Plasma cytokine profile in tropical endomyocardial fibrosis: predominance of TNF-a, IL-4 and IL-10.

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Aline S Bossa

Full Text Available BACKGROUND: The participation of immune/inflammatory mechanisms in the pathogenesis of tropical endomyocardial fibrosis (EMF has been suggested by the finding of early blood and myocardial eosinophilia. However, the inflammatory activation status of late-stage EMF patients is still unknown. METHODOLOGY/PRINCIPAL FINDINGS: We evaluated pro- and anti-inflammatory cytokine levels in plasma samples from late stage EMF patients. Cytokine levels of Tumor Necrosis Factor (TNF-α, Interferon (IFN-γ, Interleukin (IL-2, IL-4, IL-6, and IL-10 were assayed in plasma samples from 27 EMF patients and compared with those of healthy control subjects. All EMF patients displayed detectable plasma levels of at least one of the cytokines tested. We found that TNF-α, IL-6, IL-4, and IL-10 were each detected in at least 74% of tested sera, and plasma levels of IL-10, IL-4, and TNF-α were significantly higher than those of controls. Plasma levels of such cytokines positively correlated with each other. CONCLUSIONS/SIGNIFICANCE: The mixed pro- and anti-inflammatory/Th2circulating cytokine profile in EMF is consistent with the presence of a persistent inflammatory stimulus. On the other hand, the detection of increased levels of TNF-α may be secondary to the cardiovascular involvement observed in these patients, whereas IL-4 and IL-10 may have been upregulated as a homeostatic mechanism to buffer both production and deleterious cardiovascular effects of pro-inflammatory cytokines. Further studies might establish whether these findings play a role in disease pathogenesis.

Increasing Maternal Body Mass Index Is Associated with Systemic Inflammation in the Mother and the Activation of Distinct Placental Inflammatory Pathways1

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Aye, Irving L.M.H.; Lager, Susanne; Ramirez, Vanessa I.; Gaccioli, Francesca; Dudley, Donald J.; Jansson, Thomas; Powell, Theresa L.

2014-01-01

ABSTRACT Obese pregnant women have increased levels of proinflammatory cytokines in maternal circulation and placental tissues. However, the pathways contributing to placental inflammation in obesity are largely unknown. We tested the hypothesis that maternal body mass index (BMI) was associated with elevated proinflammatory cytokines in maternal and fetal circulations and increased activation of placental inflammatory pathways. A total of 60 women of varying pre-/early pregnancy BMI, undergoing delivery by Cesarean section at term, were studied. Maternal and fetal (cord) plasma were collected for analysis of insulin, leptin, IL-1beta, IL-6, IL-8, monocyte chemoattractant protein (MCP) 1, and TNFalpha by multiplex ELISA. Activation of the inflammatory pathways in the placenta was investigated by measuring the phosphorylated and total protein expression of p38-mitogen-activated protein kinase (MAPK), c-Jun-N-terminal kinase (JNK)-MAPK, signal transducer-activated transcription factor (STAT) 3, caspase-1, IL-1beta, IkappaB-alpha protein, and p65 DNA-binding activity. To determine the link between activated placental inflammatory pathways and elevated maternal cytokines, cultured primary human trophoblast (PHT) cells were treated with physiological concentrations of insulin, MCP-1, and TNFalpha, and inflammatory signaling analyzed by Western blot. Maternal BMI was positively correlated with maternal insulin, leptin, MCP-1, and TNFalpha, whereas only fetal leptin was increased with BMI. Placental phosphorylation of p38-MAPK and STAT3, and the expression of IL-1beta protein, were increased with maternal BMI; phosphorylation of p38-MAPK was also correlated with birth weight. In contrast, placental NFkappaB, JNK and caspase-1 signaling, and fetal cytokine levels were unaffected by maternal BMI. In PHT cells, p38-MAPK was activated by MCP-1 and TNFalpha, whereas STAT3 phosphorylation was increased following TNFalpha treatment. Maternal BMI is associated with elevated

Relationships Among Obesity, Type 2 Diabetes, and Plasma Cytokines in African American Women.

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Denis, Gerald V; Sebastiani, Paola; Andrieu, Guillaume; Tran, Anna H; Strissel, Katherine J; Lombardi, Frank L; Palmer, Julie R

2017-11-01

The principal objective of this investigation was to identify novel cytokine associations with BMI and type 2 diabetes (T2D). Cytokines were profiled from African American women with obesity who donated plasma to the Komen Tissue Bank. Multiplex bead arrays of analytes were used to quantify 88 cytokines and chemokines in association with clinical diagnoses of metabolic health. Regression models were generated after elimination of outliers. Among women with obesity, T2D was associated with breast adipocyte hypertrophy and with six plasma analytes, including four chemokines (chemokine [C-C motif] ligand 2, chemokine [C-C motif] ligand 16, chemokine [C-X-C motif] ligand 1, and chemokine [C-X-C motif] ligand 16) and two growth factors (interleukin 2 and epidermal growth factor). In addition, three analytes were associated with obesity independently of diabetes: interleukin 4, soluble CD40 ligand, and chemokine (C-C motif) ligand 3. Profiling of inflammatory cytokines combined with measures of BMI may produce a more personalized risk assessment for obesity-associated disease in African American women. © 2017 The Obesity Society.

The impact of maternal HIV infection on cord blood lymphocyte subsets and cytokine profile in exposed non-infected newborns

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Reis-Alves Suiellen C

2011-02-01

Full Text Available Abstract Background Children born to HIV+ mothers are exposed intra-utero to several drugs and cytokines that can modify the developing immune system, and influence the newborn's immune response to infections and vaccines. We analyzed the relation between the distribution of cord blood lymphocyte subsets and cytokine profile in term newborns of HIV+ mothers using HAART during pregnancy and compared them to normal newborns. Methods In a prospective, controlled study, 36 mother-child pairs from HIV+ mothers and 15 HIV-uninfected mothers were studied. Hematological features and cytokine profiles of mothers at 35 weeks of pregnancy were examined. Maternal and cord lymphocyte subsets as well as B-cell maturation in cord blood were analyzed by flow cytometry. The non-stimulated, as well as BCG- and PHA-stimulated production of IL2, IL4, IL7, IL10, IL12, IFN-γ and TNF-alpha in mononuclear cell cultures from mothers and infants were quantified using ELISA. Results After one year follow-up none of the exposed infants became seropositive for HIV. An increase in B lymphocytes, especially the CD19/CD5+ ones, was observed in cord blood of HIV-exposed newborns. Children of HIV+ hard drug using mothers had also an increase of immature B-cells. Cord blood mononuclear cells of HIV-exposed newborns produced less IL-4 and IL-7 and more IL-10 and IFN-γ in culture than those of uninfected mothers. Cytokine values in supernatants were similar in infants and their mothers except for IFN-γ and TNF-alpha that were higher in HIV+ mothers, especially in drug abusing ones. Cord blood CD19/CD5+ lymphocytes showed a positive correlation with cord IL-7 and IL-10. A higher maternal age and smoking was associated with a decrease of cord blood CD4+ cells. Conclusions in uninfected infants born to HIV+ women, several immunological abnormalities were found, related to the residual maternal immune changes induced by the HIV infection and those associated with antiretroviral

Cerebrospinal fluid and plasma cytokines after subarachnoid haemorrhage: CSF interleukin-6 may be an early marker of infection

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Hopkins Stephen J

2012-11-01

Full Text Available Abstract Background Cytokines and cytokine receptor concentrations increase in plasma and cerebrospinal fluid (CSF of patients following subarachnoid haemorrhage (SAH. The relationship between plasma and CSF cytokines, and factors affecting this, are not clear. Methods To help define the relationship, paired plasma and cerebrospinal fluid (CSF samples were collected from patients subject to ventriculostomy. Concentrations of key inflammatory cytokines, interleukin (IL-1ß, IL-1 receptor antagonist (IL-1Ra, IL-1 receptor 2, IL-6, IL-8, IL-10, tumour necrosis factor (TNF-α, and TNF receptors (TNF-R 1 and 2 were determined by immunoassay of CSF and plasma from 21 patients, where samples were available at three or more time points. Results Plasma concentrations of IL-1ß, IL-1Ra, IL-10, TNF-α and TNF-R1 were similar to those in CSF. Plasma TNF-R2 and IL-1R2 concentrations were higher than in CSF. Concentrations of IL-8 and IL-6 in CSF were approximately10 to 1,000-fold higher than in plasma. There was a weak correlation between CSF and plasma IL-8 concentrations (r = 0.26, but no correlation for IL-6. Differences between the central and peripheral pattern of IL-6 were associated with episodes of ventriculostomy-related infection (VRI. A VRI was associated with CSF IL-6 >10,000 pg/mL (P = 0.0002, although peripheral infection was not significantly associated with plasma IL-6. Conclusions These data suggest that plasma cytokine concentrations cannot be used to identify relative changes in the CSF, but that measurement of CSF IL-6 could provide a useful marker of VRI.

Progesterone promotes maternal–fetal tolerance by reducing human maternal T‐cell polyfunctionality and inducing a specific cytokine profile

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Eldershaw, Suzy A.; Inman, Charlotte F.; Coomarasamy, Aravinthan; Moss, Paul A. H.; Kilby, Mark D.

2015-01-01

Progesterone is a steroid hormone essential for the maintenance of human pregnancy, and its actions are thought to include promoting maternal immune tolerance of the semiallogenic fetus. We report that exposure of maternal T cells to progesterone at physiological doses induced a unique skewing of the cytokine production profile of CD4+ and CD8+ T cells, with reductions not only in potentially deleterious IFN‐γ and TNF‐α production but also in IL‐10 and IL‐5. Conversely, production of IL‐4 was increased. Maternal T cells also became less polyfunctional, focussing cytokine production toward profiles including IL‐4. This was accompanied by reduced T‐cell proliferation. Using fetal and viral antigen‐specific CD8+ T‐cell clones, we confirmed that this as a direct, nonantigen‐specific effect. Yet human T cells lacked conventional nuclear progesterone receptors, implicating a membrane progesterone receptor. CD4+ and CD8+ T cells responded to progesterone in a dose‐dependent manner, with subtle effects at concentrations comparable to those in maternal blood, but profound effects at concentrations similar to those at the maternal–fetal interface. This characterization of how progesterone modulates T‐cell function is important in understanding the normal biology of pregnancy and informing the rational use of progesterone therapy in pregnancies at risk of fetal loss. PMID:26249148

Increasing maternal body mass index is associated with systemic inflammation in the mother and the activation of distinct placental inflammatory pathways.

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Aye, Irving L M H; Lager, Susanne; Ramirez, Vanessa I; Gaccioli, Francesca; Dudley, Donald J; Jansson, Thomas; Powell, Theresa L

2014-06-01

Obese pregnant women have increased levels of proinflammatory cytokines in maternal circulation and placental tissues. However, the pathways contributing to placental inflammation in obesity are largely unknown. We tested the hypothesis that maternal body mass index (BMI) was associated with elevated proinflammatory cytokines in maternal and fetal circulations and increased activation of placental inflammatory pathways. A total of 60 women of varying pre-/early pregnancy BMI, undergoing delivery by Cesarean section at term, were studied. Maternal and fetal (cord) plasma were collected for analysis of insulin, leptin, IL-1beta, IL-6, IL-8, monocyte chemoattractant protein (MCP) 1, and TNFalpha by multiplex ELISA. Activation of the inflammatory pathways in the placenta was investigated by measuring the phosphorylated and total protein expression of p38-mitogen-activated protein kinase (MAPK), c-Jun-N-terminal kinase (JNK)-MAPK, signal transducer-activated transcription factor (STAT) 3, caspase-1, IL-1beta, IkappaB-alpha protein, and p65 DNA-binding activity. To determine the link between activated placental inflammatory pathways and elevated maternal cytokines, cultured primary human trophoblast (PHT) cells were treated with physiological concentrations of insulin, MCP-1, and TNFalpha, and inflammatory signaling analyzed by Western blot. Maternal BMI was positively correlated with maternal insulin, leptin, MCP-1, and TNFalpha, whereas only fetal leptin was increased with BMI. Placental phosphorylation of p38-MAPK and STAT3, and the expression of IL-1beta protein, were increased with maternal BMI; phosphorylation of p38-MAPK was also correlated with birth weight. In contrast, placental NFkappaB, JNK and caspase-1 signaling, and fetal cytokine levels were unaffected by maternal BMI. In PHT cells, p38-MAPK was activated by MCP-1 and TNFalpha, whereas STAT3 phosphorylation was increased following TNFalpha treatment. Maternal BMI is associated with elevated maternal

Creatinine and cytokines plasma levels related to HLA compatibility in kidney transplant patients

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Lorraine V. Alves

2015-10-01

Full Text Available ABSTRACTIntroduction:The success of kidney transplantation depends on prevention of organ rejection by the recipient’s immune system, which recognizes alloantigens present in transplanted tissue. Human leukocyte antigen (HLA typing is one of the tests used in pre-renal transplantation and represents one of the most important factors for a successful procedure.Objective:The present study evaluated creatinine and cytokines plasma levels in kidney transplant patients according to pre-transplant HLA typing.Methods:We assessed 40 renal transplanted patients selected in two transplant centers in Belo Horizonte (MG.Results:Patients were distributed into three groups according to HLA compatibility and, through statistical analysis, the group with more than three matches (H3 was found to have significantly lower post-transplant creatinine levels, compared to groups with three or fewer matches (H2 and H1, respectively. The median plasma levels of cytokines interleukin 6 (IL-6, tumor necrosis factor alpha (TNF-α, and interleukin 10 (IL-10 were evaluated according to the number of matches. Pro-inflammatory cytokines (IL-6 and TNF-α were significantly higher in groups with lower HLA compatibility. On the other hand, the regulatory cytokine IL-10 had significantly higher plasma levels in the group with greater compatibility between donor and recipient.Conclusion:These findings allow us to infer that pre-transplant HLA typing of donors and recipients can influence post-transplant renal graft function and may contribute to the development and choice of new treatment strategies.

Plasma concentrations of inflammatory cytokines rise rapidly during ECMO-related SIRS due to the release of preformed stores in the intestine.

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McILwain, R Britt; Timpa, Joseph G; Kurundkar, Ashish R; Holt, David W; Kelly, David R; Hartman, Yolanda E; Neel, Mary Lauren; Karnatak, Rajendra K; Schelonka, Robert L; Anantharamaiah, G M; Killingsworth, Cheryl R; Maheshwari, Akhil

2010-01-01

Extracorporeal membrane oxygenation (ECMO) is a life-saving support system used in neonates and young children with severe cardiorespiratory failure. Although ECMO has reduced mortality in these critically ill patients, almost all patients treated with ECMO develop a systemic inflammatory response syndrome (SIRS) characterized by a 'cytokine storm', leukocyte activation, and multisystem organ dysfunction. We used a neonatal porcine model of ECMO to investigate whether rising plasma concentrations of inflammatory cytokines during ECMO reflect de novo synthesis of these mediators in inflamed tissues, and therefore, can be used to assess the severity of ECMO-related SIRS. Previously healthy piglets (3-week-old) were subjected to venoarterial ECMO for up to 8 h. SIRS was assessed by histopathological analysis, measurement of neutrophil activation (flow cytometry), plasma cytokine concentrations (enzyme immunoassays), and tissue expression of inflammatory genes (PCR/western blots). Mast cell degranulation was investigated by measurement of plasma tryptase activity. Porcine neonatal ECMO was associated with systemic inflammatory changes similar to those seen in human neonates. Tumor necrosis factor-alpha (TNF-alpha) and interleukin-8 (IL-8) concentrations rose rapidly during the first 2 h of ECMO, faster than the tissue expression of these cytokines. ECMO was associated with increased plasma mast cell tryptase activity, indicating that increased plasma concentrations of inflammatory cytokines during ECMO may result from mast cell degranulation and associated release of preformed cytokines stored in mast cells. TNF-alpha and IL-8 concentrations rose faster in plasma than in the peripheral tissues during ECMO, indicating that rising plasma levels of these cytokines immediately after the initiation of ECMO may not reflect increasing tissue synthesis of these cytokines. Mobilization of preformed cellular stores of inflammatory cytokines such as in mucosal mast cells may have

Changes in plasma steroids and cytokines levels in betel chewing patients in Taiwan.

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Hu, Sindy; Chen, Wen-Chyuan; Hwang, Guey-Shyang; Chen, Szu-Tah; Kuo, Song-Bor; Chen, Yifen; Idova, Galina; Wang, Shyi-Wu

2016-07-01

Betel nut is the second largest economic food product in Taiwan. In Southeast Asia, the habit of chewing betel nut seems to be highly correlated with oral submucous fibrosis and oral squamous cell carcinoma. Oral submucous fibrosis is characterized by abnormal accumulation of oral submucous collagen fibers and limitation of mouth opening. Although the mechanism responsible for tissue damage is still unknown, prolonged irritation caused by betel nut and tobacco is considered to be a major factor contributing to the pathogenesis of oral submucous fibrosis. The effect of betel nut chewing on immune system remains unknown. Present study aims to investigate the change of plasma hormones including cortisol, testosterone, and inflammatory cytokine concentrations in male chewing betel nut compared with normal subjects. Heparinized blood was obtained from control group (normal young+mid-aged individuals), betel nut-chewing, and oral cancer male subjects. The study was approved by the Ethics Committee of the Chang-Gung Memorial Hospital. Written informed consent was granted by the patients. Plasma cortisol and testosterone concentrations were detected by commercial enzyme-linked immunosorbent assay (ELISA). The inflammatory cytokines, including interleukin-1β (IL-1β), IL-15, tumor necrosis factor-α (TNF-α), were analyzed by ELISA with commercial monoclonal capture antibodies and polyclonal detection antibodies. The median concentrations of plasma IL-1β, IL-15, and TNF-α were 3.14pg/ml, 3.14pg/ml, and 6.85pg/ml, respectively, in patients with oral cancer, compared with median plasma IL-1β, IL-15, and TNF-α concentration of 2.64pg/ml, 5.86pg/ml, and 5.38pg/ml, respectively, in patients with betel nut-chewing habit. In contrast, the median concentrations of plasma IL-1β, IL-15, and TNF-α in mid-aged males (aged 30-50) were 7.00pg/ml, 10.64pg/ml, and 31.73pg/ml, respectively, compared with median plasma concentration of IL-1β, IL-15, and TNF-α of 4.48pg/ml, 33.36pg

Non-invasive prenatal detection of achondroplasia using circulating fetal DNA in maternal plasma.

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Lim, Ji Hyae; Kim, Mee Jin; Kim, Shin Young; Kim, Hye Ok; Song, Mee Jin; Kim, Min Hyoung; Park, So Yeon; Yang, Jae Hyug; Ryu, Hyun Mee

2011-02-01

To perform a reliable non-invasive detection of the fetal achondroplasia using maternal plasma. We developed a quantitative fluorescent-polymerase chain reaction (QF-PCR) method suitable for detection of the FGFR3 mutation (G1138A) causing achondroplasia. This method was applied in a non-invasive detection of the fetal achondroplasia using circulating fetal-DNA (cf-DNA) in maternal plasma. Maternal plasmas were obtained at 27 weeks of gestational age from women carrying an achondroplasia fetus or a normal fetus. Two percent or less achondroplasia DNA was reliably detected by QF-PCR. In a woman carrying a normal fetus, analysis of cf-DNA showed only one peak of the wild-type G allele. In a woman expected an achondroplasia fetus, analysis of cf-DNA showed the two peaks of wild-type G allele and mutant-type A allele and accurately detected the fetal achondroplasia. The non-invasive method using maternal plasma and QF-PCR may be useful for diagnosis of the fetal achondroplasia.

Maternal and neonatal plasma antioxidant levels in normal pregnancy, and the relationship with fatty acid unsaturation

NARCIS (Netherlands)

Oostenbrug, G.S.; Mensink, R.P.; Al, M.D.M.; Houwelingen, A.C. van; Hornstra, G.

1998-01-01

During pregnancy, maternal plasma concentrations of the peroxidation-susceptible polyunsaturated fatty acids (polyenes) increase. In addition, the proportion of polyenes is higher in neonatal plasma than in maternal plasma. To study whether these increased amounts of polyenes affect antioxidant

Cytokine polymorphisms and plasma levels are associated with sleep onset insomnia in adults living with HIV/AIDS.

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Gay, Caryl L; Zak, Rochelle S; Lerdal, Anners; Pullinger, Clive R; Aouizerat, Bradley E; Lee, Kathryn A

2015-07-01

Sleep disturbance has been associated with inflammation and cytokine activity, and we previously described genetic associations between cytokine polymorphisms and sleep maintenance and duration among adults with HIV/AIDS. Although sleep onset insomnia (SOI) is also a commonly reported sleep problem, associations between cytokine biomarkers and SOI have not been adequately studied. The purpose of this study was to describe SOI in relation to cytokine plasma concentrations and gene polymorphisms in a convenience sample of 307 adults (212 men, 72 women, and 23 transgender) living with HIV/AIDS. Based on the Pittsburgh Sleep Quality Index item that asks the time it usually took to fall asleep in the past month, participants were categorized as either >30min to fall asleep (n=70, 23%) or 30min or less to fall asleep (n=237). Plasma cytokines were analyzed, and genotyping was conducted for 15 candidate genes involved in cytokine signaling: interferon-gamma (IFNG), IFNG receptor 1 (IFNGR1), interleukins (IL1R2, IL2, IL4, IL6, IL8, IL10, IL13, IL17A), nuclear factor of kappa light polypeptide gene enhancer in B cells (NFKB1 and NFKB2), and tumor necrosis factor alpha (TNFA). Demographic and clinical variables were evaluated as potential covariates. After adjusting for genomic estimates of ancestry, self-reported race/ethnicity and viral load, SOI was associated with higher IL-13 plasma levels and with six single nucleotide polymorphisms (SNPs): IL1B rs1143642 and rs1143623, IL6 rs4719714, IL13 rs1295686, NFKB1 rs4648110, and TNFA rs2857602. In addition, the IL1B rs1143642 polymorphism was associated with plasma levels of IL-1β in adjusted analyses. This study strengthens the evidence for an association between inflammation and sleep disturbance, particularly self-report of habitual SOI. In this chronic illness population, the cytokine polymorphisms associated with SOI provide direction for future personalized medicine intervention research. Copyright © 2015 Elsevier Inc

Growth Modeling of the Maternal Cytokine Milieu throughout Normal Pregnancy: Macrophage-Derived Chemokine Decreases as Inflammation/Counterregulation Increases

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Shernan G. Holtan

2015-01-01

Full Text Available Several recent studies have shown differences in the maternal immune milieu at different phases of pregnancy, but most studies have been cross-sectional or of relatively few time points. Levels of 42 cytokines were determined using a multiplex bead-based assay on archived serum from a cohort of pregnant women N=16 at median of 18 time points tested, from the first trimester through to parturition, per woman. Unconditional growth modeling was then used to determine time-dependent changes in levels of these cytokines. Macrophage-derived chemokine (MDC, aka CCL22 decreases as pregnancy progresses. IL-1β, IL-6, IL-8, IL-12p70, IL-13, IL-15, IP-10, and FLT3-ligand increase as a function of gestational weeks, and IFNα2, IL-1ra, IL-3, IL-9, IL-12p40, and soluble CD40 ligand increase as a function of trimester. As pregnancy normally progresses, a maternal shift away from a type 2-biased immune response and toward an inflammatory/counterregulatory response is observed.

[Effects of shoutai pills on expression of Th1/Th2 cytokine in maternal-fetal interface and pregnancy outcome].

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Lai, Maohua; You, Zhaoling; Ma, Hongxia; Lei, Lei; Lu, Fangguo; He, Dongmei; Liu, Huiping; Yin, Sheng

2010-11-01

To evaluate its mechanism of inducing the maternal-fetal immune tolerance by studying the effects of Shoutai pills on the expression of Th1/Th2 cytokine and pregnancy in maternal-fetal interface of mice with recurrent spontaneous abortion (RSA). The normal pregnancy and RSA model were respectively induced with CBA/J x BALB/c and CBA/J x DBA/2. The mice with RSA were randomly divided into model group and low, middle and high dose groups of Shoutai pills. The mice were killed in 14 days after administration and embryo resorption rate was counted and their decidual and placental tissues were co-cultured to detect the expressions of IL-4, IL-10, IFN-gamma and TNF-alpha with ELISA. The embryo resorption rate of the model group was significantly higher than the normal pregnancy, middle and high dose groups of Shoutai pills could decreased the embryo resorption rate of the mice with RSA (P pills could decreased the expression of IFN-gamma and TNF-alpha (P pills. Middle and high doses of Shoutai pills could increased the expression of IL-4 and IL-10 (P pills. The mechanism about Shoutai pills can change Th1 /Th2 cytokine towards Th2 bias, which induced the maternal-fetal immune tolerance.

Parvovirus B19 infection modulates the levels of cytokines in the plasma of rheumatoid arthritis patients.

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Naciute, Milda; Mieliauskaite, Diana; Rugiene, Rita; Maciunaite, Gabriele; Mauricas, Mykolas; Murovska, Modra; Girkontaite, Irute

2017-08-01

Parvovirus B19 (B19V) infection is associated with various autoimmune diseases. We investigated the levels of pro-inflammatory (IFNᵧ, TNFα, IL-2, IL-12) and anti-inflammatory (IL-4, IL-10) cytokines in the plasma of B19V DNA positive (B19 + ) and negative (B19 - ) rheumatoid arthritis (RA) patients in comparison with the control group (healthy persons). Blood samples were collected from 118 patients with RA and 49 healthy voluntaries. B19V sequence was determined in whole blood and cell-free plasma DNA by nested PCR. The levels of cytokines in the plasma and cell culture medium from Concanavalin A (ConA) or B19V VP1 protein stimulated PBMC were determined by ELISA. The levels of IL-4, IL-10, IL-12, IL-2 and TNFα were higher in plasma of RA patients in comparison with control persons. B19 + controls and RA patients had lower levels of IFNᵧ in comparison with B19 - controls and RA patients. Within RA patients the plasma levels of IFNᵧ were lower in patients with low RA disease activity or remission. Plasma level of IL-4 was increased and IL-10 level was decreased in B19 + RA patients in comparison with B19 - RA patients and did not differ between B19 + and B19 - controls. B19V infection did not affect plasma levels of IL-12, IL-2, and TNFα. ConA and B19 VP1 protein stimulated PBMC from RA patients produced less IFNᵧ than stimulated PBMC from the healthy controls. B19V infection could differently modulate the amount of cytokines in the plasma of healthy persons and RA patients. Decreased production of IFNᵧ and raised level of plasma IL-4 in RA patients could lower antiviral clearance. Copyright © 2017 Elsevier Ltd. All rights reserved.

Mature IgM-expressing plasma cells sense antigen and develop competence for cytokine production upon antigenic challenge

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Blanc, Pascal; Moro-Sibilot, Ludovic; Barthly, Lucas; Jagot, Ferdinand; This, Sébastien; de Bernard, Simon; Buffat, Laurent; Dussurgey, Sébastien; Colisson, Renaud; Hobeika, Elias; Fest, Thierry; Taillardet, Morgan; Thaunat, Olivier; Sicard, Antoine; Mondière, Paul; Genestier, Laurent; Nutt, Stephen L.; Defrance, Thierry

2016-01-01

Dogma holds that plasma cells, as opposed to B cells, cannot bind antigen because they have switched from expression of membrane-bound immunoglobulins (Ig) that constitute the B-cell receptor (BCR) to production of the secreted form of immunoglobulins. Here we compare the phenotypical and functional attributes of plasma cells generated by the T-cell-dependent and T-cell-independent forms of the hapten NP. We show that the nature of the secreted Ig isotype, rather than the chemical structure of the immunizing antigen, defines two functionally distinct populations of plasma cells. Fully mature IgM-expressing plasma cells resident in the bone marrow retain expression of a functional BCR, whereas their IgG+ counterparts do not. Antigen boost modifies the gene expression profile of IgM+ plasma cells and initiates a cytokine production program, characterized by upregulation of CCL5 and IL-10. Our results demonstrate that IgM-expressing plasma cells can sense antigen and acquire competence for cytokine production upon antigenic challenge. PMID:27924814

Plasma cytokine levels and risks of abdominal aortic aneurysms

DEFF Research Database (Denmark)

Liao, Mengyang; Liu, Cong-Lin; Lv, Bing-Jie

2015-01-01

BACKGROUND: Abdominal aortic aneurysm (AAA) is characterized by inflammatory cell accumulation in AAA lesions that produce inflammatory cytokines and advance its pathogenesis. Peripheral cytokines may predict the degree or risk of AAA. METHODS AND RESULTS: ELISA determined plasma interleukin-6 (IL6......), IL10, IL17A, IFN-γ, and C-reactive protein (CRP) from 476 AAA patients and 200 controls. AAA patients had lower IL6, IFN-γ, IL10, IL17A, and higher CRP than controls. IL10 correlated positively with IFN-γ, IL17A, or IL6, but not CRP in control or AAA populations. IL10 associated negatively...... with systolic blood pressure, whereas CRP associated positively with diastolic blood pressure and body mass index. CRP was an independent AAA risk factor and correlated positively with aortic diameters before and after adjustments for other risk factors. IFN-γ, IL17A, and CRP correlated positively with cross...

Quantitative determination of famotidine in human maternal plasma, umbilical cord plasma and urine using high-performance liquid chromatography - mass spectrometry

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Wang, Xiaoming; Rytting, Erik; Abdelrahman, Doaa R.; Nanovskaya, Tatiana N.; Hankins, Gary D.V.; Ahmed, Mahmoud S.

2013-01-01

The liquid chromatography with electrospray ionization mass spectrometry for the quantitative determination of famotidine in human urine, maternal and umbilical cord plasma was developed and validated. The plasma samples were alkalized with ammonium hydroxide and extracted twice with ethyl acetate. The extraction recovery of famotidine in maternal and umbilical cord plasma ranged from 53% to 64% and 72% to 79%, respectively. Urine samples were directly diluted with the initial mobile phase then injected into the HPLC system. Chromatographic separation of famotidine was achieved by using a Phenomenex Synergi™ Hydro-RP™ column with a gradient elution of acetonitrile and 10 mM ammonium acetate aqueous solution (pH 8.3, adjusted with ammonium hydroxide). Mass Spectrometric detection of famotidine was set in the positive mode and used a selected ion monitoring method. Carbon-13-labeled famotidine was used as internal standard. The calibration curves were linear (r2> 0.99) in the concentration ranges of 0.631-252 ng/mL for umbilical and maternal plasma samples, and of 0.075-30.0 μg/mL for urine samples. The relative deviation of method was less than 14% for intra- and inter-day assays, and the accuracy ranged between 93% and 110%. The matrix effect of famotidine in human urine, maternal and umbilical cord plasma is less than 17%. PMID:23401067

Correlation between maternal inflammatory markers and fetomaternal adiposity.

LENUS (Irish Health Repository)

Farah, Nadine

2012-10-01

Outside pregnancy, both obesity and diabetes mellitus are associated with changes in inflammatory cytokines. Obesity in pregnancy may be complicated by gestational diabetes mellitus (GDM) and\\/or fetal macrosomia. The objective of this study was to determine the correlation between maternal cytokines and fetomaternal adiposity in the third trimester in women where the important confounding variable GDM had been excluded. Healthy women with a singleton pregnancy and a normal glucose tolerance test at 28 weeks gestation were enrolled at their convenience. Maternal cytokines were measured at 28 and 37 weeks gestation. Maternal adiposity was assessed indirectly by calculating the Body Mass Index (BMI), and directly by bioelectrical impedance analysis. Fetal adiposity was assessed by ultrasound measurement of fetal soft tissue markers and by birthweight at delivery. Of the 71 women studied, the mean maternal age and BMI were 29.1 years and 29.2 kg\\/m(2) respectively. Of the women studied 32 (45%) were obese. Of the cytokines, only maternal IL-6 and IL-8 correlated with maternal adiposity. Maternal TNF-α, IL-β, IL-6 and IL-8 levels did not correlate with either fetal body adiposity or birthweight. In this well characterised cohort of pregnant non-diabetic women in the third trimester of pregnancy we found that circulating maternal cytokines are associated with maternal adiposity but not with fetal adiposity.

Interactive effects of maternal cigarette smoke, heat stress, hypoxia, and lipopolysaccharide on neonatal cardiorespiratory and cytokine responses

Science.gov (United States)

McDonald, Fiona B.; Chandrasekharan, Kumaran; Wilson, Richard J. A.

2016-01-01

Maternal cigarette smoke (CS) exposure exhibits a strong epidemiological association with Sudden Infant Death Syndrome, but other environmental stressors, including infection, hyperthermia, and hypoxia, have also been postulated as important risk factors. This study examines whether maternal CS exposure causes maladaptations within homeostatic control networks by influencing the response to lipopolysaccharide, heat stress, and/or hypoxia in neonatal rats. Pregnant dams were exposed to CS or parallel sham treatments daily for the length of gestation. Offspring were studied at postnatal days 6–8 at ambient temperatures (Ta) of 33°C or 38°C. Within each group, rats were allocated to control, saline, or LPS (200 µg/kg) treatments. Cardiorespiratory patterns were examined using head-out plethysmography and ECG surface electrodes during normoxia and hypoxia (10% O2). Serum cytokine concentrations were quantified from samples taken at the end of each experiment. Our results suggest maternal CS exposure does not alter minute ventilation (V̇e) or heart rate (HR) response to infection or high temperature, but independently increases apnea frequency. CS also primes the inflammatory system to elicit a stronger cytokine response to bacterial insult. High Ta independently depresses V̇e but augments the hypoxia-induced increase in V̇e. Moreover, higher Ta increases HR during normoxia and hypoxia, and in the presence of an immune challenge, increases HR during normoxia, and reduces the increase normally associated with hypoxia. Thus, while most environmental risk factors increase the burden on the cardiorespiratory system in early life, hyperthermia and infection blunt the normal HR response to hypoxia, and gestational CS independently destabilizes breathing by increasing apneas. PMID:27733384

The plasma levels of the cytokines in opium-addicts and the effects of opium on the cytokines secretion by their lymphocytes.

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Nabati, Saeedeh; Asadikaram, Gholamreza; Arababadi, Mohammad Kazemi; Shahabinejad, Gholamabbas; Rezaeian, Mohsen; Mahmoodi, Mehdi; Kennedy, Derek

2013-04-01

The aim of this study was to evaluate the effects of opium addiction on the secretion of IL-4, IFN-γ, IL-6 and TGF-β under in vivo and in vitro conditions. The blood samples were collected and PBMCs were cultured in RPMI1640 with and without opium for 48 h. The levels of the cytokines were measured using ELISA technique. The results showed that plasma levels of IL-4 and IFN-γ were significantly lower and IL-6 and TGF-β were higher in plasma taken from opium-addicted subjects. The concentrations of all the cytokines in opium-addicted subjects in in vitro condition were significantly lower than the control group. Addicted subjects cultured lymphocytes significantly decrease secreted IL-4, IL-6 and TGF-β but not IFN-γ in response to being cultured with opium, where as IFN-γ was increased in controls. These results may explain the frequent microbial infections and an increased tumor incidence seen in addicted patients. Copyright © 2013 Elsevier B.V. All rights reserved.

Concentration of perfluorinated compounds and cotinine in human foetal organs, placenta, and maternal plasma

DEFF Research Database (Denmark)

Mamsen, Linn Salto; Jönsson, Bo A.G.; Lindh, Christian H.

2017-01-01

levels. Foetal exposure has previously been estimated from umbilical cord plasma, but the actual concentration in foetal organs has never been measured. Objectives The concentrations of 5 PFASs and cotinine – the primary metabolite of nicotine – were measured in human foetuses, placentas, and maternal...... plasma to evaluate to what extent these compounds were transferred from mother to foetus and to determine if the PFAS concentrations were associated with maternal cigarette smoking. Methods Thirty-nine Danish women who underwent legal termination of pregnancy before gestational week 12 were included; 24...... ratio for all five PFASs and cotinine. Smokers presented 99 ng/g cotinine in plasma, 108 ng/g in placenta, and 61 ng/g in foetal organs. No correlation between the maternal cotinine concentrations and PFAS concentrations was found. Conclusions PFASs were transferred from mother to foetus, however...

The predictive value of plasma cytokines on gastroesophageal anastomotic leakage at an early stage in patients undergoing esophagectomy.

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Song, Jie-Qiong; He, Yi-Zhou; Fang, Yuan; Wu, Wei; Zhong, Ming

2017-08-01

It's difficult to diagnose gastroesophageal anastomotic leakage (GAL) at early postoperative stage. This study was conducted to evaluate the early predictive value of plasma cytokines levels on GAL in patients undergoing esophagectomy. Consecutive esophageal cancer patients who underwent esophagectomy and admitted to Surgical Intensive Care Unit (SICU) just after surgery were retrospectively analyzed. The baseline and postoperative 1 day plasma cytokine levels were collected and analyzed to evaluate the predictive value for clinically important anastomotic leakage. Area under receiver operating characteristic curve (AUROC) analysis was also performed. A total of 183 patients were included. Sixteen patients (8.74%) experienced GAL (GAL group) and the others did not (non-GAL group). The concentrations of tumor necrosis factor-alpha (TNF-α), interleukin (IL)-2R, IL-6, IL-8 and IL-10 in plasma on the first postoperative day significantly increased in the GAL group than in the non-GAL group (Pfair predictors of GAL (AUROC >0.7) and the other two cytokines were poorly predictive (AUROC <0.7). The mean length of ICU and hospital stay were significantly longer in the GAL group than in the non-GAL group (P<0.05). Plasma concentrations of IL-6, IL-8 and IL-10 on the first postoperative day can predict clinically important GAL in patients undergoing esophagectomy.

PERIPHERAL PARASITAEMIA AND ITS ASSOCIATION WITH PLASMA CYTOKINES LEVELS IN MALARIA-INFECTED PREGNANT WOMEN IN ABA, ABIA STATE, NIGERIA.

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Ifeanyichukwu, M O; Okamgba, O C; Amilo, G I; Nwokorie, E A

2017-01-01

Cytokines in pregnant female may not be a normal phenomenon as malarial infection is often associated with strong CD4+ cell activation and up-regulation of pro-inflammatory cytokines. We investigated the relationship between peripheral parasitaemia and plasma levels of cytokines among malaria infected pregnant women in Aba, Abia State, Nigeria. A total of 206 non-HIV positive asymptomatic malaria parasitaemic (n=144) and non-parasitaemic (n=62) pregnant women were recruited for this study alongside 80 non-pregnant women who served as positive (n=40) and negative (n=40) controls. Blood samples were aseptically collected from each subject and tested for HIV and malaria parasites using standard methods. Also, plasma levels of cytokines were measured using Th1/Th2 human cytokine ELISA kits (Abcam, UK). Analysis of Variance and Student's t-test were used for Comparison of groups while Pearson's Correlation Coefficient was used for tests of association. The results revealed a mean parasite density of 685.56±484.55 parasites/µl of blood. Malaria infected pregnant subjects showed significantly higher levels of IFN-γ, TNF-α, IL-4, IL-6 and IL-10 when compared with their non-infected counterparts (P< 0.05). The cytokines evaluated were higher in moderate parasitaemia than mild parasitaemia. Positive correlation existed between peripheral parasite density (PPD) and IL-4 (r= 0.24, P=0.004), PPD and IL-6 (r = 0.35, P = 0.001) as well as PPD and IL-10 (r = 0.29, P = 0.001). This study showed that increase in peripheral parasitaemia increased levels of some plasma cytokines (IL-4, IL-6 and IL-10) but not IFN-γ and TNF-α in the malaria infected pregnant women studied.

The relationship between maternal and neonatal umbilical cord plasma homocyst(e)ine suggests a potential role for maternal homocyst(e)ine in fetal metabolism.

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Malinow, M R; Rajkovic, A; Duell, P B; Hess, D L; Upson, B M

1998-02-01

Data on fetal blood homocyst(e)ine concentrations are not available. We tested the hypothesis that homocyst(e)ine crosses the maternal/placental/fetal interphases and is sequestered by the fetus. The concentration of homocyst(e)ine was determined at parturition in peripheral venous plasma from 35 nulliparous healthy pregnant women and umbilical arterial and venous plasma from their conceptus. Findings demonstrated a descending concentration gradient of plasma homocyst(e)ine from maternal vein to umbilical vein and to umbilical artery; the decrease at each interphase approximated 1 micromol/L. The neonate weight and gestational age were inversely related to maternal homocyst(e)ine concentrations. The umbilical vein to umbilical artery homocyst(e)ine decrement suggests that uptake of homocyst(e)ine occurs in the fetus. The likely incorporation of homocyst(e)ine into the fetal metabolic cycle may implicate maternal homocyst(e)ine as having a potential nutritional role in the fetus. Further studies are required to explain the role of homocyst(e)ine in fetal metabolism and development.

Stability of cell-free DNA from maternal plasma isolated following a single centrifugation step.

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Barrett, Angela N; Thadani, Henna A; Laureano-Asibal, Cecille; Ponnusamy, Sukumar; Choolani, Mahesh

2014-12-01

Cell-free fetal DNA can be used for prenatal testing with no procedure-related risk to the fetus. However, yield of fetal DNA is low compared with maternal cell-free DNA fragments, resulting in technical challenges for some downstream applications. To maximize the fetal fraction, careful blood processing procedures are essential. We demonstrate that fetal fraction can be preserved using a single centrifugation step followed by postage of plasma to the laboratory for further processing. Digital PCR was used to quantify copies of total, maternal, and fetal DNA present in single-spun plasma at time points over a two-week period, compared with immediately processed double-spun plasma, with storage at room temperature, 4°C, and -80°C representing different postage scenarios. There was no significant change in total, maternal, or fetal DNA copy numbers when single-spun plasma samples were stored for up to 1 week at room temperature and 2 weeks at -80°C compared with plasma processed within 4 h. Following storage at 4°C no change in composition of cell-free DNA was observed. Single-spun plasma can be transported at room temperature if the journey is expected to take one week or less; shipping on dry ice is preferable for longer journeys. © 2014 John Wiley & Sons, Ltd.

Analysis of SF and plasma cytokines provides insights into the mechanisms of inflammatory arthritis and may predict response to therapy.

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Wright, Helen L; Bucknall, Roger C; Moots, Robert J; Edwards, Steven W

2012-03-01

Biologic drugs have revolutionized the care of RA, but are expensive and not universally effective. To further understand the inflammatory mechanisms underlying RA and identify potential biomarkers predicting response to therapy, we measured multiple cytokine concentrations in SF of patients with inflammatory arthritides (IAs) and, in a subset of patients with RA, correlated this with response to TNF-α inhibition. SF from 42 RA patients and 19 non-RA IA patients were analysed for 12 cytokines using a multiplex cytokine assay. Cytokines were also measured in the plasma of 16 RA patients before and following treatment with anti-TNF-α. Data were analysed using Mann-Whitney U-test, Spearman's rank correlation and cluster analysis with the Kruskal-Wallis test with Dunn's post-test analysis. RA SF contained significantly elevated levels of IL-1β, IL-1ra, IL-2, IL-4, IL-8, IL-10, IL-17, IFN-γ, G-CSF, GM-CSF and TNF-α compared with other IA SF. RA patients who did not respond to anti-TNF therapy had elevated IL-6 in their SF pre-therapy (P < 0.05), whereas responders had elevated IL-2 and G-CSF (P < 0.05). Plasma cytokine concentrations were not significantly modulated by TNF inhibitors, with the exception of IL-6, which decreased after 12 weeks (P < 0.05). Cytokine profiles in RA SF vary with treatment and response to therapy. Cytokine concentrations are significantly lower in plasma than in SF and relatively unchanged by TNF inhibitor therapy. Concentrations of IL-6, IL-2 and G-CSF in SF may predict response to TNF inhibitors.

Cytokines and the neurodevelopmental basis of mental illness

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Udani eRatnayake

2013-10-01

Full Text Available Epidemiological studies suggest that prenatal exposure to different types of viral or bacterial infections may be associated with similar outcomes; i.e., an increased risk of mental illness disorders in the offspring. Infections arising from various causes have similar debilitating effects in later life, suggesting that the exact pathogen may not be the critical factor in determining the neurological and cognitive outcome in the offspring. Instead, it is thought that response of the innate immune system, specifically the increased production of inflammatory cytokines, may be the critical mediator in altering fetal brain development pre-disposing the offspring to mental illness disorders later in life. Inflammatory cytokines are essential for normal brain development. Factors such as the site of cytokine production, a change in balance between anti- and pro- inflammatory cytokines, placental transfer of cytokines, the effects of cytokines on glial cells, and the effects of glucocorticoids are important when evaluating the impact of maternal infection on fetal brain development. Although it is clear that cytokines are altered in the fetal brain following maternal infection, further evidence is required to determine if cytokines are the critical factor that alters the trajectory of brain development, subsequently leading to postnatal behavioural and neurological abnormalities.

Changes in plasma cytokines and their soluble receptors in complex regional pain syndrome.

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Alexander, Guillermo M; Peterlin, B Lee; Perreault, Marielle J; Grothusen, John R; Schwartzman, Robert J

2012-01-01

Complex Regional Pain Syndrome (CRPS) is a chronic and often disabling pain disorder. There is evidence demonstrating that neurogenic inflammation and activation of the immune system play a significant role in the pathophysiology of CRPS. This study evaluated the plasma levels of cytokines, chemokines, and their soluble receptors in 148 subjects afflicted with CRPS and in 60 gender- and age-matched healthy controls. Significant changes in plasma cytokines, chemokines, and their soluble receptors were found in subjects with CRPS as compared with healthy controls. For most analytes, these changes resulted from a distinct subset of the CRPS subjects. When the plasma data from the CRPS subjects was subjected to cluster analysis, it revealed 2 clusters within the CRPS population. The category identified as most important for cluster separation by the clustering algorithm was TNFα. Cluster 1 consisted of 64% of CRPS subjects and demonstrated analyte values similar to the healthy control individuals. Cluster 2 consisted of 36% of the CRPS subjects and demonstrated significantly elevated levels of most analytes and in addition, it showed that the increased plasma analyte levels in this cluster were correlated with disease duration and severity. The identification of biomarkers that define disease subgroups can be of great value in the design of specific therapies and of great benefit to the design of clinical trials. It may also aid in advancing our understanding of the mechanisms involved in the pathophysiology of CRPS, which may lead to novel treatments for this very severe condition. Copyright © 2012 American Pain Society. Published by Elsevier Inc. All rights reserved.

Cytokines, growth, and environment factors in bone marrow plasma of acute lymphoblastic leukemia pediatric patients

Czech Academy of Sciences Publication Activity Database

Kováč, M.; Vášková, M.; Petráčková, Denisa; Pelková, V.; Mejstříková, E.; Kalina, T.; Žaliová, M.

2014-01-01

Roč. 25, č. 1 (2014), s. 8-13 ISSN 1148-5493 R&D Projects: GA MZd NR9531 Institutional support: RVO:61388971 Keywords : pediatric acute lymphoblastic leukemia * bone marrow plasma * cytokine Subject RIV: CE - Biochemistry Impact factor: 1.960, year: 2014

Clinical signs and hematologic, cytokine, and plasma nitric oxide alterations in response to Strongylus vulgaris infection in helminth-naïve ponies.

Science.gov (United States)

Hubert, Jeremy D; Seahorn, Thomas L; Klei, Thomas R; Hosgood, Giselle; Horohov, David W; Moore, Rustin M

2004-07-01

The objective of this study was to determine the effect of infection with Strongylus vulgaris on serum cytokines and plasma nitric oxide (NO) concentrations in helminth-naive ponies. Group 1 (n = 21) was given 500 S. vulgaris L3 larvae and group 2 (n = 7) received a saline control. Ponies were monitored daily for clinical signs, and blood was collected for complete blood cell counts and serum cytokines (TNF, IL-1, IL-6) quantification. Group 1 ponies were depressed, anorexic, and febrile for variable periods of time. Plasma NO was increased on day 21 in group 1 and on days 9 and 21 in group 2. Significant increases in total white blood cell counts, fibrinogen, and plasma protein concentrations in group 1 were found. Significant decreases in red blood cell counts and packed cell volume were also noted in group 1. There were no differences in serum cytokines across time in either group of ponies. Despite the lack of proinflammatory cytokine induction with the apparent inflammatory response to S. vulgaris there is evidence of a potential role of NO.

Plasma cytokine profiles in depressed patients who fail to respond to selective serotonin reuptake inhibitor therapy.

LENUS (Irish Health Repository)

O'Brien, Sinead M

2012-02-03

OBJECTIVE: Approximately 30% of patients with depression fail to respond to a selective serotonin reuptake inhibitor (SSRI). Few studies have attempted to define these patients from a biological perspective. Studies suggest that overall patients with depression show increased production of proinflammatory cytokines. We examined pro- and anti-inflammatory cytokine levels in patients who were SSRI resistant. METHODS: Plasma concentrations of IL-6, IL-8, IL-10, TNF-alpha and sIL-6R were measured with enzyme linked immunosorbent assays (ELISA) in DSM-1V major depressives who were SSRI resistant, in formerly SSRI resistant patients currently euthymic and in healthy controls. RESULTS: Patients with SSRI-resistant depression had significantly higher production of the pro-inflammatory cytokines IL-6 (p=0.01) and TNF-alpha (p=0.004) compared to normal controls. Euthymic patients who were formerly SSRI resistant had proinflammatory cytokine levels which were similar to the healthy subject group. Anti-inflammatory cytokine levels did not differ across the 3 groups. CONCLUSION: Suppression of proinflammatory cytokines does not occur in depressed patients who fail to respond to SSRIs and is necessary for clinical recovery.

In Vitro Dialysis of Cytokine-Rich Plasma With High and Medium Cut-Off Membranes Reduces Its Procalcific Activity.

Science.gov (United States)

Willy, Kevin; Hulko, Michael; Storr, Markus; Speidel, Rose; Gauss, Julia; Schindler, Ralf; Zickler, Daniel

2017-09-01

Recently developed high-flux (HF) dialysis membranes with extended permeability provide better clearance of middle-sized molecules such as interleukins (ILs). Whether this modulation of inflammation influences the procalcific effects of septic plasma on vascular smooth muscle cells (VSMCs) is not known. To assess the effects of high cut-off (HCO) and medium cut-off (MCO) membranes on microinflammation and in vitro vascular calcification we developed a miniature dialysis model. Plasma samples from lipopolysaccharide-spiked blood were dialyzed with HF, HCO, and MCO membranes in an in vitro miniature dialysis model. Afterwards, IL-6 concentrations were determined in dialysate and plasma. Calcifying VSMCs were incubated with dialyzed plasma samples and vascular calcification was assessed. Osteopontin (OPN) and matrix Gla protein (MGP) were measured in VSMC supernatants. IL-6 plasma concentrations were markedly lower with HCO and MCO dialysis. VSMC calcification was significantly lower after incubation with MCO- and HCO-serum compared to HF plasma. MGP and OPN levels in supernatants were significantly lower in the MCO but not in the HCO group compared to HF. In vitro dialysis of cytokine-enriched plasma samples with MCO and HCO membranes reduces IL-6 levels. The induction of vascular calcification by cytokine-enriched plasma is reduced after HCO and MCO dialysis. © 2017 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Increased maternal plasma leptin in early pregnancy and risk of gestational diabetes mellitus.

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Qiu, Chunfang; Williams, Michelle A; Vadachkoria, Surab; Frederick, Ihunnaya O; Luthy, David A

2004-03-01

Emerging evidence suggests that leptin, an adipocyte-derived hormone, may have independent direct effects on both insulin secretion and action, in addition to its well documented effects on appetite and energy expenditure. Some, but not all, previously published studies suggest that maternal leptin concentrations may be increased in pregnancies complicated by gestational diabetes mellitus (GDM). We examined the association between plasma leptin concentration and GDM risk. Women were recruited before 16 weeks of gestation and were followed up until delivery. Maternal plasma leptin concentrations (collected at 13 weeks of gestation) were measured by using immunoassay. We used generalized linear models to estimate relative risks and 95% confidence intervals. GDM developed in 5.7% of the cohort (47 of 823). Elevated leptin concentrations were positively associated with GDM risk (P for trend risk of GDM (95% confidence interval 1.2, 18.0) as compared with women who had concentrations of 14.3 ng/mL or lower. We noted a strong linear component of trend in risk of GDM with increasing maternal plasma leptin concentration. Each 10-ng/mL increase in the leptin concentration was associated with a 20% increase in GDM risk (relative risk 1.2; 95% confidence interval 1.0, 1.3). Hyperleptinemia, independent of maternal adiposity, in early pregnancy appears to be predictive of an increased risk of GDM later in pregnancy. Additional larger prospective cohort studies are needed to confirm and more precisely assess the etiologic importance of hyperleptinemia in pregnancy. II-2

Maternal high fat diet is associated with decreased plasma n-3 fatty acids and fetal hepatic apoptosis in nonhuman primates.

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Wilmon F Grant

2011-02-01

Full Text Available To begin to understand the contributions of maternal obesity and over-nutrition to human development and the early origins of obesity, we utilized a non-human primate model to investigate the effects of maternal high-fat feeding and obesity on breast milk, maternal and fetal plasma fatty acid composition and fetal hepatic development. While the high-fat diet (HFD contained equivalent levels of n-3 fatty acids (FA's and higher levels of n-6 FA's than the control diet (CTR, we found significant decreases in docosahexaenoic acid (DHA and total n-3 FA's in HFD maternal and fetal plasma. Furthermore, the HFD fetal plasma n-6:n-3 ratio was elevated and was significantly correlated to the maternal plasma n-6:n-3 ratio and maternal hyperinsulinemia. Hepatic apoptosis was also increased in the HFD fetal liver. Switching HFD females to a CTR diet during a subsequent pregnancy normalized fetal DHA, n-3 FA's and fetal hepatic apoptosis to CTR levels. Breast milk from HFD dams contained lower levels of eicosopentanoic acid (EPA and DHA and lower levels of total protein than CTR breast milk. This study links chronic maternal consumption of a HFD with fetal hepatic apoptosis and suggests that a potentially pathological maternal fatty acid milieu is replicated in the developing fetal circulation in the nonhuman primate.

Cytokine, chemokine, and growth factor profile of platelet-rich plasma.

Science.gov (United States)

Mussano, F; Genova, T; Munaron, L; Petrillo, S; Erovigni, F; Carossa, S

2016-07-01

During wound healing, biologically active molecules are released from platelets. The rationale of using platelet-rich plasma (PRP) relies on the concentration of bioactive molecules and subsequent delivery to healing sites. These bioactive molecules have been seldom simultaneously quantified within the same PRP preparation. In the present study, the flexible Bio-Plex system was employed to assess the concentration of a large range of cytokines, chemokines, and growth factors in 16 healthy volunteers so as to determine whether significant baseline differences may be found. Besides IL-1b, IL-1ra, IL-4, IL-6, IL-8, IL-12, IL-13, IL-17, INF-γ, TNF-α, MCP-1, MIP-1a, RANTES, bFGF, PDGF, and VEGF that were already quantified elsewhere, the authors reported also on the presence of IL-2, IL-5, IL-7, IL-9, IL-10, IL-15 G-CSF, GM-CSF, Eotaxin, CXCL10 chemokine (IP-10), and MIP 1b. Among the most interesting results, it is convenient to mention the high concentrations of the HIV-suppressive and inflammatory cytokine RANTES and a statistically significant difference between males and females in the content of PDGF-BB. These data are consistent with previous reports pointing out that gender, diet, and test system affect the results of platelet function in healthy subjects, but seem contradictory when compared to other quantification assays in serum and plasma. The inconsistencies affecting the experimental results found in literature, along with the variability found in the content of bioactive molecules, urge further research, hopefully in form of randomized controlled clinical trials, in order to find definitive evidence of the efficacy of PRP treatment in various pathologic and regenerative conditions.

Plasma cytokine expression is associated with cardiac morbidity in chagas disease.

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Giovane Rodrigo Sousa

Full Text Available The expression of immune response appears to be associated with morbidity in Chagas disease. However, the studies in this field have usually employed small samples of patients and statistical analyses that do not consider the wide dispersion of cytokine production observed in these patients. The aim of this study was to evaluate the plasma cytokine levels in well-defined clinical polar groups of chagasic patients divided into categories that better reflect the wide cytokine profile and its relationship with morbidity. Patients infected with Trypanosoma cruzi (T. cruzi were grouped as indeterminate (IND and cardiac (CARD forms ranging from 23 to 69 years of age (mean of 45.6±11.25. The IND group included 82 individuals, ranging from 24 to 66 years of age (mean of 39.6±10.3. The CARD group included 94 patients ranging from 23 to 69 years of age (mean of 48±12.52 presenting dilated cardiomyopathy. None of the patients have undergone chemotherapeutic treatment, nor had been previously treated for T. cruzi infection. Healthy non-chagasic individuals, ranging from 29 to 55 years of age (mean of 42.6±8.8 were included as a control group (NI. IND patients have a higher intensity of interleukin 10 (IL-10 expression when compared with individuals in the other groups. By contrast, inflammatory cytokine expression, such as interferon gamma (IFN-γ, tumor necrosis factor alpha (TNF-α, interleukin 6 (IL-6, and interleukin 1 beta (IL-1β, proved to be the highest in the CARD group. Correlation analysis showed that higher IL-10 expression was associated with better cardiac function, as determined by left ventricular ejection fraction and left ventricular diastolic diameter values. Altogether, these findings reinforce the concept that a fine balance between regulatory and inflammatory cytokines represents a key element in the establishment of distinct forms of chronic Chagas disease.

The association between maternal cervicovaginal proinflammatory cytokines concentrations during pregnancy and subsequent early-onset neonatal infection.

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Kalinka, Jarosław; Krajewski, Paweł; Sobala, Wojciech; Wasiela, Małgorzata; Brzezińska-Błaszczyk, Ewa

2006-01-01

The aim of this study was to investigate the relationship between the concentration of selected proinflammatory cytokines (IL-1alpha, IL-1beta, IL-6 and IL-8) in cervicovaginal fluid, as measured in midgestation, and the risk of early-onset neonatal infection (EONI). Cervicovaginal fluids were obtained from a cohort of 114 pregnant women at 22 to 34 weeks' gestation. The samples were analyzed for the concentrations of selected proinflammatory cytokines using standard enzyme-linked immunosorbent assay technique (ELISA). Lower genital tract microbiology was diagnosed using Gram stain method according to Spiegel's criteria and by culture. Mean gestational age at the time of sampling was 29.0 weeks. Mean time between sampling and delivery was 9.3 (SD 4.7) weeks. Bacterial vaginosis (BV) was diagnosed in 27.2% of subjects and M. hominis and U. urealyticum in 22.8% and 26.3%, respectively. Out of 114 women examined, 20 (17.5%) delivered newborns with EONI. Median cervicovaginal concentrations of IL-1alpha, IL-1beta, IL-6 and IL-8 did not differ between women who delivered newborns with EONI as compared to women who delivered newborns without EONI. Women with pathological lower genital tract microflora and low IL-8 concentration (below 25(th) percentile) during pregnancy presented a significant risk of delivering newborns with EONI (OR=4.9; 95% CI, 1.1-22.8). Subjects with pathological lower genital tract microflora and a low concentration of more than one cytokine had the highest risk of delivering a newborn with EONI, OR=16.2, 95% CI, 1.1-234.0. Cytokine measurement in cervicovaginal fluid in early gestation could be useful for predicting subsequent EONI only among pregnant women with lower genital tract infection. Maternal genital tract immune hyporesponsiveness as represented by low concentrations of proinflammatory cytokines may create a permissive environment for ascending infection and may lead to subsequent EONI.

A gestational profile of placental exosomes in maternal plasma and their effects on endothelial cell migration.

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Carlos Salomon

Full Text Available Studies completed to date provide persuasive evidence that placental cell-derived exosomes play a significant role in intercellular communication pathways that potentially contribute to placentation and development of materno-fetal vascular circulation. The aim of this study was to establish the gestational-age release profile and bioactivity of placental cell-derived exosome in maternal plasma. Plasma samples (n = 20 per pregnant group were obtained from non-pregnant and pregnant women in the first (FT, 6-12 weeks, second (ST, 22-24 weeks and third (TT, 32-38 weeks trimester. The number of exosomes and placental exosome contribution were determined by quantifying immunoreactive exosomal CD63 and placenta-specific marker (PLAP, respectively. The effect of exosomes isolated from FT, ST and TT on endothelial cell migration were established using a real-time, live-cell imaging system (Incucyte. Exosome plasma concentration was more than 50-fold greater in pregnant women than in non-pregnant women (p<0.001. During normal healthy pregnancy, the number of exosomes present in maternal plasma increased significantly with gestational age by more that two-fold (p<0.001. Exosomes isolated from FT, ST and TT increased endothelial cell migration by 1.9±0.1, 1.6±0.2 and 1.3±0.1-fold, respectively compared to the control. Pregnancy is associated with a dramatic increase in the number of exosomes present in plasma and maternal plasma exosomes are bioactive. While the role of placental cell-derived exosome in regulating maternal and/or fetal vascular responses remains to be elucidated, changes in exosome profile may be of clinical utility in the diagnosis of placental dysfunction.

PLASMA CYTOKINES LEVELS IN PATIENTS UNDERGOING LONG-TERM HAEMODIALYSIS

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D. S. Polyakov

2011-01-01

Full Text Available Аbstract.  Patients  with  end-stage  renal  disease  need  their  kidney  functions  to  be  replaced.  Chronic haemodialysis represents a most common method of such substitution treatment. This procedure results in successful survival of such patients for years. Chronic haemodialysis is accompanied by a complication which is known as β2-microglobulin amyloidosis. In this case, amyloid substance consisting of β2-microglobulin (β2-MG accumulates in bones, ligaments and joints. Biological causes of β2-MG amyloidosis are still not established. To elucidate the role of inflammation in the pathogenesis of β2-MG amyloidosis, the levels of  IL-2,  IL-4,  IL-6,  IL-8,  IL-10,  GM-CSF,  IFNγ, TNFα were quantified in plasma of patients undergoing  long-term haemodialysis. Mean amounts of all the mentioned cytokines in haemodialysis patients proved to be significantly higher than in control group consisting of healthy subjects. When comparing a group receiving standard  dialysis  procedure  versus  a  subgroup  receiving  haemodiafiltration,  a  single  reliable  difference  was revealed for GM-CSF levels (p < 0.04, without any differences shown for other cytokines. With increasing terms of chronic haemodialysis, the levels of IL-2, IL-4, IL-6, IL-8, GM-CSF, IFNγ, TNFα were increased, or, at least, they did not decrease. After three years of dialysis, IL-10 concentrations were statistically indistinguishable from normal levels. In patients undergoing haemodiafiltration, plasma levels of IL-2, IL-4, IL-8, GM-CSF, IFNγ, TNFα did not drop with increasing terms of dialysis. The levels of IL-6 and IL-10 decreased after three years of dialysis, to near-normal levels.In general, these results suggest that IL-10 and IL-6 may be regarded as candidates for further studies as potential markers of β2-microglobulin amyloidosis. (Med. Immunol., 2011, vol. 13, N 2-3, pp 211-218

[Measurement of maternal plasma volume during pregnancy].

Science.gov (United States)

Uzan, S; Beaufils, M; Uzan, M; Donsimoni, R; Mareck, A; Salat-Baroux, J; Sureau, C

1988-02-01

An increased maternal plasma volume (PV) is a characteristic phenomenon of normal pregnancy, which may be related to a physiological decrease of peripheral resistances. The authors have studied the plasma volume of 1,105 patients distributed as follows: normal (387), permanently hypertensive patients (84), hypertensive patients during pregnancy (390), patients with apparently isolated RCIU (154) or with a pathological past-history during previous pregnancies (90). It appears that the PV is a sign of a severe HBP, and presents a rather early and good predictive value regarding the weight of the fetus and some complications such as severe UCIU and fetal death in utero. In case of pathological past events or pre-existing hypertension, the PV enables to differentiate rather well patients who will be prone to a complicated pregnancy. In view of these results, utilization and interpretation criteria of this parameter during pregnancies with hypertension or pregnancies in which there is a suspicion or a risk of intra-uterine growth delay, are defined.

Accumulation of pro-cancer cytokines in the plasma fraction of stored packed red cells.

Science.gov (United States)

Benson, Douglas D; Beck, Adam W; Burdine, Marie S; Brekken, Rolf; Silliman, Christopher C; Barnett, Carlton C

2012-03-01

Perioperative blood transfusion has been linked to decreased survival in pancreatic cancer; however, the exact causal mechanism has not been elucidated. Allogeneic transfusions are known to expose patients to foreign cells and lipid mediators. We hypothesize that stored packed red cells (pRBCs) contain pro-cancer cytokines that augment tumor progression. We analyzed the plasma fraction of stored pRBCs for pro-cancer cytokines and evaluated the affect of both storage time and leukocyte reduction on these mediators. Chemiarray™ analysis for pro-cancer cytokines was performed on the acellular plasma fraction of stored leukocyte-reduced (LR) and non-leukocyte-reduced (NLR) pRBCs at day 1 (D.1-fresh) and day 42 (D.42-outdate) of storage. Elevated expression of monocyte chemotactic protein-1 (MCP-1), regulated on activation, normal T cell expressed and secreted (RANTES), angiogenin, tumor necrosis factor-alpha (TNF-α), epidermal growth factor (EGF), and platelet-derived growth factor (PDGF) was found. Specific enzyme-linked immunosorbent assay was performed for each of these factors in LR and NLR blood at D.1, day 28, and D.42. Data were analyzed by ANOVA. A p value ≤ 0.05 was considered significant; N ≥ 4 per group. Migration assays were performed using inhibitors of EGF (gefitinib) and PDGF (imatinib) on murine pancreatic adenocarcinoma cells (Pan02) exposed to D.1 and D.42 LR and NLR plasma. Proliferation assays were performed on Pan02 cells to test the inhibition of PDGF. MCP-1 levels increased with storage time in LR blood, 86.3 ± 6.3 pg/ml at D.1 vs. 121.2 ± 6.1 pg/ml at D.42 (p = 0.007), and NLR blood, 78.2 ± 7.3 pg/ml at D.1 vs. 647.8 ± 220.7 pg/ml at D.42 (p = 0.02). RANTES levels are lower in LR compared to NLR stored blood, 3.0 ± 1.9 vs. 15.8 ± 0.7 pg/ml at D.42 (p Pro-cancer cytokines that can augment tumor progression were identified in pRBCs. Some of these factors are present in fresh blood. The soluble factors identified herein may represent

Characterization of plasma cytokines in an infant population cohort of challenge-proven food allergy.

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Dang, T D; Tang, M L K; Koplin, J J; Licciardi, P V; Eckert, J K; Tan, T; Gurrin, L C; Ponsonby, A-L; Dharmage, S C; Allen, K J

2013-10-01

Sensitization to food allergens indicates the production of food-specific IgE; however, sensitization is not a definite indicator of allergic reaction upon ingestion (N Engl J Med, 344, 2001, 30: J Allergy Clin Immunol, 120, 2007, 491). Currently, food challenge is the best approach to identify the presence or absence of allergy. While 95% positive predictive values (PPVs) thresholds for sIgE can assist with identifying increased likelihood of allergy among those who are sensitized, there are no specific biological markers that differentiate between allergic and sensitized individuals. To determine whether plasma serum cytokine profiles predict (i) sensitization to peanut and egg and (ii) food allergy among sensitized infants. Peanut-sensitized (PT) and egg-sensitized 14-month-old infants and nonsensitized controls enrolled in HealthNuts, a population-based study of food allergy, underwent an oral food challenge (OFC). Blood was collected within 1 h after OFC. Serum levels of Th1, Th2 and regulatory cytokines were determined in allergic (n = 79), sensitized (n = 40) and nonsensitized, nonallergic (n = 37) infants by multiplex assay. Food-sensitized infants had significantly higher plasma IL-4, IL-13, IL-12p70 and lower IL-10 levels compared to nonsensitized infants. IL-10 and IL-6 levels were significantly higher in sensitized compared with allergic infants. Egg-allergic infants had significantly higher IL-13 and IL-12p70 levels compared to peanut-allergic (PA) infants. Levels of Th2-related cytokines in plasma are higher in food-sensitized infants, irrespective of clinical food allergy status. In contrast, IL-10 levels appear to predict food allergy among sensitized infants. Differences in IL-13 and IL-12p70 between egg- and peanut-allergic infants could help explain the different resolution rates of the allergies. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Neonatal plasma polarizes TLR4-mediated cytokine responses towards low IL-12p70 and high IL-10 production via distinct factors.

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Mirjam E Belderbos

Full Text Available Human neonates are highly susceptible to infection, which may be due in part to impaired innate immune function. Neonatal Toll-like receptor (TLR responses are biased against the generation of pro-inflammatory/Th1-polarizing cytokines, yet the underlying mechanisms are incompletely defined. Here, we demonstrate that neonatal plasma polarizes TLR4-mediated cytokine production. When exposed to cord blood plasma, mononuclear cells (MCs produced significantly lower TLR4-mediated IL-12p70 and higher IL-10 compared to MC exposed to adult plasma. Suppression by neonatal plasma of TLR4-mediated IL-12p70 production, but not induction of TLR4-mediated IL-10 production, was maintained up to the age of 1 month. Cord blood plasma conferred a similar pattern of MC cytokine responses to TLR3 and TLR8 agonists, demonstrating activity towards both MyD88-dependent and MyD88-independent agonists. The factor causing increased TLR4-mediated IL-10 production by cord blood plasma was heat-labile, lost after protein depletion and independent of lipoprotein binding protein (LBP or soluble CD14 (sCD14. The factor causing inhibition of TLR4-mediated IL-12p70 production by cord blood plasma was resistant to heat inactivation or protein depletion and was independent of IL-10, vitamin D and prostaglandin E2. In conclusion, human neonatal plasma contains at least two distinct factors that suppress TLR4-mediated IL-12p70 production or induce IL-10 or production. Further identification of these factors will provide insight into the ontogeny of innate immune development and might identify novel targets for the prevention and treatment of neonatal infection.

