OBJECTIVE: This study investigates the associations of body mass index (BMI) and waist circumference (WC) with markers of systemic inflammation in midlife by race and gender. DESIGN: Data were obtained from the Survey of Midlife in the United States, a cross-sectional, observational study of Americans 35 years old or older (White men: N = 410; White women: N = 490; Black men: N = 58; Black women: N = 117). Inflammation was measured by concentrations of fibrinogen and C-reactive protein (CRP) in fasting plasma and concentrations of E-selectin and interleukin-6 (IL-6) in fasting serum. Anthropometric data were used to obtain BMI and WC. Socio-demographic and health-related factors were assessed with a survey. Multivariate models by race and gender were estimated to test the roles of BMI and WC for each inflammation marker. RESULTS: Compared to White men, Black women have higher BMI and higher levels of all four inflammation markers; White women have lower BMI, lower WC, and lower E-selectin and fibrinogen but higher CRP; and Black men have higher fibrinogen. After adjusting for socio-demographic and health-related covariates as well as perceived discrimination, WC is associated with all four markers of inflammation among White men and women; with three markers (fibrinogen, CRP, and IL-6) of inflammation among Black women; and with CRP (and marginally with fibrinogen and E-selectin) among Black men. BMI is associated with higher CRP and fibrinogen among Black men (marginally so for White men) but not for women of either race. CONCLUSIONS: WC shows more consistent associations with inflammation markers than BMI, although the relationships vary by inflammation marker and population group. Our findings suggest that WC is a risk factor for systemic inflammation among White and Black men and women, and BMI is an additional risk factor for Black men.

• MeSH
• běloši statistika a číselné údaje   MeSH
• biologické markery MeSH
• C-reaktivní protein biosyntéza   MeSH
• černoši nebo Afroameričané statistika a číselné údaje   MeSH
• dospělí MeSH
• E-selektin biosyntéza   MeSH
• fibrinogen biosyntéza   MeSH
• index tělesné hmotnosti * MeSH
• interleukin-6 biosyntéza   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mediátory zánětu MeSH
• obvod pasu * MeSH
• průřezové studie MeSH
• rizikové faktory MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• sexuální faktory MeSH
• socioekonomické faktory MeSH
• tělesné váhy a míry MeSH
• zánět etnologie   patofyziologie   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
• pozorovací studie MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Geografické názvy
• Spojené státy americké MeSH

The existence of a restrained inflammatory state in schizophrenic individuals posed the question whether anti-inflammatory drugs may exert antipsychotic effects. Therefore, the effect of ibuprofen (IB) on cytokine production by human peripheral blood mononuclear cells (PBMC) from schizophrenic patients was examined and compared to that of healthy subjects. PBMC from 25 schizophrenic patients and 24 healthy volunteers were incubated for 24 h with lipopolysaccharide (LPS) in the absence or presence of various concentrations of IB. The levels of IL-1β, IL-6, TNF-α, IL-10 and IL-1ra in the supernatants were tested applying ELISA kits. The secretion of TNF-α by cells from schizophrenic patients was significantly lower compared with controls. IB caused stimulation of TNF-α and IL-6 production by cells of the two groups and enhanced IL-1β secretion by cells from schizophrenic patients. IB inhibited IL-1ra and IL-10 generation by cells from the two groups. Without IB, IL-1ra secretion was negatively correlated with the disease severity, while 200 μg/ml of IB positively correlated with the PANSS total score. IL-10 production was positively correlated with the PANSS positive subscale score both in the absence or presence of IB. The findings suggest that the effect of IB on the production of inflammatory cytokines may benefit the health of schizophrenic patients.

• MeSH
• antagonista receptoru pro interleukin 1 metabolismus   MeSH
• cytokiny biosyntéza   MeSH
• dospělí MeSH
• ibuprofen farmakologie   MeSH
• interleukin-10 biosyntéza   MeSH
• interleukin-1beta biosyntéza   MeSH
• interleukin-6 biosyntéza   MeSH
• leukocyty mononukleární účinky léků   metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mediátory zánětu metabolismus   MeSH
• mladý dospělý MeSH
• schizofrenie krev   imunologie   MeSH
• TNF-alfa biosyntéza   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

