeSH
- C-reaktivní protein analýza MeSH
- interleukin-6 MeSH
- lidé MeSH
- nemoci nedonošenců * MeSH
- novorozenec nedonošený MeSH
- novorozenec MeSH
- novorozenecká sepse * diagnóza MeSH
- reprodukovatelnost výsledků MeSH
- retrospektivní studie MeSH
- sepse * diagnóza MeSH
- Check Tag
- lidé MeSH
- novorozenec MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Klíčová slova
- siltuximab,
- MeSH
- chemokin CXCL13 analýza MeSH
- hormony kůry nadledvin terapeutické užití MeSH
- hyperplazie velkých lymfatických uzlin * diagnóza farmakoterapie klasifikace MeSH
- interleukin-6 analýza antagonisté a inhibitory škodlivé účinky MeSH
- klinická studie jako téma MeSH
- kongresy jako téma MeSH
- léková rezistence MeSH
- lidé MeSH
- management nemoci MeSH
- monoklonální protilátky aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- multiorgánové selhání etiologie MeSH
- protinádorové látky imunologicky aktivní terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- novinové články MeSH
BACKGROUND: Targeting interleukin (IL)-6 has become a major therapeutic strategy in the treatment of immune-mediated inflammatory disease. Interference with the IL-6 pathway can be directed at the specific receptor using anti-IL-6Rα antibodies or by directly inhibiting the IL-6 cytokine. This paper is an update of a previous consensus document, based on most recent evidence and expert opinion, that aims to inform on the medical use of interfering with the IL-6 pathway. METHODS: A systematic literature research was performed that focused on IL-6-pathway inhibitors in inflammatory diseases. Evidence was put in context by a large group of international experts and patients in a subsequent consensus process. All were involved in formulating the consensus statements, and in the preparation of this document. RESULTS: The consensus process covered relevant aspects of dosing and populations for different indications of IL-6 pathway inhibitors that are approved across the world, including rheumatoid arthritis, polyarticular-course and systemic juvenile idiopathic arthritis, giant cell arteritis, Takayasu arteritis, adult-onset Still's disease, Castleman's disease, chimeric antigen receptor-T-cell-induced cytokine release syndrome, neuromyelitis optica spectrum disorder and severe COVID-19. Also addressed were other clinical aspects of the use of IL-6 pathway inhibitors, including pretreatment screening, safety, contraindications and monitoring. CONCLUSIONS: The document provides a comprehensive consensus on the use of IL-6 inhibition to treat inflammatory disorders to inform healthcare professionals (including researchers), patients, administrators and payers.
- MeSH
- COVID-19 MeSH
- dospělí MeSH
- interleukin-6 MeSH
- lidé MeSH
- receptory interleukinu-6 * antagonisté a inhibitory MeSH
- revmatoidní artritida farmakoterapie MeSH
- Stillova nemoc dospělých farmakoterapie MeSH
- zánět * farmakoterapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- konsensus - konference MeSH
- práce podpořená grantem MeSH