Neonatal Plasma Polarizes TLR4-Mediated Cytokine Responses towards Low IL-12p70 and High IL-10 Production via Distinct Factors

Science.gov (United States)

Belderbos, Mirjam E.; Levy, Ofer; Stalpers, Femke; Kimpen, Jan L.; Meyaard, Linde; Bont, Louis

2012-01-01

Human neonates are highly susceptible to infection, which may be due in part to impaired innate immune function. Neonatal Toll-like receptor (TLR) responses are biased against the generation of pro-inflammatory/Th1-polarizing cytokines, yet the underlying mechanisms are incompletely defined. Here, we demonstrate that neonatal plasma polarizes TLR4-mediated cytokine production. When exposed to cord blood plasma, mononuclear cells (MCs) produced significantly lower TLR4-mediated IL-12p70 and higher IL-10 compared to MC exposed to adult plasma. Suppression by neonatal plasma of TLR4-mediated IL-12p70 production, but not induction of TLR4-mediated IL-10 production, was maintained up to the age of 1 month. Cord blood plasma conferred a similar pattern of MC cytokine responses to TLR3 and TLR8 agonists, demonstrating activity towards both MyD88-dependent and MyD88-independent agonists. The factor causing increased TLR4-mediated IL-10 production by cord blood plasma was heat-labile, lost after protein depletion and independent of lipoprotein binding protein (LBP) or soluble CD14 (sCD14). The factor causing inhibition of TLR4-mediated IL-12p70 production by cord blood plasma was resistant to heat inactivation or protein depletion and was independent of IL-10, vitamin D and prostaglandin E2. In conclusion, human neonatal plasma contains at least two distinct factors that suppress TLR4-mediated IL-12p70 production or induce IL-10 or production. Further identification of these factors will provide insight into the ontogeny of innate immune development and might identify novel targets for the prevention and treatment of neonatal infection. PMID:22442690

Plasma cytokine IL-6 levels and subjective cognitive decline: preliminary findings.

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Keegan, Andrew P; Paris, Daniel; Luis, Cheryl A; Abdullah, Laila; Ait-Ghezala, Ghania; Beaulieu-Abdelahad, David; Pryor, Makenzie; Chaykin, Jillian; Crynen, Gogce; Crawford, Fiona; Mullan, Michael

2018-02-01

Detection of Alzheimer's disease (AD) prior to clinical inception will be paramount for introducing disease modifying treatments. We have begun collecting baseline characteristics of a community cohort for longitudinal assessment and testing of antecedent blood-based biomarkers. We describe the baseline visit from the first 131 subjects in relationship to a commonly described cytokine, interleukin 6 (IL-6). Subjects from the community presented for a free memory screening with varying degrees of memory concern. We quantified the baseline plasma levels of the cytokine IL-6 and assessed cognition (Montreal Cognitive Assessment, MoCA) and mood (Geriatric Depression Scale, GDS) in relationship to their memory concern. Baseline MoCA scores were inversely related to age, and this association was influenced by an AD risk factor, Apolipoprotein E (APOE4) carrier status. The degree of subjective cognitive decline correlated with GDS and was inversely related to MoCA scores. Interleukin 6 levels were related to age, body mass index, and years of education. It will be important to assess how these baseline IL-6 levels and forthcoming novel biomarkers relate to future cognitive decline. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Reliable test for prenatal prediction of fetal RhD type using maternal plasma from RhD negative women

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Clausen, Frederik Banch; Krog, Grethe Risum; Rieneck, Klaus

2005-01-01

The objective of this study was to establish a reliable test for prenatal prediction of fetal RhD type using maternal plasma from RhD negative women. This test is needed for future prenatal Rh prophylaxis.......The objective of this study was to establish a reliable test for prenatal prediction of fetal RhD type using maternal plasma from RhD negative women. This test is needed for future prenatal Rh prophylaxis....

An evaluation of multiplex bead-based analysis of cytokines and soluble proteins in archived lithium heparin plasma, EDTA plasma and serum samples

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Brøndum, Line; Sørensen, Brita Singers; Eriksen, Jesper Grau

2016-01-01

-13, and VEGF, LH plasma levels vs. EDTA plasma: IL-2 and IL-4. CONCLUSION: Stored serum, LH plasma, and EDTA plasma from clinical trials can be used for analysis of circulating cytokines and proteins. Variations in measurements occur, but are within reasonable ranges. The optimal type of media...... in plasma and serum from 86 head and neck cancer patients and 33 controls were evaluated: EGFR, leptin, OPN, VEGFR-1, VEGFR-2, IL-2, IL-13, PDGF-bb, TNF, PAI-1, SDF-1a, IL-4, IL-6, IL-8, eotaxin, G-CSF, VEGF, GRO-a, and HGF. RESULTS: The correlation between measurements of the same samples analyzed...... on different dates was reasonable. However, samples run on different dates could exhibit different absolute values. The 75th percentile of the fold differences for samples run on different dates was 2.2. No significant difference was found between one and four freeze-thaw cycles (except for HGF...

Development of a PCR/LDR/capillary electrophoresis assay with potential for the detection of a beta-thalassemia fetal mutation in maternal plasma.

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Yi, Ping; Chen, Zhuqin; Yu, Lili; Zheng, Yingru; Liu, Guodong; Xie, Haichang; Zhou, Yuanguo; Zheng, Xiuhui; Han, Jian; Li, Li

2010-08-01

Analysis of fetal DNA in maternal plasma has recently been introduced for non-invasive prenatal diagnosis. We have now investigated the feasibility of polymerase chain reaction (PCR)/ligase detection reaction (LDR)/capillary electrophoresis for the detection of fetal point mutations, such as the beta-thalassemia mutation, IVS2 654(C --> T), in maternal plasma DNA. The sensitivity of LDR/capillary electrophoresis was examined by quantifying the mutant PCR products in the presence of a vast excess of non-mutant competitor template, a situation that mimics the detection of rare fetal mutations in the presence of excess maternal DNA. PCR/LDR/capillary electrophoresis was applied to detect the mutation, IVS2 654(C --> T), in an experimental model at different sensitivity levels and from 10 maternal plasma samples. Our results demonstrated that this approach to detect a low abundance IVS2 654(C --> T) mutation achieved a sensitivity of approximately 1:10,000. The approach was applied to maternal plasma DNA to detect the paternally inherited fetal IVS2 654(C --> T) mutation, and the results were equivalent to those obtained by PCR/reverse dot blot of amniotic fluid cell DNA. PCR/LDR/capillary electrophoresis has a very high sensitivity that can distinguish low abundance single nucleotide differences and can detect paternally inherited fetal point mutations in maternal plasma.

Effect of aspirin desensitization on T-cell cytokines and plasma lipoxins in aspirin-exacerbated respiratory disease.

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Aksu, Kurtuluş; Kurt, Emel; Alatas, Özkan; Gülbas, Zafer

2014-01-01

The pathogenesis of aspirin-exacerbated respiratory disease (AERD) is thought to be based on, mainly, overproduction of eicosanoid lipid mediators and on defective anti-inflammatory regulators. Aspirin desensitization treatment, the mainstay of controlling asthma and rhinitis in AERD patients, however, is the least understood aspect of the disease. The study was designed to determine the effect of aspirin desensitization on T-lymphocyte cytokine expression and on plasma lipoxin levels in AERD. Spirometry, skin-prick test and asthma control test were documented and intracellular cytokine expression in T lymphocytes and plasma lipoxin levels were measured in 23 AERD patients, 17 aspirin-tolerant asthmatic (ATA) patients, and 16 healthy controls. In the AERD group nasal symptom and smell scores were assessed. Of the 23 AERD patients 15 accepted to undergo aspirin desensitization protocol and 14 of them were desensitized successfully. In the desensitized AERD group, cytokine and lipoxin measurements were repeated after 1-month aspirin treatment. CD4(+) IL-10 levels were higher in AERD patients than in healthy controls and CD4(+) interferon (IFN) gamma levels were higher in AERD and ATA patients than in controls. Plasma lipoxin-A4 and 15-epi-lipoxin-A4 levels were similar among the three study groups. In the AERD group, subjects underwent aspirin desensitization followed by a 1-month aspirin treatment. Clinical parameters improved and CD4(+) IFN-gamma levels decreased significantly. No significant change in lipoxin levels was recorded. CD4(+) IFN-gamma and CD4(+) IL-10 levels in AERD patients after 1-month aspirin desensitization treatment were similar to the healthy controls. The study confirms aspirin desensitization is effective clinically in AERD patients and suggests that IFN gamma and IL-10 expression in CD4(+) T lymphocytes may be related to the mechanism of action.

Common studied polymorphisms do not affect plasma cytokine levels upon endotoxin exposure in humans

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Taudorf, Sarah; Krabbe, K.S.; Berg, R.M.

2008-01-01

The aim of this study was to investigate to what extent single nucleotide polymorphisms (SNPs) in promoter regions of genes of Toll-like receptor (TLR)-4, tumour necrosis factor (TNF)-alpha, interleukin (IL)-18, interferon (IFN)-gamma, IL-6 and IL-10 affect the cytokine response during a controlled......-607, IFN-gamma+874, IL-6-174, IL-10-592 and IL-10-1082) and endotoxin-induced changes in plasma levels of TNF-alpha, IL-6 and IL-10. IL-18 levels were unaffected by endotoxin. In conclusion, the investigated SNPs did not affect endotoxin-induced low-grade cytokine production of TNF-alpha, IL-6, IL-18 or IL......-10 in healthy young men. Previous reports of a major heritability factor in the inflammatory response may be due to other target genes or effects in older age groups or women Udgivelsesdato: 2008/4...

Polybrominated diphenyl ethers in paired samples of maternal and umbilical cord blood plasma and associations with house dust in a Danish cohort

DEFF Research Database (Denmark)

Frederiksen, Marie; Thomsen, Cathrine; Frøshaug, May

2010-01-01

determined in placental tissue from the same individuals, and the relationship with the external exposure from house dust from the participants' homes was explored. Samples of maternal and umbilical cord plasma from a cohort of 51 pregnant women from the Copenhagen area were collected. Paired maternal...... and umbilical cord plasma were analysed for BDE-28, 37, 47, 85, 99, 100, 119, 138, 153, 154, 183, 209 and the brominated biphenyl BB-153 using automated SPE extraction and GC-HRMS for the tri- to hepta-BDEs and GC-LRMS (ECNI) for BDE-209. PBDEs were detected in all maternal and umbilical cord plasma samples...

Studies on the postnatal development of the rat liver plasma membrane following maternal ethanol ingestion

Energy Technology Data Exchange (ETDEWEB)

Rovinski, B

1984-01-01

Studies on the developing rat liver and on the structure and function of the postnatal rat liver plasma membrane were carried out following maternal consumption of alcohol during pregnancy and lactation. A developmental study of alcohol dehydrogenase (ADH) indicated that both the activity and certain kinetic properties of the enzyme from the progeny of alcohol-fed and pair-fed mothers were similar. Fatty liver, however, developed in the alcoholic progeny only after ADH appeared on a day 19 of gestation. Further studies on structural and functional changes were then undertaken on the postnatal development of the rat liver plasma membrane. Radioligand binding studies performed using the hapatic alpha{sub 1}-adrenergic receptor as a plasma membrane probe demonstrated a significant decrease in receptor density in the alcoholic progeny, but no changes in binding affinity. Finally, the fatty acid composition of constituent phospholipids and the cholesterol content of rat liver plasma membranes were determined. All these observations suggest that membrane alterations in the newborn may be partially responsible for the deleterious action(s) of maternal alcoholism at the molecular level.

Eicosanoid and cytokine levels in plasma of patients during mesenteric infarction

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N. Nathan

1997-01-01

Full Text Available Multible organ failure (MOF induced by mesenteric infarction is associated with a high mortality rate. This study reports eicosanoid and cytokine levels in the blood of three atherosclerotic patients who ultimately died from MOF induced by mesenteric infarction. High plasma levels of 6- keto-prostaglandin (PG F1α (the stable metabolite of PGI2, interleukin (IL-6 and IL-8 are observed whereas plasma tumour necrosis factor alpha (TNFα, TxB2 (the stable metabolite of TxA2, PGE2, leukotrienes (LTB4 and LTC4, and whole blood platelet-activating factor levels are not different from values obtained in similarly severe atherosclerotic patients. This short report questioned the clinical involvement of TNFα during such a pathology where a persistent translocation of endotoxin has been observed through the gut endothelial barrier. Activation of phospholipase A2 is suggested by the increase in the stable metabolite of PGI2 and might be by itself or through lipidic metabolites, a major systemic stimulus of IL-6 and IL-8 production.

Effects of taurine supplementation on hepatic markers of inflammation and lipid metabolism in mothers and offspring in the setting of maternal obesity.

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Li, Minglan; Reynolds, Clare M; Sloboda, Deborah M; Gray, Clint; Vickers, Mark H

2013-01-01

Maternal obesity is associated with obesity and metabolic disorders in offspring. However, intervention strategies to reverse or ameliorate the effects of maternal obesity on offspring health are limited. Following maternal undernutrition, taurine supplementation can improve outcomes in offspring, possibly via effects on glucose homeostasis and insulin secretion. The effects of taurine in mediating inflammatory processes as a protective mechanism has not been investigated. Further, the efficacy of taurine supplementation in the setting of maternal obesity is not known. Using a model of maternal obesity, we examined the effects of maternal taurine supplementation on outcomes related to inflammation and lipid metabolism in mothers and neonates. Time-mated Wistar rats were randomised to either: 1) control : control diet during pregnancy and lactation (CON); 2) CON supplemented with 1.5% taurine in drinking water (CT); 3) maternal obesogenic diet (high fat, high fructose) during pregnancy and lactation (MO); or 4) MO supplemented with taurine (MOT). Maternal and neonatal weights, plasma cytokines and hepatic gene expression were analysed. A MO diet resulted in maternal hyperinsulinemia and hyperleptinemia and increased plasma glucose, glutamate and TNF-α concentrations. Taurine normalised maternal plasma TNF-α and glutamate concentrations in MOT animals. Both MO and MOT mothers displayed evidence of fatty liver accompanied by alterations in key markers of hepatic lipid metabolism. MO neonates displayed a pro-inflammatory hepatic profile which was partially rescued in MOT offspring. Conversely, a pro-inflammatory phenotype was observed in MOT mothers suggesting a possible maternal trade-off to protect the neonate. Despite protective effects of taurine in MOT offspring, neonatal mortality was increased in CT neonates, indicating possible adverse effects of taurine in the setting of normal pregnancy. These data suggest that maternal taurine supplementation may

Novel methods of cytokine detection: Real-time PCR, ELISPOT, and intracellular cytokine staining

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Eliza Turlej

2009-05-01

Full Text Available Cytokines are small hormone-like proteins that play important roles in immune system control. Cytokines regulate the proliferation and differentiation of cells and hematopoiesis and act as mediators in the inflammatory reaction. Changes in cytokine levels are found in many diseases, such as sepsis, bowel inflammatory disease, autoimmune diseases, as well as graft-versus-host disease. Cytokines levels can be detected using in vivo, in vitro, and ex vivo techniques. The level of cytokine produced can be measured by immunoenzymatic test (ELISA in supernatant after cell culture with the addition of stimulant and in plasma by techniques that measure the level of cytokine secretion in cells (e.g. immunohistochemical staining, ELISPOT, and intracellular cytokine staining, and by molecular biological methods (RPA, real-time PCR, in situ hybridization, and Northern blot. Detection of cytokine mRNA in tissues is useful in the direct determination of heterogenic populations of cytokine-producing cells. Nowadays the most frequently used methods for measuring cytokine level are ELISPOT, intracellular cytokine staining with flow cytometry detection, and real-time PCR. These methods have an important clinical role in vaccine efficacy, in viral, bacterial, and verminous diagnostics, and in determining the efficacy of cancer treatment.

Multiplex Immunoassay of Plasma Cytokine Levels in Men with Alcoholism and the Relationship to Psychiatric Assessments.

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Manzardo, Ann M; Poje, Albert B; Penick, Elizabeth C; Butler, Merlin G

2016-03-29

Chronic alcohol use alters adaptive immunity and cytokine activity influencing immunological and hormone responses, inflammation, and wound healing. Brain cytokine disturbances may impact neurological function, mood, cognition and traits related to alcoholism including impulsiveness. We examined the relationship between plasma cytokine levels and self-rated psychiatric symptoms in 40 adult males (mean age 51 ± 6 years; range 33-58 years) with current alcohol dependence and 30 control males (mean age 48 ± 6 years; range 40-58 years) with no history of alcoholism using multiplex sandwich immunoassays with the Luminex magnetic-bead based platform. Log-transformed cytokine levels were analyzed for their relationship with the Symptom Checklist-90R (SCL-90R), Barratt Impulsivity Scales (BIS) and Alcoholism Severity Scale (ASS). Inflammatory cytokines (interferon γ-induced protein-10 (IP-10); monocyte chemoattractant protein-1 (MCP1); regulated on activation, normal T cell expressed and secreted (RANTES)) were significantly elevated in alcoholism compared to controls while bone marrow-derived hematopoietic cytokines and chemokines (granulocyte-colony stimulating factor (GCSF); soluble CD40 ligand (sCD40L); growth-related oncogene (GRO)) were significantly reduced. GRO and RANTES levels were positively correlated with BIS scales; and macrophage-derived chemokine (MDC) levels were positively correlated with SCL-90R scale scores (p alcoholism may influence brain function leading to increased impulsiveness and/or phobia. The novel association between RANTES and GRO and impulsivity phenotype in alcoholism should be further investigated in alcoholism and psychiatric conditions with core impulsivity and anxiety phenotypes lending support for therapeutic intervention.

Effects of environmental stress during pregnancy on maternal and fetal plasma corticosterone and progesterone in the rat

International Nuclear Information System (INIS)

Fleming, D.E.; Rhees, R.W.; Williams, S.R.; Kurth, S.M.

1986-01-01

Prenatal stress applied during a presumed critical period (third trimester) for sexual differentiation of the brain has been shown to alter development and influence sexual behavior. This experiment was designed to study the effects of environmental stress (restraint/illumination/heat) on maternal and fetal plasma corticosterone and progesterone titers. These hormones were studied since corticosterone has been shown to alter brain differentiation and progesterone has anti-androgen properties and since the secretion of both from the adrenal cortex is stimulated by ACTH. Plasma corticosterone and progesterone titers of both stressed and control gravid rats and their fetuses were measured on gestational days 18 and 20 by radioimmunoassay. Prenatal stress significantly reduced fetal body weight and fetal adrenal weight. Maternal pituitary weight was significantly increased. Prenatal stress caused a significant elevation in maternal corticosterone and progesterone titers and in fetal corticosterone titers. There was no difference between prenatal stressed and control fetal plasma progesterone levels. These data demonstrate that environmental stress significantly increases adrenal activity beyond that brought about naturally by pregnancy, and therefore may modify sequential hormonal events during fetal development

Analysis of cytokine profile and growth factors in platelet-rich plasma obtained by open systems and commercial columns.

Science.gov (United States)

Pochini, Alberto de Castro; Antonioli, Eliane; Bucci, Daniella Zanetti; Sardinha, Luiz Roberto; Andreoli, Carlos Vicente; Ferretti, Mario; Ejnisman, Benno; Goldberg, Anna Carla; Cohen, Moisés

2016-01-01

To evaluate growth factors and cytokines in samples of platelet-rich plasma obtained by three different centrifugation methods. Peripheral blood of six individuals with no hematological diseases, aged 18 to 68 years, was drawn to obtain platelet-rich plasma, using the open method and commercial columns by Medtronic and Biomet. The products obtained with the different types of centrifugation were submitted to laboratory analysis, including pro-inflammatory cytokines and chemokines by flow cytometry assays, the concentration of fibroblast growth factors-2 (FGF-2) and transforming growth factor-beta1 (TGF-β1). The diverse separation methods generated systematically different profiles regarding number of platelets and leukocytes. The Medtronic system yielded a product with the highest concentration of platelets, and the open method, with the lowest concentration of platelets. The results of cytokine analysis showed that the different types of centrifugation yielded products with high concentrations of interleukin 8, interleukin 1β. The open system resulted in a product with high levels of interleukin 6. Other cytokines and chemokines measured were similar between systems. The product obtained with the open method showed higher levels of TGF-β1 in relation to other systems and low FGF-2 levels. The formed elements, growth factors and cytokines in samples of platelet-rich plasma varied according to the centrifugation technique used. Avaliar fatores de crescimento e citocinas em amostras de plasma rico em plaquetas obtidas por três diferentes métodos de centrifugação. Foi coletado sangue periférico de seis indivíduos, sem doença hematológica, com idades entre 18 e 68 anos, para obtenção de plasma rico em plaquetas, utilizando o método aberto e sistemas comerciais das empresas Medtronic e Biomet. Os produtos obtidos com os diferentes tipos de centrifugação foram submetidos às análises laboratoriais, incluindo citocinas próinflamatórias e quimiocinas

Plasma cytokines eotaxin, MIP-1α, MCP-4, and vascular endothelial growth factor in acute lower respiratory tract infection

DEFF Research Database (Denmark)

Relster, Mette Marie; Holm, Anette; Pedersen, Court

2017-01-01

), monocyte chemoattractant protein 4 (MCP-4), and vascular endothelial growth factor (VEGF) in 40 patients hospitalized with acute lower respiratory tract infections (LRTI). The cytokines contribute to the pathogenesis of several inflammatory respiratory diseases, indicating a potential as markers for LRTI....... Patients were stratified according to etiology and severity of LRTI, based on baseline C-reactive protein and CURB-65 scores. Using a multiplex immunoassay of plasma, levels of eotaxin and MCP-4 were shown to increase from baseline until day 6 after admission to hospital. The four cytokines were unable...

Effect of Maternal Smoking on Plasma and Urinary Measures of Vitamin E Isoforms in the First Month after Extreme Preterm Birth.

Science.gov (United States)

Stone, Cosby; Qiu, Yunping; Kurland, Irwin J; Slaughter, James C; Moore, Paul; Cook-Mills, Joan; Hartert, Tina; Aschner, Judy L

2018-06-01

We examined the effect of maternal smoking on plasma and urinary levels of vitamin E isoforms in preterm infants. Maternal smoking during pregnancy decreased infant plasma alpha- and gamma-tocopherol concentrations at 1 week and 4 weeks, with 45% of infants of smokers deficient in alpha-tocopherol at 1 month after birth. Copyright © 2017 Elsevier Inc. All rights reserved.

Differences in plasma cytokine levels between elite kayakers and nonathletes.

Science.gov (United States)

Borges, G F; Rama, L; Pedreiro, S; Alves, F; Santos, A; Massart, A; Paiva, A; Teixeira, A M

2013-01-01

Regular moderate exercise has been shown to have anti-inflammatory effects that help prevent several chronic diseases. However, the effects of chronic training an elite athletes have not been the focus of much research. This study aimed to determine whether there were differences in cytokine levels (IL-1 β , IL-1ra, IL-6, IL-10, IL-18, IFN- γ , and TNF- α ) in circulating peripheral blood (PB) between elite kayakers and nonathletes. Subjects were 13 elite male kayakers, aged 20.0 ± 3 years, with average body mass of 75.0 ± 7.9 kg and 177.3 ± 7.1 cm height and with a VO2max of 58.3 ± 7.8 mL·kg(-1)·min(-1). The nonathletes were 7 men, aged 18.2 ± 1.1 years, body mass of 81.3 ± 13.8 kg, and 171.9 ± 4.5 cm height. Blood samples were collected after six weeks of offtraining and before the start of a new training season. PB leukocyte populations were determined by flow cytometry. Cytokine levels were quantified by ELISA. When nonathletes were compared with the kayakers, the latter exhibited lower plasma concentrations of IL-1 β , IL-18, and IFN- γ as well as a lower concentration of IL-1ra. Positive correlations between IL-18 and B cells in the athletes were also found. These results seem to reinforce the anti-inflammatory role of regular training.

Effects of maternal protein or energy restriction during late gestation on immune status and responses to lipopolysaccharide challenge in postnatal young goats.

Science.gov (United States)

He, Z X; Sun, Z H; Yang, W Z; Beauchemin, K A; Tang, S X; Zhou, C S; Han, X F; Wang, M; Kang, J H; Tan, Z L

2014-11-01

Knowledge of maternal malnutrition of ruminants and effects on development of the immune system of their offspring is lacking. A study was conducted to investigate the effects of maternal protein or energy restriction during late gestation on immune status of their offspring at different ages. Sixty-three pregnant goats (local breed, Liuyang black goat, 22.2 ± 1.5 kg at d 90 of gestation) were fed control (CON, ME = 9.34 MJ/kg and CP = 12.5%, DM basis), 40% protein restricted (PR), or 40% energy restricted (ER) diets from d 91 of gestation to parturition, after which all animals received an adequate diet for nutritional recovery. Plasma concentrations of complement components (C3, C4), C-reactive protein (CRP) and immunoglobulins (IgG and IgM), jejunum cytokines (IL-2, IL-6, and IL-10) expression levels and morphology in the offspring were measured. Additionally, plasma concentration of complement and IL-6, and cytokines expression levels in gastrointestinal tract obtained at 6 wk from young goats were assessed under saline or lipopolysaccharide (LPS) challenging conditions. Maternal PR or ER decreased (P 0.05) plasma CRP concentration. The IL-10 mRNA expression of jejunum from PR kids was also less (P 0.05) in any plasma or tissue immune parameters among the 3 treatments. However, when given a LPS challenge, ER and PR kids had greater (P = 0.02) IL-6 concentration compared with CON kids. Our results suggest that both PR and ER during late gestation induced short-term as well as long-lasting alterations on immune responses in their offspring, which may make the animals more susceptible to a bacterial pathogen challenge. The present findings expand the existing knowledge in immunological mechanisms responsible for the development of disease in later life.

Maternal plasma levels of cell-free β-HCG mRNA as a prenatal diagnostic indicator of placenta accrete.

Science.gov (United States)

Zhou, J; Li, J; Yan, P; Ye, Y H; Peng, W; Wang, S; Wang, X Tong

2014-09-01

Several biomarkers, including maternal serum creatinine kinase and α-fetoprotein, have been described as potential tools for the diagnosis of placental abnormalities. This study aimed to determine whether maternal plasma mRNA levels of the β subunit of human chorionic gonadotropin (β-HCG) could predict placenta accreta prenatally. Sixty-eight singleton pregnant women with prior cesarean deliveries (CDs) were classified into three groups: normal placentation (35 women, control group); placenta previa alone (21 women, placenta previa group); and both placenta previa and placenta accreta (12 women, placenta previa/accreta group). Maternal plasma concentrations of cell-free β-HCG mRNA were measured by real-time reverse-transcription polymerase chain reaction and were expressed as multiples of the median (MoM). Cell-free β-HCG mRNA concentrations (MoM, range) were significantly higher in women with placenta accreta (3.65, 2.78-7.19) than in women with placenta previa (0.94, 0.00-2.97) or normal placentation (1.00, 0.00-2.69) (Steel-Dwass test, P accreta group, the concentration of cell-free β-HCG mRNA was significantly higher among women who underwent CDs with hysterectomy (4.41, 3.49-7.19) than among women whose CDs did not result in hysterectomy (3.20, 2.78-3.70) (Mann-Whitney U test, P = 0.012). An increased level of cell-free β-HCG mRNA in the maternal plasma of women with placenta accreta may arise from direct uteroplacental transfer of cell-free placental mRNA molecules. The concentration of cell-free β-HCG mRNA in maternal plasma may be applicable to the prenatal diagnosis of placenta accreta, especially to identify women with placenta accreta likely to require hysterectomy. Copyright © 2014 Elsevier Ltd. All rights reserved.

Creatine supplementation reduces plasma levels of pro-inflammatory cytokines and PGE2 after a half-ironman competition.

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Bassit, R A; Curi, R; Costa Rosa, L F B P

2008-08-01

The effect of creatine supplementation upon plasma levels of pro-inflammatory cytokines: Interleukin (IL) 1 beta and IL-6, Tumor Necrosis Factor alpha (TNFalpha), and Interferon alpha (INF alpha) and Prostaglandin E(2) (PGE(2)) after a half-ironman competition were investigated. Eleven triathletes, each with at least three years experience of participation in this sport were randomly divided between the control and experimental groups. During 5 days prior to competition, the control group (n = 6) was supplemented with carbohydrate (20 g x d(-1)) whereas the experimental group (n = 5) received creatine (20 g x d(-1)) in a double-blind trial. Blood samples were collected 48 h before and 24 and 48 h after competition and were used for the measurement of cytokines and PGE(2). Forty-eight hours prior to competition there was no difference between groups in the plasma concentrations (pg x ml(-1), mean +/- SEM) of IL-6 (7.08 +/- 0.63), TNFalpha (76.50 +/- 5.60), INF alpha (18.32 +/- 1.20), IL-1 beta (23.42 +/- 5.52), and PGE(2) (39.71 +/- 3.8). Twenty-four and 48 h after competition plasma levels of TNFalpha, INF alpha, IL-1 beta and PGE(2) were significantly increased (P long distance triathlon competition may reduce the inflammatory response induced by this form of strenuous of exercise.

Polybrominated diphenyl ethers (PBDEs) in maternal and cord blood plasma of several northern Canadian populations

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Ryan, J.J. [Bureau Chemical Safety, Health Canada, Ottawa (Canada); Oostdam, J. van [Management Toxic Substances Div., Health Canada, Ottawa (Canada)

2004-09-15

The Northern Contaminants Program (NCP) funded by Indian and Northern Affairs Canada has carried out a number of baseline studies in Nunavut and the North West Territories of northern Canada (figure 1) to assess the exposure of indigenous peoples to a variety of chemical classes including POPs and metals. These studies, summarized by Walker et al, have used both maternal and cord human blood plasma as the media from sampling which took place in four phases over the years 1994-1999. Small amounts of individual blood plasma have remained from these investigations. We combined these individual samples into 23 composite samples of maternal and cord blood based mainly on the region and ethnicity of the donors. These composites have been used to study the exposure of northern peoples to PBDEs and to estimate, where possible, the influence of ethnicity, region of collection, and time on such exposure. Comparison is also made between the levels in plasma from northern populations and in human milk from those inhabiting the more numerous south.

Plasma concentrations and placental immunostaining of interleukin-10 and tumornecrosis factor-α as predictors of alterations in the embryo-fetal organism and the placental development of diabetic rats

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Y.K. Sinzato

2011-03-01

Full Text Available Interleukin-10 (IL-10 appears to be the key cytokine for the maintenance of pregnancy and inhibits the secretion of inflammatory cytokines such as tumor necrosis factor-α (TNF-α. However, there are no studies evaluating the profile of these cytokines in diabetic rat models. Thus, our aim was to analyze IL-10 and TNF-α immunostaining in placental tissue and their respective concentrations in maternal plasma during pregnancy in diabetic rats in order to determine whether these cytokines can be used as predictors of alterations in the embryo-fetal organism and in placental development. These parameters were evaluated in non-diabetic (control; N = 15 and Wistar rats with streptozotocin (STZ-induced diabetes (N = 15. At term, the dams (100 days of life were killed under anesthesia and plasma and placental samples were collected for IL-10 and TNF-α determinations by ELISA and immunohistochemistry, respectively. The reproductive performance was analyzed. Plasma IL-10 concentrations were reduced in STZ rats compared to controls (7.6 ± 4.5 vs 20.9 ± 8.1 pg/mL. The placental scores of immunostaining intensity did not differ between groups (P > 0.05. Prevalence analysis showed that the IL-10 expression followed TNF-α expression, showing a balance between them. STZ rats also presented impaired reproductive performance and reduced plasma IL-10 levels related to damage during early embryonic development. However, the increased placental IL-10 as a compensatory mechanism for the deficit of maternal regulation permitted embryo development. Therefore, the data suggest that IL-10 can be used as a predictor of changes in the embryo-fetal organism and in placental development in pregnant diabetic rats.

Differences in Plasma Cytokine Levels between Elite Kayakers and Nonathletes

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G. F. Borges

2013-01-01

Full Text Available Regular moderate exercise has been shown to have anti-inflammatory effects that help prevent several chronic diseases. However, the effects of chronic training an elite athletes have not been the focus of much research. This study aimed to determine whether there were differences in cytokine levels (IL-1β, IL-1ra, IL-6, IL-10, IL-18, IFN-γ, and TNF-α in circulating peripheral blood (PB between elite kayakers and nonathletes. Subjects were 13 elite male kayakers, aged 20.0±3 years, with average body mass of 75.0±7.9 kg and 177.3±7.1 cm height and with a VO2max of 58.3±7.8 mL·kg−1·min−1. The nonathletes were 7 men, aged 18.2±1.1 years, body mass of 81.3±13.8 kg, and 171.9±4.5 cm height. Blood samples were collected after six weeks of offtraining and before the start of a new training season. PB leukocyte populations were determined by flow cytometry. Cytokine levels were quantified by ELISA. When nonathletes were compared with the kayakers, the latter exhibited lower plasma concentrations of IL-1β, IL-18, and IFN-γ as well as a lower concentration of IL-1ra. Positive correlations between IL-18 and B cells in the athletes were also found. These results seem to reinforce the anti-inflammatory role of regular training.

Composition of fatty acids in the maternal and umbilical cord plasma of adolescent and adult mothers: relationship with anthropometric parameters of newborn

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Oliveira Olívia RC

2012-11-01

Full Text Available Abstract Background Considering the importance of long chain polyunsaturated fatty acids to fetal development and the lack of studies that have compared the status of fatty acids between adolescents and adults mothers, the purpose of this study was to evaluate the composition of fatty acids in maternal and umbilical cord plasma from adolescent and adults mothers. Methods Forty pregnant adolescents and forty pregnant adults were selected to assess the distribution profile of fatty acids in the maternal and umbilical cord plasma. Quantification of fatty acids in the total lipids of the sample groups was performed through the use of gas-liquid chromatography. Results The maternal and umbilical cord plasma of the adolescents showed a greater concentration of AA than did that of the adults (P  Conclusions This suggests that in situations of greater nutritional risk, as in adolescent pregnancy, n-3PUFA concentrations have a greater influence on the proper development of newborns. Moreover, variations in fatty acid concentrations in the maternal and cord plasma of adolescents and adults may indicate that pregnancy affects the LC-PUFA status of adults and adolescents in distinct ways.

Interplay of cytokines in preterm birth

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Monika Pandey

2017-01-01

Full Text Available Preterm infants (i.e., born before <37 wk of gestation are at increased risk of morbidity and mortality and long-term disabilities. Global prevalence of preterm birth (PTB varies from 5 to 18 per cent. There are multiple aetiological causes and factors associated with PTB. Intrapartum infections are conventionally associated with PTB. However, maternal genotype modulates response to these infections. This review highlights the association of cytokine gene polymorphisms and their levels with PTB. Varying PTB rates across the different ethnic groups may be as a result of genetically mediated varying cytokines response to infections. Studies on genetic variations in tumour necrosis factor-alpha, interleukin-1 alpha (IL-1α, IL-1β, IL-6, IL-10 and toll-like receptor-4 genes and their association with PTB, have been reviewed. No single polymorphism of the studied genes was found to be associated with PTB. However, increased maternal levels of IL-1β and IL-6 and low levels of IL-10 have been found to be associated with PTB.

Maternal Plasma Phosphatidylcholine Fatty Acids and Atopy and Wheeze in the Offspring at Age of 6 Years

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Katharine C. Pike

2012-01-01

Full Text Available Variation in exposure to polyunsaturated fatty acids (PUFAs might influence the development of atopy, asthma, and wheeze. This study aimed to determine whether differences in PUFA concentrations in maternal plasma phosphatidylcholine are associated with the risk of childhood wheeze or atopy. For 865 term-born children, we measured phosphatidylcholine fatty acid composition in maternal plasma collected at 34 weeks’ gestation. Wheezing was classified using questionnaires at 6, 12, 24, and 36 months and 6 years. At age of 6 years, the children underwent skin prick testing, fractional exhaled nitric oxide (FENO measurement, and spirometry. Maternal n-6 fatty acids and the ratio of n-3 to n-6 fatty acids were not associated with childhood wheeze. However, higher maternal eicosapentaenoic acid, docosahexaenoic acid, and total n-3 fatty acids were associated with reduced risk of non-atopic persistent/late wheeze (RR 0.57, 0.67 and 0.69, resp. P=0.01, 0.015, and 0.021, resp.. Maternal arachidonic acid was positively associated with FENO (P=0.024. A higher ratio of linoleic acid to its unsaturated metabolic products was associated with reduced risk of skin sensitisation (RR 0.82, P=0.013. These associations provide some support for the hypothesis that variation in exposure to n-6 and n-3 fatty acids during pregnancy influences the risk of childhood wheeze and atopy.

Plasma cytokine profiles in HIV-1 infected patients developing neuropathic symptoms shortly after commencing antiretroviral therapy: a case-control study.

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Van der Watt, Johan J; Wilkinson, Katalin A; Wilkinson, Robert J; Heckmann, Jeannine M

2014-02-10

In patients infected with human immunodeficiency virus 1 (HIV-1) neuropathic symptoms may develop within weeks of starting combination antiretroviral therapy (cART). This timing coincides with the occurrence of immune reconstitution inflammatory syndrome. Our objective was to investigate the longitudinal association of plasma cytokine and soluble receptor concentrations with incident neuropathic symptoms within 12 weeks of starting programme-based cART in a nested case-control study. One hundred and twenty adults without neuropathic symptoms and about to initiate cART were followed longitudinally for 24 weeks after cART initiation. Subjects were examined for peripheral neuropathy at baseline (pre-cART) and 2-, 4-, 12- and 24 weeks thereafter. Individuals developing neuropathic symptoms within 12 weeks of starting cART were matched in a nested case-control design with those remaining symptom-free for at least 24 weeks. Plasma was collected at each visit. Cytokines and soluble receptors were quantified using multiplex immunometric assays. Incident neuropathic symptoms occurred in 32 (27%) individuals within 12 weeks of starting cART for the first time. Cytokine concentrations increased at 2 weeks, irrespective of symptom-status, returning to baseline concentrations at 12 weeks. Compared to the control group, the symptomatic group had higher baseline levels of interleukin-1 receptor (IL-1R)-antagonist. The symptomatic group also showed greater increases in soluble interleukin-2 receptor-alpha and tumour necrosis factor (TNF) receptor-II levels at week 2 and soluble interleukin-6 receptor levels at week 12. Ratios of pro-inflammatory- vs anti-inflammatory cytokines were higher for TNF-alpha/IL-4 (p = 0.022) and interferon-gamma/IL-10 (p = 0.044) in those developing symptoms. After 24 weeks of cART, the symptomatic group showed higher CD4+ counts (p = 0.002). The initiation of cART in previously treatment naïve individuals was associated with a cytokine

Unmethylated-maspin DNA in maternal plasma is associated with severe preeclampsia.

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Qi, Yan-Hua; Teng, Fei; Zhou, Qi; Liu, Yu-Xin; Wu, Jin-Fang; Yu, Shan-Shan; Zhang, Xin; Ma, Miao-Yan; Zhou, Ni; Chen, Li-Juan

2015-09-01

Cell-free fetal DNA in maternal plasma is associated with complications of pregnancy, including preeclampsia. Determination of levels is affected by fetal gender and genetic polymorphisms. Unmethylated maspin (u-maspin) is present in the placenta, and is placental-specific. The purpose of this study was to determine whether u-maspin DNA in maternal blood could serve as a marker of preeclampsia by measuring levels in different trimesters of normal pregnancies and in those complicated by preeclampsia. This case-control study was set in a tertiary care hospital. The population consisted of 45 women with normal pregnancies (15 in the 1st trimester, 15 in the 2nd trimester, 15 in the 3rd trimester), 20 women with mild preeclampsia, 25 women with severe preeclampsia, and six women with gestational trophoblastic disease. Peripheral blood was collected and methylation-specific PCR and fluorescence quantitative PCR were performed to measure the content of u-maspin DNA in maternal blood. U-maspin DNA was 5.5-fold higher in women with severe preeclampsia than in those with a normal 3rd trimester pregnancy (p preeclampsia. © 2015 Nordic Federation of Societies of Obstetrics and Gynecology.

Identification of messenger RNA of fetoplacental source in maternal plasma of women with normal pregnancies and pregnancies with intrauterine growth restriction.

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Ayala Ramírez, Paola; García Robles, Reggie; Rojas, Juan Diego; Bermúdez, Martha; Bernal, Jaime

2012-07-01

to quantify placenta-specific RNA in plasma of women carrying foetuses with intrauterine growth restriction and pregnant women with normal pregnancies. 8 pregnant women with foetuses with intrauterine growth restriction were studied as well as 18 women with uncomplicated pregnancies in the third pregnancy trimester. Total free RNA was quantified in maternal plasma by spectrophotometry and the gene expression of hPL (Human Placental Lactogen) at the messenger RNA level through technical Real Time-Chain Reaction Polymerase. plasma RNA of fetoplacental origin was successfully detected in 100% of pregnant women. There were no statistically significant differences between the values of total RNA extracted from plasma (p= 0.5975) nor in the messenger RNA expression of hPL gene (p= 0.5785) between cases and controls. messenger RNA of fetoplacental origin can be detected in maternal plasma during pregnancy.

Plasma cytokine levels fall in preterm newborn infants on nasal CPAP with early respiratory distress.

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Carvalho, Clarissa Gutierrez; Silveira, Rita de Cassia; Neto, Eurico Camargo; Procianoy, Renato Soibelmann

2015-01-01

Early nCPAP seems to prevent ventilator-induced lung injury in humans, although the pathophysiological mechanisms underlying this beneficial effect have not been clarified yet. To evaluate plasma levels IL-1β, IL-6, IL-8, IL-10, and TNF-α immediately before the start of nCPAP and 2 hours later in preterm infants. Prospective cohort including preterm infants with 28 to 35 weeks gestational age with moderate respiratory distress requiring nCPAP. Extreme preemies, newborns with malformations, congenital infections, sepsis, surfactant treatment, and receiving ventilatory support in the delivery room were excluded. Blood samples were collected right before and 2 hours after the start of nCPAP. 23 preterm infants (birth weight 1851±403 grams; GA 32.3±1.7 weeks) were treated with nCPAP. IL-1β, IL-10, TNF-α levels were similar, IL-8 levels were reduced in 18/23 preterm infants and a significant decrease in IL-6 levels was observed after 2 hours of nCPAP. All newborns whose mothers received antenatal steroids had lower cytokine levels at the onset of nCPAP than those whose mothers didn't receive it; this effect was not sustained after 2 hours of nCPAP. Early use nCPAP is not associated with rising of plasma pro-inflammatory cytokines and it seems to be a less harmful respiratory strategy for preterm with moderate respiratory distress.

Plasma cytokine levels fall in preterm newborn infants on nasal CPAP with early respiratory distress.

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Clarissa Gutierrez Carvalho

Full Text Available Early nCPAP seems to prevent ventilator-induced lung injury in humans, although the pathophysiological mechanisms underlying this beneficial effect have not been clarified yet.To evaluate plasma levels IL-1β, IL-6, IL-8, IL-10, and TNF-α immediately before the start of nCPAP and 2 hours later in preterm infants.Prospective cohort including preterm infants with 28 to 35 weeks gestational age with moderate respiratory distress requiring nCPAP. Extreme preemies, newborns with malformations, congenital infections, sepsis, surfactant treatment, and receiving ventilatory support in the delivery room were excluded. Blood samples were collected right before and 2 hours after the start of nCPAP.23 preterm infants (birth weight 1851±403 grams; GA 32.3±1.7 weeks were treated with nCPAP. IL-1β, IL-10, TNF-α levels were similar, IL-8 levels were reduced in 18/23 preterm infants and a significant decrease in IL-6 levels was observed after 2 hours of nCPAP. All newborns whose mothers received antenatal steroids had lower cytokine levels at the onset of nCPAP than those whose mothers didn't receive it; this effect was not sustained after 2 hours of nCPAP.Early use nCPAP is not associated with rising of plasma pro-inflammatory cytokines and it seems to be a less harmful respiratory strategy for preterm with moderate respiratory distress.

Three-dimensional structure and cytokine distribution of platelet-rich fibrin.

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Bai, Meng-Yi; Wang, Ching-Wei; Wang, Jyun-Yi; Lin, Ming-Fang; Chan, Wing P

2017-02-01

Previous reports have revealed that several cytokines (including platelet-derived growth factor-BB, transforming growth factors-β1 and insulin-like growth factor-1) can enhance the rate of bone formation and synthesis of extracellular matrix in orthopaedics or periodontology. This study aimed to determine the concentration of cytokines within platelet-rich fibrin microstructures and investigate whether there are differences in the different portions of platelet-rich fibrin, which has implications for proper clinical use of platelet-rich fibrin gel. Whole blood was obtained from six New Zealand rabbits (male, 7 to 39 weeks old, weight 2.7-4 kg); it was then centrifuged for preparation of platelet-rich fibrin gels and harvest of plasma. The resultant platelet-rich fibrin gels were used for cytokine determination, histological analyses and scanning electron microscopy. All plasmas obtained were subject to the same cytokine determination assays for the purpose of comparison. Cytokines platelet-derived growth factor-BB and transforming growth factor-β1 formed concentration gradients from high at the red blood cell end of the platelet-rich fibrin gel (p=1.88×10-5) to low at the plasma end (p=0.19). Insulin-like growth factor-1 concentrations were similar at the red blood cell and plasma ends. The porosities of the platelet-rich fibrin samples taken in sequence from the red blood cell end to the plasma end were 6.5% ± 4.9%, 24.8% ± 7.5%, 30.3% ± 8.5%, 41.4% ± 12.3%, and 40.3% ± 11.7%, respectively, showing a gradual decrease in the compactness of the platelet-rich fibrin network. Cytokine concentrations are positively associated with platelet-rich fibrin microstructure and portion in a rabbit model. As platelet-rich fibrin is the main entity currently used in regenerative medicine, assessing cytokine concentration and the most valuable portion of PRF gels is essential and recommended to all physicians.

Three-dimensional structure and cytokine distribution of platelet-rich fibrin

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Meng-Yi Bai

Full Text Available OBJECTIVES: Previous reports have revealed that several cytokines (including platelet-derived growth factor-BB, transforming growth factors-β1 and insulin-like growth factor-1 can enhance the rate of bone formation and synthesis of extracellular matrix in orthopaedics or periodontology. This study aimed to determine the concentration of cytokines within platelet-rich fibrin microstructures and investigate whether there are differences in the different portions of platelet-rich fibrin, which has implications for proper clinical use of platelet-rich fibrin gel. METHODS: Whole blood was obtained from six New Zealand rabbits (male, 7 to 39 weeks old, weight 2.7-4 kg; it was then centrifuged for preparation of platelet-rich fibrin gels and harvest of plasma. The resultant platelet-rich fibrin gels were used for cytokine determination, histological analyses and scanning electron microscopy. All plasmas obtained were subject to the same cytokine determination assays for the purpose of comparison. RESULTS: Cytokines platelet-derived growth factor-BB and transforming growth factor-β1 formed concentration gradients from high at the red blood cell end of the platelet-rich fibrin gel (p=1.88×10-5 to low at the plasma end (p=0.19. Insulin-like growth factor-1 concentrations were similar at the red blood cell and plasma ends. The porosities of the platelet-rich fibrin samples taken in sequence from the red blood cell end to the plasma end were 6.5% ± 4.9%, 24.8% ± 7.5%, 30.3% ± 8.5%, 41.4% ± 12.3%, and 40.3% ± 11.7%, respectively, showing a gradual decrease in the compactness of the platelet-rich fibrin network. CONCLUSION: Cytokine concentrations are positively associated with platelet-rich fibrin microstructure and portion in a rabbit model. As platelet-rich fibrin is the main entity currently used in regenerative medicine, assessing cytokine concentration and the most valuable portion of PRF gels is essential and recommended to all physicians.

Maternal and cord plasma concentrations of beta-lipotrophin, beta-endorphin and gamma-lipotrophin at delivery; effect of analgesia.

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Browning, A J; Butt, W R; Lynch, S S; Shakespear, R A; Crawford, J S

1983-12-01

Maternal venous plasma concentrations of beta-LPH, beta-EP and gamma-LPH were compared in (i) patients undergoing vaginal delivery, 11 with an epidural block and 13 with pethidine and nitrous oxide or no analgesics; (ii) patients delivered by caesarean section, 7 under epidural block and 8 under general anaesthesia. Patients delivered by either method under epidural block had significantly lower levels of all three peptides than those receiving no epidural. There were significant negative correlations between umbilical vein beta-LPH, beta-EP and gamma-LPH concentrations and umbilical artery pH and positive correlations between beta-LPH and beta-EP but not gamma-LPH and cord PCO2 in 29 patients. There was no relation between cord levels of any of the three peptides and the method of analgesia or the route of delivery. Although concentrations of all three peptides were closely correlated to one another in either maternal or cord plasma, there was no relationship between maternal and fetal levels.

Labour analgesia with intrathecal fentanyl decreases maternal stress.

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Cascio, M; Pygon, B; Bernett, C; Ramanathan, S

1997-06-01

Lumbar epidural analgesia (LEA) decreases maternal stress as measured by maternal circulating plasma catecholamine concentrations. Intrathecal fentanyl (ITF) provides effective labour analgesia but its effect on maternal epinephrine (Epi) and norepinephrine (NE) concentrations is not known. This study assesses whether ITF reduces maternal stress in the same manner as conventional LEA. Twenty-four healthy women in active labour received either 25 micrograms ITF (n = 12) or epidural lidocaine 1.5% (n = 12) for analgesia. Venous blood samples were collected before anaesthesia and at five minute intervals for 30 min following anaesthesia for the measurement of plasma Epi and NE by high performance liquid chromatography. Maternal blood pressure (BP), heart rate (HR), visual analog scores (VAS) to pain and pruritus were recorded at the same time. Both ITF and LEA decreased pain VAS scores, maternal BP, and plasma Epi concentrations with only minimal effects on plasma NE concentrations. Intrathecal fentanyl (ITF) and LEA reduced plasma epi to a similar extent, with ITF reducing the levels slightly faster than LEA. Intrathecal fentanyl(ITF) and LEA reduced plasma Epi concentrations by 52% and 51%, respectively (P value < 0.01). We conclude that ITF is as effective as LEA in producing pain relief in the labouring patient. Intrathecal Fentanyl (ITF) is also capable of reducing maternal plasma epinephrine concentration, thus avoiding the possibly deleterious side effects of excess amounts of this catecholamine during labour.

Cell-free placental mRNA in maternal plasma to predict placental invasion in patients with placenta accreta.

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El Behery, Manal M; Rasha L, Etewa; El Alfy, Yehya

2010-04-01

To evaluate whether measuring cell-free placental mRNA in maternal plasma improves the diagnostic accuracy of ultrasound and color Doppler in detecting placental invasion in patients at risk for placenta accreta. Thirty-five singleton pregnant women of more than 28 weeks of gestation and at risk for placenta accreta underwent ultrasound and color Doppler assessment. Cell-free placental mRNA in maternal plasma was measured using real-time reverse-transcription polymerase chain reaction. Patients were classified into 2 groups based on the findings at cesarean delivery and histological examination: women with placenta accreta (n=7) and women without placenta accreta (n=28). The median MoM (multiples of the median) value of cell-free placental mRNA was significantly higher in patients with placenta accreta than in those without placenta accreta (6.50 vs 2.60; Pplacental mRNA was significantly elevated in patients with placenta increta and percreta than in those with simple accreta. Six false-positive results were found on ultrasound, all from patients without placenta accreta and an insignificant rise in cell-free placental mRNA levels. Measuring cell-free placental mRNA in maternal plasma may increase the accuracy of ultrasound and color Doppler in prenatal prediction of placental invasion in patients with suspected placenta accreta. Copyright 2009 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

Inflammatory Cytokines and Sleep Disturbance in Patients with Temporomandibular Disorders.

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Park, Ji Woon; Chung, Jin Woo

2016-01-01

To assess the degree and interrelationship of sleep disturbance and plasma cytokine levels in temporomandibular disorder (TMD) pain patients. Forty female TMD patients and 20 age-, sex-, and body mass index (BMI)-matched healthy subjects were enrolled. TMD was diagnosed using the Research Diagnostic Criteria for TMD. The TMD patients were classified as having low or high disability according to Graded Chronic Pain Scale findings. The Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS) were used to measure sleep quality. Plasma concentrations of interleukin (IL)-1β, IL-6, IL-10, tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP) were measured from blood samples collected between 9 am and noon. Statistical analyses included Kruskal-Wallis and one-way analysis of variance tests to compare results between different groups and multivariate general linear models to evaluate the effect of sleep status on cytokine levels. The high-disability group had the highest PSQI and ESS scores (P disability group exhibiting the highest values (P ≤ .001). The plasma cytokine levels were significantly correlated with PSQI scores (P disability level after adjusting for both sleep indices (both P disability, had elevated plasma cytokine levels and increased ESS and PSQI scores suggestive of sleep disturbance.

Mode of delivery and cord blood cytokines: a birth cohort study

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DuBois Andrea M

2006-09-01

Full Text Available Abstract Background The mechanisms for the association between birth by cesarean section and atopy and asthma are largely unknown. Objective To examine whether cesarean section results in neonatal secretion of cytokines that are associated with increased risk of atopy and/or asthma in childhood. To examine whether the association between mode of delivery and neonatal immune responses is explained by exposure to the maternal gut flora (a marker of the vaginal flora. Methods CBMCs were isolated from 37 neonates at delivery, and secretion of IL-13, IFN-γ, and IL-10 (at baseline and after stimulation with antigens [dust mite and cat dander allergens, phytohemagglutinin, and lipopolysaccharide] was quantified by ELISA. Total and specific microbes were quantified in maternal stool. The relation between mode of delivery and cord blood cytokines was examined by linear regression. The relation between maternal stool microbes and cord blood cytokines was examined by Spearman's correlation coefficients. Results Cesarean section was associated with increased levels of IL-13 and IFN-γ. In multivariate analyses, cesarean section was associated with an increment of 79.4 pg/ml in secretion of IL-13 by CBMCs after stimulation with dust mite allergen (P Conclusion Cesarean section is associated with increased levels of IL-13 and IFN-γ, perhaps because of lack of labor and/or reduced exposure to specific microbes (e.g., gram-positive anaerobes at birth.

Combined association of maternal and paternal family history of diabetes with plasma leptin and adiponectin in overweight Hispanic children.

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Koebnick, C; Kelly, L A; Lane, C J; Roberts, C K; Shaibi, G Q; Toledo-Corral, C M; Davis, J N; Weigensberg, M J; Goran, M I

2008-09-01

To investigate the importance of a maternal and paternal family history of Type 2 diabetes and their combined association with plasma leptin and adiponectin levels in overweight Latino children with a family history of Type 2 diabetes (T2DM). This cross-sectional study investigated the combined association of a maternal and paternal family history of T2DM with leptin and adiponectin in 175 overweight Latino children (age 11.1 +/- 1.7 years). All subjects had a family history of T2DM. Plasma adiponectin and leptin levels, body fat measured by dual-energy X-ray absorptiometry, Tanner stage, age and insulin sensitivity were assessed. After adjustment for age, gestational diabetes, insulin sensitivity and body fat, a combined maternal and paternal family history of T2DM was associated with higher leptin concentrations (P = 0.004) compared with a maternal or paternal family history alone. This association was most pronounced at Tanner stage 1 (P for interaction family history x tanner stage = 0.022). The presence of a combined maternal and paternal family history of T2DM accounted for 4% (P = 0.003) of the variation in leptin concentrations. No such combined association was observed for adiponectin levels. Maternal and paternal family history of T2DM may have an additive impact on leptin, but not on adiponectin levels independent of adiposity and insulin sensitivity in overweight Latino children. This may contribute to a further clinically relevant deterioration of metabolic health in this population.

Maternal ethanol ingestion: effect on maternal and neonatal glucose balance

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Witek-Janusek, L.

1986-01-01

Liver glycogen availability in the newborn is of major importance for the maintenance of postnatal blood glucose levels. This study examined the effect of maternal ethanol ingestion on maternal and neonatal glucose balance in the rate. Female rats were placed on 1) the Lieber-DeCarli liquid ethanol diet, 2) an isocaloric liquid pair-diet, or 3) an ad libitum rat chow diet at 3 wk before mating and throughout gestation. Blood and livers were obtained from dams and rat pups on gestational days 21 and 22. The pups were studied up to 6 h in the fasted state and up to 24 h in the fed state. Maternal ethanol ingestion significantly decreased litter size, birth weight, and growth. A significantly higher mortality during the early postnatal period was seen in the prenatal ethanol exposed pups. Ethanol significantly decreased fed maternal liver glycogen stores but not maternal plasma glucose levels. The newborn rats from ethanol ingesting dams also had significantly decreased liver glycogen stores. Despite mobilizing their available glycogen, these prenatal ethanol exposed pups became hypoglycemic by 6 h postnatal. This was more marked in the fasted pups. Ethanol did not affect maternal nor neonatal plasma insulin levels. Thus maternal ethanol ingestion reduces maternal and neonatal liver glycogen stores and leads to postnatal hypoglycemia in the newborn rat

Patterns of peripheral cytokine expression during pregnancy in two cohorts and associations with inflammatory markers in cord blood.

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Ross, Kharah MacKenzie; Miller, Gregory; Culhane, Jennifer; Grobman, William; Simhan, Hyagriv N; Wadhwa, Pathik D; Williamson, Douglas; McDade, Thomas; Buss, Claudia; Entringer, Sonja; Adam, Emma; Qadir, Sameen; Keenan-Devlin, Lauren; Leigh, Adam K K; Borders, Ann

2016-11-01

Maternal inflammation undergoes adaptations during pregnancy, and excessive inflammation has been associated with adverse outcomes. One mechanism may be maternal inflammation transmission to the fetal compartment. Links between maternal pregnancy inflammation and fetal inflammation are poorly characterized. Principal components analysis was used to extract underlying inflammation components across cytokines (IFN-γ, IL-10, IL-13, IL-6, IL-8, TNF-α) in two pregnancy cohorts (SPAH N=87, MOMS N=539) assessed during the second and third trimesters. Links between maternal inflammation over pregnancy and fetal (cord blood) inflammation were assessed. Substantial cytokine rank-order stability was observed in both cohorts, β's range .47-.96, P's blood inflammation, P's>.04. Maternal inflammation indices over pregnancy were associated with inflammation in cord blood at birth. Results have implications for understanding pregnancy inflammatory processes and how maternal inflammation may be transmitted to fetal circulation. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Neonatal Cytokine Profile in the Airway Mucosal Lining Fluid Is Skewed by Maternal Atopy

DEFF Research Database (Denmark)

Folsgaard, Nilofar V.; Chawes, Bo L.; Rasmussen, Morten A.

2012-01-01

on the cytokines and chemokines in the upper airway mucosal lining fluid of healthy neonates. Objectives: To study parental atopic imprinting on the cytokines and chemokines in the upper airway mucosal lining fluid of healthy neonates. Methods: Eighteen cytokines and chemokines were quantified in nasal mucosal...

Amniotic fluid inflammatory cytokines: potential markers of immunologic dysfunction in autism spectrum disorders.

Science.gov (United States)

Abdallah, Morsi W; Larsen, Nanna; Grove, Jakob; Nørgaard-Pedersen, Bent; Thorsen, Poul; Mortensen, Erik L; Hougaard, David M

2013-09-01

The aim of the study was to analyze cytokine profiles in amniotic fluid (AF) samples of children developing autism spectrum disorders (ASD) and controls, adjusting for maternal autoimmune disorders and maternal infections during pregnancy. AF samples of 331 ASD cases and 698 controls were analyzed for inflammatory cytokines using Luminex xMAP technology utilizing a historic birth cohort. Clinical data were retrieved from nationwide registers, and case-control differences in AF cytokine levels were assessed using chi-square tests, logistic and tobit regression models. Overall, individuals with ASD had significantly elevated AF levels of TNF-α and TNF-β compared to controls. Analyzing individuals diagnosed only with ICD-10 codes yielded significantly elevated levels of IL-4, IL-10, TNF-α and TNF-β in ASD patients. Restricting analysis to infantile autism cases showed significantly elevated levels of IL-4, TNF-α and TNF-β compared to controls with no psychiatric comorbidities. Elevated levels of IL-6 and IL-5 were found in individuals with other childhood psychiatric disorders (OCPD) when compared to controls with no psychiatric comorbidities. AF samples of individuals with ASD or OCPD showed differential cytokine profiles compared to frequency-matched controls. Further studies to examine the specificity of the reported cytokine profiles in ASD and OCPD are required.

Vitamin D treatment during pregnancy prevents autism-related phenotypes in a mouse model of maternal immune activation.

Science.gov (United States)

Vuillermot, Stephanie; Luan, Wei; Meyer, Urs; Eyles, Darryl

2017-01-01

Prenatal exposure to infection is a recognized environmental risk factor for neuropsychiatric disorders of developmental origins such as autism or schizophrenia. Experimental work in animals indicates that this link is mediated by maternal immune activation (MIA) involving interactions between cytokine-associated inflammatory events, oxidative stress, and other pathophysiological processes such as hypoferremia and zinc deficiency. Maternal administration of the viral mimic polyriboinosinic-polyribocytidylic acid (poly(I:C)) in mice produces several behavioral phenotypes in adult offspring of relevance to autism spectrum disorder (ASD) and other neurodevelopmental disorders. Here, we investigated whether some of these phenotypes might also present in juveniles. In addition, given the known immunomodulatory and neuroprotective effects of vitamin D, we also investigated whether the co-administration of vitamin D could block MIA-induced ASD-related behaviors. We co-administered the hormonally active form of vitamin D, 1α,25 dihydroxy vitamin D3 (1,25OHD), simultaneously with poly(I:C) and examined (i) social interaction, stereotyped behavior, emotional learning and memory, and innate anxiety-like behavior in juveniles and (ii) the levels of the pro-inflammatory cytokines IL-1β, IL-6 and TNF-α in maternal plasma and fetal brains. We show that like adult offspring that were exposed to MIA, juveniles display similar deficits in social approach behavior. Juvenile MIA offspring also show abnormal stereotyped digging and impaired acquisition and expression of tone-cued fear conditioning. Importantly, our study reveals that prenatal administration of 1,25OHD abolishes all these behavioral deficits in poly(I:C)-treated juveniles. However, prenatal administration of vitamin D had no effect on pro-inflammatory cytokine levels in dams or in fetal brains suggesting the anti-inflammatory actions of vitamin D are not the critical mechanism for its preventive actions in this ASD

Atrial natriuretic factor in maternal and fetal sheep

International Nuclear Information System (INIS)

Cheung, C.Y.; Gibbs, D.M.; Brace, R.A.

1987-01-01

To determine atrial natriuretic factor (ANF) concentrations in the circulation and body fluids of adult pregnant sheep and their fetuses, pregnant ewes were anesthetized with pentobarbital sodium, and the fetuses were exteriorized for sampling. ANF concentration, as measured by radioimmunoassay, was 47 +/- 6 (SE) pg/ml in maternal plasma, which was significantly higher than the 15 +/- 3 pg/ml in maternal urine. In the fetus, plasma ANF concentration was 265 +/- 49 pg/ml, 5.6 times that in maternal plasma. No umbilical arterial and venous difference in ANF concentration was observed. Fetal urine ANF concentration was significantly lower than that in fetal plasma, and was similar to that measured in amniotic and allantoic fluid. In chronically catheterized maternal and fetal sheep, fetal plasma ANF was again 5.1 times that in maternal plasma, and these levels were not different from those measured in acutely anesthetized animals. These results demonstrate that immunoreactive ANF is present in the fetal circulation at levels higher than those found in the mother. The low concentration of ANF in fetal urine suggests that ANF is probably metabolized and/or reabsorbed by the fetal kidney

The impact of maternal plasma volume expansion and antihypertensive treatment with intravenous dihydralazine on fetal and maternal hemodynamics during pre-eclampsia: a clinical, echo-Doppler and viscometric study.

NARCIS (Netherlands)

Boito, S.M.; Struijk, P.C.; Pop, G.A.M.; Visser, W. de; Steegers, E.A.P.; Wladimiroff, J.W.

2004-01-01

OBJECTIVES: To establish the effects of plasma volume expansion (PVE) followed by intravenous dihydralazine (DH) administration on maternal whole blood viscosity (WBV) and hematocrit, uteroplacental and fetoplacental downstream impedance and umbilical venous (UV) volume flow in pre-eclampsia.

Platelet-rich plasma preparation for regenerative medicine: optimization and quantification of cytokines and growth factors

Science.gov (United States)

2013-01-01

Introduction Platelet-rich plasma (PRP) is nowadays widely applied in different clinical scenarios, such as orthopedics, ophthalmology and healing therapies, as a growth factor pool for improving tissue regeneration. Studies into its clinical efficiency are not conclusive and one of the main reasons for this is that different PRP preparations are used, eliciting different responses that cannot be compared. Platelet quantification and the growth factor content definition must be defined in order to understand molecular mechanisms behind PRP regenerative strength. Standardization of PRP preparations is thus urgently needed. Methods PRP was prepared by centrifugation varying the relative centrifugal force, temperature, and time. Having quantified platelet recovery and yield, the two-step procedure that rendered the highest output was chosen and further analyzed. Cytokine content was determined in different fractions obtained throughout the whole centrifugation procedure. Results Our method showed reproducibility when applied to different blood donors. We recovered 46.9 to 69.5% of total initial platelets and the procedure resulted in a 5.4-fold to 7.3-fold increase in platelet concentration (1.4 × 106 to 1.9 × 106 platelets/μl). Platelets were highly purified, because only blood cells and leukocytes was present in the final PRP preparation. We also quantified growth factors, cytokines and chemokines secreted by the concentrated platelets after activation with calcium and calcium/thrombin. High concentrations of platelet-derived growth factor, endothelial growth factor and transforming growth factor (TGF) were secreted, together with the anti-inflammatory and proinflammatory cytokines interleukin (IL)-4, IL-8, IL-13, IL-17, tumor necrosis factor (TNF)-α and interferon (IFN)-α. No cytokines were secreted before platelet activation. TGF-β3 and IFNγ were not detected in any studied fraction. Clots obtained after platelet coagulation retained a high concentration of

Infusion of hypertonic saline before elective hysterectomy: effects on cytokines and stress hormones

DEFF Research Database (Denmark)

Kølsen-Petersen, Jens Aage; Bendtzen, Klaus; Tønnesen, Else Kirstine

2008-01-01

with the other groups (Peffect on the postoperative concentration of selected plasma cytokines and the hormonal stress......BACKGROUND: Infusion of hypertonic saline provides early haemodynamic benefits and may affect the immune system. It is unknown if infusion of hypertonic saline affects plasma cytokines and stress hormones after surgery. METHODS: Sixty-two women undergoing abdominal hysterectomy were randomized...

Influence of Radix scutellariae on Th1/Th2 cytokine balance in RU486-induced abortion in mice

Institute of Scientific and Technical Information of China (English)

ZHONG Xiuhui; SHI Wanyu; MA Aituan; WANG Xiaodan; ZHANG Jianlou; LI Xuezhong

2007-01-01

The aim of this study is to investigate the significance of Th1/Th2 cytokine balance in the uterus in the early embryo loss(or resorption),and to elucidate immunological modulation at the maternal-fetal interface with Chinese herbal medicine Radix scutellariae(Huang Qin)and its constituents(Baicalin and Baicalein).Mifepristone(RU486)was given via subcutaneous injection in the scapular area to induce abortion in mice at day 7 of gestation.The levels of uterine Thl cytokines(IFN-β,IL-2)and Th2 cytokines(IL-4,IL-10)were analyzed by enzyme-linked immunosorbent assay(ELISA),respectively.The mean values of Thl cytokines in the uterus of RU486-treated abortion mice were significantly higher(P＜0.05)than that of the control mice,but no significant difference was observed regarding to the contents of Th2 cytokines of different groups(P＞0.05).However,when the Radix scutellariae and its constituents were used to prevent RU486-induced abortion,the levels of IFN-γ and IL-2 decreased while that of IL-4 and IL-10 increased.The embryo loss induced by RU486 was closely related to the Th1/Th2 immune balance at the maternal-fetal interface.Radix scutellariae and its constituents have an anti-abortive effect through restoring the Th1/Th2 balance at the maternal-fetal interface.

Infusion of hypertonic saline before elective hysterectomy: effects on cytokines and stress hormones

DEFF Research Database (Denmark)

Kolsen-Petersen, J A; Bendtzen, K; Tonnesen, E

2008-01-01

Infusion of hypertonic saline provides early haemodynamic benefits and may affect the immune system. It is unknown if infusion of hypertonic saline affects plasma cytokines and stress hormones after surgery.......Infusion of hypertonic saline provides early haemodynamic benefits and may affect the immune system. It is unknown if infusion of hypertonic saline affects plasma cytokines and stress hormones after surgery....

Elevated specific peripheral cytokines found in major depressive disorder patients with childhood trauma exposure: a cytokine antibody array analysis.

Science.gov (United States)

Lu, Shaojia; Peng, Hongjun; Wang, Lifeng; Vasish, Seewoobudul; Zhang, Yan; Gao, Weijia; Wu, Weiwei; Liao, Mei; Wang, Mi; Tang, Hao; Li, Wenping; Li, Weihui; Li, Zexuan; Zhou, Jiansong; Zhang, Zhijun; Li, Lingjiang

2013-10-01

Taking into consideration the previous evidence of revealing the relationship of early life adversity, major depressive disorder (MDD), and stress-linked immunological changes, we recruited 22 MDD patients with childhood trauma exposures (CTE), 21 MDD patients without CTE, and 22 healthy controls without CTE, and then utilized a novel cytokine antibody array methodology to detect potential biomarkers underlying MDD in 120 peripheral cytokines and to evaluate the effect of CTE on cytokine changes in MDD patients. Although 13 cytokines were identified with highly significant differences in expressions between MDD patients and normal controls, this relationship was significantly attenuated and no longer significant after consideration of the effect of CTE in MDD patients. Depressed individuals with CTE (TD patients) were more likely to have higher peripheral levels of those cytokines. Severity of depression was associated with plasma levels of certain increased cytokines; meanwhile, the increased cytokines led to a proper separation of TD patients from normal controls during clustering analyses. Our research outcomes add great strength to the relationship between depression and cytokine changes and suggest that childhood trauma may play a vital role in the co-appearance of cytokine changes and depression. Copyright © 2013 Elsevier Inc. All rights reserved.

Maternal Diet, Metabolic State, and Inflammatory Response Exert Unique and Long-Lasting Influences on Offspring Behavior in Non-Human Primates

Directory of Open Access Journals (Sweden)

Jacqueline R. Thompson

2018-04-01

Full Text Available Nutritional status influences brain health and gestational exposure to metabolic disorders (e.g. obesity and diabetes increases the risk of neuropsychiatric disorders. The aim of the present study was to further investigate the role of maternal Western-style diet (WSD, metabolic state, and inflammatory factors in the programming of Japanese macaque offspring behavior. Utilizing structural equation modeling, we investigated the relationships between maternal diet, prepregnancy adiposity, third trimester insulin response, and plasma cytokine levels on 11-month-old offspring behavior. Maternal WSD was associated with greater reactive and ritualized anxiety in offspring. Maternal adiposity and third trimester macrophage-derived chemokine (MDC exerted opposing effects on offspring high-energy outbursts. Elevated levels of this behavior were associated with low maternal MDC and increased prepregnancy adiposity. This is the first study to show that maternal MDC levels influence offspring behavior. We found no evidence suggesting maternal peripheral inflammatory response mediated the effect of maternal diet and metabolic state on aberrant offspring behavior. Additionally, the extent of maternal metabolic impairment differentially influenced chemokine response. Elevated prepregnancy adiposity suppressed third trimester chemokines, while obesity-induced insulin resistance augmented peripheral chemokine levels. WSD also directly increased maternal interleukin-12. This is the first non-human primate study to delineate the effects of maternal diet and metabolic state on gestational inflammatory environment and subsequent offspring behavior. Our findings give insight to the complex mechanisms by which diet, metabolic state, and inflammation during pregnancy exert unique influences on offspring behavioral regulation.

Cytokine Adsorption onto the Modified Carbon Sorbent Surface in vitro in Peritonitis

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T. I. Dolgikh

2009-01-01

Full Text Available Objective: to evaluate the efficiency of cytokine sorption with carbon with a locally aminocaproic acid-modified surface from the plasma of patients with general purulent peritonitis. Materials and methods. The material of the investigation was the plasma obtained during plasmapheresis in 10 patients with acute pancreatitis complicated by pancreonecrosis and general purulent peritonitis, which was used to estimate before and after sorption the content of the cytokines: interleukin (IL-1/8, IL-4, and IL-8 by enzyme immunoassay. The sorption properties of carbon hemosor-bent and aminocaproic acid-modified sorbent were comparatively evaluated. Results. Aminocaproic acid-induced modification of the carbon adsorbent surface with its further polycondensation results in the higher content of superficial functional groups (oxygen- and nitrogen-containing that enhance the hydrophility of the surface and the specific pattern of sorption, thus acting as a means for controlling and regulating the plasma concentration of regulatory proteins, primarily the proinflammatory cytokine IL-1^3, the chemokine IL-8 and the T-helper cell clone cytokine IL-4.

Platelet-rich plasma preparation for regenerative medicine: optimization and quantification of cytokines and growth factors.

Science.gov (United States)

Amable, Paola Romina; Carias, Rosana Bizon Vieira; Teixeira, Marcus Vinicius Telles; da Cruz Pacheco, Italo; Corrêa do Amaral, Ronaldo José Farias; Granjeiro, José Mauro; Borojevic, Radovan

2013-06-07

Platelet-rich plasma (PRP) is nowadays widely applied in different clinical scenarios, such as orthopedics, ophthalmology and healing therapies, as a growth factor pool for improving tissue regeneration. Studies into its clinical efficiency are not conclusive and one of the main reasons for this is that different PRP preparations are used, eliciting different responses that cannot be compared. Platelet quantification and the growth factor content definition must be defined in order to understand molecular mechanisms behind PRP regenerative strength. Standardization of PRP preparations is thus urgently needed. PRP was prepared by centrifugation varying the relative centrifugal force, temperature, and time. Having quantified platelet recovery and yield, the two-step procedure that rendered the highest output was chosen and further analyzed. Cytokine content was determined in different fractions obtained throughout the whole centrifugation procedure. Our method showed reproducibility when applied to different blood donors. We recovered 46.9 to 69.5% of total initial platelets and the procedure resulted in a 5.4-fold to 7.3-fold increase in platelet concentration (1.4 × 10(6) to 1.9 × 10(6) platelets/μl). Platelets were highly purified, because only platelets after activation with calcium and calcium/thrombin. High concentrations of platelet-derived growth factor, endothelial growth factor and transforming growth factor (TGF) were secreted, together with the anti-inflammatory and proinflammatory cytokines interleukin (IL)-4, IL-8, IL-13, IL-17, tumor necrosis factor (TNF)-α and interferon (IFN)-α. No cytokines were secreted before platelet activation. TGF-β3 and IFNγ were not detected in any studied fraction. Clots obtained after platelet coagulation retained a high concentration of several growth factors, including platelet-derived growth factor and TGF. Our study resulted in a consistent PRP preparation method that yielded a cytokine and growth factor pool

The impact of maternal plasma volume expansion and antihypertensive treatment with intravenous dihydralazine on fetal and maternal hemodynamics during pre-eclampsia: a clinical, echo-Doppler and viscometric study.

Science.gov (United States)

Boito, S M E; Struijk, P C; Pop, G A M; Visser, W; Steegers, E A P; Wladimiroff, J W

2004-04-01

To establish the effects of plasma volume expansion (PVE) followed by intravenous dihydralazine (DH) administration on maternal whole blood viscosity (WBV) and hematocrit, uteroplacental and fetoplacental downstream impedance and umbilical venous (UV) volume flow in pre-eclampsia. In 13 pre-eclamptic women maternal and fetal hemodynamics were established by means of combined measurement of maternal arterial blood pressure (BP), WBV, hematocrit and uterine artery (UtA) resistance index (RI) in addition to umbilical artery (UA) pulsatility index (PI) and UV volume flow obtained from UV vessel area and UV time-averaged flow velocity. In each woman all parameters were measured four times at baseline, after PVE, after DH and 24 h after the start of treatment. Maternal diastolic BP, hematocrit and WBV display a significant reduction after PVE. In the fetus UA PI decreases significantly whereas a significant increase in UV cross-sectional area was detected. After maternal DH administration, arterial systolic and diastolic BP and UA PI show a significant decrease compared with the measurements following PVE. At 24 h, only maternal systolic and diastolic BP display a significant further decrease. No significant changes were established for the UtA RI, UV time-averaged velocity and UV volume flow during the entire study period. During pre-eclampsia, maternal PVE followed by DH administration results in a significant reduction in maternal diastolic BP, maternal hematocrit and WBV. Maternal PVE is associated with a significant increase in UV cross-sectional area and a non-significant rise of 11% in UV volume flow. Maternal DH administration does not result in any change in UV cross-sectional area. However, UA PI decreases significantly after both PVE and DH treatment. Copyright 2004 ISUOG.

Non-invasive markers of bone turnover and plasma cytokines differ in osteoporotic patients with multiple myeloma and monoclonal gammopathies of undetermined significance

International Nuclear Information System (INIS)

Diamond, T.; Levy, S.; Smith, A.; Day, P.; Manoharan, A.

2001-01-01

Multiple myeloma (MM) is a common malignancy manifest by bone marrow infiltration with malignant plasma cells, the production of a paraprotein and lytic bone lesions. Monoclonal gammopathy of undetermined significance (MGUS) is assumed to be the precursor of clinically apparent myeloma, with one or more additional genetic events being required for progression to MM. Elderly patients presenting with osteoporosis and skeletal fractures are not infrequently found to have elevated serum paraprotein concentrations suggestive of either MM or MGUS. Differentiating between these two clinical disorders may prove challenging, despite bone marrow biopsy evidence of plasmacytosis. The underlying pathogenesis of bone loss in these conditions is complex and may be attributed to cytokine-induced osteoclastogenesis coupled with increased osteoclastic bone resorption. In the present study, various markers of bone turnover and plasma cytokines were measured in order to determine whether they may be of value in differentiating between these two disorders. It is concluded that the urinary deoxypyridinoline excretion rate is a sensitive marker of bone resorption and of underlying bone disease activity. It may also help to differentiate between MM and MGUS

Fetal gender prediction based on maternal plasma testosterone and insulin-like peptide 3 concentrations at midgestation and late gestation in cattle.

Science.gov (United States)

Kibushi, M; Kawate, N; Kaminogo, Y; Hannan, M A; Weerakoon, W W P N; Sakase, M; Fukushima, M; Seyama, T; Inaba, T; Tamada, H

2016-10-15

We compared maternal plasma testosterone and insulin-like peptide 3 (INSL3) concentrations between dams carrying a male versus female fetus from early to late gestation and examined the application of maternal hormonal concentrations to fetal gender prediction in dairy and beef cattle. Blood samples were collected from Holstein cows or heifers (N = 31) and Japanese Black beef cows (N = 33) at 1-month intervals at 2 to 8 months of gestation. Fetal gender was confirmed by visual observation of external genitalia of calves just after birth. Plasma testosterone and INSL3 concentrations were determined by enzyme-immunoassay. Fetal genders were judged based on cutoff values of maternal testosterone and INSL3 concentrations (male, if it was ≥ cutoff value; female, if dairy cattle (P cows (P dairy cattle (P cows (P dairy cattle at 5 and 7 months and for beef cows at 5 and 6 months, whereas those values by maternal INSL3 concentrations were 71.0% to 72.4% for the dairy cattle at 6 months and beef cows at 4 and 8 months. When multiple time points of testosterone and INSL3 concentrations at several midgestation and late gestation months were considered for fetal gender prediction, predictive values were 89.3% (5-7 months) and 85.7% to 88.0% (4-6, 8 months) for the dairy and beef breeds, respectively. Maternal testosterone and INSL3 concentrations in dams carrying a male fetus were higher than those carrying a female at midgestation and/or late gestation in Holstein and Japanese Black beef cattle. Nearly, 80% accuracy was obtained for fetal gender prediction by a single time point of maternal plasma testosterone concentrations at midgestation. Nearly 90% accuracy for the prediction was obtained when multiple time points of testosterone and INSL3 concentrations from midgestation to late gestation were considered. Copyright © 2016 Elsevier Inc. All rights reserved.

The effect of the colostral cells on gene expression of cytokines in cord blood cells.

Science.gov (United States)

Hrdý, Jiří; Novotná, Olga; Kocourková, Ingrid; Prokešová, Ludmila

2017-11-01

Beneficial effect of maternal milk is acknowledged, but there is still question whether maternal milk from allergic mother is as good as from healthy one. In our study, we have assayed the effect of cells from colostrum of healthy and allergic mothers on gene expression of cytokines in cord blood cells of newborns of healthy and allergic mothers. Cytokines typical for Th1 (IL-2, IFN-gamma), Th2 (IL-4, IL-13), Tregs (IL-10, TGF-beta), and IL-8 were followed. We were not able to detect significant influence of colostral cells on gene expression of cytokines in cord blood after 2-day coculture using Transwell system. There was no difference in gene expression of cytokines in nonstimulated cord blood cells of newborns of healthy and allergic mothers, but generally increased gene expression of cytokines except IL-10 and TGF-beta after polyclonal stimulation was detected in cord blood cells of children of allergic mothers. There was no difference in IL-10 expression in stimulated cord blood cells of children of healthy and allergic mothers. Gene expression of TGF-beta was even decreased in stimulated cord blood cells of children of allergic mothers in comparison to healthy ones. We have not observed difference in the capacity of colostral cells of healthy and allergic mothers to influence gene expression of cytokines in cord blood cells, but we have described difference in the reactivity of cord blood cells between children of allergic and healthy mothers.

Noninvasive Prenatal Diagnosis of Congenital Adrenal Hyperplasia Using Cell-Free Fetal DNA in Maternal Plasma

Science.gov (United States)

Tong, Yu K.; Yuen, Tony; Jiang, Peiyong; Pina, Christian; Chan, K. C. Allen; Khattab, Ahmed; Liao, Gary J. W.; Yau, Mabel; Kim, Se-Min; Chiu, Rossa W. K.; Sun, Li; Zaidi, Mone

2014-01-01

Context: Congenital adrenal hyperplasia (CAH) is an autosomal recessive condition that arises from mutations in CYP21A2 gene, which encodes for the steroidogenic enzyme 21-hydroxylase. To prevent genital ambiguity in affected female fetuses, prenatal treatment with dexamethasone must begin on or before gestational week 9. Currently used chorionic villus sampling and amniocentesis provide genetic results at approximately 14 weeks of gestation at the earliest. This means that mothers who want to undergo prenatal dexamethasone treatment will be unnecessarily treating seven of eight fetuses (males and three of four unaffected females), emphasizing the desirability of earlier genetic diagnosis in utero. Objective: The objective of the study was to develop a noninvasive method for early prenatal diagnosis of fetuses at risk for CAH. Patients: Fourteen families, each with a proband affected by phenotypically classical CAH, were recruited. Design: Cell-free fetal DNA was obtained from 3.6 mL of maternal plasma. Using hybridization probes designed to capture a 6-Mb region flanking CYP21A2, targeted massively parallel sequencing (MPS) was performed to analyze genomic DNA samples from parents and proband to determine parental haplotypes. Plasma DNA from pregnant mothers also underwent targeted MPS to deduce fetal inheritance of parental haplotypes. Results: In all 14 families, the fetal CAH status was correctly deduced by targeted MPS of DNA in maternal plasma, as early as 5 weeks 6 days of gestation. Conclusions: MPS on 3.6 mL plasma from pregnant mothers could potentially provide the diagnosis of CAH, noninvasively, before the ninth week of gestation. Only affected female fetuses will thus be treated. Our strategy represents a generic approach for noninvasive prenatal testing for an array of autosomal recessive disorders. PMID:24606108

Bacterial translocation and plasma cytokines during transcatheter and open-heart aortic valve implantation.

Science.gov (United States)

Adrie, Christophe; Parlato, Marianna; Salmi, Lynda; Adib-Conquy, Minou; Bical, Olivier; Deleuze, Philippe; Fitting, Catherine; Cavaillon, Jean Marc; Monchi, Mehran

2015-01-01

To determine whether the good safety profile of transarterial aortic valve implantation (TAVI) is related to lower levels of systemic bacterial translocation and systemic inflammation compared with open-heart surgery. Transcatheter aortic valve implantation via the transfemoral approach is increasingly used in very high-risk patients with aortic stenosis. The outcomes seem similar to those after open-heart aortic valve replacement (OHAVR). Each of 26 consecutive high-risk patients (EuroSCORE >20% for risk of operative death) who underwent TAVI (cases) was matched to the first low-risk patient treated next in our department using elective OHAVR without coronary artery bypass (control subjects). We collected severity, outcome, and echocardiography indicators before and after surgery; complications; proinflammatory cytokine levels; and markers for microbial translocation. Despite greater illness severity, the TAVI patients had significantly lower vasopressor agent requirements, lower delirium rates, shorter hospital stays, and better hemodynamic findings compared with OHAVR patients. Vascular complications were more common after TAVI than after OHAVR (12, with seven requiring interventional therapy vs. 0, P = 0.006). Patients who underwent TAVI had lower blood transfusion requirements. Two TAVI patients died: one from iliac artery injury and the other from intracardiac prosthesis migration. Patients who underwent TAVI had lower plasma levels of endotoxin and bacterial peptidoglycan, as well as lower proinflammatory cytokine levels, suggesting less gastrointestinal bacterial translocation compared with OHAVR. Compared with OHAVR, TAVI was associated with decreases in bacterial translocation and inflammation. These differences may explain the lower delirium rate and better hemodynamic stability observed, despite the greater disease severity in TAVI patients.

Non-invasive aneuploidy detection using free fetal DNA and RNA in maternal plasma: recent progress and future possibilities.

NARCIS (Netherlands)

Go, A.T.; Vugt, J.M.G. van; Oudejans, C.B.

2011-01-01

BACKGROUND: Cell-free fetal DNA (cff DNA) and RNA can be detected in maternal plasma and used for non-invasive prenatal diagnostics. Recent technical advances have led to a drastic change in the clinical applicability and potential uses of free fetal DNA and RNA. This review summarizes the latest

Seminal Plasma HIV-1 RNA Concentration Is Strongly Associated with Altered Levels of Seminal Plasma Interferon-γ, Interleukin-17, and Interleukin-5

Science.gov (United States)

Hoffman, Jennifer C.; Anton, Peter A.; Baldwin, Gayle Cocita; Elliott, Julie; Anisman-Posner, Deborah; Tanner, Karen; Grogan, Tristan; Elashoff, David; Sugar, Catherine; Yang, Otto O.

2014-01-01

Abstract Seminal plasma HIV-1 RNA level is an important determinant of the risk of HIV-1 sexual transmission. We investigated potential associations between seminal plasma cytokine levels and viral concentration in the seminal plasma of HIV-1-infected men. This was a prospective, observational study of paired blood and semen samples from 18 HIV-1 chronically infected men off antiretroviral therapy. HIV-1 RNA levels and cytokine levels in seminal plasma and blood plasma were measured and analyzed using simple linear regressions to screen for associations between cytokines and seminal plasma HIV-1 levels. Forward stepwise regression was performed to construct the final multivariate model. The median HIV-1 RNA concentrations were 4.42 log10 copies/ml (IQR 2.98, 4.70) and 2.96 log10 copies/ml (IQR 2, 4.18) in blood and seminal plasma, respectively. In stepwise multivariate linear regression analysis, blood HIV-1 RNA level (pplasma HIV-1 RNA level. After controlling for blood HIV-1 RNA level, seminal plasma HIV-1 RNA level was positively associated with interferon (IFN)-γ (p=0.03) and interleukin (IL)-17 (p=0.03) and negatively associated with IL-5 (p=0.0007) in seminal plasma. In addition to blood HIV-1 RNA level, cytokine profiles in the male genital tract are associated with HIV-1 RNA levels in semen. The Th1 and Th17 cytokines IFN-γ and IL-17 are associated with increased seminal plasma HIV-1 RNA, while the Th2 cytokine IL-5 is associated with decreased seminal plasma HIV-1 RNA. These results support the importance of genital tract immunomodulation in HIV-1 transmission. PMID:25209674

Cytokine Responses to Acute Exercise in Healthy Older Adults: The Effect of Cardiorespiratory Fitness

Directory of Open Access Journals (Sweden)

Mark T. Windsor

2018-03-01

Full Text Available Markers of chronic inflammation increase with aging, and are associated with cardiovascular disease prevalence and mortality. Increases in fitness with exercise training have been associated with lower circulating concentrations of cytokines known to have pro-inflammatory actions (such as interleukin-6 [IL-6] and higher circulating concentrations of anti-inflammatory cytokines (interleukin-10 [IL-10]. However, the effect of cardiorespiratory fitness on acute cytokine responses to a single bout of exercise in healthy older individuals is unknown. We compared the response of plasma cytokines IL-6, tumor necrosis factor-alpha (TNF-α and IL-10 to a bout of moderate-intensity continuous and higher-intensity interval exercise between older individuals with higher and lower levels of cardiorespiratory fitness. Sixteen lower-fit (VO2peak: 22.6±2.8 mL.kg−1.min−1 and fourteen higher-fit participants (VO2peak: 37.4±5.9 mL.kg−1.min−1 completed three 24 min experimental protocols in a randomized order: (1 moderate-intensity continuous exercise (40% of peak power output [PPO]; (2 higher-intensity interval exercise (12 × 1 min intervals at 70% PPO separated by 1 min periods at 10% PPO; or (3 non-exercise control. Plasma cytokines were measured at rest, immediately after, and during 90 min of recovery following exercise or control. Plasma IL-6 concentrations at baseline were greater in the higher-fit compared to the lower-fit group (P = 0.02, with no difference in plasma IL-10 or TNF-α concentrations at baseline between groups. Plasma IL-6 and IL-10 concentrations in both groups increased immediately after all protocols (IL-6: P = 0.02, IL-10: P < 0.01. However, there was no difference in the IL-6 and IL-10 response between the exercise and non-exercise (control protocols. After all protocols, no changes in plasma TNF-α concentrations were observed in either the higher- or lower-fit groups. In this study, basal concentrations of circulating IL-6

Higher levels of ethyl paraben and butyl paraben in rat amniotic fluid than in maternal plasma after subcutaneous administration

DEFF Research Database (Denmark)

Frederiksen, Hanne; Taxvig, Camilla; Hass, Ulla

2008-01-01

to obtain more knowledge about the distribution of ethyl paraben and butyl paraben in pregnant rats and pups after perinatal exposure, the presented study was designed. The data show response and distribution of ethyl paraben and butyl paraben in maternal rat plasma, pools of amniotic fluids, placenta......, whole-body fetuses, and in fetal liver after dosing of dams with 100, 200, and 400 mg/kg body weight (bw)/day from gestational day 7 to 21. After cesarean section of dams, the fluids and tissues were collected, deconjugated, and purified by solid-phase extraction, and ethyl paraben and butyl paraben...... were analyzed by liquid chromatography-tandem mass spectrometry. Markedly higher levels of ethyl paraben compared to butyl paraben were found in all fluids and tissues. Both ethyl paraben and butyl paraben in maternal plasma, livers, and whole-body tissues from fetus seemed to be saturated after dosing...

Plasma cytokines, chemokines and cellular immune responses in pre-school Nigerian children infected with Plasmodium falciparum

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Noone Cariosa

2013-01-01

Full Text Available Abstract Background Malaria is a major cause of morbidity and mortality worldwide with over one million deaths annually, particularly in children under five years. This study was the first to examine plasma cytokines, chemokines and cellular immune responses in pre-school Nigerian children infected with Plasmodium falciparum from four semi-urban villages near Ile-Ife, Osun State, Nigeria. Methods Blood was obtained from 231 children (aged 39–73 months who were classified according to mean P. falciparum density per μl of blood (uninfected (n = 89, low density (10,000, n = 22. IL-12p70, IL-10, Nitric oxide, IFN-γ, TNF, IL-17, IL-4 and TGF-β, C-C chemokine RANTES, MMP-8 and TIMP-1 were measured in plasma. Peripheral blood mononuclear cells were obtained and examined markers of innate immune cells (CD14, CD36, CD56, CD54, CD11c AND HLA-DR. T-cell sub-populations (CD4, CD3 and γδTCR were intracellularly stained for IL-10, IFN-γ and TNF following polyclonal stimulation or stimulated with malaria parasites. Ascaris lumbricoides was endemic in these villages and all data were analysed taking into account the potential impact of bystander helminth infection. All data were analysed using SPSS 15 for windows and in all tests, p Results The level of P. falciparum parasitaemia was positively associated with plasma IL-10 and negatively associated with IL-12p70. The percentage of monocytes was significantly decreased in malaria-infected individuals while malaria parasitaemia was positively associated with increasing percentages of CD54+, CD11c+ and CD56+ cell populations. No association was observed in cytokine expression in mitogen-activated T-cell populations between groups and no malaria specific immune responses were detected. Although A. lumbricoides is endemic in these villages, an analysis of the data showed no impact of this helminth infection on P. falciparum parasitaemia or on immune responses associated with P. falciparum infection

Effect of ultra-endurance exercise on left ventricular performance and plasma cytokines in healthy trained men

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K Krzemiński

2016-01-01

Full Text Available The purpose of this study was to investigate the effect of ultra-endurance exercise on left ventricular (LV performance and plasma concentration of interleukin (IL-6, IL-10, IL-18 and tumour necrosis factoralpha (TNF-IX as well as to examine the relationships between exercise-induced changes in plasma cytokines and those in echocardiographic indices of LV function in ultra-marathon runners. Nine healthy trained men (mean age 3011.0 years participated in a 100-km ultra-marathon. Heart rate, blood pressure, ejection fraction (EF, fractional shortening (FS, ratio of early (E to late (A mitral inflow peak velocities (E/A, ratio of early (E' to late (A' diastolic mitral annulus peak velocities (E‘/A’ and E-wave deceleration time (DT were obtained by echocardiography before, immediately after and in the 90th minute of the recovery period. Blood samples were taken before each echocardiographic evaluation. The ultra-endurance exercise caused significant increases in plasma IL-6, IL-10, IL-18 and TNF-α. Echocardiography revealed significant decreases in both E and the E/A ratio immediately after exercise, without any significant changes in EF, FS, DT or the E/E’ ratio. At the 90th minute of the recovery period, plasma TNF-or and the E/A ratio did not differ significantly from the pre-exercise values, whereas FS was significantly lower than before and immediately after exercise. The increases in plasma TNF-or correlated with changes in FS (r=0.73 and DT (r=-0.73. It is concluded that ultra-endurance exercise causes alterations in LV diastolic function. The present data suggest that TNF-or might be involved in this effect.

Brief Communication: Maternal Plasma Autoantibodies Screening in Fetal Down Syndrome

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Karol Charkiewicz

2016-01-01

Full Text Available Imbalance in the metabolites levels which can potentially be related to certain fetal chromosomal abnormalities can stimulate mother’s immune response to produce autoantibodies directed against proteins. The aim of the study was to determine the concentration of 9000 autoantibodies in maternal plasma to detect fetal Down syndrome. Method. We performed 190 amniocenteses and found 10 patients with confirmed fetal Down syndrome (15th–18th weeks of gestation. For the purpose of our control we chose 11 women without confirmed chromosomal aberration. To assess the expression of autoantibodies in the blood plasma, we used a protein microarray, which allows for simultaneous determination of 9000 proteins per sample. Results. We revealed 213 statistically significant autoantibodies, whose expression decreased or increased in the study group with fetal Down syndrome. The second step was to create a classifier of Down syndrome pregnancy, which includes 14 antibodies. The predictive value of the classifier (specificity and sensitivity is 100%, classification errors, 0%, cross-validation errors, 0%. Conclusion. Our findings suggest that the autoantibodies may play a role in the pathophysiology of Down syndrome pregnancy. Defining their potential as biochemical markers of Down syndrome pregnancy requires further investigation on larger group of patients.

Relationships among Maternal Stress and Depression, Type 2 Responses, and Recurrent Wheezing at Age 3 Years in Low-Income Urban Families.

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Ramratnam, Sima K; Visness, Cynthia M; Jaffee, Katy F; Bloomberg, Gordon R; Kattan, Meyer; Sandel, Megan T; Wood, Robert A; Gern, James E; Wright, Rosalind J

2017-03-01

Maternal depression and prenatal and early life stress may influence childhood wheezing illnesses, potentially through effects on immune development. To test the hypothesis that maternal stress and/or depression during pregnancy and early life are associated with recurrent wheezing and aeroallergen sensitivity and altered cytokine responses (enhanced type 2 or reduced virus-induced cytokine responses) from stimulated peripheral blood mononuclear cells at age 3 years. URECA (Urban Environment and Childhood Asthma) is a birth cohort at high risk for asthma (n = 560) in four inner cities. Maternal stress, depression, and childhood wheezing episodes were assessed by quarterly questionnaires beginning at birth. Logistic and linear regression techniques were used to examine the relation of maternal stress/depression to recurrent wheezing and peripheral blood mononuclear cell cytokine responses at age 3 years. Overall, 166 (36%) children had recurrent wheeze at age 3 years. Measures of maternal perceived stress at Years 2 and 3 were positively associated with recurrent wheeze (P Maternal depression (any year) was significantly associated with recurrent wheezing (P ≤ 0.01). These associations were also significant when considered in a longitudinal analysis of cumulative stress and depression (P ≤ 0.02). Neither stress nor depression was significantly related to aeroallergen sensitization or antiviral responses. Contrary to our original hypothesis, prenatal and Year 1 stress and depression had significant inverse associations with several type 2 cytokine responses. In urban children at high risk for asthma, maternal perceived stress and depression were significantly associated with recurrent wheezing but not increased atopy or reduced antiviral responses.

The measurements of plasma cytokines in radiation-induced pneumonitis in lung cancer patients

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Hur, Won Joo; Youn, Seon Min; Lee, Hyung Sik; Yang, Kwang Mo; Sin, Geun Ho; Son, Choon Hee; Han, Jin Yeong; Lee, Ki Nam; Jeong, Min Ho

2000-01-01

To investigate whether changes in plasma concentrations of transforming growth factor-β 1(TGF-β 1), tumor necrosis factor-alpha (TNF-α) and interleukin-6 (lL -6) could be used to identify the development of radiation-induced pneumonitis in the lung cancer patients. Seventeen patients with lung cancer (11 NSCLC. 6 SCLC) were enrolled in a prospective study designed to evaluate clinical and molecular biologic correlation of radiation-induced pneumonitis. The study began in May 1998 and completed in July 1999. All patients were treated with radiotherapy with curative intent: 1.8 Gy per day, 5 fractions per week. Serial measurements of plasma TGF-β1, TNF--α and IL -6 were obtained in all patients before, weekly during radiotherapy and at each follow-up visits after completion of treatment. These measurements were quantified using enzyme linked immunosorbent assay (ELISA). All patients were evaluated for signs and symptoms of pneumonitis at each follow-up visits after completion of radiotherapy. High resolution CT (HRCT) scans were obtained when signs and symptoms of pneumonitis were developed after completion of radiotherapy. Thirteen patients eventually developed signs and symptoms of clinical pneumonitis while four patients did not. TGF- P 1 levels were elevated in - all 13 patients with pneumonitis, which showed characteristic pattern of elevation (38.45 ng/ml at pretreatment, 13.66 ng/ml during radiotherapy, then 60.63 ng/ml at 2-4 weeks after completion of radiotherapy). The levels of TNF--α and IL -6 were also elevated in the group of patients who developed pneumonitis but the pattern was not characteristic. Changes in plasma TGFβ-1 levels before, during and after radiotherapy appears to be a useful means by which to identify patients at risk for the development of symptomatic pneumonitis. Other cytokines like TNF--α and IL-6 shows no meaningful changes in association with radiation pneumonitis

Zinc and Regulation of Inflammatory Cytokines: Implications for Cardiometabolic Disease

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Foster, Meika; Samman, Samir

2012-01-01

In atherosclerosis and diabetes mellitus, the concomitant presence of low-grade systemic inflammation and mild zinc deficiency highlights a role for zinc nutrition in the management of chronic disease. This review aims to evaluate the literature that reports on the interactions of zinc and cytokines. In humans, inflammatory cytokines have been shown both to up- and down-regulate the expression of specific cellular zinc transporters in response to an increased demand for zinc in inflammatory conditions. The acute phase response includes a rapid decline in the plasma zinc concentration as a result of the redistribution of zinc into cellular compartments. Zinc deficiency influences the generation of cytokines, including IL-1β, IL-2, IL-6, and TNF-α, and in response to zinc supplementation plasma cytokines exhibit a dose-dependent response. The mechanism of action may reflect the ability of zinc to either induce or inhibit the activation of NF-κB. Confounders in understanding the zinc-cytokine relationship on the basis of in vitro experimentation include methodological issues such as the cell type and the means of activating cells in culture. Impaired zinc homeostasis and chronic inflammation feature prominently in a number of cardiometabolic diseases. Given the high prevalence of zinc deficiency and chronic disease globally, the interplay of zinc and inflammation warrants further examination. PMID:22852057

Male Seminal Relaxin Contributes to Induction of the Post-mating Cytokine Response in the Female Mouse Uterus

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Danielle J. Glynn

2017-06-01

Full Text Available The hormone relaxin is important in female reproduction for embryo implantation, cardiovascular function, and during labor and lactation. Relaxin is also synthesized in males by organs of the male tract. We hypothesized that relaxin might be one component of seminal plasma responsible for eliciting the female cytokine response induced in the uterus at mating. When recombinant relaxin was injected into the uterus of wild-type (Rln+/+ mice at estrus, it evoked the production of Cxcl1 mRNA and its secreted protein product CXCL1 in four of eight animals. Mating experiments were then conducted using mice with a null mutation in the relaxin gene (Rln−/− mice. qRT-PCR analysis of mRNA expression in wild-type females showed diminished uterine expression of several cytokine and chemokine genes in the absence of male relaxin. Similar differences were also noted comparing Rln−/− and Rln+/+ females mated to wild-type males. Quantification of uterine luminal fluid cytokine content confirmed that male relaxin provokes the production of CXCL10 and CSF3 in Rln+/+ females. Differences were also seen comparing Rln−/− and Rln+/+ females mated with Rln−/− males for CXCL1, CSF3, and CCL5, implying that endogenous relaxin in females might prime the uterus to respond appropriately to seminal fluid at coitus. Finally, pan-leukocyte CD45 mRNA was increased in wild-type matings compared to other combinations, implying that male and female relaxin may trigger leukocyte expansion in the uterus. We conclude that male and/or female relaxin may be important in activating the uterine cytokine/chemokine network required to initiate maternal immune adaptation to pregnancy.

Increased chemerin concentrations in fetuses of obese mothers and correlation with maternal insulin sensitivity.

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Barker, Gillian; Lim, Ratana; Rice, Gregory E; Lappas, Martha

2012-11-01

The aim of this study was to determine the effect of maternal obesity and gestational diabetes mellitus (GDM) on (i) the circulating concentrations of chemerin in cord and maternal plasma, and (ii) gene expression and release of chemerin from human placenta and adipose tissue. Chemerin concentrations were measured in maternal and cord plasma from 62 normal glucose tolerant women (NGT) and 69 women with GDM at the time of term elective Caesarean section. Placenta and adipose tissue expression and release of chemerin was measured from 22 NGT and 22 GDM women. There was no effect of maternal obesity or GDM on maternal chemerin concentrations. Chemerin concentrations were significantly higher in cord plasma from women with maternal obesity. Cord chemerin concentrations in NGT women negatively correlated with the concentrations of maternal insulin sensitivity. There was no effect of GDM on maternal and cord chemerin concentrations, and on the release of chemerin from placenta and adipose tissue. At the time of term Caesarean section, preexisting maternal obesity, and its associated insulin resistance, is associated with higher cord plasma chemerin concentrations.

Cytokine expression in malaria-infected non-human primate placentas

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M.M. Gicheru

2012-06-01

Full Text Available Malaria parasites are known to mediate the induction of inflammatory immune responses at the maternal-foetal interface during placental malaria (PM leading to adverse consequences like pre-term deliveries and abortions. Immunological events that take place within the malaria-infected placental micro-environment leading to retarded foetal growth and disruption of pregnancies are among the critical parameters that are still in need of further elucidation. The establishment of more animal models for studying placental malaria can provide novel ways of circumventing problems experienced during placental malaria research in humans such as inaccurate estimation of gestational ages. Using the newly established olive baboon (Papio anubis-Plasmodium knowlesi (P. knowlesi H strain model of placental malaria, experiments were carried out to determine placental cytokine profiles underlying the immunopathogenesis of placental malaria. Four pregnant olive baboons were infected with blood stage P. knowlesi H strain parasites on the one fiftieth day of gestation while four other uninfected pregnant olive baboons were maintained as uninfected controls. After nine days of infection, placentas were extracted from all the eight baboons through cesarean surgery and used for the processing of placental plasma and sera samples for cytokine sandwich enzyme linked immunosorbent assays (ELISA. Results indicated that the occurrence of placental malaria was associated with elevated concentrations of tumour necrosis factor alpha (TNF-α and interleukin 12 (IL-12. Increased levels of IL-4, IL-6 and IL-10 and interferon gamma (IFN-γ levels were detected in uninfected placentas. These findings match previous reports regarding immunity during PM thereby demonstrating the reliability of the olive baboon-P. knowlesi model for use in further studies.

The modulatory role of cytokines IL-4 and IL-17 in the functional activity of phagocytes in diabetic pregnant women.

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Fagundes, Danny L G; França, Eduardo L; Gonzatti, Michelangelo B; Rugde, Marilza V C; Calderon, Iracema M P; Honorio-França, Adenilda C

2018-01-01

The study investigated the role of cytokines IL-4 and IL-17 in the modulation of the functional activity of mononuclear phagocytes in diabetic pregnant women with hyperglycemia. Sixty pregnant women were assigned to the following groups: nondiabetic (ND), mild gestational hyperglycemia (MGH), gestational diabetes mellitus (GDM), or type 2 diabetes mellitus (DM2). The functional activity of phagocytes from maternal blood, cord blood, and colostrum was assessed by determining their superoxide release, phagocytosis, microbicidal activity, and intracellular Ca 2+ release. Irrespective of glycemic status, colostrum and blood cells treated with IL-4 and IL-17 increased superoxide release in the presence of enteropathogenic Escherichia coli (EPEC). The highest phagocytosis rate was observed in cells from the DM2 group treated with IL-4. In all the groups, phagocytes from colostrum, maternal blood, and cord blood exhibited higher microbicidal activity against EPEC when treated with cytokines. IL-17 increased intracellular Ca 2+ release by colostrum phagocytes in diabetic groups. The results indicate that the IL-4 and IL-17 modulate the functional activity of phagocytes in the maternal blood, cord blood, and colostrum of diabetic mother. The natural immunity resulting from the interaction between the cells and cytokines tested may be an alternative procedure to improve the prognosis of maternal and newborn infections. © 2017 APMIS. Published by John Wiley & Sons Ltd.

Clinical significance of measurement of plasma relevant cytokines (GM-CSF, IL-2, TPO, EPO) levels in patients with aplastic anemia

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Yu Tintin

2006-01-01

Objective: To investigate the role of relevant cytokines in the development and pathogenesis of aplastic anemia. Methods: Plasma GM-CSF, IL-2, TPO (with RIA) and EPO (with CLIA) contents were measured in 100 patients (acute 43, chronic 57) with aplastic anemia and 50 controls. Complete blood count was also performed in all these subjects. Results: The peripheral RBC, WBC, platelet counts and GM-CSF contents were significantly lower in the patients with aplastic anemia than those in the controls (P<0.05), while the IL-2, EPO and TPO contents were significantly higher in the patients (P<0.05). GM-CSF contents were positively correlated with the WBC numbers. EPO contents were negatively correlated with the RBC counts and TPO contents were correlated (negatively) with the platelet counts. Conclusion: There was correlationship between each blood elements (WBC, RBC, platelet) and its corresponding cytokine (GS-CSF, EPO, TPO respectively). IL-2 contents were not correlated with WBC counts. (authors)

Effects of Mind-Body Training on Cytokines and Their Interactions with Catecholamines.

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Jang, Joon Hwan; Park, Hye Yoon; Lee, Ui Soon; Lee, Kyung-Jun; Kang, Do-Hyung

2017-07-01

Mind-body training (MBT) may control reactions to stress and regulate the nervous and immune systems. The present study was designed to assess the effects of MBT on plasma cytokines and their interactions with catecholamines. The study group consisted of 80 subjects who practice MBT and a control group of 62 healthy subjects. Plasma catecholamine (norepinephrine, NE; epinephrine, E; and dopamine, DA) and cytokine (TNF-alpha, IL-6, IFN-gamma, and IL-10) levels were measured, and the differences between the MBT and control groups and the interactions of cytokines with catecholamines were investigated. A significant increase in IL-10+IFN-gamma was found in females of the MBT group compared with controls. Also, a significant increase of IL-10 (anti-inflammatory cytokine) in the MBT group was shown in a specific condition in which TNF-alpha and IL-6 (pro-inflammatory cytokines) are almost absent (≤1 ng/L) compared with controls. In the MBT group, significant positive correlations were found between IL-10 and the NE/E ratio and between IL-10 and the DA/E ratio, whereas the control group did not show any such correlations. MBT may increase IL-10, under specific conditions such as a decrease of pro-inflammatory cytokines or E, which may regulate the stress response and possibly contribute to effective and beneficial interactions between the nervous and immune systems.

Effect of fetal growth on maternal protein metabolism in postabsorptive rat

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Ling, P.R.; Bistrian, B.R.; Blackburn, G.L.; Istfan, N.

1987-01-01

Rates of protein synthesis were measured in whole fetuses and maternal tissues at 17 and 20 days of gestation in postabsorptive rats using continuous infusion of L-[1- 14 C]leucine. Fetal protein degradation rates were derived from the fractional rates of synthesis and growth. Whole-body (plasma) leucine kinetics in the mother showed a significant reduction of the fraction of plasma leucine oxidized in the mothers bearing older fetuses, a slight increase in the plasma flux, with total leucine oxidation and incorporation into protein remaining similar at the two gestational ages. Estimates of fractional protein synthesis in maternal tissues revealed an increase in placental and hepatic rates at 20 days of gestation, whereas the fractional synthetic rate in muscle remained unchanged. A model for estimation of the redistribution of leucine between plasma and tissues is described in detail. This model revealed a more efficient utilization of leucine in fetal protein synthesis in comparison with other maternal tissues, a greater dependency of the fetus on plasma supply of leucine, and a significant increase (2-fold) in the release of leucine from maternal muscle as the fetal requirements increased proportionately with its size. The latter conclusion, supported by nitrogen analysis and the ratio of bound-to-free leucine in maternal tissues, confirms the importance of maternal stores in maintaining the homeostasis of essential amino acids during late pregnancy

Cytokine expression and cytokine-based T-cell profiling in occupational medicamentosa-like dermatitis due to trichloroethylene.

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Xueqin, Yang; Wenxue, Li; Peimao, Li; Wen, Zhang; Xianqing, Huang; Zhixiong, Zhuang

2018-05-15

Early diagnosis and treatment of occupational medicamentosa-like dermatitis due to trichloroethylene (OMLDT) are absence of specific and reliable diagnostic/therapeutic biomarkers. This study was conducted on 30 cases of OMLDT, 58 workers exposed to trichloroethylene (TCE) and 40 unexposed controls in order to identify any cytokine signatures that give an index to CD4 + T cell differential and serve as biomarkers of OMLDT. Expression profiles of Th 1 , Th 2 , Th 17 and Treg cell type-specifying transcription factors and cytokines were analyzed using real time quantitative PCR (RT-qPCR) assay. To explore whether such expression profiles reflected their steady state plasma levels, a Luminex liquid fluorescence analysis was conducted. We found that the expression of transcription factors FoxP3 transcription factors (P = 0.006 and P < 0.0001) and IL-10 cytokine (P = 0.0008 and P < 0.0001) of the Treg subset were significantly higher in patients than TCE exposure workers and unexposed controls, suggesting that Treg cells were active after the occurrence of OMLDT. The transcript levels of IL-6 were significantly lower in the TCE exposure groups including patients and exposure workers as compared to the unexposed controls (P < 0.0001 and P = 0.0008). Circulating levels of assessed cytokines of IL-6 (P = 0.001 and P = 0.011) and TFN-α (P = 0.005 and P < 0.0001) were lower in the exposure groups than in the unexposed controls. Compared to the controls, the levels of IL-10 in patients were higher (P = 0.001 and P = 0.0008). There was a significantly positive correlation between the plasma levels IL-6 and IL-10 in TCE exposed workers. These alterations in the expression of transcription factors and cytokines highlight the underlying dysregulation of T cell subsets in OMLDT that reflect an immune tolerance or immune inhibition. Therefore, the elevation of IL-10 level may be a kind of pathogenesis indicator, and the decline in IL

Maternal and Cord Blood Levels of Serum Amyloid A, C-Reactive Protein, Tumor Necrosis Factor-α, Interleukin -1β, and Interleukin-8 During and After Delivery

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Luciane Marzzullo Cicarelli

2005-01-01

after delivery and try to correlate these proteins with tumor necrosis factor-α, interleukin -1β, and interleukin-8. Acute-phase proteins and cytokines were measured by ELISA in 24 healthy pregnant women undergoing vaginal delivery or Cesarean section. Cord blood samples in addition to maternal blood were collected. SAA and CRP reached the maximum maternal serum levels 24 hours after delivery, while cytokines remained constant over time. SAA and CRP were significantly higher in maternal serum than in newborn's (P<.001 at the moment of delivery. SAA and CRP, regardless of the type of delivery, reproduce the common pattern observed in most inflammatory conditions. Proinflammatory cytokine serum levels do not mirror the increase in SAA and CRP levels.

Characterization of Adsorbents for Cytokine Removal from Blood in an In Vitro Model.

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Harm, Stephan; Gabor, Franz; Hartmann, Jens

2015-01-01

Cytokines are basic targets that have to be removed effectively in order to improve the patient's health status in treating severe inflammation, sepsis, and septic shock. Although there are different adsorbents commercially available, the success of their clinical use is limited. Here, we tested different adsorbents for their effective removal of cytokines from plasma and the resulting effect on endothelial cell activation. The three polystyrene divinylbenzene (PS-DVB) based adsorbents Amberchrom CG161c and CG300m and a clinically approved haemoperfusion adsorbent (HAC) were studied with regard to cytokine removal in human blood. To induce cytokine release from leucocytes, human blood cells were stimulated with 1 ng/ml LPS for 4 hours. Plasma was separated and adsorption experiments in a dynamic model were performed. The effect of cytokine removal on endothelial cell activation was evaluated using a HUVEC-based cell culture model. The beneficial outcome was assessed by measuring ICAM-1, E-selectin, and secreted cytokines IL-8 and IL-6. Additionally the threshold concentration for HUVEC activation by TNF-α and IL-1β was determined using this cell culture model. CG161c showed promising results in removing the investigated cytokines. Due to its pore size the adsorbent efficiently removed the key factor TNF-α, outperforming the commercially available adsorbents. The CG161c treatment reduced cytokine secretion and expression of cell adhesion molecules by HUVEC which underlines the importance of effective removal of TNF-α in inflammatory diseases. These results confirm the hypothesis that cytokine removal from the blood should approach physiological levels in order to reduce endothelial cell activation.

Influence of maternal age, gestational age and fetal gender on expression of immune mediators in amniotic fluid

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Weissenbacher Tobias

2012-07-01

Full Text Available Abstract Background Variations in cytokine and immune mediator expression patterns in amniotic fluid due to gestational age, maternal age and fetal gender were investigated. Findings Amniotic fluid samples were obtained from 192 women, 82 with a mid-trimester amniocentesis (median gestational age 17 weeks and 110 with a caesarean section not in labor (median gestational age 39 weeks. Amniotic fluid was screened by commercial ELISAs for the TH1/TH2/TH17 cytokines and immune mediators IL-1 beta, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-15, IL-17, TNF alpha, GRO-alpha, MIP1alpha, MIP1beta, Histone, and IP10. Analysis was by Bonferroni correction for multiple comparisons. None of the 15 examined cytokines revealed any differences in expression patterns regarding fetal gender. Significant differences were found in IL-4, IL-10, IL-12, TNF- alpha, GRO-alpha and MIP1-beta with respect to gestational age and in GRO-alpha regarding maternal age. Conclusion Cytokines utilized as biomarkers in the diagnosis of intrauterine infections are not influenced in their expression pattern by fetal gender but may vary with respect to maternal age and gestational age.

The association between maternal psychological stress and inflammatory cytokines in allergic young children

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Mayumi Tsuji

2016-01-01

Full Text Available Background. Previous studies have shown that psychological stress is linked to asthma prevalence. Parental psychological stress may potentially influence inflammatory responses in their allergic children. The purpose of this study is to clarify the association between maternal psychological status and inflammatory response of allergic young children.Methods. The study subjects were 152 young allergic children (median age: 13 months who had not shown any allergic symptoms in the past one month. mRNA expression levels of the inflammatory response genes IL-6, IL-8, IL-10 and IL-22 were quantified by qRT-PCR. Maternal psychological status was assessed by standardized questionnaires: the Centre for Epidemiological Studies Depression Scale (CES-D for depression and the Japanese Perceived Stress Scale (JPSS for perceived stress.Results. A significant positive association was observed between maternal CES-D scores and IL-6 mRNA expression in the children with asthma. The JPSS scores were also positively associated with IL-8 mRNA expression in asthmatic children and IL-6 mRNA expression in children with allergic rhinitis. Similar trends were observed among children positive for house dust mite-specific IgE, but these associations were not significant.Conclusion. This study supports the hypothesis that maternal psychological stress affects the inflammatory response in their allergic children.

Foetal immune programming: hormones, cytokines, microbes and regulatory T cells.

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Hsu, Peter; Nanan, Ralph

2014-10-01

In addition to genetic factors, environmental cues play important roles in shaping the immune system. The first environment that the developing foetal immune system encounters is the uterus. Although physically the mother and the foetus are separated by the placental membranes, various factors such as hormones and cytokines may provide "environmental cues" to the foetal immune system. Additionally, increasing evidence suggests that prenatal maternal environmental factors, particularly microbial exposure, might significantly influence the foetal immune system, affecting long-term outcomes, a concept termed foetal immune programming. Here we discuss the potential mediators of foetal immune programming, focusing on the role of pregnancy-related hormones, cytokines and regulatory T cells, which play a critical role in immune tolerance. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Cytokines in systemic lupus erythematosus: far beyond Th1/Th2 dualism lupus: cytokine profiles.

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Guimarães, Poliana Macedo; Scavuzzi, Bruna Miglioranza; Stadtlober, Nicole Perugini; Franchi Santos, Lorena Flor da Rosa; Lozovoy, Marcell Alysson Batisti; Iriyoda, Tatiana Mayumi Veiga; Costa, Neide Tomimura; Reiche, Edna Maria Vissoci; Maes, Michael; Dichi, Isaias; Simão, Andréa Name Colado

2017-10-01

The aims of this study were to delineate cytokine profiles of systemic lupus erythematosus (SLE), construct prediction models for diagnosis and disease activity using those profiles, and to examine the associations between TNFB Ncol polymorphism, body mass index (BMI) and vitamin D levels with cytokine levels. Two hundred SLE patients and 196 healthy controls participated in this case-control study. Plasma cytokines levels of tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-1β, IL- 4, IL-6, IL-10, IL-12 and IL-17 were measured and cytokines profiles were computed. IL-6, IL-12, IL-17, IFN-γ and IL-10 levels were significantly higher in SLE, while IL-4 was lower in SLE. The Th1/Th2 and Th1+Th17/Th2 profiles were significantly higher in SLE than in healthy controls, whereas there were no significant differences in the proinflammatory cytokine profile (TNFα+IL-6+IL-1β). In total, 90.4% of all subjects were correctly classified using Th1+Th17 profile and IL-10 (positively associated) and IL-4 (negatively associated) as predictor variables (sensitivity=66.7% and specificity=96.9%). In all, 20.9% of the variance in the SLE Disease Activity Index was predicted by the Th1+Th17/Th2 ratio, IL-10 and BMI (all positively) and proinflammatory profile (inversely associated). B1/B1 genotype is accompanied by increased IL-17 and Th17/Th2 ratio, while B1/B2 genotype is accompanied by higher IL-4 and IFNγ values. 25-OH vitamin D was inversely associated with IFN-γ levels. SLE is accompanied by Th1, Th17 and Treg profile and lowered IL-4 production. Lowered vitamin D levels and B1/B1 genotype, but not BMI, contribute to changes in cytokines profiles. Future treatments should target Th1, Th2 and Th17 profiles rather than inflammatory cytokines.

Evaluation of Sample Stability and Automated DNA Extraction for Fetal Sex Determination Using Cell-Free Fetal DNA in Maternal Plasma

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Elena Ordoñez

2013-01-01

Full Text Available Objective. The detection of paternally inherited sequences in maternal plasma, such as the SRY gene for fetal sexing or RHD for fetal blood group genotyping, is becoming part of daily routine in diagnostic laboratories. Due to the low percentage of fetal DNA, it is crucial to ensure sample stability and the efficiency of DNA extraction. We evaluated blood stability at 4°C for at least 24 hours and automated DNA extraction, for fetal sex determination in maternal plasma. Methods. A total of 158 blood samples were collected, using EDTA-K tubes, from women in their 1st trimester of pregnancy. Samples were kept at 4°C for at least 24 hours before processing. An automated DNA extraction was evaluated, and its efficiency was compared with a standard manual procedure. The SRY marker was used to quantify cfDNA by real-time PCR. Results. Although lower cfDNA amounts were obtained by automated DNA extraction (mean 107,35 GE/mL versus 259,43 GE/mL, the SRY sequence was successfully detected in all 108 samples from pregnancies with male fetuses. Conclusion. We successfully evaluated the suitability of standard blood tubes for the collection of maternal blood and assessed samples to be suitable for analysis at least 24 hours later. This would allow shipping to a central reference laboratory almost from anywhere in Europe.

Impaired cytokine production and suppressed lymphocyte proliferation activity in HCV-infected cocaine and heroin ("speedball") users.

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Ríos-Olivares, Eddy; Vilá, Luis M; Reyes, Juan C; Rodríguez, José W; Colón, J Héctor M; Pagán, Nat O; Marrero, Amalia; Ríos-Orraca, Zilka M; Boukli, Nawal M; Shapshak, Paul; Robles, Rafaela R

2006-12-01

HCV-infected "speedball" users (n = 30) were selected from an original cohort of 400 intravenous drug users for cytokine analysis. Cytokine concentrations (TNF-alpha, IL-1beta, IL-6, IFN-gamma, IL-2, IL-4, IL-10 and IL-12) were determined in plasma and peripheral blood mononuclear cells (PBMC) cultures derived ex vivo from these patients. In addition, lymphocyte proliferation was measured in 49 HCV-positive "speedball" users. TNF-alpha, IL-6, IFN-gamma, IL-2, IL-4, IL-10, IL-12 cytokines and not IL-1beta were significantly increased in plasma from HCV-positive "speedball" users compared with healthy controls. Except for IL-10, all other cytokines measured were augmented in phytohemagglutinin-stimulated PBMC cultures from HCV-positive "speedball" users. Likewise, overproduction of cytokines TNF-alpha, IL-1beta, IL-6 and IFN-gamma, was consistently detected when PBMC cultures from HCV-positive "speedball" users were stimulated with a biological response modifier. However, HCV-infected "speedball" users showed significant reduction in lymphoproliferative activity. Compared with healthy subjects, there was a consistent overproduction of both TH1 and TH2 type cytokines in the plasma and PBMC's of HCV-infected "speedball" users. Furthermore, there was a persistent reduction of lymphoproliferative activity in this group. These immunologic abnormalities, coupled with the range of response between the two TH-types in HCV-infected "speedball" users, suggest impairment in the regulatory mechanism of the TH1-TH2 system.

Decreased plasma levels of factor II + VII + X correlate with increased levels of soluble cytokine receptors in patients with malaria and meningococcal infections

DEFF Research Database (Denmark)

Bygbjerg, I C; Hansen, M B; Rønn, A M

1997-01-01

The levels of coagulation factors II + VII + X and of blood platelets (thrombocytes) as well as of cytokines and soluble cytokine receptors were studied in the patients with malaria or meningococcal infections. The coagulation factors were decreased particularly in the meningococcal patients, while...... thrombocytes were lowest in the Plasmodium falciparum malaria patients. There was no correlation between factors II + VII + X and thrombocytes, but plasma levels of coagulation factors II + VII + X were found to correlate inversely with levels of soluble interleukin-2 receptor (sIL-2R) and soluble tumour...... necrosis factor-I (sTNF-RI) in patients with malaria and meningococcal infections. Elevated sIL-2R and sTNF-RI levels and decreased coagulation factors reverted to normal within 3-5 days after initiation of therapy in P. falciparum patients followed consecutively. Estimation of coagulation factors may...

Beneficial effects of cytokine induced hyperlipidemia.

Science.gov (United States)

Feingold, K R; Hardardóttir, I; Grunfeld, C

1998-01-01

Infection, inflammation and trauma induce marked changes in the plasma levels of a wide variety of proteins (acute phase response), and these changes are mediated by cytokines. The acute phase response is thought to be beneficial to the host. The host's response to injury also results in dramatic alterations in lipid metabolism and circulating lipoprotein levels which are mediated by cytokines. A large number of cytokines including TNF, the interleukins, and the interferons increase serum triglyceride levels. This rapid increase (1-2 h) is predominantly due to an increase in hepatic VLDL secretion while the late increase may be due to a variety of factors including increased hepatic production of VLDL or delayed clearance secondary to a decrease in lipoprotein lipase activity and/or apolipoprotein E levels on VLDL. In animals other than primates, cytokines also increase serum cholesterol levels, most likely by increasing hepatic cholesterol. Cytokines increase hepatic cholesterol synthesis by stimulating HMG CoA reductase gene expression and decrease hepatic cholesterol catabolism by inhibiting cholesterol 7 alpha-hydroxylase, the key enzyme in bile acid synthesis. Injury and/or cytokines also decrease HDL cholesterol levels and induce alterations in the composition of HDL. The content of SAA and apolipoprotein J increase, apolipoprotein A1 may decrease, and the cholesterol ester content decreases while free cholesterol increases. Additionally, key proteins involved in HDL metabolism are altered by cytokines; LCAT activity, hepatic lipase activity, and CETP levels decrease. These changes in lipid and lipoprotein metabolism may be beneficial in a number of ways including: lipoproteins competing with viruses for cellular receptors, apolipoproteins neutralizing viruses, lipoproteins binding and targeting parasites for destruction, apolipoproteins lysing parasites, redistribution of nutrients to cells involved in the immune response and/or tissue repair, and

Endogenous brain IL-1 mediates LPS-induced anorexia and hypothalamic cytokine expression.

Science.gov (United States)

Layé, S; Gheusi, G; Cremona, S; Combe, C; Kelley, K; Dantzer, R; Parnet, P

2000-07-01

The present study was designed to determine the role of endogenous brain interleukin (IL)-1 in the anorexic response to lipopolysaccharide (LPS). Intraperitoneal administration of LPS (5-10 microgram/mouse) induced a dramatic, but transient, decrease in food intake, associated with an enhanced expression of proinflammatory cytokine mRNA (IL-1beta, IL-6, and tumor necrosis factor-alpha) in the hypothalamus. This dose of LPS also increased plasma levels of IL-1beta. Intracerebroventricular pretreatment with IL-1 receptor antagonist (4 microgram/mouse) attenuated LPS-induced depression of food intake and totally blocked the LPS-induced enhanced expression of proinflammatory cytokine mRNA measured in the hypothalamus 1 h after treatment. In contrast, LPS-induced increases in plasma levels of IL-1beta were not altered. These findings indicate that endogenous brain IL-1 plays a pivotal role in the development of the hypothalamic cytokine response to a systemic inflammatory stimulus.

A rapid, accurate and robust particle-based assay for the simultaneous screening of plasma samples for the presence of five different anti-cytokine autoantibodies

DEFF Research Database (Denmark)

Guldager, Daniel Kring Rasmussen; von Stemann, Jakob Hjorth; Larsen, Rune

2015-01-01

suitable for larger screenings. Based on confirmed antibody binding characteristics and the resultant reactivity in this multiplex assay, a classification of the c-aAb levels was suggested. The screening results of the recipients who received blood transfusions indicate that more studies are needed...... plasma samples and pooled normal immunoglobulin preparations were used to validate the assay. Plasma samples from 98 transfusion recipients, half of whom presented with febrile reactions, were tested by the assay. RESULTS: The assay detected specific and saturable immunoglobulin G (IgG) binding to each...... cytokine autoantibodies quantities in the negative plasma samples ranged between 80% and 125%. The analytical intra- and inter-assay variations were 4% and 11%, respectively. Varying c-aAb levels were detectable in the transfusion recipients. There was no difference in c-aAb frequency between the patients...

Inflammatory Disturbances in Preeclampsia: Relationship between Maternal and Umbilical Cord Blood

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Cristina Catarino

2012-01-01

Full Text Available Preeclampsia (PE is one of the main causes of maternal and fetal mortality and morbidity. PE is associated with an inflammatory state and with oxidative stress, in maternal circulation. Our aim was to evaluate and compare the levels of oxidative stress and inflammatory markers in maternal and umbilical cord blood (UCB, in normal and PE pregnancies. We measured acute-phase proteins (CRP and α1-antitrypsin, proinflammatory cytokines (IL-6 and TNF-α, leukocyte activation (elastase, lactoferrin, sL-selectin, sVCAM, sPECAM, total antioxidant status (TAS, thiobarbituric acid reactive substances (TBARS, and uric acid levels. We studied 42 healthy pregnant women, 46 PE women, and their neonates. The concentrations of IL-6, TNF-α, α1-antitrypsin, CRP, sVCAM, uric acid, and TBARS were significantly higher, and sL-selectin was significantly lower in PE pregnant women as compared with normotensive pregnant women. In newborns uric acid, α1-antitrypsin, and CRP values were significantly higher in PE; leukocyte count, sL-selectin, lactoferrin, and the ratio elastase/α1-antitrypsin were significantly lower. Our data suggest that PE pregnancy is associated with an enhanced maternal inflammatory condition, which is reflected in fetal circulation. This enhanced inflammatory state seems to be related to endothelial dysfunction and increased cytokine synthesis, rather than with neutrophil activation.

Maternal BMI during Pregnancy: Effect on trace elements Status and ...

African Journals Online (AJOL)

Maternal BMI was significantly positively related to age, parity and socioeconomic status. While a negative relationship was found between plasma copper and maternal BMI, significantly (p < 0.05) lower zinc levels were found in underweight and obese women when compared to women with normal BMI. Maternal anaemia ...

Resistance Training Does Not Protect Against Increases in Plasma Cytokine Levels Among Germ Cell Cancer Patients During and After Chemotherapy

DEFF Research Database (Denmark)

Christensen, Jesper Frank; Tolver, Anders; Andersen, J.L.

2014-01-01

Abstract Context: Testicular germ cell cancer (GCC) patients treated with cisplatin-etoposide-bleomycin chemotherapy (BEP) have excellent prognosis but have an increased risk of late-occurring morbidities, which may be associated with changes in the inflammatory profile. Objective: The objective...... of the study was to explore plasma cytokine concentrations in GCC patients randomized to resistance training or usual care during BEP, in comparison with healthy controls. Design/Setting: This was a randomized controlled trial in GCC patients enrolled from an oncology clinic, including a healthy reference......). Changes in TNF-α correlated with pulmonary toxicity (P BEP display consistently elevated levels of systemic inflammatory markers compared with healthy...

Polymorphisms in Genes Coding for Cytokines, Mannose-Binding Lectin, Collagen Metabolism and Thrombophilia in Women with Cervical Insufficiency

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Sundtoft, Iben; Uldbjerg, Niels; Steffensen, Rudi

2015-01-01

OBJECTIVE: To study the association between cervical insufficiency and single nucleotide polymorphisms in seven genes coding for pro- and anti-inflammatory cytokine-related factors, mannose-binding lectin 2 (MBL2), collagen1α1 (COL1A1), factor II and factor V Leiden genes. METHODS: In a case......-control study, potential maternal biomarkers for cervical insufficiency were investigated in 30 women with a history of second-trimester miscarriage or preterm birth due to cervical insufficiency and in 70 control women. RESULTS: Homozygous carriers of the interleukin 6 (IL6) -174 genotype GG had an odds ratio...... (OR) of 3.1 [95% confidence interval (95% CI) 1.3-7.4, p = 0.01] and MBL2 genotypes coding for low or intermediate levels of plasma MBL had an OR of 3.3 (95% CI 1.2-9.0, p = 0.01) for cervical insufficiency compared with controls. Serum MBL levels were lower in women with cervical insufficiency than...

Elevated plasma urokinase receptor predicts low birth weight in maternal malaria

DEFF Research Database (Denmark)

Ostrowski, S R; Shulman, C E; Peshu, N

2007-01-01

-suPAR and gestational age were the only independent predictors of birth weight in multivariate linear regression adjusted for maternal-suPAR, HIV-1 infection, age, BMI, haemoglobin, peripheral parasitaemia, parity and gestational age; 1 ng/mL higher maternal-suPAR predicted -56 g (95% CI -100 to -12, P = 0.016) reduced...... birth weight. Cord-suPAR could not predict birth weight after adjusting for gestational age. Future studies are warranted to investigate whether the maternal suPAR level is increased earlier in pregnancy in women with active placental malaria infection and whether early maternal suPAR measurements can...... predict birth weight. If so, measurements of maternal suPAR early in pregnancy might then potentially identify women with increased needs for antenatal care and intervention....

Maternal and fetal alternative complement pathway activation in early severe preeclampsia.

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Hoffman, M Camille; Rumer, Kristen K; Kramer, Anita; Lynch, Anne M; Winn, Virginia D

2014-01-01

We sought to determine whether alternative complement activation fragment Bb (Bb) levels are elevated in the maternal, fetal, and placental blood in cases of severe preeclampsia (PE) compared with normotensive controls. This was a cross-sectional study of women admitted at ≥24 weeks gestation with or without severe PE. Maternal plasma was collected at the time of enrollment. Umbilical venous cord and intervillous space blood were collected at delivery. Plasma Bb levels were assessed using ELISA. Bb levels were compared between cases and controls. Median Bb levels were higher in the maternal plasma of severe PE subjects (n = 24) than in controls (n = 20), 1.45 ± 1.03 versus 0.65 ± 0.23 μg/mL, P < 0.001. In umbilical venous plasma, Bb levels were higher in severe PE subjects (n = 15) compared with controls (n = 15), 2.48 ± 1.40 versus 1.01 ± 0.57 μg/mL, P = 0.01. Activation fragment Bb is increased in the maternal and umbilical venous blood of cases of severe PE when compared with normotensive controls. These data provide support for alternative complement pathway involvement in the pathogenesis of severe PE and demonstrate that alternative complement activation occurs not only in the maternal but also in the fetal compartment. © 2013 John Wiley & Sons Ltd.

Maternal plasma cholesterol and duration of pregnancy: A prospective cohort study in Ghana.

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Oaks, Brietta M; Stewart, Christine P; Laugero, Kevin D; Adu-Afarwuah, Seth; Lartey, Anna; Vosti, Stephen A; Ashorn, Per; Dewey, Kathryn G

2017-10-01

Low plasma cholesterol may be associated with preterm birth; however, results are mixed and limited primarily to high-income countries. Our objective was to determine whether maternal plasma lipid concentrations are associated with pregnancy duration. We performed a nested cohort (n = 320) study of pregnant Ghanaian women enrolled in a randomized controlled trial. Total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, and triglyceride concentrations were analyzed in plasma at ≤20and 36 weeks gestation as continuous variables and also categorized into low, referent, or high (90th percentile). At ≤20 weeks, plasma lipid concentrations were not associated with pregnancy duration. At 36 weeks, total cholesterol and triglyceride concentrations were not associated with pregnancy duration. Higher HDL-C at 36 weeks was associated with a longer pregnancy duration (adjusted β-coefficient ± standard error: 0.05 ± 0.02 days mg -1 /dL, p = .02); pregnancy duration was 5.9 ± 2.0 (mean ± standard error) days shorter among women with low HDL-C compared with the referent group (10th-90th percentile) (p = .02) and 8.6 ± 2.6 days shorter when compared with the high HDL-C group (p = .003). Pregnancy duration was 4.9 ± 2.1 days longer among women with low low-density lipoprotein cholesterol at 36 weeks gestation when compared with the referent group (p = .051). Our data suggest that low HDL-C in the third trimester of pregnancy is associated with a shorter duration of pregnancy in this study population but do not support the hypothesis that low total cholesterol is associated with a shorter pregnancy duration. © 2016 John Wiley & Sons Ltd.

Cytokine-Modulating Strategies and Newer Cytokine Targets for Arthritis Therapy

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Shivaprasad H. Venkatesha

2014-12-01

Full Text Available Cytokines are the key mediators of inflammation in the course of autoimmune arthritis and other immune-mediated diseases. Uncontrolled production of the pro-inflammatory cytokines such as interferon-γ (IFN-γ, tumor necrosis factor α (TNFα, interleukin-6 (IL-6, and IL-17 can promote autoimmune pathology, whereas anti-inflammatory cytokines including IL-4, IL-10, and IL-27 can help control inflammation and tissue damage. The pro-inflammatory cytokines are the prime targets of the strategies to control rheumatoid arthritis (RA. For example, the neutralization of TNFα, either by engineered anti-cytokine antibodies or by soluble cytokine receptors as decoys, has proven successful in the treatment of RA. The activity of pro-inflammatory cytokines can also be downregulated either by using specific siRNA to inhibit the expression of a particular cytokine or by using small molecule inhibitors of cytokine signaling. Furthermore, the use of anti-inflammatory cytokines or cytokine antagonists delivered via gene therapy has proven to be an effective approach to regulate autoimmunity. Unexpectedly, under certain conditions, TNFα, IFN-γ, and few other cytokines can display anti-inflammatory activities. Increasing awareness of this phenomenon might help develop appropriate regimens to harness or avoid this effect. Furthermore, the relatively newer cytokines such as IL-32, IL-34 and IL-35 are being investigated for their potential role in the pathogenesis and treatment of arthritis.

Impact of gender and menstrual cycle phase on plasma cytokine concentrations.

LENUS (Irish Health Repository)

O'Brien, Sinead M

2012-02-03

OBJECTIVE: The lifetime prevalence of major depression is twice as high in females as in males. Depression is known to increase at periods where there are changes in gonadal hormones. We examined pro- and anti-inflammatory cytokine levels during the normal menstrual cycle of healthy females compared to similar time points in healthy males. METHODS: Plasma concentrations of interleukin (IL)-4, IL-6, IL-8, IL-10, tumour necrosis factor-alpha (TNF-alpha) and soluble IL-6 receptor (sIL-6R) were measured with enzyme-linked immunosorbent assays in healthy females during the normal ovulatory menstrual cycle and also in males at similar time points. RESULTS: The luteal phase of the menstrual cycle is associated with increased production of sIL-6R, IL-4 and TNF-alpha compared to the early follicular phase. No change was observed in IL-6, IL-8 and IL-10 concentration throughout the menstrual cycle. We found IL-4 positively correlated with oestrogen while TNF-alpha positively correlated with progesterone. Females were found to have significantly higher concentrations of TNF-alpha and sIL-6R across all phases of the menstrual cycle, compared to males across similar time points. CONCLUSION: The normal menstrual cycle is associated with increased production of sIL-6R, IL-4 and TNF-alpha in the luteal phase compared to the early follicular phase. Females have significantly higher concentrations of sIL-6R and TNF-alpha at all time points across the menstrual cycle than males.

Peripheral blood cytokine and chemokine profiles in juvenile localized scleroderma

Science.gov (United States)

Torok, Kathryn S.; Kurzinski, Katherine; Kelsey, Christina; Yabes, Jonathan; Magee, Kelsey; Vallejo, Abbe N.; Medsger, Thomas; Feghali-Bostwick, Carol A.

2015-01-01

Objective To evaluate peripheral blood T-helper (TH) cell associated cytokine and chemokine profiles in localized scleroderma (LS), and correlate them with clinical disease features, including disease activity parameters. Methods A 29-plex Luminex platform was used to analyze the humoral profile of plasma samples from 69 pediatric LS patients and 71 healthy pediatric controls. Cytokine/chemokine levels were compared between these two groups and within LS patients, focusing on validated clinical outcome measures of disease activity and damage in LS. Results Plasma levels of IP-10, MCP-1, IL-17a, IL-12p70, GM-CSF, PDGF-bb, IFN-α2, and IFN-γ were significantly higher in LS compared to healthy controls. Analysis within the LS group demonstrated IP-10, TNF-α and GM-CSF correlated with clinical measures of disease activity. Several cytokines/chemokines correlated with anti-histone antibody, while only a few correlated with positive ANA and single-stranded DNA antibody. Conclusion This is the first time that multiple cytokines and chemokines have been examined simultaneously LS. In general, a TH-1 (IFN-γ) and TH-17 (IL-17a) predominance was demonstrated in LS compared to healthy controls. There is also an IFN–γ signature with elevated IP-10, MCP-1 and IFN-γ, which has been previously demonstrated in systemic sclerosis, suggesting a shared pathophysiology. Within the LS patients, those with active disease demonstrated IP-10, TNF-α and GM-CSF, which may potentially serve as biomarkers of disease activity in the clinical setting. PMID:26254121

Maternal plasma pyridoxal-5'-phosphate concentrations and risk of isolated oral clefts in the Philippines.

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Tamura, Tsunenobu; Munger, Ronald G; Nepomuceno, Buena; Corcoran, Christopher; Cembrano, Joselito; Solon, Florentino

2007-04-01

We report that inadequate vitamin B-6 status of Filipino mothers, assessed by erythrocyte aspartate aminotransferase activity coefficient (EAST-AC), is associated with an increased risk for isolated cleft lip with or without cleft palate (CL/P) in their children. Its association with the status assessed by plasma pyridoxal-5'-phosphate (PLP) concentrations is unknown. In a case-control study in the Philippines including 46 cases (mothers of a child with CL/P) and 392 controls (mothers of an unaffected child), we evaluated the association between the risk for CL/P and maternal vitamin B-6 status assessed by PLP and EAST-AC. The ORs of CL/P were estimated by classifying mothers by PLP (>30, 20-30, and values, compared to those with adequate status by both values. Inadequate vitamin B-6 status assessed by maternal PLP and EAST-AC values independently and both combined was associated with an increased risk for CL/P. The association was highest when both values were considered, suggesting that the measurement of both PLP and EAST-AC provides better assessment of vitamin B-6 status than either measurement alone.

Cytokines and cytokine networks target neurons to modulate long-term potentiation.

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Prieto, G Aleph; Cotman, Carl W

2017-04-01

Cytokines play crucial roles in the communication between brain cells including neurons and glia, as well as in the brain-periphery interactions. In the brain, cytokines modulate long-term potentiation (LTP), a cellular correlate of memory. Whether cytokines regulate LTP by direct effects on neurons or by indirect mechanisms mediated by non-neuronal cells is poorly understood. Elucidating neuron-specific effects of cytokines has been challenging because most brain cells express cytokine receptors. Moreover, cytokines commonly increase the expression of multiple cytokines in their target cells, thus increasing the complexity of brain cytokine networks even after single-cytokine challenges. Here, we review evidence on both direct and indirect-mediated modulation of LTP by cytokines. We also describe novel approaches based on neuron- and synaptosome-enriched systems to identify cytokines able to directly modulate LTP, by targeting neurons and synapses. These approaches can test multiple samples in parallel, thus allowing the study of multiple cytokines simultaneously. Hence, a cytokine networks perspective coupled with neuron-specific analysis may contribute to delineation of maps of the modulation of LTP by cytokines. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Relationship between Maternal Plasma Leptin and Adiponectin Concentrations and Newborn Adiposity

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Natália P. Castro

2017-02-01

Full Text Available Increased maternal blood concentrations of leptin and decreased adiponectin levels, which are common disturbances in obesity, may be involved in offspring adiposity by programming fetal adipose tissue development. The aim of this study was to assess the relationship between maternal leptin and adiponectin concentrations and newborn adiposity. This was a cross-sectional study involving 210 healthy mother-newborn pairs from a public maternity hospital in São Paulo, Brazil. Maternal blood samples were collected after delivery and leptin and adiponectin concentrations were measured by enzyme-linked immunosorbent assay. Newborn body composition was estimated by air displacement plethysmography. The association between maternal leptin and adiponectin concentrations and newborn adiposity (fat mass percentage, FM% was evaluated by multiple linear regression, controlling for maternal age, socioeconomic status, parity, pre-pregnancy body mass index (BMI, weight gain, gestational age, and newborn age at the time of measurement. No relationship was found between maternal leptin and FM% of male or female newborn infants. Maternal adiponectin (p = 0.001 and pre-pregnancy BMI (p < 0.001; adj. R2 = 0.19 were positively associated with FM% of newborn males, indicating that maternal adiponectin is involved in fetal fat deposition in a sex-specific manner. Large-scale epidemiological, longitudinal studies are necessary to confirm our results.

The Relationship between Maternal Plasma Leptin and Adiponectin Concentrations and Newborn Adiposity.

Science.gov (United States)

Castro, Natália P; Euclydes, Verônica V; Simões, Fernanda A; Vaz-de-Lima, Lourdes R A; De Brito, Cyro A; Luzia, Liania A; Devakumar, Delan; Rondó, Patrícia H C

2017-02-23

Increased maternal blood concentrations of leptin and decreased adiponectin levels, which are common disturbances in obesity, may be involved in offspring adiposity by programming fetal adipose tissue development. The aim of this study was to assess the relationship between maternal leptin and adiponectin concentrations and newborn adiposity. This was a cross-sectional study involving 210 healthy mother-newborn pairs from a public maternity hospital in São Paulo, Brazil. Maternal blood samples were collected after delivery and leptin and adiponectin concentrations were measured by enzyme-linked immunosorbent assay. Newborn body composition was estimated by air displacement plethysmography. The association between maternal leptin and adiponectin concentrations and newborn adiposity (fat mass percentage, FM%) was evaluated by multiple linear regression, controlling for maternal age, socioeconomic status, parity, pre-pregnancy body mass index (BMI), weight gain, gestational age, and newborn age at the time of measurement. No relationship was found between maternal leptin and FM% of male or female newborn infants. Maternal adiponectin ( p = 0.001) and pre-pregnancy BMI ( p < 0.001; adj. R ² = 0.19) were positively associated with FM% of newborn males, indicating that maternal adiponectin is involved in fetal fat deposition in a sex-specific manner. Large-scale epidemiological, longitudinal studies are necessary to confirm our results.

Plasma TNF-α levels are higher in early pregnancy in patients with secondary compared with primary recurrent miscarriage

DEFF Research Database (Denmark)

Piosik, Zofia Maria; Goegebeur, Yuri; Klitkou, Louise

2013-01-01

Specific pro-inflammatory cytokine profiles in plasma may characterize women with recurrent miscarriage (RM) but the dynamics of the cytokine profiles with progressing pregnancy is largely unknown.......Specific pro-inflammatory cytokine profiles in plasma may characterize women with recurrent miscarriage (RM) but the dynamics of the cytokine profiles with progressing pregnancy is largely unknown....

Cytokine-mediated inflammation mediates painful neuropathy from metabolic syndrome.

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Can Zhang

Full Text Available Painful neuropathy (PN is a prevalent condition in patients with metabolic syndrome (MetS. However, the pathogenic mechanisms of metabolic syndrome-associated painful neuropathy (MetSPN remain unclear. In the current study, high-fat-fed mice (HF mice were used to study MetSPN. HF mice developed MetS phenotypes, including increased body weight, elevated plasma cholesterol levels, and insulin resistance in comparison with control-fat-fed (CF mice. Subsequently, HF mice developed mechanical allodynia and thermal hyperalgesia in hind paws after 8 wk of diet treatment. These pain behaviors coincided with increased densities of nociceptive epidermal nerve fibers and inflammatory cells such as Langerhans cells and macrophages in hind paw skin. To study the effect of MetS on profiles of cytokine expression in HF mice, we used a multiplex cytokine assay to study the protein expression of 12 pro-inflammatory and anti-inflammatory cytokines in dorsal root ganglion and serum samples. This method detected the elevated levels of proinflammatory cytokines, including tumor necrosis factor (TNF-α, and interleukin (IL-6, IL-1β as well as reduced anti-inflammatory IL-10 in lumbar dorsal root ganglia (LDRG of HF mice. Intraperitoneal administration of IL-10 reduced the upregulation of pro-inflammatory cytokines and alleviated pain behaviors in HF mice without affecting MetS phenotypes. Our findings suggested targeting HF-induced cytokine dysregulation could be an effective strategy for treating MetSPN.

Using blood cytokine measures to define high inflammatory biotype of schizophrenia and schizoaffective disorder.

Science.gov (United States)

Boerrigter, Danny; Weickert, Thomas W; Lenroot, Rhoshel; O'Donnell, Maryanne; Galletly, Cherrie; Liu, Dennis; Burgess, Martin; Cadiz, Roxanne; Jacomb, Isabella; Catts, Vibeke S; Fillman, Stu G; Weickert, Cynthia Shannon

2017-09-18

Increases in pro-inflammatory cytokines are found in the brain and blood of people with schizophrenia. However, increased cytokines are not evident in all people with schizophrenia, but are found in a subset. The cytokine changes that best define this subset, termed the "elevated inflammatory biotype", are still being identified. Using quantitative RT-PCR, we measured five cytokine mRNAs (IL-1β, IL-2 IL-6, IL-8 and IL-18) from peripheral blood of healthy controls and of people with schizophrenia or schizoaffective disorder (n = 165). We used a cluster analysis of the transcript levels to define those with low and those with elevated levels of cytokine expression. From the same cohort, eight cytokine proteins (IL-1β, IL-2, IL-6, IL-8, IL-10, IL-12, IFNγ and TNFα) were measured in serum and plasma using a Luminex Magpix-based assay. We compared peripheral mRNA and protein levels across diagnostic groups and between those with low and elevated levels of cytokine expression according to our transcription-based cluster analysis. We found an overall decrease in the anti-inflammatory IL-2 mRNA (p = 0.006) and an increase in three serum cytokines, IL-6 (p = 0.010), IL-8 (p = 0.024) and TNFα (p schizophrenia compared to healthy controls. A greater percentage of people with schizophrenia (48%) were categorised into the elevated inflammatory biotype compared to healthy controls (33%). The magnitude of increase in IL-1β, IL-6, IL-8 and IL-10 mRNAs in people in the elevated inflammation biotype ranged from 100 to 220% of those in the non-elevated inflammatory biotype and was comparable between control and schizophrenia groups. Blood cytokine protein levels did not correlate with cytokine mRNA levels, and plasma levels of only two cytokines distinguished the elevated and low inflammatory biotypes, with IL-1β significantly increased in the elevated cytokine control group and IL-8 significantly increased in the elevated cytokine schizophrenia group. Our results

A liquid chromatography method with single quadrupole mass spectrometry for quantitative determination of indomethacin in maternal plasma and urine of pregnant patients

Science.gov (United States)

Wang, Xiaoming; Vernikovskaya, Daria I.; Nanovskaya, Tatiana N.; Rytting, Erik; Hankins, Gary D.V.; Ahmed, Mahmoud S.

2013-01-01

A liquid chromatography with single quadrupole mass spectrometry method was developed for the quantitative determination of indomethacin in the maternal plasma and urine of pregnant patients under treatment. A deuterium-labeled isotope of indomethacin (d4-indomethacin) was used as an internal standard. The maternal plasma and urine samples were acidified with 1.0 MHCl then extracted with chloroform to achieve the extraction recovery range of 94% to 104% with variation less than 11%. Chromatographic separation was achieved by a Waters Symmetry C18 column with isocratic elution of 0.05% (v/v) formic acid aqueous solution and acetonitrile (47:53, v/v). An in-source fragmentation was applied on the single quadrupole mass spectrometer equipped with an electrospray ionization source at positive mode. The LC-ESI-MS quantification was performed in the selected ion monitoring mode targeting ions at m/z 139 for indomethacin and m/z 143 for its internal standard. The calibration curves were linear in the concentration ranges between 14.8 and 2.97×103 ng/mL for plasma samples and between 10.5 and 4.21×103 ng/mL for urine samples. The relative standard deviation of this method was less than 8% for intra- and inter-day assays, and the accuracy ranged between 90% and 108%. PMID:23474812

Maternal Vitamin D Status and Adverse Birth Outcomes in Children from Rural Western Kenya

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Eunice N. Toko

2016-12-01

Full Text Available Maternal plasma 25-hydroxyvitamin D (25(OHD status and its association with pregnancy outcomes in malaria holoendemic regions of sub-Saharan Africa is poorly defined. We examined this association and any potential interaction with malaria and helminth infections in an ongoing pregnancy cohort study in Kenya. The association of maternal plasma 25(OHD status with pregnancy outcomes and infant anthropometric measurements at birth was determined in a subset of women (n = 63. Binomial and linear regression analyses were used to examine associations between maternal plasma 25(OHD and adverse pregnancy outcomes. Fifty-one percent of the women had insufficient (<75 nmol/L and 21% had deficient (<50 nmol/L plasma 25(OHD concentration at enrollment. At birth, 74.4% of the infants had insufficient and 30% had deficient plasma 25(OHD concentrations, measured in cord blood. Multivariate analysis controlling for maternal age and body mass index (BMI at enrollment and gestational age at delivery found that deficient plasma 25(OHD levels were associated with a four-fold higher risk of stunting in neonates (p = 0.04. These findings add to the existing literature about vitamin D and its association with linear growth in resource-limited settings, though randomized clinical trials are needed to establish causation.

The Probable Effects of Cytokines in Intrauterine Infections and Perinatal Brain Injury

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Mehmet Oflaz

2013-10-01

Full Text Available Perinatal brain injuries and the subsequent development of cerebral palsy are closely associated with intrauterine infections and inflammatory response. Premature prenatal rupture of membranes and premature births are also closely linked to infections and inflammation, and the presence of both infection / inflammation and premature birth together greatly increase the risk for cerebral palsy. Periventricular leukolamacia, a common neonatal brain white matter lesion, is a major risk factor for cerebral palsy. Inflammatory cytokines released during the course of intrauterine infection play an important role in the genesis of brain white matter lesion. Maternal intrauterine infection appears to increase the risk of preterm delivery, which in turn is associated with an increased risk of intraventricular hemorrhage, neonatal white matter damage, and subsequent cerebral palsy. Proinflammatory cytokines IL-1, IL-6 and Tumor necrosis factor-%u03B1 might be the link between prenatal intrauterine infection and neonatal brain damage, and interrupting the proinflammatory cytokine cascade might prevent later disability in those born near the end of the second trimester.

Placental release of distinct DNA-associated microparticles into maternal circulation: reflective of gestation time and preeclampsia

Science.gov (United States)

Orozco, Aaron F.; Jorgez, Carolina J.; Ramos-Perez, William D.; Popek, Edwina J.; Yu, Xiaoying; Kozinetz, Claudia A.; Bischoff, Farideh Z.; Lewis, Dorothy E.

2009-01-01

Background The aim of this study was to determine whether DNA-associated micro-particles (MPs) in maternal plasma express fetal-derived human leukocyte antigen-G (HLA-G) or placental alkaline phosphatase (PLAP) and whether the levels differ between women with normotensive pregnancies and preeclampsia. Methods DNA-associated MPs expressing HLA-G or PLAP were examined in the plasma of normal pregnant women and preeclamptic patients using flow cytometric analysis. Results DNA-associated HLA-G+ MPs were significantly increased in maternal plasma compared to plasma from non-pregnant controls (p < 0.005), with highest levels found in first and second trimesters. DNA-associated PLAP+ MPs were also increased in maternal plasma compared to plasma from non-pregnant controls (p < 0.006), with highest levels in second and third trimesters. Term preeclamptic women had higher levels of DNA-associated MPs than control pregnant women. HLA-G+ MPs from the plasma of preeclamptic women had more DNA per MP than HLA-G+ MPs from the plasma of normal pregnant women (p < 0.03). Conclusions HLA-G and PLAP MPs increase in maternal circulation at different times during gestation. DNA amounts per HLA-G+ MP increase in preeclamptic women which might indicate dysfunctional extravillous cytotrophoblasts. PMID:19692120

Detection and quantitation of twenty-seven cytokines, chemokines and growth factors pre- and post-high abundance protein depletion in human plasma

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Seong-Beom Ahn

2014-06-01

Full Text Available Cytokines, chemokines and growth factors (CCGFs in human plasma are analyzed for identification of biomarkers. However concentrations of CCGFs are very low; it is difficult to identify and quantify low abundance proteins in the presence of the high abundance proteins (HAPs unless HAPs are removed prior to analysis. However, there is a concern that the low abundance proteins such as CCGFs may also be removed during the HAP depletion process. In this study, we have examined whether or not depletion of the HAPs enhances detection of the CCGFs by immuno-assays. Top 14 HAPs were depleted from 10 healthy volunteers’ plasma using MARS-14 immuno-depletion column and a total of 27 CCGFs were analyzed by bead-based multiplexed immuno-assay. All 27 CCGFs were detected in neat plasma (NP, 25 were detected in flow through fraction (FT and 21 were detected in bound protein (BP fraction. Concentrations of 22 CCGFs were significantly higher in NP compared to FT and BP. Only one CCGF had higher concentration in FT compared to NP. The remaining 2 CCGFs were not different between NP and FT. It was counter-productive for the detection of 24 CCGFs after HAP removal, primarily due to post-depletion protein precipitation and/or re-suspension of pellets.

Lack of pro-inflammatory cytokine mobilization predicts poor prognosis in patients with acute heart failure.

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Vistnes, M; Høiseth, A D; Røsjø, H; Nygård, S; Pettersen, E; Søyseth, V; Hurlen, P; Christensen, G; Omland, T

2013-03-01

The aim of this study was to gain insight in the inflammatory response in acute heart failure (AHF) by assessing (1) plasma cytokine profiles and (2) prognostic value of circulating cytokines in AHF patients. Plasma levels of 26 cytokines were quantified by multiplex protein arrays in 36 patients with congestive AHF, characterized by echocardiographic, radiologic, and clinical examinations on admission, during hospitalization and at discharge. Recurrent AHF leading to death or readmission constituted the combined end point, and all patients were followed for 120 days after discharge. Levels of 15 of the measured cytokines were higher in AHF than in healthy subjects (n=22) on admission. Low levels of MCP-1, IL-1β and a low IL-1β/IL-1ra ratio predicted fatal and non-fatal AHF within 120 days. Patients with low circulating levels of IL-1β had lower left ventricular ejection fraction and higher levels of N-terminal pro-B-type natriuretic peptide, while patients with low levels of MCP-1 had higher E/E' and inferior caval vein diameter, than patients with high levels. Immune activation, reflected in increased cytokine levels, is present in AHF patients. Interestingly, failure to increase secretion of IL-1β and MCP-1 during AHF is associated with poor outcome. Copyright © 2013 Elsevier Ltd. All rights reserved.

The peri-operative cytokine response in infants and young children following major surgery

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Hansen, Tom Giedsing; Tønnesen, Else Kirstine; Andersen, J B

1998-01-01

The peri-operative cytokine response was studied in 13 infants and young children undergoing major surgery. All children were anaesthetized with a combined general and epidural anaesthetic technique, followed by post-operative epidural analgesia with bupivacaine and fentanyl. Blood samples were...... taken before and after surgery, 24 h post-operatively, and finally, when the children were mobilized and had regained gastrointestinal function. Plasma samples were analysed for tumour necrosis factor-alpha, interleukin-1 alpha, interleukin-1 beta, interleukin-6, interferon-gamma, interleukin-10...... and the interleukin-1 receptor antagonist. The cytokine responses were highly variable. Overall, no significant changes between pre- and post-operative plasma concentrations were found. Tumour necrosis factor-alpha and the interleukin-1 receptor antagonist were detectable in all children, and a trend towards an early...

Cytokine production of in vitro stimulated peripheral lymphocytes during the course of pregnancy and pseudopregnancy in the rat

NARCIS (Netherlands)

Faas, MM; Eenling, R; van der Schaaf, G; Moes, H; Heineman, MJ; Vos, P

Problem Does maternal lymphocyte cytokine production after in vitro stimulation vary with the stage of pregnancy in the rat? Method of study Blood samples were taken during the estrus cycle in rats (n = 11). Thereafter, rats were rendered pregnant (n = 6) or pseudopregnant (n = 5) and blood samples

Chronic administration of fluoxetine and pro-inflammatory cytokine change in a rat model of depression.

Science.gov (United States)

Lu, Yanxia; Ho, Cyrus S; Liu, Xin; Chua, Anna N; Wang, Wei; McIntyre, Roger S; Ho, Roger C

2017-01-01

This study evaluated the chronic effects of fluoxetine, a commonly prescribed SSRI antidepressant, on the peripheral and central levels of inflammatory cytokines including IL-1β, IL-6, TNF-α and IL-17 over a 4-interval in a rat model of chronic mild stress (CMS) which resembles the human experience of depression. Twenty-four Sprague-Dawley rats were randomly assigned to CMS+vehicle (n = 9), CMS+fluoxetine (n = 9) and the control (n = 6) groups. Sucrose preference and forced swim tests were performed to assess behavioral change. Blood samples were collected on day 0, 60, 90 and 120 for measurement of cytokine levels in plasma. On day 120, the brain was harvested and central level of cytokines was tested using Luminex. Four months of fluoxetine treatment resulted in changes in the sucrose preference and immobility time measurements, commensurate with antidepressant effects. The CMS+vehicle group exhibited elevated plasma levels of IL-1β, IL-17, and TNF-α on day 60 or 120. Rats treated with fluoxetine demonstrated lower IL-1β in plasma and brain after 90 and 120-day treatment respectively (pfluoxetine by reducing central and peripheral levels of IL-1β in the alleviation of depressive symptoms.

Inflammation-modulating cytokine profile and lipid interaction in HIV-related risk factors for cardiovascular diseases

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Gori E

2016-11-01

Full Text Available Elizabeth Gori,1,2 Takafira Mduluza,3,4 Mudavanhu Nyagura,2 Babill Stray-Pedersen,5 Zvenyika Alfred Gomo1 1Chemical Pathology Department, College of Health Sciences, 2Preclinical Veterinary Studies Department, Faculty of Veterinary Sciences, 3Biochemistry Department, University of Zimbabwe, Harare, Zimbabwe; 4School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa; 5Institute of Clinical Medicine, University in Oslo, Oslo University Hospital, Oslo, Norway Abstract: HIV infection and antiretroviral therapy (ART are associated with changes in plasma levels of lipoproteins, thus posing the risk of cardiovascular complications in infected individuals. The alteration in plasma lipoprotein levels results from dysregulation of inflammation-modulating cytokines that control lipid metabolism. Little is understood regarding the relationship between the cytokines and serum lipid levels, which have been reported to be altered in adults receiving ART. The objective of this study was to describe the profiles of inflammation-modulating cytokines and their relationship to lipids as cardiovascular disease (CVD risk factors in HIV infection. This observational cross-sectional study measured plasma levels of interleukin (IL-10, tumor necrosis factor-alpha (TNF-α, IL-4, total cholesterol (TC, and high-density lipoprotein cholesterol (HDL-c in HIV-infected and uninfected adults. A total of 219 HIV-infected participants were enrolled from an HIV treatment center; of them, 187 were receiving ART and 32 were ART naïve, while 65 were HIV-uninfected blood donors. HIV-infected individuals had higher levels of IL-10 (HIV-infected ART-naïve [P=0.0024] and ART-receiving [P=0.033] than their uninfected counterparts. ART-naïve subjects had significantly higher plasma levels of IL-10 than ART-receiving subjects (P=0.0014. No significant difference was observed in plasma levels of IL-4 and TNF

Temporal effects of maternal and pregnancy characteristics on serum pregnancy-associated plasma protein-A and free β-human chorionic gonadotropin at 7-14 weeks' gestation

DEFF Research Database (Denmark)

Ball, S; Ekelund, C; Wright, D

2013-01-01

OBJECTIVE: The aim of this study was to investigate gestational age-dependent effects of racial origin, smoking status and mode of conception on maternal serum levels of free β-human chorionic gonadotropin (β-hCG) and pregnancy-associated plasma protein-A (PAPP-A) at 7-14 weeks' gestation. METHODS...

The role of cytokine deficiencies and cytokine autoantibodies in clinical dermatology

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Liszewski, Walter; Gniadecki, Robert

2016-01-01

due to a downregulation or absence of cytokines. Here, we review the diagnosis and clinical management of cytokine deficiency syndromes in dermatology. We will review the biology of cytokines, and the current approved indications for recombinant cytokines and anticytokine antibodies. We will also...

Sex differences in the pro-inflammatory cytokine response to endotoxin unfold in vivo but not ex vivo in healthy humans.

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Wegner, Alexander; Benson, Sven; Rebernik, Laura; Spreitzer, Ingo; Jäger, Marcus; Schedlowski, Manfred; Elsenbruch, Sigrid; Engler, Harald

2017-07-01

Clinical data indicate that inflammatory responses differ across sexes, but the mechanisms remain elusive. Herein, we assessed in vivo and ex vivo cytokine responses to bacterial endotoxin in healthy men and women to elucidate the role of systemic and cellular factors underlying sex differences in inflammatory responses. Participants received an i.v. injection of low-dose endotoxin (0.4 ng/kg body mass), and plasma TNF-α and IL-6 responses were analyzed over a period of 6 h. In parallel, ex vivo cytokine production was measured in endotoxin-stimulated blood samples obtained immediately before in vivo endotoxin administration. As glucocorticoids (GCs) play an important role in the negative feedback regulation of the inflammatory response, we additionally analyzed plasma cortisol concentrations and ex vivo GC sensitivity of cytokine production. Results revealed greater in vivo pro-inflammatory responses in women compared with men, with significantly higher increases in plasma TNF-α and IL-6 concentrations. In addition, the endotoxin-induced rise in plasma cortisol was more pronounced in women. In contrast, no sex differences in ex vivo cytokine production and GC sensitivity were observed. Together, these findings demonstrate major differences in in vivo and ex vivo responses to endotoxin and underscore the importance of systemic factors underlying sex differences in the inflammatory response.

Review: Fetal-maternal communication via extracellular vesicles - Implications for complications of pregnancies.

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Adam, Stefanie; Elfeky, Omar; Kinhal, Vyjayanthi; Dutta, Suchismita; Lai, Andrew; Jayabalan, Nanthini; Nuzhat, Zarin; Palma, Carlos; Rice, Gregory E; Salomon, Carlos

2017-06-01

The maternal physiology experiences numerous changes during pregnancy which are essential in controlling and maintaining maternal metabolic adaptations and fetal development. The human placenta is an organ that serves as the primary interface between the maternal and fetal circulation, thereby supplying the fetus with nutrients, blood and oxygen through the umbilical cord. During gestation, the placenta continuously releases several molecules into maternal circulation, including hormones, proteins, RNA and DNA. Interestingly, the presence of extracellular vesicles (EVs) of placental origin has been identified in maternal circulation across gestation. EVs can be categorised according to their size and/or origin into microvesicles (∼150-1000 nm) and exosomes (∼40-120 nm). Microvesicles are released by budding from the plasmatic membrane, whereas exosome release is by fusion of multivesicular bodies with the plasmatic membrane. Exosomes released from placental cells have been found to be regulated by oxygen tension and glucose concentration. Furthermore, maternal exosomes have the ability to stimulate cytokine release from endothelial cells. In this review, we will discuss the role of EVs during fetal-maternal communication during gestation with a special emphasis on exosomes. Copyright © 2016. Published by Elsevier Ltd.

Maternal High-Fat Diet Programming of the Neuroendocrine System and Behavior

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Sullivan, Elinor L.; Riper, Kellie M.; Lockard, Rachel; Valleau, Jeanette C.

2015-01-01

Maternal obesity, metabolic state, and diet during gestation have profound effects on offspring development. The prevalence of neurodevelopmental and mental health disorders has risen rapidly in the last several decades in parallel with the rise in obesity rates. Evidence from epidemiological studies indicates that maternal obesity and metabolic complications increase the risk of offspring developing behavioral disorders such as attention deficit hyperactivity disorder (ADHD), autism spectrum disorders (ASD), and schizophrenia. Animal models show that a maternal diet high in fat similarly disrupts behavioral programming of offspring, with animals showing social impairments, increased anxiety and depressive behaviors, reduced cognitive development, and hyperactivity. Maternal obesity, metabolic conditions, and high fat diet consumption increase maternal leptin, insulin, glucose, triglycerides, and inflammatory cytokines. This leads to increased risk of placental dysfunction, and altered fetal neuroendocrine development. Changes in brain development that likely contribute to the increased risk of behavioral and mental health disorders include increased inflammation in the brain, as well as alterations in the serotonergic system, dopaminergic system and hypothalamic pituitary adrenal (HPA) axis. PMID:25913366

Obesity Disrupts the Rhythmic Profiles of Maternal and Fetal Progesterone in Rat Pregnancy.

Science.gov (United States)

Crew, Rachael C; Mark, Peter J; Clarke, Michael W; Waddell, Brendan J

2016-09-01

Maternal obesity increases the risk of abnormal fetal growth, but the underlying mechanisms remain unclear. Because steroid hormones regulate fetal growth, and both pregnancy and obesity markedly alter circadian biology, we hypothesized that maternal obesity disrupts the normal rhythmic profiles of steroid hormones in rat pregnancy. Obesity was established by cafeteria (CAF) feeding for 8 wk prior to mating and throughout pregnancy. Control (CON) animals had ad libitum access to chow. Daily profiles of plasma corticosterone, 11-dehydrocorticosterone, progesterone, and testosterone were measured at Days 15 and 21 of gestation (term = 23 days) in maternal (both days) and fetal (Day 21) plasma. CAF mothers exhibited increased adiposity relative to CON and showed fetal and placental growth restriction. There was no change, however, in total fetal or placental mass due to slightly larger litter sizes in CAF. Nocturnal declines in progesterone were observed in maternal (39% lower) and fetal (45% lower) plasma in CON animals, but these were absent in CAF animals. CAF mothers were hyperlipidemic at both days of gestation, but this effect was isolated to the dark period at Day 21. CAF maternal testosterone was slightly lower at Day 15 (8%) but increased above CON by Day 21 (16%). Despite elevated maternal testosterone, male fetal testosterone was suppressed by obesity on Day 21. Neither maternal nor fetal glucocorticoid profiles were affected by obesity. In conclusion, obesity disrupts rhythmic profiles of maternal and fetal progesterone, preventing the normal nocturnal decline. Obesity subtly changed testosterone profiles but did not alter maternal and fetal glucocorticoids. © 2016 by the Society for the Study of Reproduction, Inc.

Differential Cytokine Changes in Patients with Myasthenia Gravis with Antibodies against AChR and MuSK.

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Vuslat Yilmaz

Full Text Available Neuromuscular transmission failure in myasthenia gravis (MG is most commonly elicited by autoantibodies (ab to the acetylcholine receptor or the muscle-specific kinase, constituting AChR-MG and MuSK-MG. It is controversial whether these MG subtypes arise through different T helper (Th 1, Th2 or Th17 polarized immune reactions and how these reactions are blunted by immunosuppression. To address these questions, plasma levels of cytokines related to various Th subtypes were determined in patients with AChR-MG, MuSK-MG and healthy controls (CON. Peripheral blood mononuclear cells (PBMC were activated in vitro by anti-CD3, and cytokines were quantified in supernatants. In purified blood CD4+ T cells, RNA of various cytokines, Th subtype specific transcription factors and the co-stimulatory molecule, CD40L, were quantified by qRT-PCR. Plasma levels of Th1, Th2 and Th17 related cytokines were overall not significantly different between MG subtypes and CON. By contrast, in vitro stimulated PBMC from MuSK-MG but not AChR-MG patients showed significantly increased secretion of the Th1, Th17 and T follicular helper cell related cytokines, IFN-γ, IL-17A and IL-21. Stimulated expression of IL-4, IL-6, IL-10 and IL-13 was not significantly different. At the RNA level, expression of CD40L by CD4+ T cells was reduced in both AChR-MG and MuSK-MG patients while expression of Th subset related cytokines and transcription factors were normal. Immunosuppression treatment had two effects: First, it reduced levels of IL12p40 in the plasma of AChR-MG and MuSK-MG patients, leaving other cytokine levels unchanged; second, it reduced spontaneous secretion of IFN-γ and increased secretion of IL-6 and IL-10 by cultured PBMC from AChR-MG, but not MuSK-MG patients. We conclude that Th1 and Th17 immune reactions play a role in MuSK-MG. Immunosuppression attenuates the Th1 response in AChR-MG and MuSK-MG, but otherwise modulates immune responses in AChR-MG and Mu

Plasma cytokine profiles at diagnosis in pediatric patients with non-hodgkin lymphoma

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Mellgren, Karin; Hedegaard, Chris Juul; Schmiegelow, Kjeld

2012-01-01

Non-Hodgkin lymphoma (NHL) has been associated with elevated levels of inflammatory and immune-regulating cytokines, and polymorphisms in the genes encoding interleukin (IL)-10 and tumor necrosis factor (TNF)-α have been associated with increased incidence of certain subtypes of NHL. The aim......, between 1995 and 2008. Cytokines and growth factors were measured in serum using the Luminex platform by application of a 30-plex kit. Levels of IL-6, IL-2R, IL-10, TNF-RI, and macrophage inflammatory protein-1α were significantly higher in patients with anaplastic large-cell lymphoma compared...... with patients diagnosed with B-cell lymphomas and lymphoblastic lymphomas. High levels of IL-4, IL-13, TNF-RI, and epidermal growth factor were associated with a poorer general condition at diagnosis. The present study suggests that NHL subgrouping and the general condition of pediatric patients at diagnosis...

Helminths and skewed cytokine profiles increase tuberculin skin test positivity in Warao Amerindians

NARCIS (Netherlands)

Verhagen, L. M.; Hermans, P. W. M.; Warris, A.; de Groot, R.; Maes, M.; Villalba, J. A.; del Nogal, B.; van den Hof, S.; Mughini Gras, L.; van Soolingen, D.; Pinelli, E.; de Waard, J. H.

2012-01-01

The immune regulatory mechanisms involved in the acquisition of Mycobacterium tuberculosis infection in children are largely unknown. We investigated the influence of parasitic infections, malnutrition and plasma cytokine profiles on tuberculin skin test (TST) positivity in Warao Amerindians in

Cytokine profiling of young overweight and obese female African American adults with prediabetes

Science.gov (United States)

Lucas, Rudolf; Parikh, Samip J.; Sridhar, Supriya; Guo, De-Huang; Bhagatwala, Jigar; Dong, Yutong; Caldwell, Ruth; Mellor, Andrew; Caldwell, William; Zhu, Haidong; Dong, Yanbin

2014-01-01

Approximately 5–10% of subjects with prediabetes become diabetic every year. Inflammation is involved in the development of obesity-related type 2 diabetes (T2D). However, to date, the relationship between inflammation and prediabetes, defined by hemoglobin A1c (HbA1c) ≥ 5.7 and prediabetes. A total of 21 otherwise healthy, overweight/obese, young adult African American females with prediabetes, together with 20 matched overweight/obese controls, were selected for this study. Plasma cytokines were assessed by multiplex cytokine profiling. Plasma concentrations of interleukin (IL)-5, IL-6, IL-7, tumor necrosis factor-α (TNF-α), and granulocyte-monocyte colony-stimulating factor (GM-CSF) were significantly higher in the prediabetic group, as compared to the control group (all p prediabetic group, but failed to reach statistical significances. Upon merging both groups, HbA1c was found to be positively correlated with IFN- γ, IL-1β, IL-2, IL-5, IL-7, IL-8, TNF-α and GM-CSF. This study demonstrates elevated levels of various pro-inflammatory cytokines in overweight/obese young subjects with prediabetes, which place them at higher risk of developing T2D and cardiovascular diseases. Our data also call for further investigations in animal models and population cohorts to establish the roles of a variety of pro-inflammatory cytokines in the early development of obesity-related T2D. PMID:23769592

Fetuin-A induces cytokine expression and suppresses adiponectin production.

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Anita M Hennige

Full Text Available BACKGROUND: The secreted liver protein fetuin-A (AHSG is up-regulated in hepatic steatosis and the metabolic syndrome. These states are strongly associated with low-grade inflammation and hypoadiponectinemia. We, therefore, hypothesized that fetuin-A may play a role in the regulation of cytokine expression, the modulation of adipose tissue expression and plasma concentration of the insulin-sensitizing and atheroprotective adipokine adiponectin. METHODOLOGY AND PRINCIPAL FINDINGS: Human monocytic THP1 cells and human in vitro differenttiated adipocytes as well as C57BL/6 mice were treated with fetuin-A. mRNA expression of the genes encoding inflammatory cytokines and the adipokine adiponectin (ADIPOQ was assessed by real-time RT-PCR. In 122 subjects, plasma levels of fetuin-A, adiponectin and, in a subgroup, the multimeric forms of adiponectin were determined. Fetuin-A treatment induced TNF and IL1B mRNA expression in THP1 cells (p<0.05. Treatment of mice with fetuin-A, analogously, resulted in a marked increase in adipose tissue Tnf mRNA as well as Il6 expression (27- and 174-fold, respectively. These effects were accompanied by a decrease in adipose tissue Adipoq mRNA expression and lower circulating adiponectin levels (p<0.05, both. Furthermore, fetuin-A repressed ADIPOQ mRNA expression of human in vitro differentiated adipocytes (p<0.02 and induced inflammatory cytokine expression. In humans in plasma, fetuin-A correlated positively with high-sensitivity C-reactive protein, a marker of subclinical inflammation (r = 0.26, p = 0.01, and negatively with total- (r = -0.28, p = 0.02 and, particularly, high molecular weight adiponectin (r = -0.36, p = 0.01. CONCLUSIONS AND SIGNIFICANCE: We provide novel evidence that the secreted liver protein fetuin-A induces low-grade inflammation and represses adiponectin production in animals and in humans. These data suggest an important role of fatty liver in the pathophysiology of insulin resistance and

Study on changes of the plasma cytokines in 60Co γ-ray irradiated blood and leukocyte reduction of whole blood

International Nuclear Information System (INIS)

Li Zhiqiang; Le Jiayi; Qu Yihua; Xu Wenhao

2006-01-01

Objective: To study the changes of IL-2, IL-6, IFN-γ and TNF-α in 60 Co γ-ray irradiated and leukocyte reduction of whole blood, and to understand the fever phenomenon in patients received blood transfusion. Methods: ELISA method was used to measure changes of the cytokines. Results: The plasma levels of IL-2, IL-6, IFN-γ and TNF-α did not change significantly with extending the conservation period both in 60 Co-irradiated and leukocyte reduction of whole blood. The frequency of fever decreaed obviously with transfusion of 60 Co-irradiated and leukocyte reduction of whole blood. Conclusion: 60 Co-irradiated blood can not only prevent transfusion associated graft-versus-host disease (TA-GVHD), but also decrease non-hemolytic febrile transfusion reactions (NHFTR) effectively. (authors)

Chronic administration of fluoxetine and pro-inflammatory cytokine change in a rat model of depression.

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Yanxia Lu

Full Text Available This study evaluated the chronic effects of fluoxetine, a commonly prescribed SSRI antidepressant, on the peripheral and central levels of inflammatory cytokines including IL-1β, IL-6, TNF-α and IL-17 over a 4-interval in a rat model of chronic mild stress (CMS which resembles the human experience of depression. Twenty-four Sprague-Dawley rats were randomly assigned to CMS+vehicle (n = 9, CMS+fluoxetine (n = 9 and the control (n = 6 groups. Sucrose preference and forced swim tests were performed to assess behavioral change. Blood samples were collected on day 0, 60, 90 and 120 for measurement of cytokine levels in plasma. On day 120, the brain was harvested and central level of cytokines was tested using Luminex. Four months of fluoxetine treatment resulted in changes in the sucrose preference and immobility time measurements, commensurate with antidepressant effects. The CMS+vehicle group exhibited elevated plasma levels of IL-1β, IL-17, and TNF-α on day 60 or 120. Rats treated with fluoxetine demonstrated lower IL-1β in plasma and brain after 90 and 120-day treatment respectively (p<0.05. There was a trend of reduction of IL-6 and TNF-α concentration. This study revealed the potential therapeutic effects of fluoxetine by reducing central and peripheral levels of IL-1β in the alleviation of depressive symptoms.

New aids for the non-invasive prenatal diagnosis of achondroplasia: dysmorphic features, charts of fetal size and molecular confirmation using cell-free fetal DNA in maternal plasma

NARCIS (Netherlands)

Chitty, L. S.; Griffin, D. R.; Meaney, C.; Barrett, A.; Khalil, A.; Pajkrt, E.; Cole, T. J.

2011-01-01

To improve the prenatal diagnosis of achondroplasia by constructing charts of fetal size, defining frequency of sonographic features and exploring the role of non-invasive molecular diagnosis based on cell-free fetal deoxyribonucleic acid (DNA) in maternal plasma. Data on fetuses with a confirmed

Academic stress-induced changes in Th1- and Th2-cytokine response

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Areej M. Assaf

2017-12-01

Full Text Available Psychological stress stimulates physiological responses releasing catecholamines and corticoids, which act via corresponding receptors on immune cells, producing a shift in the cytokine balance. These responses are variable depending on the nature of stressors. The effect of the academic stress on the production of the Th1-cytokines (TNF-α, IFN-γ, IL-1β, IL-2, IL-6 and IL-8 and Th2-cytokines (IL-1ra, IL-4, IL-5 and IL-10 on 35 medical/health sciences students after completing their questionnaires was investigated. Blood samples were taken at three stages; baseline stage at the beginning, midterm and final academic examination stages. Plasma cortisol and cytokines were measured during the three stages. The last two stages were compared with the baseline non-stress period. Results of the stress induced during the final examination stage were the highest with a significant increase in cortisol release, IL-4, IL-5 and IL-1ra release with a shift in Th1:Th2 cytokines balance towards Th2. Whereby, the midterm stage did not show significant reduction in Th1-cytokines except for TNF-α, with an increase in IFN-γ level that was reduced in the third stage. Th2 cytokine, IL-1ra, had positive correlations with Th1 cytokines; IL-2 and IFN-γ in the second stage and IL-6 cytokine in the third stage. Cortisol was positively correlated with IL-8 in the last stage and heart rates had negative correlation with IL-10 in the first and last stages. Findings of this study indicate that exam stress down-regulates Th1 with a selective up-regulation of Th2-cytokines. In conclusion, Cortisol might have a role in suppressing the release of Th1- mediated cellular immune response which could increase the vulnerability among the students to infectious diseases.

Academic stress-induced changes in Th1- and Th2-cytokine response.

Science.gov (United States)

Assaf, Areej M; Al-Abbassi, Reem; Al-Binni, Maysaa

2017-12-01

Psychological stress stimulates physiological responses releasing catecholamines and corticoids, which act via corresponding receptors on immune cells, producing a shift in the cytokine balance. These responses are variable depending on the nature of stressors. The effect of the academic stress on the production of the Th1-cytokines (TNF-α, IFN-γ, IL-1β, IL-2, IL-6 and IL-8) and Th2-cytokines (IL-1ra, IL-4, IL-5 and IL-10) on 35 medical/health sciences students after completing their questionnaires was investigated. Blood samples were taken at three stages; baseline stage at the beginning, midterm and final academic examination stages. Plasma cortisol and cytokines were measured during the three stages. The last two stages were compared with the baseline non-stress period. Results of the stress induced during the final examination stage were the highest with a significant increase in cortisol release, IL-4, IL-5 and IL-1ra release with a shift in Th1:Th2 cytokines balance towards Th2. Whereby, the midterm stage did not show significant reduction in Th1-cytokines except for TNF-α, with an increase in IFN-γ level that was reduced in the third stage. Th2 cytokine, IL-1ra, had positive correlations with Th1 cytokines; IL-2 and IFN-γ in the second stage and IL-6 cytokine in the third stage. Cortisol was positively correlated with IL-8 in the last stage and heart rates had negative correlation with IL-10 in the first and last stages. Findings of this study indicate that exam stress down-regulates Th1 with a selective up-regulation of Th2-cytokines. In conclusion, Cortisol might have a role in suppressing the release of Th1- mediated cellular immune response which could increase the vulnerability among the students to infectious diseases.

Polymorphisms in Plasmodium vivax Circumsporozoite Protein (CSP) Influence Parasite Burden and Cytokine Balance in a Pre-Amazon Endemic Area from Brazil

Science.gov (United States)

Ribeiro, Bruno de Paulo; Cassiano, Gustavo Capatti; de Souza, Rodrigo Medeiros; Cysne, Dalila Nunes; Grisotto, Marcos Augusto Grigolin; de Azevedo dos Santos, Ana Paula Silva; Marinho, Cláudio Romero Farias; Machado, Ricardo Luiz Dantas; Nascimento, Flávia Raquel Fernandes

2016-01-01

Mechanisms involved in severe P. vivax malaria remain unclear. Parasite polymorphisms, parasite load and host cytokine profile may influence the course of infection. In this study, we investigated the influence of circumsporozoite protein (CSP) polymorphisms on parasite load and cytokine profile in patients with vivax malaria. A cross-sectional study was carried out in three cities: São Luís, Cedral and Buriticupu, Maranhão state, Brazil, areas of high prevalence of P. vivax. Interleukin (IL)-2, IL-4, IL-10, IL-6, IL-17, tumor necrosis factor alpha (TNF-α, interferon gamma (IFN-γ and transforming growth factor beta (TGF-β were quantified in blood plasma of patients and in supernatants from peripheral blood mononuclear cell (PBMC) cultures. Furthermore, the levels of cytokines and parasite load were correlated with VK210, VK247 and P. vivax-like CSP variants. Patients infected with P. vivax showed increased IL-10 and IL-6 levels, which correlated with the parasite load, however, in multiple comparisons, only IL-10 kept this association. A regulatory cytokine profile prevailed in plasma, while an inflammatory profile prevailed in PBMC culture supernatants and these patterns were related to CSP polymorphisms. VK247 infected patients showed higher parasitaemia and IL-6 concentrations, which were not associated to IL-10 anti-inflammatory effect. By contrast, in VK210 patients, these two cytokines showed a strong positive correlation and the parasite load was lower. Patients with the VK210 variant showed a regulatory cytokine profile in plasma, while those infected with the VK247 variant have a predominantly inflammatory cytokine profile and higher parasite loads, which altogether may result in more complications in infection. In conclusion, we propose that CSP polymorphisms is associated to the increase of non-regulated inflammatory immune responses, which in turn may be associated with the outcome of infection. PMID:26943639

Plasma cytokine expression after lower-limb compression in rats

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Mauricio Wanderley Moral Sgarbi

2015-02-01

Full Text Available OBJECTIVES: Muscle injury due to crushing (muscle compression injury is associated with systemic manifestations known as crush syndrome. A systemic inflammatory reaction may also be triggered by isolated muscle injury. The aim of this study was to investigate the plasma levels of interleukins (IL 1, 6 and 10 and tumor necrosis factor alpha (TNF-α, which are markers for possible systemic inflammatory reactions, after isolated muscle injury resulting from lower-limb compression in rats.METHODS: Male Wistar rats were subjected to 1 h of compression of their lower limbs by means of a rubber band. The plasma levels of IL 1, 6 and 10 and TNF-α were measured 1, 2 and 4 h after the rats were released from compression.RESULTS: The plasma levels of IL 10 decreased in relation to those of the other groups, with a statistically significant difference (p < 0.05. The method used did not detect the presence of IL 1, IL 6 or TNF-α.CONCLUSION: Our results demonstrated that the changes in plasma levels of IL 10 that were found may have been a sign of the presence of circulating interleukins in this model of lower-limb compression in rats.

Insulin Resistance and Increased Muscle Cytokine Levels in Patients With Mitochondrial Myopathy

DEFF Research Database (Denmark)

Rue, Nana; Vissing, John; Galbo, Henrik

2014-01-01

CONTEXT: Mitochondrial dysfunction has been proposed to cause insulin resistance and that might stimulate cytokine production. OBJECTIVE: The objective of the study was to elucidate the association between mitochondrial myopathy, insulin sensitivity, and cytokine levels in muscle. DESIGN......: The intervention included a 120-minute hyperinsulinemic, euglycemic clamp. Another morning, microdialysis of both vastus lateralis muscles for 4 hours, including one-legged, knee extension exercise for 30 minutes, was performed. MAIN OUTCOME MEASURES: Glucose infusion rate during 90-120 minutes of insulin infusion...... was measured. Cytokine concentrations in dialysate were also measured. RESULTS: Muscle strength, percentage fat mass, and creatine kinase in plasma did not differ between groups. The maximal oxygen uptake was 21 ± 3 (SE) (P) and 36 ± 3(C) mL/kg·min (2P insulin, C-peptide, and glucagon were higher...

Human Chorionic Gonadotropin Has Anti-Inflammatory Effects at the Maternal-Fetal Interface and Prevents Endotoxin-Induced Preterm Birth, but Causes Dystocia and Fetal Compromise in Mice1

Science.gov (United States)

Furcron, Amy-Eunice; Romero, Roberto; Mial, Tara N.; Balancio, Amapola; Panaitescu, Bogdan; Hassan, Sonia S.; Sahi, Aashna; Nord, Claire; Gomez-Lopez, Nardhy

2016-01-01

Human chorionic gonadotropin (hCG) is implicated in the maintenance of uterine quiescence by down-regulating myometrial gap junctions during pregnancy, and it was considered as a strategy to prevent preterm birth after the occurrence of preterm labor. However, the effect of hCG on innate and adaptive immune cells implicated in parturition is poorly understood. Herein, we investigated the immune effects of hCG at the maternal-fetal interface during late gestation, and whether this hormone can safely prevent endotoxin-induced preterm birth. Using immunophenotyping, we demonstrated that hCG has immune effects at the maternal-fetal interface (decidual tissues) by: 1) increasing the proportion of regulatory T cells; 2) reducing the proportion of macrophages and neutrophils; 3) inducing an M1 → M2 macrophage polarization; and 4) increasing the proportion of T helper 17 cells. Next, ELISAs were used to determine whether the local immune changes were associated with systemic concentrations of progesterone, estradiol, and/or cytokines (IFNgamma, IL1beta, IL2, IL4, IL5, IL6, IL10, IL12p70, KC/GRO, and TNFalpha). Plasma concentrations of IL1beta, but not progesterone, estradiol, or any other cytokine, were increased following hCG administration. Pretreatment with hCG prevented endotoxin-induced preterm birth by 44%, proving the effectiveness of this hormone as an anti-inflammatory agent. However, hCG administration alone caused dystocia and fetal compromise, as proven by Doppler ultrasound. These results provide insight into the mechanisms whereby hCG induces an anti-inflammatory microenvironment at the maternal-fetal interface during late gestation, and demonstrate its effectiveness in preventing preterm labor/birth. However, the deleterious effects of this hormone on mothers and fetuses warrant caution. PMID:27146032

Plasma and breast-milk selenium in HIV-infected Malawian mothers are positively associated with infant selenium status but are not associated with maternal supplementation: results of the Breastfeeding, Antiretrovirals, and Nutrition study.

Science.gov (United States)

Flax, Valerie L; Bentley, Margaret E; Combs, Gerald F; Chasela, Charles S; Kayira, Dumbani; Tegha, Gerald; Kamwendo, Debbie; Daza, Eric J; Fokar, Ali; Kourtis, Athena P; Jamieson, Denise J; van der Horst, Charles M; Adair, Linda S

2014-04-01

Selenium is found in soils and is essential for human antioxidant defense and immune function. In Malawi, low soil selenium and dietary intakes coupled with low plasma selenium concentrations in HIV infection could have negative consequences for the health of HIV-infected mothers and their exclusively breastfed infants. We tested the effects of lipid-based nutrient supplements (LNS) that contained 1.3 times the Recommended Dietary Allowance of sodium selenite and antiretroviral drugs (ARV) on maternal plasma and breast-milk selenium concentrations. HIV-infected Malawian mothers in the Breastfeeding, Antiretrovirals, and Nutrition study were randomly assigned at delivery to receive: LNS, ARV, LNS and ARV, or a control. In a subsample of 526 mothers and their uninfected infants, we measured plasma and breast-milk selenium concentrations at 2 or 6 (depending on the availability of infant samples) and 24 wk postpartum. Overall, mean (± SD) maternal (range: 81.2 ± 20.4 to 86.2 ± 19.9 μg/L) and infant (55.6 ± 16.3 to 61.0 ± 15.4 μg/L) plasma selenium concentrations increased, whereas breast-milk selenium concentrations declined (14.3 ± 11.5 to 9.8 ± 7.3 μg/L) from 2 or 6 to 24 wk postpartum (all P milk selenium from 2 or 6 to 24 wk postpartum (both P milk selenium, but maternal selenium concentrations were positively associated with infant plasma selenium at 2 or 6 and 24 wk postpartum (P milk selenium concentrations. Future research should examine effects of more readily incorporated forms of selenium (ie, selenomethionine) in HIV-infected breastfeeding women.

Morphogen and proinflammatory cytokine release kinetics from PRGF-Endoret fibrin scaffolds: evaluation of the effect of leukocyte inclusion.

Science.gov (United States)

Anitua, E; Zalduendo, M M; Prado, R; Alkhraisat, M H; Orive, G

2015-03-01

The potential influence of leukocyte incorporation in the kinetic release of growth factors from platelet-rich plasma (PRP) may explain the conflicting efficiency of leukocyte platelet-rich plasma (L-PRP) scaffolds in tissue regeneration. To assess this hypothesis, leukocyte-free (PRGF-Endoret) and L-PRP fibrin scaffolds were prepared, and both morphogen and proinflammatory cytokine release kinetics were analyzed. Clots were incubated with culture medium to monitor protein release over 8 days. Furthermore, the different fibrin scaffolds were morphologically characterized. Results show that leukocyte-free fibrin matrices were homogenous while leukocyte-containing ones were heterogeneous, loose and cellular. Leukocyte incorporation produced a significant increase in the contents of proinflammatory cytokines interleukin (IL)-1β and IL-16 but not in the platelet-derived growth factors release (PRGF-Endoret, the inclusion of leukocytes induced a major increase in these cytokines, which was characterized by the presence of a latent period. The PRGF-Endoret matrices were stable during the 8 days of incubation. The inclusion of leukocytes alters the growth factors release profile and also increased the dose of proinflammatory cytokines. © 2014 Wiley Periodicals, Inc.

Interleukin-6 is increased in plasma and cerebrospinal fluid of community-dwelling domestic dogs with acute ischaemic stroke

DEFF Research Database (Denmark)

Gredal, Hanne; Thomsen, Barbara B; Boza-Serrano, Antonio

2017-01-01

itself contributes towards the cytokine response. Community-dwelling domestic dogs suffer from spontaneous ischaemic stroke, and therefore, offer the opportunity to study the cytokine response in a noninvasive set-up. The aims of this study were to investigate cytokine concentrations in plasma...... and cerebrospinal fluid (CSF) in dogs with acute ischaemic stroke and to search for correlations between infarct volume and cytokine concentrations. Blood and CSF were collected from dogs less than 72 h after a spontaneous ischaemic stroke. Infarct volumes were estimated on MRIs. Interleukin (IL)-2, IL-6, IL-8, IL......-10 and tumour necrosis factor in the plasma, CSF and brain homogenates were measured using a canine-specific multiplex immunoassay. IL-6 was significantly increased in plasma (P = 0.04) and CSF (P = 0.04) in stroke dogs compared with healthy controls. The concentrations of other cytokines...

Dysregulation of cytokine response in Canadian First Nations communities: is there an association with persistent organic pollutant levels?

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Pascal Imbeault

Full Text Available In vitro and animal studies report that some persistent organic pollutants (POPs trigger the secretion of proinflammatory cytokines. Whether POP exposure is associated with a dysregulation of cytokine response remains to be investigated in humans. We studied the strength of association between plasma POP levels and circulating cytokines as immune activation markers. Plasma levels of fourteen POPs and thirteen cytokines were measured in 39 Caucasians from a comparator sample in Québec City (Canada and 72 First Nations individuals from two northern communities of Ontario (Canada. Caucasians showed significantly higher levels of organochlorine insecticides (β-HCH, p,p'-DDE and HCB compared to First Nations. Conversely, First Nations showed higher levels of Mirex, Aroclor 1260, PCB 153, PCB 170, PCB 180 and PCB 187 compared to Caucasians. While there was no difference in cytokine levels of IL-4, IL-6, IL-10 and IL-22 between groups, First Nations had significantly greater average levels of IFNγ, IL-1β, IL-2, IL-5, IL-8, IL-12p70, IL-17A, TNFα and TNFβ levels compared to Caucasians. Among candidate predictor variables (age, body mass index, insulin resistance and POP levels, high levels of PCBs were the only predictor accounting for a small but significant effect of observed variance (∼7% in cytokine levels. Overall, a weak but significant association is detected between persistent organochlorine pollutant exposure and elevated cytokine levels. This finding augments the already existing information that environmental pollution is related to inflammation, a common feature of several metabolic disorders that are known to be especially prevalent in Canada's remote First Nations communities.

Change in cytokine levels after administration of saikokaryuukotsuboreito or testosterone in patients with symptoms of late-onset hypogonadism.

Science.gov (United States)

Tsujimura, Akira; Miyagawa, Yasushi; Okuda, Hidenobu; Yamamoto, Keisuke; Fukuhara, Shinichiro; Nakayama, Jiro; Takao, Tetsuya; Nonomura, Norio; Okuyama, Akihiko

2011-03-01

The purpose of this study was to evaluate plasma cytokine levels after treatment with saikokaryukotsuboreito (SKRBT), which is a herbal medicine, or androgen replacement treatment (ART), for patients with late-onset hypogonadism (LOH)-related symptoms. Thirty-one patients over 40 years of age with LOH-related symptoms were included in this study. SKRBT was given orally three times daily to a total of 7.5 g/day for 15 eugonadal patients and ART was give to 16 hypogonadal patients by intramuscular injection of testosterone enanthate at 125 mg each time every 2 weeks. Plasma levels of testosterone and 18 cytokines, as well as LOH-related symptoms scored according to the Aging Males' Symptoms (AMS) scale, were compared before and more than 2 months after treatment. In the ART group, the total AMS score was decreased and testosterone was increased significantly after treatment. No cytokine variables were altered significantly after the treatment. In the SKRBT group, although the total AMS score was significantly decreased, testosterone did not change. From the evaluation of cytokines, a significant increase was found in interleukin (IL)- 8, IL-13, interferon-gamma and tumour necrosis factor-alpha. We conclude that SKRBT might improve LOH-related symptoms in eugonadal patients through the beneficial effect of cytokines, a mechanism that is quite different from ART.

Effects of maternal exposure to di(2-ethylhexyl)phthalate (DEHP) during pregnancy on susceptibility to neonatal asthma

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Shin, In-Sik; Lee, Mee-Young [Basic Herbal Medicine Research Group, Korea Institute of Oriental Medicine, 483 Expo-ro, Yusung-gu, Daejeon 305-811 (Korea, Republic of); Cho, Eun-Sang [College of Veterinary Medicine, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 305-764 (Korea, Republic of); Choi, Eun-young [College of Nursing and Health, Kongju National University, 56 Gongju Daehak-ro, Gongju, Chungnam 314-701 (Korea, Republic of); Son, Hwa-Young [College of Veterinary Medicine, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 305-764 (Korea, Republic of); Lee, Kyoung-Youl, E-mail: youl10@hanmail.net [College of Nursing and Health, Kongju National University, 56 Gongju Daehak-ro, Gongju, Chungnam 314-701 (Korea, Republic of)

2014-02-01

Di(2-ethylhexyl) phthalate (DEHP) is used as a plasticizer and is widely dispersed in the environment. In this study, we investigated the effects of maternal exposure to DEHP during pregnancy on neonatal asthma susceptibility using a murine model of asthma induced by ovalbumin (OVA). Pregnant BALB/c mice received DEHP from gestation day 13 to lactation day 21. Their offspring were sensitized on postnatal days (PNDs) 9 and 15 by intraperitoneal injection of 0.5 μg OVA with 200 μg aluminum hydroxide. On PNDs 22, 23 and 24, live pups received an airway challenge of OVA for 30 min. Offspring from pregnant mice that received DEHP showed reductions in inflammatory cell count, interleukin (IL)-4, IL-13, and eotaxin in their bronchoalveolar lavage fluid and in total immunoglobulin E and OVA-specific IgE in their plasma compared with offspring from pregnant mice that did not receive DEHP treatment. These results were consistent with histological analysis and immunoblotting. Maternal exposure to DEHP reduces airway inflammation and mucus production in offspring, with a decrease in inducible nitric oxide synthase (iNOS) in the lung tissue. This study suggests that maternal exposure to DEHP during pregnancy reduces asthmatic responses induced by OVA challenge in offspring. These effects were considered to be closely related to the suppression of Th2 immune responses and iNOS expression. - Highlights: • Maternal exposure to di(2-ethylhexyl)phthalate reduces asthmatic response in pups. • Di(2-ethylhexyl)phthalate reduces eosinophilia induced by ovalbumin exposure. • Di(2-ethylhexyl)phthalate reduces T-helper type 2 cytokine production. • Di(2-ethylhexyl)phthalate attenuates airway inflammation and mucus production. • Di(2-ethylhexyl)phthalate suppresses inducible nitric oxide synthase in lung tissue.

Effects of maternal exposure to di(2-ethylhexyl)phthalate (DEHP) during pregnancy on susceptibility to neonatal asthma

International Nuclear Information System (INIS)

Shin, In-Sik; Lee, Mee-Young; Cho, Eun-Sang; Choi, Eun-young; Son, Hwa-Young; Lee, Kyoung-Youl

2014-01-01

Di(2-ethylhexyl) phthalate (DEHP) is used as a plasticizer and is widely dispersed in the environment. In this study, we investigated the effects of maternal exposure to DEHP during pregnancy on neonatal asthma susceptibility using a murine model of asthma induced by ovalbumin (OVA). Pregnant BALB/c mice received DEHP from gestation day 13 to lactation day 21. Their offspring were sensitized on postnatal days (PNDs) 9 and 15 by intraperitoneal injection of 0.5 μg OVA with 200 μg aluminum hydroxide. On PNDs 22, 23 and 24, live pups received an airway challenge of OVA for 30 min. Offspring from pregnant mice that received DEHP showed reductions in inflammatory cell count, interleukin (IL)-4, IL-13, and eotaxin in their bronchoalveolar lavage fluid and in total immunoglobulin E and OVA-specific IgE in their plasma compared with offspring from pregnant mice that did not receive DEHP treatment. These results were consistent with histological analysis and immunoblotting. Maternal exposure to DEHP reduces airway inflammation and mucus production in offspring, with a decrease in inducible nitric oxide synthase (iNOS) in the lung tissue. This study suggests that maternal exposure to DEHP during pregnancy reduces asthmatic responses induced by OVA challenge in offspring. These effects were considered to be closely related to the suppression of Th2 immune responses and iNOS expression. - Highlights: • Maternal exposure to di(2-ethylhexyl)phthalate reduces asthmatic response in pups. • Di(2-ethylhexyl)phthalate reduces eosinophilia induced by ovalbumin exposure. • Di(2-ethylhexyl)phthalate reduces T-helper type 2 cytokine production. • Di(2-ethylhexyl)phthalate attenuates airway inflammation and mucus production. • Di(2-ethylhexyl)phthalate suppresses inducible nitric oxide synthase in lung tissue

Human decidual macrophages and NK cells differentially express Toll-like receptors and display distinct cytokine profiles upon TLR stimulation.

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Marion eDuriez

2014-07-01

Full Text Available Maternofetal pathogen transmission is partially controlled at the level of the maternal uterine mucosa at the fetal implantation site (the decidua basalis, where maternal and fetal cells are in close contact. Toll-like receptors (TLRs may play an important role in initiating rapid immune responses against pathogens in the decidua basalis, however the tolerant microenvironment should be preserved in order to allow fetal development. Here we investigated the expression and functionality of TLRs expressed by decidual macrophages (dMs and NK cells (dNKs, the major decidual immune cell populations.We report for the first time that both human dMs and dNK cells express mRNAs encoding TLRs 1-9, albeit with a higher expression level in dMs. TLR2, TLR3 and TLR4 protein expression checked by flow cytometry was positive for both dMs and dNK cells. In vitro treatment of primary dMs and dNK cells with specific TLR2, TLR3, TLR4, TLR7/8 and TLR9 agonists enhanced their secretion of pro- and anti-inflammatory cytokines, as well as cytokines and chemokines involved in immune cell crosstalk. Only dNK cells released IFN-γ, whereas only dMs released IL-1β, IL-10 and IL-12. TLR9 activation of dMs resulted in a distinct pattern of cytokine expression compared to the other TLRs. The cytokine profiles expressed by dMs and dNK cells upon TLR activation are compatible with maintenance of the fetotolerant immune environment during initiation of immune responses to pathogens at the maternofetal interface.

The Role of Cytokines in the Pathophysiology of Suicidal Behavior

Science.gov (United States)

Ganança, Licínia; Oquendo, Maria A.; Tyrka, Audrey R.; Cisneros-Trujillo, Sebastian; Mann, J. John; Sublette, M. Elizabeth

2016-01-01

Objective Immune dysregulation has been implicated in depression and other psychiatric disorders. What is less clear is how immune dysregulation can affect risk of suicidal behavior. We reviewed the scientific literature concerning cytokines related to suicidal ideation, suicidal behavior and suicide, and surveyed clinical and neurobiological factors associated with cytokine levels that may modulate effects of inflammation on suicide risk. Methods We searched PubMed, Embase, Scopus and PsycINFO for relevant studies published from 1980 through February, 2015. Papers were included if they were written in English and focused on cytokine measurements in patients with suicidal behaviors. Results The literature search yielded 22 studies concerning cytokines and suicidal ideation, suicide attempts or suicide completion. The most consistent finding was elevated interleukin (IL)-6, found in 8 out of 14 studies, in CSF, blood, and postmortem brain. In one study, IL-6 in CSF was also found to be higher in violent than nonviolent attempters and to correlate with future suicide completion. Low plasma IL-2 was observed in 2 studies of suicide attempters, while divergent results were seen for tumor necrosis factor (TNF)-α, interferon (IFN)-γ, transforming growth factor (TGF)-β, IL-4, and soluble Il-2 receptors. Conclusions Given the complexity suggested by the heterogenous cytokine findings, putative mediators and moderators of inflammation on suicidal behavior merit further study. Elevated IL-6 was the most robust cytokine finding, associated with suicidal ideation and both nonfatal suicide attempts and suicides. Future studies should evaluate the predictive value of high IL-6, consider how this may alter brain function to impact suicidal behavior, and explore the potential beneficial effects of reducing IL-6 on suicide risk. PMID:26546783

Cytokines as cellular communicators

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R. Debets

1996-01-01

Full Text Available Cytokines and their receptors are involved in the pathophysiology of many diseases. Here we present a detailed review on cytokines, receptors and signalling routes, and show that one important lesson from cytokine biology is the complex and diverse regulation of cytokine activity. The activity of cytokines is controlled at the level of transcription, translation, storage, processing, posttranslational modification, trapping, binding by soluble proteins, and receptor number and/or function. Translation of this diverse regulation in strategies aimed at the control of cytokine activity will result in the development of more specific and selective drugs to treat diseases.

Determination of blood ET-1 and related cytokines in pediatric patients with bronchial asthma

International Nuclear Information System (INIS)

Qian Jiangang; Ling Wanli; Ma Yunbao; Zhang Xiaoyi

2005-01-01

Objective: To explore the role of endothelin and related cytokines (IL-5, IL-6, IL-8) in the development of bronchial asthma in pediatric patients. Methods: Plasma ET-1 (with RIA) and serum IL-5 (with ELISA), IL-6, IL-8 (with RIA) levels were measured in 42 pediatric patients with bronchial asthma and 30 controls. Results: The plasma ET-1 levels in the patients during acute attack (n=22) were significantly higher than those in patients during remission (n=20) as well as in controls (P 0.05). Levels of ET-1 were positively correlated with those of IL-5 (during attack, r=0.560, P<0.01; during remission, r=0.435, P<0.01). Conclusion: ET and the cytokines IL-5, IL-6, IL-8 participated in the pathogenesis of bronchial asthma through different mechanisms and dynamic determination of which could reflect the progression of the disease. (authors)

Neonatal immune responses to TLR2 stimulation: Influence of maternal atopy on Foxp3 and IL-10 expression

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Gold Diane R

2006-03-01

Full Text Available Abstract Background Maternal atopic background and stimulation of the adaptive immune system with allergen interact in the development of allergic disease. Stimulation of the innate immune system through microbial exposure, such as activation of the innate Toll-like-receptor 2 (TLR2, may reduce the development of allergy in childhood. However, little is known about the immunological effects of microbial stimulation on early immune responses and in association with maternal atopy. Methods We analyzed immune responses of cord blood mononuclear cells (CBMC from 50 healthy neonates (31 non-atopic and 19 atopic mothers. Cells were stimulated with the TLR2 agonist peptidoglycan (Ppg or the allergen house dust mite Dermatophagoides farinae (Derf1, and results compared to unstimulated cells. We analyzed lymphocyte proliferation and cytokine secretion of CBMC. In addition, we assessed gene expression associated with T regulatory cells including the transcription factor Foxp3, the glucocorticoid-induced TNF receptor (GITR, and the cytotoxic lymphocyte antigen 4 (CTLA4. Lymphocyte proliferation was measured by 3H-Thymidine uptake, cytokine concentrations determined by ELISA, mRNA expression of T cell markers by real-time RT-PCR. Results Ppg stimulation induced primarily IL-10 cytokine production, in addition to IFN-γ, IL-13 and TNF-α secretion. GITR was increased following Ppg stimulation (p = 0.07. Ppg-induced IL-10 production and induction of Foxp3 were higher in CBMC without, than with maternal atopy (p = 0.04, p = 0.049. IL-10 production was highly correlated with increased expression of Foxp3 (r = 0.53, p = 0.001, GITR (r = 0.47, p = 0.004 and CTLA4 (r = 0.49, p = 0.003, independent of maternal atopy. Conclusion TLR2 stimulation with Ppg induces IL-10 and genes associated with T regulatory cells, influenced by maternal atopy. Increased IL-10 and Foxp3 induction in CBMC of non-atopic compared to atopic mothers, may indicate an increased capacity to

Composition of fatty acids in the maternal and umbilical cord plasma of adolescent and adult mothers: relationship with anthropometric parameters of newborn

OpenAIRE

Oliveira, Ol?via RC; Santana, Michelle G; Santos, Fl?via S; Concei??o, Felipe D; Sardinha, F?tima LC; Veiga, Gl?ria V; Tavares do Carmo, Maria G

2012-01-01

Abstract Background Considering the importance of long chain polyunsaturated fatty acids to fetal development and the lack of studies that have compared the status of fatty acids between adolescents and adults mothers, the purpose of this study was to evaluate the composition of fatty acids in maternal and umbilical cord plasma from adolescent and adults mothers. Methods Forty pregnant adolescents and forty pregnant adults were selected to assess the distribution profile of fatty acids in the...

Circulating cytokines, chemokines and adhesion molecules in normal pregnancy and preeclampsia determined by multiplex suspension array

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Bekő Gabriella

2010-12-01

Full Text Available Abstract Background Preeclampsia is a severe complication of pregnancy characterized by an excessive maternal systemic inflammatory response with activation of both the innate and adaptive arms of the immune system. Cytokines, chemokines and adhesion molecules are central to innate and adaptive immune processes. The purpose of this study was to determine circulating levels of cytokines, chemokines and adhesion molecules in normal pregnancy and preeclampsia in a comprehensive manner, and to investigate their relationship to the clinical features and laboratory parameters of the study participants, including markers of overall inflammation (C-reactive protein, endothelial activation (von Willebrand factor antigen and endothelial injury (fibronectin, oxidative stress (malondialdehyde and trophoblast debris (cell-free fetal DNA. Results Serum levels of interleukin (IL-1beta, IL-1 receptor antagonist (IL-1ra, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p40, IL-12p70, IL-18, interferon (IFN-gamma, tumor necrosis factor (TNF-alpha, transforming growth factor (TGF-beta1, interferon-gamma-inducible protein (IP-10, monocyte chemotactic protein (MCP-1, intercellular adhesion molecule (ICAM-1 and vascular cell adhesion molecule (VCAM-1 were measured in 60 preeclamptic patients, 60 healthy pregnant women and 59 healthy non-pregnant women by multiplex suspension array and ELISA. In normal pregnancy, the relative abundance of circulating IL-18 over IL-12p70 and the relative deficiency of the bioactive IL-12p70 in relation to IL-12p40 might favour Th2-type immunity. Although decreased IL-1ra, TNF-alpha and MCP-1 concentrations of healthy pregnant relative to non-pregnant women reflect anti-inflammatory changes in circulating cytokine profile, their decreased serum IL-10 and increased IP-10 levels might drive pro-inflammatory responses. In addition to a shift towards Th1-type immunity (expressed by the increased IL-2/IL-4 and IFN-gamma/IL-4 ratios, circulating levels of

The relevance of cytokines in the radiation-induced lung reaction. Experimental basis and clinical significance

International Nuclear Information System (INIS)

Ruebe, C.E.; Ruebe, C.; Rodemann, H.P.

2004-01-01

Methods: published data on radiation-induced cytokine expression from experimental and clinical studies are reviewed. Results and conclusion: the major pro-inflammatory cytokines in the radiation response of the lung include tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), and interleukin-6 (IL-6). Transforming growth factor-β (TGF-β) appears to be of particular importance in the development of lung fibrosis. First approaches with radioprotective agents and gene therapy to modify radiation-induced cytokine expression have been investigated for prevention of late effects of irradiation lung damage in animal experiments. Preliminary data of clinical studies suggest that elevated plasma TGF-β-levels during radiotherapy may predict the development of symptomatic radiation pneumonitis. The biological impacts of endogenous radiation-induced cytokine production by tumor cells in respect of tumor behavior, potential damage to normal tissue, and clinical status of the host still need to be determined more precisely. (orig.)

Environmental enrichment delays pup-induced maternal behavior in rats.

Science.gov (United States)

Mann, Phyllis E; Gervais, Kristen J

2011-05-01

Adult, virgin rats do not spontaneously display maternal behavior when exposed to foster pups. However, continuous daily exposure of the female to foster pups for about 5-7 days can induce a set of maternal behaviors similar to those shown by postpartum dams. Induction latencies depend upon a number of factors, including the stress and anxiety levels of the female. The goal of this study was to attempt to mitigate the likely stressfulness of being singly housed during testing by enriching the rat's home cage environment and to determine if the concomitant environmental change would alter the latency to express maternal behavior. In addition, the effect of varying the number of test pups used for testing was examined. Two groups of virgin Sprague-Dawley rats were first tested on the elevated plus maze after 1 week of exposure to either control (standard housing) or enriched conditions. One week later, maternal behavior testing began using one or three pups. Upon completion of maternal behavior testing, plasma corticosterone concentrations were determined following a mild stressor. The data indicate that enrichment tends to increase anxiety-like behaviors in the elevated plus maze. In addition, enrichment delayed the onset of maternal behavior irrespective of the number of test pups. There were no effects of environmental enrichment on plasma corticosterone levels following exposure to a stressor. These results indicate that what is considered a modestly enriched environment delays the expression of pup-oriented responses and does not apparently reduce stress or improve performance on all behavioral tasks. Copyright © 2011 Wiley Periodicals, Inc.

Study on the inter-relationship between serum cytokines levels and severity of type 2 diabetes mellitus

International Nuclear Information System (INIS)

Li Yongchun; Xie Jianping

2005-01-01

Objective: To investigate the role played by serum cytokines (IL-6, IL-8, TNF-α) in the pathogenesis of diabetes mellitus. Methods: Serum IL-6, IL-8 and TNF-α levels were measured with RIA in 27 diabetic patients without complications, 18 patients with early nephro or retinopathy and 33 controls. Results: (1) Serum levels of IL-6, IL-8 and TNF-α were significantly higher in the diabetic patients than those in controls (P<0.01). (2) Levels of the cytokines in diabetic patients with early complications were significantly higher than those in patients without complications (P<0.02). (3) The serum levels of these cytokines were mutually positively correlated. Conclusion: The cytokines IL-6, IL-8 and TNF-α participated in the development and pathophysiology of diabetes mellitus and monitoring their plasma level changes would be clinically useful. (authors)

Cytokine Polymorphisms, Their Influence and Levels in Brazilian Patients with Pulmonary Tuberculosis during Antituberculosis Treatment

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Eliana Peresi

2013-01-01

Full Text Available Cytokines play an essential role during active tuberculosis disease and cytokine genes have been described in association with altered cytokine levels. Therefore, the aim of this study was to verify if IFNG, IL12B, TNF, IL17A, IL10, and TGFB1 gene polymorphisms influence the immune response of Brazilian patients with pulmonary tuberculosis (PTB at different time points of antituberculosis treatment (T1, T2, and T3. Our results showed the following associations: IFNG +874 T allele and IFNG +2109 A allele with higher IFN-γ levels; IL12B +1188 C allele with higher IL-12 levels; TNF −308 A allele with higher TNF-α plasma levels in controls and mRNA levels in PTB patients at T1; IL17A A allele at rs7747909 with higher IL-17 levels; IL10 −819 T allele with higher IL-10 levels; and TGFB1 +29 CC genotype higher TGF-β plasma levels in PTB patients at T2. The present study suggests that IFNG +874T/A, IFNG +2109A/G, IL12B +1188A/C, IL10 −819C/T, and TGFB1 +21C/T are associated with differential cytokine levels in pulmonary tuberculosis patients and may play a role in the initiation and maintenance of acquired cellular immunity to tuberculosis and in the outcome of the active disease while on antituberculosis treatment.

Dynamic alterations of bone marrow cytokine landscape of myelodysplastic syndromes patients treated with 5-azacytidine

Czech Academy of Sciences Publication Activity Database

Moudra, A.; Hubackova, Sona; Machalova, V.; Vančurová, M.; Bartek, J.; Reinis, M.; Hodny, Z.; Jonasova, A.

2016-01-01

Roč. 5, č. 10 (2016), č. článku e1183860. ISSN 2162-402X Institutional support: RVO:86652036 Keywords : 5-azacytidine * DNA damage * cytokines * bone marrow plasma Subject RIV: FD - Oncology ; Hematology Impact factor: 7.719, year: 2016

Effect of ethanol consumption during gestation on maternal-fetal amino acid metabolism in the rat

International Nuclear Information System (INIS)

Lin, G.W.

1981-01-01

The distribution of 14 C-alpha-aminoisobutyric acid (AIB), administered intravenously, in maternal, fetal and placental tissues was examined in the rat on gestation-day 21. Ethanol consumption during gestation (day 6 through 21) significantly reduced the uptake of AIB by the placenta and fetus while exerting no influence on maternal tissue AIB uptake. The concentration of fetal plasma free histidine was decreased 50% as a result of maternal ethanol ingestion, but the free histidine level of maternal plasma was not altered. Since no effect on protein content of fetal tissue could be detected, it is speculated that reduced histidine to the fetus might significantly alter the amounts of histamine and carnosine formed via their precursor. The significance of these findings in relation to the Fetal Alcohol Syndrome is discussed

Maternal diet and dioxin-like activity, bulky DNA adducts and micronuclei in mother-newborns

DEFF Research Database (Denmark)

Pedersen, Marie; Halldorsson, Thorhallur I; Autrup, Herman

2012-01-01

Maternal diet can contribute to carcinogenic exposures and also modify effects of environmental exposures on maternal and fetal genetic stability. In this study, associations between maternal diet and the levels of dioxin-like plasma activity, bulky DNA adducts in white blood cells and micronuclei...... (MN) in lymphocytes from mother to newborns were examined. From 98 pregnant women living in the greater area of Copenhagen, Denmark in 2006-2007, maternal peripheral blood and umbilical cord blood were collected, together with information on health, environmental exposure and lifestyle. Maternal diet...

Immune activation in lactating dams alters sucklings' brain cytokines and produces non-overlapping behavioral deficits in adult female and male offspring: A novel neurodevelopmental model of sex-specific psychopathology.

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Arad, Michal; Piontkewitz, Yael; Albelda, Noa; Shaashua, Lee; Weiner, Ina

2017-07-01

Early immune activation (IA) in rodents, prenatal through the mother or early postnatal directly to the neonate, is widely used to produce behavioral endophenotypes relevant to schizophrenia and depression. Given that maternal immune response plays a crucial role in the deleterious effects of prenatal IA, and lactation is a critical vehicle of immunological support to the neonate, we predicted that immune activation of the lactating dam will produce long-term abnormalities in the sucklings. Nursing dams were injected on postnatal day 4 with the viral mimic poly-I:C (4mg/kg) or saline. Cytokine assessment was performed in dams' plasma and milk 2h, and in the sucklings' hippocampus, 6h and 24h following poly-I:C injection. Male and female sucklings were assessed in adulthood for: a) performance on behavioral tasks measuring constructs considered relevant to schizophrenia (selective attention and executive control) and depression (despair and anhedonia); b) response to relevant pharmacological treatments; c) brain structural changes. Maternal poly-I:C injection caused cytokine alterations in the dams' plasma and milk, as well as in the sucklings' hippocampus. Lactational poly-I:C exposure led to sex-dimorphic (non-overlapping) behavioral abnormalities in the adult offspring, with male but not female offspring exhibiting attentional and executive function abnormalities (manifested in persistent latent inhibition and slow reversal) and hypodopaminergia, and female but not male offspring exhibiting despair and anhedonia (manifested in increased immobility in the forced swim test and reduced saccharine preference) and hyperdopaminergia, mimicking the known sex-bias in schizophrenia and depression. The behavioral double-dissociation predicted distinct pharmacological profiles, recapitulating the pharmacology of negative/cognitive symptoms and depression. In-vivo imaging revealed hippocampal and striatal volume reductions in both sexes, as found in both disorders. This is

Cytokines and Liver Diseases

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Herbert Tilg

2001-01-01

Full Text Available Cytokines are pleiotropic peptides produced by virtually every nucleated cell in the body. In most tissues, including the liver, constitutive production of cytokines is absent or minimal. There is increasing evidence that several cytokines mediate hepatic inflammation, apoptosis and necrosis of liver cells, cholestasis and fibrosis. Interestingly, the same mediators also mediate the regeneration of liver tissue after injury. Among the various cytokines, the proinflammatory cytokine tumour necrosis factor-alpha (TNF-a has emerged as a key factor in various aspects of liver disease, such as cachexia and/or cholestasis. Thus, antagonism of TNF-a and other injury-related cytokines in liver diseases merits evaluation as a treatment of these diseases. However, because the same cytokines are also necessary for the regeneration of the tissue after the liver has been injured, inhibition of these mediators might impair hepatic recovery. The near future will bring the exiting clinical challenge of testing new anticytokine strategies in various liver diseases.

IRF4 Deficiency Abrogates Lupus Nephritis Despite Enhancing Systemic Cytokine Production

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Lech, Maciej; Weidenbusch, Marc; Kulkarni, Onkar P.; Ryu, Mi; Darisipudi, Murthy Narayana; Susanti, Heni Eka; Mittruecker, Hans-Willi; Mak, Tak W.

2011-01-01

The IFN-regulatory factors IRF1, IRF3, IRF5, and IRF7 modulate processes involved in the pathogenesis of systemic lupus and lupus nephritis, but the contribution of IRF4, which has multiple roles in innate and adaptive immunity, is unknown. To determine a putative pathogenic role of IRF4 in lupus, we crossed Irf4-deficient mice with autoimmune C57BL/6-(Fas)lpr mice. IRF4 deficiency associated with increased activation of antigen-presenting cells in C57BL/6-(Fas)lpr mice, resulting in a massive increase in plasma levels of TNF and IL-12p40, suggesting that IRF4 suppresses cytokine release in these mice. Nevertheless, IRF4 deficiency completely protected these mice from glomerulonephritis and lung disease. The mice were hypogammaglobulinemic and lacked antinuclear and anti-dsDNA autoantibodies, revealing the requirement of IRF4 for the maturation of plasma cells. As a consequence, Irf4-deficient C57BL/6-(Fas)lpr mice neither developed immune complex disease nor glomerular activation of complement. In addition, lack of IRF4 impaired the maturation of Th17 effector T cells and reduced plasma levels of IL-17 and IL-21, which are cytokines known to contribute to autoimmune tissue injury. In summary, IRF4 deficiency enhances systemic inflammation and the activation of antigen-presenting cells but also prevents the maturation of plasma cells and effector T cells. Because these adaptive immune effectors are essential for the evolution of lupus nephritis, we conclude that IRF4 promotes the development of lupus nephritis despite suppressing antigen-presenting cells. PMID:21742731

Clinical significance of determination of semen plasma IL-2, IL-6, IL-8 and TNF-α contents in infertile males

International Nuclear Information System (INIS)

Sun Baoyi; Li Jun; Zhang Jiyun

2004-01-01

Objective: To explore the influence of high semen plasma contents of the cytokines (IL-2, IL-6, IL-8, TNF-α) on male fertility. Methods: Semen plasma levels of IL-2, IL-6, IL-8, and TNF-α were determined with RIA in 126 infertile and 20 fertile males. Results: Semen plasma contents of the 4 cytokines in infertile subjects were significantly higher than those in fertile ones (p 4/HP, n=15) had significantly higher contents of cytokines than those without leucocytospermia (WBC<4/HP, n=111). Besides, TNF-α contents in subjects with lower sperm activity and less motility rate as well as IL-8 contents in subjects with less sperm motility rate were both significantly higher than those in subjects with more normal sperms (p<0.01, p<0.05). Conclusion: High semen plasma cytokines contents represent existing local infection and enhanced auto-immune status, both damaging to sperms. Infertility would be the inevitable consequence. Monitoring of changes of the cytokine contents should be a part of fertility studies

The urinary cytokine/chemokine signature of renal hyperfiltration in adolescents with type 1 diabetes.

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Ron L H Har

Full Text Available Urinary cytokine/chemokine levels are elevated in adults with type 1 diabetes (T1D exhibiting renal hyperfiltration. Whether this observation extends to adolescents with T1D remains unknown. Our first objective was to determine the relationship between hyperfiltration and urinary cytokines/chemokines in normotensive, normoalbuminuric adolescents with T1D using GFR(cystatin. Our second aim was to determine the relationship between urine and plasma levels of inflammatory biomarkers, to clarify the origin of these factors.Urine and serum cytokines/chemokines (Luminex platform and GFR(cystatin were measured in normofiltering (n = 111, T1D-N, GFR<135 ml/min/1.73 m(2 and hyperfiltering (n = 31, T1D-H, GFR ≥ 135 ml/min/1.73 m(2 adolescents with T1D (ages 10-16, and in age and sex matched healthy control subjects (HC, n = 59.We noted significant step-wise increases in urinary cytokine/chemokine excretion according to filtration status with highest levels in T1D-H, with parallel trends in serum analyte concentrations. After adjusting for serum glucose at the time of sampling, differences in urinary cytokine excretion were not statistically significant. Only serum IL-2 significantly differed between HC and T1D (p = 0.0076.Hyperfiltration is associated with increased urinary cytokine/chemokine excretion in T1D adolescents, and parallel trends in serum cytokine concentration. The GFR-associated trends in cytokine excretion may be driven by the effects of ambient hyperglycemia. The relationship between hyperfiltration, glycemia, and variations in serum and urine cytokine expression and their impact on future renal and systemic vascular complications requires further study.

Effect of pregnancy on anti-HEV antibody titres, plasma cytokines and the corresponding gene expression levels in the PBMCs of patients presenting with self-recovering clinical and subclinical hepatitis E.

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Ashwini Y Ramdasi

Full Text Available High mortality in pregnant women (PR is a characteristic of hepatitis E in developing countries. To understand the pathogenesis of HEV infection in self-limiting disease during pregnancy, we compared clinical (PR-patients and subclinical-HEV-infections in pregnant women in the first (SC-PR-1 and later (2nd and 3rd, SC-PR-2+3 trimesters with the respective healthy controls and acute non-PR patients. The SC-PR-2+3 exhibited lower ALT, bilirubin levels, anti-HEV-IgM/IgG titres than the acute-PR/non-PR-patients (p<0.05-0.0001. IFNγ/IL4ratios indicated Th2/Th1 bias in non-PR and PR-patients respectively. Raised levels of 10/20 plasma cytokines in the non-PR-patients reflect predominant inflammatory response, unaltered- IFNγ/reduced-IFNα responses and a robust chemokine secretion. On contrary, the acute-PR-patients exhibited drastic reduction in majority of the cytokines relative to in the non-PR-patients. Importantly, diminished or unaltered response was noted in the acute-PR-group when compared to the corresponding controls. The only exception was sIL2RA, increasing in both patient categories. Of the 14 genes evaluated, the expression of IFNγ/IL10/IL1A/IL7/CCL2/CCL3/CXCL8/CXCL10 was higher in the non-PR patients. Of these, the expression of IFNγ/IL10/IL1A/CCL2/CCL3/CXCL8 and, additionally, IL2/IL6/TNF genes was higher in the clinical-PRs. Almost identical pattern was noted in the control-PR-2+3 category indicating no influence of HEV infection. Comparison of patient-categories identified significant elevation of IFNγ(P<0.001, CCL2(p<0.01, CXCL8(P<0.05, IL1B(p<0.05 and IL10(P<0.0001 and decrease in CXCL10(<0.05 in the PR-patients. The results suggest antibody-dependent disease severity and impaired immune response in the PR patients. Higher expression of cytokine-genes in the PBMCs did not correlate with the plasma-cytokine levels in the PR-patients.

Growth hormone concentrations in mammary secretions and plasma of the periparturient bitch and in plasma of the neonate.

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Schoenmakers, I; Kooistra, H S; Okkens, A C; Hazewinkel, H A; Bevers, M M; Mol, J A

1997-01-01

The presence of growth hormone (GH) in mammary secretions of bitches was investigated in relation to plasma GH concentrations at about the time of parturition and during the first weeks of lactation. Plasma GH concentrations in neonates were measured during the first weeks of lactation, to determine whether GH in maternal milk contributes to plasma concentrations of GH in the neonate. Gastrointestinal uptake of GH was studied by measurement of plasma bovine GH (bGH) concentrations after intragastric administration of bGH. High concentrations of GH were found in the mammary secretions of the bitches, particularly before parturition and in colostrum, exceeding maternal plasma concentration up to 100-1000 times. GH concentrations in milk were not not significantly correlated with GH concentrations in plasma of bitches or neonates. Bovine GH could not be detected in neonatal plasma for 4 h after intragastric administration of bGH. The presence of high concentrations of canine GH (cGH) in ante-partum and colostral mammary secretions is consistent with the progesterone-induced mammary biosynthesis of GH. GH in milk is probably not absorbed from the gastrointestinal tract into the blood circulation of the newborn in its intact form.

Application of real-time PCR of sex-independent insertion-deletion polymorphisms to determine fetal sex using cell-free fetal DNA from maternal plasma.

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Ho, Sherry Sze Yee; Barrett, Angela; Thadani, Henna; Asibal, Cecille Laureano; Koay, Evelyn Siew-Chuan; Choolani, Mahesh

2015-07-01

Prenatal diagnosis of sex-linked disorders requires invasive procedures, carrying a risk of miscarriage of up to 1%. Cell-free fetal DNA (cffDNA) present in cell-free DNA (cfDNA) from maternal plasma offers a non-invasive source of fetal genetic material for analysis. Detection of Y-chromosome sequences in cfDNA indicates presence of a male fetus; in the absence of a Y-chromosome signal a female fetus is inferred. We aimed to validate the clinical utility of insertion-deletion polymorphisms (INDELs) to confirm presence of a female fetus using cffDNA. Quantitative real-time PCR (qPCR) for the Y-chromosome-specific sequence, SRY, was performed on cfDNA from 82 samples at 6-39 gestational weeks. In samples without detectable SRY, qPCRs for eight INDELs were performed on maternal genomic DNA and cfDNA. Detection of paternally inherited fetal alleles in cfDNA negative for SRY confirmed a female fetus. Fetal sex was correctly determined in 77/82 (93.9%) cfDNA samples. SRY was detected in all 39 samples from male-bearing pregnancies, and none of the 43 female-bearing pregnancies (sensitivity and specificity of SRY qPCR is therefore 100%; 95% CI 91%-100%). Paternally inherited fetal alleles were detected in 38/43 samples with no SRY signal, confirming the presence of a female fetus (INDEL assay sensitivity is therefore 88.4%; 95% CI 74.1%-95.6%). Since paternally inherited fetal INDELs were not used in women bearing male fetuses, the specificity of INDELs cannot be calculated. Five cfDNA samples were negative for both SRY and INDELS. We have validated a non-invasive prenatal test to confirm fetal sex as early as 6 gestational weeks using cffDNA from maternal plasma.

Immune cell subsets, cytokine and cortisol levels during the first week of life in neonates born to pre-eclamptic mothers.

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Sava, Florentina; Toldi, Gergely; Treszl, András; Hajdú, Júlia; Harmath, Ágnes; Rigó, János; Tulassay, Tivadar; Vásárhelyi, Barna

2017-06-01

To address the hypothesis that pre-eclampsia (PE) impacts the fetal immune system, we investigated the prevalence of distinct immune cell subsets along with plasma cortisol and cytokine levels in pre-term newborns of PE mothers. Cord blood and peripheral blood samples on the 1st, 3rd and 7th postnatal days of life were collected from 14 pre-term infants affected by PE and 14 non-PE pregnancies. We measured plasma cortisol and cytokine levels with immunoassays and assessed the prevalence of T, NK and DC subsets using flow cytometry. The prevalence of CD4+ cells was lower in PE infants, while that of memory T cells was higher. Myeloid DCs had a lower prevalence in PE neonates. Cytokine and cortisol levels were lower in PE neonates. Our observations show that PE pregnancies are associated with altered newborn immune status during the first week of life. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Plasma cross-gestational sphingolipidomic analyses reveal potential first trimester biomarkers of preeclampsia.

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Aneta Dobierzewska

Full Text Available Preeclampsia (PE is a gestational disorder, manifested in the second half of pregnancy by maternal hypertension, proteinuria and generalized edema. PE is a major cause of maternal and fetal morbidity and mortality, accounting for nearly 40% of all premature births worldwide. Bioactive sphingolipids are emerging as key molecules involved in etiopathogenesis of PE, characterized by maternal angiogenic imbalance and symptoms of metabolic syndrome. The aim of this study was to compare the cross-gestational profile of circulating bioactive sphingolipids in maternal plasma from preeclamptic (PE versus normotensive control (CTL subjects with the goal of identifying sphingolipids as candidate first trimester biomarkers of PE for early prediction of the disease.A prospective cohort of patients was sampled at the first, second and third trimester of pregnancy for each patient (11-14, 22-24, and 32-36 weeks´ gestation. A retrospective stratified study design was used to quantify different classes of sphingolipids in maternal plasma. We used a reverse-phase high-performance liquid chromatography-tandem mass spectrometry (HPLC-ESI-MS/MS approach for determining different sphingolipid molecular species (sphingosine-1-phosphate (S1P, dihydro-sphingosine-1-phosphate (DH-S1P, sphingomyelins (SM and ceramides (Cer in cross-gestational samples of human plasma from PE (n = 7, 21 plasma samples across pregnancy and CTL (n = 7, 21 plasma samples across pregnancy patients.Plasma levels of angiogenic S1P did not change significantly in control and in preeclamptic patients´ group across gestation. DH-S1P was significantly decreased in second trimester plasma of PE patients in comparison to their first trimester, which could contribute to reduced endothelial barrier observed in PE. The major ceramide species (Cer 16:0 and Cer 24:0 tended to be up-regulated in plasma of control and PE subjects across gestation. The levels of a less abundant plasma ceramide species (Cer

Does maternal-fetal transfer of creatine occur in pregnant sheep?

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Baharom, Syed; De Matteo, Robert; Ellery, Stacey; Della Gatta, Paul; Bruce, Clinton R; Kowalski, Greg M; Hale, Nadia; Dickinson, Hayley; Harding, Richard; Walker, David; Snow, Rodney J

2017-07-01

Our aim was to determine the disposition of creatine in ovine pregnancy and whether creatine is transferred across the placenta from mother to fetus. Pregnant ewes received either 1 ) a continuous intravenous infusion of creatine monohydrate or saline from 122 to 131 days gestation, with maternal and fetal arterial blood and amniotic fluid samples collected daily for creatine analysis and fetal tissues collected at necropsy at 133 days for analysis of creatine content, or 2 ) a single systemic bolus injection of [ 13 C]creatine monohydrate at 130 days of gestation, with maternal and fetal arterial blood, uterine vein blood, and amniotic fluid samples collected before and for 4 h after injection and analyzed for creatine, creatine isotopic enrichment, and guanidinoacetic acid (GAA; precursor of creatine) concentrations. Presence of the creatine transporter-1 (SLC6A8) and l-arginine:glycine amidinotransferase (AGAT; the enzyme synthesizing GAA) proteins were determined by Western blots of placental cotyledons. The 10-day creatine infusion increased maternal plasma creatine concentration three- to fourfold ( P creatine content. Maternal arterial 13 C enrichment was increased ( P creatine injection without change of fetal arterial 13 C enrichment. SLC6A8 and AGAT proteins were identified in placental cotyledons, and GAA concentration was significantly higher in uterine vein than maternal artery plasma. Despite the presence of SLC6A8 protein in cotyledons, these results suggest that creatine is not transferred from mother to fetus in near-term sheep and that the ovine utero-placental unit releases GAA into the maternal circulation. Copyright © 2017 the American Physiological Society.

Choline concentrations are lower in postnatal plasma of preterm infants than in cord plasma.

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Bernhard, Wolfgang; Raith, Marco; Kunze, Rebecca; Koch, Vera; Heni, Martin; Maas, Christoph; Abele, Harald; Poets, Christian F; Franz, Axel R

2015-08-01

Choline is essential to human development, particularly of the brain in the form of phosphatidylcholine, sphingomyelin and acetylcholine, for bile and lipoprotein formation, and as a methyl group donator. Choline is actively transported into the fetus, and maternal supply correlates with cognitive outcome. Interruption of placental supply may therefore impair choline homeostasis in preterm infants. Determination of postnatal plasma concentrations of choline and its derivatives betaine and dimethylglycine (DMG) in preterm infants compared to cord and maternal blood matched for postmenstrual age (PMA). We collected plasma of very low-birth-weight infants undergoing neonatal intensive care (n = 162), cord plasma of term and preterm infants (n = 176, 24-42-week PMA), serum of parturients (n = 36), and plasma of healthy premenopausal women (n = 40). Target metabolites were analyzed with tandem mass spectrometry and reported as median (25th/75th percentiles). Cord plasma choline concentration was 41.4 (31.8-51.2) µmol/L and inversely correlated with PMA. In term but not in preterm infants, cord plasma choline was lower in girls than in boys. Prenatal glucocorticoid treatment did not affect choline levels in cord plasma, whereas betaine was decreased and DMG increased. In parturients and non-pregnant women, choline concentrations were 14.1 (10.3-16.9) and 8.8 (5.7-11.2) µmol/L, respectively, whereas betaine was lowest in parturients. After delivery, preterm infant plasma choline decreased to 20.8 (16.0-27.6) µmol/L within 48 h. Betaine and DMG correlated with plasma choline in all groups. In preterm infants, plasma choline decreases to 50 % of cord plasma concentrations, reflecting choline undernourishment and postnatal metabolic adaptation, and potentially contributing to impaired outcome.

Tsc2 Haploinsufficiency Has Limited Effects on Fetal Brain Cytokine Levels during Gestational Immune Activation

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Dan Ehninger

2014-01-01

Full Text Available Dysregulated TSC/mTOR signaling may play a pathogenetic role in forms of syndromic autism, such as autism associated with tuberous sclerosis, a genetic disorder caused by heterozygous TSC1 or TSC2 mutations. Environmental risk factors, such as gestational viral infections, may, in some cases, also contribute to the pathogenesis of autism and related neuropsychiatric disorders. We have recently found that a heterozygous Tsc2 mutation and the poly I:C model of maternal immune activation (MIA interactively perturb fetal development and adult social behavior in mice, suggesting that these factors converge on shared pathways. TSC/mTOR signaling plays an important role in the modulation of immune responses, raising the possibility that the damage caused by MIA was greater in Tsc2+/− than in wildtype fetuses because of an exacerbated immune response in the mutants. Here, cytokine antibody arrays were employed to measure relative cytokine abundances in the fetal brain and the placenta during MIA. Cytokines were induced by gestational poly I:C but there was no obvious modulatory effect of Tsc2 haploinsufficiency. The data indicate that cytokine exposure during MIA is comparable in Tsc2 haploinsufficient and wildtype control fetuses, suggesting that downstream molecular and cellular processes may account for the interactive effects of Tsc2 haploinsufficiency and MIA.

Aggression as an independent entity even in psychosis- the role of inflammatory cytokines.

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Das, Sourav; Deuri, Sailendra Kumar; Sarmah, Anil; Pathak, Kangkan; Baruah, Aparajeeta; Sengupta, Soumik; Mehta, Sumit; Avinash, Priya Ranjan; Kalita, Kamal Narayan; Hazarika, Jyoti

2016-03-15

Aggression is very common in psychosis (prevalence ranging from 34% to 70%) and is often the main or first symptom for which the patient receives medical attention. Studies have associated alteration in cytokine profiles among healthy persons with aggressive traits. We hypothesise that even among those with psychosis, aggression is an independent entity, irrespective of psychotic state and is associated with cytokine alterations. To our knowledge, this is the first study attempting to look at the inflammatory cytokines in aggressive psychotic patients. Study included 80 participants divided into four groups viz. aggressive diseased, non aggressive diseased, aggressive non diseased and non aggressive non diseased depending upon presence or absence of aggression and psychosis. Interferon gamma(IFN-G), Interleukin 10(IL10) plasma concentrations and their ratio were measured using ELISA based assay kits read at absorbance of 450 nm wavelength using Double beam spectrophotometer. The four groups were compared on measures of aggression, psychosis, Interferon Gamma levels, Interleukin 10 levels, Proinflammatory: Antiinflammatory cytokine ratio using standard statistical instruments. In patients with psychosis, the cytokines IFN-G and IL10 were significantly lower compared to those without. The cytokines IFN-G and IL10 are both significantly associated both with aggression and psychosis. IL10, but not IFN-G is associated with aggression in absence of psychosis. The proinflammatory: antiinflammatory cytokine ratio, is more significantly associated with aggression, irrespective of psychosis. In fact, there is no significant relationship between the above ratio and psychosis. Strong correlation exists between the proinflammatory: antiinflammatory cytokine ratio and aggression scores, even after controlling for severity of psychosis. It may be concluded from this study that in spite of a high prevalence of aggression in patients of psychosis, it is more likely to be an

Progesterone and estradiol exert an inhibitory effect on the production of anti-inflammatory cytokine IL-10 by activated MZ B cells.

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Bommer, I; Muzzio, D O; Zygmunt, M; Jensen, F

2016-08-01

The main message of this work is the fact that female sex hormones, progesterone and estradiol, whose levels significantly rise during pregnancy, inhibit the production of anti-inflammatory cytokine IL-10 with no apparent effect on pro-inflammatory cytokine TNF-α by activated MZ B cells. This is an important piece of information and helps to better understand how the maternal immune system controls the balance between immune tolerance and immune activation during pregnancy leading to the simultaneously acceptance of the semi-allogeneic fetus and the proper defense of the mother against pathogens during this critical period of time. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Maternal nutritional status in early pregnancy is associated with body water and plasma volume changes in a pregnancy cohort in rural Bangladesh.

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Gernand, Alison D; Christian, Parul; Schulze, Kerry J; Shaikh, Saijuddin; Labrique, Alain B; Shamim, Abu Ahmed; West, Keith P

2012-06-01

Plasma volume expansion has been associated with fetal growth. Our objective was to examine the associations between maternal nutritional status in early pregnancy and extracellular water (ECW), total body water (TBW), and percentage plasma volume change across pregnancy. In a subsample of 377 pregnant women participating in a cluster-randomized trial of micronutrient supplementation, hemoglobin, hematocrit, and multi-frequency bioelectrical impedance were measured at ~10, 20, and 32 wk of gestation. In early pregnancy, women were short (mean ± SD, 148.9 ± 5.3 cm) and thin (19.5 ± 2.5 kg/m(2)). In mixed-effects multiple regression models, a 1-unit higher BMI at ~10 wk was associated with higher ECW and TBW (0.27 and 0.66 kg per kg/m(2), respectively; P pregnancy BMI was negatively associated with gains in ECW and TBW (-0.06 and -0.14 kg per kg/m(2), respectively; P pregnancy have lower ECW and TBW in early, mid, and late pregnancy and lower late pregnancy plasma volume expansion, potentially increasing risk of fetal growth restriction.

Maternal house dust mite exposure during pregnancy enhances severity of house dust mite-induced asthma in murine offspring.

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Richgels, Phoebe K; Yamani, Amnah; Chougnet, Claire A; Lewkowich, Ian P

2017-11-01

Atopic status of the mother and maternal exposure to environmental factors are associated with increased asthma risk. Moreover, animal models demonstrate that exposure to allergens in strongly sensitized mothers influences offspring asthma development, suggesting that in utero exposures can influence offspring asthma. However, it is unclear whether maternal exposure to common human allergens such as house dust mite (HDM), in the absence of additional adjuvants, influences offspring asthma development. We sought to determine whether maternal HDM exposure influences asthma development in offspring. Pregnant female mice were exposed to PBS or HDM during pregnancy. Using offspring of PBS- or HDM-exposed mothers, the magnitude of HDM or Aspergillus fumigatus (AF) extract-induced airway hyperresponsiveness (AHR), airway inflammation, immunoglobulin production, T H 2-associated cytokine synthesis, and pulmonary dendritic cell activity was assessed. Compared with offspring of PBS-exposed mothers, offspring of HDM-exposed mothers demonstrate increased AHR, airway inflammation, T H 2 cytokine production, and immunoglobulin levels and a modest decrease in the phagocytic capacity of pulmonary macrophage populations following HDM exposure. Increased sensitivity to AF-induced airway disease was not observed. Offspring of HDM-exposed B-cell-deficient mothers also demonstrated increased HDM-induced AHR, suggesting that transfer of maternal immunoglobulins is not required. Our data demonstrate that maternal exposure to HDM during pregnancy increases asthma sensitivity in offspring in an HDM-specific manner, suggesting that vertical transmission of maternal immune responses may be involved. These findings have important implications for regulation of asthma risk, and suggest that exposure to HDM in the developed world may have underappreciated influences on the overall prevalence of allergic asthma. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by

Fetal Gender and Several Cytokines Are Associated with the Number of Fetal Cells in Maternal Blood - An Observational Study

DEFF Research Database (Denmark)

Schlütter, Jacob Mørup; Kirkegaard, Ida; Petersen, Olav Bjørn

2014-01-01

OBJECTIVE: To identify factors influencing the number of fetal cells in maternal blood. METHODS: A total of 57 pregnant women at a gestational age of weeks 11-14 were included. The number of fetal cells in maternal blood was assessed in 30 ml of blood using specific markers for both enrichment...

Systemic release of cytokines and heat shock proteins in porcine models of polytrauma and hemorrhage

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Baker, Todd A.; Romero, Jacqueline; Bach, Harold H.; Strom, Joel A.; Gamelli, Richard L.; Majetschak, Matthias

2011-01-01

Objective To define systemic release kinetics of a panel of cytokines and heat shock proteins (HSP) in porcine polytrauma/hemorrhage models and to evaluate whether they could be useful as early trauma biomarkers. Design and Setting Prospective study in a research laboratory. Subjects Twenty-one Yorkshire pigs. Measurements and Main Results Pigs underwent polytrauma (femur fractures/lung contusion, P), hemorrhage (mean arterial pressure 25-30mmHg, H), polytrauma plus hemorrhage (P/H) or sham procedure (S). Plasma was obtained at baseline, in 5-15min intervals during a 60min shock period without intervention and in 60-120min intervals during fluid resuscitation for up to 300min. Plasma was assayed for IL-1β, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12/IL-23p40, IL-13, IL-17, IL-18, IFNγ, TGFβ, TNFα, HSP40, HSP70 and HSP90 by ELISA. All animals after S, P and H survived (n=5/group). Three of six animals after P/H died. IL-10 increased during shock after P and this increase was attenuated after H. TNFα increased during the shock period after P, H and also after S. P/H abolished the systemic IL-10 and TNFα release and resulted in 20-30% increased levels of IL-6 during shock. As fluid resuscitation was initiated TNFα and IL-10 levels decreased after P, H and P/H, HSP 70 increased after P, IL-6 levels remained elevated after P/H and also increased after P and S. Conclusions Differential regulation of the systemic cytokine release after polytrauma and/or hemorrhage, in combination with the effects of resuscitation, can explain the variability and inconsistent association of systemic cytokine/HSP levels with clinical variables in trauma patients. Insults of major severity (P/H) partially suppress the systemic inflammatory response. The plasma concentrations of the measured cytokines/HSPs do not reflect injury severity or physiological changes in porcine trauma models and are unlikely to be able to serve as useful trauma biomarkers in patients. PMID:21983369

Cytokine levels as biomarkers of radiation fibrosis in patients treated with breast radiotherapy

International Nuclear Information System (INIS)

Westbury, Charlotte B; Yarnold, John R; Haviland, Joanne; Davies, Sue; Gothard, Lone; Abdi, Bahja Ahmed; Sydenham, Mark; Bowen, Jo; Stratton, Richard; Short, Susan C

2014-01-01

Radiation fibrosis is not easily measurable although clinical scores have been developed for this purpose. Biomarkers present an alternative more objective approach to quantification, and estimation in blood provides accessible samples. We investigated if blood cytokines could be used to measure established fibrosis in patients who have undergone radiotherapy for breast cancer. We studied two cohorts treated by breast-conserving surgery and radiotherapy in the UK START Trial A, one with breast fibrosis (cases) and one with no or minimal fibrosis (controls). Two candidate cytokines, plasma connective tissue growth factor (CTGF) and serum interleukin-6 (IL6) were estimated by ELISA. Comparisons between cases and controls used the t-test or Mann–Whitney test and associations between blood concentration and clinical factors were assessed using the Spearman rank correlation coefficient. Seventy patients were included (26 cases, 44 controls). Mean time since radiotherapy was 9.9 years (range 8.3-12.0). No statistically significant differences between cases and controls in serum IL6 (median (IQR) 0.84 pg/ml (0.57-1.14), 0.75 pg/ml (0.41-1.43) respectively) or plasma CTGF (331.4 pg/ml (234.8-602.9), 334.5 pg/ml (270.0-452.8) were identified. There were no significant associations between blood cytokine concentration and age, fibrosis severity, breast size or time since radiotherapy. No significant difference in IL6 or CTGF concentrations was detected between patients with breast fibrosis and controls with minimal or no fibrosis

Syndecan-1 knock-down in decidualized human endometrial stromal cells leads to significant changes in cytokine and angiogenic factor expression patterns

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Krüssel Jan-Steffen

2010-11-01

Full Text Available Abstract Background Successful embryonic implantation depends on a synchronized embryo-maternal dialogue. Chemokines, such as chemokine ligand 1 (CXCL1, play essential roles in the maternal reproductive tract leading to morphological changes during decidualization, mediating maternal acceptance towards the semi-allograft embryo and induction of angiogenesis. Chemokine binding to their classical G-protein coupled receptors is essentially supported by the syndecan (Sdc family of heparan sulfate proteoglycans. The aim of this study was to identify the involvement of Sdc-1 at the embryo-maternal interface regarding changes of the chemokine and angiogenic profile of the decidua during the process of decidualization and implantation in human endometrium. Methods A stable Sdc-1 knock-down was generated in the immortalized human endometrial stromal cell line St-T1 and was named KdS1. The ability of KdS1 to decidualize was proven by Insulin-like growth factor binding 1 (IGFBP1 and prolactin (PRL confirmation on mRNA level before further experiments were carried out. Dot blot protein analyses of decidualized knock-down cells vs non-transfected controls were performed. In order to imitate embryonic implantation, decidualized KdS1 were then incubated with IL-1beta, an embryo secretion product, vs controls. Statistical analyses were performed applying the Student's t-test with p Results The induction of the Sdc-1 knock-down revealed significant changes in cytokine and angiogenic factor expression profiles of dKdS1 vs decidualized controls. Incubation with embryonic IL-1beta altered the expression patterns of KdS1 chemokines and angiogenic factors towards inflammatory-associated molecules and factors involved in matrix regulation. Conclusions Sdc-1 knock-down in human endometrial stroma cells led to fulminant changes regarding cytokine and angiogenic factor expression profiles upon decidualization and imitation of embryonic contact. Sdc-1 appears to play an

Theory of mind as a link between oxytocin and maternal behavior.

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MacKinnon, Anna L; Carter, C Sue; Feeley, Nancy; Gold, Ian; Hayton, Barbara; Santhakumaran, Sangeetha; Zelkowitz, Phyllis

2018-06-01

Oxytocin is a neuropeptide associated with maternal behavior. However the mechanisms underlying this link remain unclear. In a previous study we observed an indirect effect of increased plasma oxytocin during late pregnancy on early postpartum maternal interactive behavior via theory of mind, as assessed by the Reading the Mind in the Eyes Test (RMET). The current study aimed to extend these findings by testing whether this indirect effect would hold longitudinally for maternal behavior at 2-3 years postpartum, as well as for an additional observational measure of maternal mind-mindedness. The original sample of 316 pregnant women (M age  = 31.92 years) was assessed at 12-14 weeks gestation (T1), 32-34 weeks gestation (T2), and 7-9 weeks postpartum (T3). Follow-up measures were taken at 2-3 years postpartum (T4). Mothers' RMET performance (T3) was associated with more structuring and less intrusive maternal behavior at 2-3 years (T4), while their tendency to use mind-related comments (T3) was associated with greater sensitivity (T4). Bootstrap estimates also revealed a significant indirect effect of plasma oxytocin levels during late pregnancy (T2) on maternal structuring and non-intrusive behavior at 2-3 years postpartum (T4) through RMET performance (T3). Results: of the current study confirm and extend the previous findings, demonstrating that theory of mind may represent a social cognitive mechanism linking endogenous oxytocin and maternal behavior. Important changes in the oxytocinergic system during late pregnancy may help prepare for motherhood by promoting the awareness of social cues, which in turn promote maternal behavior from the early postpartum to the early childhood years. Copyright © 2018 Elsevier Ltd. All rights reserved.

Plasma-mediated immune suppression : a neonatal perspective

NARCIS (Netherlands)

Belderbos, Mirjam E.; Levy, Ofer; Meyaard, Linde; Bont, Louis

Plasma is a rich mixture of immune regulatory factors that shape immune cell function. This immunomodulatory role of plasma is especially important in neonates. To maintain in utero feto-maternal tolerance and to allow for microbial colonization after birth, the neonatal immune system is biased

Cytokines as endogenous pyrogens.

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Dinarello, C A

1999-03-01

Cytokines are pleiotropic molecules mediating several pathologic processes. Long before the discovery of cytokines as immune system growth factors or as bone marrow stimulants, investigators learned a great deal about cytokines when they studied them as the endogenous mediators of fever. The terms "granulocytic" or "endogenous pyrogen" were used to describe substances with the biologic property of fever induction. Today, we recognize that pyrogenicity is a fundamental biologic property of several cytokines and hence the clinically recognizeable property of fever links host perturbations during disease with fundamental perturbations in cell biology. In this review, the discoveries made on endogenous pyrogens are revisited, with insights into the importance of the earlier work to the present-day understanding of cytokines in health and in disease.

Long-term impact of radiation on plasma concentrations of cytokines (IL-1 and IL-6) and adhesion molecules (ICAM-1 and P-selectin) in Chernobyl clean-up workers from Latvia

International Nuclear Information System (INIS)

Kurjane, N.; Kirsfinks, M.; Hagina, E.; Socnevs, A.

2001-01-01

Study was undertaken to evaluate plasma concentrations of interleukin-1beta (IL-1), interleukin-6 (IL-6), and adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) and P-selectin in persons who participated in the clean-up work of the Chernobyl NPP explosion aftereffects. 40 Chernobyl clean-up workers suffering from most common neurological diseases - polyneuropathy and encephalopathy, and 40 healthy blood donors were analyzed for plasma levels of IL-6, IL1-β, sICAM-1 and sP-selectin 13 years after the accident. The documented external radiation dosage to the investigated Chernobyl clean-up workers was exposed from 0,009 to 0,28 Gy. Significantly elevated plasma concentrations of IL-6 and P-selectin but not of IL-1β were found in Chernobyl clean-up labourers as compared to those in healthy blood donors. (p<0.01). There was no obvious association of cytokine and adhesion molecule levels with radiation doses, as individuals working in the Chernobyl area in 1986 at a time when the external radiation exposure was higher revealed similar plasma concentrations if compared to those of a later period of time (1987-1990). (authors)

HMGB1/RAGE Signaling and Pro-Inflammatory Cytokine Responses in Non-HIV Adults with Active Pulmonary Tuberculosis.

Directory of Open Access Journals (Sweden)

Grace Lui

Full Text Available We aimed to study the pathogenic roles of High-Mobility Group Box 1 (HMGB1 / Receptor-for-Advanced-Glycation-End-products (RAGE signaling and pro-inflammatory cytokines in patients with active pulmonary tuberculosis (PTB.A prospective study was conducted among non-HIV adults newly-diagnosed with active PTB at two acute-care hospitals (n = 80; age-and-sex matched asymptomatic individuals (tested for latent TB were used for comparison (n = 45. Plasma concentrations of 8 cytokines/chemokines, HMGB1, soluble-RAGE, and transmembrane-RAGE expressed on monocytes/dendritic cells, were measured. Gene expression (mRNA of HMGB1, RAGE, and inflammasome-NALP3 was quantified. Patients' PBMCs were stimulated with recombinant-HMGB1 and MTB-antigen (lipoarabinomannan for cytokine induction ex vivo.In active PTB, plasma IL-8/CXCL8 [median(IQR, 6.0(3.6-15.1 vs 3.6(3.6-3.6 pg/ml, P<0.001] and IL-6 were elevated, which significantly correlated with mycobacterial load, extent of lung consolidation (rs +0.509, P<0.001, severity-score (rs +0.317, P = 0.004, and fever and hospitalization durations (rs +0.407, P<0.001. IL-18 and sTNFR1 also increased. Plasma IL-8/CXCL8 (adjusted OR 1.12, 95%CI 1.02-1.23 per unit increase, P = 0.021 and HMGB1 (adjusted OR 1.42 per unit increase, 95%CI 1.08-1.87, P = 0.012 concentrations were independent predictors for respiratory failure, as well as for ICU admission/death. Gene expression of HMGB1, RAGE, and inflammasome-NALP3 were upregulated (1.2-2.8 fold. Transmembrane-RAGE was increased, whereas the decoy soluble-RAGE was significantly depleted. RAGE and HMGB1 gene expressions positively correlated with cytokine levels (IL-8/CXCL8, IL-6, sTNFR1 and clinico-/radiographical severity (e.g. extent of consolidation rs +0.240, P = 0.034. Ex vivo, recombinant-HMGB1 potentiated cytokine release (e.g. TNF-α when combined with lipoarabinomannan.In patients with active PTB, HMGB1/RAGE signaling and pro-inflammatory cytokines may play important

Detection of autoantibodies to cytokines

DEFF Research Database (Denmark)

Bendtzen, K; Hansen, M B; Ross, C

2000-01-01

Autoantibodies to various cytokines have been reported in normal individuals and in patients with various infectious and immunoinflammatory disorders, and similar antibodies (Ab) may be induced in patients receiving human recombinant cytokines. The clinical relevance of these Ab is often difficult...... to evaluate. Not only are in vitro neutralizing cytokine Ab not necessarily neutralizing in vivo, but assays for binding and neutralizing Ab to cytokines are often difficult to interpret. For example, denaturation of immobilized cytokines in immunoblotting techniques and immunometric assays may leave Ab...

A new paradigm for depression in new mothers: the central role of inflammation and how breastfeeding and anti-inflammatory treatments protect maternal mental health

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Kendall-Tackett Kathleen

2007-03-01

Full Text Available Abstract Background Research in the field of psychoneuroimmunology (PNI has revealed that depression is associated with inflammation manifested by increased levels of proinflammatory cytokines. Discussion The old paradigm described inflammation as simply one of many risk factors for depression. The new paradigm is based on more recent research that has indicated that physical and psychological stressors increase inflammation. These recent studies constitute an important shift in the depression paradigm: inflammation is not simply a risk factor; it is the risk factor that underlies all the others. Moreover, inflammation explains why psychosocial, behavioral and physical risk factors increase the risk of depression. This is true for depression in general and for postpartum depression in particular. Puerperal women are especially vulnerable to these effects because their levels of proinflammatory cytokines significantly increase during the last trimester of pregnancy – a time when they are also at high risk for depression. Moreover, common experiences of new motherhood, such as sleep disturbance, postpartum pain, and past or current psychological trauma, act as stressors that cause proinflammatory cytokine levels to rise. Breastfeeding has a protective effect on maternal mental health because it attenuates stress and modulates the inflammatory response. However, breastfeeding difficulties, such as nipple pain, can increase the risk of depression and must be addressed promptly. Conclusion PNI research suggests two goals for the prevention and treatment of postpartum depression: reducing maternal stress and reducing inflammation. Breastfeeding and exercise reduce maternal stress and are protective of maternal mood. In addition, most current treatments for depression are anti-inflammatory. These include long-chain omega-3 fatty acids, cognitive therapy, St. John's wort, and conventional antidepressants.

Plasma glucose, cholesterol, triglyceride, and glycerol concentrations in the postmature rabbit.

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Harlow, A C; Roux, J F; Shapiro, M I

1980-02-15

Plasma cholesterol, triglycerides, glycerol, and glucose concentrations were measured in term and postmature rabbits. The data show that the term and postmature mothers have significantly higher glycemia than their fetuses. However, triglyceride and cholesterol concentrations are lower in the postmature mother than in her fetus. Postmature fetuses are characterized by very high plasma triglyceride and cholesterol concentrations. The results demonstrate that postmaturity is accompanied by maternal and fetal lipid metabolic changes related to a decrease in the transfer of maternal fatty acids through the placenta and to a diminution in fetal liver glucose utilization. The postmature fetus is then in a relative state of fasting and must rely on its own supply of fuel (glycogen and lipids) to provide cells for growth and survival. The maternal metabolic changes can possibly be explained by a decreased utilization of maternal substrates by the fetus, the placenta becoming insufficient. The close interrelationship of fetal and maternal lipid metabolism with the activity of the placenta suggests that an accurate knowledge of the metabolic changes taking place in the fetus during alteration of the maternal environment is indispensable to the understanding of the short- and long-term effects of maternal disease on the fetus.

Apolipoprotein CIII Reduces Proinflammatory Cytokine-Induced Apoptosis in Rat Pancreatic Islets via the Akt Prosurvival Pathway

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Størling, Joachim; Juntti-Berggren, Lisa; Olivecrona, Gunilla

2011-01-01

Apolipoprotein CIII (ApoCIII) is mainly synthesized in the liver and is important for triglyceride metabolism. The plasma concentration of ApoCIII is elevated in patients with type 1 diabetes (T1D), and in vitro ApoCIII causes apoptosis in pancreatic ß-cells in the absence of inflammatory stress...... of the survival serine-threonine kinase Akt. Inhibition of the Akt signaling pathway by the phosphatidylinositol 3 kinase inhibitor LY294002 counteracted the antiapoptotic effect of ApoCIII on cytokine-induced apoptosis. We conclude that ApoCIII in the presence of T1D-relevant proinflammatory cytokines reduces...

Changes in maternal serum thioredoxin (TRX) levels after delivery in preeclamptic and normotensive pregnant women.

Science.gov (United States)

Vitoratos, Nicolaos; Vlahos, Nikos F; Economou, Emanuel; Panoulis, Konstatninos; Creatsas, George

2012-01-01

To investigate changes of maternal plasma thioredoxin (TRX) levels after delivery in preeclamptic and normotensive pregnant women. Ten normotensive women (group A) were compared to 17 women with severe preeclampsia (group B). TRX levels were assessed in maternal plasma, immediately after delivery and 12-16 weeks postpartum. There were no differences in plasma TRX levels between the two groups immediately antepartum (p = 0.095). A significant reduction in plasma TRX levels was found immediately following delivery only in normotensive group (117.76 ± 37.19 ng/mL vs. 43.45 ± 21.11 ng/mL, p = 0.002), but not in women with preeclampsia (80.42 ± 59.95 ng/mL vs. 53.82 ± 44.34 ng/mL, p = 0.12). Plasma TRX levels remained unchanged in women with preeclampsia (80.42 ± 59.95 ng/mL vs. 55.37 ± 52.23 ng/mL, p = 0.2) at 12-14 weeks postpartum.

Gestational 3,3',4,4',5-pentachlorobiphenyl (PCB 126) exposure disrupts fetoplacental unit: Fetal thyroid-cytokines dysfunction.

Science.gov (United States)

Ahmed, R G; El-Gareib, A W; Shaker, H M

2018-01-01

Exposure to polychlorinated biphenyls (PCBs) is related to several endocrine disorders. This study examined the effect of maternal exposure of 3,3',4,4',5-pentachlorobiphenyl (PCB 126) on the fetoplacental unit and fetal thyroid-cytokine axis during the pregnancy. Pregnant albino rats received PCB 126 (20 or 40μg/kgb.wt.) by oral gavage from gestation day (GD) 1 to 20. Potential effects of PCB 126 were evaluated by following the histopathological changes in the placenta by Haematoxylin and Eosin (H&E) stain and measuring the maternofetal thyroid axis (ELIZA), maternofetal body weight, and fetal growth markers (ELIZA), and cytokines (ELIZA) at embryonic day (ED) 20. Placental tissues of both treated groups showed hyperemia, hemorrhage, degeneration and apoptosis in labyrinth layer and spiral artery at GD 20. Both administrations of PCB 126 elevated serum thyrotropin (TSH) concentration, and decreased free thyroxine (FT4) and free triiodothyronine (FT3) concentrations, resulting in a maternofetal hypothyroidism. The presence of hypothyroidism increased fetal serum concentration of transforming growth factor-β (TGF-β), leptin (LEP), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and decreased the fetal serum insulin growth factor-I (IGF-I), IGF-II, insulin, adiponectin (ADP), and growth hormone (GH) in both treated groups at ED 20. However, the increase in resistin (RETN) and interferon-γ (IFN-γ) was non-significant in low-dose group and highly significant in high-dose group. Simultaneously, the reduction in body weight of the dams and fetuses was observed in both PCB 126 groups of examined day with respect to the control group. The maternal PCB 126 distorted the fetoplacental unit might disrupt the fetal thyroid-cytokines axis and prenatal development. Copyright © 2017 Elsevier Inc. All rights reserved.

Dynamic alterations of bone marrow cytokine landscape of myelodysplastic syndromes patients treated with 5-azacytidine

Czech Academy of Sciences Publication Activity Database

Moudrá, Alena; Hubáčková, Soňa; Machalová, Veronika; Vančurová, Markéta; Bartek, Jiří; Reiniš, Milan; Hodný, Zdeněk; Jonasova, A.

2016-01-01

Roč. 5, č. 10 (2016), č. článku e1183860. ISSN 2162-402X R&D Projects: GA MZd NT14174 Institutional support: RVO:68378050 Keywords : 5-azacyatidine * bone marrow plasma * cytokines * DNA damage * inflammation * myelodysplastic syndromes Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 7.719, year: 2016

Changes in the TNF-alpha/IL-10 ratio in hyperglycemia-associated pregnancies.

Science.gov (United States)

Moreli, Jusciele B; Corrêa-Silva, Simone; Damasceno, Débora C; Sinzato, Yuri K; Lorenzon-Ojea, Aline R; Borbely, Alexandre U; Rudge, Marilza V C; Bevilacqua, Estela; Calderon, Iracema M P

2015-03-01

TNF-α is a diabetogenic cytokine associated with adverse outcomes during pregnancy that can be counterbalanced by IL-10. We have investigated IL-10 and TNF-α balance at maternal and placental levels in hyperglycemia-associated pregnancies. One hundred and ninety-two pregnant women participated, which included normoglycemic women (ND) and women with mild gestational hyperglycemia (MGH), gestational diabetes mellitus (GDM) and type 2 diabetes mellitus (DM2). Maternal plasma and placental tissue IL-10 and TNF-α levels were measured by ELISA and placental TNF-α was also immunolocalized. Maternal plasma TNF-α levels were highest in GDM (p=0.0190), whereas TNF-α levels were highest in placental tissues in DM2 (p=0.0095). Immunohistochemistry also showed strong reactivity with anti-TNF-α antibody in the villous structures in the DM2 group. Conversely, IL-10 levels were lowest in maternal plasma of the DM2 group (p=0.0228). The TNF-α/IL-10 ratio in maternal plasma progressively increased with the severity of hyperglycemia (pDM2 group (p=0.0150). In both, plasma and placenta, TNF-α/IL-10 ratio were correlated with mean maternal glycemia and HbA1c levels. Alterations of placenta and serum TNF-α/IL-10 balance with predominance of TNF-α were correlated with the severity of hyperglycemia during gestation. This association may offer insight into the pathogenesis of gestational hyperglycemia and associated pregnancy outcomes. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

GPBAR1/TGR5 mediates bile acid-induced cytokine expression in murine Kupffer cells.

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Guiyu Lou

Full Text Available GPBAR1/TGR5 is a novel plasma membrane-bound G protein-coupled bile acid (BA receptor. BAs are known to induce the expression of inflammatory cytokines in the liver with unknown mechanism. Here we show that without other external stimuli, TGR5 activation alone induced the expression of interleukin 1β (IL-1β and tumor necrosis factor-α (TNF-α in murine macrophage cell line RAW264.7 or murine Kupffer cells. The TGR5-mediated increase of pro-inflammatory cytokine expression was suppressed by JNK inhibition. Moreover, the induced pro-inflammatory cytokine expression in mouse liver by 1% cholic acid (CA diet was blunted in JNK-/- mice. TGR5 activation by its ligands enhanced the phosphorylation levels, DNA-binding and trans-activities of c-Jun and ATF2 transcription factors. Finally, the induced pro-inflammatory cytokine expression in Kupffer cells by TGR5 activation correlated with the suppression of Cholesterol 7α-hydroxylase (Cyp7a1 expression in murine hepatocytes. These results suggest that TGR5 mediates the BA-induced pro-inflammatory cytokine production in murine Kupffer cells through JNK-dependent pathway. This novel role of TGR5 may correlate to the suppression of Cyp7a1 expression in hepatocytes and contribute to the delicate BA feedback regulation.

[Pattern of serum cytokines in patients with rheumatoid artritis according to PPD reactivity].

Science.gov (United States)

de León Pandolfi, Darío Ponce; Pastor Asurza, César; Beraun, Yasmina; Acevedo-Vásquez, Eduardo; Sánchez-Torres, Alfredo; Alfaro Lozano, José; Perich Campos, Risto; Cucho Venegas, Mariano; Gutiérrez Villafuerte, César; Sánchez Schwartz, César

2006-11-01

We demonstrated, in a recently published study, far more PPD negative reactivity among patients who had RA (70%) than among controls (30%). To evaluate the hypothesis that different response to PPD in RA patients is associated with different profiles of serum cytokines, we compared the serum levels of IL-2, IL-4, IL-6, IL-10, TNF alpha and IFN gamma from PPD negative and PPD positive RA patients. We also evaluated any correlations between serum cytokines and RA activity. Forty RA patients and 21 controls were enrolled. Those with an induration PPD. Disease activity was calculated using DAS28. Plasma levels of cytokines were determined using the multiplex BD TM Cytometric Bead Array Kit Assay. Of the RA patients, 27 (67.5%) had negative reaction to PPD and 13 (32.5%) a positive reaction to PPD. There was no statistical difference in sex profile, age or activity index between both negative and positive PPD RA patients. There was no significant difference in all the cytokines measured between PPD positive and PPD negative RA patients. Index activity show a positive correlation with IFN gamma (r = 0.433; p = 0.005) and IL-6 (r = 0.325; p = 0.041) in RA patients. Positive and negative tuberculin RA patients seem to show a similar cytokine serum profile. Copyright © 2006 Elsevier España S.L. Barcelona. Published by Elsevier Espana. All rights reserved.

Antibody-cytokine fusion proteins for treatment of cancer: engineering cytokines for improved efficacy and safety.

Science.gov (United States)

Young, Patricia A; Morrison, Sherie L; Timmerman, John M

2014-10-01

The true potential of cytokine therapies in cancer treatment is limited by the inability to deliver optimal concentrations into tumor sites due to dose-limiting systemic toxicities. To maximize the efficacy of cytokine therapy, recombinant antibody-cytokine fusion proteins have been constructed by a number of groups to harness the tumor-targeting ability of monoclonal antibodies. The aim is to guide cytokines specifically to tumor sites where they might stimulate more optimal anti-tumor immune responses while avoiding the systemic toxicities of free cytokine therapy. Antibody-cytokine fusion proteins containing interleukin (IL)-2, IL-12, IL-21, tumor necrosis factor (TNF)α, and interferons (IFNs) α, β, and γ have been constructed and have shown anti-tumor activity in preclinical and early-phase clinical studies. Future priorities for development of this technology include optimization of tumor targeting, bioactivity of the fused cytokine, and choice of appropriate agents for combination therapies. This review is intended to serve as a framework for engineering an ideal antibody-cytokine fusion protein, focusing on previously developed constructs and their clinical trial results. Copyright © 2014 Elsevier Inc. All rights reserved.

Effects of cytokines on the pituitary-adrenal axis in cancer patients.

Science.gov (United States)

Nolten, W E; Goldstein, D; Lindstrom, M; McKenna, M V; Carlson, I H; Trump, D L; Schiller, J; Borden, E C; Ehrlich, E N

1993-10-01

Cytokines, which include interferons (IFNs), interleukins (ILs), and tumor necrosis factor (TNF), are immunoregulatory proteins produced by lymphocytes and inflammatory cells. Several cytokines, most noteworthy IFNs and ILs, stimulate glucocorticoid secretion. In this study, the effects of variable doses and repetitive administration of IFNs and TNF on secretion of pituitary hormones and cortisol were measured. Patients were given for a period of 15 days on alternating days injections of IFN-beta (IFN-beta ser), 90 or 450 x 10(6) IU, IFN-gamma, 0.1-100 x 10(6) IU, or TNF 125-275 micrograms/m2. Sixty to 120 min after IFN-beta ser injection median levels of cortisol, adrenocorticotropin (ACTH), prolactin (PRL), and growth hormone (GH) rose two-fold. Urinary free cortisol excretion increased significantly during the day following IFN-beta ser administration. IFN-gamma > or = 30 x 10(6) IU caused a comparable rise in plasma cortisol. TNF induced two- to four-fold increases in ACTH and cortisol. The fact that increased cortisol secretion was associated with a rise in the level of ACTH as well as PRL and GH suggests that the cytokines increased cortisol by stimulating the anterior pituitary. The hormonal response induced by cytokines was unrelated to their pyrogenic effect, undiminished with repetitive treatment, and not dose-dependent above a threshold level. These observations reinforce the concept of a physiologic link between the immune system and the hypothalamic-pituitary-adrenal (HPA) axis.

Effect of thrombopoietin-receptor agonists on circulating cytokine and chemokine levels in patients with primary immune thrombocytopenia (ITP)

DEFF Research Database (Denmark)

Gudbrandsdottir, Sif; Ghanima, Waleed; Nielsen, Claus H

2017-01-01

BACKGROUND: Thrombopoietin-receptor-agonists (TPO-RAs) increase platelet production in Immune Thrombocytopenia (ITP) by stimulating Mpl. The effect of TPO-RAs on inflammatory cytokine production in ITP patients has not been well investigated. METHODS: Plasma samples from 48 ITP patients treated...

Features of Cytokine Regulation in Multidrug-Resistant Tuberculosis Depending on Severity of Endogenous Intoxication

Directory of Open Access Journals (Sweden)

L.D. Todoriko

2016-02-01

Conclusions. Comprehensive assessment of integral indices of endogenous intoxication and level of certain pro- and anti-inflammatory cytokines in the blood plasma of patients with MDR TB shows a moderate endogenous intoxication, break down of the cellular component of the immune reactivity due to the formation of conditions for the development of Mycobacterium tuberculosis resistance, with further growth of cytotoxic hypoxia and activation of systemic inflammatory response syndrome. Analysis of plasma concentration of IL-6, IL-10 and IL-18 in patients with multidrug-resistance proved, that their level depends on the nature of Mycobacterium tuberculosis resistance.

Placental-mediated increased cytokine response to lipopolysaccharides: a potential mechanism for enhanced inflammation susceptibility of the preterm fetus

Directory of Open Access Journals (Sweden)

Ross MG

2012-07-01

Full Text Available Julie L Boles,1 Michael G Ross,1 Ron Beloosesky,2 Mina Desai,1 Louiza Belkacemi11Department of Obstetrics and Gynecology, Harbor-UCLA Medical Center, Los Angeles Biomedical Research Institute at Harbor-UCLA, David Geffen School of Medicine at UCLA, University of California, Los Angeles, Torrance, CA, USA; 2Department of Obstetrics and Gynecology, Rambam Medical Center, Haifa, IsraelBackground: Cerebral palsy is a nonprogressive motor impairment syndrome that has no effective cure. The etiology of most cases of cerebral palsy remains unknown; however, recent epidemiologic data have demonstrated an association between fetal neurologic injury and infection/inflammation. Maternal infection/inflammation may be associated with the induction of placental cytokines that could result in increased fetal proinflammatory cytokine exposure, and development of neonatal neurologic injury. Therefore, we sought to explore the mechanism by which maternal infection may produce a placental inflammatory response. We specifically examined rat placental cytokine production and activation of the Toll-like receptor 4 (TLR4 pathway in response to lipopolysaccharide exposure at preterm and near-term gestational ages.Methods: Preterm (e16 or near-term (e20 placental explants from pregnant rats were treated with 0, 1, or 10 µg/mL lipopolysaccharide. Explant integrity was assessed by lactate dehydrogenase assay. Interleukin-6 and tumor necrosis alpha levels were determined using enzyme-linked immunosorbent assay kits. TLR4 and phosphorylated nuclear factor kappa light chain enhancer of activated B cells (NFκB protein expression levels were determined by Western blot analysis.Results: At both e16 and e20, lactate dehydrogenase levels were unchanged by treatment with lipopolysaccharide. After exposure to lipopolysaccharide, the release of interleukin-6 and tumor necrosis alpha from e16 placental explants increased by 4-fold and 8–9-fold, respectively (P < 0.05 versus

Optimising the collection of female genital tract fluid for cytokine analysis in pregnant women.

Science.gov (United States)

Short, C S; Quinlan, R; Bennett, P; Shattock, R J; Taylor, G P

2018-07-01

To better understand the immunology of pregnancy, study of female genital tract fluid (FGF) is desirable. However the optimum method of collection of FGF in pregnant women for immunological methods, specifically cytokine measurement, is unknown. A prospective study of HIV-uninfected pregnant women comparing two methods of FGF collection: polyvinyl acetal sponge collection of cervical fluid (CF) and menstrual cup collection of cervicovaginal fluid (CVF). Samples were collected at 3 time points across the second and third trimesters: 14-21, 22-25 and 26-31 weeks. Multiplex chemi-luminescent assays were used to measure: IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-13 and TNF-α. Optimal methodology for cytokine normalisation (sample weight, volume and total protein) was explored. All cytokines were measurable in both fluid types. IL-1β, IL-8 and IL-6 were detected at the highest concentrations (ranking order CF > CVF > plasma). CVF collection was simpler, provided the largest volume of sample (median 0.5 g) with the potential for undiluted usage, and allowed for self-insertion. CF cytokine concentrations were intrinsically associated with sample weight and protein concentration however CVF cytokines were independent of these. Both methods of collection are robust for measurement of FGF cytokines during pregnancy. We recommend CVF collection using a menstrual cup as a viable option in pregnant women for high dimensional biological techniques. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Cytokine network in scrub typhus: high levels of interleukin-8 are associated with disease severity and mortality.

Science.gov (United States)

Astrup, Elisabeth; Janardhanan, Jeshina; Otterdal, Kari; Ueland, Thor; Prakash, John A J; Lekva, Tove; Strand, Øystein A; Abraham, O C; Thomas, Kurien; Damås, Jan Kristian; Mathews, Prasad; Mathai, Dilip; Aukrust, Pål; Varghese, George M

2014-02-01

Scrub typhus, caused by Orientia tsutsugamushi, is endemic in the Asia-Pacific region. Mortality is high if untreated, and even with treatment as high as 10-20%, further knowledge of the immune response during scrub typhus is needed. The current study was aimed at comparing plasma levels of a variety of inflammatory mediators in scrub typhus patients and controls in South India in order to map the broader cytokine profile and their relation to disease severity and clinical outcome. We examined plasma levels of several cytokines in scrub typhus patients (n = 129) compared to healthy controls (n = 31) and infectious disease controls (n = 31), both in the acute phase and after recovery, by multiplex technology and enzyme immunoassays. Scrub typhus patients were characterized by marked changes in the cytokine network during the acute phase, differing not only from healthy controls but also from infectious disease controls. While most of the inflammatory markers were raised in scrub typhus, platelet-derived mediators such as RANTES were markedly decreased, probably reflecting enhanced platelet activation. Some of the inflammatory markers, including various chemokines (e.g., interleukin-8, monocyte chemoattractant peptide-1 and macrophage inflammatory protein-1β) and downstream markers of inflammation (e.g., C-reactive protein and pentraxin-3), were also associated with disease severity and mortality during follow-up, with a particular strong association with interleukin-8. Our findings suggest that scrub typhus is characterized by a certain cytokine profile that includes dysregulated levels of a wide range of mediators, and that this enhanced inflammation could contribute to disease severity and clinical outcome.

Psychological stress exerts effects on pathogenesis of hepatitis B via type-1/type-2 cytokines shift toward type-2 cytokine response.

Directory of Open Access Journals (Sweden)

YingLi He

Full Text Available BACKGROUND: Psychological and physical stress has been demonstrated to have an impact on health through modulation of immune function. Despite high prevalence of stress among patients with hepatitis B virus (HBV infection, little is known about whether and how stress exerts an effect on the course of hepatitis B. METHODS: Eighty patients with chronic hepatitis B(CHB completed the Perceived Stress Scale-10(PSS-10 and State-Trait Anxiety Inventory(STAI. Fresh whole blood was subject to flow cytometry for lymphocytes count. Plasma samples frozen at -80 °C were thawed for cytokines, alanine aminotransferase (ALT, and virus load. These patients were grouped into high or low perceived stress, state anxiety and trait anxiety groups according to the scale score. Sociodemographic, disease-specific characteristics, lymphocytes count and cytokines were compared. RESULTS: Firstly, a negative association between ALT and stress (t =  -4.308; p =  .000, state anxiety (t =  -3.085; p =  .003 and trait anxiety (t =  -4.925; p =  .000 were found. As ALT is a surrogate marker of hepatocytes injury, and liver injury is a consequence of immune responses. Next, we tested the relationship between stress/anxiety and lymphocytes. No statistical significance were found with respect to counts of total T cells, CD4+ T cell, CD8+ T cell, NK cell, and B cell count between high and low stress group. Type-2 cytokine interleukin-10 (IL-10 level was significantly higher in high stress group relative to lower counterpart (t = 6.538; p = 0.000, and type-1 cytokine interferon-gamma (IFN-γ level shown a decreased tendency in high stress group (t =  -1.702; p = 0.093. Finally, INF-γ:IL-10 ratio displayed significant decrease in high perceived stress(t =  -4.606; p = 0.000, state anxiety(t =  -5.126; p = 0.000 and trait anxiety(t =  -4.670; p = 0.000 groups relative to low counterparts. CONCLUSION: Our data show stress is not related to the lymphocyte cells

Increased concentrations of plasma IL-18 in patients with hepatic dysfunction after hepatectomy.

Science.gov (United States)

Shibata, M; Hirota, M; Nozawa, F; Okabe, A; Kurimoto, M; Ogawa, M

2000-10-01

We investigated the dynamic aspects of circulatory IL-18 and other inflammatory cytokines in patients who underwent a hepatectomy. In patients with post-operative hepatic dysfunction, plasma concentrations of these cytokines increased, reflecting severe surgical trauma. IL-6, IL-10 and IFN-gamma increased in the early phase, while IL-18 increased in the later phase after 1 week. Interestingly, the increase in the plasma IL-18 concentration was correlated with that in serum bilirubin levels in hepatectomized patients. Hence, the decrease in the hepatic metabolism of IL-18 may cause the plasma accumulation of IL-18. This mechanism was confirmed using rat experiments. Intravenously administered human IL-18 was excreted into bile. Furthermore, the plasma clearance of human IL-18 was prolonged in bile duct-ligated rats. These results suggest that IL-18 is metabolized in the liver and excreted into bile, and an increase in plasma IL-18 in patients with hepatic dysfunction reflects the decreased metabolism in the liver. Copyright 2000 Academic Press.

Regulation of embryonic hematopoiesis by a cytokine-inducible SH2 domain homolog in zebrafish.

Science.gov (United States)

Lewis, Rowena S; Noor, Suzita M; Fraser, Fiona W; Sertori, Robert; Liongue, Clifford; Ward, Alister C

2014-06-15

Cytokine-inducible SH2 domain-containing protein (CISH), a member of the suppressor of cytokine signaling family of negative feedback regulators, is induced by cytokines that activate STAT5 and can inhibit STAT5 signaling in vitro. However, demonstration of a definitive in vivo role for CISH during development has remained elusive. This study employed expression analysis and morpholino-mediated knockdown in zebrafish in concert with bioinformatics and biochemical approaches to investigate CISH function. Two zebrafish CISH paralogs were identified, cish.a and cish.b, with high overall conservation (43-46% identity) with their mammalian counterparts. The cish.a gene was maternally derived, with transcripts present throughout embryogenesis, and increasing at 4-5 d after fertilization, whereas cish.b expression commenced at 8 h after fertilization. Expression of cish.a was regulated by the JAK2/STAT5 pathway via conserved tetrameric STAT5 binding sites (TTCN3GAA) in its promoter. Injection of morpholinos targeting cish.a, but not cish.b or control morpholinos, resulted in enhanced embryonic erythropoiesis, myelopoiesis, and lymphopoiesis, including a 2- 3-fold increase in erythrocytic markers. This occurred concomitantly with increased activation of STAT5. This study indicates that CISH functions as a conserved in vivo target and regulator of STAT5 in the control of embryonic hematopoiesis. Copyright © 2014 by The American Association of Immunologists, Inc.

Maternal blood total oxypurines and erythrocyte 2,3-diphosphoglycerate levels during normal pregnancy.

Science.gov (United States)

Mizutani, S; Akiyama, H; Kurauchi, O; Taira, H; Yamada, R; Narita, O; Tomoda, Y

1985-01-01

The effects of pregnancy on the levels of maternal plasma total oxypurines (hypoxanthine, xanthine and uric acid) and erythrocyte 2,3-diphosphoglycerate (2,3-DPG) was investigated. With advancing gestation there was a slight increasing tendency in plasma total oxypurines as well as erythrocyte 2,3-DPG in pregnant women. When the ratio of 2,3-DPG to total oxypurines was calculated, the ratio was almost unchanged until week 34. After week 35, the ratio decreased to week 37; the ratios between week 37 and 40 had similar values to cord blood. The above data suggest that the changes of these metabolites in maternal peripheral blood may be indicative for hypoxia with fetoplacental tissue.

Increased osteopontin plasma levels in multiple sclerosis patients correlate with bone-specific markers

NARCIS (Netherlands)

Vogt, M.H.J.; ten Kate, J.; Drent, R.J.M.; Polman, C.H.; Hupperts, R.

2010-01-01

The pro-inflammatory cytokine osteopontin has been found to be highly expressed in multiple sclerosis lesions and plasma levels are increased during relapses in relapse-onset multiple sclerosis patients. The objective was to determine the relationship between osteopontin plasma and cerebrospinal

Effects of maternal stress during pregnancy on learning and memory via hippocampal BDNF, Arc (Arg3.1) expression in offspring.

Science.gov (United States)

Guan, Su-Zhen; Ning, Li; Tao, Ning; Lian, Yu-Long; Liu, Ji-Wen; Ng, Tzi Bun

2016-09-01

The intrauterine environment has a significant long-term impact on individual's life, this study was designed to investigate the effect of stress during pregnancy on offspring's learning and memory abilities and analyze its mechanisms from the expression of BDNF and Arc in the hippocampus of the offspring. A rat model of maternal chronic stress during pregnancy was mating from 3rd day during been subjecting to chronic unpredictable mild stress (CUMS). The body weights and behavioral changes were recorded, and plasma corticosterone levels were determined by radioimmunoassay. The learning and memory abilities of the offspring were measured by Morris water maze testing from PND 42. The expression of hippocampal BDNF and Arc mRNA and protein were respectively measured using RT-PCR and Western blotting. Results indicated that an elevation was observed in the plasma corticosterone level of rat model of maternal chronic stress during pregnancy, a reduction in the crossing and rearing movement times and the preference for sucrose. The body weight of maternal stress's offspring was lower than the control group, and the plasma corticosterone level was increased. Chronic stress during pregnancy had a significant impact on the spatial learning and memory of the offspring. The expression of BDNF mRNA and protein, Arc protein in offspring of maternal stress during pregnancy was attenuated and some relationships existed between these parameters. Collectively, these findings disclose that long-time maternal stress during pregnancy could destroy spatial learning and memory abilities of the offspring, the mechanism of which is related to been improving maternal plasma corticosterone and reduced hippocampal BDNF, Arc of offspring rats. Copyright © 2016. Published by Elsevier B.V.

Neurobiology of Maternal Stress: Role of Social Rank and Central Oxytocin in Hypothalamic-Pituitary Adrenal Axis Modulation

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Jeremy D Coplan

2015-07-01

Full Text Available Background: Chronic stress may conceivably require plasticity of maternal physiology and behavior to cope with the conflicting primary demands of infant rearing and foraging for food. In addition, social rank may play a pivotal role in mandating divergent homeostatic adaptations in cohesive social groups. We examined cerebrospinal fluid (CSF oxytocin (OT levels and hypothalamic pituitary adrenal (HPA axis regulation in the context of maternal social stress and assessed the contribution of social rank to dyadic-distance as reflective of distraction from normative maternal-infant interaction. Methods: Twelve socially-housed mother-infant bonnet macaque dyads were studied after variable foraging demand (VFD exposure compared to 11 unstressed dyads. Dyadic-distance was determined by behavioral observation. Social ranking was performed blindly by two observers. Post-VFD maternal plasma cortisol and CSF OT were compared to corresponding measures in non-VFD exposed mothers. Results: High social rank was associated with increased dyadic-distance only in VFD-exposed dyads and not in control dyads. In mothers unexposed to VFD, social rank was not related to maternal cortisol levels whereas VFD-exposed dominant versus subordinate mothers exhibited increased plasma cortisol. Maternal CSF OT directly predicted maternal cortisol only in VFD-exposed mothers. CSF OT was higher in dominant versus subordinate mothers. VFD-exposed mothers with high cortisol specifically exhibited CSF OT elevations in comparison to control groups. Conclusions: Pairing of maternal social rank to dyadic-distance in VFD presumably reduces maternal contingent responsivity, with ensuing long-term sequelae. VFD-exposure dichotomizes maternal HPA axis response as a function of social rank with relatively reduced cortisol in subordinates. OT may serve as a homeostatic buffer during maternal stress exposure.

Fetal pancreatic beta-cell function in pregnancies complicated by maternal diabetes mellitus: relationship to fetal acidemia and macrosomia.

Science.gov (United States)

Salvesen, D R; Brudenell, J M; Proudler, A J; Crook, D; Nicolaides, K H

1993-05-01

Our purpose was to investigate the relationship between fetal pancreatic beta-cell function and fetal acidemia and macrosomia in pregnancies complicated by maternal diabetes mellitus. A cross-sectional study at the Harris Birthright Research Centre for Fetal Medicine, London, was performed. In 32 pregnancies complicated by maternal diabetes mellitus cordocentesis was performed at 36 to 39 weeks' gestation for the measurement of umbilical venous blood pH, PO2, PCO2, lactate, and glucose concentration; plasma insulin immunoreactivity; and insulin/glucose ratio. A reference range for plasma insulin and insulin/glucose ratio was constructed by studying fetal blood samples from 80 women who did not have diabetes mellitus. Mean umbilical venous blood pH was significantly lower and plasma insulin immunoreactivity and insulin/glucose ratio were significantly higher than the appropriate normal mean for gestation. There were significant associations between (1) maternal and fetal blood glucose concentrations (r = 0.95, p < 0.0001), (2) fetal blood glucose and plasma insulin immunoreactivity (r = 0.57, p < 0.01), (3) fetal plasma insulin immunoreactivity and blood pH (r = -0.39, p < 0.05), and (4) fetal insulin/glucose ratio and degree of macrosomia (r = 0.76, p < 0.0001). Fetal pancreatic beta-cell hyperplasia is implicated in the pathogenesis of both fetal acidemia and macrosomia.

Metabolomics Application in Maternal-Fetal Medicine

OpenAIRE

Fanos, Vassilios; Atzori, Luigi; Makarenko, Karina; Melis, Gian Benedetto; Ferrazzi, Enrico

2013-01-01

Metabolomics in maternal-fetal medicine is still an “embryonic” science. However, there is already an increasing interest in metabolome of normal and complicated pregnancies, and neonatal outcomes. Tissues used for metabolomics interrogations of pregnant women, fetuses and newborns are amniotic fluid, blood, plasma, cord blood, placenta, urine, and vaginal secretions. All published papers highlight the strong correlation between biomarkers found in these tissues and fetal malformations, prete...

Fetal gender determination through Y-STR analysis of maternal ...

African Journals Online (AJOL)

Hanaa M.H. Aal-Hamdan

2014-10-01

Oct 1, 2014 ... Fetal gender determination through Y-STR analysis of maternal plasma during the third trimester of pregnancy. Hanaa M.H. Aal-Hamdan, Ahmed M. Refaat *, Saranya R. Babu,. Abdul Rauf Choudhry. Department of Forensic Biology, College of Forensic Sciences, Naif Arab University for Security Sciences, ...

Association between circulating ascorbic acid, α-tocopherol, 25-hydroxyvitamin D, and plasma cytokine concentrations in young adults: a cross-sectional study.

Science.gov (United States)

García-Bailo, Bibiana; Roke, Kaitlin; Mutch, David M; El-Sohemy, Ahmed; Badawi, Alaa

2012-11-16

Inflammation and oxidative stress are associated with the development of numerous chronic diseases. Circulating ascorbic acid, α-tocopherol, and 25-hydroxyvitamin D (25(OH)D) may help reduce concentrations of pro-inflammatory cytokines through their antioxidant and anti-inflammatory properties. These micronutrients may act synergistically, and they may have different anti-inflammatory effects, but previous studies have assessed the link between each of these micronutrients and inflammation in isolation without controlling for the other micronutrients. Our objective was to examine the association between circulating concentrations of ascorbic acid, α-tocopherol, and 25(OH) D and a panel of pro-inflammatory cytokines in an ethnically diverse population of young adults. Participants (n = 1,007) from the Toronto Nutrigenomics and Health study provided fasting blood samples for biomarker measurements and were subsequently categorized into tertiles for each micronutrient based on their circulating concentrations. We conducted Pearson's correlation analyses across all micronutrients and cytokines. The associations between individual micronutrients and cytokines were examined using analysis of covariance with age, sex, waist circumference, ethnicity, physical activity, season of blood collection, total cholesterol, hormonal contraceptive use among women, and the other two micronutrients as covariates. We observed weak micronutrient-cytokine correlations, moderate correlations between certain cytokines, and strong correlations between specific cytokines, particularly interleukin 1- receptor antagonist (IL-1RA), interferon-γ (IFN-γ), and platelet-derived growth factor BB (PDGF-bb). After full covariate adjustment, circulating α-tocopherol was inversely associated with IFN-γ and regulated upon activation normal T-cell expressed and secreted (RANTES). We observed an unexpected positive association between ascorbic acid and IFN-γ. 25(OH)D was not associated with

Association between circulating ascorbic acid, α-tocopherol, 25-hydroxyvitamin D, and plasma cytokine concentrations in young adults: a cross-sectional study

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García-Bailo Bibiana

2012-11-01

Full Text Available Abstract Background Inflammation and oxidative stress are associated with the development of numerous chronic diseases. Circulating ascorbic acid, α-tocopherol, and 25-hydroxyvitamin D (25(OHD may help reduce concentrations of pro-inflammatory cytokines through their antioxidant and anti-inflammatory properties. These micronutrients may act synergistically, and they may have different anti-inflammatory effects, but previous studies have assessed the link between each of these micronutrients and inflammation in isolation without controlling for the other micronutrients. Our objective was to examine the association between circulating concentrations of ascorbic acid, α-tocopherol, and 25(OH D and a panel of pro-inflammatory cytokines in an ethnically diverse population of young adults. Methods Participants (n = 1,007 from the Toronto Nutrigenomics and Health study provided fasting blood samples for biomarker measurements and were subsequently categorized into tertiles for each micronutrient based on their circulating concentrations. We conducted Pearson’s correlation analyses across all micronutrients and cytokines. The associations between individual micronutrients and cytokines were examined using analysis of covariance with age, sex, waist circumference, ethnicity, physical activity, season of blood collection, total cholesterol, hormonal contraceptive use among women, and the other two micronutrients as covariates. Results We observed weak micronutrient-cytokine correlations, moderate correlations between certain cytokines, and strong correlations between specific cytokines, particularly interleukin 1- receptor antagonist (IL-1RA, interferon-γ (IFN-γ, and platelet-derived growth factor BB (PDGF-bb. After full covariate adjustment, circulating α-tocopherol was inversely associated with IFN-γ and regulated upon activation normal T-cell expressed and secreted (RANTES. We observed an unexpected positive association between ascorbic

Differential expression of interferon-gamma and interferon-gamma-inducing cytokines in Thai patients with scrub typhus or leptospirosis

NARCIS (Netherlands)

Chierakul, Wirongrong; de Fost, Maaike; Suputtamongkol, Yupin; Limpaiboon, Roongreung; Dondorp, Arjen; White, Nicholas J.; van der Poll, Tom

2004-01-01

Interferon (IFN)-gamma plays an important role in the induction of a type 1 immune response against intracellular pathogens. We compared the plasma levels of IFN-gamma and IFN-gamma-inducing cytokines in adult Thai patients with scrub typhus, caused by the obligate intracellular bacterium Orientia

Elevated Plasma Corticosterone Decreases Yolk Testosterone and Progesterone in Chickens : Linking Maternal Stress and Hormone-Mediated Maternal Effects

NARCIS (Netherlands)

Henriksen, Rie; Groothuis, Ton G.; Rettenbacher, Sophie; Bartell, Paul A.

2011-01-01

Despite considerable research on hormone-mediated maternal effects in birds, the underlying physiology remains poorly understood. This study investigated a potential regulation mechanism for differential accumulation of gonadal hormones in bird eggs. Across vertebrates, glucocorticoids can suppress

Cytokine Network in Scrub Typhus: High Levels of Interleukin-8 Are Associated with Disease Severity and Mortality

Science.gov (United States)

Astrup, Elisabeth; Janardhanan, Jeshina; Otterdal, Kari; Ueland, Thor; Prakash, John A. J.; Lekva, Tove; Strand, Øystein A.; Abraham, O. C.; Thomas, Kurien; Damås, Jan Kristian; Mathews, Prasad; Mathai, Dilip; Aukrust, Pål; Varghese, George M.

2014-01-01

Background Scrub typhus, caused by Orientia tsutsugamushi, is endemic in the Asia-Pacific region. Mortality is high if untreated, and even with treatment as high as 10–20%, further knowledge of the immune response during scrub typhus is needed. The current study was aimed at comparing plasma levels of a variety of inflammatory mediators in scrub typhus patients and controls in South India in order to map the broader cytokine profile and their relation to disease severity and clinical outcome. Methodology/Principal Findings We examined plasma levels of several cytokines in scrub typhus patients (n = 129) compared to healthy controls (n = 31) and infectious disease controls (n = 31), both in the acute phase and after recovery, by multiplex technology and enzyme immunoassays. Scrub typhus patients were characterized by marked changes in the cytokine network during the acute phase, differing not only from healthy controls but also from infectious disease controls. While most of the inflammatory markers were raised in scrub typhus, platelet-derived mediators such as RANTES were markedly decreased, probably reflecting enhanced platelet activation. Some of the inflammatory markers, including various chemokines (e.g., interleukin-8, monocyte chemoattractant peptide-1 and macrophage inflammatory protein-1β) and downstream markers of inflammation (e.g., C-reactive protein and pentraxin-3), were also associated with disease severity and mortality during follow-up, with a particular strong association with interleukin-8. Conclusions/Significance Our findings suggest that scrub typhus is characterized by a certain cytokine profile that includes dysregulated levels of a wide range of mediators, and that this enhanced inflammation could contribute to disease severity and clinical outcome. PMID:24516677

Cytokine network in scrub typhus: high levels of interleukin-8 are associated with disease severity and mortality.

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Elisabeth Astrup

2014-02-01

Full Text Available BACKGROUND: Scrub typhus, caused by Orientia tsutsugamushi, is endemic in the Asia-Pacific region. Mortality is high if untreated, and even with treatment as high as 10-20%, further knowledge of the immune response during scrub typhus is needed. The current study was aimed at comparing plasma levels of a variety of inflammatory mediators in scrub typhus patients and controls in South India in order to map the broader cytokine profile and their relation to disease severity and clinical outcome. METHODOLOGY/PRINCIPAL FINDINGS: We examined plasma levels of several cytokines in scrub typhus patients (n = 129 compared to healthy controls (n = 31 and infectious disease controls (n = 31, both in the acute phase and after recovery, by multiplex technology and enzyme immunoassays. Scrub typhus patients were characterized by marked changes in the cytokine network during the acute phase, differing not only from healthy controls but also from infectious disease controls. While most of the inflammatory markers were raised in scrub typhus, platelet-derived mediators such as RANTES were markedly decreased, probably reflecting enhanced platelet activation. Some of the inflammatory markers, including various chemokines (e.g., interleukin-8, monocyte chemoattractant peptide-1 and macrophage inflammatory protein-1β and downstream markers of inflammation (e.g., C-reactive protein and pentraxin-3, were also associated with disease severity and mortality during follow-up, with a particular strong association with interleukin-8. CONCLUSIONS/SIGNIFICANCE: Our findings suggest that scrub typhus is characterized by a certain cytokine profile that includes dysregulated levels of a wide range of mediators, and that this enhanced inflammation could contribute to disease severity and clinical outcome.

Cross-regulation of cytokine signalling: pro-inflammatory cytokines restrict IL-6 signalling through receptor internalisation and degradation.

Science.gov (United States)

Radtke, Simone; Wüller, Stefan; Yang, Xiang-ping; Lippok, Barbara E; Mütze, Barbara; Mais, Christine; de Leur, Hildegard Schmitz-Van; Bode, Johannes G; Gaestel, Matthias; Heinrich, Peter C; Behrmann, Iris; Schaper, Fred; Hermanns, Heike M

2010-03-15

The inflammatory response involves a complex interplay of different cytokines which act in an auto- or paracrine manner to induce the so-called acute phase response. Cytokines are known to crosstalk on multiple levels, for instance by regulating the mRNA stability of targeted cytokines through activation of the p38-MAPK pathway. In our study we discovered a new mechanism that answers the long-standing question how pro-inflammatory cytokines and environmental stress restrict immediate signalling of interleukin (IL)-6-type cytokines. We show that p38, activated by IL-1beta, TNFalpha or environmental stress, impairs IL-6-induced JAK/STAT signalling through phosphorylation of the common cytokine receptor subunit gp130 and its subsequent internalisation and degradation. We identify MK2 as the kinase that phosphorylates serine 782 in the cytoplasmic part of gp130. Consequently, inhibition of p38 or MK2, deletion of MK2 or mutation of crucial amino acids within the MK2 target site or the di-leucine internalisation motif blocks receptor depletion and restores IL-6-dependent STAT activation as well as gene induction. Hence, a novel negative crosstalk mechanism for cytokine signalling is described, where cytokine receptor turnover is regulated in trans by pro-inflammatory cytokines and stress stimuli to coordinate the inflammatory response.

Allergic disease in infants up to 2 yr of age in relation to plasma omega-3 fatty acids and maternal fish oil supplementation inpregnancy and lactation

OpenAIRE

Furuhjelm, Catrin; Warstedt, Kristina; Fagerås Böttcher, Malin; Fälth-Magnusson, Karin; Larsson, Johanna; Fredriksson, Mats; Duchén, Karel

2011-01-01

We have previously reported a protective effect of maternal omega-3 long-chain polyunsaturated fatty acids (x-3 LCPUFA) supplementation in pregnancy and lactation on IgE-associated eczema and food allergy in the infant during the first year of life. Here we investigate whether the effects of the LCPUFA supplementation on IgE-associated diseases last up to 2 yr of age and assess the relationship between plasma proportions of x-3 PUFAs and the frequency and severity of infant allergic disease. ...

Serum levels of pro- and anti-inflammatory cytokines in non-pregnant women, during pregnancy, labour and abortion

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S. Vassiliadis

1998-01-01

Full Text Available Disturbance of the cytokine equilibrium has been accused for many pathological disorders. Microbial infections, autoimmune diseases, graft rejection have been correlated to over- or under-production of specific cytokines which are produced as responder molecules to the various immune stimuli. The sole naturally occurring immune reaction in the organism is developed during the gestational period where, despite the presence of a semi-allogeneic graft, maternal immunoreactivity is driven to support fetal growth. The successful embryo development has been attributed to the important intervention of cytokines where some have been characterized as indispensable and others deleterious to fetal growth. However, the physiological levels of many factors during the gestational process have not been determined. Thus, in the present study we have measured and established the values of IL-1α, IL-2, IL-3, IL-4, IL-6, IL-10, IL-12, GM-CSF, TNF- α and IFN-γ during all phases of human pregnancy (first, second and third trimester of pregnancy, labour, abortions of the first trimester as well as in the non-pregnant control state. This is an attempt to assess serum protein concentrations and present the physiological levels of these cytokines at certain time intervals providing thus a diagnostic advantage in pregnancy cases where the mother cannot immunologically support the fetus. Exploitation of this knowledge and further research may be useful for therapeutic interventions in the future.

Maternal supplementation with conjugated linoleic acid in the setting of diet-induced obesity normalises the inflammatory phenotype in mothers and reverses metabolic dysfunction and impaired insulin sensitivity in offspring.

Science.gov (United States)

Segovia, Stephanie A; Vickers, Mark H; Zhang, Xiaoyuan D; Gray, Clint; Reynolds, Clare M

2015-12-01

Maternal consumption of a high-fat diet significantly impacts the fetal environment and predisposes offspring to obesity and metabolic dysfunction during adulthood. We examined the effects of a high-fat diet during pregnancy and lactation on metabolic and inflammatory profiles and whether maternal supplementation with the anti-inflammatory lipid conjugated linoleic acid (CLA) could have beneficial effects on mothers and offspring. Sprague-Dawley rats were fed a control (CD; 10% kcal from fat), CLA (CLA; 10% kcal from fat, 1% total fat as CLA), high-fat (HF; 45% kcal from fat) or high fat with CLA (HFCLA; 45% kcal from fat, 1% total fat as CLA) diet ad libitum 10days prior to and throughout gestation and lactation. Dams and offspring were culled at either late gestation (fetal day 20, F20) or early postweaning (postnatal day 24, P24). CLA, HF and HFCLA dams were heavier than CD throughout gestation. Plasma concentrations of proinflammatory cytokines interleukin-1β and tumour necrosis factor-α were elevated in HF dams, with restoration in HFCLA dams. Male and female fetuses from HF dams were smaller at F20 but displayed catch-up growth and impaired insulin sensitivity at P24, which was reversed in HFCLA offspring. HFCLA dams at P24 were protected from impaired insulin sensitivity as compared to HF dams. Maternal CLA supplementation normalised inflammation associated with consumption of a high-fat diet and reversed associated programming of metabolic dysfunction in offspring. This demonstrates that there are critical windows of developmental plasticity in which the effects of an adverse early-life environment can be reversed by maternal dietary interventions. Copyright © 2015 Elsevier Inc. All rights reserved.

Maternal expression of the histone demethylase Kdm4a is crucial for pre-implantation development

DEFF Research Database (Denmark)

Sankar, Aditya; Kooistra, Susanne Marije; Gonzalez, Javier Martin

2017-01-01

-methylated lysine 9 and lysine 36 of histone H3 (H3K9me2/me3 and H3K36me2/me3). Here, we report that Kdm4a as a maternal factor plays a key role in embryo survival and is vital for female fertility. Kdm4a−/− female mice ovulate normally with comparable fertilization but poor implantation rates, and cannot support......-deficient oocytes displays a poor intrinsic ability to develop into blastocysts. These embryos cannot compete with healthy embryos for implantation in vivo, highlighting Kdm4a as a maternal effect gene. Thus, our study dissects an important dual role for maternal Kdm4a in determining faithful early embryonic...... healthy transplanted embryos to term. This is due to a role for Kdm4a in uterine function, where its loss causes reduced expression of key genes involved in ion transport, nutrient supply and cytokine signalling, which impact embryo survival. In addition, a significant proportion of Kdm4a...

Study of plasma adrenomedullin level in normal pregnancy and preclampsia.

Science.gov (United States)

Senna, Azza Abo; Zedan, Magda; el-Salam, Gamal E Abd; el-Mashad, Ashraf I

2008-02-06

The aim of this study was to evaluate whether maternal circulating adrenomedullin (AM) values in patients with preeclampsia are different from those in normotensive pregnant women at different gestational ages. In a prospective clinical study, 90 women aged 17 to 40 years old, were divided into 4 main groups: group I (45 women): Normotensive pregnant women at first trimester (15 women), second trimester (15 women), and third trimester (15 women) of pregnancies. Group II (15 women): Pregnant women with preeclampsia at 25 to 38 weeks of gestation. Group III (15 women): Normotensive healthy nonpregnant women. Group IV (15 women): Hypertensive nonpregnant women. The plasma AM concentration was measured in all women by using enzyme immunoassay kits. Plasma AM levels in pregnant women with normal blood pressure at different gestational ages (first, second, and third trimesters) were statistically significantly higher than those detected in nonpregnant normotensive women and significantly increased with increasing gestational age (P < .001). Moreover, there was significant positive correlation between plasma AM levels and increasing gestational age (r = 0.915, P < .001). Preeclamptic patients had the highest mean plasma AM levels compared with all other groups, which is statistically significant (P < .001) and there was a significant positive correlation between plasma AM levels and systolic blood pressure, diastolic blood pressure, severity of preeclampsia, and proteinuria in pregnant patients with preeclampsia. Maternal plasma AM concentration increases throughout pregnancy and increases as gestational age progresses. AM production starts very early in gestation, suggesting that it may have an important role in human reproduction, from implantation to delivery. Maternal plasma AM level in preeclampsia appears to be higher than that in normal pregnancy.

Maternal immunization with ovalbumin prevents neonatal allergy development and up-regulates inhibitory receptor FcγRIIB expression on B cells

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Duarte Alberto JS

2010-03-01

Full Text Available Abstract Background Preconception allergen immunization prevents neonatal allergen sensitization in mice by a complex interaction between regulatory cells/factors and antibodies. The present study assessed the influence of maternal immunization with ovalbumin (OVA on the immune response of 3 day-old and 3 week-old offspring immunized or non-immunized with OVA and evaluated the effect of IgG treatment during fetal development or neonatal period. Results Maternal immunization with OVA showed increased levels of FcγRIIb expression in splenic B cells of neonates, which were maintained for up to 3 weeks and not affected by additional postnatal OVA immunization. Maternal immunization also exerted a down-modulatory effect on both IL-4 and IFN-γ-secreting T cells and IL-4 and IL-12- secreting B cells. Furthermore, immunized neonates from immunized mothers showed a marked inhibition of antigen-specifc IgE Ab production and lowered Th2/Th1 cytokine levels, whereas displaying enhanced FcγRIIb expression on B cells. These offspring also showed reduced antigen-specific proliferative response and lowered B cell responsiveness. Moreover, in vitro evaluation revealed an impairment of B cell activation upon engagement of B cell antigen receptor by IgG from OVA-immunized mice. Finally, in vivo IgG transference during pregnancy or breastfeeding revealed that maternal Ab transference was able to increase regulatory cytokines, such as IL-10, in the prenatal stage; yet only the postnatal treatment prevented neonatal sensitization. None of the IgG treatments induced immunological changes in the offspring, as it was observed for those from OVA-immunized mothers. Conclusion Maternal immunization upregulates the inhibitory FcγRIIb expression on offspring B cells, avoiding skewed Th2 response and development of allergy. These findings contribute to the advancement of prophylactic strategies to prevent allergic diseases in early life.

Maternal MTHFR gene polymorphisms and the risk of Down ...

African Journals Online (AJOL)

Estimation of maternal plasma homocysteine (Hyc): methionine (Met) ratio and lymphocyte methotrexate (MTX) cytotoxicity to assess the occurrence of MTHFR 677C → T mutation. Results: The MTHFR 677C → T polymorphism is more prevalent among mothers of infant with DS compared with the controls, with an odd ratio ...

Neonatal thyroid function in Seveso 25 years after maternal exposure to dioxin.

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Andrea Baccarelli

2008-07-01

Full Text Available Neonatal hypothyroidism has been associated in animal models with maternal exposure to several environmental contaminants; however, evidence for such an association in humans is inconsistent. We evaluated whether maternal exposure to 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD, a persistent and widespread toxic environmental contaminant, is associated with modified neonatal thyroid function in a large, highly exposed population in Seveso, Italy.Between 1994 and 2005, in individuals exposed to TCDD after the 1976 Seveso accident we conducted: (i a residence-based population study on 1,014 children born to the 1,772 women of reproductive age in the most contaminated zones (A, very high contamination; B, high contamination, and 1,772 age-matched women from the surrounding noncontaminated area (reference; (ii a biomarker study on 51 mother-child pairs for whom recent maternal plasma dioxin measurements were available. Neonatal blood thyroid-stimulating hormone (b-TSH was measured on all children. We performed crude and multivariate analyses adjusting for gender, birth weight, birth order, maternal age, hospital, and type of delivery. Mean neonatal b-TSH was 0.98 microU/ml (95% confidence interval [CI] 0.90-1.08 in the reference area (n = 533, 1.35 microU/ml (95% CI 1.22-1.49 in zone B (n = 425, and 1.66 microU/ml (95% CI 1.19-2.31 in zone A (n = 56 (p 5 microU/ml was 2.8% in the reference area, 4.9% in zone B, and 16.1% in zone A (p < 0.001. Neonatal b-TSH was correlated with current maternal plasma TCDD (n = 51, beta = 0.47, p < 0.001 and plasma toxic equivalents of coplanar dioxin-like compounds (n = 51, beta = 0.45, p = 0.005.Our data indicate that environmental contaminants such as dioxins have a long-lasting capability to modify neonatal thyroid function after the initial exposure.

Herpes Simplex Virus Suppressive Therapy in Herpes Simplex Virus-2/Human Immunodeficiency Virus-1 Coinfected Women Is Associated With Reduced Systemic CXCL10 But Not Genital Cytokines.

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Andersen-Nissen, Erica; Chang, Joanne T; Thomas, Katherine K; Adams, Devin; Celum, Connie; Sanchez, Jorge; Coombs, Robert W; McElrath, M Juliana; Baeten, Jared M

2016-12-01

Herpes simplex virus type-2 (HSV-2) may heighten immune activation and increase human immunodeficiency virus 1 (HIV-1) replication, resulting in greater infectivity and faster HIV-1 disease progression. An 18-week randomized, placebo-controlled crossover trial of 500 mg valacyclovir twice daily in 20 antiretroviral-naive women coinfected with HSV-2 and HIV-1 was conducted and HSV-2 suppression was found to significantly reduce both HSV-2 and HIV-1 viral loads both systemically and the endocervical compartment. To determine the effect of HSV-2 suppression on systemic and genital mucosal inflammation, plasma specimens, and endocervical swabs were collected weekly from volunteers in the trial and cryopreserved. Plasma was assessed for concentrations of 31 cytokines and chemokines; endocervical fluid was eluted from swabs and assayed for 14 cytokines and chemokines. Valacyclovir significantly reduced plasma CXCL10 but did not significantly alter other cytokine concentrations in either compartment. These data suggest genital tract inflammation in women persists despite HSV-2 suppression, supporting the lack of effect on transmission seen in large scale efficacy trials. Alternative therapies are needed to reduce persistent mucosal inflammation that may enhance transmission of HSV-2 and HIV-1.

Cytokines and depression in cancer patients and caregivers

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Li M

2017-11-01

Full Text Available Madeline Li,1,2 Ekaterina Kouzmina,3 Megan McCusker,1 Danielle Rodin,4 Paul C Boutros,3,5,6 Christopher J Paige,6–8 Gary Rodin1,2 1Princess Margaret Cancer Centre, Department of Supportive Care, University Health Network, Toronto, Ontario, Canada; 2Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada; 3Informatics & Biocomputing Program, Ontario Institute for Cancer Research, Toronto, Ontario, Canada; 4Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada; 5Department of Pharmacology & Toxicology, Toronto, Ontario, Canada; 6Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada; 7Department of Immunology, University of Toronto, Toronto, Ontario, Canada; 8Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada Objective: A better understanding of the biobehavioral mechanisms underlying depression in cancer is required to translate biomarker findings into clinical interventions. We tested for associations between cytokines and the somatic and psychological symptoms of depression in cancer patients and their healthy caregivers.Patients and methods: The GRID Hamilton Rating Scale for Depression (Ham-D was administered to 61 cancer patients of mixed type and stage, 26 primary caregivers and 38 healthy controls. Concurrently, blood was drawn for multiplexed plasma assays of 15 cytokines. Multiple linear regression, adjusted for biobehavioral variables, identified cytokine associations with the psychological (Ham-Dep and somatic (Ham-Som subfactors of the Ham-D.Results: The Ham-Dep scores of cancer patients were similar to their caregivers, but their Ham-Som scores were significantly higher (twofold, p=0.016. Ham-Som was positively associated with IL-1ra (coefficient: 1.27, p≤0.001 in cancer patients, and negatively associated with IL-2 (coefficient: -0.68, p=0.018 in caregivers. Ham-Dep was negatively associated with IL-4 (coefficient: -0.67, p

Prenatal maternal cortisol concentrations predict neurodevelopment in middle childhood.

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Davis, Elysia Poggi; Head, Kevin; Buss, Claudia; Sandman, Curt A

2017-01-01

Glucocorticoids (cortisol in humans) are the end product of the hypothalamic-pituitary-adrenocortical (HPA) axis and are proposed as a key mechanism for programming fetal brain development. The present prospective longitudinal study evaluates the association between prenatal maternal cortisol concentrations and child neurodevelopment. Participants included a low risk sample of 91 mother-child pairs. Prenatal maternal plasma cortisol concentrations were measured at 19 and 31 gestational weeks. Brain development and cognitive functioning were assessed when children were 6-9 years of age. Structural magnetic resonance imaging scans were acquired and cortical thickness was determined. Child cognitive functioning was evaluated using standardized measures (Wechsler Intelligence Scale for Children IV and Expressive Vocabulary Test, Second Edition). Higher maternal cortisol concentrations during the third trimester were associated with greater child cortical thickness primarily in frontal regions. No significant associations were observed between prenatal maternal cortisol concentrations and child cortical thinning. Elevated third trimester maternal cortisol additionally was associated with enhanced child cognitive performance. Findings in this normative sample of typically developing children suggest that elevated maternal cortisol during late gestation exert lasting benefits for brain development and cognitive functioning 6-9 years later. The benefits of fetal exposure to higher maternal cortisol during the third trimester for child neurodevelopment are consistent with the role cortisol plays in maturation of the human fetus. It is plausible that more extreme elevations in maternal cortisol concentrations late in gestation, as well as exposure to pharmacological levels of synthetic glucocorticoids, may have neurotoxic effects on the developing fetal brain. Copyright © 2016. Published by Elsevier Ltd.

Curcumin suppression of cytokine release and cytokine storm. A potential therapy for patients with Ebola and other severe viral infections.

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Sordillo, Peter P; Helson, Lawrence

2015-01-01

The terminal stage of Ebola and other viral diseases is often the onset of a cytokine storm, the massive overproduction of cytokines by the body's immune system. The actions of curcumin in suppressing cytokine release and cytokine storm are discussed. Curcumin blocks cytokine release, most importantly the key pro-inflammatory cytokines, interleukin-1, interleukin-6 and tumor necrosis factor-α. The suppression of cytokine release by curcumin correlates with clinical improvement in experimental models of disease conditions where a cytokine storm plays a significant role in mortality. The use of curcumin should be investigated in patients with Ebola and cytokine storm. Intravenous formulations may allow achievement of therapeutic blood levels of curcumin. Copyright © 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Competing risks model in screening for preeclampsia by maternal factors and biomarkers at 11-13 weeks gestation.

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O'Gorman, Neil; Wright, David; Syngelaki, Argyro; Akolekar, Ranjit; Wright, Alan; Poon, Leona C; Nicolaides, Kypros H

2016-01-01

Preeclampsia affects approximately 3% of all pregnancies and is a major cause of maternal and perinatal morbidity and death. In the last decade, extensive research has been devoted to early screening for preeclampsia with the aim of reducing the prevalence of the disease through pharmacologic intervention in the high-risk group starting from the first trimester of pregnancy. The purpose of this study was to develop a model for preeclampsia based on maternal demographic characteristics and medical history (maternal factors) and biomarkers. The data for this study were derived from prospective screening for adverse obstetric outcomes in women who attended for their routine first hospital visit at 11-13 weeks gestation in 2 maternity hospitals in England. We screened 35,948 singleton pregnancies that included 1058 pregnancies (2.9%) that experienced preeclampsia. Bayes theorem was used to combine the a priori risk from maternal factors with various combinations of uterine artery pulsatility index, mean arterial pressure, serum pregnancy-associated plasma protein-A, and placental growth factor multiple of the median values. Five-fold cross validation was used to assess the performance of screening for preeclampsia that delivered at preeclampsia) and ≥37 weeks gestation (term-preeclampsia) by models that combined maternal factors with individual biomarkers and their combination with screening by maternal factors alone. In pregnancies that experienced preeclampsia, the values of uterine artery pulsatility index and mean arterial pressure were increased, and the values of serum pregnancy-associated plasma protein-A and placental growth factor were decreased. For all biomarkers, the deviation from normal was greater for early than late preeclampsia; therefore, the performance of screening was related inversely to the gestational age at which delivery became necessary for maternal and/or fetal indications. Combined screening by maternal factors, uterine artery pulsatility

Umbilical cord PUFA are determined by maternal and child fatty acid desaturase (FADS) genetic variants in the Avon Longitudinal Study of Parents and Children (ALSPAC)

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Lattka, Eva; Koletzko, Berthold; Zeilinger, Sonja; Hibbeln, Joseph R.; Klopp, Norman; Ring, Susan M.; Steer, Colin D.

2012-01-01

Fetal supply with long-chain PUFA (LC-PUFA) during pregnancy is important for brain growth and visual and cognitive development and is provided by materno–fetal placental transfer. We recently showed that maternal fatty acid desaturase (FADS) genotypes modulate the amounts of LC-PUFA in maternal blood. Whether FADS genotypes influence the amounts of umbilical cord fatty acids has not been investigated until now. The aim of the present study was to investigate the influence of maternal and child FADS genotypes on the amounts of LC-PUFA in umbilical cord venous plasma as an indicator of fetal fatty acid supply during pregnancy. A total of eleven cord plasma n-6 and n-3 fatty acids were analysed for association with seventeen FADS gene cluster SNP in over 2000 mothers and children from the Avon Longitudinal Study of Parents and Children. In a multivariable analysis, the maternal genotype effect was adjusted for the child genotype and vice versa to estimate which of the two has the stronger influence on cord plasma fatty acids. Both maternal and child FADS genotypes and haplotypes influenced amounts of cord plasma LC-PUFA and fatty acid ratios. Specifically, most analysed maternal SNP were associated with cord plasma levels of the precursor n-6 PUFA, whereas the child genotypes were mainly associated with more highly desaturated n-6 LC-PUFA. This first study on FADS genotypes and cord fatty acids suggests that fetal LC-PUFA status is determined to some extent by fetal fatty acid conversion. Associations of particular haplotypes suggest specific effects of SNP rs498793 and rs968567 on fatty acid metabolism. PMID:22877655

Platelet-Released Growth Factors Modulate the Secretion of Cytokines in Synoviocytes under Inflammatory Joint Disease

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Rasuo, Biljana; Hock, Jennifer Vanessa Phi; Kweider, Nisreen; Fragoulis, Athanassios; Sönmez, Tolga Taha; Jahr, Holger; Pufe, Thomas; Lippross, Sebastian

2017-01-01

The etiology and pathogenesis of rheumatoid arthritis (RA) are marked by a complex interplay of various cell populations and is mediated by different signaling pathways. Traditionally, therapies have primarily focused on pain relief, reducing inflammation and the recovery of joint function. More recently, however, researchers have discussed the therapeutic efficacy of autologous platelet-rich plasma (PRP). The main objective of this work is to examine the influences of platelet-released growth factor (PRGF) on human synoviocytes under inflammatory conditions. Additionally, it is checked to which extend treatment with platelet concentrate influences the release of cytokines form synoviocytes. For this purpose, an in vitro RA model was created by stimulating the cells with the TNF-α. The release of cytokines was measured by ELISA. The cytokine gene expression was analyzed by real-time PCR. It has been observed that the stimulation concentration of 10 ng/ml TNF-α resulted in a significantly increased endogenous secretion and gene expression of IL-6 and TNF-α. The anti-inflammatory effect of PRGF could be confirmed through significant reduction of TNF-α and IL-1β. An induced inflammatory condition seems to cause PRGF to inhibit the release of proinflammatory cytokines. Further study is required to understand the exact effect mechanism of PRGF on synoviocytes. PMID:29348703

Platelet-Released Growth Factors Modulate the Secretion of Cytokines in Synoviocytes under Inflammatory Joint Disease

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Mersedeh Tohidnezhad

2017-01-01

Full Text Available The etiology and pathogenesis of rheumatoid arthritis (RA are marked by a complex interplay of various cell populations and is mediated by different signaling pathways. Traditionally, therapies have primarily focused on pain relief, reducing inflammation and the recovery of joint function. More recently, however, researchers have discussed the therapeutic efficacy of autologous platelet-rich plasma (PRP. The main objective of this work is to examine the influences of platelet-released growth factor (PRGF on human synoviocytes under inflammatory conditions. Additionally, it is checked to which extend treatment with platelet concentrate influences the release of cytokines form synoviocytes. For this purpose, an in vitro RA model was created by stimulating the cells with the TNF-α. The release of cytokines was measured by ELISA. The cytokine gene expression was analyzed by real-time PCR. It has been observed that the stimulation concentration of 10 ng/ml TNF-α resulted in a significantly increased endogenous secretion and gene expression of IL-6 and TNF-α. The anti-inflammatory effect of PRGF could be confirmed through significant reduction of TNF-α and IL-1β. An induced inflammatory condition seems to cause PRGF to inhibit the release of proinflammatory cytokines. Further study is required to understand the exact effect mechanism of PRGF on synoviocytes.

Effects of feed contaminant deoxynivalenol on plasma cytokines and mRNA expression of immune genes in the intestine of broiler chickens.

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Ghareeb, Khaled; Awad, Wageha A; Soodoi, Chimidtseren; Sasgary, Soleman; Strasser, Alois; Böhm, Josef

2013-01-01

An experiment was conducted to investigate the individual and combined effects of dietary deoxynivalenol (DON) and a microbial feed additive on plasma cytokine level and on the expression of immune relevant genes in jejunal tissues of broilers. A total of 40 broiler chicks were obtained from a commercial hatchery and divided randomly into four groups (10 birds per group). Birds were reared in battery cages from one day old for 5 weeks. The dietary groups were 1) control birds fed basal diet; 2) DON group fed basal diet contaminated with 10 mg DON/ kg feed; 3) DON + Mycofix group fed basal diet contaminated with 10 mg DON/ kg feed and supplemented with a commercial feed additive, Mycofix® Select (MS) (2.5 kg/ton of feed); 4) Mycofix group fed basal diet supplemented with MS (2.5 kg/ton of feed). At 35 days, the plasma levels of tumor necrosis factor alpha (TNF-α) and interleukin 8 (IL-8) were quantified by ELISA test kits. Furthermore, the mRNA expression of TNF-α, IL-8, IL-1β, interferon gamma (IFNγ), transforming growth factor beta receptor I (TGFBR1) and nuclear factor kappa-light-chain-enhancer of activated B cells 1 (NF-κβ1) in jejunum were quantified by qRT-PCR. The results showed that the plasma TNF-α decreased in response to DON, while in combination with MS, the effect of DON was reduced. DON down-regulated the relative gene expression of IL-1β, TGFBR1 and IFN-γ, and addition of MS to the DON contaminated diet compensates these effects on IL-1β, TGFBR1 but not for IFN-γ. Furthermore, supplementation of MS to either DON contaminated or control diet up-regulated the mRNA expression of NF-κβ1. In conclusion, DON has the potential to provoke and modulate immunological reactions of broilers and subsequently could increase their susceptibility to disease. The additive seemed to have almost as much of an effect as DON, albeit on different genes.

On-site screening for maternal syphilis in an antenatal clinic

African Journals Online (AJOL)

Abstract Study objective. To determine the sensitivity, specificity, negative predictive value and positive predictive value of the rapid plasma reagin (RPR) test as performed on site in an antenatal clinic to facilitate immediate diagnosis and treatment of maternal syphilis. Design. Open, descriptive study. Setting. Antenatal ...

On-site screening for maternal syphilis in an antenatal clinic ...

African Journals Online (AJOL)

Study objective. To determine the sensitivity, specificity, negative predictive value and positive predictive value of the rapid plasma reagin (RPR) test as performed on site in an antenatal clinic to facilitate immediate diagnosis and treatment of maternal syphilis. Design. Open, descriptive study. Setting. Antenatal clinic ...

Insulin resistance and increased muscle cytokine levels in patients with mitochondrial myopathy.

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Rue, Nana; Vissing, John; Galbo, Henrik

2014-10-01

Mitochondrial dysfunction has been proposed to cause insulin resistance and that might stimulate cytokine production. The objective of the study was to elucidate the association between mitochondrial myopathy, insulin sensitivity, and cytokine levels in muscle. This was an experimental, controlled study in outpatients. Eight overnight-fasted patients (P) with various inherited mitochondrial myopathies and eight healthy subjects (C) matched for sex, age, weight, height, and physical activity participated in the study. The intervention included a 120-minute hyperinsulinemic, euglycemic clamp. Another morning, microdialysis of both vastus lateralis muscles for 4 hours, including one-legged, knee extension exercise for 30 minutes, was performed. Glucose infusion rate during 90-120 minutes of insulin infusion was measured. Cytokine concentrations in dialysate were also measured. Muscle strength, percentage fat mass, and creatine kinase in plasma did not differ between groups. The maximal oxygen uptake was 21 ± 3 (SE) (P) and 36 ± 3(C) mL/kg·min (2P fatty acids and glycerol at 120 minutes were higher in P vs C (2P myopathies, insulin sensitivity of muscle, adipose tissue, and pancreatic A cells is reduced, supporting that mitochondrial function influences insulin action. Furthermore, a local, low-grade inflammation of potential clinical importance exists in the muscle of these patients.

Maternal Melatonin Therapy Attenuated Maternal High-Fructose Combined with Post-Weaning High-Salt Diets-Induced Hypertension in Adult Male Rat Offspring

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You-Lin Tain

2018-04-01

Full Text Available Consumption of food high in fructose and salt is associated with the epidemic of hypertension. Hypertension can originate from early life. Melatonin, a pleiotropic hormone, regulates blood pressure. We examined whether maternal melatonin therapy can prevent maternal high-fructose combined with post-weaning high-salt diet-induced programmed hypertension in adult offspring. Pregnant Sprague-Dawley rats received either a normal diet (ND or a 60% fructose diet (HF during pregnancy and the lactation period. Male offspring were on either the ND or a high-salt diet (HS, 1% NaCl from weaning to 12 weeks of age and were assigned to five groups (n = 8/group: ND/ND, HF/ND, ND/HS, HF/HS, and HF/HS+melatonin. Melatonin (0.01% in drinking water was administered during pregnancy and lactation. We observed that maternal HF combined with post-weaning HS diets induced hypertension in male adult offspring, which was attenuated by maternal melatonin therapy. The beneficial effects of maternal melatonin therapy on HF/HS-induced hypertension related to regulating several nutrient-sensing signals, including Sirt1, Sirt4, Prkaa2, Prkab2, Pparg, and Ppargc1a. Additionally, melatonin increased protein levels of mammalian targets of rapamycin (mTOR, decreased plasma asymmetric dimethylarginine (ADMA and symmetric dimethylarginine levels, and increased the l-arginine-to-ADMA ratio. The reprogramming effects by which maternal melatonin therapy protects against hypertension of developmental origin awaits further elucidation.

Factor XI Deficiency Alters the Cytokine Response and Activation of Contact Proteases during Polymicrobial Sepsis in Mice.

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Charles E Bane

Full Text Available Sepsis, a systemic inflammatory response to infection, is often accompanied by abnormalities of blood coagulation. Prior work with a mouse model of sepsis induced by cecal ligation and puncture (CLP suggested that the protease factor XIa contributed to disseminated intravascular coagulation (DIC and to the cytokine response during sepsis. We investigated the importance of factor XI to cytokine and coagulation responses during the first 24 hours after CLP. Compared to wild type littermates, factor XI-deficient (FXI-/- mice had a survival advantage after CLP, with smaller increases in plasma levels of TNF-α and IL-10 and delayed IL-1β and IL-6 responses. Plasma levels of serum amyloid P, an acute phase protein, were increased in wild type mice 24 hours post-CLP, but not in FXI-/- mice, supporting the impression of a reduced inflammatory response in the absence of factor XI. Surprisingly, there was little evidence of DIC in mice of either genotype. Plasma levels of the contact factors factor XII and prekallikrein were reduced in WT mice after CLP, consistent with induction of contact activation. However, factor XII and PK levels were not reduced in FXI-/- animals, indicating factor XI deficiency blunted contact activation. Intravenous infusion of polyphosphate into WT mice also induced changes in factor XII, but had much less effect in FXI deficient mice. In vitro analysis revealed that factor XIa activates factor XII, and that this reaction is enhanced by polyanions such polyphosphate and nucleic acids. These data suggest that factor XI deficiency confers a survival advantage in the CLP sepsis model by altering the cytokine response to infection and blunting activation of the contact (kallikrein-kinin system. The findings support the hypothesis that factor XI functions as a bidirectional interface between contact activation and thrombin generation, allowing the two processes to influence each other.

Maternal diet, LCPUFA status and prematurity in Indian mothers: A cross-sectional study

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Prachi S. Ranade

2012-11-01

Full Text Available Background: Recently, certain long chain polyunsaturated fatty acids (LCPUFA have been shown to exert functional benefits with regards to gestational length. The present study examined the association of maternal LCPUFA intake, specifically Docosahexaenoic acid(DHA and Arachidonic acid (ARA, and plasma status at delivery with duration of gestation and risk of premature delivery in Indian mothers.Methods: In a cross-sectional nested case-control study, 191 mother-baby pairs [164 Full term(FT and 27 Preterm (PT] were examined for differences in maternal habitual diet pattern and plasma fatty acid composition in relation to the length of gestation.Results: The frequency of intake of n-3 fatty acid rich varieties of fish was higher (p<0.05 in FT mothers compared to PT mothers. Maternal plasma fatty acid concentration of n-3 Alpha Linolenic acid (ALA, Eicosapentaenoic acid (EPA, DHA and total n-3 fatty acids at delivery was significantly associated with intake of vegetarian ALA sources such as millets, dark whole pulses, dry fruits like walnuts, and green leafy vegetables. Among age, parity, and neonatal sex matched case-control pairs, PT mothers had significantly (p<0.01 higher levels of n-6 ARA, but lower (p<0.01 levels of n-3 DHA and total n-3 fatty acids compared to FT mothers irrespective of socioeconomic group. In fact, mothers with plasma DHA levels below median (<3.0% had ten times higher risk (OR-10.47; 95% CI: 3.03-36.48 of delivering prematurely compared to those who had plasma DHA levels above median.Conclusion: Results underscore the importance of consuming varied sources of ALA and DHAfor their role as functional lipids in determining gestational length.

Maternal-Fetal rejection reactions are unconstrained in preeclamptic women.

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Nguyen, Tina A; Kahn, Daniel A; Loewendorf, Andrea I

2017-01-01

The risk factors for preeclampsia, extremes of maternal age, changing paternity, concomitant maternal autoimmunity, and/or birth intervals greater than 5 years, suggest an underlying immunopathology. We used peripheral blood and lymphocytes from the UteroPlacental Interface (UPI) of 3rd trimester healthy pregnant women in multicolor flow cytometry-and in vitro suppression assays. The major end-point was the characterization of activation markers, and potential effector functions of different CD4-and CD8 subsets as well as T regulatory cells (Treg). We observed a significant shift of peripheral CD4 -and CD8- T cells from naïve to memory phenotype in preeclamptic women compared to healthy pregnant women consistent with long-standing immune activation. While the proportions of the highly suppressive Cytokine and Activated Treg were increased in preeclampsia, Treg tolerance toward fetal antigens was dysfunctional. Thus, our observations indicate a long-standing inflammatory derangement driving immune activation in preeclampsia; in how far the Treg dysfunction is caused by/causes this immune activation in preeclampsia will be the object of future studies.

Maternal-Fetal rejection reactions are unconstrained in preeclamptic women.

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Tina A Nguyen

Full Text Available The risk factors for preeclampsia, extremes of maternal age, changing paternity, concomitant maternal autoimmunity, and/or birth intervals greater than 5 years, suggest an underlying immunopathology. We used peripheral blood and lymphocytes from the UteroPlacental Interface (UPI of 3rd trimester healthy pregnant women in multicolor flow cytometry-and in vitro suppression assays. The major end-point was the characterization of activation markers, and potential effector functions of different CD4-and CD8 subsets as well as T regulatory cells (Treg. We observed a significant shift of peripheral CD4 -and CD8- T cells from naïve to memory phenotype in preeclamptic women compared to healthy pregnant women consistent with long-standing immune activation. While the proportions of the highly suppressive Cytokine and Activated Treg were increased in preeclampsia, Treg tolerance toward fetal antigens was dysfunctional. Thus, our observations indicate a long-standing inflammatory derangement driving immune activation in preeclampsia; in how far the Treg dysfunction is caused by/causes this immune activation in preeclampsia will be the object of future studies.

Cytokine Signature in End-Stage Renal Disease Patients on Hemodialysis

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Danyelle Romana Alves Rios

2017-01-01

Full Text Available Hemodialysis is a modality of blood filtration in which accumulated toxins and water are removed from the body. This treatment is indicated for patients at the end stage of renal disease. Vascular access complications are responsible for 20–25% of all hospitalizations in dialyzed patients. The occurrence of thrombosis in the vascular access is a serious problem that may severely compromise or even make the hemodialysis impossible, which is vital for the patient. The aim of this study was to investigate inflammatory profile in patients undergoing hemodialysis as well as the association between these alterations and vascular access thrombosis. A total of 195 patients undergoing hemodialysis have been evaluated; of which, 149 patients had not experienced vascular access thrombosis (group I and 46 patients had previously presented this complication (group II. Plasma levels of cytokines including interleukin (IL- 2, IL-4, IL-5, IL-10, TNF-α, and IFN-γ were measured by cytometric bead array. Our results showed that patients with previous thrombotic events (group II had higher levels of the IL-2, IL-4, IL-5, and IFN-γ when compared to those in group I. Furthermore, a different cytokine signature was detected in dialyzed patients according to previous occurrences or not of thrombotic events, suggesting that elevated levels of T-helper 1 and T-helper 2 cytokines might, at least in part, contribute to this complication.

Influence of Seasonality and Circulating Cytokines on Serial QuantiFERON Discordances

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Marsha L. Griffin

2018-01-01

Full Text Available Objectives. An 18-month prospective study serially tested healthcare workers (HCWs for tuberculosis infection (TBI and reported discordant QuantiFERON Gold In-Tube® (QFT results in some participants. The purpose of the current study was to investigate whether the interferon-gamma (IFN-γ measured by QFT in discordant individuals could be influenced by other circulating cytokines that vary seasonally at the time of phlebotomy. Methods. The CDC funded TBESC Task Order 18 (TO18 project to assess the use of Interferon Gamma Release Assays (IGRAs, T-SPOT.TB® and QFT, compared to the tuberculin skin test (TST for the serial testing of TBI in HCW at 4 US sites. Unstimulated plasma from 9 discordant TO18 participants at 4 different time points from the Houston site was multiplexed to determine the association between circulating cytokines and antigen stimulated IFN-γ levels. Results. IL-12, IL-1β, IL-3, GCSF, and IL-7 were associated with the amount of IFN-γ measured in response to antigen stimulation. In addition to these cytokines, a significant relationship was found between a positive QFT result and the spring season. Conclusions. Allergens during the spring season can result in the upregulation of IL-1β and IL-3, and this upregulation was observed with the amount of IFN-γ measured in discordant results.

Cytokine regulation of immune tolerance

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Wu, Jie; Xie, Aini; Chen, Wenhao

2014-01-01

The immune system provides defenses against invading pathogens while maintaining immune tolerance to self-antigens. This immune homeostasis is harmonized by the direct interactions between immune cells and the cytokine environment in which immune cells develop and function. Herein, we discuss three non-redundant paradigms by which cytokines maintain or break immune tolerance. We firstly describe how anti-inflammatory cytokines exert direct inhibitory effects on immune cells to enforce immune ...

Bone Marrow Mononuclear Cell Transplantation Restores Inflammatory Balance of Cytokines after ST Segment Elevation Myocardial Infarction.

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Kirsi Alestalo

Full Text Available Acute myocardial infarction (AMI launches an inflammatory response and a repair process to compensate cardiac function. During this process, the balance between proinflammatory and anti-inflammatory cytokines is important for optimal cardiac repair. Stem cell transplantation after AMI improves tissue repair and increases the ventricular ejection fraction. Here, we studied in detail the acute effect of bone marrow mononuclear cell (BMMNC transplantation on proinflammatory and anti-inflammatory cytokines in patients with ST segment elevation myocardial infarction (STEMI.Patients with STEMI treated with thrombolysis followed by percutaneous coronary intervention (PCI were randomly assigned to receive either BMMNC or saline as an intracoronary injection. Cardiac function was evaluated by left ventricle angiogram during the PCI and again after 6 months. The concentrations of 27 cytokines were measured from plasma samples up to 4 days after the PCI and the intracoronary injection.Twenty-six patients (control group, n = 12; BMMNC group, n = 14 from the previously reported FINCELL study (n = 80 were included to this study. At day 2, the change in the proinflammatory cytokines correlated with the change in the anti-inflammatory cytokines in both groups (Kendall's tau, control 0.6; BMMNC 0.7. At day 4, the correlation had completely disappeared in the control group but was preserved in the BMMNC group (Kendall's tau, control 0.3; BMMNC 0.7.BMMNC transplantation is associated with preserved balance between pro- and anti-inflammatory cytokines after STEMI in PCI-treated patients. This may partly explain the favorable effect of stem cell transplantation after AMI.

Possible maternal offloading of metals in the plasma, uterine and capsule fluid of pregnant ragged-tooth sharks (Carcharias taurus) on the east coast of South Africa.

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Naidoo, Kristina; Chuturgoon, Anil; Cliff, Geremy; Singh, Sanil; Ellis, Megan; Otway, Nicholas; Vosloo, Andre; Gregory, Michael

2017-07-01

We studied the possible metal offloading onto the progeny of three pregnant female ragged-tooth sharks (Carcharias taurus) (C. taurus). The presences of five metals, i.e. aluminium (Al), arsenic (As), cadmium (Cd), lead (Pb) and selenium (Se) were validated by mass spectrometry in the maternal plasma as well as the intracapsular and uterine fluids (UF) in which embryos develop. Metals were ranked in a decreasing concentration as follows: Plasma: As > Al > Se > Pb > Cd; ICF: As > Se > Al > Cd > Pb and UF: As > Se > Al > Cd > Pb. As was present in the highest concentration in all three sharks. Al, Pb and Cd were found to be the highest within the plasma, while concentrations of Se were similar in all three fluids. These results indicate that C. taurus embryos are exposed to metals during early development, but the impact of this exposure remains unknown. To the best of our knowledge, this is the first investigation to confirm the presence of metals in the fluids that surround the developing C. taurus embryos, a species that is already listed as vulnerable.

Comparative study of the cytokine/chemokine response in children with differing disease severity in enterovirus 71-induced hand, foot, and mouth disease.

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Yan Zhang

Full Text Available BACKGROUND: Enterovirus 71 (EV71 infection can lead to a rapidly progressing, life-threatening, and severe neurological disease in young children, including the development of human hand, foot, and mouth disease (HFMD. This study aims to further characterize the specific immunological features in EV71-mediated HFMD patients presenting with differing degrees of disease severity. METHODOLOGY: Comprehensive cytokine and chemokine expression were broadly evaluated by cytokine antibody array in EV71-infected patients hospitalized for HFMD compared to Coxsackievirus A16-infected patients and age-matched healthy controls. More detailed analysis using Luminex-based cytokine bead array was performed in EV71-infected patients stratified into diverse clinic outcomes. Additionally, immune cell frequencies in peripheral blood and EV71-specific antibodies in plasma were also examined. PRINCIPAL FINDINGS: Expression of several cytokines and chemokines were significantly increased in plasma from EV71-infected patients compared to healthy controls, which further indicated that: (1 GM-CSF, MIP-1β, IL-2, IL-33, and IL-23 secretion was elevated in patients who rapidly developed disease and presented with uncomplicated neurological damage; (2 G-CSF and MCP-1 were distinguishably secreted in EV71 infected very severe patients presenting with acute respiratory failure; (3 IP-10, MCP-1, IL-6, IL-8, and G-CSF levels were much higher in cerebrospinal fluid than in plasma from patients with neurological damage; (4 FACS analysis revealed that the frequency of CD19(+HLADR(+ mature B cells dynamically changed over time during the course of hospitalization and was accompanied by dramatically increased EV71-specific antibodies. Our data provide a panoramic view of specific immune mediator and cellular immune responses of HFMD and may provide useful immunological profiles for monitoring the progress of EV71-induced fatal neurological symptoms with acute respiratory failure.

Chronic infusion of lisinopril into hypothalamic paraventricular nucleus modulates cytokines and attenuates oxidative stress in rostral ventrolateral medulla in hypertension

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Li, Hong-Bao [Department of Physiology and Pathophysiology, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Qin, Da-Nian, E-mail: dnqin@stu.edu.cn [Department of Physiology, Shantou University Medical College, Shantou 515041 (China); Ma, Le [Department of Public Health, Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Miao, Yu-Wang [Department of Physiology and Pathophysiology, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Zhang, Dong-Mei [Department of Physiology, Dalian Medical University, Dalian 116044 (China); Lu, Yan [Department of Clinical Laboratory, Sanaitang Hospital, Lanzhou 730030 (China); Song, Xin-Ai [Department of Physiology and Pathophysiology, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Zhu, Guo-Qing [Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing 210029 (China); Kang, Yu-Ming, E-mail: ykang@mail.xjtu.edu.cn [Department of Physiology and Pathophysiology, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China)

2014-09-01

The hypothalamic paraventricular nucleus (PVN) and rostral ventrolateral medulla (RVLM) play a critical role in the generation and maintenance of sympathetic nerve activity. The renin–angiotensin system (RAS) in the brain is involved in the pathogenesis of hypertension. This study was designed to determine whether inhibition of the angiotensin-converting enzyme (ACE) in the PVN modulates cytokines and attenuates oxidative stress (ROS) in the RVLM, and decreases the blood pressure and sympathetic activity in renovascular hypertensive rats. Renovascular hypertension was induced in male Sprague–Dawley rats by the two-kidney one-clip (2K1C) method. Renovascular hypertensive rats received bilateral PVN infusion with ACE inhibitor lisinopril (LSP, 10 μg/h) or vehicle via osmotic minipump for 4 weeks. Mean arterial pressure (MAP), renal sympathetic nerve activity (RSNA), and plasma proinflammatory cytokines (PICs) were significantly increased in renovascular hypertensive rats. The renovascular hypertensive rats also had higher levels of ACE in the PVN, and lower level of interleukin-10 (IL-10) in the RVLM. In addition, the levels of PICs, the chemokine MCP-1, the subunit of NAD(P)H oxidase (gp91{sup phox}) and ROS in the RVLM were increased in hypertensive rats. PVN treatment with LSP attenuated those changes occurring in renovascular hypertensive rats. Our findings suggest that the beneficial effects of ACE inhibition in the PVN in renovascular hypertension are partly due to modulation cytokines and attenuation oxidative stress in the RVLM. - Highlights: • Chronic ACE inhibition in PVN on renovascular hypertension was investigated. • 2K1C resulted in sympathoexcitation, increased plasma PICs and hypertension. • 2K1C rats had higher levels of cytokines and reactive oxygen species (ROS) in RVLM. • Chronic inhibiting PVN ACE attenuates cytokines and ROS in RVLM in hypertension.

Chronic infusion of lisinopril into hypothalamic paraventricular nucleus modulates cytokines and attenuates oxidative stress in rostral ventrolateral medulla in hypertension

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Li, Hong-Bao; Qin, Da-Nian; Ma, Le; Miao, Yu-Wang; Zhang, Dong-Mei; Lu, Yan; Song, Xin-Ai; Zhu, Guo-Qing; Kang, Yu-Ming

2014-01-01

The hypothalamic paraventricular nucleus (PVN) and rostral ventrolateral medulla (RVLM) play a critical role in the generation and maintenance of sympathetic nerve activity. The renin–angiotensin system (RAS) in the brain is involved in the pathogenesis of hypertension. This study was designed to determine whether inhibition of the angiotensin-converting enzyme (ACE) in the PVN modulates cytokines and attenuates oxidative stress (ROS) in the RVLM, and decreases the blood pressure and sympathetic activity in renovascular hypertensive rats. Renovascular hypertension was induced in male Sprague–Dawley rats by the two-kidney one-clip (2K1C) method. Renovascular hypertensive rats received bilateral PVN infusion with ACE inhibitor lisinopril (LSP, 10 μg/h) or vehicle via osmotic minipump for 4 weeks. Mean arterial pressure (MAP), renal sympathetic nerve activity (RSNA), and plasma proinflammatory cytokines (PICs) were significantly increased in renovascular hypertensive rats. The renovascular hypertensive rats also had higher levels of ACE in the PVN, and lower level of interleukin-10 (IL-10) in the RVLM. In addition, the levels of PICs, the chemokine MCP-1, the subunit of NAD(P)H oxidase (gp91 phox ) and ROS in the RVLM were increased in hypertensive rats. PVN treatment with LSP attenuated those changes occurring in renovascular hypertensive rats. Our findings suggest that the beneficial effects of ACE inhibition in the PVN in renovascular hypertension are partly due to modulation cytokines and attenuation oxidative stress in the RVLM. - Highlights: • Chronic ACE inhibition in PVN on renovascular hypertension was investigated. • 2K1C resulted in sympathoexcitation, increased plasma PICs and hypertension. • 2K1C rats had higher levels of cytokines and reactive oxygen species (ROS) in RVLM. • Chronic inhibiting PVN ACE attenuates cytokines and ROS in RVLM in hypertension

Maternal Vitamin D Insufficiency Early in Pregnancy Is Associated with Increased Risk of Preterm Birth in Ethnic Minority Women in Canada.

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Tabatabaei, Negar; Auger, Nathalie; Herba, Catherine M; Wei, Shuqin; Allard, Catherine; Fink, Guy D; Fraser, William D

2017-06-01

Background: Maternal vitamin D insufficiency (plasma 25-hydroxyvitamin D [25(OH)D] rates of preterm and spontaneous preterm births. Objective: We explored the relation between maternal plasma 25(OH)D concentration in the first trimester (8-14 wk of gestation) and the risk of preterm and spontaneous preterm births (birth (distribution of vitamin D status between cases and controls for 8 ethnic minority subgroups. We explored the association between maternal plasma 25(OH)D concentration and preterm and spontaneous preterm births with the use of splines in logistic regression by ethnicity. Results: The distributions of maternal vitamin D status (75 nmol/L) were different in preterm and spontaneous preterm birth cases compared with controls but only in women of ethnic minority ( P- trend = 0.003 and 0.024, respectively). Among ethnic subgroups, sub-Saharan Africans ( P -trend = 0.030) and Arab-West Asians ( P -trend = 0.045) showed an inverse relation between maternal vitamin D status and the risk of preterm birth. Maternal plasma 25(OH)D concentrations of 30 nmol/L were associated with 4.05 times the risk of preterm birth in the total ethnic minority population (95% CI: 1.16, 14.12; P = 0.028) relative to participants with a concentration of 75 nmol/L. In contrast, there was no such association among nonethnic women (OR: 0.94; 95% CI: 0.48, 1.82; P = 0.85). There was no association when we considered only spontaneous preterm births in the total ethnic minority population (OR: 1.75; 95% CI: 0.39, 7.79; P = 0.46). Conclusion: Vitamin D insufficiency is associated with an increased risk of preterm birth in ethnic minority women in Canada. © 2017 American Society for Nutrition.

Transfer of Maternal Immunity to Newborns of Diabetic Mothers

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Eduardo Luzía França

2012-01-01

Full Text Available This study was carried out with hyperglycemic pregnant women to investigate the transfer of antibody classes to newborns across the placenta or by colostrum and the functional activity of phagocytes in maternal blood, cord blood, and colostrum from diabetes mothers. Samples from maternal blood, cord blood, and colostrum were collected from 20 normoglycemic and 20 hyperglycemic pregnant women. We determined antibodies levels, superoxide release, phagocytosis and bactericidal activity of phagocytes. We demonstrated that IgG levels in cord blood were higher in the hyperglycemic group. IgA and IgM levels were higher in maternal than in cord blood samples. Plasma antibody levels were lower in hyper- than in normoglycemic women. The colostrum of diabetic mothers had lower IgA and IgG levels. Colostrum and maternal blood phagocytes when exposed to EPEC increased the superoxide release. Cord blood phagocytes of hyperglycemic group, independently of bacteria, had higher superoxide release. Colostrum and blood phagocytes from diabetic group exhibited some phagocytic and microbicidal activity in response to EPEC. Mononuclear phagocytes from cord blood had the lowest phagocytosis, and bactericidal activity for EPEC, regardless of glycemic status. These data showed that hyperglycemia altered IgG transfer across the placenta and decreases immunoglobulin levels in maternal blood and colostrum.

Low prevalence of antibodies and other plasma factors binding to CC chemokines and IL-2 in HIV-positive patients

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Meyer, C N; Svenson, M; Larsen, Carsten Schade

2000-01-01

Neutralizing cytokine antibodies are found in healthy and diseased individuals, including patients treated with recombinant cytokines. Identification of CCR-5 as co-receptor for HIV has focused interest on CC chemokines and their potential therapeutic use. Chemokine-binding components in plasma...

Lipopolysaccharide-binding protein and leptin are associated with stress-induced interleukin-6 cytokine expression ex vivo in obesity.

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Huang, Chun-Jung; Stewart, Jennifer K; Shibata, Yoshimi; Slusher, Aaron L; Acevedo, Edmund O

2015-05-01

Obesity is associated with enhanced inflammation and mental stress, but limited information has addressed the potential additive effect of psychological stress on obesity-associated inflammation. This study examined whether obese subjects would elicit a greater host immune response (IL-6 mRNA and cytokine) to lipopolysaccharide (LPS) in response to mental stress. Blood samples for LPS-stimulated IL-6 mRNA and cytokine were collected prior to and following mental stress. Results showed that obese subjects elicited a greater LPS-induced IL-6 along with its mRNA expression following mental stress compared to normal-weight subjects. Stress-induced IL-6 cytokine response to LPS was correlated with the baseline levels of plasma LPS binding protein (LBP) and leptin. These findings are consistent with the idea that endogenous inflammatory agents (e.g., LBP and leptin), often elevated with obesity, enhance inflammatory responses to psychological stress. © 2014 Society for Psychophysiological Research.

The role of the anterodorsal thalami nuclei in the regulation of adrenal medullary function, beta-adrenergic cardiac receptors and anxiety responses in maternally deprived rats under stressful conditions.

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Suárez, M M; Rivarola, M A; Molina, S M; Levin, G M; Enders, J; Paglini, P

2004-09-01

Maternal separation can interfere with growth and development of the brain and represents a significant risk factor for adult psychopathology. In rodents, prolonged separation from the mother affects the behavioral and endocrine responses to stress for the lifetime of the animal. Limbic structures such as the anterodorsal thalamic nuclei (ADTN) play an important role in the control of neuroendocrine and sympathetic-adrenal function. In view of these findings we hypothesized that the function of the ADTN may be affected in an animal model of maternal deprivation. To test this hypothesis female rats were isolated 4.5 h daily, during the first 3 weeks of life and tested as adults. We evaluated plasma epinephrine (E) and norepinephrine (NE), cardiac adrenoreceptors and anxiety responses after maternal deprivation and variable chronic stress (VCS) in ADTN-lesioned rats. Thirty days after ADTN lesion, in non-maternally deprived rats basal plasma NE concentration was greater and cardiac beta-adrenoreceptor density was lower than that in the sham-lesioned group. Maternal deprivation induced a significant increase in basal plasma NE concentration, which was greater in lesioned rats, and cardiac beta-adrenoreceptor density was decreased in lesioned rats. After VCS plasma catecholamine concentration was much greater in non-maternally deprived rats than in maternally-deprived rats; cardiac beta-adrenoreceptor density was decreased by VCS in both maternally-deprived and non-deprived rats, but more so in non-deprived rats, and further decreased by the ADTN lesion. In the plus maze test, the number of open arm entries was greater in the maternally deprived and in the stressed rats. Thus, sympathetic-adrenal medullary activation produced by VCS was much greater in non-deprived rats, and was linked to a down regulation of myocardial beta-adrenoceptors. The ADTN are not responsible for the reduced catecholamine responses to stress in maternally-deprived rats. Maternal deprivation or

Plasma IL-8 signature correlates with pain and depressive symptomatology in patients with burning mouth syndrome: Results from a pilot study.

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Barry, Alison; O'Halloran, Ken D; McKenna, Joseph P; McCreary, Christine; Downer, Eric J

2018-02-01

Burning mouth syndrome (BMS) is a neuropathic orofacial pain condition of unknown aetiology that encompasses intra-oral burning pain without abnormal clinical findings. Psychological, neural and inflammatory processes are associated with BMS pathogenesis. Currently, studies characterising plasma cytokine/chemokine profiles with pain and depression in patients with BMS are lacking. Considering that inflammation is associated with the pathophysiology of BMS, and that inflammation is closely associated with pain and depression, we aimed to correlate depressive symptomatology and oral cavity pain with plasma cytokine/chemokine signatures in a cohort of patients with BMS. In this study, plasma protein levels of Th1 cytokines (IFN-γ, IL-2, IL-12p70, TNF-α), Th2 cytokines (IL-4, IL-10, IL-6, IL-13) and the chemokine IL-8 were assessed in patients with BMS (n = 10) and healthy volunteers (n = 10), using pro-inflammatory-10-plex assays. Clinical histories, alongside self-rated oral cavity pain intensities and depressive symptomatology were assessed using a visual analogue scale and the 16-item Quick Inventory of Depressive Symptomatology questionnaires, respectively. We present evidence that BMS is associated with increased depressive symptomatology and enhanced oral cavity pain. Plasma isolated from BMS patients display enhanced expression of the pro-inflammatory chemokine IL-8, when compared to plasma from healthy individuals. Plasma IL-8 signature correlates with pain and depressive symptomatology in the study cohort. Overall, these findings indicate that plasma IL-8 profiles are dysregulated in BMS and that modulation of IL-8 production in the disorder may be a tool in the management of BMS symptomatology. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Expression of Myostatin in Intrauterine Growth Restriction and Preeclampsia Complicated Pregnancies and Alterations to Cytokine Production by First-Trimester Placental Explants Following Myostatin Treatment.

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Peiris, Hassendrini N; Georgiou, Harry; Lappas, Martha; Kaitu'u-Lino, Tu'uhevaha; Salomón, Carlos; Vaswani, Kanchan; Rice, Gregory E; Mitchell, Murray D

2015-10-01

Preeclampsia (PE) and intrauterine growth restriction (IUGR) are major obstetric health problems. Higher levels of T-helper (Th) 1 (proinflammatory) cytokines have been observed in pregnancies complicated with PE and IUGR; this is in contrast to the predominant Th2 (anti-inflammatory) cytokine environment found in uncomplicated pregnancies. Myostatin is best known as a negative regulator of muscle development and reportedly has a role in fat deposition, glucose metabolism, and cytokine modulation (outside the placenta). Myostatin concentrations in plasma and protein expression in placental tissue are significantly higher in women with PE. Expression of myostatin in IUGR and PE-IUGR and the effect of this protein on the cytokine production from the placenta is unknown. In the current study, significant differences were identified in the expression of myostatin in pregnancies complicated with IUGR, PE, and PE with IUGR. Furthermore, cytokine production by first-trimester placental tissues was altered following myostatin treatment. © The Author(s) 2015.

Elevated myeloid-derived suppressor cells in pancreatic, esophageal and gastric cancer are an independent prognostic factor and are associated with significant elevation of the Th2 cytokine interleukin-13.

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Gabitass, Rachel F; Annels, Nicola E; Stocken, Deborah D; Pandha, Hardev A; Middleton, Gary W

2011-10-01

We undertook a comprehensive analysis of circulating myeloid-derived suppressor cells (MDSCs) and T regulatory cells (Tregs) in pancreatic, esophageal and gastric cancer patients and investigated whether MDSCs are an independent prognostic factor for survival. We evaluated a series of plasma cytokines and in particular re-evaluated the Th2 cytokine interleukin-13 (IL-13). Peripheral blood was collected from 131 cancer patients (46 pancreatic, 60 esophageal and 25 gastric) and 54 healthy controls. PBMC were harvested with subsequent flow cytometric analysis of MDSC (HLADR(-) Lin1(low/-) CD33(+) CD11b(+)) and Treg (CD4(+) CD25(+) CD127(low/-) FoxP3(+)) percentages. Plasma IL-2, IL-4, IL-5, IL-6, IL-10, IL-12 (p70), IL-13, IL-17, G-CSF, IFN-γ, TNF-α and VEGF levels were analyzed by the Bio-Plex cytokine assay. Plasma arginase I levels were analyzed by ELISA. MDSCs and Tregs were statistically significantly elevated in pancreatic, esophageal and gastric cancer compared with controls, and MDSC numbers correlated with Treg levels. Increasing MDSC percentage was associated with increased risk of death, and in a multivariate analysis, MDSC level was an independent prognostic factor for survival. A unit increase in MDSC percentage was associated with a 22% increased risk of death (hazard ratio 1.22, 95% confidence interval 1.06-1.41). Arginase I levels were also statistically significantly elevated in upper gastrointestinal cancer patients compared with controls. There was Th2 skewing for cytokine production in all three diseases, and importantly there were significant elevations of the pivotal Th2 cytokine interleukin-13, an increase that correlated with MDSC levels.

Influence of maternal diet during early pregnancy on the fatty acid profile in the fetus at late pregnancy in rats.

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Fernandes, Flavia Spreafico; Tavares do Carmo, Maria das Graças; Herrera, Emilio

2012-05-01

The aim of the study was to determine the effects of different dietary fatty acids during the first half of pregnancy on the fatty acid composition of maternal adipose tissue and of maternal and fetal plasma at mid- and late-pregnancy. Pregnant rats received soybean-, olive-, fish-, linseed- or palm-oil diets from conception to day 12 of gestation. Virgin rats receiving the same treatments were studied in parallel. At day 12, some rats were sacrificed and others were returned to the standard diet and studied at day 20. At day 12, the concentrations of most fatty acids in plasma reflected the dietary composition and individual fatty acids in lumbar adipose tissue of pregnant rats correlated with those in the diet. At day 20, the plasma concentration of each fatty acid was higher in pregnant than in both virgin rats and day-12 pregnant rats. The composition in 20-day pregnant (but not in virgin) rats resembled the diet consumed during the first 12 days. Fatty acid concentration in fetal plasma was also influenced by the maternal diet during the first 12 days of pregnancy, and long-chain polyunsaturated fatty acid (LC-PUFA) concentrations correlated with those in the mothers. In conclusion, during the first half of pregnancy maternal adipose tissue stores dietary-derived fatty acids, which are released into blood during late pregnancy enabling LC-PUFA to become available to the fetus.

Chronic Consumption of Sweeteners and Its Effect on Glycaemia, Cytokines, Hormones, and Lymphocytes of GALT in CD1 Mice

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Cristian Angel Rosales-Gómez

2018-01-01

Full Text Available Background. The consumption of sweeteners has increased in recent years, being used to control body weight and blood glucose. However, they can cause increased appetite, modification of immune function, and secretion of hormones in the GALT. Objective. To assess the effect of chronic sweetener consumption on glycaemia, cytokines, hormones, and GALT lymphocytes in CD1 mice. Material and Methods. 72 CD1 mice divided into 3 groups were used: (a baseline, (b middle, and (c final. Groups (b and (c were divided into 4 subgroups: (i Control, (ii Sucrose, (iii Sucralose, and (iv Stevia. The following were determined: body weight, hormones (GIP, insulin, and leptin, lymphocytes CD3+T cells and CD19+B cells, IgA+ plasma cells, and cytokines (IL-4, IL-5, IFN-γ, and TNF-α. Results. Sucralose reduces secretion of GIP and glycaemia but does not modify insulin concentration, increases body weight, and reduces food intake. Stevia increases the secretion of GIP, insulin, leptin, body weight, and glycaemia but keeps food consumption normal. Sucralose and Stevia showed a higher percentage of CD3+T cells, CD19+B cells, and IgA+ plasma cells in Peyer’s patches, but only Stevia in lamina propria. Conclusion. Sweeteners modulate the hormonal response of cytokines and the proliferation of lymphocytes in the intestinal mucosa.

Chronic Consumption of Sweeteners and Its Effect on Glycaemia, Cytokines, Hormones, and Lymphocytes of GALT in CD1 Mice

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Ramírez-Durán, Ninfa

2018-01-01

Background The consumption of sweeteners has increased in recent years, being used to control body weight and blood glucose. However, they can cause increased appetite, modification of immune function, and secretion of hormones in the GALT. Objective To assess the effect of chronic sweetener consumption on glycaemia, cytokines, hormones, and GALT lymphocytes in CD1 mice. Material and Methods 72 CD1 mice divided into 3 groups were used: (a) baseline, (b) middle, and (c) final. Groups (b) and (c) were divided into 4 subgroups: (i) Control, (ii) Sucrose, (iii) Sucralose, and (iv) Stevia. The following were determined: body weight, hormones (GIP, insulin, and leptin), lymphocytes CD3+T cells and CD19+B cells, IgA+ plasma cells, and cytokines (IL-4, IL-5, IFN-γ, and TNF-α). Results Sucralose reduces secretion of GIP and glycaemia but does not modify insulin concentration, increases body weight, and reduces food intake. Stevia increases the secretion of GIP, insulin, leptin, body weight, and glycaemia but keeps food consumption normal. Sucralose and Stevia showed a higher percentage of CD3+T cells, CD19+B cells, and IgA+ plasma cells in Peyer's patches, but only Stevia in lamina propria. Conclusion Sweeteners modulate the hormonal response of cytokines and the proliferation of lymphocytes in the intestinal mucosa. PMID:29854725

Maternal-fetal cholesterol transport in the second half of mouse pregnancy does not involve LDL receptor-related protein 2.

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Zwier, M V; Baardman, M E; van Dijk, T H; Jurdzinski, A; Wisse, L J; Bloks, V W; Berger, R M F; DeRuiter, M C; Groen, A K; Plösch, T

2017-08-01

LDL receptor-related protein type 2 (LRP2) is highly expressed on both yolk sac and placenta. Mutations in the corresponding gene are associated with severe birth defects in humans, known as Donnai-Barrow syndrome. We here characterized the contribution of LRP2 and maternal plasma cholesterol availability to maternal-fetal cholesterol transport and fetal cholesterol levels in utero in mice. Lrp2 +/- mice were mated heterozygously to yield fetuses of all three genotypes. Half of the dams received a 0.5% probucol-enriched diet during gestation to decrease maternal HDL cholesterol. At E13.5, the dams received an injection of D7-labelled cholesterol and were provided with 1- 13 C acetate-supplemented drinking water. At E16.5, fetal tissues were collected and maternal cholesterol transport and fetal synthesis quantified by isotope enrichments in fetal tissues by GC-MS. The Lrp2 genotype did not influence maternal-fetal cholesterol transport and fetal cholesterol. However, lowering of maternal plasma cholesterol levels by probucol significantly reduced maternal-fetal cholesterol transport. In the fetal liver, this was associated with increased cholesterol synthesis rates. No indications were found for an interaction between the Lrp2 genotype and maternal probucol treatment. Maternal-fetal cholesterol transport and endogenous fetal cholesterol synthesis depend on maternal cholesterol concentrations but do not involve LRP2 in the second half of murine pregnancy. Our results suggest that the mouse fetus can compensate for decreased maternal cholesterol levels. It remains a relevant question how the delicate system of cholesterol transport and synthesis is regulated in the human fetus and placenta. © 2016 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

Modulation of cytokine and cytokine receptor/antagonist by treatment with doxycycline and tetracycline in patients with dengue fever.

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Castro, J E Z; Vado-Solis, I; Perez-Osorio, C; Fredeking, T M

2011-01-01

Dengue virus infection can lead to dengue fever (DF) or dengue hemorrhagic fever (DHF). Disease severity has been linked to an increase in various cytokine levels. In this study, we evaluated the effectiveness of doxycycline and tetracycline to modulate serum levels of IL-6, IL-1B, and TNF and cytokine receptor/receptor antagonist TNF-R1 and IL-1RA in patients with DF or DHF. Hospitalized patients were randomized to receive standard supportive care or supportive care combined with doxycycline or tetracycline therapy. Serum cytokine and cytokine receptor/antagonist levels were determined at the onset of therapy and after 3 and 7 days. Cytokine and cytokine receptor/antagonist levels were substantially elevated at day 0. IL-6, IL-1β, and TNF remained at or above day 0 levels throughout the study period in untreated patients. Treatment with tetracycline or doxycycline resulted in a significant decline in cytokine levels. Similarly, IL-1RA and TNF-R1 serum concentrations were elevated at baseline and showed a moderate increase among untreated patients. Both drugs resulted in a significant rise in IL-1Ra levels by day 3 in patients. In contrast, treatment did not affect a similar result for TNF-R1. When compared to the control group, however, a significant rise post-treatment was seen upon intragroup analysis. Further analysis demonstrated that doxycycline was significantly more effective at modulating cytokine and cytokine receptor/antagonist levels than tetracycline.

Exposure to DEHP decreased four fatty acid levels in plasma of prepartum mice

International Nuclear Information System (INIS)

Nakashima, Ryosuke; Hayashi, Yumi; Khalequzzaman, Md.; Jia, Xiaofang; Wang, Dong; Naito, Hisao; Ito, Yuki; Kamijima, Michihiro; Gonzalez, Frank J.; Nakajima, Tamie

2013-01-01

Maternal exposure to di(2-ethylhexyl) phthalate (DEHP) decreased the plasma triglyceride in prepartum mice. To identify the fatty acid (FA) species involved and to understand the underlying mechanisms, pregnant Sv/129 wild-type (mPPARα), peroxisome proliferator-activated receptor α-null (Pparα-null) and humanized PPARα (hPPARα) mice were treated with diets containing 0%, 0.01%, 0.05% or 0.1% DEHP. Dams were dissected on gestational day 18 together with fetuses, and on postnatal day 2 together with newborns. n-3/n-6 polyunsaturated, saturated, and monounsaturated FAs in maternal plasma and in liver of wild-type offspring, and representative enzymes for FA desaturation and elongation in maternal liver, were measured. The plasma levels of linoleic acid, α-linolenic acid, palmitic acid and oleic acid were higher in the pregnant control mPPARa mice than in Ppara-null and hPPARa mice. DEHP exposure significantly decreased the levels of these four FAs only in pregnant mPPARα mice. Plasma levels of many FAs were higher in pregnant mice than in postpartum ones in a genotype-independent manner, while it was lower in the livers of fetuses than pups. DEHP exposure slightly increased hepatic arachidonic acid, α-linolenic acid, palmitoleic acid and oleic acid in fetuses, but not in pups. However, DEHP exposure did not clearly influence FA desaturase 1 and 2 nor elongase 2 and 5 expressions in the liver of all maternal mice. Taken together, the levels of plasma four FAs with shorter carbon chains were higher in pregnant mPPARα mice than in other genotypes, and DEHP exposure decreased these specific FA concentrations only in mPPARα mice, similarly to triglyceride levels

Cytokine balance in human malaria: does Plasmodium vivax elicit more inflammatory responses than Plasmodium falciparum?

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Raquel M Gonçalves

Full Text Available BACKGROUND: The mechanisms by which humans regulate pro- and anti-inflammatory responses on exposure to different malaria parasites remains unclear. Although Plasmodium vivax usually causes a relatively benign disease, this parasite has been suggested to elicit more host inflammation per parasitized red blood cell than P. falciparum. METHODOLOGY/PRINCIPAL FINDINGS: We measured plasma concentrations of seven cytokines and two soluble tumor necrosis factor (TNF-α receptors, and evaluated clinical and laboratory outcomes, in Brazilians with acute uncomplicated infections with P. vivax (n = 85, P. falciparum (n = 30, or both species (n = 12, and in 45 asymptomatic carriers of low-density P. vivax infection. Symptomatic vivax malaria patients, compared to those infected with P. falciparum or both species, had more intense paroxysms, but they had no clear association with a pro-inflammatory imbalance. To the contrary, these patients had higher levels of the regulatory cytokine interleukin (IL-10, which correlated positively with parasite density, and elevated IL-10/TNF-α, IL-10/interferon (IFN-γ, IL-10/IL-6 and sTNFRII/TNF-α ratios, compared to falciparum or mixed-species malaria patient groups. Vivax malaria patients had the highest levels of circulating soluble TNF-α receptor sTNFRII. Levels of regulatory cytokines returned to normal values 28 days after P. vivax clearance following chemotherapy. Finally, asymptomatic carriers of low P. vivax parasitemias had substantially lower levels of both inflammatory and regulatory cytokines than did patients with clinical malaria due to either species. CONCLUSIONS: Controlling fast-multiplying P. falciparum blood stages requires a strong inflammatory response to prevent fulminant infections, while reducing inflammation-related tissue damage with early regulatory cytokine responses may be a more cost-effective strategy in infections with the less virulent P. vivax parasite. The early induction

Maternal thyroid hormones enhance hatching success but decrease nestling body mass in the rock pigeon (Columba livia).

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Hsu, Bin-Yan; Dijkstra, Cor; Darras, Veerle M; de Vries, Bonnie; Groothuis, Ton G G

2017-01-01

Thyroid hormones (THs) - triiodothyronine (T3) and thyroxine (T4) - are essential for embryonic development in vertebrates. All vertebrate embryos are exposed to THs from maternal origin. As maternal TH levels are known to be essential to embryonic development, the natural variation of maternal THs probably represents a pathway of maternal effects that can modify offspring phenotype. However, potential fitness consequences of variation of maternal TH exposure within the normal physiological range and without confounding effects of the mother have never been experimentally investigated. We experimentally manipulated the levels of yolk T3 and T4 within the physiological range in a species in which the embryo develops outside the mother's body, the Rock Pigeon (Columba livia) eggs. Making use of the natural difference of yolk testosterone between the two eggs of pigeon clutches, we were also able to investigate the potential interaction between THs and testosterone. Elevated yolk TH levels enhanced embryonic development and hatching success, and reduced body mass but not tarsus length between day 14 and fledging. The yolk hormones increased plasma T4 concentrations in females but reduced it in males, in line with the effect on metabolic rate at hatching. Plasma concentrations of T3 and testosterone were not significantly affected. The effects of treatment did not differ between eggs with high or low testosterone levels. Our data indicate that natural variation in maternal yolk TH levels affects offspring phenotype and embryonic survival, potentially influencing maternal and chick fitness. Copyright © 2016 Elsevier Inc. All rights reserved.

Cytokine Response to Exercise and Its Modulation

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Katsuhiko Suzuki

2018-01-01

Strenuous exercise induces such inflammatory responses as leukocytosis (neutrophilia) and symptoms as delayed-onset muscle soreness and swelling. However, the association between inflammatory mediator cytokines and oxidative stress is not fully delineated. Herein, in addition to basic background information on cytokines, research findings on exertional effects on cytokine release and the underlying mechanisms and triggers are introduced. Then, the associations among cytokine responses, oxidat...

Cytokine signalling in embryonic stem cells

DEFF Research Database (Denmark)

Kristensen, David Møbjerg; Kalisz, Mark; Nielsen, Jens Høiriis

2006-01-01

Cytokines play a central role in maintaining self-renewal in mouse embryonic stem (ES) cells through a member of the interleukin-6 type cytokine family termed leukemia inhibitory factor (LIF). LIF activates the JAK-STAT3 pathway through the class I cytokine receptor gp130, which forms a trimeric...... pathways seem to converge on c-myc as a common target to promote self-renewal. Whereas LIF does not seem to stimulate self-renewal in human embryonic stem cells it cannot be excluded that other cytokines are involved. The pleiotropic actions of the increasing number of cytokines and receptors signalling...... via JAKs, STATs and SOCS exhibit considerable redundancy, compensation and plasticity in stem cells in accordance with the view that stem cells are governed by quantitative variations in strength and duration of signalling events known from other cell types rather than qualitatively different stem...

Increased maternal and fetal cholesterol efflux capacity and placental CYP27A1 expression in preeclampsia.

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Mistry, Hiten D; Kurlak, Lesia O; Mansour, Yosef T; Zurkinden, Line; Mohaupt, Markus G; Escher, Geneviève

2017-06-01

Preeclampsia is a pregnancy-specific condition that leads to increased cardiovascular risk in later life. A decrease in cholesterol efflux capacity is linked to CVD. We hypothesized that in preeclampsia there would be a disruption of maternal/fetal plasma to efflux cholesterol, as well as differences in the concentrations of both placental sterol 27-hydroxylase (CYP27A1) and apoA1 binding protein (AIBP). Total, HDL-, and ABCA1-mediated cholesterol effluxes were performed with maternal and fetal plasma from women with preeclampsia and normotensive controls (both n = 17). apoA1 and apoE were quantified by chemiluminescence, and 27-hydroxycholesterol (27-OHC) by GC-MS. Immunohistochemistry was used to determine placental expression/localization of CYP27A1, AIBP, apoA1, apoE, and SRB1. Maternal and fetal total and HDL-mediated cholesterol efflux capacities were increased in preeclampsia (by 10-20%), but ABCA1-mediated efflux was decreased (by 20-35%; P preeclampsia. Fetal plasma 27-OHC levels were decreased in preeclamptic samples ( P preeclampsia ( P = 0.04). Placental 27-OHC concentrations were also raised in preeclampsia ( P preeclampsia, to remove cholesterol from cells to limit lipid peroxidation and increase placental angiogenesis. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

Respiratory symptoms and ex vivo cytokine release are associated in workers processing herring

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Bønløkke, Jakob Hjort; Thomassen, Mads; Viskum, Sven

2004-01-01

in the plasma by chemiluminescence ELISA. RESULTS: Among smoking fish-factory workers the forced vital capacity (FVC) was higher (per cent predicted 92.0 vs 85.0; P=0.028) than among municipal workers. Fish rinsing water induced WBA IL-8 release to higher levels than LPS and glucan. Among non-smokers...... the induced IL-1beta release for rinsing water ( P=0.007) and the IL-8 release for skin ( P=0.001) and meat ( P=0.003) were higher in fish-factory workers than in municipal workers. The IL-1beta release for rinsing water ( P=0.028) and skin ( P=0.041) was higher among non-smokers than among smokers, and so...... was the IL-8 release for rinsing water ( P=0.008). CONCLUSIONS: Assessing the cytokine release by use of the WBA we identified substances in the occupational environment with a pro-inflammatory potential comparable to that of LPS. The cytokine release for fish constituents was highest among non-smoking fish...

Detection of autoantibodies to cytokines

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Bendtzen, K; Hansen, M B; Ross, C

2000-01-01

Autoantibodies to various cytokines have been reported in normal individuals and in patients with various infectious and immunoinflammatory disorders, and similar antibodies (Ab) may be induced in patients receiving human recombinant cytokines. The clinical relevance of these Ab is often difficul...

Effects of Socio demographic factors on plasma ascorbic acid and alpha tocopherol anti oxidants during pregnancy

International Nuclear Information System (INIS)

Sylvester, I.E.; Paul, A.

2010-01-01

Objectives: To assess the plasma levels of vitamins C and E at the various stages of pregnancy and to correlate their plasma levels with the socio-demographic factors of pregnant Nigerians. Methodology: The pregnant cases (n=180) were randomly selected according to gestational ages. And the controls (n=20) were non-pregnant women of the same age. Plasma levels of both vitamins were assayed with well established laboratory methods. Results: The mean plasma vitamins C and E in the pregnant cases was lower (by 17-23%) than controls across the three trimesters, p<0.0001. The correlation of vitamin C versus maternal age was significant; r = - 0.59, p<0.05; the mean plasma level of vitamin C declined by 57% as the maternal age increases from 22-37 years. Conclusion: The mean plasma Ascorbic acid and Alpha-tocopherol are reduced during pregnancy and socio-demographic factors have mild effects on the plasma levels of these vitamins. (author)

Role of catecholamines in maternal-fetal stress transfer in sheep.

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Rakers, Florian; Bischoff, Sabine; Schiffner, Rene; Haase, Michelle; Rupprecht, Sven; Kiehntopf, Michael; Kühn-Velten, W Nikolaus; Schubert, Harald; Witte, Otto W; Nijland, Mark J; Nathanielsz, Peter W; Schwab, Matthias

2015-11-01

We sought to evaluate whether in addition to cortisol, catecholamines also transfer psychosocial stress indirectly to the fetus by decreasing uterine blood flow (UBF) and increasing fetal anaerobic metabolism and stress hormones. Seven pregnant sheep chronically instrumented with uterine ultrasound flow probes and catheters at 0.77 gestation underwent 2 hours of psychosocial stress by isolation. We used adrenergic blockade with labetalol to examine whether decreased UBF is catecholamine mediated and to determine to what extent stress transfer from mother to fetus is catecholamine dependent. Stress induced transient increases in maternal cortisol and norepinephrine (NE). Maximum fetal plasma cortisol concentrations were 8.1 ± 2.1% of those in the mother suggesting its maternal origin. In parallel to the maternal NE increase, UBF decreased by maximum 22% for 30 minutes (P Fetal NE remained elevated for >2 hours accompanied by a prolonged blood pressure increase (P fetal NE and blood pressure increase and the shift toward anaerobic metabolism. We conclude that catecholamine-induced decrease of UBF is a mechanism of maternal-fetal stress transfer. It may explain the influence of maternal stress on fetal development and on programming of adverse health outcomes in later life especially during early pregnancy when fetal glucocorticoid receptor expression is limited. Copyright © 2015 Elsevier Inc. All rights reserved.

Changes in cytokine and biomarker blood levels in patients with colorectal cancer during dendritic cell-based vaccination

DEFF Research Database (Denmark)

Burgdorf, Stefan; Claesson, Mogens; Nielsen, Hans

2009-01-01

Introduction. Immunotherapy based on dendritic cell vaccination has exciting perspectives for treatment of cancer. In order to clarify immunological mechanisms during vaccination it is essential with intensive monitoring of the responses. This may lead to optimization of treatment and prediction......-inflammatory cytokines in serum of patients who achieved stable disease following vaccination suggest the occurrence of vaccine-induced Th1 responses. Since Th1 responses seem to be essential in cancer immunotherapy this may indicate a therapeutic potential of the vaccine....... of responding patients. The aim of this study was to evaluate cytokine and biomarker responses in patients with colorectal cancer treated with a cancer vaccine based on dendritic cells pulsed with an allogeneic melanoma cell lysate. Material and methods. Plasma and serum samples were collected prior...

Cytokines profile changers after magnetic-heat-vibromassage in chronic abacterial prostatitis with erectile disfunction

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D. G. Коren’kov

2016-01-01

Full Text Available The aim of the study was to examine the influence of magnetic-heat-vibromassage procedure in treatment of 27 patients with chronic abacterial prostatitis with erectile dysfunction, by mean of transrectal electrodes application of MAVIT® apparatus (ULP-01-“ELAT”. In the prostatic gland (PG media and blood plasma the pro-inflammatory cytokine concentrations was investigated. PG hemodynamic, and erectile dysfunction also was determined. Control group was presented by 10 healthy males (23–45 years old. Measurements were done before treatment, and after 10 procedures of PG massage, and 30 days after procedure.It was shown that chronic abacterial prostatitis with erectile dysfunction with low clinical performance is supported by pro-inflammatory cytokines produced by the PG. The usage of magnetic-heat-vibromassage procedure increased prostatic microcirculation, as well as testosterone level, and improved the erectile dysfunction in all 27 patients enrolled into the study

Maternal obesity and high-fat diet program offspring metabolic syndrome.

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Desai, Mina; Jellyman, Juanita K; Han, Guang; Beall, Marie; Lane, Robert H; Ross, Michael G

2014-09-01

We determined the potential programming effects of maternal obesity and high-fat (HF) diet during pregnancy and/or lactation on offspring metabolic syndrome. A rat model of maternal obesity was created using an HF diet prior to and throughout pregnancy and lactation. At birth, pups were cross-fostered, thereby generating 4 paradigms of maternal diets during pregnancy/lactation: (1) control (Con) diet during pregnancy and lactation (Con/Con), (2) HF during pregnancy and lactation (HF/HF), (3) HF during pregnancy alone (HF/Con), and (4) HF during lactation alone (Con/HF). Maternal phenotype during pregnancy and the end of lactation evidenced markedly elevated body fat and plasma corticosterone levels in HF dams. In the offspring, the maternal HF diet during pregnancy alone programmed increased offspring adiposity, although with normal body weight, whereas the maternal HF diet during lactation increased both body weight and adiposity. Metabolic disturbances, particularly that of hyperglycemia, were apparent in all groups exposed to the maternal HF diet (during pregnancy and/or lactation), although differences were apparent in the manifestation of insulin resistant vs insulin-deficient phenotypes. Elevated systolic blood pressure was manifest in all groups, implying that exposure to an obese/HF environment is disadvantageous for offspring health, regardless of pregnancy or lactation periods. Nonetheless, the underlying mechanism may differ because offspring that experienced in utero HF exposure had increased corticosterone levels. Maternal obesity/HF diet has a marked impact on offspring body composition and the risk of metabolic syndrome was dependent on the period of exposure during pregnancy and/or lactation. Copyright © 2014 Mosby, Inc. All rights reserved.

Maternally derived anti-fibroblast growth factor 23 antibody as new tool to reduce phosphorus requirement of chicks.

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Ren, Zhouzheng; Bütz, Daniel E; Sand, Jordan M; Cook, Mark E

2017-04-01

Novel means to reduce phosphate input into poultry feeds and increase its retention would preserve world phosphate reserves and reduce environmental impact of poultry production. Here we show that a maternally derived antibody to a fibroblast growth factor-23 (FGF-23) peptide (GMNPPPYS) alleviated phosphorus deficiency in chicks fed low non-phytate phosphorus (nPP) diets. White Leghorn laying hens were vaccinated with either an adjuvant control or the synthetic FGF-23 peptide, and chicks with control or anti-FGF-23 maternal antibodies were fed a diet containing either 0.13 or 0.45% nPP (experiment 1), and 0.20 or 0.45% nPP (experiment 2) for 14 d. In both experiments, decreasing nPP from 0.45 to 0.13 or 0.20% decreased BW gain, G:F, excreta phosphorus, plasma phosphate, and plasma FGF-23 at all time periods examined (nPP main effect, P posture scores (d 7, 14) and bone lesion scores (d 14) decreased and plasma phosphate (d 14) increased in anti-FGF-23 chicks fed 0.13% nPP, compared to those with control antibody on the same diet (P < 0.05). In experiment 2, chicks with maternal anti-FGF-23 antibody had increased tibiotarsi ash (d 14), and plasma phosphate (d 14) and 1,25(OH)2D3 (d 14) levels, compared to chicks with control antibody (antibody main effect, P < 0.05). BW gain and G:F were increased in chicks with anti-FGF-23 antibody fed 0.20% nPP, compared to control antibody chicks on the same diet, at all time periods examined (P < 0.05). In conclusion, maternally-derived anti-FGF-23 antibody increased phosphorus retention in chicks fed diets containing either 0.13 or 0.20% nPP and thereby, reduced signs of phosphorus deficiency. © 2016 Poultry Science Association Inc.

Cytokines, cytokine antagonists, and soluble adhesion molecules in pediatric OMS and other neuroinflammatory disorders.

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Pranzatelli, Michael R; Tate, Elizabeth D; McGee, Nathan R; Colliver, Jerry A

2013-03-15

To test for hypothesized disease- and treatment-induced changes in cytokines and adhesion molecules in children with opsoclonus-myoclonus syndrome (OMS). Multiplex bead assay technology was used for simultaneous measurement of 34 soluble cytokines in cerebrospinal fluid (CSF) and serum. Soluble intercellular adhesion molecule-1 (sICAM-1) and vascular cell adhesion molecule-1 (sVCAM-1) were measured by ELISA. In total, there were 388 children (239 OMS, 114 controls, and 35 other inflammatory neurological disorders (OIND)). In untreated OMS, mean CSF IL-6 was elevated 2.3-fold, but 67-fold in OIND, without significant differences in other CSF cytokines. Mean serum concentrations of sIL-2Ra (+50%) and CXCL1 (+70%) (pOMS than controls (p=0.005), as was serum CCL11 and IL-13 in treated OMS. Mean CSF CCL4 and IL-1Ra were selectively higher in IVIg-treated OMS (p≤0.0001). CSF sICAM-1 was elevated only in OIND (3.3-fold); serum sICAM-1 was higher in untreated OMS (+21%); and sVCAM-1 was not affected. No correlations with OMS severity or duration were identified. Novel cytokine, cytokine antagonist, and soluble adhesion molecule abnormalities due to OMS or treatment were found. However, the normality of much of the data strengthens previous findings implicating B cell mechanisms. Copyright © 2013 Elsevier B.V. All rights reserved.

Principal component analysis identifies patterns of cytokine expression in non-small cell lung cancer patients undergoing definitive radiation therapy.

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Susannah G Ellsworth

Full Text Available Radiation treatment (RT stimulates the release of many immunohumoral factors, complicating the identification of clinically significant cytokine expression patterns. This study used principal component analysis (PCA to analyze cytokines in non-small cell lung cancer (NSCLC patients undergoing RT and explore differences in changes after hypofractionated stereotactic body radiation therapy (SBRT and conventionally fractionated RT (CFRT without or with chemotherapy.The dataset included 141 NSCLC patients treated on prospective clinical protocols; PCA was based on the 128 patients who had complete CK values at baseline and during treatment. Patients underwent SBRT (n = 16, CFRT (n = 18, or CFRT (n = 107 with concurrent chemotherapy (ChRT. Levels of 30 cytokines were measured from prospectively collected platelet-poor plasma samples at baseline, during RT, and after RT. PCA was used to study variations in cytokine levels in patients at each time point.Median patient age was 66, and 22.7% of patients were female. PCA showed that sCD40l, fractalkine/C3, IP10, VEGF, IL-1a, IL-10, and GMCSF were responsible for most variability in baseline cytokine levels. During treatment, sCD40l, IP10, MIP-1b, fractalkine, IFN-r, and VEGF accounted for most changes in cytokine levels. In SBRT patients, the most important players were sCD40l, IP10, and MIP-1b, whereas fractalkine exhibited greater variability in CFRT alone patients. ChRT patients exhibited variability in IFN-γ and VEGF in addition to IP10, MIP-1b, and sCD40l.PCA can identify potentially significant patterns of cytokine expression after fractionated RT. Our PCA showed that inflammatory cytokines dominate post-treatment cytokine profiles, and the changes differ after SBRT versus CFRT, with vs without chemotherapy. Further studies are planned to validate these findings and determine the clinical significance of the cytokine profiles identified by PCA.

Cytokines and uveitis, a review

NARCIS (Netherlands)

de Vos, A. F.; Hoekzema, R.; Kijlstra, A.

1992-01-01

Although the exact pathogenic mechanisms underlying uveitis are unknown, cytokines appear to be involved in this inflammatory disorder. This review describes the studies in which the uveitogenic properties of several cytokines, including tumor necrosis factor (TNF), interleukin 1 (IL-1), IL-6, IL-8

Noninvasive determination of fetal rh blood group, D antigen status by cell-free DNA analysis in maternal plasma: experience in a Brazilian population.

Science.gov (United States)

Chinen, Paulo Alexandre; Nardozza, Luciano Marcondes Machado; Martinhago, Ciro Dresch; Camano, Luiz; Daher, Silvia; Pares, David Baptista da Silva; Minett, Thais; Araujo Júnior, Edward; Moron, Antonio Fernandes

2010-11-01

We evaluated the diagnostic accuracy of Rh blood group, D antigen (RHD) fetal genotyping, using real-time polymerase chain reaction in maternal blood samples, in a racially mixed population. We performed a prospective study conducted between January 2006 and December 2007, analyzing fetal RHD genotype in the plasma of 102 D- pregnant women by real-time polymerase chain reaction, targeting exons 7 and 10 of the RHD gene. Genotype results were compared with cord blood phenotype obtained after delivery or before the first intrauterine transfusion when necessary. Most of the participants (75.5%) were under 28 weeks of pregnancy, and 87.5% had at least one relative of black ancestry. By combining amplification of two exons, the accuracy of genotyping was 98%, sensitivity was 100%, and specificity was 92%. The positive likelihood ratio was 12.5, and the negative likelihood ratio was 0. The two false-positive cases were confirmed to be pseudogene RHD by real-time polymerase chain reaction. There were no differences between the patients with positive or negative Coombs test ( P = 0.479). Determination of fetal RHD status in maternal peripheral blood was highly sensitive in this racially mixed population and was not influenced by the presence of antierythrocyte antibodies. © Thieme Medical Publishers.

IgG levels in mother-father-cord trios: evidence for a large reduction of maternal IgG at birth

Energy Technology Data Exchange (ETDEWEB)

Williams, R C; Gershowitz, H

1979-01-01

Cord plasmas have a higher concentration of IgG than do the mothers, although autologous, fetal immunoglobulin G is only a small fraction of the neonate's complement. Maternal IgG levels are significantly lower than the nonpregnant adult female, a loss of about one third, which cannot be explained completely by maternal immunization of the fetus.

Prediction of Radiation Esophagitis in Non–Small Cell Lung Cancer Using Clinical Factors, Dosimetric Parameters, and Pretreatment Cytokine Levels

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Peter G. Hawkins

2018-02-01

Full Text Available Radiation esophagitis (RE is a common adverse event associated with radiotherapy for non–small cell lung cancer (NSCLC. While plasma cytokine levels have been correlated with other forms of radiation-induced toxicity, their association with RE has been less well studied. We analyzed data from 126 patients treated on 4 prospective clinical trials. Logistic regression models based on combinations of dosimetric factors [maximum dose to 2 cubic cm (D2cc and generalized equivalent uniform dose (gEUD], clinical variables, and pretreatment plasma levels of 30 cytokines were developed. Cross-validated estimates of area under the receiver operating characteristic curve (AUC and log likelihood were used to assess prediction accuracy. Dose-only models predicted grade 3 RE with AUC values of 0.750 (D2cc and 0.727 (gEUD. Combining clinical factors with D2cc increased the AUC to 0.779. Incorporating pretreatment cytokine measurements, modeled as direct associations with RE and as potential interactions with the dose-esophagitis association, produced AUC values of 0.758 and 0.773, respectively. D2cc and gEUD correlated with grade 3 RE with odds ratios (ORs of 1.094/Gy and 1.096/Gy, respectively. Female gender was associated with a higher risk of RE, with ORs of 1.09 and 1.112 in the D2cc and gEUD models, respectively. Older age was associated with decreased risk of RE, with ORs of 0.992/year and 0.991/year in the D2cc and gEUD models, respectively. Combining clinical with dosimetric factors but not pretreatment cytokine levels yielded improved prediction of grade 3 RE compared to prediction by dose alone. Such multifactorial modeling may prove useful in directing radiation treatment planning.

Relationship of cytokines and cytokine signaling to immunodeficiency disorders in the mouse

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Morawetz R.A.

1998-01-01

Full Text Available The contributions of cytokines to the development and progression of disease in a mouse model of retrovirus-induced immunodeficiency (MAIDS are controversial. Some studies have indicated an etiologic role for type 2 cytokines, while others have emphasized the importance of type 1 cytokines. We have used mice deficient in expression of IL-4, IL-10, IL-4 and IL-10, IFN-g, or ICSBP - a transcriptional protein involved in IFN signaling - to examine their contributions to this disorder. Our results demonstrate that expression of type 2 cytokines is an epiphenomenon of infection and that IFN-g is a driving force in disease progression. In addition, exogenously administered IL-12 prevents many manifestations of disease while blocking retrovirus expression. Interruption of the IFN signaling pathways in ICSBP-/- mice blocks induction of MAIDS. Predictably, ICSBP-deficient mice exhibit impaired responses to challenge with several other viruses. This immunodeficiency is associated with impaired production of IFN-g and IL-12. Unexpectedly, however, the ICSBP-/- mice also develop a syndrome with many similarities to chronic myelogenous leukemia in humans. The chronic phase of this disease is followed by a fatal blast crisis characterized by clonal expansions of undifferentiated cells. ICSBP is thus an important determinant of hematopoietic growth and differentiation as well as a prominent signaling molecule for IFNs

Magnetic resonance imaging determined visceral fat reduction associates with enhanced IL-10 plasma levels in calorie restricted obese subjects.

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Gloria Formoso

Full Text Available BACKGROUND: Obesity is characterized by a low grade chronic inflammation state. Indeed circulating pro-inflammatory cytokines, such as TNF-α and IL-6, are elevated in obese subjects, while anti-inflammatory cytokines, such as IL-10, appear to be reduced. Cytokines profile improves after weight loss, but how visceral or subcutaneous fat loss respectively affect pro- or anti-inflammatory cytokines plasma levels has not been precisely assessed. Therefore in the present study we correlated changes in circulating cytokine profile with quantitative changes in visceral and subcutaneous adipose tissue depots measured by an ad hoc Magnetic Resonance Imaging (MRI protocol before and after weight loss. MATERIALS AND METHODS: In 14 obese subjects, MRI determination of visceral and subcutaneous fat and plasma glucose, insulin, TNF-α IL-6, and IL-10 measurements were performed before and after a caloric restriction induced weight loss of at least 5% of the original body weight. RESULTS: Weight loss improved insulin sensitivity (QUICKI Index: 0.35±0.03 vs 0.37±0.04; P<0.05, increased IL-10 (3.4±1.9 vs 4.6±1.0 pg/mL; P<0.03, and reduced TNF-α and IL-6 plasma levels (2.5±1.3 vs 1.6±1.5 pg/mL, P<0.0015, 2.3±0.4 vs 1.6±0.6 pg/mL, P<0.02 respectively. A significant correlation was observed between the amount of visceral fat loss and the percentage reduction in both TNF-α (r = 0.56, p<0.05 and IL-6 (r = 0.19 p<0.05 plasma levels. In a multiple regression analysis, the amount of visceral fat loss independently correlated with the increase in IL-10 plasma levels. CONCLUSION: The reduction in visceral adipose tissue is the main driver of the improved inflammatory profile induced by weight loss.

Irisin Maternal Plasma and Cord Blood Levels in Mothers with Spontaneous Preterm and Term Delivery

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Tereza Pavlova

2018-01-01

Full Text Available Irisin, an adipomyokine identified in 2012, has been investigated in association with common pregnancy complications, including gestational diabetes mellitus, preeclampsia, and intrauterine growth restriction. The objective of this study is to examine the potential role of irisin in preterm birth (PTB by comparing its level between mothers with term and preterm labor. Maternal peripheral blood and cord blood samples were collected from 30 mothers who delivered prematurely and from 35 mothers who delivered at term. Irisin concentrations were measured in all samples using ELISA, and four common single nucleotide polymorphisms in the irisin gene were determined (rs16835198, rs726344, rs3480, and rs1746661. Univariable and multivariable regression modeling was applied to evaluate maternal and cord blood irisin concentrations in relation to preterm/term labor. Irisin concentration in umbilical cord blood was found to be associated with PTB in the univariable model (p=0.046. On the other hand, no differences in maternal blood irisin levels between mothers with preterm and term deliveries were established. To the best of our knowledge, this is the first study determining irisin levels in term and preterm deliveries in maternal peripheral blood and umbilical cord blood. Our study shows a possible association between cord blood irisin concentration and PTB occurrence.

Placental adaptations to the maternal-fetal environment: implications for fetal growth and developmental programming.

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Sandovici, Ionel; Hoelle, Katharina; Angiolini, Emily; Constância, Miguel

2012-07-01

The placenta is a transient organ found in eutherian mammals that evolved primarily to provide nutrients for the developing fetus. The placenta exchanges a wide array of nutrients, endocrine signals, cytokines and growth factors with the mother and the fetus, thereby regulating intrauterine development. Recent studies show that the placenta is not just a passive organ mediating maternal-fetal exchange. It can adapt its capacity to supply nutrients in response to intrinsic and extrinsic variations in the maternal-fetal environment. These dynamic adaptations are thought to occur to maximize fetal growth and viability at birth in the prevailing conditions in utero. However, some of these adaptations may also affect the development of individual fetal tissues, with patho-physiological consequences long after birth. Here, this review summarizes current knowledge on the causes, possible mechanisms and consequences of placental adaptive responses, with a focus on the regulation of transporter-mediated processes for nutrients. This review also highlights the emerging roles that imprinted genes and epigenetic mechanisms of gene regulation may play in placental adaptations to the maternal-fetal environment. Copyright © 2012 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Ancestry dependent DNA methylation and influence of maternal nutrition.

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Khyobeni Mozhui

Full Text Available There is extensive variation in DNA methylation between individuals and ethnic groups. These differences arise from a combination of genetic and non-genetic influences and potential modifiers include nutritional cues, early life experience, and social and physical environments. Here we compare genome-wide DNA methylation in neonatal cord blood from African American (AA; N = 112 and European American (EA; N = 91 participants of the CANDLE Study (Conditions Affecting Neurocognitive Development and Learning in Early Childhood. Our goal is to determine if there are replicable ancestry-specific methylation patterns that may implicate risk factors for diseases that have differential prevalence between populations. To identify the most robust ancestry-specific CpG sites, we replicate our results in lymphoblastoid cell lines from Yoruba African and CEPH European panels of HapMap. We also evaluate the influence of maternal nutrition--specifically, plasma levels of vitamin D and folate during pregnancy--on methylation in newborns. We define stable ancestry-dependent methylation of genes that include tumor suppressors and cell cycle regulators (e.g., APC, BRCA1, MCC. Overall, there is lower global methylation in African ancestral groups. Plasma levels of 25-hydroxy vitamin D are also considerably lower among AA mothers and about 60% of AA and 40% of EA mothers have concentrations below 20 ng/ml. Using a weighted correlation analysis, we define a network of CpG sites that is jointly modulated by ancestry and maternal vitamin D. Our results show that differences in DNA methylation patterns are remarkably stable and maternal micronutrients can exert an influence on the child epigenome.

Maternal hyperthyroidism is associated with a decreased incidence of cold-induced ascites in broiler chickens.

Science.gov (United States)

Akhlaghi, A; Zamiri, M J; Zare Shahneh, A; Jafari Ahangari, Y; Nejati Javaremi, A; Rahimi Mianji, G; Mollasalehi, M R; Shojaie, H; Akhlaghi, A A; Deldar, H; Atashi, H; Ansari Pirsaraei, Z; Zhandi, M

2012-05-01

A hypothesis was tested that providing the breeder hens with exogenous thyroxine (T(4)) would help their offspring to better survive the ascites-inducing condition during the growing period. In total, 132 broiler breeder hens were randomly assigned to one of 3 treatments: control (CON), hypothyroid [HYPO; 6-N-propyl-2-thiouracil (PTU)-treated], and hyperthyroid (HYPER; T(4)-treated). The hens were artificially inseminated, and the hatching eggs (n = 1,320) were incubated. No eggs in the HYPO group hatched. The 1-d-old male chicks (n = 288) from other groups were reared for 42 d under standard or low ambient temperature to induce ascites. Blood samples were drawn from the hens, embryos, and broilers for determination of T(4) and triiodothyronine (T(3)). The hematocrit was also determined in broilers. The PTU-treated hens had an increased BW along with lower plasma T(3) and T(4) concentrations. Plasma T(4) was higher in the HYPER hens compared with CON hens, but T(3) concentration was not different between these groups. The fertility rate was not affected by either hypo- or hyperthyroidism. The embryos in the HYPO group had lower plasma T(3) and T(4) concentrations at d 18 of embryonic development and internal pipping. Higher plasma T(4) was recorded in the HYPER birds at internal pipping, although plasma T(3) concentration was not affected at this stage. Maternal hyperthyroidism decreased the overall incidence of ascites in the cold-exposed chickens (10.0 vs. 33.4% for HYPER and CON groups, respectively). Although the effect of maternal PTU or T(4) treatment on plasma thyroid hormones and on the right ventricle-to-total ventricular weight ratio in the broilers was not significant, the cold-exposed healthy CON chicks showed higher hematocrit values, compared with the HYPER birds. It was concluded that maternal hyperthyroidism could decrease the incidence of cold-induced ascites in broiler chickens; however, probable causal mechanisms remain to be elucidated.

Maternal peanut exposure during pregnancy and lactation reduces peanut allergy risk in offspring.

Science.gov (United States)

López-Expósito, Iván; Song, Ying; Järvinen, Kirsi M; Srivastava, Kamal; Li, Xiu-Min

2009-11-01

Maternal allergy is believed to be a risk factor for peanut allergy (PNA) in children. However, there is no direct evidence of maternal transmission of PNA susceptibility, and it is unknown whether maternal peanut exposure affects the development of PNA in offspring. To investigate the influence of maternal PNA on offspring reactions to the first peanut exposure, and whether maternal low-dose peanut exposure during pregnancy and lactation influences these reactions and peanut sensitization in a murine model. Five-week-old offspring of PNA C3H/HeJ mothers (PNA-Ms) were challenged intragastrically with peanut (first exposure), and reactions were determined. In a subset of the experiment, PNA-Ms were fed a low dose of peanut (PNA-M/PN) or not fed peanut (PNA-M/none) during pregnancy and lactation. Their 5-week-old offspring were challenged intragastrically with peanut, and reactions were determined. In another subset of the experiment, offspring of PNA-M/PN or PNA-M/none were sensitized with peanut intragastrically for 6 weeks, and serum peanut-specific antibodies were determined. PNA-M offspring exhibited anaphylactic reactions at first exposure to peanut that were associated with peanut-specific IgG(1) levels and prevented by a platelet activation factor antagonist. In a subset experiment, PNA-M/PN offspring showed significantly reduced first-exposure peanut reactions, increased IgG(2a), and reduced mitogen-stimulated splenocyte cytokine production compared with PNA-M/none offspring. In an additional experiment, PNA-M/PN offspring showed reduction of peanut-specific IgE to active peanut sensitization. We show for the first time maternal transmission of susceptibility to first-exposure peanut reactions and active peanut sensitization. Low-dose peanut exposure during pregnancy and lactation reduced this risk.

The role of single nucleotide polymorphism of IL-6 and IL-10 cytokine on pain severity and pain relief after radiotherapy in multiple myeloma patients with painful bone destructions

OpenAIRE

Rudzianskiene Milda; Inciura Arturas; Juozaityte Elona; Gerbutavicius Rolandas; Simoliuniene Renata; Ugenskiene Rasa; Raulinaityte Danguole; Rudzianskas Viktoras; Kiavialaitis Greta Emilia

2014-01-01

Multiple myeloma (MM) cells interact with bone marrow stromal cells stimulating transcription and secretion of cytokines like IL-6 and IL-10, which are implicated in the progression and dissemination of MM. Regulation of cytokines secretion is under genetic control through genetic polymorphisms in their coding and promoter sequences. It seems that single nucleotide polymorphism (SNP) in the promoter region of various genes may regulate the plasma concentrat...

The relationship of CSF and plasma cytokine levels to cerebral white matter injury in the premature newborn

NARCIS (Netherlands)

Ellison, VJ; Mocatta, TJ; Winterbourn, CC; Darlow, BA; Volpe, JJ; Inder, TE

Ischemia and systemic infection are implicated in the etiology of periventricular white matter injury, a major cause of adverse motor and cognitive outcome in preterm infants. Cytokines are signaling proteins that can be produced as part of the inflammatory response to both ischemia and infection.

1,25(OH)2D3 and Ca-binding protein in fetal rats: Relationship to the maternal vitamin D status

International Nuclear Information System (INIS)

Verhaeghe, J.; Thomasset, M.; Brehier, A.; Van Assche, F.A.; Bouillon, R.

1988-01-01

The autonomy and functional role of fetal 1,25-dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ] were investigated in nondiabetic and diabetic BB rats fed diets containing 0.85% calcium-0.7% phosphorus or 0.2% calcium and phosphorus and in semistarved rats on the low calcium-phosphorus diet. The changes in maternal and fetal plasma 1,25(OH) 2 D 3 were similar: the levels were increased by calcium-phosphorus restriction and decreased by diabetes and semistarvation. Maternal and fetal 1,25(OH) 2 D 3 levels were correlated. The vitamin D-dependent calcium-binding proteins (CaBP 9K and CaBP 28K ) were measured in multiple maternal and fetal tissues and in the placenta of nondiabetic, diabetic, and calcium-phosphorus-restricted rats. The distributions of CaBP 9K and CaBP 28K in the pregnant rat were similar to that of the growing rat. The increased maternal plasma 1,25(OH) 2 D 3 levels in calcium-phosphorus-restricted rats were associated with higher duodenal CaBP 9K and renal CaBPs, but placental CaBP 9K was not different. In diabetic pregnant rats, duodenal CaBP 9K was not different. In diabetic pregnant rats, duodenal CaBP 9K tended to be lower, while renal CaBPs were normal; placental CaBP 9K was decreased. The results indicate that in the rat fetal 1,25(OH) 2 D 3 depends on maternal 1,25(OH) 2 D 3 or on factors regulating maternal 1,25(OH) 2 D 3 . The lack of changes in fetal CaBP in the presence of altered fetal plasma 1,25(OH) 2 D 3 levels confirms earlier data showing that 1,25(H) 2 D 3 has a limited hormonal function during perinatal development in the rat

Development of chronic colitis is dependent on the cytokine MIF.

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de Jong, Y P; Abadia-Molina, A C; Satoskar, A R; Clarke, K; Rietdijk, S T; Faubion, W A; Mizoguchi, E; Metz, C N; Alsahli, M; ten Hove, T; Keates, A C; Lubetsky, J B; Farrell, R J; Michetti, P; van Deventer, S J; Lolis, E; David, J R; Bhan, A K; Terhorst, C; Sahli, M A

2001-11-01

The cytokine macrophage-migration inhibitory factor (MIF) is secreted by a number of cell types upon induction by lipopolysaccharide (LPS). Because colitis is dependent on interplay between the mucosal immune system and intestinal bacteria, we investigated the role of MIF in experimental colitis. MIF-deficient mice failed to develop disease, but reconstitution of MIF-deficient mice with wild-type innate immune cells restored colitis. In addition, established colitis could be treated with anti-MIF immunoglobulins. Thus, murine colitis is dependent on continuous MIF production by the innate immune system. Because we found increased plasma MIF concentrations in patients with Crohn's disease, these data suggested that MIF is a new target for intervention in Crohn's disease.

Maternal Parity and Blood Oxidative Stress in Mother and Neonate

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Golalizadeh

2016-02-01

Full Text Available Background Parturition has been associated with free radicals, itself linked with poor pregnancy outcome. Objectives This study aimed to investigate the relationship between oxidative stress biomarkers levels of maternal and cord blood samples at the second stage of labor with the maternal parity number. Materials and Methods In this analytical cross-sectional study, subjects were selected from Fatemieh teaching hospital, Hamadan, Iran, and allocated into the two groups according to their number of parity: the primiparous group (n = 33, and multiparous group (n = 35. Maternal and umbilical cord blood samples were taken from all subjects and then assessed for catalas activity (CAT, total thiol molecules (TTM and total antioxidant capacity (TAC. Results Total antioxidant capacity levels were significantly higher in newborns of primiparous women compared to multiparous women (P = 0.006. The CAT levels were significantly lower (P = 0.04 and TAC levels significantly higher (P = 0.03 in maternal plasma of primiparous women compared to those of multiparous women. Conclusions Increment in the number of parity can lead to decrease antioxidant defense mechanisms in multiparous women and their newborns. So, control of oxidative stress is considered to be beneficial in multiparous women.

Persistent organic pollutants in maternal blood plasma and breast milk from Russian arctic populations.

Science.gov (United States)

Klopov, V; Odland, J O; Burkow, I C

1998-10-01

Under the auspices of Arctic Monitoring and Assessment Programme (AMAP), a Russian-Norwegian co-operation project was established to assess the exposure of delivering women to persistent organic pollutants (POPs) in Arctic areas of Russia. In the period 1993-95 blood and breast milk samples were collected from 94 delivering women in Yamal and Tajmyr Autonomous Regions of Siberia. Concentrations of chlorinated pesticides and polychlorinated biphenyls (PCBs) were determined by high resolution gas chromatography with electron capture detection. The POP levels in maternal plasma among the non-indigenous women were higher than the native population, especially in total PCB, HCHs (hexachlorocyclohexanes) and the DDT-group. The dietary questionnaires showed that the non-indigenous populations consumed considerably less local food items like reindeer meat and fresh water fish. There was no correlation between local food consumption and elevated levels of pollutants. Even if the indigenous groups had lower concentrations of the most important pollutants than the non-indigenous population, they were still higher than the levels measured in the Scandinavian countries of the AMAP-study and up to levels of medical concern. The most important sources of organic pollutants for the Russian Arctic populations of Yamal and Tajmyr seems to be imported food from other areas of Russia and local use of pesticides. It must be a high priority concern to further elucidate these trends and initiate prophylactic measures for the exposed population groups.

Gender-specific desensitization of group I metabotropic glutamate receptors after maternal l-glutamate intake during lactation.

Science.gov (United States)

López-Zapata, Antonio; León-Navarro, David Agustín; Crespo, María; Martín, Mairena

2018-04-22

In the present work we have studied the effect of maternal intake of l-Glutamate (l-Glu) (1 g/L) during lactation on group I mGluR transduction pathway in brain plasma membrane from 15 days-old neonates. Results obtained have shown that maternal l-glutamate intake did not significantly affect neither weights of pups nor negative geotaxis reflex, an index of neurobehavioral development, but increased l-Glu plasma level in both male and female neonates. In male neonates, maternal l-Glu intake evoked a loss of mGluR 1 whereas no variation on mGluR 5 was observed as revealed by Western-blotting assay. The loss of mGlu 1 R was accompanied by a decrease on l-Glu-stimulated phospholipase C activity suggesting, therefore, a loss of group I mGluR functionality. Concerning female neonates, no variations were detected neither mGluR 1 nor mGluR 5 and group I mGluR functionality was also preserved. Copyright © 2018 ISDN. Published by Elsevier Ltd. All rights reserved.

Association of maternal breast milk and serum levels of macronutrients, hormones, and maternal body composition with infant's body weight.

Science.gov (United States)

Khodabakhshi, Adeleh; Mehrad-Majd, Hassan; Vahid, Farhad; Safarian, Mohammad

2018-03-01

This study was aimed to investigate the association of maternal serum and breast-milk levels of macronutrients, hormones, growth factors, and maternal body composition with infant's body weight. Eighty mother-infant pairs comprised 40 with overweight or obese infant and 40 with normal-weight infant were enrolled in this study. The level of ghrelin, Leptin, adiponectin, EGF, and IGF1 in plasma and breast milk were assessed. Daily breast milk intake and macronutrient concentration along with anthropometric indices of mother-infant pairs were also assessed. No significant differences were observed in concentrations of serum hormones between two groups (p > 0.05). However, hormones levels in maternal serum were higher than those in breast milk. A significant positive correlation was found between serum EGF and ghrelin (r = 0.57, p = 0 macronutrient content was not comparable between two groups. However, the average daily breast milk consumption in obese infants was higher than normals (p = 0.001). Milk EGF and leptin were related to a decrease of 59% and 46% the odds of obese infant development, respectively. There was a significant association of milk EGF and ghrelin with birth weight (B = -0.19, p = 0.04 and B = -0.2, p = 0.04, respectively), and also serum leptin with infant's body weight at the 6th month. Our findings provide a positive association of maternal weight, daily breast milk intake, EGF, and ghrelin with infant's body weight.

Withaferin A Associated Differential Regulation of Inflammatory Cytokines

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Seema Dubey

2018-02-01

Full Text Available A role of inflammation-associated cytokines/chemokines has been implicated in a wide variety of human diseases. Here, we investigated the regulation of inflammatory cytokines released by monocyte-derived THP-1 cells following treatment with the dietary agent withaferin A (WFA. Membrane-based cytokine array profiling of the culture supernatant from adenosine triphosphate-stimulated WFA-treated THP-1 cells showed differential regulation of multiple cytokines/chemokines. A selected group of cytokines/chemokines [interleukin-1 beta (IL-1β, CCL2/MCP-1, granulocyte-macrophage colony stimulating factor, PDGF-AA, PTX3, cystatin-3, relaxin-2, TNFRSF8/CD30, and ACRP30] was validated at the transcription level using qPCR. In silico analysis for transcriptional binding factors revealed the presence of nuclear factor-kappa B (NF-κB in a group of downregulated cytokine gene promoters. WFA treatment of THP-1 cells blocks the nuclear translocation of NF-kB and corresponds with the reduced levels of cytokine secretion. To further understand the differential expression of cytokines/chemokines, we showed that WFA alters the nigericin-induced co-localization of NLRP3 and ASC proteins, thereby inhibiting caspase-1 activation, which is responsible for the cleavage and maturation of pro-inflammatory cytokines IL-1β and IL-18. These data suggest that dietary agent WFA concurrently targets NF-κB and the inflammasome complex, leading to inhibition of IL-1β and IL-18, respectively, in addition to differential expression of multiple cytokines/chemokines. Taken together, these results provide a rationale for using WFA to further explore the anti-inflammatory mechanism of cytokines/chemokines associated with inflammatory diseases.

CYTOKINE REGULATION OF ULCEROGENESIS IN GASTRODUODENAL MUCOSA

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L. V. Matveeva

2013-01-01

Full Text Available Ulcerogenesis in gastroduodenal mucosa area is a complex multistep process. Its, phases arecontrolled by interaction and activation of pro­ and antiinflammatory cytokine cascade. Present review article summarizes scientific data on impact of cytokines upon ulcerative and reparatory processes, a variety of their diagnostic and therapeutic options is defined. Evaluation of cytokine status, or, in some cases, cytokine genotyping in patients with stomach and duodenal ulcers, may predict clinical course of the disease, as well as efficiency of basic and eradication therapy, correction of the treatment.

Maternal Obesity Induces Sustained Inflammation in Both Fetal and Offspring Large Intestine of Sheep

Science.gov (United States)

Yan, Xu; Huang, Yan; Wang, Hui; Du, Min; Hess, Bret W.; Ford, Stephen P.; Nathanielsz, Peter W.; Zhu, Mei-Jun

2010-01-01

Background Both maternal obesity and inflammatory bowel diseases (IBDs) are increasing. It was hypothesized that maternal obesity induces an inflammatory response in the fetal large intestine, predisposing offspring to IBDs. Methods Nonpregnant ewes were assigned to a control (Con, 100% of National Research Council [NRC] recommendations) or obesogenic (OB, 150% of NRC) diet from 60 days before conception. The large intestine was sampled from fetuses at 135 days (term 150 days) after conception and from offspring lambs at 22.5 ± 0.5 months of age. Results Maternal obesity enhanced mRNA expression tumor necrosis factor (TNF)α, interleukin (IL)1α, IL1β, IL6, IL8, and monocyte/macrophage chemotactic protein-1 (MCP1), as well as macrophage markers, CD11b, CD14, and CD68 in fetal gut. mRNA expression of Toll-like receptor (TLR) 2 and TLR4 was increased in OB versus Con fetuses; correspondingly, inflammatory NF-κB and JNK signaling pathways were also upregulated. Both mRNA expression and protein content of transforming growth factor (TGF) β was increased. The IL-17A mRNA expression and protein content was higher in OB compared to Con samples, which was associated with fibrosis in the large intestine of OB fetuses. Similar inflammatory responses and enhanced fibrosis were detected in OB compared to Con offspring. Conclusions Maternal obesity induced inflammation and enhanced expression of proinflammatory cytokines in fetal and offspring large intestine, which correlated with increased TGFβ and IL17 expression. These data show that maternal obesity may predispose offspring gut to IBDs. PMID:21674707

The diverse applications of plasma

International Nuclear Information System (INIS)

Sharma, Mukul; Darwhekar, Gajanan; Dubey, Shivani; Jain, Sudhir Kumar

2015-01-01

Plasma being the fourth state of matter has always been an attraction for Physicists and Chemists. With the advent of time, plasma energy has been recognized in having widening horizons in the field of Biomedical Sciences. Plasma medicine can be subdivided into three main fields; Non-thermal atmospheric-pressure direct plasma for medical therapy; Plasma-assisted modification of bio-relevant surfaces and Plasma-based bio-decontamination and sterilization. The basis of the research is that as it has free carrier molecules, it has the ability to target specific cells and regulate functions like wound healing. Plasma does not harm healthy human cells but can kill bacteria and possibly even cancer cells to help treat various diseases. Nosocomial infection control, prevention and containment of contagious diseases, disinfection of medical devices, surface treatment (heat and UV sensitive surfaces) are research of interest. Recent success in generating plasma at very low temperature ie. Cold plasma makes the therapy painless. It has the ability to activate cellular responses and important mechanisms in the body. They target specific molecules such as prothrombin for blood coagulation, cytokines for killing bacteria, and angiogenesis for tissue regeneration. Plasma has bactericidal, fungicidal and virucidal properties. Plasma technology has flourishing future in diverse fields like Textiles, Nanofabrication, Automotives, Waste management, Microbiology, Food Hygiene, Medical Science like Skin treatments, sterilisation of wounds, Hand disinfection, Dental treatments etc. Food hygiene using plasma can be achieved in disinfection of food containers, food surface disinfection, hygiene in food handling, preparation and packaging. Therefore Plasma is most promising field for budding Scientist for fluorishing research in Biological Sciences

The diverse applications of plasma

Science.gov (United States)

Sharma, Mukul; Dubey, Shivani; Darwhekar, Gajanan; Jain, Sudhir Kumar

2015-07-01

Plasma being the fourth state of matter has always been an attraction for Physicists and Chemists. With the advent of time, plasma energy has been recognized in having widening horizons in the field of Biomedical Sciences. Plasma medicine can be subdivided into three main fields; Non-thermal atmospheric-pressure direct plasma for medical therapy; Plasma-assisted modification of bio-relevant surfaces and Plasma-based bio-decontamination and sterilization. The basis of the research is that as it has free carrier molecules, it has the ability to target specific cells and regulate functions like wound healing. Plasma does not harm healthy human cells but can kill bacteria and possibly even cancer cells to help treat various diseases. Nosocomial infection control, prevention and containment of contagious diseases, disinfection of medical devices, surface treatment (heat and UV sensitive surfaces) are research of interest. Recent success in generating plasma at very low temperature ie. Cold plasma makes the therapy painless. It has the ability to activate cellular responses and important mechanisms in the body. They target specific molecules such as prothrombin for blood coagulation, cytokines for killing bacteria, and angiogenesis for tissue regeneration. Plasma has bactericidal, fungicidal and virucidal properties. Plasma technology has flourishing future in diverse fields like Textiles, Nanofabrication, Automotives, Waste management, Microbiology, Food Hygiene, Medical Science like Skin treatments, sterilisation of wounds, Hand disinfection, Dental treatments etc. Food hygiene using plasma can be achieved in disinfection of food containers, food surface disinfection, hygiene in food handling, preparation and packaging. Therefore Plasma is most promising field for budding Scientist for fluorishing research in Biological Sciences.

The diverse applications of plasma

Energy Technology Data Exchange (ETDEWEB)

Sharma, Mukul, E-mail: mukulsharma@acropolis.edu.in; Darwhekar, Gajanan, E-mail: gdarwhekar@acropolis.edu.in [Acropolis Institute of Pharmaceutical Education & Research, Indore MP India (India); Dubey, Shivani, E-mail: dubeyshivani08@rediffmail.com [Mata Gujri College of Professional Studies, Indore MP India (India); Jain, Sudhir Kumar, E-mail: sudhirkjain1@rediffmail.com [School of Studies in Microbiology, Vikram University, Ujjain MP India (India)

2015-07-31

Plasma being the fourth state of matter has always been an attraction for Physicists and Chemists. With the advent of time, plasma energy has been recognized in having widening horizons in the field of Biomedical Sciences. Plasma medicine can be subdivided into three main fields; Non-thermal atmospheric-pressure direct plasma for medical therapy; Plasma-assisted modification of bio-relevant surfaces and Plasma-based bio-decontamination and sterilization. The basis of the research is that as it has free carrier molecules, it has the ability to target specific cells and regulate functions like wound healing. Plasma does not harm healthy human cells but can kill bacteria and possibly even cancer cells to help treat various diseases. Nosocomial infection control, prevention and containment of contagious diseases, disinfection of medical devices, surface treatment (heat and UV sensitive surfaces) are research of interest. Recent success in generating plasma at very low temperature ie. Cold plasma makes the therapy painless. It has the ability to activate cellular responses and important mechanisms in the body. They target specific molecules such as prothrombin for blood coagulation, cytokines for killing bacteria, and angiogenesis for tissue regeneration. Plasma has bactericidal, fungicidal and virucidal properties. Plasma technology has flourishing future in diverse fields like Textiles, Nanofabrication, Automotives, Waste management, Microbiology, Food Hygiene, Medical Science like Skin treatments, sterilisation of wounds, Hand disinfection, Dental treatments etc. Food hygiene using plasma can be achieved in disinfection of food containers, food surface disinfection, hygiene in food handling, preparation and packaging. Therefore Plasma is most promising field for budding Scientist for fluorishing research in Biological Sciences.

No evidence for sex-specific effects of the maternal social environment on offspring development in Japanese quail (Coturnix japonica).

Science.gov (United States)

Langen, Esther M A; von Engelhardt, Nikolaus; Goerlich-Jansson, Vivian C

2018-07-01

The social environment of reproducing females can cause physiological changes, with consequences for reproductive investment and offspring development. These prenatal maternal effects are often found to be sex-specific and may have evolved as adaptations, maximizing fitness of male and female offspring for their future environment. Female hormone levels during reproduction are considered a potential mechanism regulating sex allocation in vertebrates: high maternal androgens have repeatedly been linked to increased investment in sons, whereas high glucocorticoid levels are usually related to increased investment in daughters. However, results are not consistent across studies and therefore still inconclusive. In Japanese quail (Coturnix japonica), we previously found that pair-housed females had higher plasma androgen levels and tended to have higher plasma corticosterone levels than group-housed females. In the current study we investigate whether these differences in maternal social environment and physiology affect offspring sex allocation and physiology. Counter to our expectations, we find no effects of the maternal social environment on offspring sex ratio, sex-specific mortality, growth, circulating androgen or corticosterone levels. Also, maternal corticosterone or androgen levels do not correlate with offspring sex ratio or mortality. The social environment during reproduction therefore does not necessarily modify sex allocation and offspring physiology, even if it causes differences in maternal physiology. We propose that maternal effects of the social environment strongly depend upon the type of social stimuli and the timing of changes in the social environment and hormones with respect to the reproductive cycle and meiosis. Copyright © 2018 Elsevier Inc. All rights reserved.

Increased Blood Levels of Growth Factors, Proinflammatory Cytokines, and Th17 Cytokines in Patients with Newly Diagnosed Type 1 Diabetes.

Science.gov (United States)

Alnek, Kristi; Kisand, Kalle; Heilman, Kaire; Peet, Aleksandr; Varik, Karin; Uibo, Raivo

2015-01-01

The production of several cytokines could be dysregulated in type 1 diabetes (T1D). In particular, the activation of T helper (Th) type 1 (Th1) cells has been proposed to underlie the autoimmune pathogenesis of the disease, although roles for inflammatory processes and the Th17 pathway have also been shown. Nevertheless, despite evidence for the role of cytokines before and at the onset of T1D, the corresponding findings are inconsistent across studies. Moreover, conflicting data exist regarding the blood cytokine levels in T1D patients. The current study was performed to investigate genetic and autoantibody markers in association with the peripheral blood cytokine profiles by xMap multiplex technology in newly diagnosed young T1D patients and age-matched healthy controls. The onset of young-age T1D was characterized by the upregulation of growth factors, including granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin (IL)-7, the proinflammatory cytokine IL-1β (but not IL-6 or tumor necrosis factor [TNF]-α), Th17 cytokines, and the regulatory cytokines IL-10 and IL-27. Ketoacidosis and autoantibodies (anti-IA-2 and -ZnT8), but not human leukocyte antigen (HLA) genotype, influenced the blood cytokine levels. These findings broaden the current understanding of the dysregulation of systemic levels of several key cytokines at the young-age onset of T1D and provide a further basis for the development of novel immunoregulatory treatments in this disease.

Plasma fibrinogen and factor VII concentrations in adults after prenatal exposure to famine

NARCIS (Netherlands)

Roseboom, T. J.; van der Meulen, J. H.; Ravelli, A. C.; Osmond, C.; Barker, D. J.; Bleker, O. P.

2000-01-01

To assess the effect of maternal malnutrition during different stages of gestation on plasma concentrations of fibrinogen and factor VII, we investigated 725 people, aged 50 years, born around the time of the Dutch famine 1944-5. After adjustment for sex, plasma fibrinogen concentrations differed by

Stress at birth: plasma noradrenaline concentrations of women in labour and in cord blood.

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Messow-Zahn, K; Sarafoff, M; Riegel, K P

1978-03-15

Radioenzymatically measured plasma noradrenaline concentrations, present at birth in umbilical veins of 19 healthy, 17 acutely asphyxiated, and 9 chronically distressed newborn infants were found to be elevated above maternal values proportional to the degree of distress and to plasma H ion concentrations.

Drug targets in the cytokine universe for autoimmune disease.

Science.gov (United States)

Liu, Xuebin; Fang, Lei; Guo, Taylor B; Mei, Hongkang; Zhang, Jingwu Z

2013-03-01

In autoimmune disease, a network of diverse cytokines is produced in association with disease susceptibility to constitute the 'cytokine milieu' that drives chronic inflammation. It remains elusive how cytokines interact in such a complex network to sustain inflammation in autoimmune disease. This has presented huge challenges for successful drug discovery because it has been difficult to predict how individual cytokine-targeted therapy would work. Here, we combine the principles of Chinese Taoism philosophy and modern bioinformatics tools to dissect multiple layers of arbitrary cytokine interactions into discernible interfaces and connectivity maps to predict movements in the cytokine network. The key principles presented here have important implications in our understanding of cytokine interactions and development of effective cytokine-targeted therapies for autoimmune disorders. Copyright © 2012 Elsevier Ltd. All rights reserved.

Melatonin Therapy Prevents Programmed Hypertension and Nitric Oxide Deficiency in Offspring Exposed to Maternal Caloric Restriction

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You-Lin Tain

2014-01-01

Full Text Available Nitric oxide (NO deficiency is involved in the development of hypertension, a condition that can originate early in life. We examined whether NO deficiency contributed to programmed hypertension in offspring from mothers with calorie-restricted diets and whether melatonin therapy prevented this process. We examined 3-month-old male rat offspring from four maternal groups: untreated controls, 50% calorie-restricted (CR rats, controls treated with melatonin (0.01% in drinking water, and CR rats treated with melatonin (CR + M. The effect of melatonin on nephrogenesis was analyzed using next-generation sequencing. The CR group developed hypertension associated with elevated plasma asymmetric dimethylarginine (ADMA, a nitric oxide synthase inhibitor, decreased L-arginine, decreased L-arginine-to-ADMA ratio (AAR, and decreased renal NO production. Maternal melatonin treatment prevented these effects. Melatonin prevented CR-induced renin and prorenin receptor expression. Renal angiotensin-converting enzyme 2 protein levels in the M and CR + M groups were also significantly increased by melatonin therapy. Maternal melatonin therapy had long-term epigenetic effects on global gene expression in the kidneys of offspring. Conclusively, we attributed these protective effects of melatonin on CR-induced programmed hypertension to the reduction of plasma ADMA, restoration of plasma AAR, increase of renal NO level, alteration of renin-angiotensin system, and epigenetic changes in numerous genes.

Regulation of cytokines by small RNAs during skin inflammation

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Mikkelsen Jacob G

2010-07-01

Full Text Available Abstract Intercellular signaling by cytokines is a vital feature of the innate immune system. In skin, an inflammatory response is mediated by cytokines and an entwined network of cellular communication between T-cells and epidermal keratinocytes. Dysregulated cytokine production, orchestrated by activated T-cells homing to the skin, is believed to be the main cause of psoriasis, a common inflammatory skin disorder. Cytokines are heavily regulated at the transcriptional level, but emerging evidence suggests that regulatory mechanisms that operate after transcription play a key role in balancing the production of cytokines. Herein, we review the nature of cytokine signaling in psoriasis with particular emphasis on regulation by mRNA destabilizing elements and the potential targeting of cytokine-encoding mRNAs by miRNAs. The proposed linkage between mRNA decay mediated by AU-rich elements and miRNA association is described and discussed as a possible general feature of cytokine regulation in skin. Moreover, we describe the latest attempts to therapeutically target cytokines at the RNA level in psoriasis by exploiting the cellular RNA interference machinery. The applicability of cytokine-encoding mRNAs as future clinical drug targets is evaluated, and advances and obstacles related to topical administration of RNA-based drugs targeting the cytokine circuit in psoriasis are described.

Maternal plasma levels of interleukin-6, C-reactive protein, vitamins C, E and A, 8-isoprostane and oxidative status in women with preterm premature rupture of membranes.

Science.gov (United States)

Ilhan, Nevin; Celik, Ebru; Kumbak, Banu

2015-02-01

Preterm premature rupture of membranes (PPROM) is associated with significant maternal and perinatal morbidity. This study examined maternal oxidative stress in PPROM. This was a prospective cross-sectional study conducted in a university hospital. A total of 72 pregnant women were recruited into two groups, those with PPROM (38 cases) and those without PPROM (34 controls) matched for gestational age. Plasma interleukin-6, C-reactive protein, vitamins C, E and A, 8-isoprostane, total oxidant status (TOS) and antioxidant status (TAS) were determined for all study participants and the data were compared between the PPROM and control groups. Both case and control groups were comparably matched in age, parity, gestational age and smoking status. There was a significant association between low 8-isoprostane, low vitamin C and high total oxidant status and the occurrence of PPROM (p vitamin C and 8-isoprostane levels were lower and TOS higher in women with PPROM. Further research is needed to identify robust biological markers for the prevention and also prognosis of PPROM.

The risk for behavioural deficits is determined by the maternal immune response to prenatal immune challenge in a neurodevelopmental model.

Science.gov (United States)

Missault, S; Van den Eynde, K; Vanden Berghe, W; Fransen, E; Weeren, A; Timmermans, J P; Kumar-Singh, S; Dedeurwaerdere, S

2014-11-01

Schizophrenia is a highly disabling psychiatric disorder with a proposed neurodevelopmental basis. One mechanism through which genetic and environmental risk factors might act is by triggering persistent brain inflammation, as evidenced by long-lasting neuro-immunological disturbances in patients. Our goal was to investigate whether microglia activation is a neurobiological correlate to the altered behaviour in the maternal immune activation (MIA) model, a well-validated animal model with relevance to schizophrenia. A recent observation in the MIA model is the differential maternal body weight response to the immune stimulus, correlated with a different behavioural outcome in the offspring. Although it is generally assumed that the differences in maternal weight response reflect differences in cytokine response, this has not been investigated so far. Our aim was to investigate whether (i) the maternal weight response to MIA reflects differences in the maternal cytokine response, (ii) the differential behavioural phenotype of the offspring extends to depressive symptoms such as anhedonia and (iii) there are changes in chronic microglia activation dependent on the behavioural phenotype. Based on a dose-response study, MIA was induced in pregnant rats by injecting 4mg/kg Poly I:C at gestational day 15. Serum samples were collected to assess the amount of TNF-α in the maternal blood following MIA. MIA offspring were divided into weight loss (WL; n=14) and weight gain (WG; n=10) groups, depending on the maternal body weight response to Poly I:C. Adult offspring were behaviourally phenotyped for prepulse inhibition, locomotor activity with and without amphetamine and MK-801 challenge, and sucrose preference. Finally, microglia activation was scored on CD11b- and Iba1-immunohistochemically stained sections. Pregnant dams that lost weight following MIA showed increased levels of TNF-α compared to controls, unlike dams that gained weight following MIA. Poly I:C WL

Chronic infusion of enalaprilat into hypothalamic paraventricular nucleus attenuates angiotensin II-induced hypertension and cardiac hypertrophy by restoring neurotransmitters and cytokines

International Nuclear Information System (INIS)

Kang, Yu-Ming; Zhang, Dong-Mei; Yu, Xiao-Jing; Yang, Qing; Qi, Jie; Su, Qing; Suo, Yu-Ping; Yue, Li-Ying; Zhu, Guo-Qing; Qin, Da-Nian

2014-01-01

The renin–angiotensin system (RAS) in the brain is involved in the pathogenesis of hypertension. We hypothesized that inhibition of angiotensin-converting enzyme (ACE) in the hypothalamic paraventricular nucleus (PVN) attenuates angiotensin II (ANG II)-induced hypertension via restoring neurotransmitters and cytokines. Rats underwent subcutaneous infusions of ANG II or saline and bilateral PVN infusions of ACE inhibitor enalaprilat (ENL, 2.5 μg/h) or vehicle for 4 weeks. ANG II infusion resulted in higher mean arterial pressure and cardiac hypertrophy as indicated by increased whole heart weight/body weight ratio, whole heart weight/tibia length ratio, left ventricular weight/tibia length ratio, and mRNA expressions of cardiac atrial natriuretic peptide and beta-myosin heavy chain. These ANG II-infused rats had higher PVN levels of glutamate, norepinephrine, tyrosine hydroxylase, pro-inflammatory cytokines (PICs) and the chemokine monocyte chemoattractant protein-1, and lower PVN levels of gamma-aminobutyric acid, interleukin (IL)-10 and the 67-kDa isoform of glutamate decarboxylase (GAD67), and higher plasma levels of PICs, norepinephrine and aldosterone, and lower plasma IL-10, and higher renal sympathetic nerve activity. However, PVN treatment with ENL attenuated these changes. PVN microinjection of ANG II induced increases in IL-1β and IL-6, and a decrease in IL-10 in the PVN, and pretreatment with angiotensin II type 1 receptor (AT1-R) antagonist losartan attenuated these changes. These findings suggest that ANG II infusion induces an imbalance between excitatory and inhibitory neurotransmitters and an imbalance between pro- and anti-inflammatory cytokines in the PVN, and PVN inhibition of the RAS restores neurotransmitters and cytokines in the PVN, thereby attenuating ANG II-induced hypertension and cardiac hypertrophy. - Highlights: • Chronic ANG II infusion results in sympathetic hyperactivity and cardiac hypertrophy. • PVN inhibition of ACE

Chronic infusion of enalaprilat into hypothalamic paraventricular nucleus attenuates angiotensin II-induced hypertension and cardiac hypertrophy by restoring neurotransmitters and cytokines

Energy Technology Data Exchange (ETDEWEB)

Kang, Yu-Ming, E-mail: ykang@mail.xjtu.edu.cn [Department of Physiology and Pathophysiology, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Zhang, Dong-Mei [Department of Physiology, Dalian Medical University, Dalian 116044 (China); Yu, Xiao-Jing; Yang, Qing; Qi, Jie; Su, Qing [Department of Physiology and Pathophysiology, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Suo, Yu-Ping [Department of Obstetrics and Gynecology, Shanxi Provincial People' s Hospital, Taiyuan 030012 (China); Yue, Li-Ying [Department of Physiology and Pathophysiology, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Zhu, Guo-Qing [Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing 210029 (China); Qin, Da-Nian, E-mail: dnqin@stu.edu.cn [Department of Physiology, Shantou University Medical College, Shantou 515041 (China)

2014-02-01

The renin–angiotensin system (RAS) in the brain is involved in the pathogenesis of hypertension. We hypothesized that inhibition of angiotensin-converting enzyme (ACE) in the hypothalamic paraventricular nucleus (PVN) attenuates angiotensin II (ANG II)-induced hypertension via restoring neurotransmitters and cytokines. Rats underwent subcutaneous infusions of ANG II or saline and bilateral PVN infusions of ACE inhibitor enalaprilat (ENL, 2.5 μg/h) or vehicle for 4 weeks. ANG II infusion resulted in higher mean arterial pressure and cardiac hypertrophy as indicated by increased whole heart weight/body weight ratio, whole heart weight/tibia length ratio, left ventricular weight/tibia length ratio, and mRNA expressions of cardiac atrial natriuretic peptide and beta-myosin heavy chain. These ANG II-infused rats had higher PVN levels of glutamate, norepinephrine, tyrosine hydroxylase, pro-inflammatory cytokines (PICs) and the chemokine monocyte chemoattractant protein-1, and lower PVN levels of gamma-aminobutyric acid, interleukin (IL)-10 and the 67-kDa isoform of glutamate decarboxylase (GAD67), and higher plasma levels of PICs, norepinephrine and aldosterone, and lower plasma IL-10, and higher renal sympathetic nerve activity. However, PVN treatment with ENL attenuated these changes. PVN microinjection of ANG II induced increases in IL-1β and IL-6, and a decrease in IL-10 in the PVN, and pretreatment with angiotensin II type 1 receptor (AT1-R) antagonist losartan attenuated these changes. These findings suggest that ANG II infusion induces an imbalance between excitatory and inhibitory neurotransmitters and an imbalance between pro- and anti-inflammatory cytokines in the PVN, and PVN inhibition of the RAS restores neurotransmitters and cytokines in the PVN, thereby attenuating ANG II-induced hypertension and cardiac hypertrophy. - Highlights: • Chronic ANG II infusion results in sympathetic hyperactivity and cardiac hypertrophy. • PVN inhibition of ACE

Maternal diet and dioxin-like activity, bulky DNA adducts and micronuclei in mother–newborns

International Nuclear Information System (INIS)

Pedersen, Marie; Halldorsson, Thorhallur I.; Autrup, Herman; Brouwer, Abraham; Besselink, Harrie; Loft, Steffen; Knudsen, Lisbeth E.

2012-01-01

Maternal diet can contribute to carcinogenic exposures and also modify effects of environmental exposures on maternal and fetal genetic stability. In this study, associations between maternal diet and the levels of dioxin-like plasma activity, bulky DNA adducts in white blood cells and micronuclei (MN) in lymphocytes from mother to newborns were examined. From 98 pregnant women living in the greater area of Copenhagen, Denmark in 2006–2007, maternal peripheral blood and umbilical cord blood were collected, together with information on health, environmental exposure and lifestyle. Maternal diet was estimated on the basis of maternal food frequency questionnaire (FFQ) completed by the end of pregnancy. Biomarkers were detected in paired blood samples through the dioxin-responsive chemical-activated luciferase expression (CALUX) ® bioassay, 32 P-postlabelling technique and cytokinesis-block MN assay. Maternal preference for meats with dark surface were significantly associated with higher bulky DNA adducts in both maternal (β 95%CI; 0.46 (0.08, 0.84)) and cord blood (β 95%CI; 0.46 (0.05, 0.86)) before and after adjustment for potential confounders. No other significant associations between the 18 dietary variables and the biomarkers measured in maternal and fetal samples were identified. The present study suggests that maternal intake of meats with dark surface contributes to the bulky DNA adduct levels in maternal and umbilical cord blood. Relationship between food preparation and bulky DNA adducts appear to be captured by a FFQ while potential associations for other biomarkers might be more complex or need larger sample size.

Maternal diet and dioxin-like activity, bulky DNA adducts and micronuclei in mother-newborns

Energy Technology Data Exchange (ETDEWEB)

Pedersen, Marie, E-mail: mpedersen@creal.cat [Section of Environmental Health, Department of Public Health, University of Copenhagen, CSS, Oester Farimagsgade, Copenhagen K (Denmark); Halldorsson, Thorhallur I., E-mail: lur@ssi.dk [Faculty of Food Science and Nutrition, School of Health Sciences, University of Iceland Reykjavik (Iceland); Center for Fetal Programming, Department of Epidemiology, Statens Serum Institute, Copenhagen (Denmark); Autrup, Herman, E-mail: ha@mil.au.dk [School of Public Health, Department of Environmental and Occupational Medicine, Aarhus University, Aarhus (Denmark); Brouwer, Abraham, E-mail: Bram.Brouwer@bds.nl [BioDetection Systems B.V., Amsterdam (Netherlands); Besselink, Harrie, E-mail: Harrie.Besselink@bds.nl [BioDetection Systems B.V., Amsterdam (Netherlands); Loft, Steffen, E-mail: stl@sund.ku.dk [Section of Environmental Health, Department of Public Health, University of Copenhagen, CSS, Oester Farimagsgade, Copenhagen K (Denmark); Knudsen, Lisbeth E., E-mail: liek@sund.ku.dk [Section of Environmental Health, Department of Public Health, University of Copenhagen, CSS, Oester Farimagsgade, Copenhagen K (Denmark)

2012-06-01

Maternal diet can contribute to carcinogenic exposures and also modify effects of environmental exposures on maternal and fetal genetic stability. In this study, associations between maternal diet and the levels of dioxin-like plasma activity, bulky DNA adducts in white blood cells and micronuclei (MN) in lymphocytes from mother to newborns were examined. From 98 pregnant women living in the greater area of Copenhagen, Denmark in 2006-2007, maternal peripheral blood and umbilical cord blood were collected, together with information on health, environmental exposure and lifestyle. Maternal diet was estimated on the basis of maternal food frequency questionnaire (FFQ) completed by the end of pregnancy. Biomarkers were detected in paired blood samples through the dioxin-responsive chemical-activated luciferase expression (CALUX){sup Registered-Sign} bioassay, {sup 32}P-postlabelling technique and cytokinesis-block MN assay. Maternal preference for meats with dark surface were significantly associated with higher bulky DNA adducts in both maternal ({beta} 95%CI; 0.46 (0.08, 0.84)) and cord blood ({beta} 95%CI; 0.46 (0.05, 0.86)) before and after adjustment for potential confounders. No other significant associations between the 18 dietary variables and the biomarkers measured in maternal and fetal samples were identified. The present study suggests that maternal intake of meats with dark surface contributes to the bulky DNA adduct levels in maternal and umbilical cord blood. Relationship between food preparation and bulky DNA adducts appear to be captured by a FFQ while potential associations for other biomarkers might be more complex or need larger sample size.

Effects of maternal obesity on placental function and fetal development

Science.gov (United States)

Howell, Kristy R.; Powell, Theresa L.

2017-01-01

Obesity has reached epidemic proportions and pregnancies in obese mothers have increased risk for complications including gestational diabetes, hypertensive disorders, preterm birth and caesarian section. Children born to obese mothers are at increased risk of obesity and metabolic disease and are susceptible to develop neuropsychiatric and cognitive disorders. Changes in placental function not only play a critical role in the development of pregnancy complications but may also be involved in linking maternal obesity to long-term health risks in the infant. Maternal adipokines i.e., interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), leptin and adiponectin link maternal nutritional status and adipose tissue metabolism to placental function. Adipokines and metabolic hormones have direct impact on placental function by modulating placental nutrient transport. Nutrient delivery to the fetus is regulated by a complex interaction between insulin signaling, cytokine profile and insulin responsiveness, which is modulated by adiponectin and IL-1β. In addition, obese pregnant women are at risk for hypertension and preeclampsia with reduced placental vascularity and blood flow, which would restrict placental nutrient delivery to the developing fetus. These sometimes opposing signals regulating placental function may contribute to the diversity of short and long-term outcomes observed in pregnant obese women. This review focuses on the changes in adipokines and obesity-related metabolic hormones, how these factors influence placental function and fetal development to contribute to long-term metabolic and behavioral consequences of children born to obese mothers. PMID:27864335

Severe acute maternal morbidity and maternal death audit - a rapid ...

African Journals Online (AJOL)

Severe acute maternal morbidity and maternal death audit - a rapid diagnostic tool for evaluating maternal care. L Cochet, R.C. Pattinson, A.P. Macdonald. Abstract. Objective. To analyse severe acute maternal morbidity (SAMM) and maternal mortality in the Pretoria region over a 2-year period (2000 - 2001). Setting.

The involvement of inflammatory cytokines in the pathogenesis of recurrent miscarriage.

Science.gov (United States)

Giannubilo, Stefano R; Landi, Beatrice; Pozzi, Valentina; Sartini, Davide; Cecati, Monia; Stortoni, Piergiorgio; Corradetti, Alessandra; Saccucci, Franca; Tranquilli, Andrea L; Emanuelli, Monica

2012-04-01

To investigate the inflammatory cytokine expression pattern in trophoblastic tissue from women with unexplained recurrent miscarriage (RM). Trophoblasts were obtained during uterine evacuation from 11 women with RM and from 20 healthy pregnant women undergoing elective termination of pregnancy, who served as controls. The array was performed using GEArray Q Series Human Inflammatory Cytokines & Receptors Gene Array HS-015 membranes. Data were confirmed by quantitative real-time PCR. The Mann-Whitney U test was performed for statistical analysis. Microarray analysis identified three genes that were differentially expressed between RM patients and controls. We observed significant downregulation of Transforming Growth Factor beta 3 (TGF-β3) and Interleukin 25 (IL-25) (5-fold reduction and 2.5-fold reduction, respectively) and significant upregulation of CD-25, also known as Interleukin 2 receptor alpha (IL-2RA) (7-fold increase) in women with RM compared with controls. The median ΔC(t) of TGF-β3 was 8.2 (interquartile range, 7.67-8.9) in RM patients vs. 5.85 (interquartile range, 5.3-6.09) in controls; the median ΔC(t) of IL-25 was 5.18 (interquartile range, 4.46-5.76) in RM patients vs. 3.85 (interquartile range, 3.6-4.51) in controls, and the median ΔC(t) of CD-25 was 9.62 (interquartile range, 7.81-12.42) in RM patients vs. 12.44 (interquartile range, 11.02-13.86) in controls. Our results suggest that the immunological and inflammatory regulation mechanisms of the placental environment play a key role in recurrent miscarriage. The observed trophoblast cytokine expression pattern at the maternal-fetal interface confirms the immunotrophic theory, as demonstrated by a switch from a T-helper-1 (Th1) profile to a T-helper-2 (Th2) profile in women who experience recurrent miscarriages. Copyright © 2012 Elsevier Ltd. All rights reserved.

Cytokines in human milk.

Science.gov (United States)

Garofalo, Roberto

2010-02-01

Epidemiologic studies conducted in the past 30 years to investigate the protective functions of human milk strongly support the notion that breastfeeding prevents infantile infections, particularly those affecting the gastrointestinal and respiratory tracts. However, more recent clinical and experimental observations also suggest that human milk not only provides passive protection, but also can directly modulate the immunological development of the recipient infant. The study of this remarkable defense system in human milk has been difficult because of its biochemical complexity, the small concentration of certain bioactive components, the compartmentalization of some of these agents, the dynamic quantitative and qualitative changes of milk during lactation, and the lack of specific reagents to quantify these agents. However, a host of bioactive substances, including hormones, growth factors, and immunological factors such as cytokines, have been identified in human milk. Cytokines are pluripotent polypeptides that act in autocrine/paracrine fashions by binding to specific cellular receptors. They operate in networks and orchestrate the development and functions of immune system. Several different cytokines and chemokines have been discovered in human milk in the past years, and the list is growing very rapidly. This article will review the current knowledge about the increasingly complex network of chemoattractants, activators, and anti-inflammatory cytokines present in human milk and their potential role in compensating for the developmental delay of the neonate immune system. Copyright 2010. Published by Mosby, Inc.

Lutein Supplementation Increases Breast Milk and Plasma Lutein Concentrations in Lactating Women and Infant Plasma Concentrations but Does Not Affect Other Carotenoids 1 2 3

OpenAIRE

Sherry, Christina L.; Oliver, Jeffery S.; Renzi, Lisa M.; Marriage, Barbara J.

2014-01-01

Lutein is a carotenoid that varies in breast milk depending on maternal intake. Data are lacking with regard to the effect of dietary lutein supplementation on breast milk lutein concentration during lactation and subsequent plasma lutein concentration in breast-fed infants. This study was conducted to determine the impact of lutein supplementation in the breast milk and plasma of lactating women and in the plasma of breast-fed infants 2–3 mo postpartum. Lutein is the dominant carotenoid in t...

Pre-delivery fibrinogen predicts adverse maternal or neonatal outcomes in patients with placental abruption.

Science.gov (United States)

Wang, Liangcheng; Matsunaga, Shigetaka; Mikami, Yukiko; Takai, Yasushi; Terui, Katsuo; Seki, Hiroyuki

2016-07-01

Placental abruption is a severe obstetric complication of pregnancy that can cause disseminated intravascular coagulation and progress to massive post-partum hemorrhage. Coagulation disorder due to extreme consumption of fibrinogen is considered the main pathogenesis of disseminated intravascular coagulation in patients with placental abruption. The present study sought to determine if the pre-delivery fibrinogen level could predict adverse maternal or neonatal outcomes in patients with placental abruption. This retrospective medical chart review was conducted in a center for maternal, fetal, and neonatal medicine in Japan with 61 patients with placental abruption. Fibrinogen levels prior to delivery were collected and evaluated for the prediction of maternal and neonatal outcomes. The main outcome measures for maternal outcomes were disseminated intravascular coagulation and hemorrhage, and the main outcome measures for neonatal outcomes were Apgar score at 5 min, umbilical artery pH, and stillbirth. The receiver-operator curve and multivariate logistic regression analyses indicated that fibrinogen significantly predicted overt disseminated intravascular coagulation and the requirement of ≥6 red blood cell units, ≥10 fresh frozen plasma units, and ≥20 fresh frozen plasma units for transfusion. Moderate hemorrhage occurred in 71.5% of patients with a decrease in fibrinogen levels to 155 mg/dL. Fibrinogen could also predict neonatal outcomes. Umbilical artery pH neonatal outcomes with placental abruption. © 2016 Japan Society of Obstetrics and Gynecology. © 2016 Japan Society of Obstetrics and Gynecology.

Investigation on the effects of the atmospheric pressure plasma on wound healing in diabetic rats

Science.gov (United States)

Fathollah, Sara; Mirpour, Shahriar; Mansouri, Parvin; Dehpour, Ahmad Reza; Ghoranneviss, Mahmood; Rahimi, Nastaran; Safaie Naraghi, Zahra; Chalangari, Reza; Chalangari, Katalin Martits

2016-02-01

It is estimated that 15 percent of individuals with diabetes mellitus suffer from diabetic ulcers worldwide. The aim of this study is to present a non-thermal atmospheric plasma treatment as a novel therapy for diabetic wounds. The plasma consists of ionized helium gas that is produced by a high-voltage (8 kV) and high-frequency (6 kHz) power supply. Diabetes was induced in rats via an intravascular injection of streptozotocin. The plasma was then introduced to artificial xerograph wounds in the rats for 10 minutes. Immunohistochemistry assays was performed to determine the level of transforming growth factor (TGF-β1) cytokine. The results showed a low healing rate in the diabetic wounds compared with the wound-healing rate in non-diabetic animals (P diabetic rats (P treatment compared with untreated diabetic wounds (P treatment also resulted in the release of TGF-β1 cytokine from cells in the tissue medium. The findings of this study demonstrate the effect of plasma treatment for wound healing in diabetic rats.

Cytokine Response to Exercise and Its Modulation

Directory of Open Access Journals (Sweden)

Katsuhiko Suzuki

2018-01-01

Full Text Available Strenuous exercise induces such inflammatory responses as leukocytosis (neutrophilia and symptoms as delayed-onset muscle soreness and swelling. However, the association between inflammatory mediator cytokines and oxidative stress is not fully delineated. Herein, in addition to basic background information on cytokines, research findings on exertional effects on cytokine release and the underlying mechanisms and triggers are introduced. Then, the associations among cytokine responses, oxidative stress, and tissue damage are described not only in overloaded skeletal muscle, but also in other internal organs. Furthermore, we introduce preventive countermeasures against the exhaustive exercise-induced pathogenesis together with the possibility of antioxidant interventions.

Changes in cytokines, leptin, and IGF-1 levels in overtrained athletes during a prolonged recovery phase: A case-control study.

Science.gov (United States)

Joro, Raimo; Uusitalo, Arja; DeRuisseau, Keith C; Atalay, Mustafa

2017-12-01

We investigated how cytokines are implicated with overtraining syndrome (OTS) in athletes during a prolonged period of recovery. Plasma IL-6, IL-10, TNF-α, IL-1β, adipokine leptin, and insulin like growth factor-1 (IGF-1) concentrations were measured in overtrained (OA: 5 men, 2 women) and healthy control athletes (CA: 5 men, 5 women) before and after exercise to volitional exhaustion. Measurements were conducted at baseline and after 6 and 12 months. Inflammatory cytokines did not differ between groups at rest. However, resting leptin concentration was lower in OA than CA at every measurement (P IGF-1 decreased with exercise in OA (P IGF-1 were observed. In conclusion, low leptin level at rest and a pro-inflammatory cytokine response to acute exercise may reflect a chronic maladaptation state in overtrained athletes. In contrast, the accentuation of IL-6 and TNF-α responses to acute exercise seemed to associate with the progression of recovery from overtraining.

Increased Blood Levels of Growth Factors, Proinflammatory Cytokines, and Th17 Cytokines in Patients with Newly Diagnosed Type 1 Diabetes.

Directory of Open Access Journals (Sweden)

Kristi Alnek

Full Text Available The production of several cytokines could be dysregulated in type 1 diabetes (T1D. In particular, the activation of T helper (Th type 1 (Th1 cells has been proposed to underlie the autoimmune pathogenesis of the disease, although roles for inflammatory processes and the Th17 pathway have also been shown. Nevertheless, despite evidence for the role of cytokines before and at the onset of T1D, the corresponding findings are inconsistent across studies. Moreover, conflicting data exist regarding the blood cytokine levels in T1D patients. The current study was performed to investigate genetic and autoantibody markers in association with the peripheral blood cytokine profiles by xMap multiplex technology in newly diagnosed young T1D patients and age-matched healthy controls. The onset of young-age T1D was characterized by the upregulation of growth factors, including granulocyte macrophage-colony stimulating factor (GM-CSF and interleukin (IL-7, the proinflammatory cytokine IL-1β (but not IL-6 or tumor necrosis factor [TNF]-α, Th17 cytokines, and the regulatory cytokines IL-10 and IL-27. Ketoacidosis and autoantibodies (anti-IA-2 and -ZnT8, but not human leukocyte antigen (HLA genotype, influenced the blood cytokine levels. These findings broaden the current understanding of the dysregulation of systemic levels of several key cytokines at the young-age onset of T1D and provide a further basis for the development of novel immunoregulatory treatments in this disease.

Cytokines in bipolar disorder

DEFF Research Database (Denmark)

Munkholm, Klaus; Vinberg, Maj; Vedel Kessing, Lars

2012-01-01

BACKGROUND: Current research and hypothesis regarding the pathophysiology of bipolar disorder suggests the involvement of immune system dysfunction that is possibly related to disease activity. Our objective was to systematically review evidence of cytokine alterations in bipolar disorder according...... to affective state. METHODS: We conducted a systemtic review of studies measuring endogenous cytokine concentrations in patients with bipolar disorder and a meta-analysis, reporting results according to the PRISMA statement. RESULTS: Thirteen studies were included, comprising 556 bipolar disorder patients...

Cytokines: applications in domestic food animals.

Science.gov (United States)

Blecha, F

1991-01-01

Cytokines such as human, bovine, and porcine interferons and human and bovine interleukin-1 and interleukin-2 have been used in vivo in cattle and pigs. Colony-stimulating factors and tumor necrosis factor alpha have been evaluated in vitro in food animals. Studies to evaluate cytokines in domestic food animals have shown that specific and nonspecific immunomodulation is possible in immunosuppressed or pathogen-exposed animals. Cytokine prophylaxis or therapy in food animals may have the greatest potential for control of respiratory disease and mastitis.

Serum pregnancy-associated plasma protein A levels in the first, second and third trimester of pregnancy: relation to newborn anthropometric parameters and maternal tobacco smoking.

Science.gov (United States)

Chełchowska, Magdalena; Gajewska, Joanna; Mazur, Joanna; Ambroszkiewicz, Jadwiga; Maciejewski, Tomasz M; Leibschang, Jerzy

2016-12-01

The purpose of this study was to evaluate the associations of the first, second and third trimester serum pregnancy-associated plasma protein A (PAPP-A) concentrations with neonatal anthropometric parameters. The effect of tobacco smoking during pregnancy on PAPP-A level was also studied. One hundred and fifty healthy pregnant women were divided into smoking and tobacco-abstinent groups. Serum PAPP-A level was measured with the KRYPTOR rapid random-access immunoassay analyzer. The relationship between PAPP-A and newborn related outcome as well as markers of estimated intensity of cigarette smoking was evaluated by univariate and multivariate linear regression. Pregnancy-associated plasma protein A concentration was positively correlated with birth weight in the first (β = 31.6; p < 0.001), second (β = 10.6; p < 0.05), and third (β = 4.6; p < 0.001) trimester of gestation. A significant association between PAPP-A and birth body length and head circumference in the second (β = 0.02; p < 0.05) and third trimester (β = 0.01; p < 0.01) was also found. The serum PAPP-A levels were significantly lower in the smoking than in the tobacco-abstinent group in each trimester of pregnancy ( p < 0.001). The largest impact of the number of cigarettes smoked per day on PAPP-A level was found in the second (β = -1.2; p = 0.004) and third trimester (β = -2.6; p = 0.001). Maternal serum PAPP-A levels during gestation might be significant predictors for birth weight. Increased PAPP-A concentrations in the second and third trimester appeared to also be predictive for newborn body length and head circumference. Smoking alters maternal PAPP-A levels in all trimesters, with the greatest impact related to the number of cigarettes smoked per day.

The impact of maternal protein restriction during rat pregnancy upon renal expression of angiotensin receptors and vasopressin-related aquaporins

Directory of Open Access Journals (Sweden)

Cornock Ruth

2010-08-01

Full Text Available Abstract Background Maternal protein restriction during rat pregnancy is known to impact upon fetal development, growth and risk of disease in later life. It is of interest to understand how protein undernutrition influences the normal maternal adaptation to pregnancy. Here we investigated the mechanisms regulating renal haemodynamics and plasma volume during pregnancy, in the context of both normal and reduced plasma volume expansion. The study focused on expression of renal angiotensin receptors (ATR and vasopressin-related aquaporins (AQP, hypothesising that an alteration in the balance of these proteins would be associated with pregnancy per se and with compromised plasma volume expansion in rats fed a low-protein diet. Methods Female Wistar rats were mated and fed a control (18% casein or low-protein (9% casein diet during pregnancy. Animals were anaesthetised on days 5, 10, 15 and 20 of gestation (n = 8/group/time-point for determination of plasma volume using Evans Blue dye, prior to euthanasia and collection of tissues. Expression of the ATR subtypes and AQP2, 3 and 4 were assessed in maternal kidneys by PCR and western blotting. 24 non-pregnant Wistar rats underwent the same procedure at defined points of the oestrous cycle. Results As expected, pregnancy was associated with an increase in blood volume and haemodilution impacted upon red blood cell counts and haemoglobin concentrations. Expression of angiotensin II receptors and aquaporins 2, 3 and 4 was stable across all stages of the oestrus cycle. Interesting patterns of intra-renal protein expression were observed in response to pregnancy, including a significant down-regulation of AQP2. In contrast to previous literature and despite an apparent delay in blood volume expansion in low-protein fed rats, blood volume did not differ significantly between groups of pregnant animals. However, a significant down-regulation of AT2R protein expression was observed in low-protein fed animals

Caffeine synergizes with another coffee component to increase plasma GCSF: linkage to cognitive benefits in Alzheimer's mice.

Science.gov (United States)

Cao, Chuanhai; Wang, Li; Lin, Xiaoyang; Mamcarz, Malgorzata; Zhang, Chi; Bai, Ge; Nong, Jasson; Sussman, Sam; Arendash, Gary

2011-01-01

Retrospective and prospective epidemiologic studies suggest that enhanced coffee/caffeine intake during aging reduces risk of Alzheimer's disease (AD). Underscoring this premise, our studies in AD transgenic mice show that long-term caffeine administration protects against cognitive impairment and reduces brain amyloid-β levels/deposition through suppression of both β- and γ-secretase. Because coffee contains many constituents in addition to caffeine that may provide cognitive benefits against AD, we examined effects of caffeinated and decaffeinated coffee on plasma cytokines, comparing their effects to caffeine alone. In both AβPPsw+PS1 transgenic mice and non-transgenic littermates, acute i.p. treatment with caffeinated coffee greatly and specifically increased plasma levels of granulocyte-colony stimulating factor (GCSF), IL-10, and IL-6. Neither caffeine solution alone (which provided high plasma caffeine levels) or decaffeinated coffee provided this effect, indicating that caffeine synergized with some as yet unidentified component of coffee to selectively elevate these three plasma cytokines. The increase in GCSF is particularly important because long-term treatment with coffee (but not decaffeinated coffee) enhanced working memory in a fashion that was associated only with increased plasma GCSF levels among all cytokines. Since we have previously reported that long-term GCSF treatment enhances cognitive performance in AD mice through three possible mechanisms (e.g., recruitment of microglia from bone marrow, synaptogenesis, and neurogenesis), the same mechanisms could be complimentary to caffeine's established ability to suppress Aβ production. We conclude that coffee may be the best source of caffeine to protect against AD because of a component in coffee that synergizes with caffeine to enhance plasma GCSF levels, resulting in multiple therapeutic actions against AD.

Increased plasma levels of IL-6 in bacteremic periodontis patients after scaling

DEFF Research Database (Denmark)

Forner, Lone; Nielsen, Claus Henrik; Bendtzen, Klaus

2006-01-01

Bacteremia frequently occurs after dental treatment. Periodontal inflammation may influence the incidence, magnitude and duration of bacteremia. The presence of circulating oral bacteria or bacterial components may induce cytokine synthesis in blood cells, which may contribute to the development...... or exacerbation of atherosclerosis. The present study tested the hypothesis that bacteremia occurring after scaling in periodontitis patients results in altered plasma levels of cytokines. Twenty periodontitis patients were subjected to scaling. Blood samples at baseline and at 0.5, 10 and 30 minutes postscaling...

Plasticity of regulatory T cells under cytokine pressure.

Science.gov (United States)

Diaconu, Carmen C; Neagu, Ana I; Lungu, Răzvan; Tardei, Graţiela; Alexiu, Irina; Bleotu, Coralia; Economescu, Mihaela Chivu; Bumbăcea, Roxana S; Pele, Irina; Bumbăcea, Dragoş

2010-01-01

CD4+ T helper (Th) cells have been divided into different subsets as defined by their cytokine products and functions after their activation. CD4+ T cell subsets are continuously discovered and until now Th1, Th2, Th9, Th17, and regulatory T (Treg) cells have been almost unanimously recognized but yet not completely characterized. The selective production of cytokines by each of the subsets is probably the master key of the mechanisms of immune regulation. The cytokine milieu is extremely important on deciding the fate of T cells. Generally, more than one cytokine is needed for differentiating to a particular lineage and just recently it was shown that this status quo of commitment could be challenged. It is well known that cytokines bind to Type I/II cytokine receptors signaling via Janus kinases (JAKs) followed by activation of Signal Transducer and Activator of Transcription (STAT). STAT molecules work together with other transcription factors (Foxp3, RORgammat and RORalpha, T-bet, GATA3, Runx 1, NFAT, etc.) also controlled by cytokines, in modulating the Th phenotype and functions. In this review, we analyze the plasticity of Treg population focusing on the most recent discoveries on how microenvironmental cytokines refine/modify Treg phenotype and function, thus changing their fate.

Cytokine-like factor-1, a novel soluble protein, shares homology with members of the cytokine type I receptor family.

Science.gov (United States)

Elson, G C; Graber, P; Losberger, C; Herren, S; Gretener, D; Menoud, L N; Wells, T N; Kosco-Vilbois, M H; Gauchat, J F

1998-08-01

In this report we describe the identification, cloning, and expression pattern of human cytokine-like factor 1 (hCLF-1) and the identification and cloning of its murine homologue. They were identified from expressed sequence tags using amino acid sequences from conserved regions of the cytokine type I receptor family. Human CLF-1 and murine CLF-1 shared 96% amino acid identity and significant homology with many cytokine type I receptors. CLF-1 is a secreted protein, suggesting that it is either a soluble subunit within a cytokine receptor complex, like the soluble form of the IL-6R alpha-chain, or a subunit of a multimeric cytokine, e.g., IL-12 p40. The highest levels of hCLF-1 mRNA were observed in lymph node, spleen, thymus, appendix, placenta, stomach, bone marrow, and fetal lung, with constitutive expression of CLF-1 mRNA detected in a human kidney fibroblastic cell line. In fibroblast primary cell cultures, CLF-1 mRNA was up-regulated by TNF-alpha, IL-6, and IFN-gamma. Western blot analysis of recombinant forms of hCLF-1 showed that the protein has the tendency to form covalently linked di- and tetramers. These results suggest that CLF-1 is a novel soluble cytokine receptor subunit or part of a novel cytokine complex, possibly playing a regulatory role in the immune system and during fetal development.

Lutein supplementation increases breast milk and plasma lutein concentrations in lactating women and infant plasma concentrations but does not affect other carotenoids.

Science.gov (United States)

Sherry, Christina L; Oliver, Jeffery S; Renzi, Lisa M; Marriage, Barbara J

2014-08-01

Lutein is a carotenoid that varies in breast milk depending on maternal intake. Data are lacking with regard to the effect of dietary lutein supplementation on breast milk lutein concentration during lactation and subsequent plasma lutein concentration in breast-fed infants. This study was conducted to determine the impact of lutein supplementation in the breast milk and plasma of lactating women and in the plasma of breast-fed infants 2-3 mo postpartum. Lutein is the dominant carotenoid in the infant brain and the major carotenoid found in the retina of the eye. Eighty-nine lactating women 4-6 wk postpartum were randomly assigned to be administered either 0 mg/d of lutein (placebo), 6 mg/d of lutein (low-dose), or 12 mg/d of lutein (high-dose). The supplements were consumed for 6 wk while mothers followed their usual diets. Breast milk carotenoids were measured weekly by HPLC, and maternal plasma carotenoid concentrations were measured at the beginning and end of the study. Infant plasma carotenoid concentrations were assessed at the end of the study. No significant differences were found between dietary lutein + zeaxanthin intake and carotenoid concentrations in breast milk and plasma or body mass index at baseline. Total lutein + zeaxanthin concentrations were greater in the low- and high-dose-supplemented groups than in the placebo group in breast milk (140% and 250%, respectively; P Lutein supplementation did not affect other carotenoids in lactating women or their infants. Lactating women are highly responsive to lutein supplementation, which affects plasma lutein concentrations in the infant. This trial was registered at clinicaltrials.gov as NCT01747668. © 2014 American Society for Nutrition.

Cytokine profile determined by data-mining analysis set into clusters of non-small-cell lung cancer patients according to prognosis.

Science.gov (United States)

Barrera, L; Montes-Servín, E; Barrera, A; Ramírez-Tirado, L A; Salinas-Parra, F; Bañales-Méndez, J L; Sandoval-Ríos, M; Arrieta, Ó

2015-02-01

Immunoregulatory cytokines may play a fundamental role in tumor growth and metastases. Their effects are mediated through complex regulatory networks. Human cytokine profiles could define patient subgroups and represent new potential biomarkers. The aim of this study was to associate a cytokine profile obtained through data mining with the clinical characteristics of patients with advanced non-small-cell lung cancer (NSCLC). We conducted a prospective study of the plasma levels of 14 immunoregulatory cytokines by ELISA and a cytometric bead array assay in 110 NSCLC patients before chemotherapy and 25 control subjects. Cytokine levels and data-mining profiles were associated with clinical, quality of life and pathological outcomes. NSCLC patients had higher levels of interleukin (IL)-6, IL-8, IL-12p70, IL-17a and interferon (IFN)-γ, and lower levels of IL-33 and IL-29 compared with controls. The pro-inflammatory cytokines IL-1b, IL-6 and IL-8 were associated with lower hemoglobin levels, worse functional performance status (Eastern Cooperative Oncology Group, ECOG), fatigue and hyporexia. The anti-inflammatory cytokines IL-4, IL-10 and IL-33 were associated with anorexia and lower body mass index. We identified three clusters of patients according to data-mining analysis with different overall survival (OS; 25.4, 16.8 and 5.09 months, respectively, P = 0.0012). Multivariate analysis showed that ECOG performance status and data-mining clusters were significantly associated with OS (RR 3.59, [95% CI 1.9-6.7], P < 0.001 and 2.2, [1.2-3.8], P = 0.005). Our results provide evidence that complex cytokine networks may be used to identify patient subgroups with different prognoses in advanced NSCLC. These cytokines may represent potential biomarkers, particularly in the immunotherapy era in cancer research. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email

Gestational diabetes, preeclampsia and cytokine release: similarities and differences in endothelial cell function.

Science.gov (United States)

Rao, Rashmi; Sen, Suvajit; Han, Bing; Ramadoss, Sivakumar; Chaudhuri, Gautam

2014-01-01

Gestational diabetes, pre-eclampsia as well as intra-uterine infection during pregnancy affects the function of the endothelium both in the mother and the fetus leading to endothelial dysfunction. Gestational diabetes is also associated with an increased incidence of pre-eclampsia and it is likely that both the hyperglycemia as well as the release of cytokines especially TNFα during hyperglycemia may play an important role in the pathogenesis of endothelial dysfunction leading to preeclampsia. Similarly, some but not all studies have suggested that infection of the mother under certain circumstances can also lead to preeclampsia as women with either a bacterial or viral infection were at a higher risk of developing preeclampsia, compared to women without infection and infection also leads to a release in TNFα. Endothelial cells exposed to either high glucose or TNFα leads to an increase in the production of H2O2 and to a decrease in endothelial cell proliferation. The cellular and molecular mechanisms involved in this phenomenon are discussed.Gestational diabetes, pre-eclampsia as well as intra-uterine infection during pregnancy has profound effects on the fetus and long term effects on the neonate. All three conditions affect the function of the endothelium both in the mother and the fetus leading to endothelial dysfunction. Gestational diabetes is also associated with an increased incidence of pre-eclampsia and it is likely that both the hyperglycemia as well as the release of cytokines especially TNFα during hyperglycemia may play an important role in the pathogenesis of endothelial dysfunction leading to preeclampsia. It has also been suggested although not universally accepted that under certain circumstances maternal infection may also predispose to pre-eclampsia. Pre-eclampsia is also associated with the release of TNFα and endothelial dysfunction. However, the cellular and molecular mechanism(s) leading to the endothelial dysfunction by either

Acute maternal rehydration increases the urine production rate in the near-term human fetus

NARCIS (Netherlands)

Haak, MC; Aarnoudse, JG; Oosterhof, H.

OBJECTIVE: We sought to investigate the effect of a decrease of maternal plasma osmolality produced by hypotonic rehydration on the fetal urine production rate in normal near-term human fetuses. STUDY DESIGN: Twenty-one healthy pregnant women attending the clinic for antenatal care were studied

Pro-Inflammatory Cytokine Levels in HIV Infected and Uninfected Pregnant Women with and without Preeclampsia.

Science.gov (United States)

Maharaj, Niren Ray; Phulukdaree, Alisa; Nagiah, Savania; Ramkaran, Prithiksha; Tiloke, Charlette; Chuturgoon, Anil Amichund

2017-01-01

Preeclampsia and HIV/AIDS are inflammatory conditions that contribute significantly to adverse maternal and foetal outcomes. The immune reconstitution effects of HAART on inflammatory mediators has not been adequately studied in pregnancy and may impact on the inflammatory cytokine network in women with co-morbid preeclampsia. Our study evaluated changes in pro-inflammatory cytokines IL-2, TNF-α, IFN-γ and IL-6 in HIV infected preeclamptic women on HAART. A prospective experimental study was conducted at Prince Mshiyeni Memorial Hospital between July 2013 and September 2014. One hundred and ninety three pregnant women were recruited into 4 groups: uninfected normotensive (50; 26%), infected normotensive (45; 23%), uninfected preeclamptic (53; 28%) and infected preeclamptic women (45; 23%). Serum levels of cytokines TNF-α, IFN- γ, IL-2 and IL-6 were determined using commercially available kits and a Cytometric Bead Array (CBA). Comparative data was recorded and analysed descriptively. In the control groups (normotensive), significantly lower values were found in IL-2 (p = 0.010), TNF-α (p = 0.045), and IL-6 (p = 0.005); and a non-significant decrease was observed in IFN-γ (p = 0.345) in HIV infected women on HAART compared to uninfected controls. In the experimental group (preeclamptic) women, significantly reduced levels were observed in IL-2 and TNF-α (p = 0.001; p = 0.000) and non-significant decreases were observed in IFN-γ and IL-6 (p = 0.023; p = 0.086) in HIV infected women on HAART compared with uninfected preeclamptic women. Non-significant differences were observed between uninfected preeclamptic and normotensive women. In uncomplicated/normotensive pregnancies, HIV/HAART is associated with significant decreases in IL-2, TNF-α and IL-6, and in preeclamptic women significant decreases in IL-2 and TNF-α were observed. These findings suggest that HIV/HAART impacts on pro-inflammatory cytokines in women with co-morbid preeclampsia. This provides a

Pro-Inflammatory Cytokine Levels in HIV Infected and Uninfected Pregnant Women with and without Preeclampsia.

Directory of Open Access Journals (Sweden)

Niren Ray Maharaj

Full Text Available Preeclampsia and HIV/AIDS are inflammatory conditions that contribute significantly to adverse maternal and foetal outcomes. The immune reconstitution effects of HAART on inflammatory mediators has not been adequately studied in pregnancy and may impact on the inflammatory cytokine network in women with co-morbid preeclampsia. Our study evaluated changes in pro-inflammatory cytokines IL-2, TNF-α, IFN-γ and IL-6 in HIV infected preeclamptic women on HAART.A prospective experimental study was conducted at Prince Mshiyeni Memorial Hospital between July 2013 and September 2014. One hundred and ninety three pregnant women were recruited into 4 groups: uninfected normotensive (50; 26%, infected normotensive (45; 23%, uninfected preeclamptic (53; 28% and infected preeclamptic women (45; 23%. Serum levels of cytokines TNF-α, IFN- γ, IL-2 and IL-6 were determined using commercially available kits and a Cytometric Bead Array (CBA. Comparative data was recorded and analysed descriptively.In the control groups (normotensive, significantly lower values were found in IL-2 (p = 0.010, TNF-α (p = 0.045, and IL-6 (p = 0.005; and a non-significant decrease was observed in IFN-γ (p = 0.345 in HIV infected women on HAART compared to uninfected controls. In the experimental group (preeclamptic women, significantly reduced levels were observed in IL-2 and TNF-α (p = 0.001; p = 0.000 and non-significant decreases were observed in IFN-γ and IL-6 (p = 0.023; p = 0.086 in HIV infected women on HAART compared with uninfected preeclamptic women. Non-significant differences were observed between uninfected preeclamptic and normotensive women.In uncomplicated/normotensive pregnancies, HIV/HAART is associated with significant decreases in IL-2, TNF-α and IL-6, and in preeclamptic women significant decreases in IL-2 and TNF-α were observed. These findings suggest that HIV/HAART impacts on pro-inflammatory cytokines in women with co-morbid preeclampsia. This provides

Expression of acute phase proteins and inflammatory cytokines in mouse mammary gland following Staphylococcus aureus challenge and in response to milk accumulation

DEFF Research Database (Denmark)

Nazemi, Sasan; Aalbæk, Bent; Kjelgaard-Hansen, Mads

2014-01-01

We used a mouse model of pathogenic (Staphylococcus aureus) and non-pathogenic (teat sealing) mammary inflammation to investigate mRNA expression of several inflammatory cytokines and acute phase proteins (APP) in mammary tissue and liver, and the appearance of some of these factors in plasma and...

Maternal correlates of maternal child feeding practices: a systematic review.

Science.gov (United States)

McPhie, Skye; Skouteris, Helen; Daniels, Lynne; Jansen, Elena

2014-01-01

Establishing healthy eating habits early in life is one important strategy to combat childhood obesity. Given that early maternal child feeding practices have been linked to child food intake and weight, identifying the maternal correlates of maternal child feeding practices is important in order to understand the determinants of childhood obesity; this was the overall aim of the current review. Academic databases were searched for studies examining the relationship between maternal child feeding practices and parenting, personal characteristics and psychopathology of mothers with preschoolers. Papers were limited to those published in English, between January 2000 and June 2012. Only studies with mothers of normally developing children between the ages of 2 and 6 years were included. There were no restrictions regarding the inclusion of maternal nationality or socioeconomic status (SES). Seventeen eligible studies were sourced. Information on the aim, sample, measures and findings of these was summarised into tables. The findings of this review support a relationship between maternal controlling parenting, general and eating psychopathology, and SES and maternal child feeding practices. The main methodological issues of the studies reviewed included inconsistency in measures of maternal variables across studies and cross-sectional designs. We conclude that the maternal correlates associated with maternal child feeding practices are complex, and the pathways by which maternal correlates impact these feeding practices require further investigation. © 2012 John Wiley & Sons Ltd.

Cytokine profile of cervical cancer cells

NARCIS (Netherlands)

Hazelbag, S; Fleuren, GJ; Baelde, JJ; Schuuring, E; Kenter, GG; Gorter, A

2001-01-01

Objective. In patients with cervical carcinoma, the presence of cytokines produced by T(H)2 cells, and the presence of an eosinophilic inflammatory infiltrate, has been associated with a less effective immune response and tumor progression. In the present study, we have investigated the cytokine

Cytokine profile of cervical cancer cells

NARCIS (Netherlands)

Hazelbag, S; Fleuren, GJ; Baelde, JJ; Schuuring, E; Kenter, GG; Gorter, A

Objective. In patients with cervical carcinoma, the presence of cytokines produced by T(H)2 cells, and the presence of an eosinophilic inflammatory infiltrate, has been associated with a less effective immune response and tumor progression. In the present study, we have investigated the cytokine

Inherited Variation in Cytokine, Acute Phase Response, and Calcium Metabolism Genes Affects Susceptibility to Infective Endocarditis

Directory of Open Access Journals (Sweden)

Anastasia V. Ponasenko

2017-01-01

Full Text Available Infective endocarditis (IE is a septic inflammation of the endocardium. Recognition of microbial patterns, cytokine and acute phase responses, hemostasis features, and alterations in plasma lipid and calcium profile all have been reported to affect pathogenesis and clinical course of IE. Having recruited 123 patients with IE and 300 age-, sex-, and ethnicity-matched healthy blood donors, we profiled their genomic DNA for 35 functionally significant polymorphisms within the 22 selected genes involved in the abovementioned pathways, with the further genetic association analysis. We found that the G/A genotype of the rs1143634 polymorphism within the IL1B gene, the G/T genotype of the rs3212227 polymorphism within the IL12B gene, the A/G genotype of the rs1130864 polymorphism within the CRP gene, and the G allele of the rs1801197 polymorphism within the CALCR gene were associated with a decreased risk of IE whereas the T/T genotype of the rs1205 polymorphism within the CRP gene was associated with a higher risk of IE. Furthermore, heterozygous genotypes of the rs1143634 and rs3212227 polymorphisms were associated with the higher plasma levels of IL-1β and IL-12, respectively. Our results indicate that inherited variation in the cytokine, acute phase response, and calcium metabolism pathways may be linked to IE.

Inherited Variation in Cytokine, Acute Phase Response, and Calcium Metabolism Genes Affects Susceptibility to Infective Endocarditis

Science.gov (United States)

Rutkovskaya, Natalia V.; Kondyukova, Natalia V.; Odarenko, Yuri N.; Kazachek, Yana V.; Tsepokina, Anna V.; Barbarash, Leonid S.

2017-01-01

Infective endocarditis (IE) is a septic inflammation of the endocardium. Recognition of microbial patterns, cytokine and acute phase responses, hemostasis features, and alterations in plasma lipid and calcium profile all have been reported to affect pathogenesis and clinical course of IE. Having recruited 123 patients with IE and 300 age-, sex-, and ethnicity-matched healthy blood donors, we profiled their genomic DNA for 35 functionally significant polymorphisms within the 22 selected genes involved in the abovementioned pathways, with the further genetic association analysis. We found that the G/A genotype of the rs1143634 polymorphism within the IL1B gene, the G/T genotype of the rs3212227 polymorphism within the IL12B gene, the A/G genotype of the rs1130864 polymorphism within the CRP gene, and the G allele of the rs1801197 polymorphism within the CALCR gene were associated with a decreased risk of IE whereas the T/T genotype of the rs1205 polymorphism within the CRP gene was associated with a higher risk of IE. Furthermore, heterozygous genotypes of the rs1143634 and rs3212227 polymorphisms were associated with the higher plasma levels of IL-1β and IL-12, respectively. Our results indicate that inherited variation in the cytokine, acute phase response, and calcium metabolism pathways may be linked to IE. PMID:28659664

Demystifying the cytokine network: Mathematical models point the way.

Science.gov (United States)

Morel, Penelope A; Lee, Robin E C; Faeder, James R

2017-10-01

Cytokines provide the means by which immune cells communicate with each other and with parenchymal cells. There are over one hundred cytokines and many exist in families that share receptor components and signal transduction pathways, creating complex networks. Reductionist approaches to understanding the role of specific cytokines, through the use of gene-targeted mice, have revealed further complexity in the form of redundancy and pleiotropy in cytokine function. Creating an understanding of the complex interactions between cytokines and their target cells is challenging experimentally. Mathematical and computational modeling provides a robust set of tools by which complex interactions between cytokines can be studied and analyzed, in the process creating novel insights that can be further tested experimentally. This review will discuss and provide examples of the different modeling approaches that have been used to increase our understanding of cytokine networks. This includes discussion of knowledge-based and data-driven modeling approaches and the recent advance in single-cell analysis. The use of modeling to optimize cytokine-based therapies will also be discussed. Copyright © 2016 Elsevier Ltd. All rights reserved.

Suppressor of cytokine signalling-3 expression inhibits cytokine-mediated destruction of primary mouse and rat pancreatic islets and delays allograft rejection

DEFF Research Database (Denmark)

Rønn, S G; Börjesson, A; Bruun, C

2008-01-01

The pro-inflammatory cytokines IL-1 and IFNgamma are critical molecules in immune-mediated beta cell destruction leading to type 1 diabetes mellitus. Suppressor of cytokine signalling (SOCS)-3 inhibits the cytokine-mediated destruction of insulinoma-1 cells. Here we investigate the effect of SOCS...

Lutein Supplementation Increases Breast Milk and Plasma Lutein Concentrations in Lactating Women and Infant Plasma Concentrations but Does Not Affect Other Carotenoids123

Science.gov (United States)

Sherry, Christina L.; Oliver, Jeffery S.; Renzi, Lisa M.; Marriage, Barbara J.

2014-01-01

Lutein is a carotenoid that varies in breast milk depending on maternal intake. Data are lacking with regard to the effect of dietary lutein supplementation on breast milk lutein concentration during lactation and subsequent plasma lutein concentration in breast-fed infants. This study was conducted to determine the impact of lutein supplementation in the breast milk and plasma of lactating women and in the plasma of breast-fed infants 2–3 mo postpartum. Lutein is the dominant carotenoid in the infant brain and the major carotenoid found in the retina of the eye. Eighty-nine lactating women 4–6 wk postpartum were randomly assigned to be administered either 0 mg/d of lutein (placebo), 6 mg/d of lutein (low-dose), or 12 mg/d of lutein (high-dose). The supplements were consumed for 6 wk while mothers followed their usual diets. Breast milk carotenoids were measured weekly by HPLC, and maternal plasma carotenoid concentrations were measured at the beginning and end of the study. Infant plasma carotenoid concentrations were assessed at the end of the study. No significant differences were found between dietary lutein + zeaxanthin intake and carotenoid concentrations in breast milk and plasma or body mass index at baseline. Total lutein + zeaxanthin concentrations were greater in the low- and high-dose–supplemented groups than in the placebo group in breast milk (140% and 250%, respectively; P Lutein supplementation did not affect other carotenoids in lactating women or their infants. Lactating women are highly responsive to lutein supplementation, which affects plasma lutein concentrations in the infant. This trial was registered at clinicaltrials.gov as NCT01747668. PMID:24899160

Inverse correlation between maternal plasma asymmetric dimethylarginine (ADMA) and birthweight percentile in women with impaired placental perfusion: circulating ADMA as an NO-independent indicator of fetal growth restriction?

Science.gov (United States)

Tsikas, Dimitrios; Bollenbach, Alexander; Savvidou, Makrina D

2018-02-01

L-Arginine (Arg) is the enzymatic precursor of nitric oxide (NO) which has multiple biological functions. Asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) are endogenous inhibitors of NO. We hypothesized that the ADMA and SDMA have additional biological functions in pregnancy, beyond NO synthesis, and may play a role in the regulation of birthweight (BW). To investigate this issue, we measured the plasma concentration of ADMA, SDMA, Arg and the NO metabolites nitrite and nitrate, at 23-25 weeks of gestation in women with normal placental function (Group 1) and in women with impaired placental perfusion; 19 of these women had normal outcome (Group 2), 14 had a fetus that was growth restricted (Group 3), and 10 women eventually developed preeclampsia (Group 4). BW percentile was found to inversely correlate with maternal plasma ADMA concentration in Group 3 (r = - 0.872, P restriction in women with impaired placental perfusion independent of NO.

Maternal Mortality in a Nigerian Maternity Hospital | Olopade ...

African Journals Online (AJOL)

Despite recent focus on maternal mortality in Nigeria, its rates remain unacceptably high in Nigeria. A retrospective case-control study was carried out at Adeoyo Maternity Hospital, Ibadan between January 2003 and December 2004. This was to determine the maternal mortality ratio in a secondary health facility, to identify ...

[Maternal phenylketonuria].

Science.gov (United States)

Bókay, János; Kiss, Erika; Simon, Erika; Szőnyi, László

2013-05-05

Elevated maternal phenylalanine levels during pregnancy are teratogenic, and may result in embryo-foetopathy, which could lead to stillbirth, significant psychomotor handicaps and birth defects. This foetal damage is known as maternal phenylketonuria. Women of childbearing age with all forms of phenylketonuria, including mild variants such as hyperphenylalaninaemia, should receive detailed counselling regarding their risks for adverse foetal effects, optimally before contemplating pregnancy. The most assured way to prevent maternal phenylketonuria is to maintain the maternal phenylalanine levels within the optimal range already before conception and throughout the whole pregnancy. Authors review the comprehensive programme for prevention of maternal phenylketonuria at the Metabolic Center of Budapest, they survey the practical approach of the continuous maternal metabolic control and delineate the outcome of pregnancies of mothers with phenylketonuria from the introduction of newborn screening until most recently.

T helper-2 cytokine/regulatory T-cell gene polymorphisms and their relation with risk of psoriasis in a South Indian Tamil cohort.