Inflammatory changes, both in the arterial wall and adipose tissue, play a crucial role in the development of atherosclerosis. We measured the gene expression of tumor necrosis factor-alpha (TNFalpha), monocyte chemoattractant protein-1 (MCP-1), and interleukin 6 (IL-6) in adipose tissue (AT) of living kidney donors (LKD) and patients with peripheral arterial disease (PAD). Quantitative polymerase chain reaction (qPCR) and flow cytometry analyses were performed in subcutaneous (SAT), visceral (VAT), and perivascular adipose tissue (PVAT). Data of PAD patients showed significantly higher expression in VAT in all three genes (TNFalpha 5-fold, p<0.05; MCP-1 3.6-fold, p<0.05; IL-6 18.8-fold, p<0.001). The differences in PVAT and SAT were less significant. Total body pro-inflammatory status was documented by higher TNFalpha concentration in patients (4.86+/-1.4 pg/ml) compared to LKDs (2.14+/-0.9 pg/ml; p<0.001), as was hsCRP (11.8+/-7.0 in PAD; 1.5+/-0.48 in LKDs; p=0.017). We found no age-dependent relationship between gene expression vs. TNFalpha and hsCRP concentrations in both compared groups. No effect of the atherosclerosis score on gene expression and circulating inflammatory markers within the PAD group was observed. Our results suggest that the AT of PAD patients infiltrated with macrophages produces more cytokines involved in the development of inflammation and atherosclerosis.

• MeSH
• ateroskleróza genetika   metabolismus   patologie   MeSH
• biologické markery metabolismus   MeSH
• chemokin CCL2 biosyntéza   genetika   MeSH
• dospělí MeSH
• exprese genu MeSH
• interleukin-6 biosyntéza   genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mediátory zánětu metabolismus   MeSH
• TNF-alfa biosyntéza   genetika   MeSH
• tuková tkáň metabolismus   patologie   MeSH
• žijící dárci MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

AIMS: Endoglin is a transmembrane glycoprotein, that plays an important role in regulating endothelium. Proteolytic cleavage of membrane endoglin releases soluble endoglin (sEng), whose increased plasma levels have been detected in diseases related to the cardiovascular system. It was proposed that sEng might damage vascular endothelium, but detailed information about the potential mechanisms involved is not available. Thus, we hypothesized that sEng contributes to endothelial dysfunction, leading to a pro-inflammatory phenotype by a possible modulation of the TGF-β and/or inflammatory pathways. MAIN METHODS: Human umbilical vein endothelial cells (HUVECs) and Human embryonic kidney cell line (HEK293T) were treated with different sEng concentration and time in order to reveal possible effect on biomarkers of inflammation and TGF-β signaling. IL6 and NFκB reporter luciferase assays, quantitative real-time PCR analysis, Western blot analysis and immunofluorescence flow cytometry were used. KEY FINDINGS: sEng treatment results in activation of NF-κB/IL-6 expression, increased expression of membrane endoglin and reduced expression of Id-1. On the other hand, no significant effects on other markers of endothelial dysfunction and inflammation, including eNOS, peNOS(S1177), VCAM-1, COX-1, COX-2 and ICAM-1 were detected. SIGNIFICANCE: As a conclusion, sEng treatment resulted in an activation of NF-κB, IL-6, suggesting activation of pro-inflammatory phenotype in endothelial cells. The precise mechanism of this activation and its consequence remains to be elucidated. A combined treatment of sEng with other cardiovascular risk factors will be necessary in order to reveal whether sEng is not only a biomarker of cardiovascular diseases, but also a protagonist of endothelial dysfunction.

• MeSH
• endoglin biosyntéza   MeSH
• endoteliální buňky pupečníkové žíly (lidské) metabolismus   MeSH
• HEK293 buňky MeSH
• inhibitor diferenciace 1 biosyntéza   MeSH
• interleukin-6 biosyntéza   MeSH
• lidé MeSH
• NF-kappa B biosyntéza   MeSH
• regulace genové exprese * MeSH
• rozpustnost MeSH
• signální transdukce * MeSH
• zánět chemicky indukované   metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

The mode of delivery plays a crucial role in infant gastrointestinal tract colonisation, which in the case of caesarean section is characterised by the presence of clostridia and low bifidobacterial counts. Gut colonisation can be modified by probiotics, prebiotics or synbiotics. Human milk oligosaccharides (HMOs) are infant prebiotics that show a bifidogenic effect. Moreover, genome sequencing of Bifidobacterium longum subsp. infantis within the infant microbiome revealed adaptations for milk utilisation. This study aimed to evaluate the synbiotic effect of B. longum subsp. infantis, HMOs and human milk (HM) both in vitro and in vivo (in a humanised mouse model) in the presence of faecal microbiota from infants born by caesarean section. The combination of B. longum and HMOs or HM reduced the clostridia and G-bacteria counts both in vitro and in vivo. The bifidobacterial population in vitro significantly increased and produce high concentrations of acetate and lactate. In vitro competition assays confirmed that the tested bifidobacterial strain is a potential probiotic for infants and, together with HMOs or HM, acts as a synbiotic. It is also able to inhibit potentially pathogenic bacteria. The synbiotic effects identified in vitro were not observed in vivo. However, there was a significant reduction in clostridia counts in both experimental animal groups (HMOs + B. longum and HM + B. longum), and a specific immune response via increased interleukin (IL)-10 and IL-6 production. Animal models do not perfectly mimic human conditions; however, they are essential for testing the safety of functional foods.

• MeSH
• acetáty metabolismus   MeSH
• Bifidobacterium longum subsp. infantis * MeSH
• císařský řez MeSH
• feces mikrobiologie   MeSH
• gastrointestinální trakt mikrobiologie   MeSH
• interleukin-10 biosyntéza   MeSH
• interleukin-6 biosyntéza   MeSH
• laktáty metabolismus   MeSH
• lidé MeSH
• mateřské mléko chemie   MeSH
• myši MeSH
• novorozenec MeSH
• oligosacharidy aplikace a dávkování   MeSH
• prebiotika aplikace a dávkování   MeSH
• probiotika aplikace a dávkování   MeSH
• střevní mikroflóra účinky léků   MeSH
• synbiotika aplikace a dávkování   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• novorozenec MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Naše studie se zabývá kinetikou akutní zánětlivé reakce (interleukinů a vaskulárního endoteliálního růstového faktoru VEGF) po traumatu mozku ve vztahu k aktivaci mikrogliálních mozkových buněk u pacientů s expanzní kontuzí v rámci sekundárního traumatu mozku. Interleukin IL-6, monocyt chemoatrahující protein (MCP-1) a VEGF mají rozdílný časový nástup u skupin pacientů s rozvojem a bez rozvoje expanzní kontuze mozku (p<0.05). Hodnoty VEGF v krvi byly významně vyšší u pacientů s nekomplikovanou mozkovou kontuzí ve srovnání s nižšími hodnotami u pacientů s expanzní kontuzí mozku. Pacienti s rozvojem sepse měli výrazný vzestup koncentrací TNF alpha a interleukinu IL-8 v průběhu prvních 72 hodin. P-selektin glykoprotein ligand PSGL a CD68 imunopozitivní mikrogliové elementy byly detekovány u obou typů, ložiskových i difuzních poranění mozku, zejména v perivaskulárních prostorech a imunopozitivita korelovala s nálezem telolysosomů v cytoplasmě mikroglie. Pozorovali jsme, že některé polymorfismy genů PAI-1, MTHFR, eNOS, VEGF a Apo E při genetickém vyšetření pacientů s traumatem mozku byly spojené s projevem ucpávání kapilár nahromaděnými leukocyty u případů expanzních kontuzí mozku.

Our present study was aimed to investigate time-profile kinetics of interleukins, vascular endothelial growth factor (VEGF) in acute inflammatory response following traumatic brain injury, and the influence of activated microglial cells in patients who developed severe space occupying lesion (SOL) of secondary traumatic brain injury. Interleukins IL-6, monocyte chemo attractant protein (MCP-1), and VEGF had a significant different time-profile kinetics (p<0.05) in patient with, and without expansive traumatic brain contusions (SOL). The serum VEGF was significantly higher in trauma patients with uncomplicated brain contusions, and lower in patients with SOL. The patients with septic complications developed the sudden increase of TNF alpha and IL-8 within the first 72 hours. Our data suggested PSGL and CD68 immunopositivity of microglial cells in both focal and diffuse TBI, predominantly in perivascular space correlated with telolysosome formation in cytoplasma. Polymorphism of PAI-1, MTHFR, eNOS, VEGF, and Apo E genes in TBI were in patients with SOL were bound to show up leucocyte plugging in capillaries.

• MeSH
• chemokin CCL2 biosyntéza   fyziologie   chemie   MeSH
• imunohistochemie MeSH
• interleukin-6 biosyntéza   fyziologie   chemie   MeSH
• interleukin-8 fyziologie   MeSH
• lidé MeSH
• polymorfismus genetický MeSH
• poranění mozku * genetika   patofyziologie   MeSH
• TNF-alfa biosyntéza   fyziologie   chemie   MeSH
• vaskulární endoteliální růstové faktory biosyntéza   fyziologie   chemie   MeSH
• zánět patofyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH

Complex regulation of the wound healing process involves multiple interactions among stromal tissue cells, inflammatory cells, and the extracellular matrix. Low molecular weight hyaluronan (LMW HA) derived from the degradation of high molecular weight hyaluronan (HMW HA) is suggested to activate cells involved in wound healing through interaction with HA receptors. In particular, receptor CD44 is suggested to mediate cell response to HA of different MW, being the main cell surface HA receptor in stromal tissue and immune cells. However, the response of dermal fibroblasts, the key players in granulation tissue formation within the wound healing process, to LMW HA and their importance for the activation of immune cells is unclear. In this study we show that LMW HA (4.3kDa) induced pro-inflammatory cytokine IL-6 and chemokines IL-8, CXCL1, CXCL2, CXCL6 and CCL8 gene expression in normal human dermal fibroblasts (NHDF) that was further confirmed by increased levels of IL-6 and IL-8 in cell culture supernatants. Conversely, NHDF treated by HMW HA revealed a tendency to decrease the gene expression of these cytokine and chemokines when compared to untreated control. The blockage of CD44 expression by siRNA resulted in the attenuation of IL-6 and chemokines expression in LMW HA treated NHDF suggesting the involvement of CD44 in LMW HA mediated NHDF activation. The importance of pro-inflammatory mediators produced by LMW HA triggered NHDF was evaluated by significant activation of blood leukocytes exhibited as increased production of IL-6 and TNF-α. Conclusively, we demonstrated a pro-inflammatory response of dermal fibroblasts to LMW HA that was transferred to leukocytes indicating the significance of LMW HA in the inflammatory process development during the wound healing process.

• MeSH
• antigeny CD44 metabolismus   MeSH
• chemokiny biosyntéza   genetika   MeSH
• fibroblasty účinky léků   imunologie   MeSH
• interleukin-6 biosyntéza   genetika   metabolismus   MeSH
• interleukin-8 biosyntéza   MeSH
• kyselina hyaluronová farmakologie   MeSH
• leukocyty účinky léků   metabolismus   MeSH
• lidé MeSH
• malá interferující RNA metabolismus   MeSH
• mediátory zánětu metabolismus   MeSH
• messenger RNA genetika   metabolismus   MeSH
• molekulová hmotnost MeSH
• přirozená imunita účinky léků   genetika   MeSH
• signální transdukce účinky léků   genetika   MeSH
• škára cytologie   MeSH
• TNF-alfa biosyntéza   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Deciphering the mechanisms that allow the induction of strong immune responses is crucial to developing efficient vaccines against infectious diseases and cancer. Based on the discovery that the adenylate cyclase from Bordetella pertussis binds to the CD11b/CD18 integrin, we developed a highly efficient detoxified adenylate cyclase-based vector (CyaA) capable of delivering a large variety of Ags to the APC. This vector allows the induction of protective and therapeutic immunity against viral and tumoral challenges as well as against transplanted tumors in the absence of any added adjuvant. Two therapeutic vaccine candidates against human papilloma viruses and melanoma have been developed recently, based on the CyaA vector, and are currently in clinical trials. We took advantage of one of these highly purified vaccines, produced under good manufacturing practice-like conditions, to decipher the mechanisms by which CyaA induces immune responses. In this study, we demonstrate that CyaA binds both human and mouse CD11b(+) dendritic cells (DCs) and induces their maturation, as shown by the upregulation of costimulatory and MHC molecules and the production of proinflammatory cytokines. Importantly, we show that DCs sense CyaA through the TLR4/Toll/IL-1R domain-containing adapter-inducing IFN-β pathway, independent of the presence of LPS. These findings show that CyaA possesses the intrinsic ability to not only target DCs but also to activate them, leading to the induction of strong immune responses. Overall, this study demonstrates that Ag delivery to CD11b(+) DCs in association with TLR4/Toll/IL-1R domain-containing adapter-inducing IFN-β activation is an efficient strategy to promote strong specific CD8(+) T cell responses.

• MeSH
• adaptorové proteiny vezikulární transportní imunologie   MeSH
• adenylátcyklasový toxin imunologie   MeSH
• antigeny CD11b imunologie   MeSH
• antigeny CD80 biosyntéza   MeSH
• antigeny CD86 biosyntéza   MeSH
• Bordetella pertussis imunologie   MeSH
• buněčná diferenciace imunologie   MeSH
• cytotoxické T-lymfocyty imunologie   MeSH
• dendritické buňky cytologie   imunologie   MeSH
• interferon beta imunologie   MeSH
• interleukin-1beta biosyntéza   MeSH
• interleukin-6 biosyntéza   MeSH
• kultivované buňky MeSH
• myši inbrední C57BL MeSH
• myši knockoutované MeSH
• myši MeSH
• receptor interferonu alfa-beta genetika   MeSH
• receptory interleukinu-1 imunologie   MeSH
• signální transdukce imunologie   MeSH
• TNF-alfa biosyntéza   MeSH
• toll-like receptor 4 imunologie   MeSH
• tyrosin genetika   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

HI-6 is used as an antidote to nerve agents. It can also act as an antagonist to acetylcholine receptors (AChRs) including the nicotinic receptor, α 7 nAChR which is involved in regulating the immune response through macrophages. This experiment investigated the efficacy of HI-6 to regulate the immune response. Laboratory BALB/c mice received HI-6 and/or keyhole limpet hemocyanin (KLH) as an antigen. Antibody production was investigated after either 21 or 65 days when either single or repeated dose of antigen was applied. We confirmed that HI-6 significantly improved vaccination efficacy when KLH was given in a dose of 1mg/kg. The effect was dose dependent. A combination of HI-6 and KLH produced a vaccination of almost the same efficacy as that for Freund's complete adjuvant. The findings point at the suitability of HI-6 for improving vaccination efficacy at the level of immunity regulation by the nervous system.

• MeSH
• adjuvancia imunologická farmakologie   MeSH
• antidota farmakologie   MeSH
• ELISA MeSH
• Freundovo adjuvans MeSH
• hemokyanin imunologie   MeSH
• imunita účinky léků   MeSH
• imunizace * MeSH
• interleukin-6 analýza   biosyntéza   MeSH
• myši inbrední BALB C MeSH
• myši MeSH
• oximy farmakologie   MeSH
• protilátky analýza   MeSH
• pyridinové sloučeniny farmakologie   MeSH
• rovnováha Th1-Th2 účinky léků   MeSH
• tvorba protilátek účinky léků   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: Current research implicates interleukin (IL)-6 as a key component of the nervous-system response to injury with various effects. METHODS: We used unilateral chronic constriction injury (CCI) of rat sciatic nerve as a model for neuropathic pain. Immunofluorescence, ELISA, western blotting and in situ hybridization were used to investigate bilateral changes in IL-6 protein and mRNA in both lumbar (L4-L5) and cervical (C7-C8) dorsal root ganglia (DRG) following CCI. The operated (CCI) and sham-operated (sham) rats were assessed after 1, 3, 7, and 14 days. Withdrawal thresholds for mechanical hyperalgesia and latencies for thermal hyperalgesia were measured in both ipsilateral and contralateral hind and fore paws. RESULTS: The ipsilateral hind paws of all CCI rats displayed a decreased threshold of mechanical hyperalgesia and withdrawal latency of thermal hyperalgesia, while the contralateral hind and fore paws of both sides exhibited no significant changes in mechanical or thermal sensitivity. No significant behavioral changes were found in the hind and fore paws on either side of the sham rats, except for thermal hypersensitivity, which was present bilaterally at 3 days. Unilateral CCI of the sciatic nerve induced a bilateral increase in IL-6 immunostaining in the neuronal bodies and satellite glial cells (SGC) surrounding neurons of both lumbar and cervical DRG, compared with those of naive control rats. This bilateral increase in IL-6 protein levels was confirmed by ELISA and western blotting. More intense staining for IL-6 mRNA was detected in lumbar and cervical DRG from both sides of rats following CCI. The DRG removed from sham rats displayed a similar pattern of staining for IL-6 protein and mRNA as found in naive DRG, but there was a higher staining intensity in SGC. CONCLUSIONS: Bilateral elevation of IL-6 protein and mRNA is not limited to DRG homonymous to the injured nerve, but also extended to DRG that are heteronymous to the injured nerve. The results for IL-6 suggest that the neuroinflammatory reaction of DRG to nerve injury is propagated alongside the neuroaxis from the lumbar to the remote cervical segments. This is probably related to conditioning of cervical DRG neurons to injury.

• MeSH
• ELISA MeSH
• funkční lateralita fyziologie   MeSH
• fyzikální stimulace MeSH
• hybridizace in situ MeSH
• hyperalgezie metabolismus   MeSH
• imunohistochemie MeSH
• interleukin-6 biosyntéza   genetika   MeSH
• krční obratle MeSH
• krysa rodu rattus MeSH
• lumbosakrální krajina MeSH
• měření bolesti MeSH
• messenger RNA biosyntéza   genetika   MeSH
• nemoci sedacího nervu metabolismus   MeSH
• neuralgie metabolismus   MeSH
• počítačové zpracování obrazu MeSH
• potkani Wistar MeSH
• receptory interleukinu-6 biosyntéza   genetika   MeSH
• spinální ganglia metabolismus   MeSH
• stenóza MeSH
• úžinové syndromy metabolismus   MeSH
• vysoká teplota diagnostické užití   MeSH
• western blotting MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH