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Sample records for placental cytokine profile

  1. Altered cytokine network in gestational diabetes mellitus affects maternal insulin and placental-fetal development.

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    Wedekind, Lauren; Belkacemi, Louiza

    2016-01-01

    Pregnancy is characterized by an altered inflammatory profile, compared to the non-pregnant state with an adequate balance between pro-and anti-inflammatory cytokines needed for normal development. Cytokines are small secreted proteins expressed mainly in immunocompetent cells in the reproductive system. From early developmental stages onward, the secretory activity of placenta cells clearly contributes to increase local as well as systemic levels of cytokines. The placental production of cytokines may affect mother and fetus independently. In turn because of this unique position at the maternal fetal interface, the placenta is also exposed to the regulatory influence of cytokines from maternal and fetal circulations, and hence, may be affected by changes in any of these. Gestational diabetes mellitus (GDM) is associated with an overall alteration of the cytokine network. This review discusses the changes that occur in cytokines post GDM and their negative effects on maternal insulin and placental-fetal development.

  2. Human placental trophoblasts express the immunosuppressive cytokine IL-35.

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    Mao, Haiting; Gao, Wenjuan; Ma, Chao; Sun, Jintang; Liu, Jia; Shao, Qianqian; Song, Bingfeng; Qu, Xun

    2013-07-01

    Studies of maternal-fetal tolerance focus on defining mechanisms for establishment of immunological privilege within the uterus during pregnancy. Fetal trophoblasts play a key role in maternal tolerance, in part through cytokines production. As a novel inhibitory cytokine, IL-35 is produced by Foxp3(+) regulatory T cells (Tregs) and mediates maximal suppression of Tregs. The purpose of the study is to analyze the expression of IL-35 in first-trimester human placental trophoblasts. IL-35 expression was detected at both protein and mRNA levels by immunohistochemical staining and quantitative real-time PCR method, respectively and secretion of IL-35 was measured by ELISA assay. Our results demonstrated that human trophoblasts constitutively expressed IL-35. Ebi3 and p35 (two subunits of IL-35) mRNA was shown to be co-expressed in trophoblast cells. Moreover, large amounts of secreted IL-35 were detected in the supernatants of trophoblast cells. But we did not detect the constitutive expression of IL-35 in decidual stromal cells. Our findings confirmed for the first time that first-trimester human trophoblast cells expressed and secreted IL-35, which might contribute to their suppressive capacity to maternal immune cells. Therefore, IL-35 may be an important factor of the cytokine network regulating local immune responses during human pregnancy.

  3. Protein Profiling of Preeclampsia Placental Tissues

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    Shu, Chang; Liu, Zitao; Cui, Lifeng; Wei, Chengguo; Wang, Shuwen; Tang, Jian Jenny; Cui, Miao; Lian, Guodong; Li, Wei; Liu, Xiufen; Xu, Hongmei; Jiang, Jing; Lee, Peng; Zhang, David Y.

    2014-01-01

    Preeclampsia is a multi-system disorder involved in pregnancy without an effective treatment except delivery. The precise pathogenesis of this complicated disorder is still not completely understood. The objective of this study is to evaluate the alterations of protein expression and phosphorylations that are important in regulating placental cell function in preterm and term preeclampsia. Using the Protein Pathway Array, 38 proteins in placental tissues were found to be differentially expressed between preterm preeclampsia and gestational age matched control, while 25 proteins were found to be expressed differentially between term preeclampsia and matched controls. Among these proteins, 16 proteins and their associated signaling pathways overlapped between preterm and term preeclampsia, suggesting the common pathogenesis of two subsets of disease. On the other hand, many proteins are uniquely altered in either preterm or term preeclampsia and correlated with severity of clinical symptoms and outcomes, therefore, providing molecular basis for these two subsets of preeclampsia. Furthermore, the expression levels of some of these proteins correlated with neonatal small for gestational age (PAI-1 and PAPP-A) and adverse outcomes (Flt-1) in women with preterm preeclampsia. These proteins could potentially be used as candidate biomarkers for predicting outcomes of preeclampsia. PMID:25392996

  4. Protein profiling of preeclampsia placental tissues.

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    Shu, Chang; Liu, Zitao; Cui, Lifeng; Wei, Chengguo; Wang, Shuwen; Tang, Jian Jenny; Cui, Miao; Lian, Guodong; Li, Wei; Liu, Xiufen; Xu, Hongmei; Jiang, Jing; Lee, Peng; Zhang, David Y; He, Jin; Ye, Fei

    2014-01-01

    Preeclampsia is a multi-system disorder involved in pregnancy without an effective treatment except delivery. The precise pathogenesis of this complicated disorder is still not completely understood. The objective of this study is to evaluate the alterations of protein expression and phosphorylations that are important in regulating placental cell function in preterm and term preeclampsia. Using the Protein Pathway Array, 38 proteins in placental tissues were found to be differentially expressed between preterm preeclampsia and gestational age matched control, while 25 proteins were found to be expressed differentially between term preeclampsia and matched controls. Among these proteins, 16 proteins and their associated signaling pathways overlapped between preterm and term preeclampsia, suggesting the common pathogenesis of two subsets of disease. On the other hand, many proteins are uniquely altered in either preterm or term preeclampsia and correlated with severity of clinical symptoms and outcomes, therefore, providing molecular basis for these two subsets of preeclampsia. Furthermore, the expression levels of some of these proteins correlated with neonatal small for gestational age (PAI-1 and PAPP-A) and adverse outcomes (Flt-1) in women with preterm preeclampsia. These proteins could potentially be used as candidate biomarkers for predicting outcomes of preeclampsia.

  5. Distinct First Trimester Cytokine Profiles for Gestational Hypertension and Preeclampsia.

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    Tangerås, Line H; Austdal, Marie; Skråstad, Ragnhild B; Salvesen, Kjell Å; Austgulen, Rigmor; Bathen, Tone F; Iversen, Ann-Charlotte

    2015-11-01

    Gestational hypertension and preeclampsia involve dysregulated maternal inflammatory responses to pregnancy, but whether such responses differ between the disorders has not been determined. We aimed to investigate disease-specific early pregnancy serum cytokine profiles of women subsequently developing gestational hypertension or preeclampsia for new insight into the underlying pathogeneses and differences between the disorders. The study cohort consisted of 548 pregnant Norwegian women who were either multiparous with previous gestational hypertension or preeclampsia or were nulliparous. Maternal sera at gestational weeks 11(0)-13(6) were assayed for 27 cytokines, C-reactive protein, total cholesterol, high-density lipoprotein, triglyceride, creatinine, calcium, uric acid, and placental growth factor. Compared with normotensive women, women with both hypertensive conditions presented an atherogenic lipid profile at early gestation, but only those later developing gestational hypertension had significantly higher serum levels of interleukin (IL)-5 and IL-12. Comparing the 2 hypertensive pregnancy disorders, women subsequently developing gestational hypertension had higher serum levels of IL-1β, IL-5, IL-7, IL-8, IL-13, basic fibroblast growth factor, and vascular endothelial growth factor than the women subsequently developing preeclampsia. This study identifies early pregnancy differences in serum cytokine profiles for gestational hypertension and preeclampsia. © 2015 American Heart Association, Inc.

  6. Cytokine profile in murine toxoplasmosis

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    Funda Dogruman-Al; Isil Fidan; Bekir Celebi; Emine Yesilyurt; Berna Erdal; Cahit Babur; Semra Kustimur

    2011-01-01

    Objective: To investigate which cytokines are produced after acute infection of mice withToxoplasma gondii (T. Gondii) RH strain. Methods: Mus domesticus domesticus mice in infected group were inoculated with with highly virulent T. Gondii RH strain by intraperitoneally. Serum samples were obtained from infected and non-infected mice for cytokine levels for ELISA assay. Results: The concentrations of tumor necrosis factor-α, interferonγ, interleukin (IL)-10 and IL-12 in the cardiac blood sample of the infected mice were significantly higher than those in uninfected controls (P0.05). Conclusions: According to our findings, immune response into T helper type 1 was predominant during acute T. gondii infection. Further characterization and purification of Toxoplasma molecule(s) implicated in the regulation of cytokines could lead to the development of new drug prospects to control Toxoplasma infection.

  7. Association between Placental Lesions, Cytokines and Angiogenic Factors in Pregnant Women with Preeclampsia.

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    Ingrid C Weel

    Full Text Available Preeclampsia (PE is considered the leading cause of maternal and perinatal morbidity and mortality. The placenta seems to play an essential role in this disease, probably due to factors involved in its formation and development. The present study aimed to investigate the association between placental lesions, cytokines and angiogenic factors in pregnant women with preeclampsia (PE. We evaluated 20 normotensive pregnant women, 40 with early-onset PE and 80 with late-onset PE. Placental samples were analyzed for histopathology, immunohistochemistry and determination of granulocyte-macrophage colony-stimulating factor (GM-CSF, interleukin-10 (IL-10, transforming growth factor-beta 1 (TGF-β1, tumor necrosis factor-alpha (TNF-α, placental growth factor (PlGF, vascular endothelial growth factor (VEGF, fms-like tyrosine-kinase-1 (Flt-1 and endoglin (Eng levels. Higher percentages of increased syncytial knots and increased perivillous fibrin deposits, and greater levels of TNF-α, TGF-β1and Flt-1 were detected in placentas from early-onset PE. Levels of IL-10, VEGF and PlGF were decreased in PE versus normotensive placentas. Both the TNF-α/IL-10 and sFlt-1/PlGF ratios were higher in placental homogenate of early-onset PE than late-onset PE and control groups. The more severe lesions and the imbalance between TNF-α/IL-10 and PlGF/sFlt-1 in placentas from early-onset PE allows differentiation of early and late-onset PE and suggests higher placental impairment in early-onset PE.

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

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    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

  9. Significance and changes of peripheral blood, placental tissue cytokines and NO in patients with hypertensive disorders of pregnancy

    Institute of Scientific and Technical Information of China (English)

    Jie-Ning Zou; Li Xiong; Jin-Tao Zhou

    2015-01-01

    Objective:To investigate significance and changes of placental tissue cytokines and NO levels in peripheral blood of patients with hypertensive disorders of pregnancy and their relationship. Methods: A total of 75 cases of hypertensive disorders of pregnancy were selected as researching objects, including 26 cases of pregnancy-induced hypertension subgroup, 29 cases of patients with mild preeclampsia and 20 cases of subgroups severe preeclampsia subgroups;another 45 cases of healthy pregnant women were also selected as the control group. The maternal blood and placental tissue factor (TNF-α, IL-6, hs-CRP) and NO levels of the four groups were compared.Results:Peripheral blood and placental tissue cytokine levels of patients with hypertensive disorders of pregnancy were significantly higher, NO levels were significantly lower than the control group (P<0.01). In subgroups peripheral blood and placenta cytokine levels were gradually increased, NO levels were increased with gestational hypertension disease degree (P<0.05); NO was significantly negatively correlated with TNF-α, IL-6, hs-CRP levels (P<0.01).Conclusions: During pregnancy, monitoring of TNF-α, IL-6, hs-CRP and NO in placental tissue is helpful in prediction and evaluation of early hypertensive disorders of pregnancy, and is also helpful in treatment.

  10. Characterization of immune cells and cytokine localization in the rat utero-placental unit mid- to late gestation.

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    Tessier, Daniel R; Raha, Sandeep; Holloway, Alison C; Yockell-Lelièvre, Julien; Tayade, Chandrakant; Gruslin, Andrée

    2015-08-01

    The success of pregnancy is dependent on the precise regulation of the immune response within the utero-placental environment. Rats are beginning to be widely used as a model for human immune-related pregnancy complications. However, our knowledge of immune cells and cytokine localization in the rat utero-placental tissue is limited. The current study aimed to localize the immune cell populations, including uterine natural killer (uNK) cells, neutrophils, and macrophages within the rat utero-placental unit at two crucial gestational ages, gestational days 15.5 and 18.5. In addition, we characterized the distribution of the cytokines TNFα, IFNγ, and IL-10 in the utero-placental regions at both the above-mentioned gestational ages. Our study has demonstrated co-localization TNFα and IFNγ with uNK cells in perivascular regions of the rat mesometrial triangle at both gestational ages. Neutrophils and IL-10-positive cells were localized at the maternal-fetal interface and in the spiral artery lumen of the rat mesometrial triangle at both gestational ages. TNFα and IL-10 demonstrated a temporal change in the localization from GD15.5 to GD18.5, which coincides with the leading edge of trophoblast invasion into the mesometrial triangle. The current study furthers our knowledge of the localization of uterine immune cells and relevant cytokines, and provides a base from which to research the function of these immune cells and cytokines during rat pregnancy as a model to study human immune-related pregnancy complications.

  11. Caspase-1-mediated Cytokine Release from Gestational Tissues, Placental and Cord Blood

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    Raheela N Khan

    2015-06-01

    Full Text Available Distinguishing between fetal and maternal inflammatory responses is necessary for understanding the immune interplay either side of the placenta. Fetal immunity reaches maturity during extrauterine life and while basic inflammatory responses afford a certain degree of protection in utero fetuses are vulnerable to infection. With the discovery of inflammasomes – intracellular scaffolds that facilitate the elaboration of reactions resulting in the release of mature interleukin-1 IL-1 - it is necessary to consider how are inflammatory stimuli are processed. The purinergic P2X7 receptor located on haematopoietic cells is a key intermediary in signal transduction initiated at Toll-like receptors (TLR terminating in release of the mature IL-1 product. We demonstrate herein that IL-1 release from fetal membranes and mononuclear cells isolated from cord, placental and maternal blood, obtained at term, is P2X7- and caspase-1 dependent. The P2X7-dependent release of the cytokine, which was highest from choriodecidua, was attenuated by progesterone (P4, prolactin and an NFkB inhibitor. The NLRP3 inflammasome appears necessary for the processing of IL-1 in gestational tissues and leukocytes.

  12. EFFECTS OF SECRETABLE PLACENTAL FACTORS UPON SECRETION OF CYTOKINES BY THP-1 MONOCYTE-LIKE CELLS

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    Ya. S. Onokhina

    2013-01-01

    Full Text Available Abstract. Мonocytes in feto-placental circulation are exposed to factors secreted by placental tissue. These factors influence monocyte functions in pregnancy. In present study, an in vitro model (monocyte-like THP-1 cells was used for assessing effects of soluble placental factors obtained from women with physiological pregnancies, or preeclampsia cases. The following effects of placental factors were revealed: increased secretion of VEGF by THP-1 cells along with decreased secretion of IL-6, IL-8 and MCP-1 under the influence of placental factors from the I. trimester of pregnancy in comparison with III. trimester. Secretion of IL-6 and MCP-1 by THP-1 cells was increased, and secretion of soluble TNFRII was decreased upon co-cultivation with soluble placental factors from the women with preeclampsia, as compared with placental products from physiological pregnancies.The work is supported by grants ГК № 02.740.11.0711 from Ministry of Education and Science, and НШ-3594.2010.7 grant from the President of Russian Federation.

  13. 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 pro

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

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    Salomon, Carlos; Torres, Maria Jose; Kobayashi, Miharu; Scholz-Romero, Katherin; Sobrevia, Luis; Dobierzewska, Aneta; Illanes, Sebastian E; Mitchell, Murray D; Rice, Gregory E

    2014-01-01

    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 (pexosomes present in maternal plasma increased significantly with gestational age by more that two-fold (pExosomes 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.

  15. 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.

  16. Pro-inflammatory cytokines profiles in Nigerian pregnant women infected withPlasmodium falciparum malaria

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    Nmorsi OPG; Isaac C; Ohaneme BA; Obiazi HAK

    2010-01-01

    Objective:To investigate the pro-inflammatory cytokines profiles in in Nigerian pregnant women infected withPlasmodium falciparum (P. falciparum) malaria.Methods: Peripheral, and placental blood samples were collected from96 consenting volunteers comprising76 P. falciparium infected pregnant women and 20 healthy uninfected pregnant women in Ekpoma, Nigeria, and subjected to ELISA for cytokines evaluation.Results: Increased serum concentrations of interferon-gamma(IFN-γ) was observed in infected pregnant women than their uninfected counterparts[(31.2±20.9)pg/mL vs (1.8±0.9) pg/mL] and these differences were statistically significant(″2= 26.18,P0.05). The interleukin-6 (IL-6) was significantly elevated in infected pregnant women (81.0±26.1 pg/mL) than in the uninfected pregnant women [(25.0±5.0) pg/mL](″2 = 29.58,P<0.05). In all, mean cytokines concentration of IL-6, IL-12 andIFN-γ in the placental blood from infected pregnant women were (53.5±23.4) pg/mL, (8.7±6.9) pg/mL and(16.4±4.0) pg/mL, respectively. The multigravidae had a higher haemoglobin level of 10.2 g/dL and birth weight of3 000 g than the primigrivadae with lower haemoglobin level of7.5g/dL and birth weight of2 430 g. Conclusions: The elevatedIFN-γamong the malarous pregnant women implicates it as the major cytokine mediator in the host responses to systematicP. falciparummalaria in our locality.

  17. INVESTIGATION OF CYTOKINE PROFILE IN PATIENTS WITH REACTIVE ARTHRITIS

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    T. V. Gaponova

    2008-01-01

    Full Text Available Abstract. Pathogenesis of reactive arthritis (ReA is not clear yet. Several trials suggest that increased production of proinflammatory cytokines is responsible for development of arthritis in ReA, while other studies report that Th1 cytokine response in ReA is impaired in favor of Th2 response. The aim of our study was to investigate serum levels of cytokines IL-1β, IL-4, IL-6, TNFα, IFNγ and IL-1Ra in the patients with ReA of different etiology, as compared with infection-related arthritis. The results of our study had demonstrated that serum levels of IL-1β and TNFα in the patients with ReA were significantly higher, whereas IL-1Ra, IL-4, IL-6 proved to be significantly lower than in healthy controls. Serum levels of IL-6 were significantly higher in patients with chronic ReA, as compared to the cases of acute and recurrent ReA. No significant differences in cytokine profiles were found between the patients with ReA, and the persons with infection-related arthritis. The data obtained are, generally, suggestive for proinflammatory Th1 cytokine profile in ReA patients studied, this confirming the mostly assumed pathogenetic hypothesis for reactive arthritis where an underlying cytokine imbalance is suggested. (Med. Immunol., 2008, vol. 10, N 2-3, pp 167-172.

  18. Human astrocytes: secretome profiles of cytokines and chemokines.

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    Sung S Choi

    Full Text Available Astrocytes play a key role in maintenance of neuronal functions in the central nervous system by producing various cytokines, chemokines, and growth factors, which act as a molecular coordinator of neuron-glia communication. At the site of neuroinflammation, astrocyte-derived cytokines and chemokines play both neuroprotective and neurotoxic roles in brain lesions of human neurological diseases. At present, the comprehensive profile of human astrocyte-derived cytokines and chemokines during inflammation remains to be fully characterized. We investigated the cytokine secretome profile of highly purified human astrocytes by using a protein microarray. Non-stimulated human astrocytes in culture expressed eight cytokines, including G-CSF, GM-CSF, GROα (CXCL1, IL-6, IL-8 (CXCL8, MCP-1 (CCL2, MIF and Serpin E1. Following stimulation with IL-1β and TNF-α, activated astrocytes newly produced IL-1β, IL-1ra, TNF-α, IP-10 (CXCL10, MIP-1α (CCL3 and RANTES (CCL5, in addition to the induction of sICAM-1 and complement component 5. Database search indicated that most of cytokines and chemokines produced by non-stimulated and activated astrocytes are direct targets of the transcription factor NF-kB. These results indicated that cultured human astrocytes express a distinct set of NF-kB-target cytokines and chemokines in resting and activated conditions, suggesting that the NF-kB signaling pathway differentially regulates gene expression of cytokines and chemokines in human astrocytes under physiological and inflammatory conditions.

  19. Cytokine profile in two siblings with neonatal lupus erythematosus.

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    Shimozawa, Hironori; Kono, Yumi; Matano, Miyuki; Suzuki, Yume; Koike, Yasunori; Yada, Yukari; Yamagata, Takanori; Takahashi, Naoto

    2015-12-01

    We studied the cytokine profile of two siblings with neonatal lupus erythematosus (NLE) born to a mother positive for serum anti-Ro and -La antibodies, who did not receive any medication during the two pregnancies. The first sibling was found to have complete atrioventricular block in utero and became severely ill after birth. He fulfilled the diagnostic criteria for hemophagocytic lymphohistiocytosis on day 2. The second sibling did not have any fetal symptoms. He was generally stable after birth, but with typical skin rash. Laboratory data suggested that they both had hypercytokinemia during the neonatal period, requiring corticosteroid treatment. Interleukin (IL)-6, interferon-γ, IL-8 and monocyte chemotactic protein-1 were elevated in both cases, while IL-12, IL-13 and IL-17 were elevated only in the second sibling. Comparison of the cytokine profiles suggests the potential roles of different cytokines in the onset and clinical manifestations of NLE.

  20. CYTOKINE PROFILE FEATURES IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE

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    E. Р. Kalinina

    2012-01-01

    Full Text Available Abstract. We studied cytokine profile in blood and exhaled breath condensate (EBC in patients with chronic obstructive pulmonary disease (COPD being in remission state. It is shown that pro- and anti-inflammatory cytokine contents depended on the disease severity, both in whole blood and EBC of the COPD patients. We have revealed an increase in TNFα, s-TNFα RI, TGF-β1 and bFGF in EBC of patients with COPD manifestations, thus being indicative for progression of metabolic changes in lung tissue, and advanced stage of respiratory functional disturbances. Cytokine profile abnormalities in COPD patients resulting, in part, from systemic and local disorders of cellular immunity, represent a major pathogenetic mechanism determining the disease progression.

  1. Changes of the cytokine profile in inflammatory bowel diseases

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    Gy(o)rgyi Müzes; Béla Molnár; Zsolt Tulassay; Ferenc Sipos

    2012-01-01

    Cytokines are indispensable signals of the mucosaassociated immune system for maintaining normal gut homeostasis.An imbalance of their profile in favour of inflammation initiation may lead to disease states,such as that is observed in inflammatory bowel diseases (IBD).Although Crohn's disease (CD) is often described as a prototype of T-helper 1-type diseases,and ulcerative colitis (UC) is traditionally viewed as a T-helper 2-mediated condition,the classic paradigm,which categorises cytokines into pro-and anti-inflammatory groups,has recently been changed.The inflammation regulatory pathways may not be mutually exclusive as individual cytokines can have diverse and even opposing functions in various clinical and immunological settings.None the less there are many common immunological responses in IBD that are mediated by cytokines.Although they regulate and influence the development,course and recurrence of the inflammatory process,the concrete pathogenic role of these small signaling molecules is sometimes not unambiguous in the subtypes of the disease.Our aim is to review the current information about pro-and anti-inflammatory effects of traditionally studied and recently discovered cytokines in the pathogenesis of UC and CD.The better understanding of their production and functional activity may lead to the development of new therapeutic modalities.

  2. Cytokine profile of rats fed a diet containing shrimp

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    Elizabeth Lage Borges

    2013-02-01

    Full Text Available OBJECTIVE: Studies have shown that shrimps reduced the tensile strength of scars in rat skin. The aim of the present study was to assess the cytokine profile of rats fed shrimp. METHODS: Group 1 (control received a regular diet and Group 2 (experimental received a diet containing 33% shrimp for nine days. The two diets contained the same amounts of proteins, fats and carbohydrates. Serum cytokine levels were determined by ELISA and a segment of the jejunum was taken to investigate its histological morphology and eosinophil infiltrate. RESULTS: The experimental group had lower serum levels of interleukin-4 (IL-4 (14.4±1.9 versus 18.11±2.6pg/mL; p<0.05 and IL-10 (5.0±0.98 versus 7.5±1.2pg/mL; p<0.05 and higher levels of IL-6 (17.8±2.3 versus 3.2±0.4pg/mL, p<0.001 than controls. Morphologically, the shrimp-based diet caused an architectural disorganization of the intestinal mucosa and a greater amount of eosinophils in the jejunal villus. CONCLUSION: Our data suggests that shrimp consumption leads to a significant increase in the cytokine IL-6, a decrease in the immunomodulatory cytokine IL-10 in the serum of rats, and high eosinophil infiltration in the jejunum. The cytokine profile typical of inflammation and the histological aspect of the jejunum are compatible with food allergy.

  3. Cytokine profile and lymphocyte subsets in type 2 diabetes

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    C.O. Francisco

    2016-01-01

    Full Text Available Type 2 diabetes mellitus (T2D is a metabolic disease with inflammation as an important pathogenic background. However, the pattern of immune cell subsets and the cytokine profile associated with development of T2D are unclear. The objective of this study was to evaluate different components of the immune system in T2D patients' peripheral blood by quantifying the frequency of lymphocyte subsets and intracellular pro- and anti-inflammatory cytokine production by T cells. Clinical data and blood samples were collected from 22 men (51.6±6.3 years old with T2D and 20 nonsmoking men (49.4±7.6 years old who were matched for age and sex as control subjects. Glycated hemoglobin, high-sensitivity C-reactive protein concentrations, and the lipid profile were measured by a commercially available automated system. Frequencies of lymphocyte subsets in peripheral blood and intracellular production of interleukin (IL-4, IL-10, IL-17, tumor necrosis factor-α, and interferon-γ cytokines by CD3+ T cells were assessed by flow cytometry. No differences were observed in the frequency of CD19+ B cells, CD3+CD8+ and CD3+CD4+ T cells, CD16+56+ NK cells, and CD4+CD25+Foxp3+ T regulatory cells in patients with T2D compared with controls. The numbers of IL-10- and IL-17-producing CD3+ T cells were significantly higher in patients with T2D than in controls (P<0.05. The frequency of interferon-γ-producing CD3+ T cells was positively correlated with body mass index (r=0.59; P=0.01. In conclusion, this study shows increased numbers of circulating IL-10- and IL-17-producing CD3+ T cells in patients with T2D, suggesting that these cytokines are involved in the immune pathology of this disease.

  4. Cytokine profiles of seventeen cytokines, growth factors and chemokines in cord blood and its relation to perinatal clinical findings.

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    Takahashi, Naoto; Uehara, Ritei; Kobayashi, Mami; Yada, Yukari; Koike, Yasunori; Kawamata, Ryou; Odaka, Jun; Honma, Yoko; Momoi, Mariko Y

    2010-03-01

    Few papers have investigated the cytokine profiles of multiple cytokines in cord blood. We obtained cord blood samples from 224 infants admitted to our neonatal intensive care unit. Cytokine profiles of 17 cytokines were investigated using cytometric bead array technology. We found a wide variety of cytokines of various levels which ranged from 0.59pg/ml (in Interleukin (IL)-4) to 222.0pg/ml (in macrophage inflammatory protein-1beta. Pro-inflammatory cytokines were highly correlated with each other and with granulocyte-colony stimulating factor and IL-8. On the contrary, IL-5, IL-13, and IL-17 did not show any significant correlation with other cytokines. Several maternal factors were strongly related to several cytokines in cord blood. IL-6, IL-8 and monocyte chemotactic protein-1 were closely related to certain neonatal diseases in preterm neonates. Some cytokines may be regulated independently of each other, while others appear to work as a network affecting physiological and pathological conditions in the fetus.

  5. The correlation between histologic placentitis and amnionitis and the amnioniotic fluid's inflammatory cytokines in case of spontaneous pre-term labor with intact membrane

    Directory of Open Access Journals (Sweden)

    Agus Abadi

    2001-12-01

    Full Text Available Pre-term labor is presumed to result from spreading of lower genital infection to upper part, subsequently to decidual and choioamniotic tissues. Host response to this injury include the expression of protein which is responsible to the inflammatory reactions. The expression of the inflammatory cytokines such as IL-1β, IL-6, IL-8 and TNF-α increase in case of infection.These cytokines may play an essential role in the pathophysiology of spontaneous pretem labor with intact membrane.An observational analytic cohort study was caried out on cases of spontaneous pre-tefln labor with intact membrane. The objectives of this study are to examine the relationship between l the histologic amnionitis and placentitis and the incidence of preterm delivery,2 the expression of amniotic fluid's IL-1β, IL-6, IL-8 and TNF-α and the incidence of preterm delivery, 3 the level of amniotic fluid's IL-1β, IL-6, IL-8 and TNF-α and the grade of histologic amnionitis and placentitis in case of pre-term labor with intact membrane. Cases of spontaneous Pre'teftn labor with intact membrane which underwent transabdominal amniocentesis at admission and managed as standard procedure for pre-term labor with intact membrane. Atl of the cases were observed until the delivery of the baby, eithir preterm or term. The membrane and the placentawere cut postnatally and then the histologic acute inflammation eyaluated based on the criteria of Salafia.The level of amniotic fluid IL-1β, IL-6, IL-8 and TNF-α were analyzed quantitatively by Elisa method. This study showed thet the degree of histologic amnionitis and placentitis, and the level of amniotic fluid's IL-1β, IL-6, IL-8 and TNF-α were significantly higher in pre-term compared to terrn deliveries (p<0.05 and lhere were a positive correlation between the grade of histoLogic inflammation and the level of amniotic fluid's cytokines (Spearmann Rank Conelation test; p<0,05 in cases of preterm labor with intact membrane. The

  6. Placental determinants of fetal growth: identification of key factors in the insulin-like growth factor and cytokine systems using artificial neural networks

    Directory of Open Access Journals (Sweden)

    Faleschini Elena

    2008-06-01

    Full Text Available Abstract Background Changes and relationships of components of the cytokine and IGF systems have been shown in placenta and cord serum of fetal growth restricted (FGR compared with normal newborns (AGA. This study aimed to analyse a data set of clinical and biochemical data in FGR and AGA newborns to assess if a mathematical model existed and was capable of identifying these two different conditions in order to identify the variables which had a mathematically consistent biological relevance to fetal growth. Methods Whole villous tissue was collected at birth from FGR (N = 20 and AGA neonates (N = 28. Total RNA was extracted, reverse transcribed and then real-time quantitative (TaqMan RT-PCR was performed to quantify cDNA for IGF-I, IGF-II, IGFBP-1, IGFBP-2 and IL-6. The corresponding proteins with TNF-α in addition were assayed in placental lysates using specific kits. The data were analysed using Artificial Neural Networks (supervised networks, and principal component analysis and connectivity map. Results The IGF system and IL-6 allowed to predict FGR in approximately 92% of the cases and AGA in 85% of the cases with a low number of errors. IGF-II, IGFBP-2, and IL-6 content in the placental lysates were the most important factors connected with FGR. The condition of being FGR was connected mainly with the IGF-II placental content, and the latter with IL-6 and IGFBP-2 concentrations in placental lysates. Conclusion These results suggest that further research in humans should focus on these biochemical data. Furthermore, this study offered a critical revision of previous studies. The understanding of this system biology is relevant to the development of future therapeutical interventions possibly aiming at reducing IL-6 and IGFBP-2 concentrations preserving IGF bioactivity in both placenta and fetus.

  7. Placental growth factor and soluble c-kit receptor dynamics characterize the cytokine signature of imatinib in prostate cancer and bone metastases.

    Science.gov (United States)

    Mathew, Paul; Wen, Sijin; Morita, Satoshi; Thall, Peter F

    2011-07-01

    To assess the hypothesis that the dynamics of plasma angiogenic and inflammatory cytokines after docetaxel chemotherapy with or without the c-kit/abl/platelet-derived growth factor receptor (PDGFR) inhibitor imatinib mesylate for prostate cancer are associated with outcome, the kinetics of 17 plasma cytokines before versus after chemotherapy were assessed and associations with progression-free survival (PFS) examined. After adjusting for multiple tests, significantly different declines in placental growth factor (PIGF), soluble vascular endothelial growth factor receptor-1 (VEGFR1), VEGF, and soluble c-kit were observed with docetaxel plus imatinib (n=41) compared to docetaxel alone (n=47). Based on a piecewise linear regression model for change in concentration of each cytokine as a function of the probability of change in p-PDGFR in vivo, only the dynamics of PIGF (Pmodel for PFS, a rise in human matrix metalloproteinase 9 after docetaxel alone associated with a longer PFS. Distinct plasma angiogenic cytokines are modified by imatinib and partitioned by in vivo p-PDGFR dynamics after docetaxel chemotherapy for metastatic prostate cancer. Plasma PIGF and soluble c-kit kinetics are candidate biomarkers of imatinib effect. The predictive value of human matrix metalloproteinase 9 kinetics for docetaxel efficacy requires prospective validation.

  8. Distinct Cytokine and Chemokine Profiles in Autism Spectrum Disorders

    Science.gov (United States)

    Han, Yvonne M. Y.; Cheung, Winnie K. Y.; Wong, Chun Kwok; Sze, Sophia L.; Cheng, Timmy W. S.; Yeung, Michael K.; Chan, Agnes S.

    2017-01-01

    Previous studies have shown that immunological factors are involved in the pathogenesis of autism spectrum disorders (ASDs). However, this research has been conducted almost exclusively in Western contexts, and only a handful of studies on immune measures have been conducted in Asian populations, such as Chinese populations. The present study examined whether immunological abnormalities are associated with cognitive deficits and problem behaviors in Chinese children with ASD and whether these children show different immunological profiles. Thirteen typically developing (TD) children and 22 children with ASD, aged 6–17 years, participated voluntarily in the study. Executive functions and short-term memory were measured using neuropsychological tests, and behavioral measures were assessed using parent ratings. The children were also assessed on immunological measures, specifically, the levels of cytokines and chemokines in the blood serum. Children with ASD showed greater deficits in cognitive functions, as well as altered levels of immunological measures, including CCL2, CCL5, and CXCL9 levels, compared to TD children, and the cognitive functions and associated behavioral deficits of children with ASD were significantly associated with different immunological measures. The children were further sub-classified into ASD with only autistic features (ASD-only) or ASD comorbid with attention deficit hyperactivity disorder (ASD + ADHD). The comorbidity results showed that there were no differences between the two groups of ASD children in any of the cognitive or behavioral measures. However, the results pertaining to immunological measures showed that the children with ASD-only and ASD + ADHD exhibited distinct cytokine and chemokine profiles and that abnormal immunologic function was associated with cognitive functions and inattention/hyperactivity symptoms. These results support the notion that altered immune functions may play a role in the selective

  9. Cytokine Profiles during Invasive Nontyphoidal Salmonella Disease Predict Outcome in African Children

    Science.gov (United States)

    Gilchrist, James J.; Heath, Jennifer N.; Msefula, Chisomo L.; Gondwe, Esther N.; Naranbhai, Vivek; Mandala, Wilson; MacLennan, Jenny M.; Molyneux, Elizabeth M.; Graham, Stephen M.; Drayson, Mark T.; Molyneux, Malcolm E.

    2016-01-01

    Nontyphoidal Salmonella is a leading cause of sepsis in African children. Cytokine responses are central to the pathophysiology of sepsis and predict sepsis outcome in other settings. In this study, we investigated cytokine responses to invasive nontyphoidal Salmonella (iNTS) disease in Malawian children. We determined serum concentrations of 48 cytokines with multiplexed immunoassays in Malawian children during acute iNTS disease (n = 111) and in convalescence (n = 77). Principal component analysis and logistic regression were used to identify cytokine signatures of acute iNTS disease. We further investigated whether these responses are altered by HIV coinfection or severe malnutrition and whether cytokine responses predict inpatient mortality. Cytokine changes in acute iNTS disease were associated with two distinct cytokine signatures. The first is characterized by increased concentrations of mediators known to be associated with macrophage function, and the second is characterized by raised pro- and anti-inflammatory cytokines typical of responses reported in sepsis secondary to diverse pathogens. These cytokine responses were largely unaltered by either severe malnutrition or HIV coinfection. Children with fatal disease had a distinctive cytokine profile, characterized by raised mediators known to be associated with neutrophil function. In conclusion, cytokine responses to acute iNTS infection in Malawian children are reflective of both the cytokine storm typical of sepsis secondary to diverse pathogens and the intramacrophage replicative niche of NTS. The cytokine profile predictive of fatal disease supports a key role of neutrophils in the pathogenesis of NTS sepsis. PMID:27170644

  10. Cytokine Profiles during Invasive Nontyphoidal Salmonella Disease Predict Outcome in African Children.

    Science.gov (United States)

    Gilchrist, James J; Heath, Jennifer N; Msefula, Chisomo L; Gondwe, Esther N; Naranbhai, Vivek; Mandala, Wilson; MacLennan, Jenny M; Molyneux, Elizabeth M; Graham, Stephen M; Drayson, Mark T; Molyneux, Malcolm E; MacLennan, Calman A

    2016-07-01

    Nontyphoidal Salmonella is a leading cause of sepsis in African children. Cytokine responses are central to the pathophysiology of sepsis and predict sepsis outcome in other settings. In this study, we investigated cytokine responses to invasive nontyphoidal Salmonella (iNTS) disease in Malawian children. We determined serum concentrations of 48 cytokines with multiplexed immunoassays in Malawian children during acute iNTS disease (n = 111) and in convalescence (n = 77). Principal component analysis and logistic regression were used to identify cytokine signatures of acute iNTS disease. We further investigated whether these responses are altered by HIV coinfection or severe malnutrition and whether cytokine responses predict inpatient mortality. Cytokine changes in acute iNTS disease were associated with two distinct cytokine signatures. The first is characterized by increased concentrations of mediators known to be associated with macrophage function, and the second is characterized by raised pro- and anti-inflammatory cytokines typical of responses reported in sepsis secondary to diverse pathogens. These cytokine responses were largely unaltered by either severe malnutrition or HIV coinfection. Children with fatal disease had a distinctive cytokine profile, characterized by raised mediators known to be associated with neutrophil function. In conclusion, cytokine responses to acute iNTS infection in Malawian children are reflective of both the cytokine storm typical of sepsis secondary to diverse pathogens and the intramacrophage replicative niche of NTS. The cytokine profile predictive of fatal disease supports a key role of neutrophils in the pathogenesis of NTS sepsis.

  11. Cytokine profile of murine malaria: stage-related production of inflammatory and anti-inflammatory cytokines.

    Science.gov (United States)

    Bakir, Hanaa Y; Tomiyama, Chikako; Abo, Toru

    2011-06-01

    Balance between inflammatory and anti-inflammatory cytokines may be important in malaria presentation and outcome. To clarify cytokine interactions that produce pathology of malaria and control infection, C57BL/6 mice were infected with 10(4) parasitized RBCs from a non-lethal strain of Plasmodium yoelii. Kinetics was monitored showing the course of parasitemia, and cytokines were determined by RT-PCR from liver and spleen tissues. Inflammatory cytokines such as interferon-γ (IFNγ), interleukin (IL)-12, IL-6, tumor necrosis factor-α (TNFα) and anti-inflammatory cytokines, including IL-4 and IL-10, were investigated as key molecules that interact with immune cells in the activation of the immune responses. The production of IFNγ mRNA was found to be higher on day 7 than on day 21 after infection, and IL-12 and IL-6 showed higher expression in the liver than in the spleen. Though TNFα was highly expressed on day 14 after infection and on day 21 in the liver, such expression was decreased on day 21 in the spleen. Anti-inflammatory cytokines showed high expression in both the liver and spleen. The results suggest that a relative balance between inflammatory and anti-inflammatory cytokines is crucial and that the increase of inflammatory cytokine levels during the acute phase of malaria may reflect an early and effective immune response.The counteraction effect of anti-inflammatory cytokines is thought to play a role in limiting progression from uncomplicated malaria to severe life-threatening complications.

  12. Cytokine profiles in osteoporosis suggest a proresorptive bias.

    Science.gov (United States)

    Azizieh, Fawaz; Raghupathy, Raj; Shehab, Diaa; Al-Jarallah, Khaled; Gupta, Renu

    2017-09-01

    As the immune system is suggested to contribute to the pathophysiology of osteoporosis in menopause, we compared the levels of proresorptive and antiresorptive cytokines produced by peripheral blood mononuclear cells (PBMCs) from postmenopausal women with normal and low bone mineral density (BMD). Seventy-one postmenopausal women were studied; 25 had normal BMD and 46 had low BMD. Participants were categorized as normal (n = 25), osteopenic (n = 31), and osteoporotic (n = 15) based on T-scores. Levels of 10 cytokines produced by mitogen-stimulated PBMCs were measured by Multiplex ELISA. PBMCs from women with low BMD produced higher levels of the proresorptive cytokines tumor necrosis factor-alpha, interleukin (IL)-6, IL-12, and IL-17 (P = 0.014, 0.012, 0.011, and 0.049), and lower levels of the antiresorptive cytokines IL-4, IL-10, and IL-23 (P = 0.003, 0.018, and 0.025) compared with women with normal BMD. Proresorptive cytokines were similar in osteopenic and osteoporotic women, but both had higher levels than women with normal BMD. Osteoporotic women produced lower levels of the antiresorptive cytokines IL-4, IL-10, IL-13, and IL-23 compared with the normal BMD group (P = 0.001, 0.05, 0.05, and 0.026), and lower levels of IL-4 as compared with osteopenic women (P = 0.05). Osteopenic women produced lower levels of IL-4 and IL-10 compared with the normal BMD group (P = 0.025 and 0.038). Ratios of proresorptive to antiresorptive cytokines suggest a stronger proresorptive cytokine bias in women with low BMD. Most of the ratios are lowest in the normal BMD group, modest in osteopenic women, and highest in the osteoporotic group. Women with low BMD have a proresorptive cytokine bias.

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

    NARCIS (Netherlands)

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

    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 Vene

  14. Cytokine secretion profiles of human keratinocytes during Trichophyton tonsurans and Arthroderma benhamiae infections.

    Science.gov (United States)

    Shiraki, Yumi; Ishibashi, Yoshio; Hiruma, Masataro; Nishikawa, Akemi; Ikeda, Shigaku

    2006-09-01

    Dermatophytes cause intractable superficial infections in humans. Arthroderma benhamiae, a zoophilic dermatophyte, triggers severe inflammatory responses in humans, while Trichophyton tonsurans, an anthropophilic dermatophyte, triggers minimal ones. Cytokines and other factors derived from keratinocytes play important roles in inflammatory and immune responses in the skin. The authors performed an in vitro investigation to determine the human keratinocyte cytokine profiles during dermatophyte infection. The human keratinocyte cell line PHK16-0b was infected with A. benhamiae or T. tonsurans for 24 h, and the cytokines secreted were analysed using a human cytokine antibody array. Marked differences were observed in the cytokine profiles of the cells infected with the two dermatophytes. A. benhamiae infection resulted in the secretion of a broad spectrum of cytokines, including proinflammatory cytokines, chemokines, and immunomodulatory cytokines. In contrast, T. tonsurans-infected keratinocytes secreted only limited cytokines, including eotaxin-2, interleukin (IL)-8 and IL-16. cDNA microarray analysis confirmed that A. benhamiae infection upregulated genes encoding IL-1beta, IL-2, IL-4, IL-6, IL-10, IL-13, IL-15, IL-16, IL-17 and interferon (IFN)-gamma, while T. tonsurans infection upregulated only a few genes, such as those encoding IL-1beta and IL-16. RT-PCR demonstrated that infection by both dermatophytes enhanced IL-8 mRNA expression in keratinocytes. These results suggest that A. benhamiae-induced secretion of several cytokines from keratinocytes may be involved in a severe inflammatory response, and that the limited cytokine secretion from keratinocytes in response to T. tonsurans infection may result in a minimal inflammatory response in the skin. These cytokine profiles may aid in proving the clinical features of dermatophytosis.

  15. T-Helper Cytokine Profiles in Patients with Kawasaki Disease.

    Science.gov (United States)

    Lee, Sang Bum; Kim, Young Hyun; Hyun, Myung Chul; Kim, Yeo Hyang; Kim, Hee Sun; Lee, Young Hwan

    2015-11-01

    Kawasaki disease is an acute systemic vasculitis of which pathogenesis suspected is caused by immune dysregulation. The goal of this study is to evaluate the activation pattern of T helper cell type 1 (Th1) and T helper cell type 2 (Th2) in patients with Kawasaki disease. Prospective study of 60 patients (male 36, female 24) with diagnosis of Kawasaki disease were enrolled. One hundred and eighty blood samples from these patients were collected according to the different clinical stages {before initial intravenous immunoglobulin (IVIG), 5 days after initial IVIG, 2 months after initial IVIG}. The plasma level of Th1 cytokines; interferon-gamma (IFN-γ) & interleukin (IL)-2 and Th2 cytokines; IL-4 & IL-10 were measured by enzyme-liked immunosorbent assay. In all patients, the plasma level of Th1 cytokines (IFN-γ, IL-2) and Th2 cytokines (IL-4 and IL-10) were markedly elevated during the acute stage of Kawasaki disease. Since then, the plasma level of all these cytokines decreased significantly along with the process of clinical stages. Regardless of the existence of coronary artery lesion or no response to initial IVIG treatment, there were no significant differences between them. These data suggest that both Th1 and Th2 cells may be activated simultaneously during the acute stage of Kawasaki disease. Further studies are therefore required to establish the difference of activation pattern of T helper cells between Kawasaki disease and other inflammatory diseases.

  16. Cytokine profile associated with human chronic schistosomiasis mansoni

    Directory of Open Access Journals (Sweden)

    Andréa Magalhães

    2004-08-01

    Full Text Available This study objective was to evaluate the cytokines associated with early events of hepatic fibrosis in schistosomiasis mansoni. Hepatic fibrosis was classified by ultrasonography in 94 patients. Immunological evaluation was performed by measurement of secreted cytokines (interleukin IL-5, IL-10, IL-13, interferon-gamma, tumor necrosis factor-alpha and transforming growth factors-beta in peripherl blood mononuclear cells stimulated by Schistosoma mansoni antigens. Significantly, higher levels of IL-5, IL-10 and IL-13 were found in supernatants of SEA-stimulated PBMC from subjects with degree III hepatic fibrosis as compared to patients with degree I or II fibrosis, Significant increases in IL-5 and IL-13 levels were also observed in some of the subjects who remained untreated for one year following initial assessment and developed more serious fibrosis during this period. The data suggests a role for type 2 cytokines in early stages of hepatic fibrosis in human schistosomiasis mansoni.

  17. Serum cytokine profile in patients with pancreatic cancer.

    Science.gov (United States)

    Torres, Carolina; Perales, Sonia; Alejandre, María José; Iglesias, José; Palomino, Rogelio J; Martin, Miguel; Caba, Octavio; Prados, José C; Aránega, Antonia; Delgado, Juan R; Irigoyen, Antonio; Ortuño, Francisco M; Rojas, Ignacio; Linares, Ana

    2014-10-01

    Pancreatic ductal adenocarcinoma is a deadly disease because of late diagnosis and chemoresistance. We aimed to find a panel of serum cytokines representing diagnostic and predictive biomarkers for pancreatic cancer. A cytokine antibody array was performed to simultaneously identify 507 cytokines in sera of patients with pancreatic cancer and healthy controls. The nonparametric Mann-Whitney U test was used to pairwise compare the controls, the pretreated patients, and the posttreated patients. Fold changes greater than or equal to 1.5 or less than or equal to 1/1.5 were considered significant. Receiver operating characteristic curves were used to assess the performance of the model. A leave-one-out cross-validation was used for estimating prediction error. Comparing the sera of pretreated patients against the control samples, the cytokines fibroblast growth factor 10 (FGF-10/keratinocyte growth factor-2 (KGF-2), chemokine (C-X-C motif) ligand 11 interferon inducible T cell alpha chemokine (I-TAC)/chemokine [C-X-C motif] ligand 11 (CXCL11), oncostatin M (OSM), osteoactivin/glycoprotein nonmetastatic melanoma protein B, and stem cell factor (SCF) were found significantly overexpressed. Besides, the cytokines CD30 ligand/tumor necrosis factor superfamily, member 8 (TNFSF8), chordin-like 2, FGF-10/KGF-2, growth/differentiation factor 15, I-TAC/CXCL11, OSM, and SCF were differentially expressed in response to treatment. We propose a role for FGF-10/KGF-2, I-TAC/CXCL11, OSM, osteoactivin/glycoprotein nonmetastatic melanoma protein B, and SCF as novel diagnostic biomarkers. CD30 ligand/TNFSF8, chordin-like 2, FGF-10/KGF-2, growth/differentiation factor 15, I-TAC/CXCL11, OSM, and SCF might represent as predictive biomarkers for gemcitabine and erlotinib response of patients with pancreatic cancer.

  18. Global Cytokine Profiles and Association With Clinical Characteristics in Patients With Irritable Bowel Syndrome.

    Science.gov (United States)

    Bennet, Sean M P; Polster, Annikka; Törnblom, Hans; Isaksson, Stefan; Capronnier, Sandrine; Tessier, Aurore; Le Nevé, Boris; Simrén, Magnus; Öhman, Lena

    2016-08-01

    Evidence suggests that patients with irritable bowel syndrome (IBS) have an altered cytokine profile, although it is unclear whether cytokines are linked with symptom severity. We aimed to determine whether global serum and mucosal cytokine profiles differ between IBS patients and healthy subjects and whether cytokines are associated with IBS symptoms. Serum from 144 IBS patients and 42 healthy subjects was analyzed for cytokine levels of interleukin (IL)-5, IL-6, IL-8, IL-10, IL-12p70, IL-13, IL-17A, interferon (IFN)-γ, and tumor necrosis factor (TNF) by MSD MULTI-ARRAY. In total, 109 IBS and 36 healthy sigmoid colon biopsies were analyzed for mRNA expression of IL-8, IL-10, TNF, and FOXP3 by quantitative reverse transcription PCR. Multivariate discrimination analysis evaluated global cytokine profiles. Rectal sensitivity, oroanal transit time, and psychological and gastrointestinal symptom severity were also assessed. Global cytokine profiles of IBS patients and healthy subjects overlapped, but cytokine levels varied more in IBS patients. Serum levels of IL-6 and IL-8 tended to be increased and levels of IFN-γ tended to be decreased in IBS patients. Mucosal mRNA expression of IL-10 and FOXP3 tended to be decreased in IBS patients. Within both the full study cohort and IBS patients alone, serum level of TNF was associated with looser stool pattern, while subjects with more widespread somatic symptoms had increased serum levels of IL-6. Although neither IBS bowel habit subgroups nor patients with possible post-infectious IBS were associated with distinct cytokine profiles, a small cluster of IBS patients with comparatively elevated immune markers was identified. Global cytokine profiles did not discriminate IBS patients from healthy subjects, but cytokine profiles were more varied among IBS patients than among healthy subjects, and a small subgroup of patients with enhanced immune activity was identified. Also, association of inflammatory cytokines with some

  19. Serum cytokine profiles of children with human enterovirus 71-associated hand, foot, and mouth disease.

    Science.gov (United States)

    Han, Jun; Wang, Ying; Gan, Xing; Song, Juan; Sun, Peng; Dong, Xiao-Ping

    2014-08-01

    Cytokine profiles may impact the pathogenicity and severity of hand, foot, and mouth disease caused by human enterovirus (HEV) 71. In 91 severe or mild HEV 71-associated hand, foot, and mouth disease children, serum was collected between days 2 and 10 or day >10. Serum cytokines including Type 1 T helper (Th1) cytokines: interleukin (IL)-2, interferon-gamma (IFN-γ), IL-12, and IL-18, Type 1 T helper (Th2) cytokines: IL-4, IL-10, IL-13, proinflammatory cytokines: IL-1α, IL-1β, IL-6, IL-8, IL-17, and tumor necrosis factor alpha (TNF-α), were assessed during the early stage and recovery. In the patients with mild illness, the peaks of IL-8 and IL-10 were observed on day 6 and that of IL-18 was on day 4. In the patients with severe illness, all cytokines spiked on day 3 and peaked on day 11. All cytokines except IL-6, IL-8, IL-18, and TNF-α were significantly correlated with immunoglobulin M levels by the end of the disease course. Cytokine profile variations between the patients with mild and severe illness may indicate prognosis and strain virulence, useful in clinical treatment of patients.

  20. Subnormal Cytokine Profile in the Tear Fluid of Keratoconus Patients

    Science.gov (United States)

    Jun, Albert S.; Cope, Leslie; Speck, Caroline; Feng, Xiaojun; Lee, Seakwoo; Meng, Huan; Hamad, Abdel; Chakravarti, Shukti

    2011-01-01

    Keratoconus, historically viewed as a non-inflammatory disease, is an ectatic corneal disorder associated with progressive thinning of the corneal stroma. Recently, a few inflammatory mediators have been reported to be elevated in the tear fluid of keratoconus patients. Consequently, we investigated a wide range of inflammation regulating cytokines in the tears and sera of keratoconus and control subjects. Interleukin (IL)-1β, IL-4, IL-6, IL-10, IL-12, IL-13, IL-17, interferon (IFN)-γ, chemokine C-C motif ligand 5 (CCL5) and tumor necrosis factor (TNF)-α were tested in tear samples and sera of keratoconus and control individuals by multiplex immuno-bead assays. Selected cytokines were further tested by standard ELISA on pooled tear samples. All cytokines in the sera were generally low, with no significant changes between keratoconus and control subjects. However, in tear fluids, clear differences were detected between the two groups. These differences include increased IL-6, and decreased IL-12, TNF-α, IFN-γ, IL-4, IL-13 and CCL5 in keratoconus compared to control tear fluids. The decreases in IL-12, TNF-α and CCL5 were statistically significant, while the IL-13 decrease was statistically significant in the severe keratoconus group only. IL-17 could not be detected by multiplex immuno-bead assay, but showed an increase in keratoconus by conventional ELISA on a limited number of pooled tear samples. Our findings confirm increased IL-6, but dispute earlier reports of increased TNF-α, and suggest a cytokine imbalance in keratoconus disrupting corneal homeostasis. Moreover, an increase in IL-17 suggests tissue degenerative processes at work, contributing to the thinning and weakening of the corneal connective tissue in keratoconus. PMID:21298010

  1. Impact of Exogenous Gonadotropin Stimulation on Circulatory and Follicular Fluid Cytokine Profiles

    Directory of Open Access Journals (Sweden)

    N. Ellissa Baskind

    2014-01-01

    Full Text Available Background. The natural cycle is the prototype to which we aspire to emulate in assisted reproduction techniques. Increasing evidence is emerging that controlled ovarian hyperstimulation (COH with exogenous gonadotropins may be detrimental to oogenesis, embryo quality, and endometrial receptivity. This research aimed at assessing the impact of COH on the intrafollicular milieu by comparing follicular fluid (FF cytokine profiles during stimulated in vitro fertilization (IVF and modified natural cycle (MNC IVF. Methods. Ten women undergoing COH IVF and 10 matched women undergoing MNC IVF were recruited for this pilot study. 40 FF cytokine concentrations from individual follicles and plasma were measured by fluid-phase multiplex immunoassay. Demographic/cycle/cytokine data were compared and correlations between cytokines were computed. Results. No significant differences were found between COH and MNC groups for patient and cycle demographics, including outcome. Overall mean FF cytokine levels were higher in the MNC group for 29/40 cytokines, significantly so for leukaemia inhibitory factor and stromal cell-derived factor-1α. Furthermore, FF MNC cytokine correlations were significantly stronger than for COH data. Conclusions. These findings suggest that COH perturbs intrafollicular cytokine networks, in terms of both cytokine levels and their interrelationships. This may impact oocyte maturation/fertilization and embryo developmental competence.

  2. Cytokine profiles in peripheral blood and whole blood cell cultures associated with aggressive periodontitis, juvenile idiopathic arthritis, and rheumatoid arthritis

    DEFF Research Database (Denmark)

    Poulsen, Anne Havemose; Sørensen, Lars Korsbaek; Stoltze, Kaj

    2005-01-01

    Cytokines play a key role in the pathogenesis of inflammatory diseases. An obvious question is whether patients with aggressive periodontitis, juvenile idiopathic arthritis, or rheumatoid arthritis share blood cytokine profiles distinguishing them from individuals free of disease....

  3. Cytokine profiles in peripheral blood and whole blood cell cultures associated with aggressive periodontitis, juvenile idiopathic arthritis, and rheumatoid arthritis

    DEFF Research Database (Denmark)

    Poulsen, Anne Havemose; Sørensen, Lars Korsbaek; Stoltze, Kaj

    2005-01-01

    Cytokines play a key role in the pathogenesis of inflammatory diseases. An obvious question is whether patients with aggressive periodontitis, juvenile idiopathic arthritis, or rheumatoid arthritis share blood cytokine profiles distinguishing them from individuals free of disease....

  4. Differential cytokine profiles in juvenile idiopathic arthritis subtypes revealed by cluster analysis.

    Science.gov (United States)

    van den Ham, Henk-Jan; de Jager, Wilco; Bijlsma, Johannes W J; Prakken, Berent J; de Boer, Rob J

    2009-08-01

    With the introduction of high-throughput biomarker measurements, traditional analysis of these markers is increasingly difficult. Using samples from a diverse group of patients, we tested the applicability of cluster analysis to these data. Using this method, we aim to visualize some of the patterns specific to certain disease groups. In particular, we focus on juvenile idiopathic arthritis (JIA), a multifactorial autoimmune disorder that ultimately leads to chronic inflammation of the joints. Cytokine measurements were performed using multiplex immunoassays. Using heuristic clustering methods, we set out to compare the pattern of 30 cytokines in plasma and SF of JIA, RA, OA, or diabetes type II patients and healthy controls. Analysis shows that oligo- and polyarticular JIA have similar biomarker profiles, both in plasma and SF. Systemic onset JIA (SoJIA) has a profile distinct from other JIA subtypes, suggesting that they involve different inflammatory processes. SoJIA samples do, however, cluster together with RA in SF, suggesting that these two conditions have similar cytokine profiles. Furthermore, we identify several clusters of ILs and chemokines that are co-expressed, suggesting that they are co-regulated. We show that previously undetected clusters of cytokines and patients can be identified by applying cluster analysis to multiplex data. Cytokine clusters identified in plasma and SF samples were quite different, which underscore the differential cytokine signalling in these two compartments, and suggest that plasma samples may not be suitable for estimating joint biomarker profiles and inflammation.

  5. Cytokines and Cytokine Profiles in Human Autoimmune Diseases and Animal Models of Autoimmunity

    Directory of Open Access Journals (Sweden)

    Manfred Kunz

    2009-01-01

    Full Text Available The precise pathomechanisms of human autoimmune diseases are still poorly understood. However, a deepened understanding of these is urgently needed to improve disease prevention and early detection and guide more specific treatment approaches. In recent years, many new genes and signalling pathways involved in autoimmunity with often overlapping patterns between different disease entities have been detected. Major contributions were made by experiments using DNA microarray technology, which has been used for the analysis of gene expression patterns in chronic inflammatory and autoimmune diseases, among which were rheumatoid arthritis, systemic lupus erythematosus, psoriasis, systemic sclerosis, multiple sclerosis, and type-1 diabetes. In systemic lupus erythematosus, a so-called interferon signature has been identified. In psoriasis, researchers found a particular immune signalling cluster. Moreover the identification of a new subset of inflammatory T cells, so-called Th17 T cells, secreting interleukin (IL-17 as one of their major cytokines and the identification of the IL-23/IL-17 axis of inflammation regulation, have significantly improved our understanding of autoimmune diseases. Since a plethora of new treatment approaches using antibodies or small molecule inhibitors specifically targeting cytokines, cellular receptors, or signalling mechanisms has emerged in recent years, more individualized treatment for affected patients may be within reach in the future.

  6. Systemic Cytokine Profiles in Strongyloides stercoralis Infection and Alterations following Treatment.

    Science.gov (United States)

    Anuradha, Rajamanickam; Munisankar, Saravanan; Bhootra, Yukti; Jagannathan, Jeeva; Dolla, Chandrakumar; Kumaran, Paul; Shen, Kui; Nutman, Thomas B; Babu, Subash

    2015-11-23

    Strongyloides stercoralis is a soil-transmitted helminth organism that infects ~50 to 100 million people worldwide. Despite its widespread prevalence, very little is known about the immune response that characterizes human S. stercoralis infection. To study the systemic cytokine profile characteristic of Strongyloides infection, we measured the circulating levels of a large panel of pro- and anti-inflammatory cytokines in asymptomatic, infected individuals (n = 32) and compared them to those in uninfected, controls (n = 24). Infected individuals exhibited significantly lower circulating levels of proinflammatory cytokines (gamma interferon [IFN-γ], tumor necrosis factor alpha [TNF-α], and interleukin-1β [IL-1β]) and significantly higher levels of anti-inflammatory cytokines (IL-4, IL-5, IL-9, IL-10, IL-13, IL-27, IL-37, and transforming growth factor β [TGF-β]). Moreover, treatment of Strongyloides infection resulted in a significant reversal of the cytokine profile, with increased levels of proinflammatory (IFN-γ, TNF-α, IL-2, IL-17A, IL-17F, IL-22, IL-23, and IL-1β) and decreased levels of anti-inflammatory (IL-4, IL-5, IL-9, IL-10, IL-13, IL-27, IL-37, and TGF-β) cytokines following treatment. Thus, S. stercoralis infection is characterized by alterations in the levels of systemic cytokines, reflecting major alterations in the underlying immune response to this chronic helminth infection.

  7. SOME FEATURES OF CYTOKINE PROFILE IN SEVERE PYOINFLAMMATORY DISEASES OF FACE AND NECK

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    L. M. Karzakova

    2012-01-01

    Full Text Available Abstract. This work presents immunological data of one-hundred patients with severe pyoinflammatory diseases of face and neck area. Upon laboratory evaluation of patients with such pathology, it was shown that production of IL-1β, IL-2, IL-6, IL-8, IL-10, Rа-IL-1β is induced in this cohort. A clinically unfavorable pattern of cytokine profile was specified in patients with severe pyoinflammatory diseases of face and neck region. Its common feature is an imbalance in cytokine network associated with overproduction of immunosuppressive cytokines.

  8. Serum cytokine and chemokine profiles in patients with chronic inflammatory demyelinating polyneuropathy.

    Science.gov (United States)

    Beppu, Minako; Sawai, Setsu; Misawa, Sonoko; Sogawa, Kazuyuki; Mori, Masahiro; Ishige, Takayuki; Satoh, Mamoru; Nomura, Fumio; Kuwabara, Satoshi

    2015-02-15

    To identify serum cytokine networks specific to chronic inflammatory demyelinating polyneuropathy (CIDP), serum samples of two subgroups (18 patients with typical CIDP and 12 patients with multifocal acquired demyelinating sensory and motor neuropathy [MADSAM]) were analyzed with multiplex magnetic bead-based cytokine assay. TNF-α, HGF, MIP-1β and IL-1β levels were significantly higher in total CIDP patients than in normal controls. Of these, HGF levels were elevated in typical CIDP patients, but not in MADSAM patients. Patients with high HGF levels showed good responses to steroid treatment. Different cytokine profiles among the CIDP subtypes presumably reflect differences in pathophysiology.

  9. Review of cytokine profiles in patients with hepatitis

    Institute of Scientific and Technical Information of China (English)

    Qiao-Ling Sun; Wei Ran

    2004-01-01

    The development of T helper 1 versus T helper 2 cells is a major branch point in the immune response and is an important determinant of the body's response to an infectious pathogen, leading to protection of the host or dissemination of the disease. Resent studies have shown that there exist macrophage activation states in parallel to the T helper cell type 1/2 paradigm, and the T helper 1 development process is governed to a great degree by cytokine IL-12 provided mainly by antigen presenting cells such as macrophages and dendritic cells. A model in patients with hepatitis is proposed that links the pathogen,macrophage activation and T helper cell polarization.

  10. Distinct profiles of effector cytokines mark the different phases of Crohn's disease.

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    Francesca Zorzi

    Full Text Available OBJECTIVE: Crohn's Disease (CD-associated inflammation is supposed to be driven by T helper (Th1/Th17 cell-derived cytokines, even though there is evidence that the mucosal profile of cytokine may vary with the evolution of the disease. We aimed at comparing the pattern of effector cytokines in early and established lesions of CD. DESIGN: Mucosal samples were taken from the neo-terminal ileum of CD patients undergoing ileocolonic resection, with (early lesions or without post-operative recurrence, and terminal ileum of CD patients with long-standing disease undergoing intestinal resection (established lesions. Inflammatory cell infiltrate was examined by immunofluorescence and cytokine expression was analysed by real-time PCR, flow-cytometry and ELISA. RESULTS: Before the appearance of endoscopic lesions, the mucosa of the neo-terminal ileum contained high number of T cells and macrophages, elevated levels of Th1-related cytokines and TNF-α and slightly increased IL-17A expression. Transition from this stage to endoscopic recurrence was marked by abundance of Th1 cytokines, marked increase in IL-17A, and induction of IL-6 and IL-23, two cytokines involved in the control of Th17 cell responses. In samples with established lesions, there was a mixed Th1/Th17 response with no TNF-α induction. Expression of IL-4 and IL-5 was up-regulated in both early and established lesions even though the fraction of IL-4-producing cells was lower than that of cells producing either interferon-γ or IL-17A. CONCLUSIONS: Distinct mucosal profiles of cytokines are produced during the different phases of CD. A better understanding of the cytokines temporally regulated in CD tissue could help optimize therapeutic interventions in CD.

  11. Cytokine profile in human eyes: contribution of a new cytokine combination for differential diagnosis between intraocular lymphoma or uveitis.

    Science.gov (United States)

    Fisson, Sylvain; Ouakrim, Hanane; Touitou, Valérie; Baudet, Sylvie; Ben Abdelwahed, Rym; Donnou, Sabrina; Miloudi, Amine; Galand, Claire; Bodaghi, Bahram; Lehoang, Phuc; Brissard, Martine; Le Garff-Tavernier, Magali; Fridman, Wolf Herman; Sautès-Fridman, Catherine; Cassoux, Nathalie; Merle-Béral, Hélène

    2013-01-01

    Primary intraocular lymphoma (PIOL), also called primary vitreoretinal lymphomas, often masquerades as uveitis. This misdiagnosis can result in subsequent brain involvement and oculocerebral lymphoma (OCL). In this study, we sought to characterize the helper T-cell type 1 (Th1)/Th2 cytokine profile in vitreous samples from patients with PIOL, OCL, uveitis and controls with non-inflammatory disease. Vitreous and aqueous humor samples from 87 patients with PIOL (n = 30), OCL (n = 12), uveitis (n = 34), and retinal detachment (RD) without hemorrhage (n = 11) were analyzed and their concentrations of interleukin (IL)-2, IL-4, IL-6, IL-10, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α were determined by flow cytometric bead arrays (CBA). The IL-10 levels determined by CBA were compared with those by ELISA. IL-10 concentrations measured by CBA and ELISA were highly correlated. IL-2, IL-4, and TNFα were not detected in any sample. The only cytokine detected at a significant level in samples from RD vitreous was IL-6. The IL-10/IL-6 ratio, as previously reported, was slightly higher in PIOL than in uveitis samples, but not for all patients. Cytokine profiles from PIOL and OCL samples did not differ. The combination of the IL-10/IL-6 and IL-10/IFNγ ratios was highly informative for discriminating PIOL/OCL from uveitis samples and for therapeutic follow up of PIOL. This strategy might be very helpful as an initial screening to rule out PIOL in patients thought to have uveitis.

  12. Identification of neurotoxic cytokines by profiling Alzheimer's disease tissues and neuron culture viability screening.

    Science.gov (United States)

    Wood, Levi B; Winslow, Ashley R; Proctor, Elizabeth A; McGuone, Declan; Mordes, Daniel A; Frosch, Matthew P; Hyman, Bradley T; Lauffenburger, Douglas A; Haigis, Kevin M

    2015-11-13

    Alzheimer's disease (AD) therapeutics based on the amyloid hypothesis have shown minimal efficacy in patients, suggesting that the activity of amyloid beta (Aβ) represents only one aspect of AD pathogenesis. Since neuroinflammation is thought to play an important role in AD, we hypothesized that cytokines may play a direct role in promoting neuronal death. Here, we profiled cytokine expression in a small cohort of human AD and control brain tissues. We identified AD-associated cytokines using partial least squares regression to correlate cytokine expression with quantified pathologic disease state and then used neuron cultures to test whether cytokines up-regulated in AD tissues could affect neuronal viability. This analysis identified cytokines that were associated with the pathological severity. Of the top correlates, only TNF-α reduced viability in neuron culture when applied alone. VEGF also reduced viability when applied together with Aβ, which was surprising because VEGF has been viewed as a neuro-protective protein. We found that this synthetic pro-death effect of VEGF in the context of Aβ was commensurate with VEGFR-dependent changes in multiple signaling pathways that govern cell fate. Our findings suggest that profiling of tissues combined with a culture-based screening approach can successfully identify new mechanisms driving neuronal death.

  13. Cerebrospinal fluid and serum cytokine profiles in narcolepsy with cataplexy: a case-control study.

    Science.gov (United States)

    Dauvilliers, Yves; Jaussent, Isabelle; Lecendreux, Michel; Scholz, Sabine; Bayard, Sophie; Cristol, Jean Paul; Blain, Hubert; Dupuy, Anne-Marie

    2014-03-01

    Recent advances in the identification of susceptibility genes and environmental exposures provide strong support that narcolepsy-cataplexy is an immune-mediated disease. Only few serum cytokine studies with controversial results were performed in narcolepsy and none in the cerebrospinal fluid. We measured a panel of 12 cytokines by a proteomic approach in the serum of 35 patients with narcolepsy-cataplexy compared to 156 healthy controls, and in the cerebrospinal fluid of 34 patients with narcolepsy-cataplexy compared to 17 non-narcoleptic patients; and analyzed the effect of age, duration and severity of disease on the cytokine levels. After multiple adjustments we reported lower serum IL-2, IL-8, TNF-α, MCP-1 and EGF levels, and a tendency for higher IL-4 level in narcolepsy compared to controls. Significant differences were only found for IL-4 in cerebrospinal fluid, being higher in narcolepsy. Positive correlations were found in serum between IL-4, daytime sleepiness, and cataplexy frequency. The expression of some pro-inflammatory cytokines (MCP-1, VEGF, EGF, IL2, IL-1β, IFN-γ) in either serum or CSF was negatively correlated with disease severity and duration. No correlation was found for any specific cytokine in 18 of the patients with narcolepsy with peripheral and central samples collected the same day. Significant decreased pro/anti-inflammatory cytokine profiles were found at peripheral and central levels in narcolepsy, together with a T helper 2/Th1 serum cytokine secretion imbalance. To conclude, we showed some evidence for alterations in the cytokine profile in patients with narcolepsy-cataplexy compared to controls at peripheral and central levels, with the potential role of IL-4 and significant Th1/2 imbalance in the pathophysiology of narcolepsy.

  14. Aspergillus flavus induces granulomatous cerebral aspergillosis in mice with display of distinct cytokine profile.

    Science.gov (United States)

    Anand, R; Shankar, J; Tiwary, B N; Singh, A P

    2015-04-01

    Aspergillus flavus is one of the leading Aspergillus spp. resulting in invasive aspergillosis of central nervous system (CNS) in human beings. Immunological status in aspergillosis of central nervous system remains elusive in case of both immunocompetent and immunocompromised patients. Since cytokines are the major mediators of host response, evaluation of disease pathology along with cytokine profile in brain may provide snapshots of neuro-immunological response. An intravenous model of A. flavus infection was utilized to determine the pathogenicity of infection and cytokine profile in the brain of male BALB/c mice. Enumeration of colony forming units and histopathological analyses were performed on the brain tissue at distinct time periods. The kinetics of cytokines (TNF-α, IFN-γ, IL-12/IL-23p40, IL-6, IL-23, IL-17A and IL-4) was evaluated at 6, 12, 24, 48, 72 and 96h post infection (hPI) in brain homogenates using murine cytokine specific enzyme linked immunosorbent assay. Histological analysis exhibited the hyphae with leukocyte infiltrations leading to formation of granulomata along with ischemia and pyknosis of neurons in the brain of infected mice. Diseased mice displayed increased secretion of IFN-γ, IL-12p40 and IL-6 with a concomitant reduction in the secretion of Th2 cytokine IL-4, and Th17 promoting cytokine, IL-23 during the late phase of infection. A.flavus induced inflammatory granulomatous cerebral aspergillosis in mice, characterized by a marked increase in the Th1 cytokines and neurons undergoing necrosis. A marked increase in necrosis of neurons with concurrent inflammatory responses might have led to the host mortality during late phase of infection.

  15. Cytokine expression profile of dengue patients at different phases of illness.

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    Anusyah Rathakrishnan

    Full Text Available BACKGROUND: Dengue is an important medical problem, with symptoms ranging from mild dengue fever to severe forms of the disease, where vascular leakage leads to hypovolemic shock. Cytokines have been implicated to play a role in the progression of severe dengue disease; however, their profile in dengue patients and the synergy that leads to continued plasma leakage is not clearly understood. Herein, we investigated the cytokine kinetics and profiles of dengue patients at different phases of illness to further understand the role of cytokines in dengue disease. METHODS AND FINDINGS: Circulating levels of 29 different types of cytokines were assessed by bead-based ELISA method in dengue patients at the 3 different phases of illness. The association between significant changes in the levels of cytokines and clinical parameters were analyzed. At the febrile phase, IP-10 was significant in dengue patients with and without warning signs. However, MIP-1β was found to be significant in only patients with warning signs at this phase. IP-10 was also significant in both with and without warning signs patients during defervescence. At this phase, MIP-1β and G-CSF were significant in patients without warning signs, whereas MCP-1 was noted to be elevated significantly in patients with warning signs. Significant correlations between the levels of VEGF, RANTES, IL-7, IL-12, PDGF and IL-5 with platelets; VEGF with lymphocytes and neutrophils; G-CSF and IP-10 with atypical lymphocytes and various other cytokines with the liver enzymes were observed in this study. CONCLUSIONS: The cytokine profile patterns discovered between the different phases of illness indicate an essential role in dengue pathogenesis and with further studies may serve as predictive markers for progression to dengue with warning signs.

  16. Cytokine profiles show heterogeneity of interferon-β response in multiple sclerosis patients

    DEFF Research Database (Denmark)

    Hegen, Harald; Adrianto, Indra; Lessard, Christopher J

    2016-01-01

    OBJECTIVE: To evaluate serum cytokine profiles for their utility to determine the heterogeneous responses to interferon (IFN)-β treatment in patients with multiple sclerosis (MS). METHODS: Patients with relapsing-remitting MS (RRMS) or clinically isolated syndrome receiving de novo IFN-β treatmen...

  17. Colonic lesions, cytokine profiles, and gut microbiota in plasminogen-deficient mice

    DEFF Research Database (Denmark)

    Vestergaard, Bill; Krych, Lukasz; Lund, Leif R.;

    2015-01-01

    closure. Colonic lesions in plg(tm1Jld) mice, which were characterized by necrotizing ulcerations and cystically dilated glands, were restricted to the intermediate and distal parts of the colon. The cytokine profile was indicative of chronic tissue damage, but the genetic modification did not change...

  18. Cytokine profiles of patients with enterohemorrhagic Escherichia coli O111-induced hemolytic-uremic syndrome.

    Science.gov (United States)

    Shimizu, Masaki; Kuroda, Mondo; Sakashita, Natsumi; Konishi, Michio; Kaneda, Hisashi; Igarashi, Noboru; Yamahana, Junya; Taneichi, Hiromichi; Kanegane, Hirokazu; Ito, Mika; Saito, Shigeru; Ohta, Kazuhide; Taniguchi, Takumi; Furuichi, Kengo; Wada, Takashi; Nakagawa, Masaru; Yokoyama, Hitoshi; Yachie, Akihiro

    2012-12-01

    Proinflammatory cytokines are related to the pathogenesis of enterohemorrhagic Escherichia coli (EHEC) infection and hemolytic-uremic syndrome (HUS). We assessed the kinetics of the release of cytokines such as neopterin, interleukin (IL)-6, IL-8 and tumour necrosis factor (TNF)-α and the soluble forms of type I and II TNF receptors during EHEC O111-induced HUS (EHEC O111/HUS). Fourteen patients with EHEC O111/HUS were enrolled in this study. Serum concentrations of all cytokines other than TNF-α were significantly elevated in patients with severe HUS compared with those in patients with mild HUS. Although serum concentrations of TNF-α were not significantly higher in patients with severe HUS, most patients with acute encephalopathy showed elevated TNF-α levels. Serum concentrations of these cytokines rapidly and markedly increased, and massive hypercytokinaemia developed 1 day before the diagnosis of HUS in patients with severe HUS. Changes in the number of white blood cells and concentration of serum lactate dehydrogenase were significantly larger between the onset of hemorrhagic colitis and the time of the diagnosis of HUS in patients with severe HUS compared with those in patients with mild HUS. Proinflammatory cytokines play an important role in the pathogenesis of EHEC infection and development of severe complications, including HUS and encephalopathy. Monitoring the cytokine profile may be useful for assessing disease activity of EHEC O111 infections.

  19. Sarcoidosis and tuberculosis cytokine profiles: indistinguishable in bronchoalveolar lavage but different in blood.

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    Muhunthan Thillai

    Full Text Available BACKGROUND: The clinical, radiological and pathological similarities between sarcoidosis and tuberculosis can make disease differentiation challenging. A complicating factor is that some cases of sarcoidosis may be initiated by mycobacteria. We hypothesised that immunological profiling might provide insight into a possible relationship between the diseases or allow us to distinguish between them. METHODS: We analysed bronchoalveolar lavage (BAL fluid in sarcoidosis (n = 18, tuberculosis (n = 12 and healthy volunteers (n = 16. We further investigated serum samples in the same groups; sarcoidosis (n = 40, tuberculosis (n = 15 and healthy volunteers (n = 40. A cross-sectional analysis of multiple cytokine profiles was performed and data used to discriminate between samples. RESULTS: We found that BAL profiles were indistinguishable between both diseases and significantly different from healthy volunteers. In sera, tuberculosis patients had significantly lower levels of the Th2 cytokine interleukin-4 (IL-4 than those with sarcoidosis (p = 0.004. Additional serum differences allowed us to create a linear regression model for disease differentiation (within-sample accuracy 91%, cross-validation accuracy 73%. CONCLUSIONS: These data warrant replication in independent cohorts to further develop and validate a serum cytokine signature that may be able to distinguish sarcoidosis from tuberculosis. Systemic Th2 cytokine differences between sarcoidosis and tuberculosis may also underly different disease outcomes to similar respiratory stimuli.

  20. Vitamin D and Inflammatory Cytokines in Healthy and Preeclamptic Pregnancies

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    David Barrera

    2015-08-01

    Full Text Available Preeclampsia is a pregnancy disease characterized by hypertension and proteinuria. Among several disorders, the imbalance of inflammatory cytokines and the alteration of vitamin D metabolism have been reported in preeclampsia. The effects of calcitriol upon inflammatory cytokines has been demonstrated. In healthy pregnant women there is a shift toward a Th2 cytokine profile, which is necessary for an adequate pregnancy outcome. As compared with normal pregnancy, high pro-inflammatory and low anti-inflammatory cytokine levels have been observed in preeclamptic women. Preeclampsia has been associated with low calcitriol levels and vitamin D deficiency is correlated with a higher risk of the development of this disease. It has been demonstrated that placenta is a source as well as the target of calcitriol and cytokines and placental dysfunction has been associated with preeclampsia. Therefore, the present manuscript includes a review about serum calcitriol levels in non-pregnant, pregnant, and preeclamptic women as well as a review on the fetoplacental vitamin D metabolism in healthy and preeclamptic pregnancies. In addition, circulating and fetoplacental inflammatory cytokines in healthy and preeclamptic pregnancies are reviewed. Finally, the effects of calcitriol upon placental pro-inflammatory cytokines are also explored. In conclusion, maternal and placental calcitriol levels are low in preeclampsia which may explain, at least in part, high pro-inflammatory cytokine levels in this disease.

  1. Vitamin D and Inflammatory Cytokines in Healthy and Preeclamptic Pregnancies.

    Science.gov (United States)

    Barrera, David; Díaz, Lorenza; Noyola-Martínez, Nancy; Halhali, Ali

    2015-08-04

    Preeclampsia is a pregnancy disease characterized by hypertension and proteinuria. Among several disorders, the imbalance of inflammatory cytokines and the alteration of vitamin D metabolism have been reported in preeclampsia. The effects of calcitriol upon inflammatory cytokines has been demonstrated. In healthy pregnant women there is a shift toward a Th2 cytokine profile, which is necessary for an adequate pregnancy outcome. As compared with normal pregnancy, high pro-inflammatory and low anti-inflammatory cytokine levels have been observed in preeclamptic women. Preeclampsia has been associated with low calcitriol levels and vitamin D deficiency is correlated with a higher risk of the development of this disease. It has been demonstrated that placenta is a source as well as the target of calcitriol and cytokines and placental dysfunction has been associated with preeclampsia. Therefore, the present manuscript includes a review about serum calcitriol levels in non-pregnant, pregnant, and preeclamptic women as well as a review on the fetoplacental vitamin D metabolism in healthy and preeclamptic pregnancies. In addition, circulating and fetoplacental inflammatory cytokines in healthy and preeclamptic pregnancies are reviewed. Finally, the effects of calcitriol upon placental pro-inflammatory cytokines are also explored. In conclusion, maternal and placental calcitriol levels are low in preeclampsia which may explain, at least in part, high pro-inflammatory cytokine levels in this disease.

  2. Plasma cytokine profiling in sibling pairs discordant for autism spectrum disorder

    Science.gov (United States)

    2013-01-01

    Objective Converging lines of evidence point to the existence of immune dysfunction in autism spectrum disorder (ASD), which could directly affect several key neurodevelopmental processes. Previous studies have shown higher cytokine levels in patients with autism compared with matched controls or subjects with other developmental disorders. In the current study, we used plasma-cytokine profiling for 25 discordant sibling pairs to evaluate whether these alterations occur within families with ASD. Methods Plasma-cytokine profiling was conducted using an array-based multiplex sandwich ELISA for simultaneous quantitative measurement of 40 unique targets. We also analyzed the correlations between cytokine levels and clinically relevant quantitative traits (Vineland Adaptive Behavior Scale in Autism (VABS) composite score, Social Responsiveness Scale (SRS) total T score, head circumference, and full intelligence quotient (IQ)). In addition, because of the high phenotypic heterogeneity of ASD, we defined four subgroups of subjects (those who were non-verbal, those with gastrointestinal issues, those with regressive autism, and those with a history of allergies), which encompass common and/or recurrent endophenotypes in ASD, and tested the cytokine levels in each group. Results None of the measured parameters showed significant differences between children with ASD and their related typically developing siblings. However, specific target levels did correlate with quantitative clinical traits, and these were significantly different when the ASD subgroups were analyzed. It is notable that these differences seem to be attributable to a predisposing immunogenetic background, as no other significant differences were noticed between discordant sibling pairs. Interleukin-1β appears to be the cytokine most involved in quantitative traits and clinical subgroups of ASD. Conclusions In the present study, we found a lack of significant differences in plasma-cytokine levels between

  3. Association of cytokine and matrix metalloproteinase profiles with disease activity and function in ankylosing spondylitis

    Science.gov (United States)

    2012-01-01

    Introduction The pathology of ankylosing spondylitis (AS) suggests that certain cytokines and matrix metalloproteinases (MMPs) might provide useful markers of disease activity. Serum levels of some cytokines and MMPs have been found to be elevated in active disease, but there is a general lack of information about biomarker profiles in AS and how these are related to disease activity and function. The purpose of this study was to investigate whether clinical measures of disease activity and function in AS are associated with particular profiles of circulating cytokines and MMPs. Methods Measurement of 30 cytokines, five MMPs and four tissue inhibitors of metalloproteinases was carried out using Luminex® technology on a well-characterised population of AS patients (n = 157). The relationship between biomarker levels and measures of disease activity (Bath ankylosing spondylitis disease activity index (BASDAI)), function (Bath ankylosing spondylitis functional index) and global health (Bath ankylosing spondylitis global health) was investigated. Principal component analysis was used to reduce the large number of biomarkers to a smaller set of independent components, which were investigated for their association with clinical measures. Further analyses were carried out using hierarchical clustering, multiple regression or multivariate logistic regression. Results Principal component analysis identified eight clusters consisting of various combinations of cytokines and MMPs. The strongest association with the BASDAI was found with a component consisting of MMP-8, MMP-9, hepatocyte growth factor and CXCL8, and was independent of C-reactive protein levels. This component was also associated with current smoking. Hierarchical clustering revealed two distinct patient clusters that could be separated on the basis of MMP levels. The high MMP cluster was associated with increased C-reactive protein, the BASDAI and the Bath ankylosing spondylitis functional index. Conclusions

  4. Cytokine profile in the synovial fluid of patients with temporomandibular joint disorders: A systematic review.

    Science.gov (United States)

    Kellesarian, Sergio Varela; Al-Kheraif, Abdulaziz A; Vohra, Fahim; Ghanem, Alexis; Malmstrom, Hans; Romanos, Georgios E; Javed, Fawad

    2016-01-01

    The aim of this study was to review the cytokine profiles in the synovial fluid (SF) of patients with temporomandibular joint disorders (TMJD). Databases were searched from 1965 till September 2015 using different combinations of the following key words: "Temporomandibular joint"; "Cytokine"; "disorder"; and "synovial fluid" and "inflammation". Titles and abstracts of studies identified using the above-described protocol were screened and checked for agreement. Full-texts of articles judged by title and abstract to be relevant were read and independently evaluated. Hand-searching of the reference lists of potentially relevant original and review articles was also performed. The pattern of the present systematic review was customized to mainly summarize the relevant data. Fifteen studies were included. In 12 studies, cytokine profile of patients with TMJD was assessed using enzyme linked immunosorbent assay; and in 2 studies, histological analysis was performed to assess the cytokine profile of patients with TMJD. Patients with TMJD presented raised levels of interleukin (IL)-6 in 8 studies, IL-1beta (1β) in 5 studies and tumor necrosis factor-alpha (TNF-α) in 5 studies. Two studies showed no significant difference in TNF-α levels in patients with and without TMJD; and IL-1β levels were comparable in patients with and without TMJD in 2 studies. Raised levels of IL-6, TNF-α, IL-1β, IL-8, and IFN-γ in the SF have been associated with inflammation in patients with TMJD. Cytokines IL-10, osteoclastogenesis inhibitory factor/osteoprotegerin (OCIF/OPG), and VEGF found in the SF of TMJs could have an anti-inflammatory effect.

  5. SOME FEATURES OF CYTOKINE PROFILE IN PATIENTS WITH GOUT AND INSULIN RESISTANCE SYNDROME

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    N. N. Kushnarenko

    2011-01-01

    Full Text Available Abstract. Blood serum levels of cytokines (Il-1β, TNFα, IL-2, IL-4, IL-6, IL-8, IL-10, IL-20, IL-23,  cytokine soluble receptors (SRp55 TNFα, SR IL-6, as well as markers of insulin resistance were studied in  a group of male patients with primary gout. Increased levels of the above cytokines and deficiency of soluble  IL-6 receptors in blood serum were most pronounced in gouty patients with insulin resistance syndrome. Close  links were revealed between serum uric acid and insulin contents in gouty patients. Significant correlations were  found between the levels of insulin, some cytokines (IL-4, IL-6, TNFα, and soluble receptors (SRp55 TNFα,  SR IL-6, thus presuming a certain role of impaired cytokine profile for development of insulin resistance  syndrome in such cohort of patients. (Med. Immunol., 2011, vol. 13, N 6, pp 627-630 

  6. Some cytokine profiles of T-helper cells in lesions of advanced periodontitis.

    Science.gov (United States)

    Berglundh, Tord; Liljenberg, Birgitta; Lindhe, Jan

    2002-08-01

    The aim of the present study was to analyze some cytokine profiles of T-helper cells in periodontitis lesions. 22 adult patients (7 females and 15 males, aged 24-66 years) with advanced and generalized chronic periodontitis were recruited. Clinical and radiographical characteristics of periodontal disease was assessed. From each patient a gingival biopsy was obtained from one randomly selected diseased interproximal site. The soft tissue sample was prepared for immunohistochemical analysis. Double staining was performed to detect cells positive for both the CD4 marker and different cytokines, i.e. interleukin (IL)-2, IL-4, IL-6 and interferon-gamma (IFN-gamma). The lesions in advanced periodontitis contained similar proportions of cells positive for the different cytokine markers examined. In addition, the number of cells expressing cytokine profiles for either T helper-1 (IFN-gamma + IL-2) or T helper-2 (IL-4 + IL-6) was similar. It is suggested that the lesions of periodontitis are regulated by a combined Th-1 and Th-2 function.

  7. Analysis of the cytokine profile in the duodenal mucosa of refractory coeliac disease patients.

    Science.gov (United States)

    Caruso, Roberta; Marafini, Irene; Sedda, Silvia; Del Vecchio Blanco, Giovanna; Giuffrida, Paolo; MacDonald, Thomas T; Corazza, Gino Roberto; Pallone, Francesco; Di Sabatino, Antonio; Monteleone, Giovanni

    2014-03-01

    RCD [refractory CD (coeliac disease)] is characterized by severe symptoms/signs of malabsorption and mucosal damage unresponsive to a GFD (gluten-free diet). The pathogenesis of RCD is not fully understood. In the present paper, we have characterized the mucosal profile of effector cytokines in RCD. Duodenal biopsies were taken from patients with RCD, patients with active CD and normal controls and were analysed for inflammatory cytokines by real-time PCR and ELISA. IFN (interferon)-γ and IL (interleukin)-21 transcripts were increased in active CD patients but not in RCD patients as compared with normal controls, whereas IL-17A RNA was up-regulated in both active CD and RCD. No significant increase in IL-15 transcripts was observed in both active CD and RCD, whereas IL-15 protein was increased in active CD. IL-6 and TNF (tumour necrosis factor)-α were up-regulated only in RCD. As a proof, we present the case of a woman affected by RCD who responded to anti-TNF-α treatment with improvement of malabsorptive symptoms/signs but no healing of mucosal lesions. The findings indicate that the profile of mucosal effector cytokines differs between RCD and active CD and suggest that TNF-α, IL-6 and IL-17A, but not Th1-type cytokines, could drive the detrimental response in this condition.

  8. Gene Expression Profile of Human Cytokines in Response to B.pseudomallei Infection

    Science.gov (United States)

    2017-04-19

    the gene expression of 84 important cytokines by real time quantitative 32 polymerase chain reaction (RT qPCR) was used. We analyzed 26 melioidosis...The PCR reaction and thermal profile recommended by the 168 manufacturer were followed. 26 melioidosis cases (identified as confirmed or 169...by PCR . All samples for the study were collected 116 between September 2014 and April 2016. 117 Patients who were culture positive for B

  9. Cytokines profile and peripheral blood mononuclear cells morphology in Rett and autistic patients.

    Science.gov (United States)

    Pecorelli, Alessandra; Cervellati, Franco; Belmonte, Giuseppe; Montagner, Giulia; Waldon, PhiAnh; Hayek, Joussef; Gambari, Roberto; Valacchi, Giuseppe

    2016-01-01

    A potential role for immune dysfunction in autism spectrum disorders (ASD) has been well established. However, immunological features of Rett syndrome (RTT), a genetic neurodevelopmental disorder closely related to autism, have not been well addressed yet. By using multiplex Luminex technology, a panel of 27 cytokines and chemokines was evaluated in serum from 10 RTT patients with confirmed diagnosis of MECP2 mutation (typical RTT), 12 children affected by classic autistic disorder and 8 control subjects. The cytokine/chemokine gene expression was assessed by real time PCR on mRNA of isolated peripheral blood mononuclear cells (PBMCs). Moreover, ultrastructural analysis of PBMCs was performed using transmission electron microscopy (TEM). Significantly higher serum levels of interleukin-8 (IL-8), IL-9, IL-13 were detected in RTT compared to control subjects, and IL-15 shows a trend toward the upregulation in RTT. In addition, IL-1β and VEGF were the only down-regulated cytokines in autistic patients with respect to RTT. No difference in cytokine/chemokine profile between autistic and control groups was detected. These data were also confirmed by ELISA real time PCR. At the ultrastructural level, the most severe morphological abnormalities were observed in mitochondria of both RTT and autistic PBMCs. In conclusion, our study shows a deregulated cytokine/chemokine profile together with morphologically altered immune cells in RTT. Such abnormalities were not quite as evident in autistic subjects. These findings indicate a possible role of immune dysfunction in RTT making the clinical features of this pathology related also to the immunology aspects, suggesting, therefore, novel possible therapeutic interventions for this disorder.

  10. Intrahepatic cytokine profile in renal-transplant patients infected by hepatitis C virus.

    Science.gov (United States)

    Kamar, Nassim; Rostaing, Lionel; Sandres-Saune, Karine; Selves, Janick; Barthe, Carole; Dubois, Martine; Alric, Laurent; Durand, Dominique; Izopet, Jacques

    2005-08-01

    In order to examine the immunopathogenesis of hepatitis C virus (HCV)-related liver injury in renal-transplant patients, intra-hepatic cytokine profiles were examined in 38 liver biopsies from 38 patients by measuring messenger RNA (mRNA) concentrations by a real-time PCR method of a Th1 cytokine (i.e., interferon (IFN)-gamma), a Th2 cytokines (i.e., interleukine (IL)-10), a proinflammatory cytokine (i.e., IL-8), and a potent fibrogenic factor (transforming growth factor [TGF]-beta). There was no significant difference in TGF-beta, IFN-gamma, IL-10, or IL-8 levels of expression according to liver-activity grade, liver-fibrosis stage, the concentration of HCV RNA at liver biopsies, or the HCV genotype. However, IFN-gamma/beta-actin mRNA concentration was higher than the IL-10/beta-actin mRNA concentration in patients with F3 Metavir score. Median IFN-gamma/beta-actin mRNA concentration tended to be higher in patients with A3 and A4 Metavir activity grades compared with those with A0 and A1 activity grades. There was a significant correlation between the duration of HCV infection and both TGF-beta/beta-actin (r(2)=0.19, P=0.04) and IL-8/beta-actin mRNA concentrations (r(2)=0.19, P=0.03). IFN-gamma/beta-actin mRNA concentration also increased according to the duration of HCV (r(2)=0.19, P=0.07). Finally, there was a significant correlation between the duration of HCV infection and liver fibrosis stage (r(2)=0.17, P=0.045). Intrahepatic Th1 cytokine profile seems to be predominant in patients with extensive fibrosis and activity scores, suggesting that it might be responsible for liver injury in renal transplant patients.

  11. [Cytokine profile changes in children with juvenile idiopathic arthritis-associated uveitis].

    Science.gov (United States)

    Drozdova, E A; Yadykina, E V; Mezentseva, E A; Nikushkina, K V

    to identify the differences between serum cytokine profiles in juvenile idiopathic arthritis (JIA) with or without uveal tract inflammation. Serum cytokine profiles were studied in two groups of patients: 20 children with JIA and JIA-associated uveitis and 33 children, who had no signs of uveitis under basic therapy for their JIA. All the patients showed drug remission of articular syndrome. Inflammation of the choroid took the form of chronic anterior uveitis. The process was active in 95% of cases. The control group consisted of 35 children without rheumatic disease or other acute condition at the time of examination. Groups were comparable in terms of age and sex. Serum levels of TNF-α, IFN-γ, IL-17, IL-10 were measured by the enzyme multiplied immunoassay technique. A statistically significant increase in TNF-α, IFN-γ, IL-17, and IL-10 levels was found in all patients as compared to the control group. A comparison drawn between serum cytokine levels of JIA patients and those, who also suffered from JIA-associated uveitis, revealed a decrease in IFN-γ and an increase in IL-10 in the latter group. There was also a statistically significant positive correlation between TNF-α and IFN-γ serum levels in patients with JIA-associated uveitis. Development of uveitis in patients with drug remission of JIA occurs on the background of cytokine imbalance in the serum, in particular, increased concentrations of proinflammatory TNF-α and IL-17 cytokines along with reduced IFN-γ and increased IL-10 levels. This may be regarded as risk factors for ocular inflammation and should be taken into account when making treatment decisions.

  12. Cytokines profile in hypertensive patients with left ventricular remodeling and dysfunction.

    Science.gov (United States)

    Kuznetsova, Tatiana; Haddad, Francois; Knez, Judita; Rosenberg-Hasson, Yael; Sung, Janine; Cauwenberghs, Nicholas; Thijs, Lutgarde; Karakikes, Ioannis; Maecker, Holden; Mahaffey, Kenneth W; Wu, Joseph C; Staessen, Jan A

    2015-12-01

    There is strong evidence that inflammatory mediators play a key role in the progression to heart failure in patients with systemic hypertension (HTN). The present study aimed to identify a set of cytokines that are associated with early left ventricular (LV) remodeling and dysfunction as captured by echocardiography in patients with HTN in a cross-sectional case-control study nested within the FLEMish study on ENvironment, Genes and Health Outcome. We identified three groups of participants from the cohort: normotensive subjects (normotension; n = 30), HTN with normal LV structure and function (HTN [LV-]; n = 30), and HTN with evidence of adverse LV remodeling (HTN [LV+]; n = 50). We measured cytokines using a 63-plex Luminex platform. Using partial least squares-discriminant analysis, we constructed three latent variables from the measured cytokines that explained 35%-45% of the variance between groups. We identified five common cytokines (interleukin 18, monokine induced by gamma interferon, hepatocyte growth factor, epithelial neutrophil-activating peptide 78, and vascular endothelial growth factor D) with a stable signal which had a major impact on the construction of the latent variables. Among these cytokines, after adjustment for confounders, interleukin 18 remained significantly different between HTN participants with and without LV involvement (P = .02). Moreover, granulocyte-macrophage colony-stimulating factor and leptin showed a consistent upward trend in all HTN patients compared with normotensive subjects. In conclusion, in HTN patients with LV remodeling or/and dysfunction, we identified a set of cytokines strongly associated with LV maladaptation. We also found a distinct profile of inflammatory biomarkers that characterize HTN.

  13. Differential intragraft cytokine messenger RNA profiles during rejection and repair of clinical heart transplants. A longitudinal study

    NARCIS (Netherlands)

    de Groot-Kruseman, Hester A; Mol, Wendy M; Niesters, Hubert G M; Maat, Alex P W; van Gelder, Teun; Balk, Aggie H M M; Weimar, Willem; Baan, Carla C

    2003-01-01

    After clinical heart transplantation, ischemia, acute rejection, and repair mechanisms can trigger the up-regulation of cytokines. To investigate the cytokine profile early after transplantation, we monitored messenger RNA (mRNA) expression levels of tumor necrosis factor-alpha (TNF-alpha), monocyte

  14. Prevalence, hemodynamics, and cytokine profile of effusive-constrictive pericarditis in patients with tuberculous pericardial effusion.

    Directory of Open Access Journals (Sweden)

    Mpiko Ntsekhe

    Full Text Available BACKGROUND: Effusive constrictive pericarditis (ECP is visceral constriction in conjunction with compressive pericardial effusion. The prevalence of proven tuberculous ECP is unknown. Whilst ECP is distinguished from effusive disease on hemodynamic grounds, it is unknown whether effusive-constrictive physiology has a distinct cytokine profile. We conducted a prospective study of prevalence and cytokine profile of effusive-constrictive disease in patients with tuberculous pericardial effusion. METHODS: From July 2006 through July 2009, the prevalence of ECP and serum and pericardial levels of inflammatory cytokines were determined in adults with tuberculous pericardial effusion. The diagnosis of ECP was made by combined pericardiocentesis and cardiac catheterization. RESULTS: Of 91 patients evaluated, 68 had tuberculous pericarditis. The 36/68 patients (52.9%; 95% confidence interval [CI]: 41.2-65.4 with ECP were younger (29 versus 37 years, P=0.02, had a higher pre-pericardiocentesis right atrial pressure (17.0 versus 10.0 mmHg, P 15 mmHg (odds ratio [OR] = 48, 95%CI: 8.7-265; P 200 pg/ml (OR=10, 95%CI: 1.1, 93; P=0.04 were independently associated with ECP. CONCLUSION: Effusive-constrictive disease occurs in half of cases of tuberculous pericardial effusion, and is characterized by greater elevation in the pre-pericardiocentesis right atrial pressure and pericardial and serum IL-10 levels compared to patients with effusive non-constrictive tuberculous pericarditis.

  15. Cytokine profiles and hepatic injury in occult hepatitis C versus chronic hepatitis C virus infection.

    Science.gov (United States)

    Mousa, N; Eldars, W; Eldegla, H; Fouda, O; Gad, Y; Abousamra, N; Elmasry, E; Arafa, M

    2014-01-01

    Occult hepatitis C virus (HCV) infection is a new entity that should be considered when diagnosing patients with abnormal liver functions of unknown origin. This work was carried out to evaluate T-helper 1/T-helper 2 (Th1/Th2) cytokine profiles in patients with occult HCV infection versus chronic hepatitis C (CHC) infection, also to investigate any association between theses cytokines and liver histological features in both groups. Serum levels of Th1 cytokines (IL-2, IFN-gamma) and Th2 (IL-4 and IL-10) were measured in 35 patients with occult HCV infection compared to 50 patients with chronic hepatitis C infection and 30 healthy controls. We have found that Th1 cytokines were significantly increased in patients with CHC infection than in both occult HCV infection and control groups (p less than 0.001). On the other hand, serum IL-4 levels were higher in occult HCV infection than in CHC and control groups (p less than 0.001). Furthermore, serum IL-10 levels were higher in both patient groups vs control group (pless than 0.001), with no significant difference between CHC and occult HCV groups. Finally, only serum IL-10 levels were significantly higher among patients with high activity (A2-A3) than those with low activity (A0-A1) in both CHC and occult HCV groups (p=0.038, p=0.025, respectively). Patients with occult HCV infection exhibited a distinct immunoregulatory cytokine pattern that is shifted towards the Th2 arm.

  16. 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

    2013-10-01

    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 cytokines involved in the inflammatory response in overweight/obese subjects with 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 pcytokines, interferon-γ (IFN-γ), IL-1β, IL-2, IL-4, IL-8, IL-10, IL-12p70 and IL-13, seemed to be elevated in the 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.

  17. Expression profiling of pattern recognition receptors and selected cytokines in miniature dachshunds with inflammatory colorectal polyps.

    Science.gov (United States)

    Igarashi, Hirotaka; Ohno, Koichi; Maeda, Shingo; Kanemoto, Hideyuki; Fukushima, Kenjiro; Uchida, Kazuyuki; Tsujimoto, Hajime

    2014-05-15

    Inflammatory colorectal polyps (ICRPs) are commonly seen in miniature dachshund (MD) dogs; typically, multiple polyps form with severe neutrophil infiltration. ICRP is thought to be a novel form of inflammatory bowel disease (IBD), but its etiology has not been investigated. The innate immune system is implicated in the pathogenesis of both human and canine IBD. Therefore, the aim of the current study was to evaluate the messenger RNA (mRNA) expression profiles of pattern recognition receptors (PRRs) and cytokines in ICRPs. Polyp tissues were collected by colonoscopic biopsies from 24 MDs with ICRPs. Non-polypoid colonic mucosa was collected from all MDs with ICRPs and 21 clinically healthy beagles (as the controls). The expression levels of the mRNAs encoding toll-like receptors (TLRs) 1-10; nucleotide-binding oligomerization domain (NOD)-like receptors NOD1 and NOD2; and cytokines IL-1β, IL-6, IL-8/CXCL8, and TNF-α were evaluated by quantitative real-time RT-PCR. Three of the 10 well-known candidate reference genes were selected as housekeeper genes based on analyses from the GeNorm, NormFinder, and BestKeeper programs. Levels of TLR1, TLR2, TLR4, TLR6, TLR7, TLR8, TLR9, TLR10, NOD2, and all cytokines were significantly upregulated in the polyps relative to those in the controls. There was significant decrease in the expression levels of TLR3 and NOD1 in the polyp tissues compared to the non-polypoid colonic mucosa obtained from MDs with ICRPs. All upregulated PRR mRNAs were positively correlated with all proinflammatory cytokine mRNAs. This study demonstrated the dysregulation of PRRs and proinflammatory cytokines in ICRPs of MDs, which may play an important role in the pathogenesis of this disease.

  18. ACUTE PHASE PROTEINS, LIPID PROFILE AND PROINFLAMMATORY CYTOKINES IN HEALTHY AND BRONCHOPNEUMONIC WATER BUFFALO CALVES

    Directory of Open Access Journals (Sweden)

    Sabry M. El-Bahr

    2013-01-01

    Full Text Available The aim of the present study was to evaluate the diagnostic value of Acute Phase Proteins (APP, lipid profiles and proinflammatory cytokines in healthy and bronchopneumonic water buffalo calves. Therefore, sixty water buffalo calves (9±1 month old, 175±15 kg were divided into two equal groups, the first group represented healthy, control, calves whereas calves of the second group were affected with bronchopneumonia. Total leukocytic and differential counts were determined. Serum total protein, albumin, Triacylglyceol (TAG, low density lipoprotein cholesterol (LDL-c, High Density Lipoprotein cholesterol (HDL-c, Total cholesterol, Alanine Amino Transferase (ALT, Aspartate Amino Transferase (AST, Alkaline Phosphatase (ALP, Fibrinogen (Fb, Haptaglobin (Hp, Serum Amyloid A (SAA, Tumor Necrosis Factor-alpha (TNF-α, Interleukins (IL1β, IL-12 and Interferon-gamma (IFN-γ were also determined. In addition, Bronchoalveolar Lavage (BAL was collected and analyzed. The present findings indicated that, total leukocytic and neutrophils counts were significantly (p<0.05 higher in pneumonic water buffalo calves compare with control. The examined biochemical parameters were significantly (p<0.05 increased in pneumonic calves except for total protein, albumin, cholesterol and HDL-c which were significantly (p<0.05 lower compare with control. Serum concentrations of investigated APP and proinflammatory cytokines were significantly (p<0.05 higher in pneumonic water buffalo calves than those of control. The present study demonstrated that, APP, lipid profile and proinflammatory cytokines perhaps served as biomarkers of bronchopneumonia in water buffalo calves. However, future studies with higher baseline sampling are still needed to establish and validate reference values for APP and cytokines in water buffalo calves.

  19. Neutrophil Functions and Cytokines Expression Profile in Buffaloes with Impending Postpartum Reproductive Disorders

    Directory of Open Access Journals (Sweden)

    Manas Kumar Patra

    2013-10-01

    Full Text Available The study was conducted to correlate the periparturient immune status in terms of neutrophil functions and cytokine expression in peripheral blood mononuclear cell culture with impending postpartum reproductive disorders in buffaloes. Forty pregnant buffaloes were observed for occurrence of postpartum reproductive disorders (PRD, i.e., metritis, endometritis and delayed uterine involution etc., during one week prepartum to four weeks postpartum period. A representative number (n = 6 of buffaloes that did not develop any PRD were included in group I (healthy, control, while the animals which experienced PRD were assigned into group II (PRD, n = 8. The blood samples were collected at weekly interval from one week prepartum to four weeks postpartum period considering the day of calving as ‘d 0’. Differential leucocytes counts, superoxide and hydrogen peroxide production activity in isolated neutrophils and the mRNA expression profile of cytokines i.e., IL-2, IL-4 and IFN-γ in PBMC culture were studied in all the samples. A higher total leucocytes, neutrophil and band cells count along with impaired neutrophil functions i.e., lowered level of production of superoxide and hydrogen peroxide before parturition and during early postpartum period were observed in buffaloes developing PRD. Further, a lower expression of IL-2, IFN-γ and IL-4 mRNA in PBMC culture was observed at calving in buffaloes that subsequently developed PRD at later postpartum. Thus, suppression in neutrophil function and cytokine expression at prepartum to early postpartum period predisposes the buffaloes to develop postpartum reproductive disorders. Hence, monitoring of neutrophils function and cytokine expression profile would be effective to predict certain reproductive disorders at late pregnancy or immediately after parturition in buffaloes. In future, this may be a novel approach for determining suitable management and therapeutic decisions for prevention of commonly

  20. Neonatal high-permeability pulmonary edema based on serial cytokine profiles and KL-6 in serum: case report.

    Science.gov (United States)

    Nakamura, Toshihiko; Nakamura, Mari; Takahashi, Naoto

    2017-03-22

    A newborn male with pulmonary edema was delivered at term by elective Caesarian section. Cytokine profiles of 17 cytokines and KL-6 in cord blood and serial serum values were investigated. The cord blood values of all 17 cytokines and KL-6 were within normal limits. Subsequently, IL-6, IL-8, IL-10, IL-13, IL-17, and IFNγ rapidly elevated during the first several hours after birth and dramatically decreased thereafter, whereas KL-6 rose to 611 U/ml on the 3(rd) day of life and then gradually decreased. These cytokines may induce pulmonary permeability, and KL-6 secreted in lining fluid could result in influx into the bloodstream. This is the first report that we have differentiated neonatal pulmonary edema from TTN by the measurement of serial cytokine profiles and KL-6 in serum.

  1. Longitudinal Study of Cytokine Expression, Lipid Profile and Neuronal Growth Factors in Human Breast Milk from Term and Preterm Deliveries.

    Science.gov (United States)

    Collado, Maria Carmen; Santaella, Marina; Mira-Pascual, Laia; Martínez-Arias, Elena; Khodayar-Pardo, Parisá; Ros, Gaspar; Martínez-Costa, Cecilia

    2015-10-19

    Breast milk (BM) is considered as a reference for infant nutrition. The role of bioactive components, such as cytokines, hormones, growth factors (GFs) and fatty acids (FAs) is poorly known, but they might be implicated in immune response development. The aim of this study was to identify the lipid profile and the spectrum of cytokines and neuronal GF in BM samples and analyse the influence of gestational age and lactation time on these components. This study used a longitudinal prospective method for the characterization of cytokines, FAs and GFs global profiles in 120 BM samples from 40 healthy mothers (20 preterm and 20 term) collected as colostrum, transitional and mature milk. The cytokines were analysed by protein array (Ray Bio® Human Cytokine Array G6. Ray Biotech, Inc. Norcross, GA, USA) and the FAs were analysed by gas chromatography. The FA profile was similar between the term and the preterm BM samples. Omega-3-α-linoleic and docosahexaenoic acid (DHA) and omega-6-linoleic acid were the most abundant in the term and preterm samples during lactation. Omega-3 ETA and omega-3 EPA we observed exclusively in the preterm samples. The cytokine profile showed a different trend based on gestational age. A significantly higher expression of neurotrophic factors was found in the mature preterm milk samples as compared to the mature term samples. Our study is the first to identify the influence and interactions of perinatal factors on cytokine, GFs and FAs in human milk.

  2. Different cytokine profiles of skin-derived T cell cultures from patients with atopic dermatitis and psoriasis

    DEFF Research Database (Denmark)

    Martel, Britta Cathrina; Dyring-Andersen, Beatrice; Skov, Lone

    2016-01-01

    OBJECTIVES: To investigate differences in expression of surface markers, cytokine profiles, and presence of CD4(+)CD8(+) T cells in skin-derived T cell cultures from patients with extrinsic atopic dermatitis (AD), intrinsic AD, and psoriasis expanded in the presence of IL-2 and IL-4. MATERIAL: Skin...... biopsies from patients with extrinsic AD (n = 6), intrinsic AD (n = 9) and psoriasis (n = 9). METHODS: Skin-derived T cell cultures were analyzed for expression of six surface markers, 11 intracellular cytokines, and three T cell subtype signature transcription factors by flow cytometry, and secreted...... cytokines by multiplex. RESULTS: A different IFN-γ profile emerged between the extrinsic AD and psoriatic T cell cultures; however, there was no difference in IL-17 profile. No differences with regard to cytokine expression were found between extrinsic AD and intrinsic AD cultures; however, cutaneous...

  3. CYTOKINE PROFILE OF TH1- AND TH2-DEPENDENT VARIANTS OF CHRONIC GVHD

    Directory of Open Access Journals (Sweden)

    O. T. Kudaeva

    2012-01-01

    Full Text Available Abstract. Induction of chronic GVHD in the DBA/2→(C57Bl/6xDBA/2 F1 semi-allogeneic murine model results into development of Th1- and Th2-dependent immunopathological conditions that are characterized by different cytokine profiles. Chronic GVHD is accompanied by a sharp increase in IgE levels, thus presuming considerable IL-4 production. In recipients with Th2-dependent GvHD variant, elevated contents of serum IL-6, IL-7 and TNFα were also observed, which, along with other effects, may support polyclonal activation of B cells, thus leading to development of autoimmune pathology.

  4. Expression Profile of Intravitreous Cytokines, Chemokines and Growth Factors in Patients with Fuchs Heterochromic Iridocyclitis

    Directory of Open Access Journals (Sweden)

    Kaori Suzuki

    2010-05-01

    Full Text Available Purpose: To report the postoperative courses of 2 patients with Fuchs heterochromic iridocyclitis (FHI and the concentrations of various cytokines, chemokines and growth factors in vitreous fluid samples to obtain insights into pathobiochemical aspects. Subjects: The patients were a 27- and a 47-year-old woman. Phacoemulsification and aspiration, intraocular lens (IOL implantation, and pars plana vitrectomy were performed to treat their cataracts and vitreous opacities. During their early postoperative periods, inflammatory cells precipitated on the IOL and intraocular pressure was increased in both patients. Methods: At the time of surgery, undiluted vitreous fluid specimens were collected. The concentrations of multiple cytokines, chemokines and growth factors were measured by a bead array immunodetection system. Results: The levels of interleukin-1ra, -5, -6, -8, -10 and -13, interferon-inducible 10-kDa protein, monocyte chemoattractant protein 1, macrophage inflammatory protein 1β, and regulated upon activation, normal T-cell expressed and secreted (RANTES were significantly elevated in vitreous fluid in both patients. Conclusion: Although the postoperative course was generally favorable in patients with FHI, steroid instillation was necessary for a few months postoperatively, as precipitates easily formed on the IOL surface and elevated intraocular pressure. The profiles of intravitreal concentrations of cytokines, chemokines and growth factors may characterize postoperative inflammatory reactions.

  5. Serum cytokines profiles in Nigerian children withAscaris lumbricoides infection

    Institute of Scientific and Technical Information of China (English)

    Irior Dominic Osagie; Abu Maliki

    2010-01-01

    Objective:To investigate the cytokines profile in the serum of some Nigerian children with Ascaris lumbricoides (A. lumbricoides) infection and relations between the intensity of infection, age and the concentration of these cytokines.Methods: Feacal samples from consenting children were examined using formol ether concentration techniques and Kato-Katz thick smear technique. Sera of 96 children comprising 76A. lumbricoides infection and 20 controls were subjected to enzymes-linked immunosorbent assay.Results: The mean sera concentration of tumor necrosis factor alpha (TNF-α), interleukin-4 (IL-4), interleukin-5 (IL-5), interleukin-10 (IL-10) were (16.7±7.6) pg/mL, (4.6±0.8)pg/mL, (391.6±52.0) pg/mL and (181.2±30.4) pg/mL, respectively. The control subjects had the following mean serum cytokines: TNF-α(2.9±1.8) pg/m, IL-4 (4.0±0.1) pg/mL, IL-5 (125.1±50.1) pg/mL, IL-10 (74.5±54.2) pg/mL, respectively. The difference between the sera cytokines concentration of theA. lumbricoides infected children and their controls were statistically significant for TNF-α, IL- 5 and IL-10(χ2= 9.99,P< 0.05;χ2 = 137.24,P < 0.05;χ2 = 44.30,P < 0.05, respectively). The intensity of infection correlated positively with TNF-α, and IL-5 (r = 0.93 and 0.98, respectively) while IL-4 and IL- 10 correlated negatively with the intensity of infection (r = -0.62 and 0.99, respectively). TNF-α, IL-4 and IL-5 correlated positively with age (r = 0.19, 0.33 and 0. 66, respectively). The mean cytokines between those with mild and moderate infections were statistically significant for TNF-α, IL-5 and IL-10 (χ2 = 3.60, 4.52 and 5.30, respectively). The ratio of TNF-α: IL-10 was 0.092.Conclusions: Elevated IL-5, IL-10 and TNF-α found in the sera of the volunteers with Ascariasis implicates these cytokines as key mediators in the host responses toA. lumbriocoides infection in our studied area.

  6. Mammalian Placentation

    DEFF Research Database (Denmark)

    Carter, Anthony Michael; Mess, A. M.

    2014-01-01

    This guide to animal models of human placentation assesses the strengths and weaknesses of species in common use. We argue that structural differences from human placenta, though important in some contexts, are less of a drawback than differences in reproductive strategy. Many laboratory rodents...... to consider animal models with longer gestations and well-developed neonates. Placentation in different orders of mammal is surveyed and their proximity to humans described in an evolutionary context. Animal models are then compared with the human in terms of the functional anatomy, physiology, and immunology...... have brief gestations resulting in the birth of poorly developed young. They can provide useful insights on placental development and function relevant to early human pregnancy. However, to model the events of a 9-month gestation, which imposes added requirements on the placenta, it is necessary...

  7. The Cytokine Temporal Profile in Rat Cortex after Controlled Cortical Impact

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    Clifton L Dalgard

    2012-01-01

    Full Text Available Cerebral inflammatory responses may initiate secondary cascades following traumatic brain injury. Changes in the expression of both cytokines and chemokines may activate, regulate, and recruit innate and adaptive immune cells associated with secondary degeneration, as well as alter a host of other cellular processes. In this study, we quantified the temporal expression of a large set of inflammatory mediators in rat cortical tissue after brain injury. Following a controlled cortical impact on young adult male rats, cortical and hippocampal tissue of the injured hemisphere and matching contralateral material was harvested at early (4, 12 and 24 hours and extended (3, and 7 days timepoints post-procedure. Naïve rats that received only anesthesia were used as controls. Processed brain homogenates were assayed for chemokine and cytokine levels utilizing an electrochemilumenscence-based multiplex ELISA platform. The temporal profile of cortical tissue samples revealed a multi-phasic injury response following brain injury. CXCL1, IFNγ, IL4, and IL5 reached peak concentrations 4 hours post-injury and immediately returned to levels not different from control tissue. The levels of IL1b, IL13, and TNFa were also highest at 4 hours post-injury although their expression remained significantly above levels in uninjured tissue at extended time points. Additionally, IL1b and IL13 levels displayed a biphasic temporal profile in response to injury, which may suggest their involvement in an anti-inflammatory process. Interestingly, CCL2 and CCL20 did not reach peak levels until 1 day post-injury. Peak CCL2 levels were significantly higher than peak levels of any other inflammatory mediator measured, thus suggesting a possible use as a biomarker. Fully elucidating chemokine and cytokine signaling properties after brain injury may provide increased insight into a number of secondary cascade events that are initiated or regulated by inflammatory responses.

  8. Serum cytokine and periodontal profiles in relation to disease activity of rheumatoid arthritis in Japanese adults.

    Science.gov (United States)

    Kobayashi, Tetsuo; Murasawa, Akira; Komatsu, Yasutaka; Yokoyama, Tomoko; Ishida, Kohei; Abe, Asami; Yamamoto, Kouji; Yoshie, Hiromasa

    2010-05-01

    Rheumatoid arthritis (RA) and periodontitis are common chronic inflammatory conditions and share many pathologic features. A similar profile of cytokines is involved in the pathogenesis of the two diseases. The relationship between the disease activity of RA and the periodontal condition remains unclear. This study examines whether the disease activity of RA affects serum cytokine and periodontal profiles. The study subjects consisted of 84 Japanese adults with RA and 22 race-matched control individuals. After periodontal and rheumatologic examination, the disease activity of RA was determined with the Disease Activity Score including 28 joints using C-reactive protein (DAS28-CRP). Serum levels of cytokines including interleukin (IL)-1beta, IL-6, IL-12, IL-12 p40, IL-18, and tumor necrosis factor-alpha (TNF-alpha) were determined by an enzyme-linked immunosorbent assay. High-sensitive CRP was also measured with a latex particle-enhanced nephelometric method. Of 84 patients with RA, 28 and 56 patients exhibited low and moderate to high disease activity, respectively. Serum levels of IL-6, TNF-alpha, and CRP were significantly different between the two groups (P <0.05). Additionally, a significant correlation was observed between DAS28-CRP and percentage of sites with bleeding on probing (BOP) (P = 0.008) and between serum TNF-alpha levels and percentage of sites with BOP (P = 0.01) in 56 patients with RA with moderate to high activity. These results suggest that the disease activity of RA correlated with serum levels of IL-6, TNF-alpha, and CRP, and it might influence BOP in the patients with moderate to high disease activity.

  9. Actual concepts in rhinosinusitis: a review of clinical presentations, inflammatory pathways, cytokine profiles, remodeling, and management.

    Science.gov (United States)

    Eloy, Philippe; Poirrier, Anne Lise; De Dorlodot, Clotilde; Van Zele, Thibaut; Watelet, Jean Baptiste; Bertrand, Bernard

    2011-04-01

    Rhinosinusitis (RS) is a heterogeneous group of diseases. It is a significant and increasing health problem that affects about 15% of the population in Western countries. It has a substantial impact on patients' health-related quality of life and daily functioning and represents a huge financial burden to society and the health care system as a result of the direct and indirect costs. In addition, RS is not well-understood, and little is known about the etiology and pathophysiology. In the past decade, many papers have been published that have changed our understanding of RS. RS is commonly classified into acute and chronic RS based on symptom duration. In acute RS, an inflammatory reaction initiated by a viral infection characterizes most uncomplicated, mild to moderate cases. Therefore, the first line of treatment for these cases are intranasal steroids and not antibiotics. In severe and complicated cases, antibiotics combined with topical steroids remain the treatment of choice. On the other hand, chronic RS is actually subdivided into two distinct entities (chronic rhinosinusitis with and without polyps), as growing evidence indicates that these entities have specific inflammatory pathways and cytokine profiles. The authors review recent data regarding the clinical presentations, cytokine profiles, tissue remodeling, and modalities of treatment for each form of RS.

  10. Cytokine profile in severe Gram-positive and Gram-negative abdominal sepsis.

    Science.gov (United States)

    Surbatovic, Maja; Popovic, Nada; Vojvodic, Danilo; Milosevic, Ivan; Acimovic, Gordana; Stojicic, Milan; Veljovic, Milic; Jevdjic, Jasna; Djordjevic, Dragan; Radakovic, Sonja

    2015-06-16

    Sepsis is a principal cause of death in critical care units worldwide and consumes considerable healthcare resources. The aim of our study was to determine whether the early cytokine profile can discriminate between Gram-positive and Gram-negative bacteraemia (GPB and GNB, respectively) and to assess the prognostic value regarding outcome in critically ill patients with severe abdominal sepsis. The outcome measure was hospital mortality. Blood samples were obtained from 165 adult patients with confirmed severe abdominal sepsis. Levels of the proinflammatory mediators TNF-α, IL-8, IL-12 and IFN-γ and the anti-inflammatory mediators IL-1ra, IL-4, IL-10 and TGF-β1 were determined and correlated with the nature of the bacteria isolated from the blood culture and outcome. The cytokine profile in our study indicated that the TNF-α levels were 2-fold, IL-8 were 3.3-fold, IFN-γ were 13-fold, IL-1ra were 1.05-fold, IL-4 were 1.4-fold and IL-10 were 1.83-fold higher in the GNB group compared with the GPB group. The TNF-α levels were 4.7-fold, IL-8 were 4.6-fold, IL-1ra were 1.5-fold and IL-10 were 3.3-fold higher in the non-survivors compared with the survivors.

  11. Moderate exercise training modulates cytokine profile and sleep in elderly people.

    Science.gov (United States)

    Santos, R V T; Viana, V A R; Boscolo, R A; Marques, V G; Santana, M G; Lira, F S; Tufik, S; de Mello, M T

    2012-12-01

    Aging causes several physiological alterations, including alterations in sleep. It is possible that difficulty sleeping can be exacerbated by increased inflammation in older individuals. Moderate exercise training may be a modality of non-pharmacological treatment for sleep disorders and inflammation. We aimed to assess the effects of moderate exercise training on sleep in elderly people as well as their cytokine profiles. Additionally, we examined the effect of exercise training on quality of life parameters using a SF-36 questionnaire. Twenty-two male, sedentary, healthy, elderly volunteers performed moderate training for 60 min/day, 3 days/week for 24 week at a work rate equivalent to their ventilatory aerobic threshold. The environment was kept at a temperature of 23 ± 2°C, with a humidity of 60 ± 5%. Blood and polysomnograph were collected twice: at baseline (1 week before training began) and after 6 months of training. Training increased aerobic capacity parameters (pexercise training was shown to improve quality of life parameters. Our results suggest that 6 months of training can improve sleep in the elderly and is related to the anti-inflammatory effect of moderate training, which modifies cytokine profiles. Copyright © 2012 Elsevier Ltd. All rights reserved.

  12. Cytokine Profile of Children Hospitalized with Virologically-Confirmed Dengue during Two Phase III Vaccine Efficacy Trials.

    Directory of Open Access Journals (Sweden)

    Anke Harenberg

    2016-07-01

    Full Text Available Two large-scale efficacy studies with the recombinant yellow fever-17D-dengue virus, live-attenuated, tetravalent dengue vaccine (CYD-TDV candidate undertaken in Asia (NCT01373281 and Latin America (NCT01374516 demonstrated significant protection against dengue disease during two years' active surveillance (active phase. Long-term follow up of participants for breakthrough disease leading to hospitalization is currently ongoing (hospital phase.We assessed the cytokine profile in acute sera from selected participants hospitalized (including during the active phase up to the beginning of the second year of long-term follow up for both studies. The serum concentrations of 38 cytokines were measured in duplicate using the Milliplex Human Cytokine MAGNETIC BEAD Premixed 38 Plex commercial kit (Millipore, Billerica, MA, USA. Partial least squares discriminant analyses did not reveal any difference in the overall cytokine profile of CYD-TDV and placebo recipients hospitalized for breakthrough dengue regardless of stratification used. In addition, there was no difference in the cytokine profile for breakthrough dengue among those aged <9 years versus those aged ≥ 9 years.These exploratory findings show that CYD-TDV does not induce a particular immune profile versus placebo, corroborating the clinical profile observed.

  13. Cytokine Expression Profile in Aqueous Humor and Sera of Patients with Acute Anterior Uveitis.

    Science.gov (United States)

    Chen, W; Zhao, B; Jiang, R; Zhang, R; Wang, Y; Wu, H; Gordon, L; Chen, L

    2015-01-01

    To evaluate cytokine expression profile in aqueous humor and sera in patients with HLAB27 associated acute anterior uveitis (AAU) and idiopathic AAU. Twenty patients with AAU and 17 controls were recruited from August 2012 to March 2013. Study subjects with uveitis were divided into two groups: 9 patients with idiopathic AAU and 11 patients with HLA-B27 associated AAU. Complete ophthalmological examinations were performed and clinical features of each group were clearly documented. Aqueous humor and sera were collected and the concentration of 15 immune mediators (IL-1β, IL-4, IL-6, IL-10, IL-17A, IL-17F, IL-21, IL-22, IL-23, IL-25, IL-31, IL-33, TNF-α, IFN-γ, sCD40L) were measured in both aqueous humor and sera simultaneously by multiplex immunoassay. There were significantly higher levels of multiple cytokines in aqueous humor in patients with uveitis compared to controls, including IL-1β, IL-6, IL-10, IL-17a, IL-17f, IL-21, IL-25, IL-31, IFN-γ, TNF-α, and sCD40L. The levels of IL-17a in aqueous humor correlated significantly with disease activity in patients with idiopathic AAU, while the level of IFN-γ in aqueous humor correlated significantly with disease activity in patients with HLA-B27 associated AAU. There was no significant difference in serum cytokine expression between uveitis patients and controls except IL-6, elevated in patients with both idiopathic and HLA-B27 associated AAU. Cytokine expression pattern in the aqueous humor, in contrast to that in serum, may reflect intraocular immune reactions during active inflammation in patients with AAU. Both Th1 and Th17 are involved in immunopathogenesis of HLA-B27 associated and idiopathic AAU, but a different cytokine pattern was identified in these two clinical entities. A predominant Th17-driven immune response may play an important role in the immunopathogenesis of idiopathic AAU, while Th1 dominant immune response may be responsible for the inflammation in HLA-B27 associated AAU.

  14. Serum cytokine profiles of Khorasan veterans 23 years after sulfur mustard exposure.

    Science.gov (United States)

    Riahi-Zanjani, Bamdad; Balali-Mood, Mahdi; Mousavi, Seyed-Reza; Karimi, Gholamreza; Sadeghi, Mahmood; Shirmast, Elham; Mahmoudi, Mahmoud

    2014-12-01

    Sulfur mustard (SM) is an incapacitating chemical warfare agent that was used against Iranian soldiers during the period from 1983 to 1988. We have investigated serum cytokines profiles of Khorasan veterans who were exposed to SM >23 years earlier. Forty-four male Iranian veterans who had >40% disabilities due to delayed complications of SM poisoning and had disabilities were investigated. A total of 30 healthy male volunteers (relatives of the veterans) were selected as the control group. Cytokine levels were measured in the serum of case and control subjects using commercial ELISA kits. Hematologic parameters (white/red blood cell counts, hemoglobin levels, immune cell differentials) were also performed on blood samples from the study subjects. The results indicated that serum levels of ICAM-1 were significantly higher in the samples from SM-exposed veterans (772.8 [± 15.1] ng/ml [p=0.014] vs. control values of 710.2 [± 20.0] ng/ml). On the other hand, serum IL-1β, IL-8 levels and TNFα, were significantly lower for the veterans than the controls (IL-1β: 3.8 [± 0.1] vs. 4.3 [± 0.2] pg/ml, p=0.037; IL-8: 21.0 [± 6.1] vs. 84.6 [± 20.3] pg/ml, p=0.002; TNFα: 4.5 [± 0.1] vs. 5.5 [± 0.1] pg/ml, p=0.027). Levels of other assayed cytokines, e.g., IL-2, -4, -5, -6, -10, and -12, IFNγ, TNFβ, and sVCAM-1 were not significantly different between the study populations. None of the assayed hematologic parameters appeared to differ as well. It seems possible that dysfunctions could have been induced in the innate immune functions of the SM-exposed veterans as a result of these changes in cytokine expression and that these, in turn, may have contributed to the increased incidence of a myriad of diseases that have been documented in these veterans, including cancers. Future studies must focus on examining the significance of these changes in circulating cytokines and their potential contribution to the development of different diseases in veterans exposed to SM.

  15. DYNAMICS OF CYTOKINE PROFILE IN PATIENTS WITH RHEUMATOID ARTHRITIS AS INFLUENCED BY INFLIXIMAB (REMIKEID ADMINISTRATION

    Directory of Open Access Journals (Sweden)

    E. S. Zhugrova

    2008-01-01

    Full Text Available Abstract. Rheumatoid arthritis (RA is a chronic autoimmune systemic disease with predominantly destructive lesions of peripheral joints, with prevalence of 0.6 to 1.6% in general population. An important pathogenetic role in this disease is now attributed to imbalance between pro- and antiinflammatory cytokines. Clinical introduction of biological preparations, such as Infliximab (monoclonal antibodies to TNFα within last years have changed therapeutic approach to treatment of rheumatic diseases. The aim of our research was to evaluate dynamics of pro- and antiinflammatory cytokine profile in the patients with rheumatoid arthritis (RА during combined therapy with Infliximab and Methotrexate (MT. The study included 30 patients (27 females, 3 males, mean age of 52.5±2.0 years who received combined therapy with МТ and Infliximab (Inx. Inx was initially injected at a single dose of 3 mg/kg intravenously, followed by administration 2 and 6 weeks later, and then repeated every 8 weeks. Regular examination of the patients included clinical and laboratory studies (ESR, levels of IL-6, IL-8, TNFα, IL-4, IL-10, GSM-CSF, IFNγ. Levels of antibodies against Infliximab in the groups of RА patients were determined before treatment and 22 weeks later. Efficiency of the therapy was estimated according to DAS28 3V Index and to HAQ Questionnaire.Upon decreased activity of disease, as assessed by DAS28, and improvement of HAQ parameters, a marked decrease in proinflammatory cytokine levels (IL-6, IL-8, TNFα was detected, that confirming a pathogenetic significance of cytokine in RА patients. In patients with marked clinical effect (group I, an initially normal contents of TNFα was found in blood serum, and this group showed better response to Infliximab therapy, than groups II and III (resp., moderate and absent response with initially high contents of TNFα and other cytokines, that was proven by correlations with ACR criteria and HAQ functional index

  16. Antibody Array-Generated Profiles of Cytokine Release from THP-1 Leukemic Monocytes Exposed to Different Amphotericin B Formulations

    OpenAIRE

    Turtinen, Lloyd W.; Prall, David N.; Bremer, Lindsay A.; Nauss, Rachel E.; Hartsel, Scott C.

    2004-01-01

    Cytokine antibody arrays were used to establish the profiles of cytokine release from THP-1 monocytes exposed to different amphotericin B (AMB) drug delivery systems. Fungizone (FZ) and Amphotec (ABCD) caused the release of significantly more inflammatory molecules and the release of inflammatory molecules at higher levels than either AmBisome (L-AMB) or Abelcet (ABLC) after 6 h of treatment. Specifically, tumor necrosis factor alpha (TNF-α), interleukin-8 (IL-8), GRO-(αβγ), monocyte chemoatt...

  17. T cell clones from Schistosoma haematobium infected and exposed individuals lacking distinct cytokine profiles for Th1/Th2 polarisation

    Directory of Open Access Journals (Sweden)

    Mduluza T

    2001-01-01

    Full Text Available T cell clones were derived from peripheral blood mononuclear cells of Schistosoma haematobium infected and uninfected individuals living in an endemic area. The clones were stimulated with S. haematobium worm and egg antigens and purified protein derivative. Attempts were made to classify the T cell clones according to production of the cytokines IL-4, IL-5 and IFN-gamma. All the T cell clones derived were observed to produce cytokines used as markers for the classification of Th1/Th2 subsets. However, the 'signature' cytokines marking each subset were produced at different levels. The classification depended on the dominating cytokine type, which was having either Th0/1 or Th0/2 subsets. The results indicated that no distinct cytokine profiles for polarisation of Th1/Th2 subsets were detected in these S. haematobium infected humans. The balance in the profiles of cytokines marking each subset were related to infection and re-infection status after treatment with praziquantel. In the present study, as judged by the changes in infection status with time, the T cell responses appeared to be less stable and more dynamic, suggesting that small quantitative changes in the balance of the cytokines response could result in either susceptibility or resistant to S. haematobium infection.

  18. CYTOKINE PROFILE IN VISCERAL OBESITY AND ADVERSE CARDIOVASCULAR PROGNOSIS OF MYOCARDIAL INFARCTION

    Directory of Open Access Journals (Sweden)

    O. V. Gruzdeva

    2015-01-01

    Full Text Available Presence of myocardial infarction in patients with obesity can lead to an uncontrolled increase in proinflammatory cytokines and unfavorable course of the pathological process. Objective: to study the relationship of key inflammatory factors and the development of complications at different terms after myocardial infarction in patients with visceral obesity. The study involved 94 men with myocardial infarction. Visceral obesity was diagnosed by multi-slice computed tomography (LightspeedVCT 64 ,General Electric,USA. On the 1st and 12th day of hospitalization, we determined serum concentrations of interleukins (TNFα, IL-1β, IL-6, IL-8 IL-10 and IL-12, and C-reactive protein. Adverse cardiovascular events were documented during the next year. The most informative indicators were identified by a stepwise logistic regression analysis. In patients with myocardial infarction an imbalance of cytokine profile revealed, i.e., an increase in proinflammatory markers (TNFα, IL-1β, IL-6, IL-8, IL-12, CRP, along with decrease in IL-10, being more pronounced in cases of visceral obesity. Among the studied markers, closest relationship was observed between visceral obesity and serum concentrations of IL-6 and CRP. Over the year, adverse cardiovascular events proved to be more frequent in patients with visceral obesity. Post-infarction complication risk was associated with higher concentrations of IL-6, IL-12 and IL-10 deficiency. Hence, development of adverse cardiovascular events within a year after myocardial infarction is more typical to the patients with visceral obesity, and is accompanied by activation of proinflammatory cytokines and IL-10 deficiency.

  19. Impact of placental Plasmodium falciparum malaria on the profile of some oxidative stress biomarkers in women living in Yaoundé, Cameroon.

    Science.gov (United States)

    Megnekou, Rosette; Djontu, Jean Claude; Bigoga, Jude Daiga; Medou, Fabrice Mbah; Tenou, Sandrine; Lissom, Abel

    2015-01-01

    Impact of the pathophysiology of Plasmodium falciparum placental malaria (PM) on the profile of some oxidative stress biomarkers and their relationship with poor pregnancy outcomes in women remain unknown. Between 2013 and 2014, peripheral blood and placenta tissue from 120 Cameroonian women at delivery were assessed for maternal haemoglobin and, parasitaemia respectively. Parasite accumulation in the placenta was investigated histologically. The levels of oxidative stress biomarkers Malondialdehyde (MDA), Nitric Oxide (NO), Superoxide dismutase (SOD), Catalase (CAT) and Gluthatione (GSH) in the supernatant of teased placenta tissues were determined by Colorimetric enzymatic assays. Parasitaemia was inversely related to haemoglobin levels and birth weight (P <0.001 and 0.012, respectively). The level of lipid peroxide product (MDA) was significantly higher in the malaria infected (P = 0.0047) and anaemic (P = 0.024) women compared to their non-infected and non-anaemic counterparts, respectively. A similar trend was observed with SOD levels, though not significant. The levels of MDA also correlated positively with parasitaemia (P = 0.0024) but negatively with haemoglobin levels (P = 0.002). There was no association between parasitaemia, haemoglobin level and the other oxidative stress biomarkers. From histological studies, levels of MDA associated positively and significantly with placenta malaria infection and the presence of malaria pigments. The levels of SOD, NO and CAT increased with decreasing leukocyte accumulation in the intervillous space. Baby birth weight increased significantly with SOD and CAT levels, but decreased with levels of GSH. Placental P. falciparum infection may cause oxidative stress of the placenta tissue with MDA as a potential biomarker of PM, which alongside GSH could lead to poor pregnancy outcomes (anaemia and low birth weight). This finding contributes to the understanding of the pathophysiology of P. falciparum placental malaria in

  20. Modulation of macrophage cytokine profiles during solid tumor progression: susceptibility to Candida albicans infection

    Directory of Open Access Journals (Sweden)

    Venturini James

    2009-06-01

    Full Text Available Abstract Background In order to attain a better understanding of the interactions between opportunist fungi and their hosts, we investigated the cytokine profile associated with the inflammatory response to Candida albicans infection in mice with solid Ehrlich tumors of different degrees. Methods Groups of eight animals were inoculated intraperitoneally with 5 × 106 C. albicans 7, 14 or 21 days after tumor implantation. After 24 or 72 hours, the animals were euthanized and intraperitoneal lavage fluid was collected. Peritoneal macrophages were cultivated and the levels of IFN-γ, TNF-α, IL-12, IL-10 and IL-4 released into the supernatants were measured by ELISA. Kidney, liver and spleen samples were evaluated for fungal dissemination. Tumor-free animals and animals that had only been subjected to C. albicans infection were used as control groups. Results Our results demonstrated that the mice produced more IFN-γ and TNF-α and less IL-10, and also exhibited fungal clearance, at the beginning of tumor evolution. With the tumor progression, this picture changed: IL-10 production increased and IFN-γ and TNF-α release decreased; furthermore, there was extensive fungal dissemination. Conclusion Our results indicate that solid tumors can affect the production of macrophage cytokines and, in consequence, affect host resistance to opportunistic infections.

  1. [Lymphocyte subsets, dendritic cells and cytokine profiles in mice with melanoma treated with Uncaria tomentosa].

    Science.gov (United States)

    Lozada-Requena, Iván; Núñez, César; Alvárez, Yubell; Kahn, Laura; Aguilar, José

    2015-10-01

    To evaluate the immunomodulatory effect on lymphocyte subsets, dendritic cells (DC), Th1 / Th2 / Th17 and inflammatory cytokines on systemic level and/or in the tumor microenvironment of mice with or without melanoma. Peripheral blood and/or primary tumors samples were obtained of mice with B16 melanoma treated or not with a hydroalcoholic extract of Uncaria tomentosa (UT) with 5.03% of pentacyclic oxindole alkaloids (UT-POA) obtained from the bark of the plant. All cell assays and cytokine measurements were performed by flow cytometry. UT-POA systemically increased CD4/CD8a relation while cell activation was inversely proportional; increased the proportion of DCm; induced a pro-inflammatory Th1 profile and reduced Th17 response. TNF-α and IL-17A positively and negatively correlated with CD4/CD8a relation. The increase of Th1 (TNF-α) may result in the increase of CD4 or M1 macrophage activation. Although UT-POA shows increased DCm, is not dose-dependent. Th17(IL-17A) decreased can support the function of CD8a lymphocytes. UT-POA shows better systemic immunomodulatory effects than intratumoral.

  2. Uncaria tomentosa aqueous-ethanol extract triggers an immunomodulation toward a Th2 cytokine profile.

    Science.gov (United States)

    Domingues, Alexandre; Sartori, Alexandrina; Valente, Ligia Maria Marino; Golim, Marjorie Assis; Siani, Antonio Carlos; Viero, Rosa Marlene

    2011-08-01

    Uncaria tomentosa (Willd.) DC (Rubiaceae) is a large woody vine that is native to the Amazon and Central American rainforests and is used widely in traditional medicine for its immunomodulatory and antiinflammatory activities. The present work used in vivo immunotoxic and in vitro immunomodulatory experiments to investigate the effects of a pentacyclic oxindole alkaloid extract from U. tomentosa bark on lymphocyte phenotype, Th1/Th2 cytokine production, cellular proliferation and cytotoxicity. For the in vivo immunotoxicity testing, BALB/c male mice were treated once a day with 125, 500 or 1250 mg/kg of U. tomentosa extract for 28 days. For the in vitro protocol, lymphocytes were cultured with 10-500 μg/mg of the extract for 48 h. The extract increased the cellularity of splenic white pulp and the thymic medulla and increased the number of T helper lymphocytes and B lymphocytes. Also, a large stimulatory effect on lymphocyte viability was observed. However, mitogen-induced T lymphocyte proliferation was significantly inhibited at higher concentrations of U. tomentosa extract. Furthermore, an immunological polarization toward a Th2 cytokine profile was observed. These results suggest that the U. tomentosa aqueous-ethanol extract was not immunotoxic to mice and was able to modulate distinct patterns of the immune system in a dose-dependent manner. Copyright © 2011 John Wiley & Sons, Ltd.

  3. Preferential Th1 cytokine profile of phosphoantigen-stimulated human Vγ9Vδ2 T cells.

    LENUS (Irish Health Repository)

    Dunne, Margaret R

    2010-01-01

    Human Vγ9Vδ2 T cells recognise pyrophosphate-based antigens (phosphoantigens) and have multiple functions in innate and adaptive immunity, including a unique ability to activate other cells of the immune system. We used flow cytometry and ELISA to define the early cytokine profiles of Vγ9Vδ2 T cells stimulated in vitro with isopentenyl pyrophosphate (IPP) and (E)-4-hydroxy-3-methyl-but-2 enyl pyrophosphate (HMB-PP) in the absence and presence of IL-2 and IL-15. We show that fresh Vγ9Vδ2 T cells produce interferon-γ (IFN-γ) and tumour necrosis factor-α (TNF-α) within 4 hours of stimulation with phosphoantigen, but neither IL-10, IL-13, nor IL-17 was detectable up to 72 hours under these conditions. Cytokine production was not influenced by expression or lack, thereof, of CD4 or CD8. Addition of IL-2 or IL-15 caused expansion of IFN-γ-producing Vγ9Vδ2 T cells, but did not enhance IFN-γ secretion after 24-72 hours. Thus, phosphoantigen-stimulated Vγ9Vδ2 T cells have potential as Th1-biasing adjuvants for immunotherapy.

  4. Anticonvulsant effect of cannabidiol in the pentylenetetrazole model: Pharmacological mechanisms, electroencephalographic profile, and brain cytokine levels.

    Science.gov (United States)

    Vilela, Luciano R; Lima, Isabel V; Kunsch, Érica B; Pinto, Hyorrana Priscila P; de Miranda, Aline S; Vieira, Érica Leandro M; de Oliveira, Antônio Carlos P; Moraes, Marcio Flávio D; Teixeira, Antônio L; Moreira, Fabricio A

    2017-10-01

    Cannabidiol (CBD), the main nonpsychotomimetic compound from Cannabis sativa, inhibits experimental seizures in animal models and alleviates certain types of intractable epilepsies in patients. Its pharmacological profile, however, is still uncertain. Here we tested the hypothesis that CBD anticonvulsant mechanisms are prevented by cannabinoid (CB1 and CB2) and vanilloid (TRPV1) receptor blockers. We also investigated its effects on electroencephalographic (EEG) activity and hippocampal cytokines in the pentylenetetrazole (PTZ) model. Pretreatment with CBD (60mg/kg) attenuated seizures induced by intraperitoneal, subcutaneous, and intravenous PTZ administration in mice. The effects were reversed by CB1, CB2, and TRPV1 selective antagonists (AM251, AM630, and SB366791, respectively). Additionally, CBD delayed seizure sensitization resulting from repeated PTZ administration (kindling). This cannabinoid also prevented PTZ-induced EEG activity and interleukin-6 increase in prefrontal cortex. In conclusion, the robust anticonvulsant effects of CBD may result from multiple pharmacological mechanisms, including facilitation of endocannabinoid signaling and TRPV1 mechanisms. These findings advance our understanding on CBD inhibition of seizures, EEG activity, and cytokine actions, with potential implications for the development of new treatments for certain epileptic syndromes. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Kinetics of cytokine profile in response to Mycobacterium bovis BCG and Streptococcus pyogenes activated cells.

    Science.gov (United States)

    Verma, Vivek; Kumar, Parveen; Dhanda, Rakesh Singh; Yadav, Manisha

    2016-06-01

    The infection of epithelial cells is a necessary step for Mycobacterium bovis BCG dissemination, but the mechanism of mycobacterial epithelial interactions is not completely understood. Similarly, Streptococcus pyogenes is a strictly human pathogen that favorably colonizes the skin and the pharynx. Effective cytokine secretion is essential in order to fabricate a suitable inflammatory response against an infection. In this data article, the cytokine profile in BCG and S. pyogenes activated THP-1 cell line in media after the acute phase of infection by ELISA is described. The interleukin-8 level was increased in response to both BCG and S. pyogenes, but was quite prominent after 24 h and further increased upto 72 h post infection. On the other hand, an increase in IL-6 response to S. pyogenes was observed while there was no response to BCG even after 48 h of infection. A low level of TNF-α was detected upon BCG and S. pyogenes infection.

  6. Maternal immune stimulation reduces both placental morphologic damage and down-regulated placental growth-factor and cell cycle gene expression caused by urethane: are these events related to reduced teratogenesis?

    Science.gov (United States)

    Sharova, L V; Sharov, A A; Sura, P; Gogal, R M; Smith, B J; Holladay, S D

    2003-07-01

    Activation of the maternal immune system in mice decreased cleft palate caused by the chemical teratogen, urethane. Direct and indirect mechanisms for this phenomenon have been suggested, including maternal macrophages that cross the placenta to find and eliminate pre-teratogenic cells, or maternal immune proteins (cytokines) that cross placenta to alleviate or partially alleviate toxicant-mediated effects in the developing fetus. A third mechanism to explain improved fetal developmental outcome in teratogen-challenged pregnant mice might involve beneficial effects of immune stimulation on the placenta. In the present experiments, urethane treatment altered placental morphology and impaired placental function, the latter indicated by down-regulated activity of cell cycle genes and of genes encoding cytokines and growth factors. Maternal immune stimulation with either Freund's complete adjuvant (FCA) or interferon-gamma (IFNgamma) reduced morphologic damage to the placenta caused by urethane and normalized expression of several genes that were down-regulated by urethane. Urethane treatment also shifted placental cytokine gene expression toward a T cell helper 1 (Th1) profile, while immunostimulation tended to restore a Th2 profile that may be more beneficial to pregnancy and fetal development. These data suggest that the beneficial effects of maternal immune stimulation on fetal development in teratogen-exposed mice may, in part, result from improved placental structure and function.

  7. Colonic lesions, cytokine profiles, and gut microbiota in plasminogen-deficient mice

    DEFF Research Database (Denmark)

    Vestergaard, Bill; Krych, Lukasz; Lund, Leif R.

    2015-01-01

    Plasminogen-deficient (FVB/NPan-plg(tm1Jld), plg(tm1Jld)) mice, which are widely used as a wound-healing model, are prone to spontaneous rectal prolapses. The aims of this study were 1) to evaluate the fecal microbiome of plg(tm1Jld) mice for features that might contribute to the development...... of rectal prolapses and colonic inflammation and 2) to assess the relevance of the inflammatory phenotype to the variability in wound healing in this model. The (plgtm1Jld) mice exhibited delayed wound healing, and they could be divided into 3 distinct groups that differed according to the time until wound...... closure. Colonic lesions in plg(tm1Jld) mice, which were characterized by necrotizing ulcerations and cystically dilated glands, were restricted to the intermediate and distal parts of the colon. The cytokine profile was indicative of chronic tissue damage, but the genetic modification did not change...

  8. Cytokine mRNA profiles in pigs exposed prenatally and postnatally to Schistosoma japonicum

    DEFF Research Database (Denmark)

    Techau, Michala E.; Johansen, Maria V.; Aasted, Bent;

    2007-01-01

    The pig is a natural host for Schistosoma japonicum and a useful animal model of human infection. The aim of the present study was to assess the differences between the cytokine profiles in prenatally or postnatally S. japonicum exposed pigs. Seven prenatally exposed pigs, 7 postnatally exposed...... pigs and 4 uninfected control pigs were compared 27 weeks post exposure. Variables included worm burdens, tissue egg counts, liver pathology and mRNA levels of IL-2, IL-4, IL-10, IL-12, TNF-alpha, TGF-beta 1 and IFN-gamma in the liver and the caecum, assessed by RT-PCR. Infection intensity and level...... of septal fibrosis were significantly higher in the postnatal group compared to the prenatal group (P TNF-alpha (P

  9. Prostaglandin E2 in tick saliva regulates macrophage cell migration and cytokine profile

    Science.gov (United States)

    2013-01-01

    Background Ticks are obligate hematophagous ectoparasites that suppress the host’s immune and inflammatory responses by secreting immuno-modulatory and anti-inflammatory molecules in their saliva. In previous studies we have shown that tick salivary gland extract (SGE) and saliva from Dermacentor variabilis have distinct effects on platelet-derived growth factor (PDGF)-stimulated IC-21 macrophage and NIH3T3-L1 fibroblast migration. Since tick saliva contains a high concentration of prostaglandin E2 (PGE2), a potent modulator of inflammation, we used a PGE2 receptor antagonist to evaluate the role of PGE2 in the different migratory responses induced by saliva and its impact on macrophage cytokine profile. Methods Adult ticks were fed on female New Zealand white rabbits for 5-8 days. Female ticks were stimulated with dopamine/theophylline to induce salivation and saliva was pooled. Competitive enzyme immunoassays (EIA) were used to measure saliva PGE2 content and the changes in macrophage intracellular cyclic adenosine monophosphate (cAMP) levels. The effects of tick saliva on macrophage and fibroblast migration were assessed in the absence and presence of the PGE2 receptor antagonist, AH 6809, using blind well chamber assays. A cytokine antibody array was used to examine the effects of tick saliva on macrophage cytokine secretion. Statistical significance was determined by one-way ANOVA; Student Newman-Kuels post-test was used for multiple comparisons. Results The saliva-induced increase in PDGF-stimulated macrophage migration was reversed by AH 6809. The inhibition of PDGF-stimulated fibroblast migration by saliva was also antagonist-sensitive. Tick saliva induced macrophages to secrete copious amounts of PGE2, and conditioned medium from these cells caused an AH 6809-sensitive inhibition of stimulated fibroblast migration, showing that macrophages can regulate fibroblast activity. We show that tick saliva decreased the secretion of the pro

  10. 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

    Directory of Open Access Journals (Sweden)

    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.

  11. Placental economies

    DEFF Research Database (Denmark)

    Lee, Jieun

    2016-01-01

    and sustained through the relations and practices of care that animate the placenta in different forms. On the basis of an ethnographic fieldwork conducted in Korea, this article focuses on two different forms of care (lab workers’ care of cells, and pregnant women’s care of fetuses) that enable the (re......Thinking with the vital materiality of placentas as it is evinced in a placental stem cell research lab in Korea, this article explores the relations and practices of care that are essential to the circulation of biological matters as infrastructure of tissue economies. I attend to the flows...... of care that sustain tissue economies with the notion of ‘placental economies’. Shifting attention from donor subjects and tissue objects to practices and relations of care as an infrastructure for the circulation of tissues, I explore how the vitality of biological matters is an achievement made...

  12. Mammalian Placentation

    DEFF Research Database (Denmark)

    Carter, Anthony Michael; Mess, A. M.

    2014-01-01

    This guide to animal models of human placentation assesses the strengths and weaknesses of species in common use. We argue that structural differences from human placenta, though important in some contexts, are less of a drawback than differences in reproductive strategy. Many laboratory rodents...... to consider animal models with longer gestations and well-developed neonates. Placentation in different orders of mammal is surveyed and their proximity to humans described in an evolutionary context. Animal models are then compared with the human in terms of the functional anatomy, physiology, and immunology...... of the placenta. This information is collated both to assess common animal models such as mouse, sheep, and primates and to introduce some alternatives that we consider worthy of attention....

  13. Unconventional cytokine profiles and development of T cell memory in long-term survivors after cancer vaccination

    DEFF Research Database (Denmark)

    Kyte, Jon Amund; Trachsel, Sissel; Risberg, Bente

    2009-01-01

    display unconventional cytotoxicity and specifically kill tumor cells expressing mutated TGFbeta receptor II. Cytokine profiling on the long-term survivors demonstrates high IFN gamma/IL10-ratios, favoring immunity over tolerance, and secretion of multiple chemokines likely to mobilize the innate...... and adaptive immune system. Interestingly, these pro-inflammatory cytokine profiles do not follow a Th1/Th2-delineation. Most IFN gamma(high)/IL4(low)/IL10(low) cultures include high concentrations of hallmark Th2-cytokines IL-5 and IL-13. This does not reflect a mixture of Th1- and Th2-clones, but applies......Cancer vaccine trials frequently report on immunological responses, without any clinical benefit. This paradox may reflect the challenge of discriminating between effective and pointless immune responses and sparse knowledge on their long-term development. Here, we have analyzed T cell responses...

  14. Cytokine expression in malaria-infected non-human primate placentas

    Directory of Open Access Journals (Sweden)

    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.

  15. Maternal-fetal hepatic and placental metabolome profiles are associated with reduced fetal growth in a rat model of maternal obesity

    DEFF Research Database (Denmark)

    Mumme, Karen; Gray, Clint; Reynolds, Clare M.

    2016-01-01

    : Metabolomic profiling was used to reveal altered maternal and fetal metabolic pathways in a model of diet induced obesity during pregnancy, leading to reduced fetal growth. Methods: We examined the metabolome of maternal and fetal livers, and placenta following a high fat and salt intake. Sprague–Dawley rats...... were assigned to (a) control diet (CD; 1 % salt, 10 % kcal from fat), (b) high salt diet (SD; 4 % salt, 10 % kcal from fat), (c) high fat diet (HF; 1 % salt, 45 % kcal from fat) or (d) high-fat high-salt diet (HFSD; 4 % salt, 45 % kcal from fat) 21 days prior to pregnancy and during gestation......Introduction: Maternal obesity is associated with a range of pregnancy complications, including fetal growth restriction (FGR), whereby a fetus fails to reach its genetically determined growth. Placental insufficiency and reduced nutrient transport play a role in the onset of FGR. Objectives...

  16. Cytokine profiles from shipping through sickness and recovery in cattle either mass-medicated with gamithromycin or sham-treated

    Science.gov (United States)

    Bovine respiratory disease (BRD) is estimated to be responsible for 75% of morbidity and 50% of mortality in beef cattle feeding operations, and mass medication of cattle upon arrival at feeding facilities is a common practice to control BRD. Our objectives were to determine if cytokine profiles di...

  17. Proinflammatory and anti-inflammatory cytokine profile in pediatric patients with irritable bowel syndrome.

    Science.gov (United States)

    Vázquez-Frias, R; Gutiérrez-Reyes, G; Urbán-Reyes, M; Velázquez-Guadarrama, N; Fortoul-van der Goes, T I; Reyes-López, A; Consuelo-Sánchez, A

    2015-01-01

    There is evidence that patients with irritable bowel syndrome (IBS) have a low degree of inflammation in the intestinal mucosa. The aim of the study was to evaluate the profile of pro- and anti-inflammatory cytokines in plasma in Mexican pediatric patients with IBS. Fifteen patients with IBS according to Rome III criteria for childhood and 15 healthy children, matched by age and sex, were included in the study. Plasma levels of tumoral necrosis factor alpha (TNF-α), interleukins 10 and 12 (IL-10, IL-12) and transforming growth factor beta (TGF-β) were quantified and compared between groups. Plasma levels of IL-10 were lower in patients with IBS (86.07+21.3 pg/mL vs. 118.71+58.62 pg/mL: P=.045) and IL-12 levels were higher in patients with IBS compared to the control group of healthy children (1,204.2±585.9 pg/mL vs. 655.04±557.80 pg/mL; P=.011). The IL-10/IL-12 index was lower in patients with IBS (0.097±0.07 vs. 0.295±0.336; P=.025). Plasma concentration of TGF-β was higher in patients with IBS (545.67±337.69 pg/mL vs. 208.48±142.21 pg/mL; P=.001). There was no difference in plasma levels of TNF-α between groups. This study suggests that children with IBS have a state of altered immune regulation. This is consistent with the theory of low-grade inflammatory state in these patients. Further studies are needed to elucidate the role played by these cytokines, specifically TGF-β in the pathogenesis of IBS. Copyright © 2014 Asociación Mexicana de Gastroenterología. Published by Masson Doyma México S.A. All rights reserved.

  18. Ex vivo PBMC cytokine profile in familial Mediterranean fever patients: Involvement of IL-1β, IL-1α and Th17-associated cytokines and decrease of Th1 and Th2 cytokines.

    Science.gov (United States)

    Ibrahim, José-Noel; Jounblat, Rania; Delwail, Adriana; Abou-Ghoch, Joelle; Salem, Nabiha; Chouery, Eliane; Megarbane, André; Medlej-Hashim, Myrna; Lecron, Jean-Claude

    2014-10-01

    In order to clarify the inflammatory mechanism underlying familial Mediterranean fever (FMF), we aimed to evaluate the ex vivo cytokine profile of FMF patients during acute attacks and attack-free periods, and compare it with that of healthy controls. The study included 34 FMF patients, of whom 9 were studied during attack and remission and 24 healthy controls. Cytokine levels were evaluated by Luminex technology in serum and supernatants of PBMC (Peripheral Blood Mononuclear Cells) cultures with and without 24h stimulation of monocytes by LPS and T lymphocytes by anti-CD3/CD28 beads. Levels of IL-6 and TNF-α were higher in unstimulated and LPS-stimulated PBMC supernatants of FMF patients in crises compared to controls. In response to LPS stimulation, higher levels of IL-1β and IL-1α were found in PBMC supernatants of patients during crises compared to those in remission and to controls. IFN-γ and IL-4 levels were the lowest in unstimulated and anti-CD3/CD28 stimulated PBMCs supernatants of patients during crises compared to remission and controls. The Th17 cytokines IL-17 and IL-22 were respectively higher in anti-CD3/CD28 stimulated PBMC supernatants of FMF patients during and between crises compared to controls. Amongst cytokines tested in serum, only IL-6 and TNFα were enhanced in FMF patients. The ex vivo study represents an interesting approach to evaluate cytokines' involvement in FMF. Our results suggest an ongoing subclinical inflammation and define an elevated inflammatory cytokine signature, distinctly for M694V homozygous patients. The absence of spontaneous IL-1β release by PBMCs reflects no constitutive activation of the inflammasome in FMF physiopathology.

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

    Science.gov (United States)

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

    2014-06-01

    cytokines and activation of placental p38-MAPK and STAT3 inflammatory pathways, without changes in fetal systemic inflammatory profile. Activation of p38-MAPK by MCP-1 and TNFalpha, and STAT3 by TNFalpha, suggests a link between elevated proinflammatory cytokines in maternal plasma and activation of placental inflammatory pathways. We suggest that inflammatory processes associated with elevated maternal BMI may influence fetal growth by altering placental function. © 2014 by the Society for the Study of Reproduction, Inc.

  20. Mastitis Pathogens with High Virulence in a Mouse Model Produce a Distinct Cytokine Profile In Vivo

    Science.gov (United States)

    Johnzon, Carl-Fredrik; Artursson, Karin; Söderlund, Robert; Guss, Bengt; Rönnberg, Elin; Pejler, Gunnar

    2016-01-01

    Mastitis is a serious medical condition of dairy cattle. Here, we evaluated whether the degree of virulence of mastitis pathogens in a mouse model can be linked to the inflammatory response that they provoke. Clinical isolates of Staphylococcus aureus (S. aureus) (strain 556 and 392) and Escherichia coli (E. coli) (676 and 127), and laboratory control strains [8325-4 (S. aureus) and MG1655 (E. coli)], were injected i.p. into mice, followed by the assessment of clinical scores and inflammatory parameters. As judged by clinical scoring, E. coli 127 exhibited the largest degree of virulence among the strains. All bacterial strains induced neutrophil recruitment. However, whereas E. coli 127 induced high peritoneal levels of CXCL1, G-CSF, and CCL2, strikingly lower levels of these were induced by the less virulent bacterial strains. High concentrations of these compounds were also seen in blood samples taken from animals infected with E. coli 127, suggesting systemic inflammation. Moreover, the levels of CXCL1 and G-CSF, both in the peritoneal fluid and in plasma, correlated with clinical score. Together, these findings suggest that highly virulent clinical mastitis isolates produce a distinct cytokine profile that shows a close correlation with the severity of the bacterial infection. PMID:27713743

  1. Cytokine Profiles in Malawian Children Presenting with Uncomplicated Malaria, Severe Malarial Anemia, and Cerebral Malaria.

    Science.gov (United States)

    Mandala, Wilson L; Msefula, Chisomo L; Gondwe, Esther N; Drayson, Mark T; Molyneux, Malcolm E; MacLennan, Calman A

    2017-04-01

    Proinflammatory cytokines are involved in clearance of Plasmodium falciparum, and very high levels of these cytokines have been implicated in the pathogenesis of severe malaria. In order to determine how cytokines vary with disease severity and syndrome, we enrolled Malawian children presenting with cerebral malaria (CM), severe malarial anemia (SMA), and uncomplicated malaria (UCM) and healthy controls. We analyzed serum cytokine concentrations in acute infection and in convalescence. With the exception of interleukin 5 (IL-5), cytokine concentrations were highest in acute CM, followed by SMA, and were only mildly elevated in UCM. Cytokine concentrations had fallen to control levels when remeasured at 1 month of convalescence in all three clinical malaria groups. Ratios of IL-10 to tumor necrosis factor alpha (TNF-α) and of IL-10 to IL-6 followed a similar pattern. Children presenting with acute CM had significantly higher concentrations of TNF-α (P Mandala et al.

  2. Distinct effects of calorie restriction on adipose tissue cytokine and angiogenesis profiles in obese and lean mice

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    Kurki Eveliina

    2012-06-01

    Full Text Available Abstract Background Obesity associates with low-grade inflammation and adipose tissue remodeling. Using sensitive high-throughput protein arrays we here investigated adipose tissue cytokine and angiogenesis-related protein profiles from obese and lean mice, and in particular, the influence of calorie restriction (CR. Methods Tissue samples from visceral fat were harvested from obese mice fed with a high-fat diet (60% of energy, lean controls receiving low-fat control diet as well as from obese and lean mice kept under CR (energy intake 70% of ad libitum intake for 50 days. Protein profiles were analyzed using mouse cytokine and angiogenesis protein array kits. Results In obese and lean mice, CR was associated with 11.3% and 15.6% reductions in body weight, as well as with 4.0% and 4.6% reductions in body fat percentage, respectively. Obesity induced adipose tissue cytokine expressions, the most highly upregulated cytokines being IL-1ra, IL-2, IL-16, MCP-1, MIG, RANTES, C5a, sICAM-1 and TIMP-1. CR increased sICAM-1 and TIMP-1 expression both in obese and lean mice. Overall, CR showed distinct effects on cytokine expressions; in obese mice CR largely decreased but in lean mice increased adipose tissue cytokine expressions. Obesity was also associated with increased expressions of angiogenesis-related proteins, in particular, angiogenin, endoglin, endostatin, endothelin-1, IGFBP-3, leptin, MMP-3, PAI-1, TIMP-4, CXCL16, platelet factor 4, DPPIV and coagulation factor III. CR increased endoglin, endostatin and platelet factor 4 expressions, and decreased IGFBP-3, NOV, MMP-9, CXCL16 and osteopontin expressions both in obese and lean mice. Interestingly, in obese mice, CR decreased leptin and TIMP-4 expressions, whereas in lean mice their expressions were increased. CR decreased MMP-3 and PAI-1 only in obese mice, whereas CR decreased FGF acidic, FGF basic and coagulation factor III, and increased angiogenin and DPPIV expression only in lean mice

  3. Multiple cytokine expression profiles reveal immune-based differences in occult hepatitis B genotype H-infected Mexican Nahua patients

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    Nora Alma Fierro

    2011-12-01

    Full Text Available A high prevalence of occult hepatitis B (OHB genotype H infections has been observed in the native Mexican Nahua population. In addition, a low incidence of hepatitis B virus (HBV-associated hepatocellular carcinoma has been described in Mexico. The immune response to infection among OHB-infected patients has been poorly evaluated in vivo. Therefore, we assessed the expression profiles of 23 cytokines in OHB genotype H-infected Nahua patients. A total of 41 sera samples from natives of the Nahua community were retrospectively analysed. Based on their HBV antibody profiles, patients were stratified into two groups: OHB patients (n = 21 and patients that had recovered from HBV infection (n = 20. Herein, we report distinctive cytokines profiles in OHB-infected individuals. Compared to healthy controls (n = 20 and patients who resolved HBV infection, OHB-infected patients displayed an increase in interleukin (IL-2 secretion in addition to a characteristic inflammation profile (decrease in IL-8 and tumour necrosis factor-alpha levels and increased levels of tumour growth factor-beta. IL-15 and interferon-gamma levels were reduced in OHB-infected individuals when compared to those patients who resolved HBV infection. In contrast, OHB patients showed an increase in monocyte chemoattractant protein (MCP-1 and MCP-2 compared to healthy controls and patients who resolved HBV infection. These findings suggest that cytokine expression can influence the severity of OHB disease and could lead to new investigation into the treatment of liver and other infectious diseases.

  4. TH1/TH2 Cytokine profile in relapsing-remitting multiple sclerosis patients treated with Glatiramer acetate or Natalizumab

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    Oreja-Guevara Celia

    2012-09-01

    Full Text Available Abstract Background The balance between T helper cells Th2- and Th1-related cytokines plays a key role in multiple sclerosis (MS. A shift from a Th1 towards a Th2 cytokine profile could have a beneficial effect on the clinical course of the disease. The objective of this study was to assess Th2/Th1 cytokine profile in relapsing-remitting MS (RRMS patients receiving an immunosuppressive treatment with natalizumab (NAT, or an immunomodulatory treatment with glatiramer acetate (GA after one year of treatment. Methods This was an observational cross-sectional study. All consecutive patients diagnosed with RRMS who had received GA or NAT for 12 months were included in the study. We determined serum levels of Th1 and Th2 cytokines (interleukin [IL]-1a, IL-1b, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-13, monocyte chemotactic protein [MCP]-1, tumor-necrosis factor [TNF]-α, interferon [IFN]-γ and granulocyte macrophage colony stimulating factor [GM-CSF] by flow cytometry. Th2/Th1 bias was defined based on the ratio of IL-4, IL-5, IL-6 or IL-10 Th2 cytokines and proinflammatory INF-γ or TNF-α Th1 cytokines. Results Eleven patients under treatment with NAT and 12 patients treated with GA were evaluated. RRMS patients treated with NAT showed significantly higher levels of IL-6 (p  Conclusion In conclusion, our findings suggest that GA promotes a superior Th2-biased anti-inflammatory response as compared with NAT in the systemic circulation of RRMS patients. Future studies with larger cohorts will determine whether this immune Th2 shift in GA patients is associated with a beneficial effect on disease outcome.

  5. Macaques with Rapid Disease Progression and Simian Immunodeficiency Virus Encephalitis Have a Unique Cytokine Profile in Peripheral Lymphoid Tissues

    Science.gov (United States)

    Orandle, Marlene S.; Williams, Kenneth C.; MacLean, Andrew G.; Westmoreland, Susan V.; Lackner, Andrew A.

    2001-01-01

    The influence of host cytokine response on viral load, disease progression, and neurologic lesions was investigated in the simian immunodeficiency virus (SIV)-infected macaque model of AIDS. Cytokine gene expression (interleukin-1β [IL-1β], IL-2, IL-6, IL-10, gamma interferon [IFN-γ], and tumor necrosis factor alpha [TNF-α]) and viral loads were evaluated by semiquantitative reverse transcription-PCR in lymph nodes of 5 control animals and 28 animals infected with SIVmac251 at the terminal stages of AIDS. Infected animals showed higher expression of IFN-γ, IL-6, and IL-10 mRNAs compared with controls. Levels of all cytokines were comparable between animals with rapid (survival, 200 days) disease progression. However, among rapid progressors, the eight animals with SIV encephalitis had a unique cytokine profile (increased IL-2, IL-6, and IFN-γ) that was associated with higher viral loads. These observations provide evidence that host cytokine responses may influence SIV neuropathogenesis independent of disease progression. PMID:11287599

  6. Cytokine profiling in the prefrontal cortex of Parkinson's Disease and Multiple System Atrophy patients

    DEFF Research Database (Denmark)

    Rydbirk, Rasmus; Elfving, Betina; Andersen, Mille Dahl

    2017-01-01

    . Cytokines, which are the main inflammatory signalling molecules, have been identified in blood and cerebrospinal fluid of PD patients, but studies investigating the human brain levels are scarce. It is documented that neurotrophins, necessary for survival of brain cells and known to interact with cytokines...

  7. Cytokine profiles and phenotype regulation of antigen presenting cells by genotype-I porcine reproductive and respiratory syndrome virus isolates

    Directory of Open Access Journals (Sweden)

    Gimeno Mariona

    2011-01-01

    Full Text Available Abstract The present study examined the immunological response of antigen presenting cells (APC to genotype-I isolates of porcine reproductive and respiratory syndrome virus (PRRSV infection by analysing the cytokine profile induced and evaluating the changes taking place upon infection on immunologically relevant cell markers (MHCI, MHCII, CD80/86, CD14, CD16, CD163, CD172a, SWC9. Several types of APC were infected with 39 PRRSV isolates. The results show that different isolates were able to induce different patterns of IL-10 and TNF-α. The four possible phenotypes based on the ability to induce IL-10 and/or TNF-α were observed, although different cell types seemed to have different capabilities. In addition, isolates inducing different cytokine-release profiles on APC could induce different expression of cell markers.

  8. Cytokine profiling in immigrants with clinical malaria after extended periods of interrupted exposure to Plasmodium falciparum.

    Directory of Open Access Journals (Sweden)

    Gemma Moncunill

    Full Text Available Immunity to malaria is believed to wane with time in the absence of exposure to Plasmodium falciparum infection, but immunoepidemiological data on longevity of immunity remain controversial. We quantified serum cytokines and chemokines by suspension array technology as potential biomarkers for durability of immunity in immigrants with clinical malaria after years without parasite exposure. These were compared to serum/plasma profiles in naïve adults (travelers and semi-immune adults under continuous exposure, with malaria, along with immigrant and traveler patients without malaria. Immigrants had higher levels of IL-2, IL-5 and IL-8 compared to semi-immune adults with malaria (P≤0.0200. Time since immigration correlated with increased IL-2 (rho=0.2738P=0.0495 and IFN-γ (rho=0.3044P=0.0282. However, immigrants did not show as high IFN-γ concentrations as travelers during a first malaria episode (P<0.0001. Immigrants and travelers with malaria had higher levels of IFN-γ, IL-6, and IL-10 (P<0.0100 than patients with other diseases, and IL-8 and IL-1β were elevated in immigrants with malaria (P<0.0500. Therefore, malaria patients had a characteristic strong pro-inflammatory/Th1 signature. Upon loss of exposure, control of pro-inflammatory responses and tolerance to P. falciparum appeared to be reduced. Understanding the mechanisms to maintain non-pathogenic effector responses is important to develop new malaria control strategies.

  9. Characteristic Cytokine and Chemokine Profiles in Encephalitis of Infectious, Immune-Mediated, and Unknown Aetiology.

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    Benedict D Michael

    Full Text Available Encephalitis is parenchymal brain inflammation due to infectious or immune-mediated processes. However, in 15-60% the cause remains unknown. This study aimed to determine if the cytokine/chemokine-mediated host response can distinguish infectious from immune-mediated cases, and whether this may give a clue to aetiology in those of unknown cause.We measured 38 mediators in serum and cerebrospinal fluid (CSF of patients from the Health Protection Agency Encephalitis Study. Of serum from 78 patients, 38 had infectious, 20 immune-mediated, and 20 unknown aetiology. Of CSF from 37 patients, 20 had infectious, nine immune-mediated and eight unknown aetiology.Heat-map analysis of CSF mediator interactions was different for infectious and immune-mediated cases, and that of the unknown aetiology group was similar to the infectious pattern. Higher myeloperoxidase (MPO concentrations were found in infectious than immune-mediated cases, in serum and CSF (p = 0.01 and p = 0.006. Serum MPO was also higher in unknown than immune-mediated cases (p = 0.03. Multivariate analysis selected serum MPO; classifying 31 (91% as infectious (p = 0.008 and 17 (85% as unknown (p = 0.009 as opposed to immune-mediated. CSF data also selected MPO classifying 11 (85% as infectious as opposed to immune-mediated (p = 0.036. CSF neutrophils were detected in eight (62% infective and one (14% immune-mediated cases (p = 0.004; CSF MPO correlated with neutrophils (p<0.0001.Mediator profiles of infectious aetiology differed from immune-mediated encephalitis; and those of unknown cause were similar to infectious cases, raising the hypothesis of a possible undiagnosed infectious cause. Particularly, neutrophils and MPO merit further investigation.

  10. In ovo delivery of Newcastle disease virus conjugated hybrid calcium phosphate nanoparticle and to study the cytokine profile induction

    Energy Technology Data Exchange (ETDEWEB)

    Viswanathan, Kaliyaperumal [Translational Research Platform for Veterinary Biologicals (TRPVB), Tamil Nadu Veterinary and Animal Sciences University, Chennai 600 051, Tamil Nadu (India); Rathish, P.; Gopinath, V.P.; Janice, R. [Department of Animal Biotechnology, Madras Veterinary College, Tamil Nadu Veterinary and Animal Sciences University, Chennai 600 007 (India); Dhinakar Raj, G., E-mail: dhinakarrajg@tanuvas.org.in [Department of Animal Biotechnology, Madras Veterinary College, Tamil Nadu Veterinary and Animal Sciences University, Chennai 600 007 (India); Translational Research Platform for Veterinary Biologicals (TRPVB), Tamil Nadu Veterinary and Animal Sciences University, Chennai 600 051, Tamil Nadu (India)

    2014-12-01

    In this report, the hybrid calcium phosphate (CaP) nanoparticles were synthesized and functionalized with Newcastle disease virus (NDV). These nanoparticles were synthesized by a combination of co-precipitation and polymerization process and functionalized with amino propyl triethoxy silane before coupling to NDV. The 5-dimethylthiazol-2-yl-2, 5-diphenyltetrazolium bromide (MTT) assay of chicken spleen cells incubated with these nanoparticles indicated that, these particles did not exert any significant cytotoxicity. The effects of hybrid CaP nanoparticles on cell cycle were assayed using a flow cytometer. The results demonstrated that the cell viability and proliferation capacity of spleen cells were not affected by hybrid CaP nanoparticles compared with their control cells. The hybrid CaP nanoparticles were characterized by scanning/transmission electron microscopy (SEM/TEM); Fourier transformed infrared spectroscopy (FTIR), X-ray diffraction patterns (XRD), Raman spectroscopy and energy-dispersive X-ray spectroscopy (EDX). These methods revealed that NDV was successfully conjugated on nanoparticles. The ability of the hybrid CaP nanoparticles to induce different cytokine mRNAs in the spleen cells of 18-day old embryonated chicken eggs (ECEs) was studied by quantitative real time polymerase chain reaction (qRT-PCR). NDV conjugated particles induced a high expression of Th1 cytokines such as interferon (IFN)-α, tumor necrosis factor (TNF)-α of and Th2 cytokines, interleukin (IL) 6 and IL-10. Uncoupled NDV induced only Th1 cytokines, IFN-α, INF-γ and TNF-α. The hybrid particles alone did not induce any cytokines. This confirmed that nanoparticle coupling could induce differential cytokine profiles and hence can be used as an alternate strategy to direct favorable immune responses in animals or chickens using appropriate vaccination carrier. - Highlights: • NDV conjugated hybrid CaP NP induced differential cytokine profiles in embryonated chicken eggs.

  11. 17DD and 17D-213/77 yellow fever substrains trigger a balanced cytokine profile in primary vaccinated children.

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    Ana Carolina Campi-Azevedo

    Full Text Available BACKGROUND: This study aimed to compare the cytokine-mediated immune response in children submitted to primary vaccination with the YF-17D-213/77 or YF-17DD yellow fever (YF substrains. METHODS: A non-probabilistic sample of eighty healthy primary vaccinated (PV children was selected on the basis of their previously known humoral immune response to the YF vaccines. The selected children were categorized according to their YF-neutralizing antibody titers (PRNT and referred to as seroconverters (PV-PRNT(+ or nonseroconverters (PV-PRNT(-. Following revaccination with the YF-17DD, the PV-PRNT(- children (YF-17D-213/77 and YF-17DD groups seroconverted and were referred as RV-PRNT(+. The cytokine-mediated immune response was investigated after short-term in vitro cultures of whole blood samples. The results are expressed as frequency of high cytokine producers, taking the global median of the cytokine index (YF-Ag/control as the cut-off. RESULTS: The YF-17D-213/77 and the YF-17DD substrains triggered a balanced overall inflammatory/regulatory cytokine pattern in PV-PRNT(+, with a slight predominance of IL-12 in YF-17DD vaccinees and a modest prevalence of IL-10 in YF-17D-213/77. Prominent frequency of neutrophil-derived TNF-α and neutrophils and monocyte-producing IL-12 were the major features of PV-PRNT(+ in the YF-17DD, whereas relevant inflammatory response, mediated by IL-12(+CD8(+ T cells, was the hallmark of the YF-17D-213/77 vaccinees. Both substrains were able to elicit particular but relevant inflammatory events, regardless of the anti-YF PRNT antibody levels. PV-PRNT(- children belonging to the YF-17DD arm presented gaps in the inflammatory cytokine signature, especially in terms of the innate immunity, whereas in the YF-17D-213/77 arm the most relevant gap was the deficiency of IL-12-producing CD8(+T cells. Revaccination with YF-17DD prompted a balanced cytokine profile in YF-17DD nonresponders and a robust inflammatory profile in YF-17D

  12. Multiple Serum Cytokine Profiling to Identify Combinational Diagnostic Biomarkers in Attacks of Familial Mediterranean Fever

    Science.gov (United States)

    Koga, Tomohiro; Migita, Kiyoshi; Sato, Shuntaro; Umeda, Masataka; Nonaka, Fumiaki; Kawashiri, Shin-Ya; Iwamoto, Naoki; Ichinose, Kunihiro; Tamai, Mami; Nakamura, Hideki; Origuchi, Tomoki; Ueki, Yukitaka; Masumoto, Junya; Agematsu, Kazunaga; Yachie, Akihiro; Yoshiura, Koh-Ichiro; Eguchi, Katsumi; Kawakami, Atsushi

    2016-01-01

    Abstract The precise cytokine networks in the serum of individuals with familial Mediterranean fever (FMF) that are associated with its pathogenesis have been unknown. Here, we attempted to identify specific biomarkers to diagnose or assess disease activity in FMF patients. We measured serum levels of 45 cytokines in 75 FMF patients and 40 age-matched controls by multisuspension cytokine array. FMF in “attack” or “remission” was classified by Japan College of Rheumatology-certified rheumatologists according to the Tel Hashomer criteria. Cytokines were ranked by their importance by a multivariate classification algorithm. We performed a logistic regression analysis to determine specific biomarkers for discriminating FMF patients in attack. To identify specific molecular networks, we performed a cluster analysis of each cytokine. Twenty-nine of the 45 cytokines were available for further analyses. Eight cytokines’ serum levels were significantly elevated in the FMF attack versus healthy control group. Nine cytokines were increased in FMF attack compared to FMF remission. Multivariate classification algorithms followed by a logistic regression analysis revealed that the combined measurement of IL-6, IL-18, and IL-17 distinguished FMF patients in attack from the controls with the highest accuracy (sensitivity 89.2%, specificity 100%, and accuracy 95.5%). Among the FMF patients, the combined measurement of IL-6, G-CSF, IL-10, and IL-12p40 discriminated febrile attack periods from remission periods with the highest accuracy (sensitivity 75.0%, specificity 87.9%, and accuracy 84.0%). Our data identified combinational diagnostic biomarkers in FMF patients based on the measurement of multiple cytokines. These findings help to improve the diagnostic performance of FMF in daily practice and extend our understanding of the activation of the inflammasome leading to enhanced cytokine networks. PMID:27100444

  13. Cytokine investigations in organs and tissues of experimental animals under prenatal hypoxic conditions of varying severity

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    Talgat Kudaibergenov

    2011-04-01

    Full Text Available The paper presents the research results of varying severity experimental hypoxia influences on the content of cytokines (IGF-1, TNF-α, IL-1β, IL-4, IL-6, IFN-γ in organs, tissues and cells (blood, liver, brain, uterus, adrenal glands, placenta, placental lymphocytes and macrophages of pregnant rats. The results showed the increase of pro-inflammatory cytokines synthesis on the local and system levels during experimental hypoxia augmentation. There was found the difference between placental lymphocytes and macrophages secretion. These changes of cytokine profile leads to local deficiency of anti-inflammatory factors and indicate on development of pregnancy complications and “mother-placenta-fetus” system dysfunction.

  14. Distinct chemokine receptor and cytokine expression profile in secondary progressive MS

    DEFF Research Database (Denmark)

    Sørensen, Torben Lykke; Sellebjerg, F

    2001-01-01

    Chemokines, small chemotactic cytokines, have been implicated in active relapsing-remitting MS (RRMS). However, the role of chemokines and chemokine receptors has not been specifically studied in secondary progressive MS (SPMS)....

  15. Cytokine profiles in crevicular fluid during orthodontic tooth movement of short and long durations

    NARCIS (Netherlands)

    Ren, Yijin; Hazemeijer, Heleen; de Haan, Bart; Qu, Ning; de Vos, Paul

    2007-01-01

    Background: Orthodontic treatment induces a distortion of the extracellular matrix of the periodontium, resulting in alterations in cytoskeletal configuration. Cytokines are known to facilitate this process by inducing cellular proliferation, differentiation, and stimulation of periodontal remodelin

  16. Cytokine profile after oral food challenge in infants with food protein-induced enterocolitis syndrome

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    Mitsuaki Kimura

    2017-07-01

    Conclusions: These results suggest that IL-2 and IL-8 are involved in the antigen-specific immune responses in most patients with FPIES. Further studies are needed to elucidate the significance of these cytokine in the pathogenesis of FPIES.

  17. CEREBROSPINAL FLUID FROM PRETERM PIGS WITH NECROTIZING ENTEROCOLITIS HAS ALTERED CYTOKINE PROFILE AND PROMOTES HIPPOCAMPAL NEURITOGENESIS

    DEFF Research Database (Denmark)

    Pankratova, Stanislava; Sun, J.; Li, Y.

    2016-01-01

    Background and aims Necrotizing enterocolitis (NEC) in preterm infants is associated with neurodevelopmental delay and cerebral palsy. We hypothesized that intestinal NEC lesions affect inflammatory cytokines in cerebrospinal fluid (CSF) which in turn may affect neurite differentiation. Methods...

  18. 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...... lining fluid in 309 neonates from the novel unselected Copenhagen Prospective Study on Asthma in Childhood (COPSAC) birth cohort. Measurements and Main Results: Maternal, but not paternal, atopic status (asthma, hay fever, or eczema with or without sensitization) was associated with general down......-regulation of all 18 mediators assessed by principal component analysis (overall P = 0.015). Conclusions: Maternal atopy, but not paternal atopy, showed a strong linkage with a suppressed mucosal cytokine and chemokine signature in asymptomatic neonates, suggesting imprinting by the maternal milieu in utero...

  19. 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.

  20. Cytokines profiling by multiplex analysis in experimental arthritis: which pathophysiological relevance for articular versus systemic mediators?

    Science.gov (United States)

    Paquet, Joseph; Goebel, Jean-Christophe; Delaunay, Camille; Pinzano, Astrid; Grossin, Laurent; Cournil-Henrionnet, Christel; Gillet, Pierre; Netter, Patrick; Jouzeau, Jean-Yves; Moulin, David

    2012-03-13

    We have taken advantage of the large screening capacity of a multiplex immunoassay to better define the respective contribution of articular versus systemic cytokines in experimental arthritis. We performed a follow up (from 7 hours to 14 days) multiplex analysis of 24 cytokines in synovial fluid and sera of rats developing Antigen-Induced Arthritis (AIA) and confronted their protein level changes with molecular, biochemical, histological and clinical events occurring in the course of the disease. The time-scheduled findings in arthritic joints correlated with time-dependent changes of cytokine amounts in joint effusions but not with their blood levels. From seven hours after sensitization, high levels of chemokines (MCP-1, MIP1α, GRO/KC, RANTES, eotaxin) were found in synovial fluid of arthritic knees whereas perivascular infiltration occurred in the synovium; local release of inflammatory cytokines (IFNγ, IL-1β, IL-6) preceded the spreading of inflammation and resulted in progressive degradation of cartilage and bone. Finally a local overexpression of several cytokines/adipocytokines poorly described in arthritis (IL-13, IL-18, leptin) was observed. Distinct panels of cytokines were found in arthritic fluid during AIA, and the expected effect of mediators correlated well with changes occurring in joint tissues. Moreover, multiplex analysis could be helpful to identify new pathogenic mediators and to elucidate the mechanisms supporting the efficacy of putative targeted therapies.

  1. Characteristic cerebrospinal fluid cytokine/chemokine profiles in neuromyelitis optica, relapsing remitting or primary progressive multiple sclerosis.

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    Takuya Matsushita

    Full Text Available BACKGROUND: Differences in cytokine/chemokine profiles among patients with neuromyelitis optica (NMO, relapsing remitting multiple sclerosis (RRMS, and primary progressive MS (PPMS, and the relationships of these profiles with clinical and neuroimaging features are unclear. A greater understanding of these profiles may help in differential diagnosis. METHODS/PRINCIPAL FINDINGS: We measured 27 cytokines/chemokines and growth factors in CSF collected from 20 patients with NMO, 26 with RRMS, nine with PPMS, and 18 with other non-inflammatory neurological diseases (OND by multiplexed fluorescent bead-based immunoassay. Interleukin (IL-17A, IL-6, CXCL8 and CXCL10 levels were significantly higher in NMO patients than in OND and RRMS patients at relapse, while granulocyte-colony stimulating factor (G-CSF and CCL4 levels were significantly higher in NMO patients than in OND patients. In NMO patients, IL-6 and CXCL8 levels were positively correlated with disability and CSF protein concentration while IL-6, CXCL8, G-CSF, granulocyte-macrophage colony-stimulating factor (GM-CSF and IFN-γ were positively correlated with CSF neutrophil counts at the time of sample collection. In RRMS patients, IL-6 levels were significantly higher than in OND patients at the relapse phase while CSF cell counts were negatively correlated with the levels of CCL2. Correlation coefficients of cytokines/chemokines in the relapse phase were significantly different in three combinations, IL-6 and GM-CSF, G-CSF and GM-CSF, and GM-CSF and IFN-γ, between RRMS and NMO/NMOSD patients. In PPMS patients, CCL4 and CXCL10 levels were significantly higher than in OND patients. CONCLUSIONS: Our findings suggest distinct cytokine/chemokine alterations in CSF exist among NMO, RRMS and PPMS. In NMO, over-expression of a cluster of Th17- and Th1-related proinflammatory cytokines/chemokines is characteristic, while in PPMS, increased CCL4 and CXCL10 levels may reflect on-going low grade T cell

  2. In vitro cytokine profiles and viability of different human cells treated with whole cell lysate of Mycobacterium avium subsp. paratuberculosis

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    Rani Pittu

    2012-09-01

    Full Text Available Abstract Mycobacterium avium subsp. paratuberculosis (MAP is a zoonotic pathogen, a very slow growing bacterium which is difficult to isolate and passage in conventional laboratory culture. Although its association with Johne’s disease or paratuberculosis of cattle is well established, it has been only putatively linked to Crohn’s disease in humans. Further, MAP has been recently suggested to be a trigger for other autoimmune diseases such as type-1 diabetes mellitus (T1DM. Recently, some studies have indicated that exposure to MAP is associated with elevated levels of antibodies against MAP lysate although the exact mechanism and significance of the same remains unclear. Further, the cytokine profiles relevant in MAP associated diseases of humans and their exact role in the pathophysiology are not clearly known. We performed in vitro cytokine analyses after exposing different cultured human cells to the whole cell lysate of MAP and found that MAP lysate induces secretion of cytokines IL-1β, IL-6, IL-8, IL-10 and TNF-α by human peripheral blood mononuclear cells (PBMCs. Also, it induces secretion of IL-8 by cultured human stomach adenocarcinoma cells (AGS and PANC-1(human pancreatic carcinoma cell line cells. We also found that MAP lysate induced cytotoxicity in PANC-1cells. Collectively, these results provide a much needed base-line data set of cytokines broadly signifying a MAP induced cellular response by human cells.

  3. Involvement of IL-18 in the expansion of unique hepatic T cells with unconventional cytokine profiles during Schistosoma mansoni infection.

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    Keishi Adachi

    Full Text Available Infection with schistosomes invokes severe fibrotic granulomatous responses in the liver of the host. Schistosoma mansoni infection induces dramatic fluctuations in Th1 or Th2 cytokine responses systemically; Th1 reactions are provoked in the early phase, whilst Th2 responses become dominant after oviposition begins. In the liver, various unique immune cells distinct from those of conventional immune competent organs or tissues exist, resulting in a unique immunological environment. Recently, we demonstrated that S. mansoni infection induces unique CD4+ T cell populations exhibiting unconventional cytokine profiles in the liver of mice during the period between Th1- and Th2-phases, which we term the transition phase. They produce both IFN-γ and IL-4 or both IFN-γ and IL-13 simultaneously. Moreover, T cells secreting triple cytokines IFN-γ, IL-13 and IL-4 were also induced. We term these cells Multiple Cytokine Producing Hepatic T cells (MCPHT cells. During the transition phase, when MCPHT cells increase, IL-18 secretion was up-regulated in the liver and sera. In S. mansoni-infected IL-18-deficient mice, expansion of MCPHT cells was curtailed. Thus our data suggest that IL-18 produced during S. mansoni infection play a role in the expansion of MCPHT cells.

  4. Profile of IL-2, IL-4, IL-10, IFN- ? , TNF- ? and KC-like cytokines in pregnant bitches

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    M.A.R. Feliciano

    2014-08-01

    Full Text Available The aim of this study was to determine the profile of IL-2, IL-4, IL-10, IFN-γ, and TNF-α cytokines and KC-like cells (natural killer in pregnant bitches, unpublished values for the species. A total of 27 females of the Shi Tzu, Pug, English Bulldog and French breeds, weighing 4-20kg and aged 4-6 years were used. Blood samples were collected from bitches during the anestrous and on the 2nd, 5th, 6th, 7th and 8th week of pregnancy. Serum levels of cytokines were measured by panel MILLIPLEX MAP (CCYTO-90K, MILLIPORE, Billerica, Massachusetts, USA validated for dogs. Twenty four females showed physiological pregnancy and three bitches showed pathological pregnancy. There was no difference between cytokine values during anestrous and gestational weeks of bitches (P>0.05. However, it was possible to verify the physiological behavior of serum levels during modulation of immune response in the gestational process of animals. In animals with gestational disorders, abnormal values for IL-2, IL-4 and INF-y were noted. It was concluded that serum levels of cytokines evaluated in pregnant bitches can help the better understanding of physiological and pathological gestational processes and correlated immunology in this species.

  5. Pregnancy Complications: Placental Abruption

    Science.gov (United States)

    ... wall of the uterus (womb) and supplies the baby with food and oxygen through the umbilical cord. Placental abruption ... wall of the uterus (womb) and supplies the baby with food and oxygen through the umbilical cord. Placental abruption ...

  6. Different profile of cytokine synthesis according to the severity of acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Raquel Laveda; José Ma Palazón; José Sánchez-Payá; José Such; Miguel Pérez-Mateo; Juan Martínez; Carlos Mu(n)oz; Juan Carlos Penalva; Jesus Sáez; Germán Belda; Salvador Navarro; Faust Feu; Anton Mas

    2005-01-01

    AIM: To evaluate the cellular synthetic ability of cytokines involved in pro- and anti-inflammatory reactions in patients with AP.METHODS: Sixty-seven patients with AP (16 severe,51 mild) and 10 controls were included in the study.Cultures of whole blood were performed in samples obtained within the first 72 h from the onset of pain.Serum levels of interleukins (IL) 6, 8, 10, and TNF-α were measured at baseline and in the supernatant of cultures with (functional reserve) or without stimulation with phytohemaglutinin.RESULTS: Basal levels of cytokines were significantly higher in patients with severe AP. A significant increase of all pro-inflammatory cytokines vs basal levels was observed in the supernatant after 24 h of whole blood cultures in patients, but not in controls. In contrast, IL-10 increased significantly in the supernatant of cultures only in patients with mild AP. Cells showed a statistically significant functional reserve for all IL in patients with mild, but only for pro-inflammatory cytokines in patients with severe AP.CONCLUSION: A marked activation of immune system may be observed in patients with AP, being balanced between pro- and anti-inflammatory cytokines in patients with mild but not severe AP. A reduced functional reserve for the synthesis of IL-10 may be observed in patients with severe AP, which might lead to a worst prognosis.

  7. Th-1, Th-2 Cytokines Profile among Madurella mycetomatis Eumycetoma Patients.

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    Amre Nasr

    2016-07-01

    Full Text Available Eumycetoma is a progressive and destructive chronic granulomatous subcutaneous inflammatory disease caused by certain fungi, the most common being Madurella mycetomatis. The host defence mechanisms against fungi usually range from an early non-specific immune response to activation and induction of specific adaptive immune responses by the production of Th-1 and Th-2 cytokines. The aim of this study is to determine the levels of Th-1 and Th-2 cytokines in patients infected with Madurella mycetomatis, and the association between their levels and disease prognosis. This is a descriptive cross-sectional study conducted at the Mycetoma Research Centre, University of Khartoum, Sudan, where 70 patients with confirmed M. mycetomatis eumycetoma were enrolled; 35 with, and 35 without surgical excision. 70 healthy individuals from mycetoma endemic areas were selected as controls. The levels of serum cytokines were determined by cytometric bead array technique. Significantly higher levels of the Th-1 cytokines (IFN-γ, TNF-α, IL-1β and IL-2 were recorded in patients treated with surgical excision, compared to those treated without surgical excision. In contrast, the Th-2 cytokines (IL-4, IL-5, IL-6 and IL-10 were significantly lower in patients treated with surgical excision compared to those treated without surgical excision. In conclusion, the results of this study suggest that cell-mediated immunity can have a role to play in the pathogenesis of eumycetoma.

  8. Th-1, Th-2 Cytokines Profile among Madurella mycetomatis Eumycetoma Patients.

    Science.gov (United States)

    Nasr, Amre; Abushouk, Amir; Hamza, Anhar; Siddig, Emmanuel; Fahal, Ahmed H

    2016-07-01

    Eumycetoma is a progressive and destructive chronic granulomatous subcutaneous inflammatory disease caused by certain fungi, the most common being Madurella mycetomatis. The host defence mechanisms against fungi usually range from an early non-specific immune response to activation and induction of specific adaptive immune responses by the production of Th-1 and Th-2 cytokines. The aim of this study is to determine the levels of Th-1 and Th-2 cytokines in patients infected with Madurella mycetomatis, and the association between their levels and disease prognosis. This is a descriptive cross-sectional study conducted at the Mycetoma Research Centre, University of Khartoum, Sudan, where 70 patients with confirmed M. mycetomatis eumycetoma were enrolled; 35 with, and 35 without surgical excision. 70 healthy individuals from mycetoma endemic areas were selected as controls. The levels of serum cytokines were determined by cytometric bead array technique. Significantly higher levels of the Th-1 cytokines (IFN-γ, TNF-α, IL-1β and IL-2) were recorded in patients treated with surgical excision, compared to those treated without surgical excision. In contrast, the Th-2 cytokines (IL-4, IL-5, IL-6 and IL-10) were significantly lower in patients treated with surgical excision compared to those treated without surgical excision. In conclusion, the results of this study suggest that cell-mediated immunity can have a role to play in the pathogenesis of eumycetoma.

  9. Placental gene-expression profiles of intrahepatic cholestasis of pregnancy reveal involvement of multiple molecular pathways in blood vessel formation and inflammation.

    Science.gov (United States)

    Du, QiaoLing; Pan, YouDong; Zhang, YouHua; Zhang, HaiLong; Zheng, YaJuan; Lu, Ling; Wang, JunLei; Duan, Tao; Chen, JianFeng

    2014-07-07

    Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-associated liver disease with potentially deleterious consequences for the fetus, particularly when maternal serum bile-acid concentration >40 μM. However, the etiology and pathogenesis of ICP remain elusive. To reveal the underlying molecular mechanisms for the association of maternal serum bile-acid level and fetal outcome in ICP patients, DNA microarray was applied to characterize the whole-genome expression profiles of placentas from healthy women and women diagnosed with ICP. Thirty pregnant women recruited in this study were categorized evenly into three groups: healthy group; mild ICP, with serum bile-acid concentration ranging from 10-40 μM; and severe ICP, with bile-acid concentration >40 μM. Gene Ontology analysis in combination with construction of gene-interaction and gene co-expression networks were applied to identify the core regulatory genes associated with ICP pathogenesis, which were further validated by quantitative real-time PCR and histological staining. The core regulatory genes were mainly involved in immune response, VEGF signaling pathway and G-protein-coupled receptor signaling, implying essential roles of immune response, vasculogenesis and angiogenesis in ICP pathogenesis. This implication was supported by the observed aggregated immune-cell infiltration and deficient blood vessel formation in ICP placentas. Our study provides a system-level insight into the placental gene-expression profiles of women with mild or severe ICP, and reveals multiple molecular pathways in immune response and blood vessel formation that might contribute to ICP pathogenesis.

  10. Increased Calpain Correlates with Th1 Cytokine Profile in PBMCs from MS Patients

    Science.gov (United States)

    Imam, Sarah A.; Guyton, Mary K.; Haque, Azizul; Vandenbark, Arthur; Tyor, William R.; Ray, Swapan K.; Banik, Naren L.

    2007-01-01

    Multiple sclerosis (MS) is a devastating autoimmune demyelinating disease of the CNS. This study investigated whether expression and activity of the calcium-activated protease calpain correlated with Th1/Th2 dysregulation in MS patients during states of relapse and remission. Calpain expression and activity were significantly increased in peripheral blood mononuclear cells (PBMCs) from MS patients, compared to controls, with the highest expression and activity noted during relapse. Th1 cytokines were highest and Th2 cytokines were lowest in MS patients during relapse. Treatment with calpain inhibitor, calpeptin, decreased Th1 cytokines in PBMCs from MS patients. Calpain inhibitor also reduced degradation of myelin basic protein (MBP) by inhibiting the calpain secreted from MBP-specific T cells. Taken together, these results suggested calpain involvement in Th1/Th2 dysregulation in MS patients. PMID:17765980

  11. Multiplex cytokine profile from dengue patients: MIP-1beta and IFN-gamma as predictive factors for severity

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    Bozza Patricia T

    2008-06-01

    Full Text Available Abstract Background Dengue virus pathogenesis is not yet fully understood and the identification of patients at high risk for developing severe disease forms is still a great challenge in dengue patient care. During the present study, we evaluated prospectively the potential of cytokines present in plasma from patients with dengue in stratifying disease severity. Methods Seventeen-cytokine multiplex fluorescent microbead immunoassay was used for the simultaneous detection in 59 dengue patients. GLM models using bimodal or Gaussian family were determined in order to associate cytokines with clinical manifestations and laboratory diagnosis. Results IL-1β, IFN-γ, IL-4, IL-6, IL-13, IL-7 and GM-CSF were significantly increased in patients with severe clinical manifestations (severe dengue when compared to mild disease forms (mild dengue. In contrast, increased MIP-1β levels were observed in patients with mild dengue. MIP-1β was also associated with CD56+NK cell circulating rates. IL-1β, IL-8, TNF-α and MCP-1 were associated with marked thrombocytopenia. Increased MCP-1 and GM-CSF levels correlated with hypotension. Moreover, MIP-1β and IFN-γ were independently associated with both dengue severity and disease outcome. Conclusion Our data demonstrated that the use of a multiple cytokine assay platform was suitable for identifying distinct cytokine profiles associated with the dengue clinical manifestations and severity. MIP-β is indicated for the first time as a good prognostic marker in contrast to IFN-γ that was associated with disease severity.

  12. Cytokine and chemokine profiles in fibromyalgia, rheumatoid arthritis and systemic lupus erythematosus: a potentially useful tool in differential diagnosis.

    Science.gov (United States)

    Wallace, Daniel J; Gavin, Igor M; Karpenko, Oleksly; Barkhordar, Farnaz; Gillis, Bruce S

    2015-06-01

    Making a correct diagnosis is pivotal in the practice of clinical rheumatology. Occasionally, the consultation fails to provide desired clarity in making labeling an individual as having fibromyalgia (FM), systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA). A chemokine and cytokine multiplex assay was developed and tested with the goal of improving and achieving an accurate differential diagnosis. 160 patients with FM, 98 with RA and 100 with SLE fulfilling accepted criteria were recruited and compared to 119 controls. Supernatant cytokine concentrations for IL-6, IL-8, MIP-1 alpha and MIP-1 beta were determined using the Luminex multiplex immunoassay bead array technology after mitogenic stimulation of cultured peripheral blood mononuclear cells. Each patient's profile was scored using a logistical regression model to achieve statistically determined weighting for each chemokine and cytokine. Among the 477 patients evaluated, the mean scores for FM (1.7 ± 1.2; 1.52-1.89), controls (-3.56 ± 5.7; -4.59 to -2.54), RA (-0.68 ± 2.26; -1.12 to -0.23) and SLE (-1.45 ± 3.34, -2.1 to -0.79). Ninety-three percent with FM scored positive compared to only 11% of healthy controls, 69% RA or 71% SLE patients had negative scores. The sensitivity, specificity, positive predictive and negative predictive value for having FM compared to controls was 93, 89, 92 and 91%, respectively (p < 2.2 × 10(-16)). Evaluating cytokine and chemokine profiles in stimulated cells reveals patterns that are uniquely present in patients with FM. This assay can be a useful tool in assisting clinicians in differentiating systemic inflammatory autoimmune processes from FM and its related syndromes and healthy individuals.

  13. INTERACTION OF CYTOKINE CASCADE WITH PSYCHOLOGICAL PROFILE IN PATIENTS WITH ACUTE CORONARY SYNDROME

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    M. A. Shalenkova

    2013-01-01

    Full Text Available Abstract. The role of immune factors in development of atherosclerotic process and anxiety-depressive disorders is of utmost importance. Serum levels of IL-6 and -10 were studied in forty-nine patients with acute coronary syndrome, as well as their interactions with psychological state of the patients. Serum concentrations of the cytokines proved to be higher in unstable angina. A correlation was confirmed between the cytokine levels and co-morbidity with affective disorders in acute ischaemic heart disease.

  14. Different profiles of cytokine expression during mild and severe acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Zilvinas; Dambrauskas; Nathalia; Giese; Antanas; Gulbinas; Thomas; Giese; Pascal; O; Berberat; Juozas; Pundzius; Giedrius; Barauskas; Helmut; Friess

    2010-01-01

    AIM:To study secretion patterns of proand anti-in-flammatory cytokines, and activation of various cellular subsets of leukocytes in peripheral blood.METHODS: We have conducted a prospective obser-vational study. One hundred and eight patients with a diagnosis of acute pancreatitis and onset of the disease within last 72 h were included in this study. The mRNA expression of 25 different types of cytokines in white blood cells was determined by quantitative real time polymerase chain reaction. Levels of 8 dif...

  15. Whole Blood Activation Results in Altered T Cell and Monocyte Cytokine Production Profiles by Flow Cytometry

    Science.gov (United States)

    Crucian, Brian E.; Sams, Clarence F.

    2001-01-01

    An excellent monitor of the immune balance of peripheral circulating cells is to determine their cytokine production patterns in response to stimuli. Using flow cytometry, a positive identification of cytokine producing cells in a mixed culture may be achieved. Recently, the ability to assess cytokine production following a whole-blood activation culture has been described. In this study, whole blood activation was compared to traditional PBMC activation and the individual cytokine secretion patterns for both T cells, T cell subsets and monocytes was determined by flow cytometry. RESULTS: For T cell cytokine assessment (IFNg/IL-10 and IL-21/L-4) following PMA +ionomycin activation: (1) a Significantly greater percentages of T cells producing IFNgamma and IL-2 were observed following whole-blood culture and (2) altered T cell cytokine production kinetics were observed by varying whole blood culture times. Four-color analysiS was used to allow assessment of cytokine production by specific T cell subsets. It was found that IFNgamma production was significantly elevated in the CD3+/CD8+ T cell population as compared to the CD3+/CD8- population following five hours of whole blood activation. Conversely, IL-2 and IL-10 production were Significantly elevated in the CD3+/CD8- T cell population as compared to the CD3+/CD8+ population. Monocyte cytokine production was assessed in both culture systems following LPS activation for 24 hours. A three-color flow cytometric was used to assess two cytokines (IL-1a/IL-12 and TNFa/IL-10) in conjunction with CD14. Nearly all monocytes were stimulated to produce IL-1a, IL-12 and TNFa. equally well in both culture systems, however monocyte production of IL-10 was significantly elevated in whole blood culture as compared to PBMC culture. IL-12 producing monocytes appeared to be a distinct subpopulation of the IL-1a producing set, whereas IL-10 and TNFa producing monocytes were largely mutually exclusive. IL-10 and TNFa producing

  16. Haptoglobin phenotype prevalence and cytokine profiles during Plasmodium falciparum infection in Dogon and Fulani ethnic groups living in Mali.

    Science.gov (United States)

    Perdijk, Olaf; Arama, Charles; Giusti, Pablo; Maiga, Bakary; Troye-Blomberg, Marita; Dolo, Amagana; Doumbo, Ogobara; Persson, Jan-Olov; Boström, Stéphanie

    2013-11-25

    The Fulani are known to have a lower parasitaemia and less clinical episodes of malaria as compared to the Dogon sympatric ethnic group, living in Mali. Higher circulating malaria-specific antibody titers and increased pro-inflammatory cytokine levels have been shown in Fulani individuals. Several studies have tried to link haptoglobin (Hp) phenotypes with susceptibility to malaria, but without consensus. This study investigated the role of Hp phenotypes and cytokine levels in Dogon and Fulani during asymptomatic Plasmodium falciparum infection. Two different cohorts were combined in this study: a 2008 cohort with 77 children aged between two and ten years and a 2001 cohort, with 82 children and adults, aged between 11 and 68 years. Hp phenotypes in plasma were measured by Western Blot. Circulating levels of sCD163, IL-6, IL-10, IFN-γ and TNF were measured by ELISA. Multiple regression analysis was performed to associate Hp phenotypes with cytokine profiles. In addition, in vitro stimulation of peripheral blood mononuclear cells (PBMCs) with Hp:Hb complexes was performed and cytokine release in corresponding supernatants were measured using cytometric bead array. The results revealed a higher Hp2-2 phenotype prevalence in the Fulani. The Hp2-2 phenotype was associated with a higher susceptibility to P. falciparum infection in Dogon, but not in Fulani. In concordance with previous studies, Fulani showed increased inflammatory mediators (IL-6, IFN-γ) and additionally also increased sCD163 levels compared to Dogon, irrespective of infection. Furthermore, infected individuals showed elevated sCD163 levels compared to uninfected individuals, in both Fulani and Dogon. Multiple regression analysis revealed that the Hp1-1 phenotype was associated with higher levels of TNF and IFN-γ, as compared to the Hp2-2 phenotype. In vitro stimulation of PBMCs with Hb:Hp1-1 complexes resulted in a pro-inflammatory cytokine profile, whilst stimulation with Hb:Hp2-2 complexes showed

  17. Cerebrospinal fluid cytokine profiles predict risk of early mortality and immune reconstitution inflammatory syndrome in HIV-associated cryptococcal meningitis.

    Directory of Open Access Journals (Sweden)

    Joseph N Jarvis

    2015-04-01

    Full Text Available Understanding the host immune response during cryptococcal meningitis (CM is of critical importance for the development of immunomodulatory therapies. We profiled the cerebrospinal fluid (CSF immune-response in ninety patients with HIV-associated CM, and examined associations between immune phenotype and clinical outcome. CSF cytokine, chemokine, and macrophage activation marker concentrations were assayed at disease presentation, and associations between these parameters and microbiological and clinical outcomes were examined using principal component analysis (PCA. PCA demonstrated a co-correlated CSF cytokine and chemokine response consisting primarily of Th1, Th2, and Th17-type cytokines. The presence of this CSF cytokine response was associated with evidence of increased macrophage activation, more rapid clearance of Cryptococci from CSF, and survival at 2 weeks. The key components of this protective immune-response were interleukin (IL-6 and interferon-γ, IL-4, IL-10 and IL-17 levels also made a modest positive contribution to the PC1 score. A second component of co-correlated chemokines was identified by PCA, consisting primarily of monocyte chemotactic protein-1 (MCP-1 and macrophage inflammatory protein-1α (MIP-1α. High CSF chemokine concentrations were associated with low peripheral CD4 cell counts and CSF lymphocyte counts and were predictive of immune reconstitution inflammatory syndrome (IRIS. In conclusion CSF cytokine and chemokine profiles predict risk of early mortality and IRIS in HIV-associated CM. We speculate that the presence of even minimal Cryptococcus-specific Th1-type CD4+ T-cell responses lead to increased recruitment of circulating lymphocytes and monocytes into the central nervous system (CNS, more effective activation of CNS macrophages and microglial cells, and faster organism clearance; while high CNS chemokine levels may predispose to over recruitment or inappropriate recruitment of immune cells to the CNS and

  18. Pro- and Anti-Inflammatory Cytokines during Immune Stimulation: Modulation of Iron Status and Red Blood Cell Profile

    Directory of Open Access Journals (Sweden)

    A. M. Koorts

    2011-01-01

    Full Text Available Forty-eight patients were subdivided according to C-reactive protein (CRP levels, resulting in 19 patients with normal (2.8 ± 2.8 mg/L and 29 with elevated (82.2 ± 76.2 mg/L CRP levels. The elevated CRP group had iron and red blood cell (RBC profiles characteristic of chronic immune stimulation (CIS, and the normal CRP group, profiles of true iron deficiency. Normal relationships between storage iron, bioavailable iron, and RBC indices were absent in the elevated CRP group—implying the role of iron as major determinant of the RBC profile to be diminished during CIS. The elevated CRP group had significant increases in proinflammatory cytokines (INF-γ, TNF-α, Il-1β, Il-6, and Il-8. Anti-inflammatory cytokine levels were normal, except for Il-10, supporting previous indications that Il-10 contributes to reducing bioavailable iron. Regression analysis suggested decreases in transferrin to be related to increases in Il-8 and an increase in ferritin to be related to a decrease in Il-12 levels. TGF-β levels were positively related to transferrin and negatively to ferritin.

  19. Pro- and Anti-Inflammatory Cytokines during Immune Stimulation: Modulation of Iron Status and Red Blood Cell Profile

    Science.gov (United States)

    Koorts, A. M.; Levay, P. F.; Becker, P. J.; Viljoen, M.

    2011-01-01

    Forty-eight patients were subdivided according to C-reactive protein (CRP) levels, resulting in 19 patients with normal (2.8 ± 2.8 mg/L) and 29 with elevated (82.2 ± 76.2 mg/L) CRP levels. The elevated CRP group had iron and red blood cell (RBC) profiles characteristic of chronic immune stimulation (CIS), and the normal CRP group, profiles of true iron deficiency. Normal relationships between storage iron, bioavailable iron, and RBC indices were absent in the elevated CRP group—implying the role of iron as major determinant of the RBC profile to be diminished during CIS. The elevated CRP group had significant increases in proinflammatory cytokines (INF-γ, TNF-α, Il-1β, Il-6, and Il-8). Anti-inflammatory cytokine levels were normal, except for Il-10, supporting previous indications that Il-10 contributes to reducing bioavailable iron. Regression analysis suggested decreases in transferrin to be related to increases in Il-8 and an increase in ferritin to be related to a decrease in Il-12 levels. TGF-β levels were positively related to transferrin and negatively to ferritin. PMID:21547258

  20. Workers’ cytokines profiling upon exposure to MWCNT aerosol in occupational settings

    Science.gov (United States)

    Fatkhutdinova, L. M.; Khaliullin, T. O.; Zalyalov, R. R.; Vasilyeva, O. L.; Valeeva, I. Kh; Mustafin, I. G.

    2015-11-01

    Recent studies have found that upon pulmonary exposure to multi-walled carbon nanotubes (MWCNTs) animals develop primarily fibrosis and granulomas in lungs. In vitro and in vivo studies also give reason to assume that local exposure could be related to remote effects, including immune system and the endothelium. To investigate the remote effect hypothesis, we have analyzed blood, nasal lavage and induced sputum samples taken from workers in the frame of the Russian epidemiological study on Carbon Nanotubes Exposure and Risk Assessment (CNT-ERA). In serum and nasal lavage no significant differences between exposure and control groups were observed with a high variability to the cytokines content. In the samples of induced sputum from exposed workers the content of IL-1b, IL-6, IL-8, TNF-a, IL-4, IL-5, IFN-g exceeded the control group values, but after the regression models construction and bootstrap analysis, significant differences were found only for IL-1b. This study could not provide evidences of blood cytokines changes following local cytokine production in airways in workers exposed to MWCNTs. Cytokines variability in serum and nasal lavage may indicate the absence of severe systemic inflammatory response upon the existing occupational exposure to MWCNTs. Other systemic responses (including allergy-like or autoimmune reactions) should be regarded as well.

  1. Proinflammatory and anti-inflammatory cytokine profile in pediatric patients with irritable bowel syndrome

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    R. Vázquez-Frias

    2015-01-01

    Conclusions: This study suggests that children with IBS have a state of altered immune regulation. This is consistent with the theory of low-grade inflammatory state in these patients. Further studies are needed to elucidate the role played by these cytokines, specifically TGF-β in the pathogenesis of IBS.

  2. Metformin as a new therapy for endometriosis, its effects on both clinical picture and cytokines profile

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    Ashraf Ahmed Foda

    2012-12-01

    Conclusion: Metformin therapy in patients with endometriosis resulted in a significant reduction in the symptomatic cases, increased chance of pregnancy, and a decrease in the levels of serum cytokines, suggesting that it may have a therapeutic potential as an anti-endometriotic drug.

  3. Differential cytokine gene expression profiles in the three pathological forms of sheep paratuberculosis

    Directory of Open Access Journals (Sweden)

    Rhind Susan M

    2007-08-01

    Full Text Available Abstract Background Johne's disease is a chronic inflammatory disease of the gut caused by infection with Mycobacterium avium subspecies paratuberculosis (MAP. Symptoms include wasting, diarrhoea, loss of condition and eventual death. Three forms of Johne's disease have been described in sheep – paucibacillary, multibacillary and asymptomatic. The paucibacillary form is characterized by an inflammatory, Th1-type immune response. The multibacillary form of the disease, which disseminates the infection, is characterized by macrophage infiltration mediated by a Th2-type immune response, and asymptomatic animals have no clinical symptoms or pathology but are infected with MAP. What determines these three forms of the disease is unknown. To further understand these differences, we used real-time RT-PCR to compare the expression of thirteen cytokine and cytokine-related genes in ileal tissue from sheep with the three forms of the disease. Results Three pathological forms of sheep paratuberculosis were defined on the basis of histopathology, cytochemistry (Zeihl-Neelsen and IS900 PCR. Paucibacillary lesions have largely T cell and eosinophil infiltration and are ZN negative; multibacillary lesions have macrophage infiltration and large numbers of acid-fast bacteria. The pauci- and multibacillary forms are linked to the differential expression of IFNγ and IL-10 respectively. In addition the increased levels of the proinflammatory cytokines (IL-1β and TNFα, IL-8, IL-18 and TRAF-1 in both diseased forms is indicative of persistent inflammatory lesions. No changes were seen in IL-1α in any sheep ileum tissues. Asymptomatic animals are IS900+ with normal histology but have significantly decreased levels of IL-18 and increased levels TNFα. Conclusion We have quantified the expression levels of thirteen cytokine and cytokine related genes in three forms of ovine paratuberculosis using real-time PCR analyses and confirm that sheep pauci- and

  4. Cytokine profile of NALT during acute stress and its possible effect on IgA secretion.

    Science.gov (United States)

    Gutiérrez-Meza, Juan Manuel; Jarillo-Luna, Rosa Adriana; Rivera-Aguilar, Victor; Miliar-García, Angel; Campos-Rodríguez, Rafael

    2017-08-01

    Stress stimuli affect the immune system responses that occur at mucosal membranes, particularly IgA secretion. It has been suggested that acute stress increases the levels of IgA and that sympathetic innervation plays an important role in this process. We herein explore in a murine model how acute stress affects the Th1/Th2/Treg cytokine balance in NALT, and the possible role of glucocorticoids in this effect. Nine-week-old male CD1 mice were divided into three groups: unstressed (control), stressed (subjected to 4h of immobilization), and stressed after pretreatment with a single dose of the corticosterone receptor antagonist RU-486. The parameters evaluated included plasma corticosterone and epinephrine, IgA levels in nasal fluid (by ELISA), the percentage of CD19(+)B220(+)IgA(+) lymphocytes and CD138(+)IgA(+) plasma cells, and the mRNA expression of heavy α chain, J chain and pIgR. Moreover, the gene and protein expression of Th1 cytokines (TNFα, IL-2 and INF-γ), Th2 cytokines (IL-4 and IL-5) and Treg cytokines (IL-10 and TGFβ) were determined in nasal mucosa. The results show that acute stress generated a shift towards the dominance of an anti-inflammatory immune response (Th2 and Treg cytokines), evidenced by a significant rise in the amount of T cells that produce IL4, IL-5 and IL-10. This immune environment may favor IgA biosynthesis by CD138(+)IgA(+) plasma cells, a process mediated mostly by glucocorticoids. Copyright © 2017 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

  5. CYTOKINE PROFILE FEATURES IN THE PATIENTS WITH NONALLERGIC BRONCHIAL ASTHMA WITH CO-EXISTING TYPE 2 DIABETES MELLITUS

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    L. N. Sorokina

    2017-01-01

    Full Text Available Thirty-five patients with non-allergic bronchial asthma (NABA, 22 patients with NABA and diabetes mellitus type 2 (DT2, 23 subjects with DT2, and 31 healthy controls were enrolled into the study. ELISA assays for IL-4, IL-10, IL-6, IFNγ were performed by means of a standardized protocol using immunoassay kits purchased from VectorBest, and Cytokine. In asthma patients complicated by DT2, the pattern of bronchial asthma was ascribed to NABA. This finding may be consistent with a theory of specific insulin-receptor interactions in asthma. The NABA patients with type 2 diabetes mellitus exhibited a significant increase in IL-6, IFNγ, and decrease of IL-4, as compared with healthy controls and NABA. Moreover, we have revealed an increase of IL-4, IL-6, IFNγ, when compared with DT2. Hence, the patients with coexistence of non-allergic bronchial asthma and DT2 were characterized by a specific cytokine profile of pro- and anti-inflammatory cytokines, which may correlate with increased glycation and deterioration of lung function. 

  6. Cytokine profile during latent and slowly progressive primary tuberculosis: a possible role for interleukin-15 in mediating clinical disease.

    Science.gov (United States)

    Abebe, F; Mustafa, T; Nerland, A H; Bjune, G A

    2006-01-01

    Recently, mouse models for latent (LTB) and slowly progressive primary tuberculosis (SPTB) have been established. However, cytokine profiles during the two models are not well established. Using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) we studied the expression levels of interleukin (IL)-2, IL-4, IL-10, IL-12, IL-15, interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha during the course of LTB and SPTB in the lungs and spleens of B6D2F1Bom mice infected with the H37Rv strain of Mycobacterium tuberculosis (Mtb). The results show that, except for IL-4, cytokine expression levels were significantly higher during SPTB than LTB in both the lungs and spleens. During LTB, all the cytokines (except IL-2 in the lungs) had higher expression levels during the initial period of infection both in the lungs and spleens. During SPTB, the expression levels of IL-15 increased significantly from phases 1 to 3 in the lungs. The expression levels of IL-10, IL-12 and IFN-gamma increased significantly from 2 to 3 in the lungs. IL-10 and IL-15 increased significantly from phases 2 to 3, whereas that of TNF-alpha decreased significantly and progressively from phases 1 to 3 in the spleens. Over-expression of proinflammatory cytokines during active disease has been well documented, but factor(s) underlying such over-expression is not known. In the present study, there was a progressive and significant increase in the expression levels of IL-15, together with Th1 cytokines (IL-12 and IFN-gamma) during SPTB but a significant decrease during LTB. IL-15 is known to up-regulate the production of proinflammatory cytokines, IL-1beta, IL-8, IL-12, IL-17, IFN-gamma and TNF-alpha and has an inhibitory effect on activation-induced cell death. IL-15 is known to be involved in many proinflammatory disease states such as rheumatoid arthritis, sarcoidosis, inflammatory bowel diseases, autoimmune diabetes, etc. Our results, together with the above observations

  7. [The cytokine profile in the acute period of tick-borne neuroinfections in children].

    Science.gov (United States)

    Poponnikova, T V; Bedareva, T Iu; Vakhrameeva, T N; Galieva, G Iu

    2010-01-01

    Clinical peculiarities and blood levels of several cytokines were studied in 199 children, aged from 1 to 15 years, in the acute period of different tick-borne infections. The mixed infection manifested itself by the more severe progression of general clinical presentations compared to monoinfections. Etiologically unspecific changes of blood concentrations of cytokines in the acute period of the disease were found. These data were associated with different clinical forms of tick-borne infections. The decrease in the interferon gamma production was associated with the most severe disease progression with focal nervous system disorders. The use of cycloferon as immune modulator in the complex therapy led to the increase in the interferon gamma level and the decrease of general clinical manifestations during tick-borne encephalitis and mixed infection.

  8. [Cytokine profiles of multiple myeloma and Waldenström macroglobulinemia].

    Science.gov (United States)

    Sedlaříková, L; Sadílková, K; Kubiczková, L; Hájek, R; Sevčíková, S

    2014-01-01

    Multiple myeloma (MM) and Waldenström macroglobulinemia (WM) are malignant disorders of B lymphocytes. These diseases are characterized by monoclonal immunoglobulin production and bone marrow infiltration, which further lead to disease manifestation mainly via osteolytic lesions and disruption of hematopoiesis. The bone marrow microenvironment plays a crucial role in pathogenesis of both of these diseases, as it is well known that interaction between malignant cells and bone marrow cells facilitates both survival and growth of these tumor cells. The interactions are mediated by several different factors, including cytokines. Their production leads to tumor cell growth, proliferation and survival contributing to pathogenesis of MM and WM. In this review, we focus on function of the most important cytokines in both these diseases.

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

    Directory of Open Access Journals (Sweden)

    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

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

    DEFF Research Database (Denmark)

    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...

  11. Early Cytokine Profile Changes In Interstitial And Necrotic Forms Of Acute Pancreatitis

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    Kostic Irena

    2015-03-01

    Full Text Available Acute pancreatitis (AP is a common, potentially lethal, acute inflammatory process with a highly variable clinical course. The aim of this study was to analyse early changes in the serum concentrations of pro- and anti-inflammatory cytokines in the peripheral blood of patients with the interstitial form of acute pancreatitis (IAP and necrotic acute pancreatitis (NAP, especially in those patients who had lethal outcomes.

  12. Eosinophil-derived neurotoxin, elastase, and cytokine profile in effusion from eosinophilic otitis media.

    Science.gov (United States)

    Uchimizu, Hirotaka; Matsuwaki, Yoshinori; Kato, Masahiko; Otori, Nobuyosi; Kojima, Hiromi

    2015-09-01

    Eosinophilic otitis media (EOM) is an intractable disease characterized by a remarkably viscous effusion and accumulation of numerous eosinophils in both the middle ear effusion and the mucosa. The key factors in EOM pathogenesis remain unclear. The purpose of this study is to identify the important factors involved in EOM pathogenesis. Middle ear effusion samples were collected from 12 patients with EOM and 9 patients with secretory otitis media (SOM), as controls. Multiple cytokines in the effusion were measured using a Bio-Plex™ Human Cytokine 27-Plex panel. Eosinophil-derived neurotoxin (EDN) and elastase were measured by ELISA. The concentrations of EDN, elastase, and each cytokine were compared between the EOM and SOM groups. Furthermore, in the EOM group, each cytokine was examined for correlation with EDN and elastase. EDN and elastase concentrations were significantly higher in the EOM group than in the SOM group (p < 0.05). IL-5, IL-1β, MIP-1α, G-CSF, IL-1ra, IL-4, IFN-γ, MIP-1β, IL-10, TNF-α, VEGF, and IL-2 concentration was significantly higher in the EOM group than in the SOM group (p < 0.05). Significant positive correlations were found between EDN and IL-1ra, IL-2, IL-5, IL-9, IL-13, eotaxin, MIP-1α, PDGF-BB, and RANTES in the EOM group (p < 0.05). Our study showed that IL-5, IL-2, MIP-1α, and IL-1ra are the important factors involved in EOM pathogenesis. Furthermore, not only eosinophil, but also neutrophil are involved in middle ear inflammation of EOM. Copyright © 2015 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

  13. 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.

  14. CpG Oligodeoxynucleotides Induce Differential Cytokine and Chemokine Gene Expression Profiles in Dapulian and Landrace Pigs.

    Science.gov (United States)

    Hu, Jiaqing; Yang, Dandan; Wang, Hui; Li, Chuanhao; Zeng, Yongqing; Chen, Wei

    2016-01-01

    Oligodeoxynucleotides containing unmethylated CpG motifs (CpG ODN) mimic the immunostimulatory activity of microbial DNA by interacting with Toll-like receptor 9 (TLR9) to activate both the innate and adaptive immune responses in different species. However, few studies have been published to compare the effects of CpG ODN on different pig breeds. Therefore, in this study, whole blood gene expression profiles of DPL and Landrace pigs treated with CpG ODN were studied using RNA-seq technology. Five Hundred differentially expressed genes (DEGs) were identified between the two breeds. DPL pigs had significantly higher number of immune-relevant DEGs than the Landrace pigs after CpG ODN treatment. Pathway analysis showed that cytokine-cytokine receptor interaction and chemokine signaling pathway were the major enriched pathways of the immune-relevant DEGs. Further in vitro experiments showed that PBMCs of the DPL pigs had significantly higher levels of TLR9 mRNA than those of the Landrace pigs, both before and after CpG ODN stimulation. Cytokine and chemokine induction in the PBMCs of both breeds were also measured after CpG ODN stimulation. Our data showed that mRNA levels of cytokines (IFNα, IL8, IL12 p40) and chemokines (CXCL9, CXCL13) were significantly higher in the PBMCs of the DPL pigs than those of the Landrace pigs. Taken together, our data provide new information regarding the pig breed difference in response to CpG ODN stimulation and that higher levels of TLR9 mRNA in DPL pigs may be a major contributor for disease resistance.

  15. Profiles of acute cytokine and antibody responses in patients infected with avian influenza A H7N9.

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    Rui Huang

    Full Text Available The influenza A H7N9 virus outbreak in Eastern China in the spring of 2013 represented a novel, emerging avian influenza transmission to humans. While clinical and microbiological features of H7N9 infection have been reported in the literature, the current study investigated acute cytokine and antibody responses in acute H7N9 infection. Between March 27, 2013 and April 23, 2013, six patients with confirmed H7N9 influenza infection were admitted to Drum Tower Hospital, Nanjing, China. Acute phase serum cytokine profiles were determined using a high-throughput multiplex assay. Daily H7 hemagglutinin (HA-specific IgG, IgM, and IgA responses were monitored by ELISA. Neutralizing antibodies specific for H7N9 viruses were determined against a pseudotyped virus expressing the novel H7 subtype HA antigen. Five cytokines (IL-6, IP-10, IL-10, IFNγ, and TNFα were significantly elevated in H7N9-infected patients when compared to healthy volunteers. Serum H7 HA-specific IgG, as well as IgM and IgA responses, were detected within 8 days of disease onset and increased in a similar pattern during acute infection. Neutralizing antibodies developed shortly after the appearance of binding antibody responses and showed similar kinetics as a fraction of the total H7 HA-specific IgG responses. H7N9 infection resulted in hallmark serum cytokine increases, which correlated with fever and disease persistence. The novel finding of simultaneous development of IgG, IgM, and IgA responses in acute H7N9 infection points to the potential for live influenza viruses to elicit fast and potent protective antibodies to limit the infection.

  16. Assessment of the cytokine profile in peripheral blood mononuclear cells of naturally Sarcoptes scabiei var. canis infested dogs.

    Science.gov (United States)

    Singh, Shanker K; Dimri, Umesh; Sharma, Bhaskar; Saxena, Meeta; Kumari, Priyambada

    2014-12-15

    The mechanism of cytokine secretion from T lymphocytes plays an important role in the immune response of dogs and parasitic skin infestations. Assessment of the cytokine profile of naturally S. scabiei var. canis infested dogs could augment understanding of the pathobiology of canine sarcoptic mange. Therefore, the present study examined the cytokines in peripheral blood mononuclear cells of dogs suffering from sarcoptic mange. Thirteen dogs naturally infected with sarcoptic mange participated in the study. The dogs were found positive for S. scabiei var. canis mites in skin scraping examinations and revealed at least three clinical inclusion criteria. Another five clinically healthy dogs were kept as healthy controls. Peripheral blood mononuclear cells were isolated from heparinized blood samples and used for extraction of mRNA. Further, cDNA was synthesized by using 1 mg of mRNA by reverse transcription using oligonucleotide primers. Relative levels of cytokine expression were compared with normalized glyceraldehyde-3-phosphate dehydrogenase (GAPDH) transcripts. The levels of interleukin-4, interleukin-5 and transforming growth factor beta (TGF-β) mRNA expression in dogs with sarcoptic mange were significantly higher (P ≤ 0.01), whereas the level of tumor necrosis factor alpha (TNF-α) was significantly lower (P ≤ 0.01) in comparison with the healthy dogs. No remarkable difference was seen for interleukin-2 mRNA expression between these animals. An overproduction IL-4 and IL-5 might be involved in immuno-pathogenesis of canine sarcoptic mange. S. scabiei var. canis mites possibly induce an overproduction of TGF-β and reduced expression of TNF-α and thus could be conferring the immune suppression of infested dogs.

  17. CpG Oligodeoxynucleotides Induce Differential Cytokine and Chemokine Gene Expression Profiles in Dapulian and Landrace Pigs

    Directory of Open Access Journals (Sweden)

    Jiaqing Hu

    2016-12-01

    Full Text Available Oligodeoxynucleotides containing unmethylated CpG motifs (CpG ODN mimic the immunostimulatory activity of microbial DNA by interacting with Toll-like receptor 9 (TLR9 to activate both the innate and adaptive immune responses in different species. However, few studies have been published to compare the effects of CpG ODN on different pig breeds. Therefore, in this study, whole blood gene expression profiles of DPL and Landrace pigs treated with CpG ODN were studied using RNA-seq technology. 500 differentially expressed genes (DEGs were identified between the two breeds. DPL pigs had significantly higher number of immune-relevant DEGs than the Landrace pigs after CpG ODN treatment. Pathway analysis showed that cytokine-cytokine receptor interaction and chemokine signaling pathway were the major enriched pathways of the immune-relevant DEGs. Further in vitro experiments showed that PBMCs of the DPL pigs had significantly higher levels of TLR9 mRNA than those of the Landrace pigs, both before and after CpG ODN stimulation. Cytokine and chemokine induction in the PBMCs of both breeds were also measured after CpG ODN stimulation. Our data showed that mRNA levels of cytokines (IFNα, IL8, IL12 p40 and chemokines (CXCL9, CXCL13 were significantly higher in the PBMCs of the DPL pigs than those of the Landrace pigs. Taken together, our data provide new information regarding the pig breed difference in response to CpG ODN stimulation and that higher levels of TLR9 mRNA in DPL pigs may be a major contributor for disease resistance.

  18. Antibody array-generated profiles of cytokine release from THP-1 leukemic monocytes exposed to different amphotericin B formulations.

    Science.gov (United States)

    Turtinen, Lloyd W; Prall, David N; Bremer, Lindsay A; Nauss, Rachel E; Hartsel, Scott C

    2004-02-01

    Cytokine antibody arrays were used to establish the profiles of cytokine release from THP-1 monocytes exposed to different amphotericin B (AMB) drug delivery systems. Fungizone (FZ) and Amphotec (ABCD) caused the release of significantly more inflammatory molecules and the release of inflammatory molecules at higher levels than either AmBisome (L-AMB) or Abelcet (ABLC) after 6 h of treatment. Specifically, tumor necrosis factor alpha (TNF-alpha), interleukin-8 (IL-8), GRO-(alphabetagamma), monocyte chemoattractant protein-1 (MCP-1), RANTES, IL-10, and IL-6 were detected and semiquantified with a chemiluminscence imaging system. TNF-alpha, IL-8, and MCP-1 were the most predominant; however, little if any TNF-alpha was present in ABLC- or L-AMB-treated cultures. The TNF- alpha and IL-8 levels determined by quantitative enzyme-linked immunosorbent assay correlated with the relative cytokine levels measured by using the antibody arrays. Although the viabilities of THP-l monocytes in all AMB-treated cultures were similar by trypan blue exclusion, the amount of lactic dehydrogenase released was significantly larger in FZ- and ABCD-treated cultures than in L-AMB- and ABLC-treated cultures, indicating more membrane perturbations with those formulations. Membrane cation channel formation was also measured in model cholesterol-containing large unilamellar vesicles to directly assess the ion channel formation ability of the system. Only FZ and ABCD induced significant ion currents at concentrations less than 1.5 x 10(-5) M. These results may help provide rationales for the immediate cytokine-mediated side effects observed with FZ and ABCD and the reduced side effects observed with L-AMB and ABLC.

  19. Cerebrospinal fluid and serum cytokine profiling to detect immune control of infectious and inflammatory neurological and psychiatric diseases.

    Science.gov (United States)

    Maxeiner, Horst-Guenter; Marion Schneider, E; Kurfiss, Sina-Tatjana; Brettschneider, Johannes; Tumani, Hayrettin; Bechter, Karl

    2014-09-01

    The present study aimed at profiling inflammatory cytokines for neurological and psychiatric diseases. A total of 86 patients with meningitis, multiple sclerosis, tension-type headache, idiopathic facial nerve palsy (IFNP), affective and schizophrenic disorders were tested for both, serum and cerebrospinal fluid (CSF) using a multiplexed cytokine ELISA for IFN-γ, TNF-α, IL-1β, IL-2, IL-4, IL-5, IL-8/CXCL8, IL-10, IL12p70, IL-13 and IL-17. Cases with viral and bacterial meningitis had unequivocally higher cytokine concentrations in the CSF when compared with serum. Bacterial meningitis was unique by extremely elevated IL-17, TNF-α and IL-1β, indicating a plethora of inflammatory pathways, selectively activated in the CSF. In relapsing multiple sclerosis, IFN-γ and IL-10 were elevated in both, serum and CSF, but IL-12p70, IL-5, IL-13, and TNF-α were more prominent in serum than in CSF. Qualitatively similar biomarker patterns were detected in patients with idiopathic facial nerve palsy and tension-type cephalgia. Affective and schizophrenic disorders clearly present with an inflammatory phenotype in the CSF and also serum, the cytokines determined were in general higher in schizophrenia. Except IFN-γ, schizophrenic patients had higher IL-12p70 and a trend of higher IL-10 and IL-13 in serum suggesting a more prominent TH2-type counter regulatory immune response than in affective disorders. These differences were also mirrored in the CSF. Elevated IL-8 appears to be the most sensitive marker for inflammation in the CSF of all diseases studied, whereas TNF-α was restricted to peripheral blood. With the exception of IL-8, all but viral and bacterial meningitis, studied, displayed higher means of elevated lymphokine concentrations in the serum than in the CSF. This observation supports the concept of immunological crosstalk between periphery and intrathecal immunity in neurological and psychiatric diseases.

  20. Multiplex cytokine profiling with highly pathogenic material: use of formalin solution in luminex analysis.

    Science.gov (United States)

    Dowall, Stuart D; Graham, Victoria A; Tipton, Thomas R W; Hewson, Roger

    2009-08-31

    Work with highly pathogenic material mandates the use of biological containment facilities, involving microbiological safety cabinets and specialist laboratory engineering structures typified by containment level 3 (CL3) and CL4 laboratories. Consequences of working in high containment are the practical difficulties associated with containing specialist assays and equipment often essential for experimental analyses. In an era of increased interest in biodefence pathogens and emerging diseases, immunological analysis has developed rapidly alongside traditional techniques in virology and molecular biology. For example, in order to maximise the use of small sample volumes, multiplexing has become a more popular and widespread approach to quantify multiple analytes simultaneously, such as cytokines and chemokines. The luminex microsphere system allows for the detection of many cytokines and chemokines in a single sample, but the detection method of using aligned lasers and fluidics means that samples often have to be analysed in low containment facilities. In order to perform cytokine analysis in materials from high containment (CL3 and CL4 laboratories), we have developed an appropriate inactivation methodology after staining steps, which although results in a reduction of median fluorescent intensity, produces statistically comparable outcomes when judged against non-inactivated samples. This methodology thus extends the use of luminex technology for material that contains highly pathogenic biological agents.

  1. Detection of intracytoplasmic Th1/Th2 cytokine profiles in patients with sepsis and severe sepsis

    Directory of Open Access Journals (Sweden)

    Ahmadinejad Z

    2007-06-01

    Full Text Available Background: Sepsis is the leading cause of death in critically ill patients throughout the world. The incidence is increasing despite the major advances in the development of antimicrobial agents and other supportive treatments. Based on multiple studies, it has been shown that patient outcome depends on Th1 and Th2 cytokine response. Moreover, whenever the Th2 response is predominant, the sepsis is more severe. The aim of this study was to evaluate the correlation between cytokine levels and the severity of sepsis in patients. Methods: A cross-sectional study on the cellular levels of several pro-inflammatory cytokines was carried out in patients with sepsis and severe sepsis. The study included 37 patients (24 men and 13 women, 26 of them had sepsis and 11 had the severe form of sepsis Thirty-seven healthy volunteers served as controls. The average age of the patients was 57 years (±23.3 years, with a range of 21 to 92 years. From the whole blood of the subjects, we separated the monocytes and leukocytes, which were then cultured. Using an ELISA method, we measured levels of IFN- and IL-12 (associated with Th1, and IL-4 and IL-10 (associated with Th2 in the cultured cells with and without cell stimulation. Results: No correlation was found for IFN- production in the cells of patients with sepsis and severe sepsis, regardless of whether the patients had died or survived. However, IL-12 levels were significantly decreased in severe sepsis compared with those of sepsis patients (P=0.048. Furthermore, the cells of expired patients also had significantly decreased IL-12 levels compared with those of surviving patients (P=0.028. We also found that the levels of IFN-, IL-4, and IL-10 were decreased in patients compared with those of controls, which correlated to their production. However, there was no correlation for IL-12 production between the cells of the patients compared with those of the controls. There was also no correlation for

  2. Polymorphisms within the IL-1 gene cluster: effects on cytokine profiles in peripheral blood and whole blood cell cultures of patients with aggressive periodontitis, juvenile idiopathic arthritis, and rheumatoid arthritis

    DEFF Research Database (Denmark)

    Poulsen, Anne Havemose; Sørensen, Lars Korsbaek; Bendtzen, Klaus

    2007-01-01

    Genetic polymorphisms of cytokines have been associated with the susceptibility, severity, and clinical outcome of inflammatory diseases, such as periodontitis and chronic arthritis. An important question to address is how interleukin (IL)-1 polymorphisms affect the cytokine profiles of patients...

  3. Effects of Shewanella putrefaciens on innate immunity and cytokine expression profile upon high stocking density of gilthead seabream specimens.

    Science.gov (United States)

    Cordero, Héctor; Morcillo, Patricia; Meseguer, José; Cuesta, Alberto; Esteban, M Ángeles

    2016-04-01

    High stocking density increases the number of emerging diseases triggering economic losses worldwide. Probiotics provide an effective and natural solution for preventing some diseases through an improvement of innate immune system among others. In the present work dietary administration of the probiotic Shewanella putrefaciens (known as Pdp11) was evaluated under stress by high stocking density after 2 and 4 weeks of administration to gilthead seabream (Sparus aurata) specimens. Results showed an increase in cellular peroxidase and respiratory burst activity as well as a modulation of cytokine profile when Pdp11 was administered to fish reared at high stocking density. Overall, our results showed how Pdp11 is not only able to improve to some extent the cellular and humoral immunity but also to increase the gene expression profile of pro-inflammatory cytokines such as il1b or il6 in response to high stocking density in gilthead seabream. These findings may support the potential use of this probiotic as functional feed against stress in fish farms. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. [Comparative estimation of cytokine profile among patients with exogenous allergic and idiopathic fibrosing alveolitis].

    Science.gov (United States)

    Makhmudova, S Iu

    2009-05-01

    To study some indicators of cytokine status among the patients with pneumonia alveolitis 89 patients have been examined. 60 of those patients suffer from exogenous allergic alveolitis (EAA) and - 60 from idiopathic fibrosing alveolitis (IFA). The average age is 36.4+/-3.0. The patients were devided into three groups: I group - 21 (23.6%) patients with acute disease, II group - 25 (28.1%) patients with subacute disease, III group - 43 (48.3%) patients with chronic disease. The level of IL-1beta and IL-8 in blood serum and bronchoalveolar wash-out (BWO) measured by IFA test system. It is identified that the contents of IL-1beta in blood serum of EAA patients exceeded on 7.2%, the contents of IL-8 exceeded on 14.6% among IFA patients - reliable rise IL-1beta on 35.4% (<0.05) and IL-8 on 31.6% (<0.05). The level of proinflammatory cytokines (IL-1beta and IL-8) in peripheric blood corresponded with the level of disease. Along with progressing of disease the contents of cytokine in respiratory space, too high, increased among 21 patients with acute disease, in 13 cases (61.9%) BWO was high in IL-1beta and in 80.8% cases of IL-8. in II group among 25 patients with subacute disease high level of IL-1beta marked in 56.0%, Il-8 in 84% cases; patients in III group high concentration of IL-1beta registered in 51.2%; Il-8 in 81.4% of patients.

  5. Altered profile of regulatory T cells and associated cytokines in mild and moderate dengue.

    Science.gov (United States)

    Tillu, H; Tripathy, A S; Reshmi, P V; Cecilia, D

    2016-03-01

    The pathogenesis of dengue is immune-mediated. Regulatory T cells suppress immune response and may contribute to better prognosis. The present study evaluates Tregs and cytokines in dengue patients in the context of disease severity, time of sampling and immune status. The cohort included 90 patients (51 mild, 39 moderate) and 27 healthy controls. Frequencies of Tregs, CD4(+)CD25(-)Foxp3(+) T cells and CD3(+), CD3(+)CD4(+) and CD3(+)CD8(+) T cells were enumerated by flow cytometry. Circulating levels of 15 cytokines/chemokines were measured using Luminex technology and mRNA levels of Foxp3, IL-10 and TGF-β were assessed by real-time polymerase chain reaction (PCR). Significantly higher frequencies of Tregs were observed in mild cases, especially during post-defervescence. The difference between mild and moderate cases was more evident in secondary infections. Frequencies of T cells were higher in mild cases but during pre-defervescence. On the other hand, the levels of IL-6, IL-7, IL-8, TNF-α and IL-10 were significantly higher in moderate cases. IL-6 and IL-8 levels correlated negatively with Treg frequencies during post-defervescence and in secondary infections. Higher levels of IL-10 and TGF-β in moderate cases were not reflected by their corresponding mRNA levels. Platelet counts correlated positively with Treg frequencies and TGF-β levels, and negatively with IL-10 levels. Higher Treg frequencies may favour a beneficial outcome in dengue. Higher cytokine levels may indirectly contribute to disease severity by exerting an inhibitory influence on Tregs. The dichotomy between mRNA and proteins levels for IL-10 and TGF-β is suggestive of increased translational efficiency.

  6. Cytokine Profiles in Adult Mink Infected with Aleutian Mink Disease Parvovirus

    Science.gov (United States)

    Jensen, P. V.; Castelruiz, Y.; Aasted, B.

    2003-01-01

    The aim of this study was to examine the levels of gamma interferon (IFN-γ)-, interleukin 4 (IL-4)-, and IL-8-producing cells in peripheral blood mononuclear cells from mink infected with the Aleutian mink disease parvovirus (ADV). As expected, ADV-infected mink developed high plasma gamma globulin values (hypergammaglobulinemia) and enhanced quantities of CD8-positive (CD8+) cells in the blood during the infection. We quantified the percentages of IFN-γ- and IL-4-positive lymphocytes and IL-8-positive monocytes up to week 38 after virus challenge. The results clearly indicated marked increases in the percentages of IFN-γ- and IL-4-producing lymphocytes during ADV infection. The total number of IL-8-producing monocytes in the blood of ADV-infected mink stayed fairly constant during the infection. In order to characterize the phenotype of the cytokine-producing cells, we performed double-labeling fluorescence-activated cell sorter (FACS) experiments with CD8 surface labeling in one channel and cytokine intracellular staining in the other. We found that most IFN-γ and IL-4 in ADV-infected mink was produced by CD8+ cells, while in the uninfected mink, these cytokines were primarily produced by a cell type that was not CD8 (possibly CD4-positive cells). We also observed that IL-8 was almost exclusively produced by monocytes. All of the above findings led us to conclude that both Th1- and Th2-driven immune functions are found in mink plasmacytosis. PMID:12805443

  7. Cervical Microbiome and Cytokine Profile at Various Stages of Cervical Cancer: A Pilot Study

    Science.gov (United States)

    Bahena-Román, Margarita; Téllez-Sosa, Juan; Martínez-Barnetche, Jesús; Cortina-Ceballos, Bernardo; López-Estrada, Guillermina; Delgado-Romero, Karina; Burguete-García, Ana I.; Cantú, David; García-Carrancá, Alejandro; Madrid-Marina, Vicente

    2016-01-01

    Cervical cancer (CC) is caused by high-risk human papillomavirus persistence due to the immunosuppressive tumor microenvironment mediated by cytokines. Vaginal microbiota determines the presence of certain cytokines locally. We assessed the association between cervical microbiota diversity and the histopathological diagnosis of each stage of CC, and we evaluated mRNA cervical expression levels of IL-4, IL-6, IL-10, TGF-β1, TNF-α and IFN-γ across the histopathological diagnosis and specific bacterial clusters. We determined the cervical microbiota by high throughput sequencing of 16S rDNA amplicons and classified it in community state types (CST). Mean difference analyses between alpha-diversity and histopathological diagnosis were carried out, as well as a β-diversity analysis within the histological diagnosis. Cervical cytokine mRNA expression was analyzed across the CSTs and the histopathological diagnoses. We found a significant difference in microbiota's diversity in NCL-HPV negative women vs those with squamous intraepithelial lesions (SIL) and CC(p = 0.006, p = 0.036).When β-diversity was evaluated, the CC samples showed the highest variation within groups (pbacteria in women with normal cytology were L. crispatus and L. iners, whereas for SIL, it was Sneathia spp. and for CC, Fusobacterium spp. We found higher median cervical levels of IL-4 and TGF-β1 mRNA in the CST dominated by Fusobacterium spp. These results suggest that the cervical microbiota may be implicated in cervical cancer pathology. Further cohort studies are needed to validate these findings. PMID:27115350

  8. Chemical profiling with cytokine stimulating investigations of Sutherlandia frutescens L.R. (Br.) (Fabaceae)

    CSIR Research Space (South Africa)

    Faleschini, MT

    2013-03-01

    Full Text Available the co-stimulation of PMA (represented by odd numbers in Figure 5 a and b). When PMA (number 2 in Figure 5 a and b) was added to the cell culture system alone, there was a higher production of IL8 (4551.95 ? 410.85 pg/ml) and an improvement... a and b), contributed to a marked increased release of the TNF and IL8 cytokines (229.45 ? 13.89 for TNF and 5967.93 ? 226.86 pg/ml for IL8). The aqueous extracts and fractions I and II, together with PMA, displayed a marked decrease of IL8 being...

  9. Lymphocyte subsets, dendritic cells and cytokine profiles in mice with melanoma treated with Uncaria tomentosa

    OpenAIRE

    Lozada-Requena, Iván; Laboratorio de Inmunología. Departamento de Ciencias Celulares y Moleculares. Facultad de Ciencias y Filosofía. Universidad Peruana Cayetano Heredia. Lima, Perú. EMINDES SAC (empresa de investigación y desarrollo en cáncer). Lima, Perú.; Núñez, César; Laboratorio de Inmunología. Departamento de Ciencias Celulares y Moleculares. Facultad de Ciencias y Filosofía. Universidad Peruana Cayetano Heredia. Lima, Perú. EMINDES SAC (empresa de investigación y desarrollo en cáncer). Lima, Perú.; Alvárez, Yubell; Laboratorio de Inmunología. Departamento de Ciencias Celulares y Moleculares. Facultad de Ciencias y Filosofía. Universidad Peruana Cayetano Heredia. Lima, Perú.; Kahn, Laura; Laboratorio de Inmunología. Departamento de Ciencias Celulares y Moleculares. Facultad de Ciencias y Filosofía. Universidad Peruana Cayetano Heredia. Lima, Perú.; Aguilar, José; Laboratorio de Inmunología. Departamento de Ciencias Celulares y Moleculares. Facultad de Ciencias y Filosofía. Universidad Peruana Cayetano Heredia. Lima, Perú.

    2015-01-01

    Objectives. To evaluate the immunomodulatory effect on lymphocyte subsets, dendritic cells (DC), Th1 / Th2 / Th17 and inflammatory cytokines on systemic level and/or in the tumor microenvironment of mice with or without melanoma. Materials and methods: Peripheral blood and/or primary tumors samples were obtained of mice with B16 melanoma treated or not with a hydroalcoholic extract of Uncaria tomentosa (UT) with 5.03% of pentacyclic oxindole alkaloids (UT-POA) obtained from the bark of the pl...

  10. Cytokine profile in Egyptian hepatitis C virus genotype-4 in relation to liver disease progression

    Institute of Scientific and Technical Information of China (English)

    Abdel-Rahman N Zekri; Mohammed S El-Din Ashour; Ahmed Hassan; Hanaa M Alam El-Din; Amal MR El-Shehaby; Maha A Abu-Shady

    2005-01-01

    AIM: To observe the imbalance between T helper cell Th1 and Th2 cytokines in several chronic hepatitis disease at different stages of disease progression.METHODS: We measured the cytokine levels of Th1 (IL-2 and IL-2R), Th2 (IL-10) and the pro-inflammatory cytokines (IL-6 and IL-6R and TNF and TNF-RⅠ and Ⅱ)by the ELISA technique in the sera of 33 hepatocellular carcinoma (HCC) patients and 20 chronic liver disease (CLD) patients. In addition, 20 asymptomatic hepatitis C virus carriers and 20 healthy subjects negative for hepatitis C virus(HCV) markers served as controls.RESULTS: Anti-HCV antibodies were found to be positive in 94% of HCC cases and 75% of CLD cases.On the other hand, HCV viremia was detected using RTPCR in 67% of HCC cases and 65% of CLD cases. HBsAg was positive in 9% of HCC cases and 30% of CLD cases.Also bilharzial-Ab was positive in 55% of HCC cases,65% of CLD cases and in 70% of asymptomatic carriers (ASC). HCC patients had significantly higher values of IL-2R, TNF-RⅡ (P<0.001), and TNF-RⅠ (P>0.05), but lower TNFα (P<0.001) and IL-6 (P = 0.032) in comparison to ASC. But, in comparison to non-cancer controls, HCC patients had higher values of IL-2R, IL-6R, TNF-RⅠ and TNF-RⅡ, but lower TNF-α (P<0.001). CLD patients had higher IL-2R, TNF-RⅠ, and TNF-RⅡ (P<0.001) than ASC. But, in comparison to non-cancer controls, CLD patients had higher values of IL-2R, TNF-RⅠ and TNF-RⅡ, but lower TNF-α (P<0.001). IL-10 was higher (though not significantly) in HCC and CLD patients than in symptomatic carriers and non-cancer controls.CONCLUSION: Liver disease progression from CLD to HCC due to HCV genotype-4 infection is associated with an imbalance between Th1 and Th2 cytokines. IL-2R,TNF-RⅠ, and TNF-RⅡ could be used as potential markers.

  11. A unique protein profile of peripheral neutrophils from COPD patients does not reflect cytokine-induced protein profiles of neutrophils in vitro

    Directory of Open Access Journals (Sweden)

    Koenderman Leo

    2011-09-01

    Full Text Available Abstract Background Inflammation, both local and systemic, is a hallmark of chronic obstructive pulmonary disease (COPD. Inflammatory mediators such as TNFα and GM-CSF are secreted by lung epithelium, alveolar macrophages and other inflammatory cells and are thought to be important contributors in the pathogenesis of COPD. Indeed, neutrophils are activated by these cytokines and these cells are one of the major inflammatory cell types recruited to the pulmonary compartment of COPD patients. Furthermore, these inflammatory mediators are found in the peripheral blood of COPD patients and, therefore, we hypothesized that TNFα/GM-CSF-induced protein profiles can be found in peripheral neutrophils of COPD patients. Methods Using fluorescence 2-dimensional difference gel electrophoresis we investigated differentially regulated proteins in peripheral neutrophils from COPD patients and healthy age-matched control subjects. Furthermore, protein profiles from COPD patients were compared with those of neutrophils of healthy age-matched controls that were stimulated with TNFα and/or GM-CSF in vitro. Protein gels were compared using DeCyder 7.0 software. Results We identified 7 significantly regulated protein spots between peripheral neutrophils from COPD patients and age-matched healthy control subjects. Stimulation of peripheral neutrophils with TNFα, GM-CSF or TNFα + GM-CSF in vitro resulted in 13, 20 and 22 regulated protein spots, respectively. However, these cytokine-induced protein differences did not correspond with the protein differences found in neutrophils from COPD patients. Conclusion These results show that neutrophils from COPD patients have a unique protein profile compared to neutrophils from healthy age-matched controls. Furthermore, the neutrophil profiles of COPD patients do not reflect putative dominant signals induced by TNFα, GM-CSF or their combination. Our results indicate that systemic neutrophil responses in COPD patients

  12. Structural and topographic dynamics of pulmonary histopathology and local cytokine profiles in Paracoccidioides brasiliensis conidia-infected mice.

    Directory of Open Access Journals (Sweden)

    Damaris Lopera

    2011-07-01

    Full Text Available BACKGROUND: Paracoccidioidomycosis (PCM, an endemic systemic mycosis caused by the fungus Paracoccidioides brasiliensis (Pb, usually results in severe lung damage in patients. METHODS AND FINDINGS: Considering the difficulties to sequentially study the infection in humans, this work was done in mice inoculated intranasally with infective Pb-conidia. Lungs of control and Pb-infected mice were studied after 2-hours, 4, 8, 12 and 16-weeks post-infection (p.i in order to define histopathologic patterns of pulmonary lesions, multiplex-cytokine profiles and their dynamics during the course of this mycosis. Besides the nodular/granulomatous lesions previously informed, results revealed additional non-formerly described lung abnormalities, such as periarterial sheath inflammation and pseudotumoral masses. The following chronologic stages occurring during the course of the experimental infection were defined: Stage one (2-hours p.i: mild septal infiltration composed by neutrophils and macrophages accompanied by an intense "cytokine burst" represented by significant increases in IL-1α, IL-1β, IL-4, IL-5, IL-6, IL-10, IL12p70, IL-13, IL-17, Eotaxin, G-CSF, MCP1, MIP1α, GM-CSF, IFN-γ, MIP1β and TNFα levels. Stage two (4-weeks p.i: presence of nodules, evidence of incipient periarterial- and intense but disperse parenchymal- inflammation, abnormalities that continued to be accompanied by hyper-secretion of those cytokines and chemokines mentioned in the first stage of infection. Stages three and four (8 and 12-weeks p.i.: fungal proliferation, inflammation and collagenesis reached their highest intensity with particular involvement of the periarterial space. Paradoxically, lung cytokines and chemokines were down-regulated with significant decreases in IL-2,IL-3,IL-5,IL-9,IL-13,IL-15,GM-CSF,IFN-γ,MIP1β and TNFα. Stage five (16-weeks p.i.: inflammation decreased becoming limited to the pseudotumoral masses and was accompanied by a "silent" cytokine

  13. Structural and Topographic Dynamics of Pulmonary Histopathology and Local Cytokine Profiles in Paracoccidioides brasiliensis Conidia-Infected Mice

    Science.gov (United States)

    Cruz, Oswaldo G.; Restrepo, Angela; Cano, Luz Elena; Lenzi, Henrique Leonel

    2011-01-01

    Background Paracoccidioidomycosis (PCM), an endemic systemic mycosis caused by the fungus Paracoccidioides brasiliensis (Pb), usually results in severe lung damage in patients. Methods and Findings Considering the difficulties to sequentially study the infection in humans, this work was done in mice inoculated intranasally with infective Pb-conidia. Lungs of control and Pb-infected mice were studied after 2-hours, 4, 8, 12 and 16-weeks post-infection (p.i) in order to define histopathologic patterns of pulmonary lesions, multiplex-cytokine profiles and their dynamics during the course of this mycosis. Besides the nodular/granulomatous lesions previously informed, results revealed additional non-formerly described lung abnormalities, such as periarterial sheath inflammation and pseudotumoral masses. The following chronologic stages occurring during the course of the experimental infection were defined: Stage one (2-hours p.i): mild septal infiltration composed by neutrophils and macrophages accompanied by an intense “cytokine burst” represented by significant increases in IL-1α, IL-1β, IL-4, IL-5, IL-6, IL-10, IL12p70, IL-13, IL-17, Eotaxin, G-CSF, MCP1, MIP1α, GM-CSF, IFN-γ, MIP1β and TNFα levels. Stage two (4-weeks p.i): presence of nodules, evidence of incipient periarterial- and intense but disperse parenchymal- inflammation, abnormalities that continued to be accompanied by hyper-secretion of those cytokines and chemokines mentioned in the first stage of infection. Stages three and four (8 and 12-weeks p.i.): fungal proliferation, inflammation and collagenesis reached their highest intensity with particular involvement of the periarterial space. Paradoxically, lung cytokines and chemokines were down-regulated with significant decreases in IL-2,IL-3,IL-5,IL-9,IL-13,IL-15,GM-CSF,IFN-γ,MIP1β and TNFα. Stage five (16-weeks p.i.): inflammation decreased becoming limited to the pseudotumoral masses and was accompanied by a “silent” cytokine response

  14. Different cytokine profile and eosinophil activation are involved in rhinovirus- and RS virus-induced acute exacerbation of childhood wheezing.

    Science.gov (United States)

    Kato, Masahiko; Tsukagoshi, Hiroyuki; Yoshizumi, Masakazu; Saitoh, Mika; Kozawa, Kunihisa; Yamada, Yoshiyuki; Maruyama, Kenichi; Hayashi, Yasuhide; Kimura, Hirokazu

    2011-02-01

    Because little information is available on eosinophil activation and cytokine response in virus-induced wheezing, we attempted to detect respiratory viruses and measure eosinophil cationic protein (ECP), and 27 types of cytokines/chemokines in both serum and nasal secretions from children with wheezing. This study was an observational, case-control investigation of 267 subjects, who were visited and/or hospitalized with acute respiratory symptoms (with wheezing: men, 115; women, 59; mean/median age, 3.6/3.0 years) or who were visited for regular physical examination and treatment (non-symptomatic wheezing: men, 48; women, 31; mean/median, 5.0/4.7 years), and 14 control subjects (controls: men, 9; women, 5; mean/median, 3.6/3.7 years). We detected viruses in nasal secretions from 174 patients with acute exacerbations of wheezing using antigen detection kits or reverse transcription-polymerase chain reaction, followed by direct DNA sequencing analysis. We measured peripheral eosinophil counts, and serum concentrations of ECP and 27 cytokines/chemokines using a multiplex bead-based assay in patients with wheezing or non-symptomatic wheezing. We also examined nasal ECP and 27 cytokines/chemokines in patients with wheezing. Of 174 samples from wheezing exacerbations, rhinovirus was detected in 59; respiratory syncytial (RS) virus in 44; enterovirus in 17; other viruses in 19; and no viruses in 35. Serum concentrations of ECP, IL-5, IL-6, IL-1ra, and IP-10 were significantly elevated in rhinovirus-induced wheezing compared with non-symptomatic wheezing. Similarly, serum ECP, IL-5, and IP-10 were significantly higher in rhinovirus-induced wheezing than in controls. On the other hand, IL-1ra and IP-10, but not ECP and IL-5 were significantly higher in RS virus-induced wheezing than in controls. Furthermore, only IL-5 was significantly elevated in the rhinovirus group compared with the RS virus group in both serum and nasal secretions. Different cytokine profile and

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

    Directory of Open Access Journals (Sweden)

    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

  16. Placental transfusion: a review

    Science.gov (United States)

    Katheria, A C; Lakshminrusimha, S; Rabe, H; McAdams, R; Mercer, J S

    2017-01-01

    Recently there have been a number of studies and presentations on the importance of providing a placental transfusion to the newborn. Early cord clamping is an avoidable, unphysiologic intervention that prevents the natural process of placental transfusion. However, placental transfusion, although simple in concept, is affected by multiple factors, is not always straightforward to implement, and can be performed using different methods, making this basic procedure important to discuss. Here, we review three placental transfusion techniques: delayed cord clamping, intact umbilical cord milking and cut-umbilical cord milking, and the evidence in term and preterm newborns supporting this practice. We will also review several factors that influence placental transfusion, and discuss perceived risks versus benefits of this procedure. Finally, we will provide key straightforward concepts and implementation strategies to ensure that placental-to-newborn transfusion can become routine practice at any institution. PMID:27654493

  17. Inflammatory cytokine profile and circulating cortisol levels in malnourished children with necrotizing ulcerative gingivitis.

    Science.gov (United States)

    Enwonwu, Cyril O; Phillips, Reshma S; Savage, Kofo O

    2005-09-01

    Necrotizing ulcerative gingivitis (NUG), a periodontal disease traditionally associated with stressful lifestyles in young adults in developed countries, is very prevalent in socioeconomically deprived Nigerian children. Random incident cases (153) of NUG, along with their neighborhood village counterparts of comparable age and without NUG, as control, were recruited for this study. Anthropometric evaluation revealed widespread malnutrition and poor health in both groups of children, with more severe stunting in NUG cases. The poor nutritional status of the village children, with and without NUG, was also confirmed by markedly reduced levels of circulating micronutrients. Compared with the neighborhood children, NUG victims showed significant (p children, as well as some micronutrient deficiencies. The findings suggest that NUG is associated with dysregulated cytokine production, with a complex interplay of elevated levels of pro- and anti-inflammatory mediators. Such changes may serve as the common link between the seemingly unrelated risk conditions (e.g. stressful life styles, smoking, microbial infections, diabetes, malnutrition, alcoholism) traditionally implicated in the genesis of NUG, and all known to promote an increase in the blood level of cortisol, as well as a Th(1) to Th(2) cytokine shift.

  18. Chemo-enzymatic synthesis and in vitro cytokine profiling of tailor-made oligofructosides

    Directory of Open Access Journals (Sweden)

    Homann Arne

    2012-11-01

    Full Text Available Abstract Background It is well known that carbohydrates play fundamental roles in cell signaling and infection processes as well as tumor formation and progression. However, the interaction pathways and cellular receptors targeted by carbohydrates and glycoconjugates remain poorly examined and understood. This lack of research stems, at least to a major part, from accessibility problems of large, branched oligosaccharides. Results To test glycan - cell interactions in vitro, a variety of tailored oligosaccharides was synthesized chemo-enzymatically. Glycosyltransferases from the GRAS organisms Bacillus megaterium (SacB and Aspergillus niger (Suc1 were used in this study. Substrate engineering of these glycosyltransferases generally acting on sucrose leads to the controlled formation of novel tailored di-, tri- and tetrasaccharides. Already industrially used as prebiotics in functional food, the immunogenic potential of novel oligosaccharides was characterized in this study. A differential secretion of CXCL8 and CCL2 was observed upon oligosaccharide co-cultivation with colorectal epithelial Caco-2 cells. Conclusion Pure carbohydrates are able to stimulate a cytokine response in human endothelial cells in vitro. The type and amount of cytokine secretion depends on the type of co-cultivated oligosaccharide.

  19. Bacterial vaginosis in pregnant adolescents: proinflammatory cytokine and bacterial sialidase profile. Cross-sectional study.

    Science.gov (United States)

    Ferreira, Carolina Sanitá Tafner; Marconi, Camila; Parada, Cristina Maria de Lima Garcia; Duarte, Marli Teresinha Cassamassimo; Gonçalves, Ana Paula Oliveira; Rudge, Marilza Vieira Cunha; Silva, Márcia Guimarães da

    2015-01-01

    Bacterial vaginosis occurs frequently in pregnancy and increases susceptibility to sexually transmitted infections (STI). Considering that adolescents are disproportionally affected by STI, the aim of this study was to evaluate the cervicovaginal levels of interleukin (IL)-1 beta, IL-6, IL-8 and bacterial sialidase in pregnant adolescents with bacterial vaginosis. Cross-sectional study at mother and child referral units in Belém, Pará, Brazil. Vaginal samples from 168 pregnant adolescents enrolled were tested for trichomoniasis and candidiasis. Their vaginal microbiota was classified according to the Nugent criteria (1991) as normal, intermediate or bacterial vaginosis. Cervical infection due to Chlamydia trachomatisand Neisseria gonorrhoeae was also assessed. Cytokine and sialidase levels were measured, respectively, using enzyme-linked immunosorbent assays and MUAN conversion in cervicovaginal lavages. Forty-eight adolescents (28.6%) were excluded because they tested positive for some of the infections investigated. The remaining 120 adolescents were grouped according to vaginal flora type: normal (n = 68) or bacterial vaginosis (n = 52). Their cytokine and sialidase levels were compared between the groups using the Mann-Whitney test (P vaginosis had higher levels of IL-1 beta, IL-6 and IL-8 (P vaginosis. Not only IL-1 beta and sialidase levels, but also IL-6 and IL-8 levels are higher in pregnant adolescents with bacterial vaginosis, thus indicating that this condition elicits a more pronounced inflammatory response in this population, which potentially increases vulnerability to STI acquisition.

  20. Cerebrospinal fluid Th1/Th2 cytokine profiles in children with enterovirus 71-associated meningoencephalitis.

    Science.gov (United States)

    Li, Huajun; Li, Shuxian; Zheng, Jianfeng; Cai, Chunyan; Ye, Bin; Yang, Jun; Chen, Zhimin

    2015-03-01

    Enterovirus 71 (EV71) infection can cause severe neurological complications including meningoencephalitis (ME) in some patients with hand, foot and mouth disease (HFMD). However, to date no studies have reported changes in cytokine concentrations and their correlations with clinical variables in patients with ME following EV71 infection. In this study, responses of Th1/Th2 cytokine, including IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ, in cerebrospinal fluid (CSF) from patients with EV71-related HFMD with ME and patients with febrile convulsions (FC) were analyzed using cytometric bead array technology. It was found that CSF IL-6 and IFN-γ concentrations were significantly higher in patients with EV71-related ME than in those with FC. Additionally, both CSF IL-6 and IFN-γ concentrations were correlated with CSF cytology, fever duration and duration of hospital stay. More interestingly, a positive correlation between CSF IL-6 and IFN-γ concentrations was observed. Finally, receiver operating characteristic analysis revealed that when a cutoff value of 9.40 pg/mL was set for IL-6, the sensitivity and specificity were 84.5% and 85.5%, respectively, for discriminating EV71-related ME from FC. In conclusion, IL-6 and IFN-γ may be associated with EV71-induced neuropathology. © 2015 The Societies and Wiley Publishing Asia Pty Ltd.

  1. Cellular responses and cytokine profiles in Ascaris lumbricoides and Trichuris trichiura infected patients.

    Science.gov (United States)

    Geiger, Stefan M; Massara, Cristiano L; Bethony, Jeffrey; Soboslay, Peter T; Carvalho, Omar S; Corrêa-Oliveira, Rodrigo

    2002-01-01

    The impact of intestinal helminth infection, i.e. Ascaris lumbricoides and Trichuris trichiura, on cellular responsiveness and cytokine production was investigated in young adults. Ascaris-specific cellular responsiveness was higher in parasite-free endemic controls than in patients infected with T. trichiura, or A. lumbricoides, or patients co-infected with both parasites. Also, mitogen-induced tumour necrosis factor (TNF)-alpha, interleukin (IL)-12 and interferon (IFN)-gamma secretion by peripheral blood mononuclear cells (PBMC) was higher in negative endemic controls than in infected individuals. Ascaris antigen-specific production of TNF-alpha, IL-12 and IFN-gamma was low in singly Ascaris as well as in co-infected patients, whereas secretion of IL-10 and IL-13 was elevated and similarly high in all patient groups. The detection of Trichuris-specific and Ascaris-specific IgG4 revealed significantly higher serum antibody levels in Trichuris or Ascaris patients when compared to endemic controls (P Trichuris patients with a high parasite load presented reduced cellular reactivity and lower type 1 TNF-alpha, IFN-gamma and IL-12 responses when compared with endemic controls, whereas type 2 IL-10 and IL-13 productions were similar in all groups from the endemic area. The former may support parasite persistence, whereas substantial type 2 cytokine release may promote protective immunity, suggesting an adaptation of the host to control the parasite burden while minimizing immune-mediated host self-damage.

  2. Clinical and cytokine profile evaluation in Northeast Brazilian psoriasis plaque-type patients.

    Science.gov (United States)

    Cardoso, Pablo Ramon Gualberto; Lima, Emerson Vasconcelos de Andrade; Lima, Mariana Modesto de Andrade; Rêgo, Moacyr Jesus Barreto de Melo; Marques, Claudia Diniz Lopes; Pitta, Ivan da Rocha; Duarte, Angela Luzia Branco Pinto; Pitta, Maira Galdino da Rocha

    2016-03-01

    Psoriasis is a common, enigmatic, and recurrent disease. The precise etiology and pathogenesis of psoriasis are still unclear. Psoriasis has been treated as an inflammatory disorder related to an underlying Th1/Th17-dominated immune response. Interleukins are involved in the development of psoriasis lesions through Th-17-associated inflammation. Th1 and Th17 cytokines are found in skin lesions and in the peripheral blood of psoriasis patients. We sought to analyze serum levels of IL-1-β, IL-8, IL-9, IL-27, IL-29, IL-35, IFN-γ, TNF and TGF-β in patients with psoriasis and healthy control volunteers. Blood samples were collected from fifty-three patients with psoriasis and thirty-five healthy controls. Serum cytokines concentrations were determined using an enzyme-linked immunosorbent assay. Serum IL-8, IL-9, IL-27, IL-29 and TNF levels were statistically significant in psoriasis patients. Detectable serum IL-9 levels were found in 47 patients of the 53 in the psoriasis group. Interleukins-8, 27, 29 and TNF levels measured in the serum of psoriasis patients were slightly elevated as compared to healthy controls in a weakly significant way. On the other hand, there were highly significant differences in IL-9 levels between the two groups.

  3. Cytokine profiles linked to fatal outcome in infective prosthetic valve endocarditis.

    Science.gov (United States)

    Bustamante, Juan; Arévalo, Adolfo; Tamayo, Eduardo; Sarria, Cristina; Aguilar-Blanco, Eva M; Heredia, Maria; Almansa, Raquel; Rico, Lucia; Iglesias, Verónica; Bermejo-Martin, Jesús F

    2014-06-01

    Infective endocarditis is a disease normally of bacterial cause which affects the endocardic tissue, specifically the valves (native or prosthetic). It is a serious illness and mortality rates remain high, ranging between 20% and 40%. Previous reports have evidenced the potential role of cytokines in the diagnosis of this disease, but no information is available on their relationship with outcome. We recruited 26 consecutive patients with late prosthetic valve endocarditis requiring surgical treatment according to Duke criteria. Eight cytokines were measured in plasma in the first 24 h following diagnosis by using a Bio-Rad multiplex assay. Levels of IL-6, IL-8 and interferon gamma (IFN-γ) were higher in non survivors. Receiver operating characteristic curve analysis evidenced that IL-6, IL-8 and IFN-γ behaved as good diagnostic tests for identifying those patients with fatal outcome (area under the curve, CI 95%, p): IL-6: [0.81 (0.61-1.00) 0.012]; IL-8 [0.76 (0.56-0.96) 0.035]; IFN-γ [0.79 (0.59-0.99) 0.021]. Levels of IL-6, IL-8 and IFN-γ correlated positively between them, indicating that they are produced as consequence of a simultaneous response to the infection. Our findings support the participation of IL-6, IL-8 and IFN-γ in the events linked to fatal outcome in infective prosthetic valve endocarditis.

  4. Envelope specific T cell responses & cytokine profiles in chikungunya patients hospitalized with different clinical presentations

    Science.gov (United States)

    Tripathy, Anuradha S.; Tandale, Babasaheb V.; Balaji, Saravana S.; Hundekar, Supriya L.; Ramdasi, Ashwini Y.; Arankalle, Vidya A.

    2015-01-01

    Background & objectives: Since the 2006 massive outbreaks, chikungunya (CHIK) is a major public health concern in India. The aim of this study was to assess envelope specific immune responses in patients with chikungunya infection. Methods: This study included 46 hospitalized patients with chikungunya virus infection (encephalitis, n=22, other systemic involvement, OSI, n=12, classical, n=12) and six controls from Ahmedabad city, Gujarat, India. T cell responses and the levels of Th1, pro/ anti-inflammatory cytokines against the CHIK virus envelope antigens were assessed by lymphocyte proliferation assay and by cytometric bead array in flow cytometry, respectively. Results: Lymphoproliferative response was uniform among the patients. Comparisons of cytokines revealed significantly higher levels of interleukin (IL)-4 and IL-5 in encephalitis, OSI and classical patients versus controls. The levels of tumour necrosis factor (TNF)-α were higher in classical patients categories compared to the controls. Interferon (IFN)-γ levels were lower in encephalitis patients versus control. Interpretation & conclusions: Our findings showed recognition of T cell epitopes on the envelope region of chikungunya virus by all patient categories. Lower level of IFN-γ may be associated with the severity of disease in these patients. PMID:25900956

  5. Bacteria and Toll-like receptor and cytokine mRNA expression profiles associated with canine arthritis.

    Science.gov (United States)

    Riggio, Marcello P; Lappin, David F; Bennett, David

    2014-08-15

    The major forms of inflammatory canine arthritis are immune-mediated arthritis (IMA) and septic arthritis (SA), although some cases of cruciate disease (CD) are associated with significant levels of synovitis. In this study, the bacteria associated with canine arthritis were identified and mRNA expression levels of Toll-like receptors (TLRs) and pro-inflammatory cytokines determined. Of the 40 synovial fluid samples analysed, bacteria were isolated from 12 samples by culture (2 CD, 10 SA) and detected in 4 samples (3 CD, 1 SA) using culture-independent methods. Statistically significant increases in TLR2, tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-12 mRNA expression were seen in all disease groups compared to normal controls. All disease groups had decreased mRNA expression of other TLRs compared to normal controls, but this did not reach statistical significance. Synovial fluid cell counts revealed that the highest number and proportion of mononuclear cells and neutrophils were found in the IMA and SA samples, respectively. Age had an effect on the TLR and cytokine mRNA expression profiles: TNF-α (p=0.043) and IL-12 (p=0.025) mRNA expression was increased and TLR4 mRNA expression was reduced (p=0.033) in dogs up to 4 years of age compared to older animals. In the 10 SA samples from which bacteria were isolated, statistically significant increases in TLR2, TLR7, TNF-α and IL-6 mRNA expression were observed. It is concluded that canine arthritis is associated with increased mRNA levels of pro-inflammatory cytokines, which could in some cases be mediated by bacteria through activation of TLR2.

  6. Altered Th17/Treg Ratio in Nasal Polyps With Distinct Cytokine Profile: Association With Patterns of Inflammation and Mucosal Remodeling.

    Science.gov (United States)

    Wu, Dawei; Wang, Jianting; Zhang, Min

    2016-03-01

    Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous disease that can be classified as eosinophilic or noneosinophilic. Nasal polyps can exhibit different types of mucosal inflammation and responses to treatment. Imbalanced ratios of T-helper 17(Th17) and regulatory T (Treg) cells may contribute to the pathogenesis of nasal polyps.This study assessed the frequency of Th17 and Treg cells and related cytokines in patients with nasal polyps and tested for associations with mucosal remodeling.Surgical samples from 12 controls and 33 CRSwNP patients were analyzed histopathologically. The frequency of Th17 and Treg cells in peripheral blood mononuclear cells (PBMCs) and tissues were determined using flow cytometry. Th17 and Treg cells-related cytokines in plasma were measured by Cytometric Bead Array (CBA) multiplex assays and enzyme-linked immunosorbent assays (ELISAs).Eosinophilic CRSwNP (ECRSwNP) patients exhibited robust eosinophilia, whereas non-ECRSwNP patients were characterized by neutrophilia. Compared with non-ECRSwNP, an increased Th17/Treg ratio in ECRSwNP was associated with a less increased frequency of Th17 cells and a more striking reduction of Treg cells. An altered Th17/Treg cell ratio was positively correlated with eosinophilic and neutrophilic infiltration, submucosal basement membrane thickness, and the degree of subepithelial collagen deposition. Compared with non-ECRSwNP, ECRSwNP had higher levels of IL-17A and IL-4, and lower levels of IL-10 and TGF-β1, whereas non-ECRSwNP showed higher levels of IFN-γ and IL-6.Th17/Treg cell imbalance in nasal polyps (both in tissues and PBMCs) with distinct cytokine profile may contribute to different inflammatory patterns (eosinophilic versus neutrophilic inflammation) and corresponding features of mucosal remodeling. Effective strategies can be designed to target a Th17/Treg imbalance to restore immune homeostasis in nasal polyps.

  7. Urinary cytokine profiles according to the site of blockade of the renin-angiotensin system in nephrectomized rats

    Directory of Open Access Journals (Sweden)

    Nilo César do Vale Baracho

    Full Text Available Abstract Introduction: It is still unknown how the pharmacological inhibition of the Renin Angiotensin System (RAS impacts the levels of inflammation and fibrosis biomarkers. Objective: This study sought to evaluate the effect of enalapril, candesartan and aliskiren on urinary levels of cytokines in a model of chronic kidney disease (CKD. Methods: Male Wistar rats were submitted to surgical removal of ¾ of renal parenchyma to induce CKD (¾ nephrectomy, or subjected to sham surgery (control. Animals were then randomized into five groups: Sham surgery receiving vehicle; ¾ Nephrectomy receiving vehicle; ¾ Nephrectomy receiving enalapril (10 mg/kg; ¾ Nephrectomy receiving candesartan (10 mg/kg and ¾ Nephrectomy receiving aliskiren (10 mg/kg. Urine output, water intake, mean arterial pressure (MAP and urinary concentrations of creatinine, urea, albuminuria, Na+, K+, interleukin (IL -1β, IL-6, IL-10 and transforming growth factor beta (TGF-β were measured. Results: Nephrectomy significantly impaired renal function, increased MAP and altered the levels of all evaluated cytokines in urine. Enalapril, candesartan and aliskiren improved renal function and decreased MAP and IL-6 when compared to vehicle-treated nephrectomized group. Candesartan and aliskiren decreased IL-1β, while only candesartan reduced TGF-β and only aliskiren increased IL-10. Conclusion: Enalapril, candesartan and aliskiren presented similar effects on improving renal function and reducing MAP and urinary levels of IL-6 in rats with CKD. On the other hand, cytokine profile differed according to the treatment, suggesting that differential mechanisms were triggered in response to the site of RAS blockade.

  8. Evaluation of Relaxin Blood Profiles of Horses as A Means of Assessing Placental Function in High-Risk Pregnancies And Responsiveness to Therapeutic Strategies

    Science.gov (United States)

    Placental insufficiency is regarded as the primary factor contributing to late-term abortion and perinatal death of foals. Often when problems associated with late-term pregnancy in the horse are manifest the condition is well-advanced and therapeutic intervention may not be effective in rescuing th...

  9. Evaluation of Systemic Relaxin Blood Profiles in Horses as A Means of Assessing Placental Function in High-Risk Pregnancies and Responsiveness to Therapeutic Strategies

    Science.gov (United States)

    Placental insufficiency is regarded as the primary factor contributing to late-term abortion and perinatal death of foals. Often when problems associated with late-term pregnancy in the horse are manifest the condition is well-advanced and therapeutic intervention may not be effective in rescuing th...

  10. Unfavorable cytokine and adhesion molecule profiles during and after pregnancy, in women with gestational diabetes mellitus.

    Science.gov (United States)

    Roca-Rodríguez, María Del Mar; López-Tinoco, Cristina; Fernández-Deudero, Álvaro; Murri, Mora; García-Palacios, María Victoria; García-Valero, María Del Amor; Tinahones, Francisco José; Aguilar-Diosdado, Manuel

    2017-01-01

    Gestational diabetes mellitus is a significant risk factor for metabolic syndrome and cardiovascular disease. To assess the relationships between components of the metabolic syndrome and cytokine and adhesion molecule levels in women with GDM during pregnancy and after delivery. A prospective case-control study on a sample of 126 pregnant women (63 with and 63 without gestational diabetes mellitus). In an intra-subject analysis, 41 women with history of gestational diabetes mellitus and 21 controls were re-assessed in the postpartum period. Clinical data and levels of cytokines and adhesion molecules were recorded during weeks 24-29 of pregnancy and 12 months after delivery. In the postpartum period, there were significantly higher levels of tumor necrosis factor alpha in both cases and controls, and of adiponectin in controls. Cases showed higher leptin levels, with no significant differences during and after pregnancy. No significant differences were seen in adhesion molecules and interleukin-6 between cases and controls during pregnancy and in the postpartum period, but levels of both were higher in cases. During pregnancy and after delivery, adiponectin decreased in cases and increased in controls. Significant positive correlations were seen between adiponectin and fasting blood glucose levels and vascular cell adhesion molecule-1, and also between leptin and tumor necrosis factor alpha levels. The results suggest that increased inflammation and transient hyperglycemia during pregnancy would represent a latent form of metabolic syndrome, with an increased risk for type 2 diabetes mellitus and future cardiovascular disease. Copyright © 2017 SEEN. Publicado por Elsevier España, S.L.U. All rights reserved.

  11. Postoperative changes in serum cytokines profile and nitric oxide levels in patients with cystic echinococcosis

    Directory of Open Access Journals (Sweden)

    Refik M.

    2005-09-01

    Full Text Available The aim of the present study was to examine serum cytokines and nitric oxide (NO levels in patients with cystic echinococcosis (CE. 28 patients with CE were studied and all underwent surgery. Serum levels of tumour necrosis factor-alpha (TNF-α, interleukin IL- 1β, receptor of soluble IL-2R (sIL-2R, IL-6, IL-8, nitrate/nitrite, and C-reactive protein (CRP were determined before and after induction of treatment. Data were compared with those obtained from 28 healthy volunteers. IL-6 was elevated in all CE patients (100%. IL-8 was increased in 11/28 (39.3%. Increased levels of IL-2R and TNF-α were found in a limited number of them particularly those showing cysts in the central area of the liver (5/28, 6/28. IL-1β level was not elevated in any patient except in secondary severe CE. CRP and nitrate/nitrite levels were also increased. A positive correlation between CRP and IL-6 (r = 0.74; p < 0.001 was found confirming the link between inflammation due to CE and activation of monocytes. All patients completely recovered and the levels of the studied parameters reverted to normal levels except one patient in whom severe recurrent disease occurred two years after the first operation. These results suggest that there are different immunoregulatory events and cytokines response during CE and may be in part related to slight monocytosis and in part to Th2 activation. IL-6, NO and CRP were unambiguously involved in the host parasite interaction and therefore may be useful markers in monitoring CE management and evaluating surgical stress.

  12. Bacterial vaginosis in pregnant adolescents: proinflammatory cytokine and bacterial sialidase profile. Cross-sectional study

    Directory of Open Access Journals (Sweden)

    Carolina Sanitá Tafner Ferreira

    Full Text Available ABSTRACT CONTEXT AND OBJECTIVE: Bacterial vaginosis occurs frequently in pregnancy and increases susceptibility to sexually transmitted infections (STI. Considering that adolescents are disproportionally affected by STI, the aim of this study was to evaluate the cervicovaginal levels of interleukin (IL-1 beta, IL-6, IL-8 and bacterial sialidase in pregnant adolescents with bacterial vaginosis. DESIGN AND SETTING: Cross-sectional study at mother and child referral units in Belém, Pará, Brazil. METHODS: Vaginal samples from 168 pregnant adolescents enrolled were tested for trichomoniasis and candidiasis. Their vaginal microbiota was classified according to the Nugent criteria (1991 as normal, intermediate or bacterial vaginosis. Cervical infection due to Chlamydia trachomatisand Neisseria gonorrhoeae was also assessed. Cytokine and sialidase levels were measured, respectively, using enzyme-linked immunosorbent assays and MUAN conversion in cervicovaginal lavages. Forty-eight adolescents (28.6% were excluded because they tested positive for some of the infections investigated. The remaining 120 adolescents were grouped according to vaginal flora type: normal (n = 68 or bacterial vaginosis (n = 52. Their cytokine and sialidase levels were compared between the groups using the Mann-Whitney test (P < 0.05. RESULTS: The pregnant adolescents with bacterial vaginosis had higher levels of IL-1 beta, IL-6 and IL-8 (P < 0.05. Sialidase was solely detected in 35 adolescents (67.2% with bacterial vaginosis. CONCLUSIONS: Not only IL-1 beta and sialidase levels, but also IL-6 and IL-8 levels are higher in pregnant adolescents with bacterial vaginosis, thus indicating that this condition elicits a more pronounced inflammatory response in this population, which potentially increases vulnerability to STI acquisition.

  13. 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.

  14. Cytokine profile in PFAPA syndrome suggests continuous inflammation and reduced anti-inflammatory response.

    Science.gov (United States)

    Stojanov, Silvia; Hoffmann, Florian; Kéry, Anja; Renner, Ellen D; Hartl, Dominik; Lohse, Peter; Huss, Kristina; Fraunberger, Peter; Malley, James D; Zellerer, Stephanie; Albert, Michael H; Belohradsky, Bernd H

    2006-06-01

    PFAPA syndrome is characterized by periodic episodes of high fever, aphthous stomatitis, pharyngitis, and/or cervical adenitis. It is of unknown etiology and manifests usually before 5 years of age. We determined serum and intracellular cytokine levels in six PFAPA patients (4 males, 2 females, mean age 8 years (+/- 1.2 SEM), range 4-13) during the symptom-free period as well as 6-12 hours and 18-24 hours after fever onset. Values were compared to age-matched, healthy controls. Febrile PFAPA attacks led to a significant increase in IL-6 and IFN-gamma serum concentrations compared to symptom-free periods and to controls, with IL-1beta, TNF-alpha and IL-12p70 levels being significantly higher than in controls. Lymphocytic IFN-gamma and CD8+ IL-2 production was consistently significantly elevated compared to healthy children. During the asymptomatic period, serum concentrations of IL-1beta, IL-6, TNF-alpha and IL-12p70 were significantly increased compared to controls. Intracellular TNF-alpha synthesis was not elevated at any time point. Soluble TNFRp55 levels were even lower in between febrile episodes, reaching values comparable to controls during attacks, whereas soluble TNFRp75 levels increased during attacks compared to healthy children. Anti-inflammatory IL-4 in serum was at all times lower in PFAPA patients compared to controls with no difference in levels of intracellular IL-4 and IL-10 or serum IL-10. The observed increase of pro-inflammatory mediators, even between febrile attacks, suggests a dysregulation of the immune response in PFAPA syndrome, with continuous pro-inflammatory cytokine activation and a reduced anti-inflammatory response.

  15. Alteration of cytokine profiles in mice exposed to chronic low-dose ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Suk Chul [Radiation Health Research Institute, Korea Hydro and Nuclear Power Co., Ltd., 388-1, Ssangmun-dong, Dobong-gu, Seoul 132-703 (Korea, Republic of); Lee, Kyung-Mi [Global Research Lab, BAERI Institute, Department of Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul 136-705 (Korea, Republic of); Kang, Yu Mi [Radiation Health Research Institute, Korea Hydro and Nuclear Power Co., Ltd., 388-1, Ssangmun-dong, Dobong-gu, Seoul 132-703 (Korea, Republic of); Kim, Kwanghee [Global Research Lab, BAERI Institute, Department of Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul 136-705 (Korea, Republic of); Kim, Cha Soon; Yang, Kwang Hee; Jin, Young-Woo [Radiation Health Research Institute, Korea Hydro and Nuclear Power Co., Ltd., 388-1, Ssangmun-dong, Dobong-gu, Seoul 132-703 (Korea, Republic of); Kim, Chong Soon [Department of Nuclear Medicine, Haeundae Paik Hospital, Inje University, Busan 612-030 (Korea, Republic of); Kim, Hee Sun, E-mail: hskimdvm@khnp.co.kr [Radiation Health Research Institute, Korea Hydro and Nuclear Power Co., Ltd., 388-1, Ssangmun-dong, Dobong-gu, Seoul 132-703 (Korea, Republic of)

    2010-07-09

    While a high-dose of ionizing radiation is generally harmful and causes damage to living organisms, a low-dose of radiation has been shown to be beneficial in a variety of animal models. To understand the basis for the effect of low-dose radiation in vivo, we examined the cellular and immunological changes evoked in mice exposed to low-dose radiation at very low (0.7 mGy/h) and low (3.95 mGy/h) dose rate for the total dose of 0.2 and 2 Gy, respectively. Mice exposed to low-dose radiation, either at very low- or low-dose rate, demonstrated normal range of body weight and complete blood counts. Likewise, the number and percentage of peripheral lymphocyte populations, CD4{sup +} T, CD8{sup +} T, B, or NK cells, stayed unchanged following irradiation. Nonetheless, the sera from these mice exhibited elevated levels of IL-3, IL-4, leptin, MCP-1, MCP-5, MIP-1{alpha}, thrombopoietin, and VEGF along with slight reduction of IL-12p70, IL-13, IL-17, and IFN-{gamma}. This pattern of cytokine release suggests the stimulation of innate immunity facilitating myeloid differentiation and activation while suppressing pro-inflammatory responses and promoting differentiation of naive T cells into T-helper 2, not T-helper 1, types. Collectively, our data highlight the subtle changes of cytokine milieu by chronic low-dose {gamma}-radiation, which may be associated with the functional benefits observed in various experimental models.

  16. Cytokine Profile in Chronic Periodontitis Patients with and without Obesity: A Systematic Review and Meta-Analysis

    Science.gov (United States)

    Abduljabbar, Tariq; Abu Hassan, Mohamed Ibrahim; Vohra, Fahim

    2016-01-01

    To investigate the cytokine profile as biomarkers in the gingival crevicular fluid (GCF) of chronic periodontitis (CP) patients with and without obesity, MEDLINE/PubMed, EMBASE, ScienceDirect, and SCOPUS databases were combined with handsearching of articles published from 1977 up to May 2016 using relevant MeSH terms. Meta-analyses were conducted separately for each of the cytokines: resistin, adiponectin, TNF-α, leptin, IL-6, IL-8, and IL-1β. Forest plots were produced reporting standardized mean difference of outcomes and 95% confidence intervals. Eleven studies were included. Three studies showed comparable levels of leptin among obese and nonobese patients with CP. Four studies reported comparable levels of interleukin- (IL-) 6 and resistin whereas five studies reported comparable levels of adiponectin. Two studies reported similar levels of CRP in patients with periodontitis with and without obesity. One study showed higher levels of tumor necrosis factor-alpha in obese patients with CP. One study showed higher levels of IL-1β and IL-8 in obese patients with CP. The level of localized periodontal inflammation may have a greater influence on the GCF proinflammatory biomarker levels as compared to systemic obesity. Whether patients having chronic periodontitis with obesity have elevated proinflammatory GCF biomarkers levels compared to nonobese individuals remains debatable. PMID:27795608

  17. Heavy metal mediated innate immune responses of the Indian green frog, Euphlyctis hexadactylus (Anura: Ranidae): Cellular profiles and associated Th1 skewed cytokine response.

    Science.gov (United States)

    Jayawardena, Uthpala A; Ratnasooriya, Wanigasekara D; Wickramasinghe, Deepthi D; Udagama, Preethi V

    2016-10-01

    Immune cell and cytokine profiles in relation to metal exposure though much studied in mammals has not been adequately investigated in amphibians, due mainly to lack of suitable reagents for cytokine profiling in non-model species. However, interspecies cross reactivity of cytokines permitted us to assay levels of IFNγ, TNFα, IL6 and IL10in a common anuran, the Indian green frog (Euphlyctis hexadactylus), exposed to heavy metals (Cd, Cr, Cu, Zn and Pb, at ~5ppm each) under field and laboratory settings in Sri Lanka. Enumeration of immune cells in blood and melanomacrophages in the liver, assay of serum and hepatic cytokines, and Th1/Th2 cytokine polarisation were investigated. Immune cell counts indicated overall immunosuppression with decreasing total WBC and splenocyte counts while neutrophil/lymphocyte ratio increased with metal exposure, indicating metal mediated stress. Serum IL6 levels of metal exposed frogs reported the highest (~9360pg/mL) of all cytokines tested. Significantly elevated IFNγ production (Pfrogs. Th1/Th2 cytokine ratio in both serum and liver tissue homogenates was Th1 skewed due to significantly higher production of pro-inflammatory cytokines, IFNγ in serum and TNFα in the liver (P<0.01).Metal mediated aggregations of melanomacrophages in the liver were positively and significantly (P<0.05) correlated with the hepatic expression of TNFα, IL6 and IL10 activity. Overall, Th1 skewed response may well be due to oxidative stress mediated nuclear factor κ-light chain enhancer of activated B cells (NFκB) which enhances the transcription of pro-inflammatory cytokines. Xenobiotic stress has recently imposed an unprecedented level of threat to wildlife, particularly to sensitive species such as amphibians. Therefore, understanding the interactions between physiological stress and related immune responses is fundamental to conserve these environmental sentinels in the face of emerging eco-challenges.

  18. Cytokine profile of conditioned medium from human tumor cell lines after acute and fractionated doses of gamma radiation and its effect on survival of bystander tumor cells.

    Science.gov (United States)

    Desai, Sejal; Kumar, Amit; Laskar, S; Pandey, B N

    2013-01-01

    Cytokines are known to play pivotal roles in cancer initiation, progression and pathogenesis. Accumulating evidences suggest differences in basal and stress-induced cytokine profiles of cancers with diverse origin. However, a comprehensive investigation characterising the cytokine profile of various tumor types after acute and fractionated doses of gamma-irradiation, and its effect on survival of bystander cells is not well known in literature. In the present study, we have evaluated the cytokine secretion profile of human tumor cell lines (HT1080, U373MG, HT29, A549 and MCF-7) either before (basal) or after acute (2, 6 Gy) and fractionated doses (3×2 Gy) of gamma-irradiation in culture medium obtained from these cells by multiplex bead array/ELISA. Moreover, clonogenic assays were performed to evaluate the effect of conditioned medium (CM) on the survival and growth of respective cells. Based on the screening of 28 analytes, our results showed that the basal profiles of these cell lines varied considerably in terms of the number and magnitude of secreted factors, which was minimum in MCF-7. Interestingly, TNF-α, IL-1β, PDGF-AA, TGF-β1, fractalkine, IL-8, VEGF and GCSF were found in CM of all the cell lines. However, secretion of certain cytokines was cell line-specific. Moreover, CM caused increase in clonogenic survival of respective tumor cells (in the order HT1080>U373MG>HT29>A549>MCF-7), which was correlated with the levels of IL-1β, IL-6, IL-8, GMCSF and VEGF in their CM. After irradiation, the levels of most of the cytokines increased markedly in a dose dependent manner. The fold change in cytokine levels was lower in irradiated conditioned medium (ICM) of tumor cells collected after fractionated than respective acute dose, except in MCF-7. Interestingly, amongst these cell lines, the radiation-induced fold increase in cytokine levels was maximum in ICM of A549 cells. Moreover, bystander A549 cells treated with respective ICM showed dose dependent

  19. Oral supplementation of diabetic mice with propolis restores the proliferation capacity and chemotaxis of B and T lymphocytes towards CCL21 and CXCL12 by modulating the lipid profile, the pro-inflammatory cytokine levels and oxidative stress

    National Research Council Canada - National Science Library

    Al Ghamdi, Ahmad A; Badr, Gamal; Hozzein, Wael N; Allam, Ahmed; Al-Waili, Noori S; Al-Wadaan, Mohammed A; Garraud, Olivier

    2015-01-01

    .... To further elucidate the potential benefits of propolis, the present study investigated the effect of dietary supplementation with propolis on the plasma cytokine profiles, free radical levels, lipid...

  20. Chronic resveratrol intake reverses pro-inflammatory cytokine profile and oxidative DNA damage in ageing hybrid mice.

    Science.gov (United States)

    Wong, Yee Ting; Gruber, Jan; Jenner, Andrew M; Tay, Francis Eng Hock; Ruan, Runsheng

    2011-09-01

    Thymic involution and shrinkage of secondary lymphoid organs are leading causes of the deterioration of the T-cell compartment with age. Inflamm-aging, a sustained inflammatory status, has been associated with chronic diseases and shortened longevity. This is the first study to investigate the effect of treating aging hybrid mice with long-term, low-dose resveratrol (RSV) in drinking water by assessing multiple immunological markers and profiles in the immune system. We found that hybrid mice exhibited marked age-related changes in the CD3+CD4+, C3+CD8+, CD4+CD25+, CD4M and CD8M surface markers. RSV reversed surface phenotypes of old mice to that of young mice by maintaining the CD4+ and CD8+ population in splenocytes as well as reducing CD8+CD44+ (CD8M) cells in the aged. RSV also enhanced the CD4+CD25+ population in old mice. Interestingly, pro-inflammatory status in young mice was transiently elevated by RSV but it consequently mitigated the age-dependent increased pro-inflammatory cytokine profile while preserving the anti-inflammatory cytokine condition in the old mice. Age-dependent increase in 8OHdG, an oxidative DNA damage marker was ameliorated by RSV. Immunological-focused microarray gene expression analysis showed that only the CD72 gene was significantly downregulated in the 12-month RSV-treated mice compared to age-matched controls. Our study indicates that RSV even at low physiological relevant levels is able to affect the immune system without causing marked gene expression changes.

  1. Alteration in lymphocyte responses, cytokine and chemokine profiles in chickens infected with genotype VII and VIII velogenic Newcastle disease virus.

    Science.gov (United States)

    Rasoli, Mehdi; Yeap, Swee Keong; Tan, Sheau Wei; Moeini, Hassan; Ideris, Aini; Bejo, Mohd Hair; Alitheen, Noorjahan Banu Mohamed; Kaiser, Pete; Omar, Abdul Rahman

    2014-01-01

    Newcastle disease (ND) is a highly contagious avian disease and one of the major causes of economic losses in the poultry industry. The emergence of virulent NDV genotypes and repeated outbreaks of NDV in vaccinated chickens have raised the need for fundamental studies on the virus-host interactions. In this study, the profiles of B and T lymphocytes and macrophages and differential expression of 26 immune-related genes in the spleen of specific-pathogen-free (SPF) chickens, infected with either the velogenic genotype VII NDV strain IBS002 or the genotype VIII NDV strain AF2240, were evaluated. A significant reduction in T lymphocyte population and an increase in the infiltration of IgM+ B cells and KUL01+ macrophages were detected in the infected spleens at 1, 3 and 4 days post-infection (dpi) (P<0.05). The gene expression profiles showed an up-regulation of CCLi3, CXCLi1, CXCLi2 (IL-8), IFN-γ, IL-12α, IL-18, IL-1β, IL-6, iNOS, TLR7, MHCI, IL-17F and TNFSF13B (P<0.05). However, these two genotypes showed different cytokine expression patterns and viral load. IBS002 showed higher viral load than AF2240 in spleen at 3 and 4dpi and caused a more rapid up-regulation of CXCLi2, IFN-γ, IL-12α, IL-18, IL-1β, iNOS and IL-10 at 3dpi. Meanwhile, the expression levels of CCLI3, CXCLi1, IFN-γ, IL-12α, IL-1β and iNOS genes were significantly higher in AF2240 at 4dpi. In addition, the expression levels of IL-10 were significantly higher in the IBS002-infected chickens at 3 and 4dpi. Hence, infection with velogenic genotype VII and VIII NDV induced different viral load and production of cytokines and chemokines associated with inflammatory reactions.

  2. Characterization of virus-primed CD8+ T cells with a type 1 cytokine profile

    DEFF Research Database (Denmark)

    Christensen, Jan Pravsgaard; Stenvang, J P; Marker, O

    1996-01-01

    parameters of cell-mediated immunity, splenic T cells appear which are able to release high amounts of IFN- gamma, but not IL-5, IL-10 or tumor necrosis factor-alpha upon short-term stimulation with anti-CD3 in vitro. A similar profile is observed analyzing T cells taken from an inflammatory site...

  3. First Trimester Pregnancy Loss and the Expression of alternatively spliced NKp30 isoforms in Maternal Blood and Placental Tissue

    Directory of Open Access Journals (Sweden)

    Avishai eShemesh

    2015-06-01

    Full Text Available In this study, we aimed to investigate whether first trimester pregnancy loss is associated with differences in expression of NKp30 splice variants (isoforms in maternal peripheral blood or placental tissue. We conducted a prospective case-control study; a total of 33 women undergoing dilation and curettage due to first trimester pregnancy loss were further subdivided into groups with sporadic or recurrent pregnancy loss. The control group was comprised of women undergoing elective termination of pregnancy. The qPCR approach was employed to assess the relative expression of NKp30 isoforms as well as the total expression of NKp30 and NKp46 receptors between the selected groups. Results show that in both PBMC and placental tissue, NKp46 and NKp30 expression was mildly elevated in the pregnancy loss groups compared with the elective group. In particular, NKp46 elevation was significant. Moreover, expression analysis of NKp30 isoforms manifested a different profile between PBMC and the placenta. NKp30-a and NKp30-b isoforms in the placental tissue, but not in PBMC, showed a significant increase in the pregnancy loss groups compared with the elective group. Placental expression of NKp30 activating isoforms -a and -b in the pregnancy loss groups was negatively correlated with PLGF expression. In contrast, placental expression of these isoforms in the elective group was positively correlated with TNFα, IL-10 and VEGF-A expression. The altered expression of NKp30 activating isoforms in placental tissue from patients with pregnancy loss compared to the elective group and the different correlations with cytokine expression point to the involvement of NKp30-mediated function in pregnancy loss.

  4. Cytokine and chemokine profiles of aqueous humor and serum in horses with uveitis measured using multiplex bead immunoassay analysis.

    Science.gov (United States)

    Curto, Elizabeth; Messenger, Kristen M; Salmon, Jacklyn H; Gilger, Brian C

    2016-12-01

    To determine whether horses with clinically diagnosed Equine Recurrent Uveitis (ERU) and those with Leptospirosis infection have a specific cytokine profile in their aqueous humor (AH) and serum that differs from horses with uveitis secondary to other ocular inflammatory processes and from horses with normal eyes. Twenty-five client-owned horses with uveitis that were presented to the North Carolina State University Ophthalmology Service, and four University-owned horses without history or clinical signs of ocular disease. Samples of AH and serum were obtained from horses with ERU (n=13), acute or non-recurrent uveitis (UV; n=7), uveitis secondary to infectious keratitis (IK; n=5), and normal eyes (N; n=4). Cytokine levels in AH and serum were quantified using a multiplex bead immunoassay. Leptospiral antibody titers in serum and AH and PCR for Leptospiral DNA in AH were performed. In the AH of horses with ERU, increased levels of IL-1a, IL-4, IL-6, IL-8, IL-12p70, FGF-2, G-CSF, and RANTES were measured compared to UV, IK and N eyes, but the differences were not significant. However, IL-10 was significantly higher in ERU eyes compared to IK and N (P=0.029; 0.013), and IP-10 in ERU eyes was significantly higher than in UV and N (P=0.004). Furthermore, MCP-1 was significantly higher in ERU than N (P=0.04). In the serum, increased levels of IL-1a, IL-4, IL-6, IL-8, IL-12p70, fractalkine, and G-CSF were measured in horses with ERU, but the levels were not significantly higher than those observed in UV, IK, or N horses. However, serum IP-10 levels in horses with ERU were significantly higher than in UV and N horses (P=0.005) and MCP-1 levels were significantly higher in ERU than N (P=0.03). Horses with marked ocular inflammation had significantly higher serum levels of G-CSF, IL-1a, fractalkine, IL-13, IL-4, IL-17a, IL-12p70, IFN-γ, and MCP-1. Elevated IL-10 in AH was significantly associated with disease chronicity, both overall and in ERU eyes (P=0.049), and in

  5. Sytemic inflammation in cachexia - is tumour cytokine expression profile the culprit?

    Directory of Open Access Journals (Sweden)

    Emidio Marques De Matos-Neto

    2015-12-01

    Full Text Available Cachexia affects about 80 percent of gastrointestinal cancer patients. This multifactorial syndrome resulting in involuntary and continuous weight loss is accompanied by systemic inflammation and immune cell infiltration in various tissues. Understanding the interactions between tumor, immune cells and peripheral tissues could help attenuating systemic inflammation. Therefore, we investigated inflammation in the subcutaneous adipose tissue and in the tumor, in weight stable and cachectic cancer patients with same diagnosis, in order to establish correlations between tumor microenvironment and secretory pattern with adipose tissue and systemic inflammation. Infiltrating monocyte phenotypes of subcutaneous and tumor vascular-stromal fraction were identified by flow cytometry. Gene and protein expression of inflammatory and chemotactic factors was measured with qRT-PCR and Multiplex Magpix® system, respectively. Subcutaneous vascular-stromal fraction exhibited no differences in regard to macrophage subtypes, while in the tumor, the percentage of M2 macrophages was decreased in the cachectic patients, in comparison to weight-stable counterparts. CCL3, CCL4 and IL-1β expression was higher in the adipose tissue and tumor tissue in cachectic group. In both tissues chemotactic factors were positively correlated with IL-1β. Furthermore, positive correlations were found for the content of chemoattractants and cytokines in the tumor and adipose tissue. The results strongly suggest that the crosstalk between the tumor and peripheral tissues is more pronounced in cachectic patients, compared to weight-stable patients with the same tumor diagnosis.

  6. Evolution of cytokine profile during the treatment of cerebral toxoplasmosis in HIV-infected patients.

    Science.gov (United States)

    Meira, Cristina da Silva; Pereira-Chioccola, Vera Lucia; Vidal, José Ernesto; Motoie, Gabriela; Costa-Silva, Thaís Alves da; Gava, Ricardo

    2015-11-01

    This study was to follow IFN-γ, TNF-α and IL-10 modulation of peripheral blood mononuclear cells (PBMC) from HIV/cerebral toxoplasmosis patients (CT) during specific treatment. The results were compared with two other groups: HIV patients that had CT at least one year before (P/CT) and individuals with chronic toxoplasmosis (CHR). Blood samples (63) collected from three groups were analyzed. CT, 15 patients (3 blood samples collected one day before Toxoplasma gondii treatment; 7 and 15days during the treatment). P/CT, 5 patients (one blood sample collected at least, one year after the treatment). CHR, 13 individuals with chronic toxoplasmosis (one blood sample). Cytokine levels were assessed by ELISA after PBMC stimulation with T. gondii antigen. CT patients had low IFN-γ; discrete increase at 7th and 15th days; and the levels were recovered in cured patients (P/CT). CT patients had high TNF-α in the beginning of the treatment. TNF-α levels decrease during the treatment (7th and 15th) and in those patients who were treated (P/CT). IL-10 levels were almost similar in CT and P/CT groups but low when compared with CHR individuals. The evolution of the infection was correlated to restoration of IFN-γ response and a decrease of the inflammation. The evaluation of the immune response can provide valuable information and better monitoring of patients during specific treatment.

  7. Cytokine expression profiles of immune imbalance in post-mononucleosis chronic fatigue

    Directory of Open Access Journals (Sweden)

    Broderick Gordon

    2012-09-01

    Full Text Available Abstract Background As Chronic Fatigue Syndrome (CFS has been known to follow Epstein-Bar virus (EBV and other systemic infections; our objective was to describe differences in immune activation in post-infective CFS (PI-CFS patients and recovered controls. We studied 301 adolescents prospectively over 24 months following the diagnosis of monospot-positive infectious mononucleosis (IM. We found an incidence of CFS at 6, 12 and 24 months of 13%, 7% and 4% respectively. Methods Using chemiluminescent imaging we measured the concentrations of IL-1a, 1b, 2, 4, 5, 6, 8, 10, 12 (p70, 13, 15, 17 and 23, IFN-γ, TNF-α and TNF-β in duplicate plasma samples available in bio-bank from 9 PI-CFS subjects and 12 recovered controls at 24 months post-infection. Results Standard comparative analysis indicated significant differences in IL-8 and 23 across subject groups. In constructing a linear classification model IL-6, 8 and 23 were selected by two different statistical approaches as discriminating features, with IL-1a, IL-2 and IFN-γ also selected in one model or the other. This supported an assignment accuracy of better than 80% at a confidence level of 0.95 into PI-CFS versus recovered controls. Conclusion These results suggest that co-expression patterns in as few as 5 cytokines associated with Th17 function may hold promise as a tool for the diagnosis of post-infectious CFS.

  8. Clinical and echocardiographic features of children with rheumatic heart disease and their serum cytokine profile.

    Science.gov (United States)

    Ali, Sulafa Khalid Mohamed; Eldaim, Inaam Noor; Osman, Samia Hassan; Bakhite, Sahar Mohamed

    2012-01-01

    Acute rheumatic fever (ARF) and rheumatic heart disease (RHD) constitute important public health problems in developing countries. Children with ARF and RHD seen at Children's Hospital-Sudan from May 2008-2009 were examined clinically and by echocardiography. Blood cytokines (interleukin 10 (IL10), Tumor necrosis factor alpha (TNF- alpha) and interferon gamma (IFN-gamma) were done. Thirty six children were enrolled; 63% had established RHD, and 37% ARF. Mitral regurgitation (MR) was the most common lesion (94%).Ninety five percent of the valve lesions were severe. The serum interleukin IL10 level ranged between 3-6 pg/ml. TNF alpha levels were 9- 100 pg/ml in 12 patients (40%), 101-1000 pg/ml in 10 patients (33%), more than 1000 in 8 patients (26%). The level of IFN gamma ranged between 2-7 pg/m in all patients except 2 (84 and 135 pg/ml). RHD is manifested with severe valvular lesions and a high TNF alpha indicating and ongoing inflammation.

  9. DNA Methylation Profiles of Selected Pro-Inflammatory Cytokines in Alzheimer Disease.

    Science.gov (United States)

    Nicolia, Vincenzina; Cavallaro, Rosaria A; López-González, Irene; Maccarrone, Mauro; Scarpa, Sigfrido; Ferrer, Isidre; Fuso, Andrea

    2017-01-01

    By means of functional genomics analysis, we recently described the mRNA expression profiles of various genes involved in the neuroinflammatory response in the brains of subjects with late-onset Alzheimer Disease (LOAD). Some of these genes, namely interleukin (IL)-1β and IL-6, showed distinct expression profiles with peak expression during the first stages of the disease and control-like levels at later stages. IL-1β and IL-6 genes are modulated by DNA methylation in different chronic and degenerative diseases; it is also well known that LOAD may have an epigenetic basis. Indeed, we and others have previously reported gene-specific DNA methylation alterations in LOAD and in related animal models. Based on these data, we studied the DNA methylation profiles, at single cytosine resolution, of IL-1β and IL-6 5'-flanking region by bisulphite modification in the cortex of healthy controls and LOAD patients at 2 different disease stages: Braak I-II/A and Braak V-VI/C. Our analysis provides evidence that neuroinflammation in LOAD is associated with (and possibly mediated by) epigenetic modifications. © 2017 American Association of Neuropathologists, Inc. All rights reserved.

  10. Pro-inflammatory cytokine profile in dairy cows: consequences for new lactation

    Directory of Open Access Journals (Sweden)

    Erminio Trevisi

    2015-07-01

    Full Text Available To verify the potential relevance of proinflammatory cytokine (PIC with periparturient health problems and performances, the changes of plasma interleukin-1beta (IL-1β and interleukin-6 (IL-6 have been investigated in 21 Holstein-Friesian cows from 35 d before to 28 d after parturition. The overall PIC concentration was higher during late pregnancy compared to the first month of lactation, but showed a high variability among the cows. Therefore, cows were retrospectively divided in 3 groups according to the values of area under the concentration curve of IL- 1β concentrations from -35 d before to the day of parturition and designated as up (UPIL1, intermediate (INIL1 and low (LOIL1 IL-1β group. The concentrations of IL-6 and to some extent the concentrations of albumin and reactive oxygen metabolites (ROMs were well related to the grouping based on IL-1β concentrations. After calving the UPIL1 cows showed a more severe acute phase reaction (APR, based on the marked increase of haptoglobin and the lower plasma albumin concentrations during the first week of lactation, and the highest oxidative stress, based on the higher concentrations of ROMs. Moreover, the UPIL1 group showed higher number of mastitis, lower feed intake and milk yield compared with INIL1 and LOIL1. Our results demonstrated that cows with the highest PIC concentrations in the last month of pregnancy showed the worse health status in early lactation (clinical and subclinical problems and a lower milk yield. Thus, these data support the utility of PIC measurement in late pregnancy as prognostic markers for a risky transition period.

  11. The Relationship of Cytokines IL-13 and IL-17 with Autoantibodies Profile in Early Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Isabela Siloşi

    2016-01-01

    Full Text Available Aims. In the present study, we aimed to assess the concentrations of IL-13 and IL-17 in serum of patients with early rheumatoid arthritis (eRA, the investigation of correlation between the concentrations of these cytokines and disease activity score, and the concentration of some autoantibodies and the evaluation of the utility of IL-13 and -17 concentration measurements as markers of disease activity. Materials and Methods. Serum samples were collected from 30 patients and from 28 controls and analysed parameters. Results. The serum concentrations of IL-13, IL-17, anti-CCP, and IgM-RF were statistically significantly higher in patients with eRA, compared to the controls. IL-13 concentrations in the severe and moderate groups with eRA were statistically higher than in the mild and control groups. Also, in the case of IL-17, serum concentrations increased proportionally with the disease activity of eRA. We observe that concentrations of IL-13 and -17 did not correlate with autoantibodies. IL-17 concentration significantly positively correlated with CRP, while IL-13 concentration significantly negatively correlated with CRP. Disease activity score, DAS28, was strongly positively correlated with levels of ESR and weakly positively correlated with concentrations of anti-RA33 autoantibodies. IL-13 has a higher diagnostic utility than IL-17, CRP, ESR, IgM-RF, and anti-CCP as markers of disease activity. Conclusions. The presence of higher IL-13 and IL-17 serum levels in patients, compared with those of controls, confirms that these markers, found with high specificity, might be involved in the pathogenesis of eRA. IL-13 and IL-17 might be of better usefulness in the prediction of eRA activity status than IgM-RF and anti-CCP.

  12. Cytokine profile and clinical metabolic alterations in HIV-1 infected individuals with and without lipodistrophy

    Directory of Open Access Journals (Sweden)

    L. C. R. Pontes-Cardoso

    2007-01-01

    Full Text Available The extensive use of Highly Active Antiretroviral Therapy (HAART has transformed HIV infection into a chronic condition. Thus, metabolic alterations including lipodystrophy and dyslipidemia have been associated with the use of such medications. The objective of the present study was to analyze clinical metabolic alterations and the profile of TNF-alpha, IFN-Y, IL-2, IL-10, and TNF-alpha type II soluble receptor in serum of HIV-1 individuals with and without lipodystrophy. Eighty-four adults were evaluated, 42 males and 42 females, mean age 37 years, and HAART time of at least 15 months. Two groups were formed, G1: 42 individuals with lipodystrophy, and G2: 42 without lipodistropy. From the HAART used, stavudine was more associated with the lipodystrophy group and zidovudine with the non-lipodystrophy group. CD4 and CD8 values, viral load, glucose, albumin, and lipids were not different between groups, except for triglycerides, which were high in the lipodystrophy group, and HDL, whose concentration was reduced in G1. TNF-alpha, TNF-RII, and IL-10 profiles were high and had positive correlation; IL-2 and IFN-gamma had reduced levels in the lipodystrophy group. High TNF-alpha and its receptor levels seem to be associated with lipodystrophy development in individuals under HAART therapy.

  13. 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

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

    Directory of Open Access Journals (Sweden)

    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

  15. Cytokine and C-reactive protein profiles induced by porcine circovirus type 2 experimental infection in 3-week-old piglets

    DEFF Research Database (Denmark)

    Stevenson, L.S.; McCullough, K.; Vincent, I.;

    2006-01-01

    The purpose of this study was to determine serum profiles of cytokines at a protein level and C-reactive protein (CRP) during the development of postweaning multisystemic wasting syndrome (PMWS) in experimentally inoculated pigs. Levels of serum IFN-alpha, IL-6, IL-10, and CRP were examined for a...

  16. Heavy metal mediated innate immune responses of the Indian green frog, Euphlyctis hexadactylus (Anura: Ranidae): Cellular profiles and associated Th1 skewed cytokine response

    Energy Technology Data Exchange (ETDEWEB)

    Jayawardena, Uthpala A.; Ratnasooriya, Wanigasekara D.; Wickramasinghe, Deepthi D.; Udagama, Preethi V., E-mail: dappvr@yahoo.com

    2016-10-01

    Immune cell and cytokine profiles in relation to metal exposure though much studied in mammals has not been adequately investigated in amphibians, due mainly to lack of suitable reagents for cytokine profiling in non-model species. However, interspecies cross reactivity of cytokines permitted us to assay levels of IFNγ, TNFα, IL6 and IL10in a common anuran, the Indian green frog (Euphlyctis hexadactylus), exposed to heavy metals (Cd, Cr, Cu, Zn and Pb, at ~ 5 ppm each) under field and laboratory settings in Sri Lanka. Enumeration of immune cells in blood and melanomacrophages in the liver, assay of serum and hepatic cytokines, and Th1/Th2 cytokine polarisation were investigated. Immune cell counts indicated overall immunosuppression with decreasing total WBC and splenocyte counts while neutrophil/lymphocyte ratio increased with metal exposure, indicating metal mediated stress. Serum IL6 levels of metal exposed frogs reported the highest (~ 9360 pg/mL) of all cytokines tested. Significantly elevated IFNγ production (P < 0.05) was evident in heavy metal exposed frogs. Th1/Th2 cytokine ratio in both serum and liver tissue homogenates was Th1 skewed due to significantly higher production of pro-inflammatory cytokines, IFNγ in serum and TNFα in the liver (P < 0.01).Metal mediated aggregations of melanomacrophages in the liver were positively and significantly (P < 0.05) correlated with the hepatic expression of TNFα, IL6 and IL10 activity. Overall, Th1 skewed response may well be due to oxidative stress mediated nuclear factor κ-light chain enhancer of activated B cells (NFκB) which enhances the transcription of pro-inflammatory cytokines. Xenobiotic stress has recently imposed an unprecedented level of threat to wildlife, particularly to sensitive species such as amphibians. Therefore, understanding the interactions between physiological stress and related immune responses is fundamental to conserve these environmental sentinels in the face of emerging eco

  17. Chronic hepatitis C and persistent occult hepatitis C virus infection are characterized by distinct immune cell cytokine expression profiles.

    Science.gov (United States)

    Pham, T N Q; Mercer, S E; Michalak, T I

    2009-08-01

    Hepatitis C virus (HCV) replicates in immune cells in both chronic hepatitis C (CHC) and occult HCV infection, but the extent of virus replication in this compartment in these opposing infection forms varies greatly. It was unknown whether this could be linked to HCV genotype or to differences in host gene expression shaping the immune response, and whether HCV replication in immune cells is sensitive to endogenous antiviral cytokines. In this study, we uncovered that significantly greater HCV load in peripheral blood mononuclear cells (PBMC), but not in plasma, coincided with HCV genotypes 2 and 3 in CHC, but with genotype 1 in residual occult infection after clinical resolution of hepatitis C. Moreover, PBMC from individuals with occult infection transcribed significantly greater levels of IFN-alpha, IFN-gamma and TNF-alpha, but less interleukin (IL)-10 than those from CHC. In CHC, PBMC with low HCV load expressed significantly more IFN-gamma but less IL-12 than did cells with high virus content. In occult infection, HCV RNA detection in PBMC was associated with much lower IFN-alpha and IL-12 expression. Further, HCV replication in T lymphocytes could be completely eliminated by activation of endogenous IFN-gamma in CHC, but of IFN-alpha in occult infection. In conclusion, CHC and persistent occult HCV infection are characterized by clearly different profiles of antiviral cytokine response in circulating immune cells which are also different from those of healthy individuals. Higher expression of IL-10, combined with lower transcription of IFN-alpha, IFN-gamma and TNF-alpha, is associated with a more robust HCV replication in immune cells.

  18. Differential S1P Receptor Profiles on M1- and M2-Polarized Macrophages Affect Macrophage Cytokine Production and Migration

    Science.gov (United States)

    Müller, Jan; von Bernstorff, Wolfram; Heidecke, Claus-Dieter

    2017-01-01

    Introduction. Macrophages are key players in complex biological processes. In response to environmental signals, macrophages undergo polarization towards a proinflammatory (M1) or anti-inflammatory (M2) phenotype. Sphingosine 1-phosphate (S1P) is a bioactive lysophospholipid that acts via 5 G-protein coupled receptors (S1P1–5) in order to influence a broad spectrum of biological processes. This study assesses S1P receptor expression on macrophages before and after M1 and M2 polarization and performs a comparative analysis of S1P signalling in the two activational states of macrophages. Methods. Bone marrow derived macrophages (BMDM) from C57 BL/6 mice were cultured under either M1- or M2-polarizing conditions. S1P-receptor expression was determined by quantitative RT-PCR. Influence of S1P on macrophage activation, migration, phagocytosis, and cytokine secretion was assessed in vitro. Results. All 5 S1P receptor subclasses were expressed in macrophages. Culture under both M1- and M2-polarizing conditions led to significant downregulation of S1P1. In contrast, M1-polarized macrophages significantly downregulated S1P4. The expression of the remaining three S1P receptors did not change. S1P increased expression of iNOS under M2-polarizing conditions. Furthermore, S1P induced chemotaxis in M1 macrophages and changed cytokine production in M2 macrophages. Phagocytosis was not affected by S1P-signalling. Discussion. The expression of different specific S1P receptor profiles may provide a possibility to selectively influence M1- or M2-polarized macrophages.

  19. Microdialysis Sampling from Wound Fluids Enables Quantitative Assessment of Cytokines, Proteins, and Metabolites Reveals Bone Defect-Specific Molecular Profiles.

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    Yvonne Förster

    Full Text Available Bone healing involves a variety of different cell types and biological processes. Although certain key molecules have been identified, the molecular interactions of the healing progress are not completely understood. Moreover, a clinical routine for predicting the quality of bone healing after a fracture in an early phase is missing. This is mainly due to a lack of techniques to comprehensively screen for cytokines, growth factors and metabolites at their local site of action. Since all soluble molecules of interest are present in the fracture hematoma, its in-depth assessment could reveal potential markers for the monitoring of bone healing. Here, we describe an approach for sampling and quantification of cytokines and metabolites by using microdialysis, combined with solid phase extractions of proteins from wound fluids. By using a control group with an isolated soft tissue wound, we could reveal several bone defect-specific molecular features. In bone defect dialysates the neutrophil chemoattractants CXCL1, CXCL2 and CXCL3 were quantified with either a higher or earlier response compared to dialysate from soft tissue wound. Moreover, by analyzing downstream adaptions of the cells on protein level and focusing on early immune response, several proteins involved in the immune cell migration and activity could be identified to be specific for the bone defect group, e.g. immune modulators, proteases and their corresponding inhibitors. Additionally, the metabolite screening revealed different profiles between the bone defect group and the control group. In summary, we identified potential biomarkers to indicate imbalanced healing progress on all levels of analysis.

  20. Cytokine serum profiles in allergic and non-allergic asthma. Increased production of IL-10 by non-allergic asthmatic patients.

    Science.gov (United States)

    Sánchez-Guerrero, I; Vegara, R P; Herrero, N; García-Alonso, A M; Luna, A; Alvarez, M R

    1997-01-01

    Studies were undertaken to determine whether differences in serum cytokine balances could be involved in the pathogenesis of allergic and in non-allergic asthma. At this propose, interferon-gamma, tumor necrosis factor-alpha, interleukin-2, interleukin-4, interleukin-6, and interleukin-10 were measured by enzimoimmunoassay. The analysis was performed on 24 allergic and 24 non-allergic asthmatic patients and 16 healthy subjects. IFN-gamma and TNF-alpha, included into the type 1 cytokines, appeared significantly increased in the allergic with respect to the non-allergic asthmatic patients (p = 0.01) and (p < 0.001) respectively, while IL-10, which belongs to the type 2 cytokines, was significantly increased in the non-allergic asthmatic (p < 0.001). The IL-6 analysis did not show any significant difference in either of the study group. The most interesting finding was the high serum IL-10 values detected in intrinsic asthmatic patients, which in turn, suggests that this cytokine could participate in the regulation of different immunological features that occurs in non-allergic asthma, and maybe it could indicate a higher stimulated state of cells in this type of asthma. The data presented in this report show a different cytokine profile in serum from allergic and non-allergic asthmatic patients and denote a stronger prevalence of type 2 cytokines in intrinsic asthma.

  1. Hemorrhagic shock shifts the serum cytokine profile from pro- to anti-inflammatory after experimental traumatic brain injury in mice.

    Science.gov (United States)

    Shein, Steven L; Shellington, David K; Exo, Jennifer L; Jackson, Travis C; Wisniewski, Stephen R; Jackson, Edwin K; Vagni, Vincent A; Bayır, Hülya; Clark, Robert S B; Dixon, C Edward; Janesko-Feldman, Keri L; Kochanek, Patrick M

    2014-08-15

    Secondary insults, such as hemorrhagic shock (HS), worsen outcome from traumatic brain injury (TBI). Both TBI and HS modulate levels of inflammatory mediators. We evaluated the addition of HS on the inflammatory response to TBI. Adult male C57BL6J mice were randomized into five groups (n=4 [naïve] or 8/group): naïve; sham; TBI (through mild-to-moderate controlled cortical impact [CCI] at 5 m/sec, 1-mm depth), HS; and CCI+HS. All non-naïve mice underwent identical monitoring and anesthesia. HS and CCI+HS underwent a 35-min period of pressure-controlled hemorrhage (target mean arterial pressure, 25-27 mm Hg) and a 90-min resuscitation with lactated Ringer's injection and autologous blood transfusion. Mice were sacrificed at 2 or 24 h after injury. Levels of 13 cytokines, six chemokines, and three growth factors were measured in serum and in five brain tissue regions. Serum levels of several proinflammatory mediators (eotaxin, interferon-inducible protein 10 [IP-10], keratinocyte chemoattractant [KC], monocyte chemoattractant protein 1 [MCP-1], macrophage inflammatory protein 1alpha [MIP-1α], interleukin [IL]-5, IL-6, tumor necrosis factor alpha, and granulocyte colony-stimulating factor [G-CSF]) were increased after CCI alone. Serum levels of fewer proinflammatory mediators (IL-5, IL-6, regulated upon activation, normal T-cell expressed, and secreted, and G-CSF) were increased after CCI+HS. Serum level of anti-inflammatory IL-10 was significantly increased after CCI+HS versus CCI alone. Brain tissue levels of eotaxin, IP-10, KC, MCP-1, MIP-1α, IL-6, and G-CSF were increased after both CCI and CCI+HS. There were no significant differences between levels after CCI alone and CCI+HS in any mediator. Addition of HS to experimental TBI led to a shift toward an anti-inflammatory serum profile--specifically, a marked increase in IL-10 levels. The brain cytokine and chemokine profile after TBI was minimally affected by the addition of HS.

  2. Malnutrition in Healthy Individuals Results in Increased Mixed Cytokine Profiles, Altered Neutrophil Subsets and Function.

    Science.gov (United States)

    Takele, Y; Adem, E; Getahun, M; Tajebe, F; Kiflie, A; Hailu, A; Raynes, J; Mengesha, B; Ayele, T A; Shkedy, Z; Lemma, M; Diro, E; Toulza, F; Modolell, M; Munder, M; Müller, I; Kropf, P

    2016-01-01

    Malnutrition is commonly associated with increased infectious disease susceptibility and severity. Whereas malnutrition might enhance the incidence of disease as well as its severity, active infection can in turn exacerbate malnutrition. Therefore, in a malnourished individual suffering from a severe infection, it is not possible to determine the contribution of the pre-existing malnutrition and/or the infection itself to increased disease severity. In the current study we focussed on two groups of malnourished, but otherwise healthy individuals: moderately malnourished (BMI: 18.4-16.5) and severely malnourished (BMI <16.5) and compared several immune parameters with those of individuals with a normal BMI (≥18.5). Our results show a similar haematological profile in all three groups, as well as a similar ratio of CD4+ and CD8+ T cells. We found significant correlations between low BMI and increased levels of T helper (Th) 1 (Interferon (IFN)-γ, (interleukin (IL)-2, IL-12), Th2 (IL-4, IL-5, IL-13), as well as IL-10, IL-33 and tumor necrosis factor-α, but not IL-8 or C reactive protein. The activities of arginase, an enzyme associated with immunosuppression, were similar in plasma, peripheral blood mononuclear cells (PBMC) and neutrophils from all groups and no differences in the expression levels of CD3ζ, a marker of T cell activation, were observed in CD4+ and CD8+T cells. Furthermore, whereas the capacity of neutrophils from the malnourished groups to phagocytose particles was not impaired, their capacity to produce reactive oxygen species was impaired. Finally we evaluated the frequency of a subpopulation of low-density neutrophils and show that they are significantly increased in the malnourished individuals. These differences were more pronounced in the severely malnourished group. In summary, our results show that even in the absence of apparent infections, healthy malnourished individuals display dysfunctional immune responses that might contribute to

  3. The cytokine-mediated crosstalk between primary human acute myeloid cells and mesenchymal stem cells alters the local cytokine network and the global gene expression profile of the mesenchymal cells

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    Håkon Reikvam

    2015-11-01

    Full Text Available Interactions between acute myeloid leukemia (AML blasts and neighboring stromal cells are important for disease development and chemosensitivity. However, the molecular mechanisms involved in the cytokine-mediated crosstalk between mesenchymal stem cells (MSCs and AML cells are largely unknown. Leukemic cells derived from 18 unselected AML patients were cultured with bone marrow MSCs derived from healthy donors; the populations then being separated by a semipermeable membrane. Coculture had only minor effects on MSC proliferation. The unique cytokine network in cocultures was determined by high constitutive MSC release of certain cytokines (especially IL-6 and vascular endothelial growth factor and constitutive release of a wide range of soluble mediators by primary AML cells. However, the AML cell release varied considerably between patients, and these differences between patients were also reflected in the coculture levels even though supra-additive effects were seen for many mediators. These effects on the local cytokine network were dependent on a functional crosstalk between the two cell subsets. The crosstalk altered the global gene expression profile of the MSCs, especially expression of genes encoding proteins involved in downstream signaling from Toll like receptors, NFκB signaling and CCL/CXCL chemokine release. Thus, primary AML cells alter the functional phenotype of normal MSCs.

  4. LEVELS OF BRAIN-SPECIFIC S-100B PROTEIN, SPECIFIC ANTIBODIES AND CYTOKINE PROFILE IN THE PATIENTS WITH ALCOHOL-INDUCED DELIRIUM STATES

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    N. N. Tsybikov

    2008-01-01

    Full Text Available Abstract. Present article deals with our results concerning brain-specific S-100B protein levels, anti-S-100B autoantibodies of IgM and IgG classes, like as cytokine profiles of blood serum and cerebrospinal fluid in the patients with alcohol-induced delirium state. The results obtained provide an evidence of association between alcoholic psychosis and destruction of brain tissue, development of autoimmune reactions and altered cytokine status, thus, probably, resulting into disintegration of immune and neuroendocrine systems.

  5. Placental gene therapy

    OpenAIRE

    David, A. L.; Ashcroft, R

    2009-01-01

    Gene therapy uses genetic material as a drug delivery vehicle to express therapeutic proteins. Placental gene therapy may be useful for correction of two important obstetric conditions, foetal growth restriction and pre-eclampsia in which there is a failure of the physiological trophoblast remodelling of the uterine spiral arteries in early pregnancy. The patient in this scenario is the foetus. Placental gene therapy might be justifiable when: there is reasonable certainty that the foetus wil...

  6. Conjugated bilirubin affects cytokine profiles in hepatitis A virus infection by modulating function of signal transducer and activator of transcription factors.

    Science.gov (United States)

    Castro-García, Flor P; Corral-Jara, Karla F; Escobedo-Melendez, Griselda; Sandoval-Hernandez, Monserrat A; Rosenstein, Yvonne; Roman, Sonia; Panduro, Arturo; Fierro, Nora A

    2014-12-01

    Hepatitis A virus (HAV) infection is the major cause of acute liver failure in paediatric patients. The clinical spectrum of infection is variable, and liver injury is determined by altered hepatic enzyme function and bilirubin concentration. We recently reported differences in cytokine profiles between distinct HAV-induced clinical courses, and bilirubin has been recognized as a potential immune-modulator. However, how bilirubin may affect cytokine profiles underlying the variability in the course of infection has not been determined. Herein, we used a transcription factor (TF) binding site identification approach to retrospectively analyse cytokine expression in HAV-infected children and to predict the entire set of TFs associated with the expression of specific cytokine profiles. The results suggested that modulation of the activity of signal transducers and activators of transcription proteins (STATs) may play a central role during HAV infection. This led us to compare the degree of STAT phosphorylation in peripheral blood lymphoid cells (PBLCs) from paediatric patients with distinct levels of conjugated bilirubin (CB). Low CB levels in sera were associated with increased STAT-1 and STAT-5 phosphorylation. A positive correlation was observed between the serum interleukin-6 (IL-6) content and CB values, whereas higher levels of CB correlated with reduced serum IL-8 values and with a reduction in the proportion of PBLCs positive for STAT-5 phosphorylation. When CB was used to stimulate patients' PBLCs in vitro, the levels of IL-6 and tumour necrosis factor-α were increased. The data showed that bilirubin plays a role in STAT function and affects cytokine profile expression during HAV infection.

  7. Gene expression profiles of some cytokines, growth factors, receptors, and enzymes (GM-CSF, IFNγ, MMP-2, IGF-II, EGF, TGF-β, IGF-IIR) during pregnancy in the cat uterus.

    Science.gov (United States)

    Agaoglu, Ozgecan Korkmaz; Agaoglu, Ali Reha; Guzeloglu, Aydin; Aslan, Selim; Kurar, Ercan; Kayis, Seyit Ali; Schäfer-Somi, Sabine

    2016-03-01

    Early pregnancy is one of the most critical periods of pregnancy, and many factors such as cytokines, enzymes, and members of the immune system have to cooperate in a balanced way. In the present study, the gene expression profiles of factors associated with pregnancy such as EGF, transforming growth factor beta, granulocyte-macrophage colony-stimulating factor, interferon gamma, insulin-like growth factor 2, insulin-like growth factor 2 receptor, and matrix metalloproteinase 2 were analyzed in uterine tissues of female cats. The cats were assigned to five groups: G1 (embryo positive, n = 7; 7th day after mating), G2 (after implantation, n = 7; 20th day after mating), G3 (midgestation, n = 7; 24-25th day after mating), G4 (late gestation, n = 7; 30-45th day after mating), G5 (oocyte group, n = 7; 7th day after estrus). Tissue samples from the uterus and placenta were collected after ovariohysterectomy. Relative messenger RNA levels were determined by real-time polymerase chain reaction. All the factors examined were detected in all tissue samples. In the course of pregnancy, significantly higher expression of EGF and matrix metalloproteinase 2 in G2 than in G1 was observed (P < 0.05). Insulin-like growth factor 2 expression was higher in all groups than in G1 (P < 0.05). Upregulation of EGF during implantation was detected. The expression of interferon gamma was significantly higher in G3 than in G1 (P < 0.05). Transforming growth factor beta and granulocyte-macrophage colony-stimulating factor were constantly expressed in all groups. In conclusion, the expressions of these factors in feline uterine tissue at different stages of pregnancy might indicate that these factors play roles in the development of pregnancy such as trophoblast invasion, vascularization, implantation, and placentation.

  8. Distinct cytokine release profiles from human endothelial and THP-1 macrophage-like cells exposed to different amphotericin B formulations.

    Science.gov (United States)

    Turtinen, Lloyd W; Bremer, Lindsay A; Prall, David N; Schwartzhoff, Jenifer; Hartsel, Scott C

    2005-01-01

    Amphotericin B(AmB) formulations, Fungizone, and Amphotec caused substantially greater proinflammatory cytokine release than AmBisome (L-AMB) and Abelcet in TPA differentiated THP-1 macrophages as determined by antibody based protein arrays. Lipopolysaccharide but not AmB induced significant pro-inflammatory cytokines in human endothelial cells.

  9. Anthelmintic Therapy Modifies the Systemic and Mycobacterial Antigen-Stimulated Cytokine Profile in Helminth-Latent Mycobacterium tuberculosis Coinfection.

    Science.gov (United States)

    Anuradha, Rajamanickam; Munisankar, Saravanan; Bhootra, Yukthi; Dolla, Chandrakumar; Kumaran, Paul; Nutman, Thomas B; Babu, Subash

    2017-04-01

    Helminth infections are known to modulate cytokine responses in latent tuberculosis (LTB). However, very few studies have examined whether this modulation is reversible upon anthelmintic therapy. We measured the systemic and mycobacterial (TB) antigen-stimulated levels of type 1, type 2, type 17, and regulatory cytokines in individuals with LTB and with or without coexistent Strongyloides stercoralis infection before and after anthelmintic therapy. Our data reveal that individuals with LTB and coexistent S. stercoralis infection have significantly lower levels of systemic and TB antigen-stimulated type 1 (gamma interferon [IFN-γ], tumor necrosis factor alpha [TNF-α], and interleukin-2 [IL-2]) and type 17 (IL-17A and/or IL-17F) cytokines and significantly higher levels of systemic but not TB antigen-stimulated type 2 (IL-4 and IL-5) and regulatory (transforming growth factor beta [TGF-β]) cytokines. Anthelmintic therapy resulted in significantly increased systemic levels of type 1 and/or type 17 cytokines and in significantly decreased systemic levels of type 2 and regulatory (IL-10 and TGF-β) cytokines. In addition, anthelmintic therapy resulted in significantly increased TB antigen-stimulated levels of type 1 cytokines only. Our data therefore confirm that the modulation of systemic and TB antigen-stimulated cytokine responses in S. stercoralis-LTB coinfection is reversible (for the most part) by anthelmintic treatment. Copyright © 2017 American Society for Microbiology.

  10. Association of self-reported symptoms with serum levels of vitamin D and multivariate cytokine profile in healthy women

    Science.gov (United States)

    Azizieh, Fawaz Y; Alyahya, Khulood O; Dingle, Kamaludin

    2017-01-01

    Background Although a large number of studies have investigated possible relationships among serum levels of vitamin D or cytokines with disease progress and prognosis, similar studies on self-reported symptoms are still controversial. The overall objective of this study was to look into the association between serum levels of vitamin D or cytokines with self-reported symptoms related to musculoskeletal pain, sleep disorders, and premenstrual syndrome (PMS) in healthy adult women. Subjects and methods Venous blood samples were collected from 117 healthy adult women, and serum levels of vitamin D, pro-inflammatory cytokines (IL-1β, IL-6, IL-8, IL-17, IFN-γ, and TNF-α) and anti-inflammatory cytokines (IL-4, IL-10, and IL-13) were measured. Groups were tested for differences in single parameters, pro-:anti-inflammatory cytokine ratios, and differences in multivariate patterns. Results There were no significant associations between serum levels of vitamin D and any of the self-reported symptoms studied. However, serum levels of certain pro-inflammatory cytokines were significantly higher in subjects with musculoskeletal pain (IL-8, P=0.008), sleep disorders (IFN-γ, P=0.02), and PMS (IL-8 and TNF-α, P=0.009 and 0.002, respectively) compared to subjects who reported no symptoms. The pro-:anti-inflammatory cytokine ratios showed pro-inflammatory cytokine dominance in subjects with self-reported symptoms, particularly in the groups with deficient levels of vitamin D. However, the multivariate cytokine-pattern analysis was significantly different between PMS groups only. Conclusion These data point to a possible role of pro-inflammatory cytokines as a contributing factor in self-reported symptoms related to musculoskeletal pain, sleep disorders, and PMS.

  11. Modulation of monocyte/macrophage-derived cytokine and chemokine profile by persistent Hepatitis C virus (HCV infection leads to chronic inflammation

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    Penelope Mavromara

    2012-02-01

    Full Text Available HCV infection presents a major public health problem, with more than 170 million people infected worldwide. Chronicity and persistence of infection constitute the hallmark of the disease. Although HCV is a hepatotropic virus, subsets of immune cells have been found to be permissive to infection and viral replication. Peripheral blood monocytes, attracted to the site of infection and differentiated into macrophages, and resident hepatic macrophages, known as Kupffer cells, are important mediators of innate immunity, through production of several chemokines and cytokines in addition to their phagocytic activity. HCV proteins have been shown to modulate the cytokine and chemokine production profile of monocytes/macrophages, as it is suggested by both in vitro and clinical studies. This modified expression profile appears crucial for the establishment of aberrant inflammation that leads to liver cirrhosis and hepatocellular carcinoma.

  12. Impaired liver regeneration in Ldlr-/- mice is associated with an altered hepatic profile of cytokines, growth factors, and lipids.

    Science.gov (United States)

    Pauta, Montse; Rotllan, Noemi; Vales, Frances; Fernandez-Hernando, Ana; Allen, Ryan M; Ford, David A; Marí, Montserrat; Jiménez, Wladimiro; Baldán, Angel; Morales-Ruiz, Manuel; Fernández-Hernando, Carlos

    2013-10-01

    It is widely recognized that in the early stages of liver regeneration after partial hepatectomy, the hepatocytes accumulate a significant amount of lipids. The functional meaning of this transient steatosis and its effect on hepatocellular proliferation are not well defined. In addition, the basic mechanisms of this lipid accumulation are not well understood although some studies suggest the participation of the Low Density Lipoprotein Receptor (Ldlr). To address these questions, we studied the process of liver regeneration in Ldlr null mice and wild type mice following partial hepatectomy. Ldlr deficiency was associated with a significant decrease in serum albumin concentration, during early stages of liver regeneration, and a delayed hepatic regeneration. Remnant livers of Ldlr(-)(/)(-) showed a time-shifted expression of interleukin-6 (IL6) and a defective activation of tumor necrosis factor-α (TNFα) and hepatocyte growth factor (HGF) expression in early phases of liver regeneration. Unexpectedly, Ldlr(-)(/)(-) showed no significant differences in the content of lipid droplets after partial hepatectomy compared to wild type mice. However, lipidomic analysis of the regenerating liver from Ldlr(-)(/)(-) revealed a lipid profile compatible with liver quiescence: high content of cholesterol esters and ceramide, and low levels of phosphatidylcholine. Ldlr deficiency is associated with significant changes in the hepatic lipidome that affect cytokine-growth factor signaling and impair liver regeneration. These results suggest that the analysis of the hepatic lipidome may help predict the success of liver regeneration in the clinical environment, specifically in the context of pre-existing liver steatosis. Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  13. CyProQuant-PCR: a real time RT-PCR technique for profiling human cytokines, based on external RNA standards, readily automatable for clinical use

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    Mercereau-Puijalon Odile

    2005-03-01

    Full Text Available Abstract Background Real-time PCR is becoming a common tool for detecting and quantifying expression profiling of selected genes. Cytokines mRNA quantification is widely used in immunological research to dissect the early steps of immune responses or pathophysiological pathways. It is also growing to be of clinical relevancy to immuno-monitoring and evaluation of the disease status of patients. The techniques currently used for "absolute quantification" of cytokine mRNA are based on a DNA standard curve and do not take into account the critical impact of RT efficiency. Results To overcome this pitfall, we designed a strategy using external RNA as standard in the RT-PCR. Use of synthetic RNA standards, by comparison with the corresponding DNA standard, showed significant variations in the yield of retro-transcription depending the target amplified and the experiment. We then developed primers to be used under one single experimental condition for the specific amplification of human IL-1β, IL-4, IL-10, IL-12p40, IL-13, IL-15, IL-18, IFN-γ, MIF, TGF-β1 and TNF-α mRNA. We showed that the beta-2 microglobulin (β2-MG gene was suitable for data normalisation since the level of β2-MG transcripts in naïve PBMC varied less than 5 times between individuals and was not affected by LPS or PHA stimulation. The technique, we named CyProQuant-PCR (Cytokine Profiling Quantitative PCR was validated using a kinetic measurement of cytokine transcripts under in vitro stimulation of human PBMC by lipopolysaccharide (LPS or Staphylococcus aureus strain Cowan (SAC. Results obtained show that CyProQuant-PCR is powerful enough to precociously detect slight cytokine induction. Finally, having demonstrated the reproducibility of the method, it was applied to malaria patients and asymptomatic controls for the quantification of TGF-β1 transcripts and showed an increased capacity of cells from malaria patients to accumulate TGF-β1 mRNA in response to LPS. Conclusion

  14. Risk factors of placental abruption

    OpenAIRE

    2013-01-01

    Background: Placental abruption is one of the most common causes of bleeding during pregnancy. Multiple factors are known to be associated with increase of risk of placental abruption such as alcohol, cocaine use and cigarette smoking. The objective of this study was to identify risk factors for placental abruption in an Iranian women population. Materials and Methods: In a retrospective case - control study birth records included 78 cases with placental abruption and 780 randomly selected co...

  15. Study on the T-helper cell 1/2 cytokine profile in blister fluid of patients with herpes zoster and its clinical significance.

    Science.gov (United States)

    Zhang, Meifang; Wu, Na; Yang, Li; Zhang, Jie; Sun, Xiaoyan; Zhong, Shiyu; Ma, Xueliang; Wang, Yili

    2011-12-01

    Herpes zoster (HZ) is a Varicella zoster virus infection disease. Previous studies have presumed the connection between development of HZ and involvement of cellular immunity in peripheral blood. However, whether cellular immunity plays a role in the local skin lesion has not been addressed. To explore the levels of T-helper cell (Th)1/Th2 type cytokine profiles in the blister fluid of the skin lesions from the patients with HZ and its role in pathogenesis, we used the cytometric bead array kit to compare the levels of cytokines (interleukin [IL]-2, tumor necrosis factor [TNF]-α, IL-10 and IL-4) in blister fluid from 46 patients with those from the suction blister fluids from 20 volunteers without any infectious disease (the control group). The results indicated that the levels of Th1 cytokines, IL-2 and TNF-α in the blister fluid from the patients' skin lesions were significantly lower than those from the control group, whereas the levels of Th2 cytokines IL-10 and IL-4 were significantly higher than those in the control group. Moreover, significant variation of the levels of Th1/Th2 cytokines (IL-2, TNF-α, IL-10 and IL-4) in the blister fluid from the HZ patients' lesions was also observed among different stages of the disease. It is concluded that a cytokine imbalance was present in the local lesions of patients with HZ during disease development. Our data suggested that the Th immunity was associated with disease activity, which may play an important role in the pathogenesis of HZ. © 2011 Japanese Dermatological Association.

  16. AUTOANTIBODIES AND CYTOKINE PROFILE IN PATIENTS WITH GRAVES–BASEDOW DISEASE AND THEIR DYNAMICS DURING THIONAMIDE THERAPY

    Directory of Open Access Journals (Sweden)

    E. V. Markelova

    2008-01-01

    Full Text Available Abstract. Role of cytokines in autoimmune reactions in Graves–Basedow disease (GBD is undisputable. It has been shown, that dynamic alterations in serum Th1 and Th2 marker cytokines are dependent on disease stage. At initial phase of autoimmune thyrotoxicosis, the maximal values were shown for IL-1α, IL-8, IFNγ and IL-10. A direct correlation is proven between the degree of disease severity, and the levels of proinflammatory (IL-1α, IL-8, IFNγ, as well as anti-inflammatory cytokines (IL-10, like as with production of antibodies against thyroid receptors. During conventional treatment with standard doses of thiamazol, the levels of cytokines are significantly decreased. These data extend our knowledge on pathogenetic mechanisms of the disorder. Moreover, they allow of developing an algorithm for assessment of therapeutic efficiency and probability of relapses in autoimmune thyrotoxicosis. (Med. Immunol., 2008, vol. 10, N 2-3, pp 245-250.

  17. Pro- versus anti-inflammatory cytokine profile in African children with acute oro-facial noma (cancrum oris, noma).

    Science.gov (United States)

    Phillips, Reshma S; Enwonwu, Cyril O; Falkler, William A

    2005-01-01

    Fresh noma is a severe orofacial necrosis with an astonishingly rapid development. It is seen mainly in malnourished children less than 4 years old from developing countries. Cytokines play a central role in oral mucosal inflammation. We therefore studied the relevance of circulating cytokines to noma, and the key microorganisms associated with the lesion. Nigerian village children with acute noma (n=68) and their neighborhood village (n=63) as well as urban (n=45) counterparts of comparable age and free of overt infections were evaluated for serum cytokine levels by ELISA. Oral bacteria were studied by polymerase chain reaction. Evaluation of random cases of the village and noma children showed marked depletion (pnoma children than in the healthy urban children, but less so when compared to their neighborhood village counterparts. The increase in levels of the anti-inflammatory/regulatory cytokines (IL-4, IL-10 and TGF-beta) was less marked relative to the pro-inflammatory cytokines. Bacteria observed at the highest frequencies in noma lesions were P. intermedia (83%), T. forsythensis (83%), P. gingivalis (50%), C. rectus (50%) and T. denticola (50%). We conclude that noma is an immunopathological response to potent bacterial factors resulting in uncontrolled production of cytokines and possibly other, still unknown, inflammatory mediators.

  18. The Maternal Cytokine and Chemokine Profile of Naturally Conceived Gestations Is Mainly Preserved during In Vitro Fertilization and Egg Donation Pregnancies

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    Alicia Martínez-Varea

    2015-01-01

    Full Text Available This prospective longitudinal study aimed at comparing maternal immune response among naturally conceived (NC; n=25, in vitro fertilization (IVF; n=25, and egg donation (ED; n=25 pregnancies. The main outcome measures were, firstly, to follow up plasma levels of interleukin (IL 1beta, IL2, IL4, IL5, IL6, IL8, IL10, IL17, interferon gamma, tumor necrosis factor-alpha (TNFα, transforming growth factor-beta (TGFβ, regulated upon activation normal T-cell expressed and secreted (RANTES, stromal cell-derived factor 1 alpha (SDF1α, and decidual granulocyte-macrophage colony-stimulating factor (GM-CSF during the three trimesters of pregnancy during the three trimesters of pregnancy; secondly, to evaluate if the cytokine and chemokine pattern of ED pregnant women differs from that of those with autologous oocytes and, thirdly, to assess if women with preeclampsia show different cytokine and chemokine profile throughout pregnancy versus women with uneventful pregnancies. Pregnant women in the three study groups displayed similar cytokine and chemokine pattern throughout pregnancy. The levels of all quantified cytokines and chemokines, except RANTES, TNFα, IL8, TGFβ, and SDF1α, rose in the second trimester compared with the first, and these higher values remained in the third trimester. ED pregnancies showed lower SDF1α levels in the third trimester compared with NC and IVF pregnancies. Patients who developed preeclampsia displayed higher SDF1α plasma levels in the third trimester.

  19. Cytokine responses to Schistosoma haematobium in a Zimbabwean population: contrasting profiles for IFN-γ, IL-4, IL-5 and IL-10 with age

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    Mduluza Takafira

    2007-11-01

    Full Text Available Abstract Background The rate of development of parasite-specific immune responses can be studied by following their age profiles in exposed and infected hosts. This study determined the cytokine-age profiles of Zimbabweans resident in a Schistosoma haematobium endemic area and further investigated the relationship between the cytokine responses and infection intensity. Methods Schistosome adult worm antigen-specific IFN-γ, IL-4, IL-5 and IL-10 cytokine responses elicited from whole blood cultures were studied in 190 Zimbabweans exposed to S. haematobium infection (aged 6 to 40 years old. The cytokines were measured using capture ELISAs and the data thus obtained together with S. haematobium egg count data from urine assays were analysed using a combination of parametric and nonparametric statistical approaches. Results Age profiles of schistosome infection in the study population showed that infection rose to peak in childhood (11–12 years followed by a sharp decline in infection intensity while prevalence fell more gradually. Mean infection intensity was 37 eggs/10 ml urine (SE 6.19 eggs/10 ml urine while infection prevalence was 54.7%. Measurements of parasite-specific cytokine responses showed that IL-4, IL-5 and IL-10 but not IFN-γ followed distinct age-profiles. Parasite-specific IL-10 production developed early, peaking in the youngest age group and declining thereafter; while IL-4 and IL-5 responses were slower to develop with a later peak. High IL-10 producers were likely to be egg positive with IL-10 production increasing with increasing infection intensity. Furthermore people producing high levels of IL-10 produced little or no IL-5, suggesting that IL-10 may be involved in the regulation of IL-5 levels. IL-4 and IFN-γ did not show a significant relationship with infection status or intensity and were positively associated with each other. Conclusion Taken together, these results show that the IL-10 responses develop early

  20. A clinical and laboratory study evaluating the profile of cytokine levels in relapsing remitting and secondary progressive multiple sclerosis.

    Science.gov (United States)

    Pasquali, Livia; Lucchesi, Cinzia; Pecori, Chiara; Metelli, Maria Rita; Pellegrini, Silvia; Iudice, Alfonso; Bonuccelli, Ubaldo

    2015-01-15

    The main aim of the study was to evaluate levels of cytokines IL-1ra, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-17, TNF-alfa, TGB-beta1 and IFN-gamma in 30 patients with relapsing remitting (RRMS) compared to 30 secondary progressive multiple sclerosis (SPMS) in a peripheral blood sample. Statistical analysis showed significant higher levels of IL-17 and INF-gamma, which are cytokines with pro-inflammatory properties, and lower levels of TGF-beta1, a molecule with immunosuppressant activity, in RRMS compared to SPMS. These results underline the existence of a different cytokines dysregulation in RRMS compared to SPMS phases with higher pro-inflammatory activity in RRMS.

  1. Lipopolysaccharide-Induced Profiles of Cytokine, Chemokine, and Growth Factors Produced by Human Decidual Cells Are Altered by Lactobacillus rhamnosus GR-1 Supernatant.

    Science.gov (United States)

    Li, Wei; Yang, Siwen; Kim, Sung O; Reid, Gregor; Challis, John R G; Bocking, Alan D

    2014-07-01

    The aim of this study was to assess the effects of bacterial lipopolysaccharide (LPS) and Lactobacillus rhamnosus GR-1 supernatant (GR-1SN) on secretion profiles of cytokines, chemokines, and growth factors from primary cultures of human decidual cells. Lipopolysaccharide significantly increased the output of proinflammatory cytokines (interleukin [IL]-1B, IL-2, IL-6, IL-12p70, IL-15, IL-17A, interferon gamma [IFN-γ], and tumor necrosis factor [TNF]); anti-inflammatory cytokines (IL-1RN, IL-4, IL-9, and IL-10); chemokines (IL-8, eotaxin, IFN-inducible protein 10 [IP-10], monocyte chemoattractant protein 1 [MCP-1], macrophage inflammatory protein-1α [MIP-1α], macrophage inflammatory protein-1β [MIP-1β], and regulated on activation normal T cell expressed and secreted [RANTES]); and growth factors (granulocyte colony-stimulating factor [CSF] 3, CSF-2, and vascular endothelial growth factor A [VEGFA]). Lactobacillus rhamnosus GR-1SN alone significantly increased CSF-3, MIP-1α MIP-1β, and RANTES but decreased IL-15 and IP-10 output. The GR-1SN also significantly or partially reduced LPS-induced proinflammatory cytokines TNF, IFN-γ, IL-1β, IL-2 IL-6, IL-12p70, IL-15, IL-17, and IP-10; partially reduced LPS-induced anti-inflammatory cytokines IL-1RN, IL-4 and IL-10, and LPS-induced VEGFA output but did not affect CSF-3, MIP-1α, MIP-1β, MCP-1, IL-8, and IL-9. Our results demonstrate that GR-1SN attenuates the inflammatory responses to LPS by human decidual cells, suggesting its potential role in ameliorating intrauterine infection.

  2. Cytokines profile and antibodies in response to Plasmodium vivax infection in a population of the south of Bolivar, Colombia

    OpenAIRE

    2013-01-01

    Introduction: malaria is an important cause of disease and death in tropical countries.Inflammatory cytokines produced by the innate immune system play an important rolein the regulation of the adaptive immunity in front of the Malaria blood-stage. However,the role of these mediators in the pathogenesis of the disease by P. vivax is unclear.Objective: determine the serum levels of cytokines and IgG in infected patients with P.vivax and correlate these molecules with the severity of the diseas...

  3. Macaques with Rapid Disease Progression and Simian Immunodeficiency Virus Encephalitis Have a Unique Cytokine Profile in Peripheral Lymphoid Tissues

    OpenAIRE

    2001-01-01

    The influence of host cytokine response on viral load, disease progression, and neurologic lesions was investigated in the simian immunodeficiency virus (SIV)-infected macaque model of AIDS. Cytokine gene expression (interleukin-1β [IL-1β], IL-2, IL-6, IL-10, gamma interferon [IFN-γ], and tumor necrosis factor alpha [TNF-α]) and viral loads were evaluated by semiquantitative reverse transcription-PCR in lymph nodes of 5 control animals and 28 animals infected with SIVmac251 at the terminal st...

  4. A retrospective study of cytokine profiles changes in mice with FVIII inhibitor development after AAV mediated gene therapy in hemophilia A mouse model.

    Science.gov (United States)

    Sun, Junjiang; Yuan, Zhenhua; Abajas, Yasmina L; Szollosi, Dorreen E; Hu, Genlin; Hua, Baolai; Xiao, Xiao; Li, Chengwen

    2017-09-19

    The development of inhibitory autoantibodies to the infused clotting factor VIII is a major complication for severe hemophilia A management. Novel therapy options for hemophilia have significantly progressed in the last decade and a gene therapy cure for hemophilia is translating into reality. However, mechanistic studies of FVIII autoantibodies (FVIII inhibitors) have lagged behind and remain a challenge for both protein replacement and gene therapy. FVIII inhibitor formation is assumed to be a classical T cell-dependent immune response in which cytokines/chemokines play an important role. The study of cytokine profile changes during FVIII inhibitor development may be helpful to understand the mechanism of inhibitor development and to explore potential novel approaches that will minimize the risk. After FVIII-/- mice were treated with intravenous administration of an AAV8 vector encoding human FVIII, FVIII expression peaked at week 2 (W2), and FVIII inhibitor was thoroughly developed at week 8 (W8). W8 plasma that showed positive FVIII inhibitor, and W2 samples with negative FVIII inhibitor ("Anti-FVIII(+)"), were subjected to multiplex cytokines measurement, W8 and W2 samples were both negative for FVIII inhibitor ("Anti-FVIII(-)") as the control. In comparison to mice in the "Anti-FVIII(-)" group, the mice in group of "Anti-FVIII(+)", especially at higher titers, exhibited significantly elevated pro-inflammatory cytokines of IL-1, IL-6, IL-12p40, MCP-1, MIP-1, MIP-2, and TNFα. The anti-inflammatory cytokine of TGFβ was decreased at W2 in both groups. Multivariate analysis of the risk factors for FVIII inhibitor development showed peak FVIII activity at W2, IL-6 and TNFα at W8 were positively correlated with inhibitor formation, and age starting gene therapy was negatively correlated. Collectively, the elevated monocyte derived pro-inflammatory cytokines/chemokines, together with the decreased anti-inflammatory cytokine of TGFβ at an early time point, may

  5. Comparative expression profile of NOD1/2 and certain acute inflammatory cytokines in thermal-stressed cell culture model of native and crossbred cattle

    Science.gov (United States)

    Bhanuprakash, V.; Singh, Umesh; Sengar, Gyanendra Singh; Raja, T. V.; Sajjanar, Basavraj; Alex, Rani; Kumar, Sushil; Alyethodi, R. R.; Kumar, Ashish; Sharma, Ankur; Kumar, Suresh; Bhusan, Bharat; Deb, Rajib

    2017-05-01

    Thermotolerance depends mainly on the health and immune status of the animals. The variation in the immune status of the animals may alter the level of tolerance of animals exposed to heat or cold stress. The present study was conducted to investigate the expression profile of two important nucleotide binding and oligomerization domain receptors (NLRs) (NOD1 and NOD2) and their central signalling molecule RIP2 gene during in vitro thermal-stressed bovine peripheral blood mononuclear cells (PBMCs) of native (Sahiwal) and crossbred (Sahiwal X HF) cattle. We also examined the differential expression profile of certain acute inflammatory cytokines in in vitro thermal-stressed PBMC culture among native and its crossbred counterparts. Results revealed that the expression profile of NOD1/2 positively correlates with the thermal stress, signalling molecule and cytokines. Present findings also highlighted that the expression patterns during thermal stress were comparatively superior among indigenous compared to crossbred cattle which may add references regarding the better immune adaptability of Zebu cattle.

  6. Comparative expression profile of NOD1/2 and certain acute inflammatory cytokines in thermal-stressed cell culture model of native and crossbred cattle

    Science.gov (United States)

    Bhanuprakash, V.; Singh, Umesh; Sengar, Gyanendra Singh; Raja, T. V.; Sajjanar, Basavraj; Alex, Rani; Kumar, Sushil; Alyethodi, R. R.; Kumar, Ashish; Sharma, Ankur; Kumar, Suresh; Bhusan, Bharat; Deb, Rajib

    2016-11-01

    Thermotolerance depends mainly on the health and immune status of the animals. The variation in the immune status of the animals may alter the level of tolerance of animals exposed to heat or cold stress. The present study was conducted to investigate the expression profile of two important nucleotide binding and oligomerization domain receptors (NLRs) (NOD1 and NOD2) and their central signalling molecule RIP2 gene during in vitro thermal-stressed bovine peripheral blood mononuclear cells (PBMCs) of native (Sahiwal) and crossbred (Sahiwal X HF) cattle. We also examined the differential expression profile of certain acute inflammatory cytokines in in vitro thermal-stressed PBMC culture among native and its crossbred counterparts. Results revealed that the expression profile of NOD1/2 positively correlates with the thermal stress, signalling molecule and cytokines. Present findings also highlighted that the expression patterns during thermal stress were comparatively superior among indigenous compared to crossbred cattle which may add references regarding the better immune adaptability of Zebu cattle.

  7. Temporal profiling of cytokine-induced genes in pancreatic β-cells by meta-analysis and network inference

    DEFF Research Database (Denmark)

    Lopes, Miguel; Kutlu, Burak; Miani, Michela;

    2014-01-01

    Type 1 Diabetes (T1D) is an autoimmune disease where local release of cytokines such as IL-1β and IFN-γ contributes to β-cell apoptosis. To identify relevant genes regulating this process we performed a meta-analysis of 8 datasets of β-cell gene expression after exposure to IL-1β and IFN-γ. Two o...

  8. Cytokine profiling of tumor interstitial fluid of the breast and its relationship with lymphocyte infiltration and clinicopathological characteristics

    DEFF Research Database (Denmark)

    Espinoza, Jaime A.; Jabeen, Shakila; Batra, Richa

    2016-01-01

    normal interstitial fluid (NIF) samples, and 25 matched serum samples obtained from BC patients with Luminex xMAP multiplex technology. Eleven cytokines exhibited significantly higher levels in the TIF samples compared with the NIF samples: interleukin (IL)-7, IL-10, fibroblast growth factor-2, IL-13...

  9. The central nervous system environment controls effector CD4+ T cell cytokine profile in experimental allergic encephalomyelitis

    DEFF Research Database (Denmark)

    Krakowski, M L; Owens, T

    1997-01-01

    In experimental allergic encephalomyelitis (EAE), CD4+ T cells infiltrate the central nervous system (CNS). We derived CD4+ T cell lines from SJL/J mice that were specific for encephalitogenic myelin basic protein (MBP) peptides and produced both Th1 and Th2 cytokines. These lines transferred EAE...

  10. Functional variability in butyrylcholinesterase activity regulates intrathecal cytokine and astroglial biomarker profiles in patients with Alzheimer's disease

    DEFF Research Database (Denmark)

    Darreh-Shori, Taher; Vijayaraghavan, Swetha; Aeinehband, Shahin

    2013-01-01

    and that this might be of clinical relevance. The dissociation between astroglial markers and inflammatory cytokines indicates that a proper activation and maintenance of astroglial function is a beneficial response, rather than a disease-driving mechanism. Further studies are needed to explore the therapeutic...

  11. Adipose Tissue Promotes a Serum Cytokine Profile Related to Lower Insulin Sensitivity after Chronic Central Leptin Infusion

    Science.gov (United States)

    Burgos-Ramos, Emma; Canelles, Sandra; Perianes-Cachero, Arancha; Arilla-Ferreiro, Eduardo; Argente, Jesús; Barrios, Vicente

    2012-01-01

    Obesity is an inflammatory state characterized by an augment in circulating inflammatory factors. Leptin may modulate the synthesis of these factors by white adipose tissue decreasing insulin sensitivity. We have examined the effect of chronic central administration of leptin on circulating levels of cytokines and the possible relationship with cytokine expression and protein content as well as with leptin and insulin signaling in subcutaneous and visceral adipose tissues. In addition, we analyzed the possible correlation between circulating levels of cytokines and peripheral insulin resistance. We studied 18 male Wistar rats divided into controls (C), those treated icv for 14 days with a daily dose of 12 μg of leptin (L) and a pair-fed group (PF) that received the same food amount consumed by the leptin group. Serum leptin and insulin were measured by ELISA, mRNA levels of interferon-γ (IFN-γ), interleukin-2 (IL-2), IL-4, IL-6, IL-10 and tumor necrosis factor-α (TNF-α) by real time PCR and serum and adipose tissue levels of these cytokines by multiplexed bead immunoassay. Serum leptin, IL-2, IL-4, IFN-γ and HOMA-IR were increased in L and TNF-α was decreased in PF and L. Serum leptin and IL-2 levels correlate positively with HOMA-IR index and negatively with serum glucose levels during an ip insulin tolerance test. In L, an increase in mRNA levels of IL-2 was found in both adipose depots and IFN-γ only in visceral tissue. Activation of leptin signaling was increased and insulin signaling decreased in subcutaneous fat of L. In conclusion, leptin mediates the production of inflammatory cytokines by adipose tissue independent of its effects on food intake, decreasing insulin sensitivity. PMID:23056516

  12. Adipose tissue promotes a serum cytokine profile related to lower insulin sensitivity after chronic central leptin infusion.

    Science.gov (United States)

    Burgos-Ramos, Emma; Canelles, Sandra; Perianes-Cachero, Arancha; Arilla-Ferreiro, Eduardo; Argente, Jesús; Barrios, Vicente

    2012-01-01

    Obesity is an inflammatory state characterized by an augment in circulating inflammatory factors. Leptin may modulate the synthesis of these factors by white adipose tissue decreasing insulin sensitivity. We have examined the effect of chronic central administration of leptin on circulating levels of cytokines and the possible relationship with cytokine expression and protein content as well as with leptin and insulin signaling in subcutaneous and visceral adipose tissues. In addition, we analyzed the possible correlation between circulating levels of cytokines and peripheral insulin resistance. We studied 18 male Wistar rats divided into controls (C), those treated icv for 14 days with a daily dose of 12 μg of leptin (L) and a pair-fed group (PF) that received the same food amount consumed by the leptin group. Serum leptin and insulin were measured by ELISA, mRNA levels of interferon-γ (IFN-γ), interleukin-2 (IL-2), IL-4, IL-6, IL-10 and tumor necrosis factor-α (TNF-α) by real time PCR and serum and adipose tissue levels of these cytokines by multiplexed bead immunoassay. Serum leptin, IL-2, IL-4, IFN-γ and HOMA-IR were increased in L and TNF-α was decreased in PF and L. Serum leptin and IL-2 levels correlate positively with HOMA-IR index and negatively with serum glucose levels during an ip insulin tolerance test. In L, an increase in mRNA levels of IL-2 was found in both adipose depots and IFN-γ only in visceral tissue. Activation of leptin signaling was increased and insulin signaling decreased in subcutaneous fat of L. In conclusion, leptin mediates the production of inflammatory cytokines by adipose tissue independent of its effects on food intake, decreasing insulin sensitivity.

  13. Placental apoptosis in recurrent miscarriage

    Directory of Open Access Journals (Sweden)

    Tarek A. Atia

    2017-09-01

    Full Text Available Apoptosis is an interactive and dynamic biological process involved in all phases of embryogenesis. We aimed to study the effect of placental apoptosis on recurrent miscarriage (RM. Placental tissue samples were collected from 40 women with RM (study group and 30 women with sporadic spontaneous abortion (control group. Samples were prepared and stained immunohistochemically with markers for both the apoptotic protein (p53 and anti-apoptotic Bcl-2 antibodies. Our results showed that expression of the apoptotic (p53 protein was significantly increased in the placental tissues of the RM group (p = 0.003. By contrast, the expression of anti-apoptotic (Bcl-2 antibodies was significantly increased in the placental tissues of the control group (p = 0.025. We concluded that placental apoptosis plays a crucial role in pregnancy continuation. However, increased p53 expression in placental tissue in early pregnancy could negatively affect pregnancy continuation.

  14. Human Lymph Node-Derived Fibroblastic and Double-Negative Reticular Cells Alter Their Chemokines and Cytokines Expression Profile Following Inflammatory Stimuli

    Science.gov (United States)

    Severino, Patricia; Palomino, Diana Torres; Alvarenga, Heliene; Almeida, Camila Bononi; Pasqualim, Denise Cunha; Cury, Adriano; Salvalaggio, Paolo Rogério; De Vasconcelos Macedo, Antonio Luiz; Andrade, Maria Claudina; Aloia, Thiago; Bromberg, Silvio; Rizzo, Luiz Vicente; Rocha, Fernanda Agostini; Marti, Luciana C.

    2017-01-01

    Lymph node (LN) is a secondary lymphoid organ with highly organized and compartmentalized structure. LNs harbor B, T, and other cells among fibroblastic reticular cells (FRCs). FRCs are characterized by both podoplanin (PDPN/gp38) expression and by the lack of CD31 expression. FRCs are involved in several immune response processes but mechanisms underlying their function are still under investigation. Double-negative cells (DNCs), another cell population within LNs, are even less understood. They do not express PDPN or CD31, their localization within the LN is unknown, and their phenotype and function remain to be elucidated. This study evaluates the gene expression and cytokines and chemokines profile of human LN-derived FRCs and DNCs during homeostasis and following inflammatory stimuli. Cytokines and chemokines secreted by human FRCs and DNCs partially diverged from those identified in murine models that used similar stimulation. Cytokine and chemokine secretion and their receptors expression levels differed between stimulated DNCs and FRCs, with FRCs expressing a broader range of chemokines. Additionally, dendritic cells demonstrated increased migration toward FRCs, possibly due to chemokine-induced chemotaxis since migration was significantly decreased upon neutralization of secreted CCL2 and CCL20. Our study contributes to the understanding of the biology and functions of FRCs and DNCs and, accordingly, of the mechanisms involving them in immune cells activation and migration. PMID:28261205

  15. CYTOKINE PROFILE AND ADHESION MOLECULES IN THE PATIENTS WITH CHRONIC OBSTRUCTIVE LUNG DISEASE COMBINED WITH BRONCHIAL ASTHMA

    Directory of Open Access Journals (Sweden)

    T. G. Shapovalova

    2010-01-01

    Full Text Available The study involved 56 patients with chronic obstructive pulmonary disease (COPD, stage III-IV, 38 patients with severe bronchial asthma (BA, and 45 patients with a combination of COPD stage III-IV and bronchial asthma at exacerbation period. In all the patients, we have measured blood levels of pro-inflammatory (IL-6, IL -8, TNFα and anti-inflammatory (IL-4 cytokines, amounts of cell adhesion molecules (ICAM- 1, VCAM-1, along with assessment of contractile myocardial functional disorders by means of Doppler echocardiography. Highest rates of pro-inflammatory cytokines and adhesion molecules were found in the group of patients with combined pathology, along with most significant signs of myocardial hypertrophy, both in right and left heart compartments, accompanied by a decrease in contractile myocardial function.

  16. The central nervous system environment controls effector CD4+ T cell cytokine profile in experimental allergic encephalomyelitis

    DEFF Research Database (Denmark)

    Krakowski, M L; Owens, T

    1997-01-01

    in vitro. Although CNS antigen-presenting cells (APC) supported increased production of interferon (IFN)-gamma mRNA by these T cells, there was no increase in the interleukin (IL)-4 signal, whereas splenic APC induced increases in both IFN-gamma and IL-4. mRNA for IL-12 (p40 subunit) was up......-regulated in both infiltrating macrophages and resident microglia from mice with EAE. We have thus shown that a Th1 cytokine bias within the CNS can be induced by CNS APC, and that IL-12 is up-regulated in microglial cells within the CNS of mice with EAE. Microglia may therefore control Th1 cytokine responses...

  17. Live and Heat-Killed Lactobacillus rhamnosus ATCC 7469 May Induce Modulatory Cytokines Profiles on Macrophages RAW 264.7.

    Science.gov (United States)

    Jorjão, Adeline Lacerda; de Oliveira, Felipe Eduardo; Leão, Mariella Vieira Pereira; Carvalho, Cláudio Antonio Talge; Jorge, Antonio Olavo Cardoso; de Oliveira, Luciane Dias

    2015-01-01

    This study aimed to evaluate the capacity of Lactobacillus rhamnosus and/or its products to induce the synthesis of cytokines (TNF-α, IL-1β, IL-4, IL-6, IL-10, and IL-12) by mouse macrophages (RAW 264.7). Three microorganism preparations were used: live L. rhamnosus (LLR) suspension, heat-killed L. rhamnosus (HKLR) suspension, and the supernatant of a heat-killed L. rhamnosus (SHKLR) suspension, which were cultured with macrophages (37°C, 5% CO2) for 2 h and 30 min. After that, cells were cultured for 16 h. The supernatants were used for the quantitation of cytokines, by ELISA. The results were compared with the synthesis induced by lipopolysaccharide (LPS) and analysed, using ANOVA and Tukey test, 5%. LLR and HKLR groups were able to significantly increase the production of TNF-α, IL-6, and IL-10 (P 0.05). All the L. rhamnosus suspensions were not able to produce detectable levels of IL-1β or significant levels of IL-4 and IL-12 (P > 0.05). In conclusion, live and heat-killed L. rhamnosus suspensions were able to induce the synthesis of different cytokines with proinflammatory (TNF-α and IL-6) or regulatory (IL-10) functions, suggesting the role of strain L. rhamnosus ATCC 7469 in the modulation or in the stimulation of immune responses.

  18. Chemokine/cytokine profiling after rituximab: reciprocal expression of BCA-1/CXCL13 and BAFF in childhood OMS.

    Science.gov (United States)

    Pranzatelli, Michael R; Tate, Elizabeth D; Travelstead, Anna L; Verhulst, Steven J

    2011-03-01

    The aim of the study was to test the hypothesis that B-cell repopulation following rituximab (anti-CD20) therapy is orchestrated by chemokines and non-chemokine cytokines. Twenty-five children with opsoclonus-myoclonus syndrome (OMS) received rituximab with or without conventional agents. A comprehensive panel of 40 chemokines and other cytokines were measured in serum by ELISA and multiplexed fluorescent bead-based immunoassay. Serum BAFF concentration changed dramatically (even after first infusion) and inversely with B-cell depletion/repopulation and CXCL13 concentration at 1, 3, and 6 months. Negative correlations were found for BAFF concentration vs blood B cell percentage and serum CXCL13 concentration; positive correlations with serum rituximab concentrations. Six months after initiation of therapy, no significant difference in the levels of APRIL, CXCL10, IL-6, or 17 other cytokines/chemokines were detected. These data reveal a major role for BAFF in peripheral B cell repopulation following rituximab-induced B-cell depletion, and novel changes in CXCL13. ClinicalTrials.gov NCT0024436.

  19. Live and Heat-Killed Lactobacillus rhamnosus ATCC 7469 May Induce Modulatory Cytokines Profiles on Macrophages RAW 264.7

    Directory of Open Access Journals (Sweden)

    Adeline Lacerda Jorjão

    2015-01-01

    Full Text Available This study aimed to evaluate the capacity of Lactobacillus rhamnosus and/or its products to induce the synthesis of cytokines (TNF-α, IL-1β, IL-4, IL-6, IL-10, and IL-12 by mouse macrophages (RAW 264.7. Three microorganism preparations were used: live L. rhamnosus (LLR suspension, heat-killed L. rhamnosus (HKLR suspension, and the supernatant of a heat-killed L. rhamnosus (SHKLR suspension, which were cultured with macrophages (37°C, 5% CO2 for 2 h and 30 min. After that, cells were cultured for 16 h. The supernatants were used for the quantitation of cytokines, by ELISA. The results were compared with the synthesis induced by lipopolysaccharide (LPS and analysed, using ANOVA and Tukey test, 5%. LLR and HKLR groups were able to significantly increase the production of TNF-α, IL-6, and IL-10 (P0.05. All the L. rhamnosus suspensions were not able to produce detectable levels of IL-1β or significant levels of IL-4 and IL-12 (P>0.05. In conclusion, live and heat-killed L. rhamnosus suspensions were able to induce the synthesis of different cytokines with proinflammatory (TNF-α and IL-6 or regulatory (IL-10 functions, suggesting the role of strain L. rhamnosus ATCC 7469 in the modulation or in the stimulation of immune responses.

  20. INDICATORS OF IMMUNE STATUS, CYTOKINE PROFILE IN SICKLY CHILDREN AND OPTIMIZATION OF APPROACHES TO PREVENTION OF ARI

    Directory of Open Access Journals (Sweden)

    S. A. Sokolov

    2013-01-01

    Full Text Available The authors have investigated the level of lymphocyte subpopulation, immunoglobulins IgA, IgM, IgG and the concentration of 10 cytokines in blood serum of 67 sickly children. All of them have chronic somatic pathology. The authors have ascertained absence of significant differences in immunological indicators. When the level of subpopulation composition of lymphocytes and IgG, IgA, IgM in the blood serum is normal, such children have a higher concentration of antiphlogistic cytokines 1L-1β, IL-12p70, IL-8 whereas the balance of Th/Th2-cells is preserved. It is kept up by cytokines IL-2, IFN-γ, TNF-α, IL-4, IL-5, IL-10 inthe conditions of chronic inflammatory process. The maintenance of this balance is the main goal and it should provide the basis for immunological correction of sickly children with chronic somatic pathology. The most appropriate drug for immunological correction in our research is ribosomal immunоmodulator Ribomunyl.

  1. Blocking Endogenous Leukemia Inhibitory Factor During Placental Development in Mice Leads to Abnormal Placentation and Pregnancy Loss.

    Science.gov (United States)

    Winship, Amy; Correia, Jeanne; Krishnan, Tara; Menkhorst, Ellen; Cuman, Carly; Zhang, Jian-Guo; Nicola, Nicos A; Dimitriadis, Evdokia

    2015-08-14

    The placenta forms the interface between the maternal and fetal circulation and is critical for the establishment of a healthy pregnancy. Specialized trophoblast cells derived from the embryonic trophectoderm play a pivotal role in the establishment of the placenta. Leukemia inhibitory factor (LIF) is one of the predominant cytokines present in the placenta during early pregnancy. LIF has been shown to regulate trophoblast adhesion and invasion in vitro, however its precise role in vivo is unknown. We hypothesized that LIF would be required for normal placental development in mice. LIF and LIFRα were immunolocalized to placental trophoblasts and fetal vessels in mouse implantation sites during mid-gestation. Temporally blocking LIF action during specific periods of placental development via intraperitoneal administration of our specific LIFRα antagonist, PEGLA, resulted in abnormal placental trophoblast and vascular morphology and reduced activated STAT3 but not ERK. Numerous genes regulating angiogenesis and oxidative stress were altered in the placenta in response to LIF inhibition. Pregnancy viability was also significantly compromised in PEGLA treated mice. Our data suggest that LIF plays an important role in placentation in vivo and the maintenance of healthy pregnancy.

  2. Placental Aromatase Is Deficient in Placental Ischemia and Preeclampsia.

    Directory of Open Access Journals (Sweden)

    Alejandra Perez-Sepulveda

    Full Text Available Preeclampsia is a maternal hypertensive disorder with uncertain etiology and a leading cause of maternal and fetal mortality worldwide, causing nearly 40% of premature births delivered before 35 weeks of gestation. The first stage of preeclampsia is characterized by reduction of utero-placental blood flow which is reflected in high blood pressure and proteinuria during the second half of pregnancy. In human placenta androgens derived from the maternal and fetal adrenal glands are converted into estrogens by the enzymatic action of placental aromatase. This implies that alterations in placental steroidogenesis and, subsequently, in the functionality or bioavailability of placental aromatase may be mechanistically involved in the pathophysiology of PE.Serum samples were collected at 32-36 weeks of gestation and placenta biopsies were collected at time of delivery from PE patients (n = 16 and pregnant controls (n = 32. The effect of oxygen tension on placental cells was assessed by incubation JEG-3 cells under 1% and 8% O2 for different time periods, Timed-mated, pregnant New Zealand white rabbits (n = 6 were used to establish an in vivo model of placental ischemia (achieved by ligature of uteroplacental vessels. Aromatase content and estrogens and androgens concentrations were measured.The protein and mRNA content of placental aromatase significantly diminished in placentae obtained from preeclamptic patients compared to controls. Similarly, the circulating concentrations of 17-β-estradiol/testosterone and estrone/androstenedione were reduced in preeclamptic patients vs. controls. These data are consistent with a concomitant decrease in aromatase activity. Aromatase content was reduced in response to low oxygen tension in the choriocarcinoma JEG-3 cell line and in rabbit placentae in response to partial ligation of uterine spiral arteries, suggesting that reduced placental aromatase activity in preeclamptic patients may be associated with chronic

  3. Targeting beta- and alpha-adrenergic receptors differentially shifts Th1, Th2, and inflammatory cytokine profiles in immune organs to attenuate adjuvant arthritis

    Directory of Open Access Journals (Sweden)

    Dianne eLorton

    2014-08-01

    Full Text Available The sympathetic nervous system (SNS regulates host defense responses and restores homeostasis. SNS-immune regulation is altered in rheumatoid arthritis (RA and rodent models of RA, characterized by nerve remodeling in immune organs and defective adrenergic receptor (AR signaling to immune cell targets that typically promotes or suppresses inflammation via α- and β2-AR activation, respectively, and indirectly drives humoral immunity by blocking Th1 cytokine secretion. Here, we investigate how β2-AR stimulation and/or α-AR blockade at disease onset affects disease pathology and cytokine profiles in relevant immune organs from male Lewis rats with adjuvant-induced arthritis (AA. Rats challenged to induce AA were treated with terbutaline (TERB, a β2-AR agonist (600 μg/kg/day and/or phentolamine (PHEN, an α-AR antagonist (5.0 mg/kg/day or vehicle from disease onset through severe disease. We report that in spleen, mesenteric (MLN and draining lymph node (DLN cells, TERB reduces proliferation, an effect independent of IL-2. TERB also fails to shift Th cytokines from a Th1 to Th2 profile in spleen and MLN (no effect on IFN-γ and DLN (greater IFN-γ cells. In splenocytes, TERB, PHEN and co-treatment (PT promotes an anti-inflammatory profile (greater IL-10 and lowers TNF-α (PT only. In DLN cells, drug treatments do not affect inflammatory profiles, except PT, which raised IL-10. In MLN cells, TERB or PHEN lowers MLN cell secretion of TNF-α or IL-10, respectively. Collectively, our findings indicate disrupted β2-AR, but not α-AR signaling in AA. Aberrant β2-AR signaling consequently derails the sympathetic regulation of lymphocyte expansion, Th cell differentiation, and inflammation in the spleen, DLNs and MLNs that is required for immune system homeostasis. Importantly, this study provides potential mechanisms through which reestablished balance between α- and β2-AR function in the immune system ameliorates inflammation and joint

  4. Interleukin-21 Induces Proliferation and Proinflammatory Cytokine Profile of Fibroblast-like Synoviocytes of Patients with Rheumatoid Arthritis.

    Science.gov (United States)

    Xing, R; Yang, L; Jin, Y; Sun, L; Li, C; Li, Z; Zhao, J; Liu, X

    2016-01-01

    Fibroblast-like synoviocytes (FLS) play a pivotal role in the pathogenesis of rheumatoid arthritis (RA) through aggressive proliferation and invasion, and certain proinflammatory cytokines may affect synoviocyte proliferation. To evaluate whether interleukin-21 (IL-21) could promote proliferation and proinflammatory cytokine production by RA-FLS, immunohistochemistry and immunoblotting were performed to observe the expression of IL-21 receptor (IL-21R) in synovial tissues and FLS from RA and osteoarthritis (OA) patients. The MTS assay was used to analyse RA-FLS proliferation. The concentrations of IL-6 and tumour necrosis factor-α (TNF-α) in culture supernatants were determined by enzyme-linked immunosorbent assay (ELISA). The signalling pathways triggered by IL-21 were characterized by immunoblotting. IL-21R was upregulated in the synovial tissues and FLS of RA patients as compared with OA patients. IL-21 stimulated RA-FLS proliferation and promoted the production of TNF-α and IL-6 and blockade of IL-21/IL-21R pathway with IL-21R.Fc attenuated IL-21-induced proliferation and secretion of TNF-α and IL-6. Moreover, IL-21 induced activation of the ERK1/2, PI3K/AKT and STAT3 pathways, and blockade of these pathways attenuated IL-21-induced proliferation and secretion of TNF-α and IL-6. These results suggest that IL-21 could promote RA-FLS proliferation and production of proinflammatory cytokines. Therefore, therapeutic strategies targeting IL-21 might be effective for the treatment of RA.

  5. Iloprost treatment summer-suspension: effects on skin thermal properties and cytokine profile in systemic sclerosis patients.

    Science.gov (United States)

    Auriemma, M; Vianale, G; Reale, M; Costantini, E; Di Nicola, M; Romani, G L; Merla, A; Muraro, R; Amerio, P

    2013-04-01

    Aim of the study was to assess whether Iloprost treatment summer suspension modifies systemic cytokines levels, cutaneous thermal properties and functional response to a cold-induced stress in patients affected by systemic sclerosis (SSc). Twenty-eight patients fulfilling the American College of Rheumatology (ACR) criteria for SSc were included in the study. Patients recorded number, duration and pain-severity of Raynaud phenomenon (RP). Pain-severity was determined by a visual analog scale. Cytokines expression and production in peripheral blood mononuclear cells and serum were evaluated by RT-PCR and ELISA assay. Basal finger temperature (Tb), distal-dorsal difference temperature (DTdd) and thermal recovery time (tr) from cold stress were measured by means of functional infrared imaging (fIR). Measurements were performed in late spring, during routine Iloprost therapy (1-3 days infusion of 0.5-2 ng/kg every month), and in late summer after a therapy-withdrawal period. Deterioration of SSc patients' skin thermal properties was observed in the period of therapy withdrawal (Tb reduction and tr enhancement; no DTdd differences) despite the improvement in symptoms of RP. A reduction in IL-12/23p40 gene expression was recorded after therapy withdrawal and a direct correlation between IL-12/23p40 and IL-23p19 gene expression was observed, stronger after therapy suspension. Our data suggest that Iloprost treatment summer suspension may induce the loss of the therapy beneficial effect on microcirculation despite the objective reduction of RP, thus favouring a continuous use of Iloprost in absence of severe side effects. Iloprost showed to modulate only IL-23 expression corroborating the idea that this cytokine is crucial for SSc development and progression.

  6. The Profile of the Serum Levels of Inflammatory Cytokines TNF-a,IL-6, IL-10 and Captopril Intervention in Reno-hypertensive Rats

    Institute of Scientific and Technical Information of China (English)

    Li Zhongchen; Liu Fengying

    2005-01-01

    Objectives To observe the profile of the serum levels of inflammatory cytokines interleukin-6 (IL-6), tumor necrosis factor (TNF-o) and interleukin-10 (IL-10) and evaluate the effects of angiotensin- converting enzyme inhibitor-Captopril on them in renohypertensive rats. Methods Using reformed two-kidney-one-clip (2K 1C ) method, renal hypertensive rats (RHR) were obtained by ligating abdominal aorta.30 Wistar rats were randomized into three groups:sham-operation group (A)、 model control group ( B ) and captopril group (C). All rats were killed after being given the trial drugs 5 weeks, ELISA assays were used to detect the levels of IL-6 and IL-10, the levels of TNF-alpha were measured with radioimmtmoassays.hypertrophy was aggravated in group B significantly,the ratio of left ventricle and body weight(LV/BW) was 0.00318 ±0.00030 (B)and 0.00256 ±0.00040 (A)respectively(P < 0.001 ), the levels of IL-6 and TNF-o increased significantly (P < 0.001 and P < 0.002respectively), whereas the levels of IL-10 were not compared with group B, the LV/BW was 0.00266 ±0.00018 (C) and 0.00318±0.00030 (B) respectively(P < 0.001), the levels of IL-6 and TNF-α decreased significantly ( P < 0.01), whereas the levels of IL-10were not changed between the two groups (P > 0.05);Conclusions Angiotensin converting enzyme inhibitor-captopril can lower the serum levels of proinflammatory cytokines IL-6 and TNF-α effectively,but can not increase the levels of anti-inflammatory cytokine IL-10, it suggests that captopril may have a feature to prevent or slow the development of hypertensive complications by means of lowering the levels of pro-inflammatory cytokines but not by increasing anti-inflammatory cytokine IL-10.

  7. T Cell Activation and Cytokine Profile of Tuberculosis and HIV-Positive Individuals during Antituberculous Treatment and Efavirenz-Based Regimens.

    Science.gov (United States)

    da Silva, Tatiana P; Giacoia-Gripp, Carmem B W; Schmaltz, Carolina A; Sant Anna, Flavia M; Rolla, Valeria; Morgado, Mariza G

    2013-01-01

    The profile of immune activation markers in tuberculosis and HIV-infected patients is already known. The impact of simultaneous infections on the immune parameters is still not fully explored. We conducted a prospective study to estimate trajectories of activated T cell subsets and the profile of anti- and pro-inflammatory cytokines in a group of HIV-TB individuals, previously naïve for HAART, recruited from a randomized clinical trial during TB treatment and first antiretroviral therapy with efavirenz. Patients were evaluated according to the immunosuppression levels at baseline as group 1 (CD4200 cells/mm(3)). These parameters were measured at the time of HAART initiation (started about 30 days after the onset of TB treatment) and at the follow-up visits after 30, 60, 90 and 180 days. Trajectories were estimated using least squares estimates of the coefficients of a restricted cubic spline function in time after adjusting for subject effects, bootstrapping it 500 times. Increase of CD4 T cell counts and suppression of HIV viral load were observed for all patients under HAART and TB treatment. Descendent trajectories were observed for the activated CD8(+)/CD38(+) and CD3(+)/HLA-DR(+) T cell subsets, and for plasma concentration of gamma- interferon (IFN-γ). Except for TNF-α and IL-2 discrete variations were observed for the other cytokines. Differences in the trajectories of these parameters were observed for groups 1 and 2. Higher values of IFN-γ, IL-2, IL-6 and IL-10 were observed for group 1 from the baseline to two months after treatment initiation, whereas reduced levels of TNF-α were observed for this group between 60 and 120 days of HAART. Independent of the immunosuppression profile at baseline, HIV-TB patients under HAART were able to recover the CD4(+) T cell counts, and control viral replication and immune activation parameters over time.

  8. Intestinal parasites coinfection does not alter plasma cytokines profile elicited in acute malaria in subjects from endemic area of Brazil.

    Science.gov (United States)

    Sánchez-Arcila, Juan Camilo; Perce-da-Silva, Daiana de Souza; Vasconcelos, Mariana Pinheiro Alves; Rodrigues-da-Silva, Rodrigo Nunes; Pereira, Virginia Araujo; Aprígio, Cesarino Junior Lima; Lima, Cleoni Alves Mendes; Fonseca e Fonseca, Bruna de Paula; Banic, Dalma Maria; Lima-Junior, Josué da Costa; Oliveira-Ferreira, Joseli

    2014-01-01

    In Brazil, malaria is prevalent in the Amazon region and these regions coincide with high prevalence of intestinal parasites but few studies explore the interaction between malaria and other parasites. Therefore, the present study evaluates changes in cytokine, chemokine, C-reactive protein, and nitric oxide (NO) concentrations in 264 individuals, comparing plasma from infected individuals with concurrent malaria and intestinal parasites to individuals with either malaria infection alone and uninfected. In the studied population 24% of the individuals were infected with Plasmodium and 18% coinfected with intestinal parasites. Protozoan parasites comprised the bulk of the intestinal parasites infections and subjects infected with intestinal parasites were more likely to have malaria. The use of principal component analysis and cluster analysis associated increased levels of IL-6, TNF-α, IL-10, and CRP and low levels of IL-17A predominantly with individuals with malaria alone and coinfected individuals. In contrast, low levels of almost all inflammatory mediators were associated predominantly with individuals uninfected while increased levels of IL-17A were associated predominantly with individuals with intestinal parasites only. In conclusion, our data suggest that, in our population, the infection with intestinal parasites (mainly protozoan) does not modify the pattern of cytokine production in individuals infected with P. falciparum and P. vivax.

  9. Th1 and Th2 cytokine profile in patients with early onset periodontitis and their healthy siblings

    Directory of Open Access Journals (Sweden)

    Jiřina Bártová

    2000-01-01

    Full Text Available Early onset periodontitis (EOP is a chronic inflammatory periodontal disease with a strong genetic link affecting individuals aged 17 to 25. In the familial studies we tested the hypothesis about the role of Th1 and Th2 cytokines in the pathogenesis of EOP disease. The study involved 6 individuals with EOP disease and their 6 siblings with healthy periodontium. Actinobacillus actinomycetemcomitans (A. a., a bacterium typical for EOP, was detected in all people studied. Th1 and Th2 cytokine production was measured after in vitro stimulation. Peripheral blood mononuclear cells (PBMC were isolated and cultivated for 24 h and 7 days with PWM, A. a. or Escherichia coli. The levels of IL–4, IFN-gamma, IgA, IgG and IgM were measured by ELISA methods. After in vitro stimulation of PBMC, a significantly higher production of IL–4 and significantly lower production of IFN-gamma were found in the group of patients compared with their healthy siblings. The increased level of IL–4 in patients was in good agreement with an increased level of IgM after stimulation of lymphocytes with E. coli. These results support Seymour’s hypothesis according to which patients with progressive disease primarily activate Th2 lymphocytes while non-susceptible individuals activate Th1 lymphocytes.

  10. Cytokine Profiles from Antigen-Stimulated Whole-Blood Samples among Patients with Pulmonary or Nonmeningeal Disseminated Coccidioidomycosis.

    Science.gov (United States)

    Ampel, Neil M; Nesbit, Lance A; Nguyen, Chinh T; Chavez, Suzette; Knox, Kenneth S; Johnson, Suzanne M; Pappagianis, Demosthenes

    2015-08-01

    The outcome of coccidioidomycosis depends on a robust specific cellular immune response. A T-helper type 1 (Th1) cellular immune response has been previously associated with resolution of clinical illness. However, the precise elements of this response and whether cytokines not involved with the Th1 response play a role in coccidioidomycosis are not known. Whole-blood samples were obtained from subjects with active coccidioidomycosis and controls and incubated for 18 h with T27K, a coccidioidal antigen preparation. The supernatant was then assayed for gamma interferon (IFN-γ), interleukin-2 (IL-2), tumor necrosis factor alpha (TNF-α), IL-4, IL-6, IL-10, and IL-17A. A total of 43 subjects, 16 with acute pneumonia, 9 with pulmonary sequelae of nodules and cavities, and 18 with nonmeningeal disseminated coccidioidomycosis, were studied. Compared to concentrations in healthy immune and nonimmune donors, the median concentration of IL-17A was significantly higher in those with active coccidioidomycosis (for both, P coccidioidomycosis is distinct in that IL-17A is persistently present. In addition, those with nonmeningeal disseminated disease have an increased inflammatory cytokine response and diminished Th1 responses that modulate over time. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  11. Intestinal Parasites Coinfection Does Not Alter Plasma Cytokines Profile Elicited in Acute Malaria in Subjects from Endemic Area of Brazil

    Directory of Open Access Journals (Sweden)

    Juan Camilo Sánchez-Arcila

    2014-01-01

    Full Text Available In Brazil, malaria is prevalent in the Amazon region and these regions coincide with high prevalence of intestinal parasites but few studies explore the interaction between malaria and other parasites. Therefore, the present study evaluates changes in cytokine, chemokine, C-reactive protein, and nitric oxide (NO concentrations in 264 individuals, comparing plasma from infected individuals with concurrent malaria and intestinal parasites to individuals with either malaria infection alone and uninfected. In the studied population 24% of the individuals were infected with Plasmodium and 18% coinfected with intestinal parasites. Protozoan parasites comprised the bulk of the intestinal parasites infections and subjects infected with intestinal parasites were more likely to have malaria. The use of principal component analysis and cluster analysis associated increased levels of IL-6, TNF-α, IL-10, and CRP and low levels of IL-17A predominantly with individuals with malaria alone and coinfected individuals. In contrast, low levels of almost all inflammatory mediators were associated predominantly with individuals uninfected while increased levels of IL-17A were associated predominantly with individuals with intestinal parasites only. In conclusion, our data suggest that, in our population, the infection with intestinal parasites (mainly protozoan does not modify the pattern of cytokine production in individuals infected with P. falciparum and P. vivax.

  12. Cytokine mRNA profiles in bronchoalveolar cells of piglets experimentally infected in utero with porcine reproductive and respiratory syndrome virus: Association of sustained expression of IFN-gamma and IL-10 after viral clearance

    DEFF Research Database (Denmark)

    Johnsen, C. K.; Bøtner, Anette; Kamstrup, Søren;

    2002-01-01

    An experimental model was used to investigate mRNA cytokine profiles in bronchoalvolar cells (BALC) from piglets, infected in utero with porcine reproductive and respiratory syndrome virus (PRRSV). The BALC's were analyzed for the cytokines TNF-alpha, IFN-gamma, IL-8, IL-10, and IL-12(p40) by real...... elevated in all three age groups. Virus was reduced by 50% in 4-week-old piglets and cleared by 6 weeks of age. The sustained expression of IFNgamma and reduction of IL-10 production indicate an important role for these cytokines in immunity to PRRSV....

  13. Effect of Treatment with Intranasal Corticosteroid and Oral Antihistamine on Cytokine Profiles of Peripheral Blood Mononuclear Cells of Patients with Allergic Rhinitis Sensitive to Chenopodium album

    Directory of Open Access Journals (Sweden)

    Shokrollah Farrokhi

    2010-12-01

    Full Text Available Patients with allergic rhinitis (AR show increased production of the Th2-related cytokines. Almost always, intranasal corticosteroid (INC and antihistamine are used as routine therapy of AR. This study was performed to determine the in vitro secretion of cytokines profiles of PBMCs in patients with AR sensitive to Chenopodium album (Ch.a pollens before and after treatment with INC (Fluticasone propionate and oral antihistamine (Loratadine. PBMCs of 20 patients with AR, were tested in vitro for cytokine production. These cells were stimulated with natural or recombinant Ch.a. The levels of IL-4, IL-13 and IFN-, were measured in supernatants of cultured cell 96h after stimulation using ELISA. The PBMCs of 20 normal individuals were also similarly treared for comparison of results. The production of IL-4 by the patients' cells stimulated with either Ch.a or rCh.a was significantly higher than normal levels before therapy (p=0.04 and p=0.02, respectively. After therapy, a significant decrease in production of IL-4 and a significant increase in production of IL-10 were found in PBMCs stimulated with natural Ch.a, in comparison to the results before stimulation (p=0.03 for IL-4; p=0.04 for IL-10. Similarly, these results were seen in the production of IL-4 and IL-10 stimulated with rCh.a allergen after therapy in comparison to the results before stimulation (p=0.01 for IL-4; p=0.03 for IL-10. This study suggests INC (Fluticasone propionate and oral antihistamine (Loratadine have the capacity to inhibit the production of IL-4 and shift Th2/Th1 responses, probably due to increase the level of immunoregulatory IL-10. Therefore, it could be concluded that therapy with INC and antihistamine has pharmacologic and immunologic therapeutic effects on AR patients.

  14. APOPTOSIS SYSTEM AND ITS RELATIONS TO HEPATOCELLULAR DAMAGE AND SOME INDEXES OF LOCAL CYTOKINE PROFILE CHRONIC HCV INFECTION

    Directory of Open Access Journals (Sweden)

    L. Ph. Skljar

    2008-01-01

    Full Text Available Abstract. At present time, some conflicting data concern a possible importance of apoptosis in pathogenesis of chronic hepatitis C. A significant role is ascribed to FAS/FAS-L, as a factor of hepatocyte apoptosis. CD95+ levels at the cell surfaces were studied in liver homogenates. A significant decrease in CD95+ cells was revealed in liver samples from the patients with higher histological indexes of hepatitis activity and fibrosis. A reverse relationship between CD95+ level and local concentrations of cytokines (TNFα, IL-1, IL-10, as well as significant direct correlation with IFNγ, IL-2 values were detected, thus suggesting a failure of compensatory mechanisms of immune regulation, and predominance of anti-apoptotic viral potential over protective cellular responses. (Med. Immunol., vol. 10, N 4-5, pp 415-422.

  15. Effect of oat bran on time to exhaustion, glycogen content and serum cytokine profile following exhaustive exercise

    Directory of Open Access Journals (Sweden)

    Frollini Anelena B

    2010-10-01

    Full Text Available Abstract The aim of this study was to evaluate the effect of oat bran supplementation on time to exhaustion, glycogen stores and cytokines in rats submitted to training. The animals were divided into 3 groups: sedentary control group (C, an exercise group that received a control chow (EX and an exercise group that received a chow supplemented with oat bran (EX-O. Exercised groups were submitted to an eight weeks swimming training protocol. In the last training session, the animals performed exercise to exhaustion, (e.g. incapable to continue the exercise. After the euthanasia of the animals, blood, muscle and hepatic tissue were collected. Plasma cytokines and corticosterone were evaluated. Glycogen concentrations was measured in the soleus and gastrocnemius muscles, and liver. Glycogen synthetase-α gene expression was evaluated in the soleus muscle. Statistical analysis was performed using a factorial ANOVA. Time to exhaustion of the EX-O group was 20% higher (515 ± 3 minutes when compared with EX group (425 ± 3 minutes (p = 0.034. For hepatic glycogen, the EX-O group had a 67% higher concentrations when compared with EX (p = 0.022. In the soleus muscle, EX-O group presented a 59.4% higher glycogen concentrations when compared with EX group (p = 0.021. TNF-α was decreased, IL-6, IL-10 and corticosterone increased after exercise, and EX-O presented lower levels of IL-6, IL-10 and corticosterone levels in comparison with EX group. It was concluded that the chow rich in oat bran increase muscle and hepatic glycogen concentrations. The higher glycogen storage may improve endurance performance during training and competitions, and a lower post-exercise inflammatory response can accelerate recovery.

  16. Effects of home-based bench step exercise on inflammatory cytokines and lipid profiles in elderly Japanese females: A randomized controlled trial.

    Science.gov (United States)

    Nishida, Yuichiro; Tanaka, Keitaro; Hara, Megumi; Hirao, Noriko; Tanaka, Hiroaki; Tobina, Takuro; Ikeda, Masaharu; Yamato, Hiroshi; Ohta, Masanori

    2015-01-01

    The purpose of the current study was to investigate the effects of a 12-week home-based bench step exercise program on inflammatory cytokines and lipid profiles in elderly females. Sixty-two postmenopausal females (65-85 years of age) were randomized to either the bench step exercise group (n=31) or the control group (n=31). The subjects in the bench step exercise group were instructed to perform bench step exercises at the exercise intensity corresponding to lactate threshold (LT), three times per day 10-20 min each session, for a goal of ≥140 min/week at home for 12 weeks. At baseline and 12 weeks, circulating levels of nine inflammatory cytokines (high-molecular-weight adiponectin, interleukin-4 [IL-4], IL-5, IL-6, IL-8, IL-15, tumor necrosis factor-α [TNF-α], TNF-β and interferon-γ [IFN-γ]) and serum lipids including high-density lipoprotein cholesterol (HDL-C) were measured. The bench step training at the LT significantly increased HDL-C levels and decreased IFN-γ concentrations in the subjects with lower (exercise group (ρ=-0.56, pexercise group. The bench step exercise-induced reduction in the IFN-γ levels may partially explain the degree of improvement in the HDL-C levels with the exercise program. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  17. Evaluation of Toll-Like receptor 2 and 4 RNA expression and the cytokine profile in postmenopausal women with metabolic syndrome.

    Directory of Open Access Journals (Sweden)

    Claudio Lera Orsatti

    Full Text Available OBJECTIVE: To evaluate the gene expression of Toll-Like (TLR-2 and TLR-4 receptors and cytokine profile in postmenopausal women with or without metabolic syndrome (MetS. METHODS: In this cross-sectional study, 311 Brazilian women (age≥45 years and amenorrhea≥12 months were included. Women showing three or more of the following diagnostic criteria were diagnosed as positive for MetS: waist circumference>88 cm, triglycerides≥150 mg/dL, HDL cholesterol0.05. A greater production of IL-6 was associated with TLR-2 and TLR-4 expressions and greater production of TNF-α was associated only with TLR-2 expression (P>0.05. Only the lower quartile of IL-10 was associated with the presence of the MetS (P>0.05. CONCLUSIONS: TLR-2 and TLR-4 expressions were associated with increased pro-inflammatory cytokines, IL-6 and TNF-α, with no association with biomarkers of MetS. The low concentrations of IL-10 may suggest an anti-inflammatory modulation in postmenopausal women with MetS.

  18. Risk factors of placental abruption

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    Hooria Seyedhosseini Ghaheh

    2013-01-01

    Full Text Available Background: Placental abruption is one of the most common causes of bleeding during pregnancy. Multiple factors are known to be associated with increase of risk of placental abruption such as alcohol, cocaine use and cigarette smoking. The objective of this study was to identify risk factors for placental abruption in an Iranian women population. Materials and Methods: In a retrospective case - control study birth records included 78 cases with placental abruption and 780 randomly selected controls were investigated. Statistical analysis for comparing the studied risk factors between groups was performed using Pearson ′ s Chi-square test along with presenting relevant odds ratio (OR. Results: From 7301 deliveries included in the study, 78 (1% was complicated placental abruption. Women aged 35 or more likely for experiencing (OR = 3.650, 95% confidence interval [CL] = 1.57-6.83 and those who had a previous cesarean section (OR = 2.65, 95% CL = 3.91- 33.41 were in higher risk for placental abruption ([50 cases] 64% vs. [28 cases] 36% P < 0.01. Conclusion: The results indicate that among the placental abruption is one of the most common causes of bleeding during the pregnancy and one of the major obstetrical emergency.

  19. Risk factors of placental abruption

    Science.gov (United States)

    Ghaheh, Hooria Seyedhosseini; Feizi, Awat; Mousavi, Maryam; Sohrabi, Davood; Mesghari, Leila; Hosseini, Zahra

    2013-01-01

    Background: Placental abruption is one of the most common causes of bleeding during pregnancy. Multiple factors are known to be associated with increase of risk of placental abruption such as alcohol, cocaine use and cigarette smoking. The objective of this study was to identify risk factors for placental abruption in an Iranian women population. Materials and Methods: In a retrospective case – control study birth records included 78 cases with placental abruption and 780 randomly selected controls were investigated. Statistical analysis for comparing the studied risk factors between groups was performed using Pearson's Chi-square test along with presenting relevant odds ratio (OR). Results: From 7301 deliveries included in the study, 78 (1%) was complicated placental abruption. Women aged 35 or more likely for experiencing (OR = 3.650, 95% confidence interval [CL] = 1.57-6.83) and those who had a previous cesarean section (OR = 2.65, 95% CL = 3.91- 33.41) were in higher risk for placental abruption ([50 cases] 64% vs. [28 cases] 36% P < 0.01). Conclusion: The results indicate that among the placental abruption is one of the most common causes of bleeding during the pregnancy and one of the major obstetrical emergency. PMID:24174950

  20. Placental perfusion - a human alternative

    DEFF Research Database (Denmark)

    Mose, Tina; Knudsen, Lisbeth E

    2006-01-01

    Foetal exposures to environmental and medicinal products have impact on the growth of the foetus (e.g. cigarette smoke) and development of organs (e.g. methylmercury and Thalidomide). Perfusion studies of the human term placenta enable investigation of placental transport of chemical substances...... between the mother and foetus. Dual perfusion of a single cotyledon in the human placenta can contribute to a better understanding of the placental barrier, transport rate and mechanisms of different substances and placental metabolism. The perfusion system has recently been established in Copenhagen...

  1. Cytokine-dependent and–independent gene expression changes and cell cycle block revealed in Trypanosoma cruzi-infected host cells by comparative mRNA profiling

    Directory of Open Access Journals (Sweden)

    Burleigh Barbara A

    2009-05-01

    Full Text Available Abstract Background The requirements for growth and survival of the intracellular pathogen Trypanosoma cruzi within mammalian host cells are poorly understood. Transcriptional profiling of the host cell response to infection serves as a rapid read-out for perturbation of host physiology that, in part, reflects adaptation to the infective process. Using Affymetrix oligonucleotide array analysis we identified common and disparate host cell responses triggered by T. cruzi infection of phenotypically diverse human cell types. Results We report significant changes in transcript abundance in T. cruzi-infected fibroblasts, endothelial cells and smooth muscle cells (2852, 2155 and 531 genes respectively; fold-change ≥ 2, p-value T. cruzi-infected fibroblasts and endothelial cells transwell plates were used to distinguish cytokine-dependent and -independent gene expression profiles. This approach revealed the induction of metabolic and signaling pathways involved in cell proliferation, amino acid catabolism and response to wounding as common themes in T. cruzi-infected cells. In addition, the downregulation of genes involved in mitotic cell cycle and cell division predicted that T. cruzi infection may impede host cell cycle progression. The observation of impaired cytokinesis in T. cruzi-infected cells, following nuclear replication, confirmed this prediction. Conclusion Metabolic pathways and cellular processes were identified as significantly altered at the transcriptional level in response to T. cruzi infection in a cytokine-independent manner. Several of these alterations are supported by previous studies of T. cruzi metabolic requirements or effects on the host. However, our methods also revealed a T. cruzi-dependent block in the host cell cycle, at the level of cytokinesis, previously unrecognized for this pathogen-host cell interaction.

  2. Enhanced and enduring protection against tuberculosis by recombinant BCG-Ag85C and its association with modulation of cytokine profile in lung.

    Directory of Open Access Journals (Sweden)

    Ruchi Jain

    Full Text Available BACKGROUND: The variable efficacy (0-80% of Mycobacterium bovis Bacille Calmette Guréin (BCG vaccine against adult tuberculosis (TB necessitates development of alternative vaccine candidates. Development of recombinant BCG (rBCG over-expressing promising immunodominant antigens of M. tuberculosis represents one of the potential approaches for the development of vaccines against TB. METHODS/PRINCIPAL FINDINGS: A recombinant strain of BCG - rBCG85C, over expressing the antigen 85C, a secretory immuno-dominant protein of M. tuberculosis, was evaluated for its protective efficacy in guinea pigs against M. tuberculosis challenge by aerosol route. Immunization with rBCG85C resulted in a substantial reduction in the lung (1.87 log(10, p<0.01 and spleen (2.36 log(10, p<0.001 bacillary load with a commensurate reduction in pathological damage, when compared to the animals immunized with the parent BCG strain at 10 weeks post-infection. rBCG85C continued to provide superior protection over BCG even when post-challenge period was prolonged to 16 weeks. The cytokine profile of pulmonary granulomas revealed that the superior protection imparted by rBCG85C was associated with the reduced levels of pro-inflammatory cytokines - interleukin (IL-12, interferon (IFN-gamma, tumor necrosis factor (TNF-alpha, moderate levels of anti-inflammatory cytokine - transforming growth factor (TGF-beta along with up-regulation of inducible nitric oxide synthase (iNOS. In addition, the rBCG85C vaccine induced modulation of the cytokine levels was found to be associated with reduced fibrosis and antigen load accompanied by the restoration of normal lung architecture. CONCLUSIONS/SIGNIFICANCE: These results clearly indicate the superiority of rBCG85C over BCG as a promising prophylactic vaccine against TB. The enduring protection observed in this study gives enough reason to postulate that if an open-ended study is carried out with low dose of infection, rBCG85C vaccine in all

  3. Plasma profile of pro-inflammatory cytokines and chemokines in cocaine users under outpatient treatment: influence of cocaine symptom severity and psychiatric co-morbidity.

    Science.gov (United States)

    Araos, Pedro; Pedraz, María; Serrano, Antonia; Lucena, Miguel; Barrios, Vicente; García-Marchena, Nuria; Campos-Cloute, Rafael; Ruiz, Juan J; Romero, Pablo; Suárez, Juan; Baixeras, Elena; de la Torre, Rafael; Montesinos, Jorge; Guerri, Consuelo; Rodríguez-Arias, Marta; Miñarro, José; Martínez-Riera, Roser; Torrens, Marta; Chowen, Julie A; Argente, Jesús; Mason, Barbara J; Pavón, Francisco J; Rodríguez de Fonseca, Fernando

    2015-07-01

    The treatment for cocaine use constitutes a clinical challenge because of the lack of appropriate therapies and the high rate of relapse. Recent evidence indicates that the immune system might be involved in the pathogenesis of cocaine addiction and its co-morbid psychiatric disorders. This work examined the plasma pro-inflammatory cytokine and chemokine profile in abstinent cocaine users (n = 82) who sought outpatient cocaine treatment and age/sex/body mass-matched controls (n = 65). Participants were assessed with the diagnostic interview Psychiatric Research Interview for Substance and Mental Diseases according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR). Tumor necrosis factor-alpha, chemokine (C-C motif) ligand 2/monocyte chemotactic protein-1 and chemokine (C-X-C motif) ligand 12 (CXCL12)/stromal cell-derived factor-1 (SDF-1) were decreased in cocaine users, although all cytokines were identified as predictors of a lifetime pathological use of cocaine. Interleukin-1 beta (IL-1β), chemokine (C-X3-C motif) ligand 1 (CX3CL1)/fractalkine and CXCL12/SDF-1 positively correlated with the cocaine symptom severity when using the DSM-IV-TR criteria for cocaine abuse/dependence. These cytokines allowed the categorization of the outpatients into subgroups according to severity, identifying a subgroup of severe cocaine users (9-11 criteria) with increased prevalence of co-morbid psychiatric disorders [mood (54%), anxiety (32%), psychotic (30%) and personality (60%) disorders]. IL-1β was observed to be increased in users with such psychiatric disorders relative to those users with no diagnosis. In addition to these clinical data, studies in mice demonstrated that plasma IL-1β, CX3CL1 and CXCL12 were also affected after acute and chronic cocaine administration, providing a preclinical model for further research. In conclusion, cocaine exposure modifies the circulating levels of pro-inflammatory mediators. Plasma

  4. Functional variability in butyrylcholinesterase activity regulates intrathecal cytokine and astroglial biomarker profiles in patients with Alzheimer's disease.

    Science.gov (United States)

    Darreh-Shori, Taher; Vijayaraghavan, Swetha; Aeinehband, Shahin; Piehl, Fredrik; Lindblom, Rickard P F; Nilsson, Bo; Ekdahl, Kristina N; Långström, Bengt; Almkvist, Ove; Nordberg, Agneta

    2013-11-01

    Butyrylcholinesterase (BuChE) activity is associated with activated astrocytes in Alzheimer's disease brain. The BuChE-K variant exhibits 30%-60% reduced acetylcholine (ACh) hydrolyzing capacity. Considering the increasing evidence of an immune-regulatory role of ACh, we investigated if genetic heterogeneity in BuChE affects cerebrospinal fluid (CSF) biomarkers of inflammation and cholinoceptive glial function. Alzheimer's disease patients (n = 179) were BCHE-K-genotyped. Proteomic and enzymatic analyses were performed on CSF and/or plasma. BuChE genotype was linked with differential CSF levels of glial fibrillary acidic protein, S100B, interleukin-1β, and tumor necrosis factor (TNF)-α. BCHE-K noncarriers displayed 100%-150% higher glial fibrillary acidic protein and 64%-110% higher S100B than BCHE-K carriers, who, in contrast, had 40%-80% higher interleukin-1β and 21%-27% higher TNF-α compared with noncarriers. A high level of CSF BuChE enzymatic phenotype also significantly correlated with higher CSF levels of astroglial markers and several factors of the innate complement system, but lower levels of proinflammatory cytokines. These individuals also displayed beneficial paraclinical and clinical findings, such as high cerebral glucose utilization, low β-amyloid load, and less severe progression of clinical symptoms. In vitro analysis on human astrocytes confirmed the involvement of a regulated BuChE status in the astroglial responses to TNF-α and ACh. Histochemical analysis in a rat model of nerve injury-induced neuroinflammation, showed focal assembly of astroglial cells in proximity of BuChE-immunolabeled sites. In conclusion, these results suggest that BuChE enzymatic activity plays an important role in regulating intrinsic inflammation and activity of cholinoceptive glial cells and that this might be of clinical relevance. The dissociation between astroglial markers and inflammatory cytokines indicates that a proper activation and maintenance of

  5. Serum cytokine/chemokine profiles in patients with dengue fever (DF) and dengue hemorrhagic fever (FHD) by using protein array.

    Science.gov (United States)

    Oliveira, Renato Antonio Dos Santos; Cordeiro, Marli Tenório; Moura, Patrícia Muniz Mendes Freire de; Baptista Filho, Paulo Neves Bapti; Braga-Neto, Ulisses de Mendonça; Marques, Ernesto Torres de Azevedo; Gil, Laura Helena Vega Gonzales

    2017-04-01

    DENV infection can induce different clinical manifestations varying from mild forms to dengue fever (DF) or the severe hemorrhagic fever (DHF). Several factors are involved in the progression from DF to DHF. No marker is available to predict this progression. Such biomarker could allow a suitable medical care at the beginning of the infection, improving patient prognosis. The aim of this study was to compare the serum expression levels of acute phase proteins in a well-established cohort of dengue fever (DF) and dengue hemorrhagic fever (DHF) patients, in order to individuate a prognostic marker of diseases severity. The serum levels of 36 cytokines, chemokines and acute phase proteins were determined in DF and DHF patients and compared to healthy volunteers using a multiplex protein array and near-infrared (NIR) fluorescence detection. Serum levels of IL-1ra, IL-23, MIF, sCD40 ligand, IP-10 and GRO-α were also determined by ELISA. At the early stages of infection, GRO-α and IP-10 expression levels were different in DF compared to DHF patients. Besides, GRO-α was positively correlated with platelet counts and IP-10 was negatively correlated with total protein levels. These findings suggest that high levels of GRO-α during acute DENV infection may be associated with a good prognosis, while high levels of IP-10 may be a warning sign of infection severity. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Sodium arsenite mediated immuno-disruption through alteration of transcription profile of cytokines in chicken splenocytes under in vitro system.

    Science.gov (United States)

    Das, Subhashree; Pan, Diganta; Bera, Asit Kumar; Rana, Tanmoy; Bhattacharya, Debasis; Bandyapadyay, Subhasis; De, Sumanta; Sreevatsava, V; Bhattacharya, Somnath; Das, Subrata Kumar; Bandyopadhayay, Sandip

    2011-01-01

    Arsenic is a ubiquitously found metalloid that commonly contaminates drinking water and agricultural food. To understand the ecotoxicological effects of arsenic in environment, it is essential to ameliorate the deleterious effects on human and animal health, particularly on the immune response. We investigated the effects of inorganic arsenic (iAs) on the immune response of chicken splenocytes. Both 1 and 10 mM concentrations of sodium arsenite treatment significantly reduced (Ptreatment also revealed time dependent differences. Relative quantification of expression of IFNγ and IL2 revealed that both genes were significantly down regulated (P<0.001) at both concentrations at each time point. iNOS gene was rapidly down regulated in splenocytes at 24 h at the high doses of As treated splenocyte, a gradual decreasing trend at low doses. Down regulation of IL-2 gene expression in response to As was further evidenced by a significant reduction (P<0.001) in the release of IL-2 into the splenocyte culture medium. We suggest that arsenic, a potent immunotoxic agent, modulates non-specific immune responses and alters the expression of cytokines in a dose and time dependent manner.

  7. Placental Transmogrification of the lung

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jin Woo; Park, Il Hwan; Kwon, Woo Cheol; Eom, Min Seob; Kim, Young Ju; Hwan, Joong Hwan [Yonsei University Wonju College of Medicine, Wonju (Korea, Republic of)

    2013-12-15

    Placental transmogrification is a very rare lung disease, where the alveoli resemble the chorionic villi of placenta, and this change is a characteristic finding. A 31-year-old female patient presented with cough and dyspnea that had begun 2 weeks prior to admission. Along with giant bulla found in the left upper lung field, subsegmental consolidation was also identified in the lingular segment on plain chest radiograph and CT scan. Wedge resection was performed to remove the bulla. Pathologic examination of the resected bulla revealed destruction of the normal structures and characteristic villous and papillary changes. These changes led to a diagnosis of placental transmogrification. We made an encounter of an unusual placental transmogrification which had different image findings from other reported transmogrification cases. Thus, we report an atypical placental transmogrification case where both consolidation and giant bulla coexist.

  8. Placental abruption: a persisting killer

    Directory of Open Access Journals (Sweden)

    Shakuntala Amirchand Chhabra

    2014-06-01

    Full Text Available Background: Placental abruption, common disorder in obstetric practice, enigma too, is uniquely fraught with dangers to mother baby. Objectives of study were to study trends of placental abruption, risk factors, management strategies to learn more for reduction in morbidity-mortality of mother-baby, even with low resources, also get insight for future research. Methods: Records of cases of placental abruption managed over 27 years (between 1985 to 2011 were divided into three yearly blocks, A to I and analysed. Details including operative procedures like dilatation-curettage, Caesarean Section (CS or Ante-Partum Haemorrhage (APH in past, disorders like chronic hypertension, threatened abortion, pregnancy specific hypertension, diabetes, anaemia in index pregnancy, management done maternal-neonatal outcome were analysed using stata 6 software. Results: There were 66,459 births during analysis period with 667 cases of placental abruption, 1% births, increasing trends from, 0.73% between 1985-1987 to, 1.11% in 2009-2011. In these 667 cases of placental abruption, 211 (32.5% perinatal deaths occurred. Ratio of perinatal deaths due to placental abruption to overall perinatal deaths increased from 2.12% (8 cases between 1985-1987 (Block A to 5.12% (37 cases between 2009-2011 (Block I. Case fatality in cases of placental abruption has been fluctuating between 3 to 5% till 2004, contributing to around 12-15%, maternal mortality, with no fatality in last 7 years. Conclusions: Cases of placental abruption have been increasing with no obvious reason. In recent past maternal deaths could be prevented but perinatal deaths, have been persisting actually more in last decade. [Int J Reprod Contracept Obstet Gynecol 2014; 3(3.000: 604-609

  9. Histopathological placental lesions in mild gestational hyperglycemic and diabetic women

    Directory of Open Access Journals (Sweden)

    Rudge Marilza VC

    2011-08-01

    Full Text Available Abstract Objective To investigate and compare the incidence of histopathological placental lesions in mild gestational hyperglycemia, gestational diabetes and overt diabetes at term and preterm gestation. Research design and methods One-hundred-and-thirty-one placental samples were collected from Diabetes mellitus (DM positive screened patients. Two diagnostic tests, glycemic profile and 100 g oral glucose tolerance test (OGTT in parallel identified 4 groups normoglycemic, mild gestational hyperglycemia (MGH, gestational DM (GDM or overt DM (DM. Placental tissue specimens and sections from 4 groups were obtained by uniform random sampling and stained with hematoxylin-eosin. Results Placentas from MGH group presented 17 types of histopathological change and higher rates of syncytial nodes and endarteritis. GDM placentas presented only nine types of histopathological change, high rates of dysmaturity, low rates of calcification and no syncytial nodes. Overt DM placentas showed 22 types of histopathological change, 21 of which were present in the preterm period. There were histopathological similarities between MGH and DM placentas, but the former exhibited a higher incidence of endarteritis, which has been described as a "post-mortem" phenomenon. Conclusion Our results confirmed that the distinct placental changes associated with DM and MGH depend on gestational period during which the diabetic insult occurs. It may reasonably be inferred that subclinical maternal hyperglycemia during pregnancy, as showed in MGH group, is responsible for increased placental endarteritis, a postmortem lesion in the live fetus.

  10. Evolution of the Macrophage CD163 Phenotype and Cytokine Profiles in a Human Model of Resolving Inflammation

    Directory of Open Access Journals (Sweden)

    Betsy J. Evans

    2013-01-01

    Full Text Available Cantharidin skin blisters were examined over two days to model the acute and resolving phases of inflammation in human skin. Four blisters were created by topical administration of cantharidin (0.1% v/v to the forearm of healthy volunteers, with IRB approval. Duplicate skin blisters were aspirated at 16 and 40 hours to model the proinflammatory and resolving phases, respectively. There was a significant increase in leukocyte infiltrate at 40 h with appearance of a “resolving macrophage” phenotype CD14+CD163+ by flow cytometry. Neutrophils acquired apoptotic markers at 40 h and were observed to be phagocytosed by macrophagic “Reiter’s” cells. Multiplex cytokine analysis demonstrated that monocyte chemoattractant protein (MCP-1/CCL2, interleukin- (IL- 6, IL-8/CXCL8, macrophage inflammatory protein (MIP1α/CCL3, MIP-1β/CCL4, tumor necrosis factor- (TNF- α, and eotaxin (CCL11 were all significantly upregulated at 16 h compared with 40 h. In contrast, immunoregulatory transforming growth factor- (TGF- β, macrophage-derived chemokine (MDC/CCL22, and interferon-inducible protein (IP-10/CXCL10 were significantly elevated at 40 h. Our results demonstrate that the phases of inflammation and resolution can be discriminated in a two-day model of dermal wound healing. This confirms and extends our understanding of wound repair in humans and provides a powerful research tool for use in clinical settings and to track the molecular benefits of therapeutic intervention.

  11. Serum profile of cytokines interferon gamma and interleukin-10 in ewes subjected to artificial insemination by cervical retraction.

    Science.gov (United States)

    Alvares, C T G; Cruz, J F; Romano, C C; Brandão, F Z

    2016-04-15

    This study evaluated the influence of artificial insemination (AI) by cervical retraction (CRI) on serum levels of interferon gamma (IFNγ) and interleukin-10 (IL-10) in ewes. Synchronized pluriparous Santa Inês ewes were subjected to natural mating (NM, n = 8) and AI, which was performed for a fixed time (55 ± 1 hour) by CRI (n = 8) or laparoscopy (n = 8). Ewes were classified as pregnant, with return to estrus (RE) or with embryonic loss (EL). Blood samples were collected on Day 0, Day 3, Day 5, Day 12, and Day 17 (Day 0 = AI/NM) for progesterone dosage and cytokines were quantified from Day 0 to Day 12. Progesterone levels were constant, except for a decrease in ewes with RE at Day 17 (P IL-10 levels at any time, with averages of 642.1, 713.2, and 741.2 pg/mL for IFNγ and 667.1, 616.8, and 721.1 pg/mL for IL-10 when using CRI, laproscopy, and NM, respectively. Regarding the physiological status, ewes with EL had lower serum levels of IFNγ and IL-10 than pregnant ewes and ewes with RE, regardless of the reproductive method used, with averages of 769.1, 714.9, and 555.7 pg/mL for IFNγ and 713.8, 699.3, and 578.7 pg/mL for IL-10 in pregnant ewes, ewes with RE and EL, respectively (P IL-10 and does not induce an inflammatory reaction that can compromise pregnancy.

  12. Lipidomics of Mesenchymal Stromal Cells: Understanding the Adaptation of Phospholipid Profile in Response to Pro-Inflammatory Cytokines.

    Science.gov (United States)

    Campos, Ana Margarida; Maciel, Elisabete; Moreira, Ana S P; Sousa, Bebiana; Melo, Tânia; Domingues, Pedro; Curado, Liliana; Antunes, Brígida; Domingues, M Rosário M; Santos, Francisco

    2016-05-01

    Mesenchymal stromal cells (MSCs) present anti-inflammatory properties and are being used with great success as treatment for inflammatory and autoimmune diseases. In clinical applications MSCs are subjected to a strong pro-inflammatory environment, essential to their immunosuppressive action. Despite the wide clinical use of these cells, how MSCs exert their effect remains unclear. Several lipids are known to be involved in cell's signaling and modulation of cellular functions. The aim of this paper is to examine the variation in lipid profile of MSCs under pro-inflammatory environment, induced by the presence of tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ), using the most modern lipidomic approach. Major changes in lipid molecular profile of phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS), lysoPC (LPC), and sphingomyelin (SM) classes were found. No changes were observed in the phosphatidylinositol (PI) profile. The levels of PC species with shorter fatty acids (FAs), mainly C16:0, decreased under pro-inflammatory stimuli. The level of PC(40:6) also decreased, which may be correlated with enhanced levels of LPC(18:0), which is known to be an anti-inflammatory LPC, observed in MSCs subjected to TNF-α and IFN-γ. Simultaneously, the relative amounts of PC(36:1) and PC(38:4) increased. TNF-α and IFN-γ also enhanced the levels of PE(40:6) and decreased the levels of PE(O-38:6). Higher expression of PS(36:1) and SM(34:0) along with a decrease in PS(38:6) levels were observed. These results indicate that lipid metabolism and signaling are modulated during MSCs activation, which suggests that lipids may be involved in MSCs functional and anti-inflammatory activities.

  13. Cytokine profiles in pregnant gilts experimentally infected with porcine reproductive and respiratory syndrome virus and relationships with viral load and fetal outcome

    Science.gov (United States)

    In spite of extensive research, immunologic control mechanisms against Porcine Reproductive and Respiratory Syndrome virus (PRRSv) remain poorly understood. Cytokine responses have been exhaustively studied in nursery pigs and show contradictory results. Since no detailed reports on cytokine respons...

  14. CpG Oligodeoxynucleotides Induce Differential Cytokine and Chemokine Gene Expression Profiles in Dapulian and Landrace Pigs

    OpenAIRE

    Jiaqing Hu; Yongqing Zeng; Wei Chen; Hui Wang; Dandan Yang; Chuanhao Li

    2016-01-01

    Oligodeoxynucleotides containing unmethylated CpG motifs (CpG ODN) mimic the immunostimulatory activity of microbial DNA by interacting with Toll-like receptor 9 (TLR9) to activate both the innate and adaptive immune responses in different species. However, few studies have been published to compare the effects of CpG ODN on different pig breeds. Therefore, in this study, whole blood gene expression profiles of DPL and Landrace pigs treated with CpG ODN were studied using RNA-seq technology. ...

  15. Placental Growth Factor Administration Abolishes Placental Ischemia-Induced Hypertension.

    Science.gov (United States)

    Spradley, Frank T; Tan, Adelene Y; Joo, Woo S; Daniels, Garrett; Kussie, Paul; Karumanchi, S Ananth; Granger, Joey P

    2016-04-01

    Preeclampsia is a pregnancy-specific disorder of new-onset hypertension. Unfortunately, the most effective treatment is early delivery of the fetus and placenta. Placental ischemia appears central to the pathogenesis of preeclampsia because placental ischemia/hypoxia induced in animals by reduced uterine perfusion pressure (RUPP) or in humans stimulates release of hypertensive placental factors into the maternal circulation. The anti-angiogenic factor soluble fms-like tyrosine kinase-1 (sFlt-1), which antagonizes and reduces bioavailable vascular endothelial growth factor and placental growth factor (PlGF), is elevated in RUPP rats and preeclampsia. Although PlGF and vascular endothelial growth factor are both natural ligands for sFlt-1, vascular endothelial growth factor also has high affinity to VEGFR2 (Flk-1) causing side effects like edema. PlGF is specific for sFlt-1. We tested the hypothesis that PlGF treatment reduces placental ischemia-induced hypertension by antagonizing sFlt-1 without adverse consequences to the mother or fetus. On gestational day 14, rats were randomized to 4 groups: normal pregnant or RUPP±infusion of recombinant human PlGF (180 μg/kg per day; AG31, a purified, recombinant human form of PlGF) for 5 days via intraperitoneal osmotic minipumps. On day 19, mean arterial blood pressure and plasma sFlt-1 were higher and glomerular filtration rate lower in RUPP than normal pregnant rats. Infusion of recombinant human PlGF abolished these changes seen with RUPP along with reducing oxidative stress. These data indicate that the increased sFlt-1 and reduced PlGF resulting from placental ischemia contribute to maternal hypertension. Our novel finding that recombinant human PlGF abolishes placental ischemia-induced hypertension, without major adverse consequences, suggests a strong therapeutic potential for this growth factor in preeclampsia.

  16. Interleukin-1 family cytokines and their regulatory proteins in normal pregnancy and pre-eclampsia.

    Science.gov (United States)

    Southcombe, J H; Redman, C W G; Sargent, I L; Granne, I

    2015-09-01

    Maternal systemic inflammation is a feature of pre-eclampsia, a condition in pregnancy characterized by hypertension and proteinuria. Pre-eclampsia is caused by the placenta; many placental factors contribute to the syndrome's progression, and proinflammatory cytokines have been identified previously as one such mediator. The interleukin (IL)-1 family of cytokines are key regulators of the inflammatory network, and two naturally occurring regulatory molecules for IL-1 family cytokines, IL-1RA and sST2, have been found previously to be elevated in maternal blood from women with pre-eclampsia. Here we investigate more recently identified IL-1 family cytokines and regulatory molecules, IL-1RAcP, IL-37, IL-18BP, IL-36α/β/γ/Ra and IL-38 in pre-eclampsia. Pregnant women have more circulating IL-18BP and IL-36Ra than non-pregnant women, and sIL-1RAcP is elevated from women with pre-eclampsia compared to normal pregnancies. The placenta expresses all the molecules, and IL-37 and IL-18BP are up-regulated significantly in pre-eclampsia placentas compared to those from normal pregnancies. Together, these changes contribute to the required inhibition of maternal systemic cytotoxic immunity in normal pregnancy; however, in pre-eclampsia the same profile is not seen. Interestingly, the increased circulating levels of sIL-1RAcP and increased placental IL-18BP and IL-37, the latter of which we show to be induced by hypoxic damage to the placenta, are all factors which are anti-inflammatory. While the placenta is often held responsible for the damage and clinical symptoms of pre-eclampsia by the research community, here we show that the pre-eclampsia placenta is also trying to prevent inflammatory damage to the mother.

  17. Imaging and assessment of placental function.

    LENUS (Irish Health Repository)

    Moran, Mary

    2011-09-01

    The placenta is the vital support organ for the developing fetus. This article reviews current ultrasound (US) methods of assessing placental function. The ability of ultrasound to detect placental pathology is discussed. Doppler technology to investigate the fetal, placental, and maternal circulations in both high-risk and uncomplicated pregnancies is discussed and the current literature on the value of three-dimensional power Doppler studies to assess placental volume and vascularization is also evaluated. The article highlights the need for further research into three-dimensional ultrasound and alternative methods of placental evaluation if progress is to be made in optimizing placental function assessment.

  18. Does malaria affect placental development? Evidence from in vitro models.

    Directory of Open Access Journals (Sweden)

    Alexandra J Umbers

    Full Text Available BACKGROUND: Malaria in early pregnancy is difficult to study but has recently been associated with fetal growth restriction (FGR. The pathogenic mechanisms underlying malarial FGR are poorly characterized, but may include impaired placental development. We used in vitro methods that model migration and invasion of placental trophoblast into the uterine wall to investigate whether soluble factors released into maternal blood in malaria infection might impair placental development. Because trophoblast invasion is enhanced by a number of hormones and chemokines, and is inhibited by pro-inflammatory cytokines, many of which are dysregulated in malaria in pregnancy, we further compared concentrations of these factors in blood between malaria-infected and uninfected pregnancies. METHODOLOGY/PRINCIPAL FINDINGS: We measured trophoblast invasion, migration and viability in response to treatment with serum or plasma from two independent cohorts of Papua New Guinean women infected with Plasmodium falciparum or Plasmodium vivax in early pregnancy. Compared to uninfected women, serum and plasma from women with P. falciparum reduced trophoblast invasion (P = .06 and migration (P = .004. P. vivax infection did not alter trophoblast migration (P = .64. The P. falciparum-specific negative effect on placental development was independent of trophoblast viability, but associated with high-density infections. Serum from P. falciparum infected women tended to have lower levels of trophoblast invasion promoting hormones and factors and higher levels of invasion-inhibitory inflammatory factors. CONCLUSION/SIGNIFICANCE: We demonstrate that in vitro models of placental development can be adapted to indirectly study the impact of malaria in early pregnancy. These infections could result in impaired trophoblast invasion with reduced transformation of maternal spiral arteries due to maternal hormonal and inflammatory disturbances, which may contribute to FGR by

  19. Molecules consolidate the placental mammal tree

    NARCIS (Netherlands)

    Springer, M.S.; Stanhope, M.J.; Madsen, O.; Jong, W.W.W. de

    2004-01-01

    Deciphering relationships among the orders of placental mammals remains an important problem in evolutionary biology and has implications for understanding patterns of morphological character evolution, reconstructing the ancestral placental genome, and evaluating the role of plate tectonics and dis

  20. Molecules consolidate the placental mammal tree

    NARCIS (Netherlands)

    Springer, M.S.; Stanhope, M.J.; Madsen, O.; Jong, W.W.W. de

    2004-01-01

    Deciphering relationships among the orders of placental mammals remains an important problem in evolutionary biology and has implications for understanding patterns of morphological character evolution, reconstructing the ancestral placental genome, and evaluating the role of plate tectonics and

  1. Placental lactogen levels in diabetic pregnancy.

    Science.gov (United States)

    Ursell, W; Brudenell, M; Chard, T

    1973-04-14

    A prospective study has been carried out of placental lactogen levels in pregnancy complicated by diabetes mellitus. The levels were higher than those in normal pregnant subjects; the higher levels were related to increased placental and fetal weight but more closely to the former; and lower levels were found when there was clinical evidence of placental dysfunction. Those patients requiring the largest insulin increment for the control of their diabetes in the pregnancy have placental lactogen levels in the higher range.

  2. Intrapritoneal Hemorrhage after Placental Abruption

    Directory of Open Access Journals (Sweden)

    Nahid Sakhavar

    2012-06-01

    Full Text Available A placental abruption or abruptio placentae (where in the placental lining has separated from the uterus of the mother is one of the complications caused by trauma during pregnancy. It lets the blood flow to infiltrate in the uterine lining and to develop Couvelaire uterus (also known as uteroplacental apoplexy and uterine atony (a condition in which a woman's uterine muscles lose the ability to contract after childbirth; however, it rarely develops considerable hemoperitoneum which needs hysterectomy. In this report, a unique case of placental abruption caused by trauma in a 28-year-old Afghan woman is introduced in which severity and duration of trauma because of delay in reaching health equipped center led to developing massive hemoperitoneum (infiltration of great amount of blood into the abdominal cavity and its complications.

  3. Plasma placental lactogen in pregnancy.

    Science.gov (United States)

    Raghuramulu, N

    1978-01-01

    Plasma placental lactogen (HPL) and urinary oestrogen levels were investigated in pregnant women belonging to low and high socio-economic groups. Plasma HPL levels increased progressively with increasing gestation in women of both the socio-economic groups. The mean values in the two groups were not statistically different at any period of gestation. No correlation was observed between the birth weight of the infant and the maternal plasma placental lactogen levels at term. A positive correlation was observed between urinary oestrogen excretion and plasma HPL concentration.

  4. Transcriptional profiles of cytokine/chemokine factors of immune cell-homing to the parasitic lesions: a comprehensive one-year course study in the liver of E. multilocularis-infected mice.

    Directory of Open Access Journals (Sweden)

    Junhua Wang

    Full Text Available Pathogenesis of chronically developing alveolar echinococcosis (AE is characterized by a continuous, granulomatous, periparasitic infiltration of immune cells surrounding the metacestode of Echinococcus multilocularis (E.multilocularis in the affected liver. A detailed cytokine and chemokine profile analysis of the periparasitic infiltrate in the liver has, however, not yet been carried out in a comprehensive way all along the whole course of infection in E. multilocularis intermediate hosts. We thus assessed the hepatic gene expression profiles of 18 selected cytokine and chemokine genes using qRT-PCR in the periparasitic immune reaction and the subsequent adjacent, not directly affected, liver tissue of mice from day 2 to day 360 post intra-hepatic injection of metacestode. DNA microarray analysis was also used to get a more complete picture of the transcriptional changes occurring in the liver surrounding the parasitic lesions. Profiles of mRNA expression levels in the hepatic parasitic lesions showed that a mixed Th1/Th2 immune response, characterized by the concomitant presence of IL-12α, IFN-γ and IL-4, was established very early in the development of E. multilocularis. Subsequently, the profile extended to a combined tolerogenic profile associating IL-5, IL-10 and TGF-β. IL-17 was permanently expressed in the liver, mostly in the periparasitic infiltrate; this was confirmed by the increased mRNA expression of both IL-17A and IL-17F from a very early stage, with a subsequent decrease of IL-17A after this first initial rise. All measured chemokines were significantly expressed at a given stage of infection; their expression paralleled that of the corresponding Th1, Th2 or Th17 cytokines. In addition to giving a comprehensive insight in the time course of cytokines and chemokines in E. multilocularis lesion, this study contributes to identify new targets for possible immune therapy to minimize E. multilocularis-related pathology and to

  5. T-bet/GATA-3 ratio is a surrogate measure of Th1/Th2 cytokine profiles and may be novel targets for CpG ODN treatment in asthma patients

    Institute of Scientific and Technical Information of China (English)

    DONG Liang; CHEN Ming; ZHANG Qi; LI Li-zheng; XU Xiao-qun; XIAO Wei

    2006-01-01

    @@ Naive helper T (Th) cells are divided into two subsets, Th1 and Th2. Th1 cells produce predominantly interferon-γ (IFN-γ), and Th2 cells produce interleukin-4 (IL-4), IL-5 and IL-13, but not IFN-γ.1 In asthma, an imbalance in the Th1/Th2 cytokine ratio characterized with a shift towards a predominantly Th2 cytokine profile in asthma occurs.2 The differentiation of naive helper T cells towards Th1 or Th2 cells is regulated by the ranscription factors T-box expressed in T-cells (T-bet) and GATA-binding protein-3 (GATA-3).3 We therefore hypothesized that the altered Th1/Th2cytokine expression in asthma is the result of a shift from T-bet to GATA-3 profile. In this study, we demonstrated that the ratio of T-bet/GATA-3 could predict the imbalance of Th1/Th2 cytokine in asthma patients.

  6. Placental diversity in malagasy tenrecs

    DEFF Research Database (Denmark)

    Enders, A C; Blankenship, T N; Goodman, S M;

    2007-01-01

    Placentation in tenrecs of the subfamily Oryzorictinae, family Tenrecidae, has not been described previously. The structure of the placenta of this group and especially of the genus Microgale was investigated to determine its similarity or dissimilarity to previously described placentas of the te...

  7. PLACENTAL SIZE AND PERINATAL OUTCOMES

    Directory of Open Access Journals (Sweden)

    Nagamani

    2015-03-01

    Full Text Available BACKGROUND : The human placenta, a transient organ or pregnancy provides information about fetal well - being and pregnancy outcome . AIMS: To study the placental ultrasound characters in relation to perinatal outcomes . SETTINGS: Tertiary care hospital in southern India . METHODS AND MATERIAL S: The study sample comprised 500 consecutive women who presented to the Depart ment of Obstetrics and Gynecology at the King George Hospital who met the inclusion criteria. Ultrasonographic study was performed using a transabdominal 3.5 MHz volume transducer. Post natally the weight of the baby and of the placenta was recorded. Perina tal outcome was assessed by birth weight, APGAR score and the need for admission in neonatal intensive care unit. STATISTICAL ANALYSIS : Pearson’s correlation analysis and Chi square test was used. Statistical significance was considered at a p value <0.05 . RESULTS: The mean placental thickness was 3.10 cm; 76% (n:380 had normal thickness. Mean placental diameter was 21.306 cm, and its weight varied from 310 women 62% (n:310. Correlation of placental thickness (normal and abnormal, with birth weight, the difference was significant ( <0.001. CONCLUSION: Ultrasound forms a readily available, fairly safe, effective non - invasive method to identify and prevent fetal malnutrition in a cost - effective way.

  8. Neonatal modulation of serum cytokine profiles by a specific mixture of anti-inflammatory neutral and acidic oligosaccharides in preterm infants.

    Science.gov (United States)

    van den Berg, Jolice P; van Zwieteren, Ninke; Westerbeek, Elisabeth A M; Garssen, Johan; van Elburg, Ruurd M

    2013-10-01

    Infections are common in preterm infants and cause differences in cytokine levels. Aim of this study was to measure cytokine levels in preterm infants during the first year of life and to determine the effect of feeding a specific non-digestible carbohydrate mixture (scGOS/lcFOS/pAOS). Furthermore, other perinatal factors in relation to these cytokine levels were analysed. In a randomized controlled trial, preterm infants (GA Cytokine levels (IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-17, IFN-γ, and TNF-α) were analysed at 5 time points during the study: before start of the study, at day 7, at day 14 and at 5 and 12 months after the start of the intervention. In total, 55 preterm infants in the scGOS/lcFOS/pAOS group and 58 in the placebo group were included. During the neonatal period cytokine levels increased, followed by a decrease at 5 months and 12 months. Enteral supplementation of the non-digestible oligosaccharides decreased cytokine levels at day 7 but not at day 14, indicating a temporarily anti-inflammatory effect. In the neonatal period, serious infection before sampling increased all cytokine levels. In conclusion, enteral supplementation of this specific non-digestible oligosaccharide mixture decreased cytokine levels in preterm infants at day 7 of life, although this effect disappeared thereafter.

  9. Triazole fungicide tebuconazole disrupts human placental trophoblast cell functions.

    Science.gov (United States)

    Zhou, Jinghua; Zhang, Jianyun; Li, Feixue; Liu, Jing

    2016-05-05

    Triazole fungicides are one of the top ten classes of current-use pesticides. Although exposure to triazole fungicides is associated with reproductive toxicity in mammals, limited information is available regarding the effects of triazole fungicides on human placental trophoblast function. Tebuconazole (TEB) is a common triazole fungicide that has been extensively used for fungi control. In this work, we showed that TEB could reduce cell viability, disturb normal cell cycle distribution and induce apoptosis of human placental trophoblast cell line HTR-8/SVneo (HTR-8). Bcl-2 protein expression decreased and the level of Bax protein increased after TEB treatment in HTR-8 cells. The results demonstrated that this fungicide induced apoptosis of trophoblast cells via mitochondrial pathway. Importantly, we found that the invasive and migratory capacities of HTR-8 cells decreased significantly after TEB administration. TEB altered the expression of key regulatory genes involved in the modulation of trophoblast functions. Taken together, TEB suppressed human trophoblast invasion and migration through affecting the expression of protease, hormones, angiogenic factors, growth factors and cytokines. As the invasive and migratory abilities of trophoblast are essential for successful placentation and fetus development, our findings suggest a potential risk of triazole fungicides to human pregnancy.

  10. Impaired liver regeneration in Ldlr−/− mice is associated with an altered hepatic profile of cytokines, growth factors and lipids

    Science.gov (United States)

    Pauta, Montse; Rotllan, Noemi; Vales, Frances; Allen, Ryan M.; Ford, David A.; Marí, Montserrat; Jiménez, Wladimiro; Baldán, Ángel

    2014-01-01

    Background & Aims It is widely recognized that in the early stages of liver regeneration after partial hepatectomy the hepatocytes accumulate a significant amount of lipids. The functional meaning of this transient steatosis and its effect on hepatocellular proliferation are not well defined. In addition, the basic mechanisms of this lipid accumulation are not well understood although some studies suggest the participation of the Low Density Lipoprotein Receptor (Ldlr). Methods To address these questions we studied the process of liver regeneration in Ldlr null mice and wild-type mice following 75% partial hepatectomy. Results Ldlr deficiency was associated with a significant decrease in serum albumin concentration, during early stages of liver regeneration, and a delayed hepatic regeneration. Remnant livers of Ldlr−/− showed a time-shifted expression of interleukin-6 (IL-6) and a defective activation of tumor necrosis factor-α (TNFα) and hepatocyte growth factor (HGF) expression in early phases of liver regeneration. Unexpectedly, Ldlr−/− showed no significant differences in the content of lipid droplets after partial hepatectomy compared to wild-type mice. However, lipidomic analysis of the regenerating liver from Ldlr−/− revealed a lipid profile compatible with liver quiescence: high content of cholesterol esters and ceramide, and low levels of phosphatidylcholine. Conclusion Ldlr deficiency is associated with significant changes in the hepatic lipidome that affect cytokine-growth factor signaling and impair liver regeneration. These results suggest that the analysis of the hepatic lipidome may help to predict the success of liver regeneration in the clinical environment, specifically in the context of pre-existing liver steatosis. PMID:23712050

  11. Triazole fungicide tebuconazole disrupts human placental trophoblast cell functions

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Jinghua [Key Laboratory of Environmental Remediation and Ecological Health, Ministry of Education, Zhejiang University, Hangzhou 310058 (China); Zhang, Jianyun [Research Center for Air Pollution and Health, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou 310058 (China); Li, Feixue [Zhejiang Key Laboratory of Organ Development and Regeneration, Institute of Developmental and Regenerative Biology, College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou 310036 (China); Liu, Jing, E-mail: jliue@zju.edu.cn [Key Laboratory of Environmental Remediation and Ecological Health, Ministry of Education, Zhejiang University, Hangzhou 310058 (China); Research Center for Air Pollution and Health, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou 310058 (China)

    2016-05-05

    Highlights: • Tebuconazole (TEB) inhibited the proliferation of human placental trophoblasts. • TEB changed cell cycle distribution of G1 and G2 phases of trophoblasts. • TEB induced apoptosis of trophoblasts via mitochondrial pathway. • TEB decreased the invasive and migratory capacities of trophoblasts. • TEB altered the mRNA levels of key regulatory genes in trophoblasts - Abstract: Triazole fungicides are one of the top ten classes of current-use pesticides. Although exposure to triazole fungicides is associated with reproductive toxicity in mammals, limited information is available regarding the effects of triazole fungicides on human placental trophoblast function. Tebuconazole (TEB) is a common triazole fungicide that has been extensively used for fungi control. In this work, we showed that TEB could reduce cell viability, disturb normal cell cycle distribution and induce apoptosis of human placental trophoblast cell line HTR-8/SVneo (HTR-8). Bcl-2 protein expression decreased and the level of Bax protein increased after TEB treatment in HTR-8 cells. The results demonstrated that this fungicide induced apoptosis of trophoblast cells via mitochondrial pathway. Importantly, we found that the invasive and migratory capacities of HTR-8 cells decreased significantly after TEB administration. TEB altered the expression of key regulatory genes involved in the modulation of trophoblast functions. Taken together, TEB suppressed human trophoblast invasion and migration through affecting the expression of protease, hormones, angiogenic factors, growth factors and cytokines. As the invasive and migratory abilities of trophoblast are essential for successful placentation and fetus development, our findings suggest a potential risk of triazole fungicides to human pregnancy.

  12. Placental immunopathology in the FIV-infected cat: a role for inflammation in compromised pregnancy?

    Science.gov (United States)

    Coats, Karen S; Boudreaux, Crystal E; Clay, Brittany T; Lockett, Nikki N; Scott, Veronica L

    2010-03-15

    In utero transmission of feline immunodeficiency virus (FIV) occurs frequently in queens experimentally infected with FIV-B-2542 and other FIV isolates. Fetal infection has been detected as early as 3-4 weeks gestation, and the incidence of fetal infection increases with progressing gestation. Reproductive failure occurs commonly, including fetal resorptions and developmentally-arrested fetuses, demonstrating that fetal demise occurs early in gestation. Precise, temporal immunomodulation within the placenta is essential for successful pregnancy. Placental Th1 and Th2 cytokines must be appropriately balanced, typically favoring Th2 cytokines at the maternal-fetal interface. Abnormal inflammatory cytokine expression often accompanies miscarriage. Regulatory T cells (Tregs) play an essential role in maternal tolerance of the semi-allogeneic fetus by suppressing inflammation. We are using the FIV-infected cat to examine the relationship between lentivirus-induced placental immunopathology and reproductive outcome. Using TaqMan real time reverse transcriptase (RT)-PCR, we measured relative expression of key immunomodulators in the placentas of FIV-B-2542-infected and control cats, including placentas from both viable and nonviable pregnancies. Our data associate significantly-increased expression of inflammatory cytokines with failed pregnancies, identify Treg markers in the placentas, and provide preliminary evidence that Tregs or other cells bearing similar activation markers may be involved in pregnancy maintenance. Our data suggest that placental inflammation in the FIV-infected cat may compromise pregnancy.

  13. Cytokine profile of rats fed a diet containing shrimp Perfil das citocinas de ratos alimentados com dieta de camarão

    Directory of Open Access Journals (Sweden)

    Elizabeth Lage Borges

    2013-02-01

    Full Text Available OBJECTIVE: Studies have shown that shrimps reduced the tensile strength of scars in rat skin. The aim of the present study was to assess the cytokine profile of rats fed shrimp. METHODS: Group 1 (control received a regular diet and Group 2 (experimental received a diet containing 33% shrimp for nine days. The two diets contained the same amounts of proteins, fats and carbohydrates. Serum cytokine levels were determined by ELISA and a segment of the jejunum was taken to investigate its histological morphology and eosinophil infiltrate. RESULTS: The experimental group had lower serum levels of interleukin-4 (IL-4 (14.4±1.9 versus 18.11±2.6pg/mL; pOBJETIVO: Estudos mostraram que a dieta suplementada com camarão reduziu a resistência cicatricial na pele de ratos. Nesse contexto, o objetivo do presente estudo foi avaliar o perfil das citocinas de ratos que receberam dieta adicionada com camarão. MÉTODOS: Foram comparados um grupo controle e um grupo experimental, que receberam uma dieta enriquecida com camarão (33% durante nove dias. As duas dietas continham quantidades semelhantes de proteínas, lipídeos, e carboidratos. Os níveis séricos de citocinas foram avaliados por ELISA, assim como um segmento de jejuno foi obtido para exame histológico da morfologia e infiltrado de eosinófilos. RESULTADOS: A dieta adicionada com camarão diminuiu os níveis séricos de IL-4 (14,4±1,9 versus 18,11±2,6pg/mL, p<0,05 e IL-10 (5,0±0,98 versus 7,5±1,2pg/mL, p<0,05 e aumentou os níveis séricos de IL-6 (3,2±0,4 versus 17,8±2,3pg/mL, p<0,001 quando comparada com os animais controle. Morfologicamente, a dieta adicionada com camarão causou uma desorganização da arquitetura da mucosa intestinal, juntamente com uma abundância de eosinófilos nas vilosidades jejunais. CONCLUSÃO: Os dados sugerem que a ingestão de dieta adicionada com camarão leva a um aumento significativo da citocina IL-6, juntamente com uma diminuição da citocina

  14. Characterization of placental cholesterol transport

    DEFF Research Database (Denmark)

    Lindegaard, Marie L; Wassif, Christopher A; Vaisman, Boris

    2008-01-01

    Patients with Smith-Lemli-Opitz syndrome (SLOS) are born with multiple congenital abnormalities. Postnatal cholesterol supplementation is provided; however, it cannot correct developmental malformations due to in utero cholesterol deficit. Increased transport of cholesterol from maternal to fetal...... circulation might attenuate congenital malformations. The cholesterol transporters Abca1, Abcg1, and Sr-b1 are present in placenta; however, their potential role in placental transport remains undetermined. In mice, expression analyses showed that Abca1 and Abcg1 transcripts increased 2-3-fold between...... embryonic days 13.5 and 18.5 in placental tissue; whereas, Sr-b1 expression decreased. To examine the functional role of Abca1, Abcg1 and Sr-b1 we measured the maternal-fetal transfer of (14)C-cholesterol in corresponding mutant embryos. Disruption of either Abca1 or Sr-b1 decreased cholesterol transfer...

  15. Effects of prior acute exercise on circulating cytokine concentration responses to a high-fat meal.

    Science.gov (United States)

    Brandauer, Josef; Landers-Ramos, Rian Q; Jenkins, Nathan T; Spangenburg, Espen E; Hagberg, James M; Prior, Steven J

    2013-08-01

    High-fat meal consumption alters the circulating cytokine profile and contributes to cardiometabolic diseases. A prior bout of exercise can ameliorate the triglyceride response to a high-fat meal, but the interactive effects of exercise and high-fat meals on cytokines that mediate cardiometabolic risk are not fully understood. We investigated the effects of prior exercise on the responses of circulating tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-8, leptin, retinol-binding protein 4 (RBP4), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), placental growth factor (PlGF), and soluble fms-like tyrosine kinase-1 (sFlt-1) to a high-fat meal. Ten healthy men were studied before and 4 h after ingestion of a high-fat meal either with or without ∼50 min of endurance exercise at 70% of VO2 max on the preceding day. In response to the high-fat meal, lower leptin and higher VEGF, bFGF, IL-6, and IL-8 concentrations were evident (P exercise (P exercise and the high-fat meal on sFlt-1 (P exercise and 218% with prior exercise (P exercise does not affect all high-fat meal-induced changes in circulating cytokines, but does affect fasting or postprandial concentrations of IL-6, leptin, and sFlt-1. These data may reflect a salutary effect of prior exercise on metabolic responses to a high-fat meal.

  16. Placental chimerism in early human pregnancy

    Directory of Open Access Journals (Sweden)

    Ashutosh Halder

    2005-01-01

    Full Text Available Background0 : Human chimerism is rare and usually uncovered through investigations of ambiguous genitalia or blood grouping or prenatal diagnosis. Most of the publications on placental chimerism are mainly case reports. There is no systematic search with sensitive techniques for placental chimerism in human. Aim0 : This study was aimed to asses placental chimerism through two sensitive molecular techniques i.e., interphase fluorescent in situ hybridization and quantitative fluorescent PCR. Material and methods0 : Placental chimerism was analyzed using X & Y dual color fluorescent in-situ hybridization onto 154 placentae from natural conceptions, obtained at termination of pregnancy between 7 to 16 weeks of gestation. Results0 : Three cases of placental sex chromosome chimerism were observed (1.95%. Exclusion of maternal contamination and diagnosis was confirmed later by quantitative fluorescent PCR. Conclusion0 : This finding indicates that placental chimerism in early human pregnancy is not rare.

  17. Altered fetal growth, placental abnormalities, and stillbirth.

    Science.gov (United States)

    Bukowski, Radek; Hansen, Nellie I; Pinar, Halit; Willinger, Marian; Reddy, Uma M; Parker, Corette B; Silver, Robert M; Dudley, Donald J; Stoll, Barbara J; Saade, George R; Koch, Matthew A; Hogue, Carol; Varner, Michael W; Conway, Deborah L; Coustan, Donald; Goldenberg, Robert L

    2017-01-01

    Worldwide, stillbirth is one of the leading causes of death. Altered fetal growth and placental abnormalities are the strongest and most prevalent known risk factors for stillbirth. The aim of this study was to identify patterns of association between placental abnormalities, fetal growth, and stillbirth. Population-based case-control study of all stillbirths and a representative sample of live births in 59 hospitals in 5 geographic areas in the U.S. Fetal growth abnormalities were categorized as small (90th percentile) for gestational age at death (stillbirth) or delivery (live birth) using a published algorithm. Placental examination by perinatal pathologists was performed using a standardized protocol. Data were weighted to account for the sampling design. Among 319 singleton stillbirths and 1119 singleton live births at ≥24 weeks at death or delivery respectively, 25 placental findings were investigated. Fifteen findings were significantly associated with stillbirth. Ten of the 15 were also associated with fetal growth abnormalities (single umbilical artery; velamentous insertion; terminal villous immaturity; retroplacental hematoma; parenchymal infarction; intraparenchymal thrombus; avascular villi; placental edema; placental weight; ratio birth weight/placental weight) while 5 of the 15 associated with stillbirth were not associated with fetal growth abnormalities (acute chorioamnionitis of placental membranes; acute chorioamionitis of chorionic plate; chorionic plate vascular degenerative changes; perivillous, intervillous fibrin, fibrinoid deposition; fetal vascular thrombi in the chorionic plate). Five patterns were observed: placental findings associated with (1) stillbirth but not fetal growth abnormalities; (2) fetal growth abnormalities in stillbirths only; (3) fetal growth abnormalities in live births only; (4) fetal growth abnormalities in stillbirths and live births in a similar manner; (5) a different pattern of fetal growth abnormalities in

  18. Cytokine profile and proviral load among Japanese immigrants and non-Japanese infected with HTLV-1 in a non-endemic area of Brazil.

    Science.gov (United States)

    Domingos, João Américo; Soares, Luana Silva; Bandeira, Larissa M; Bonin, Camila Mareti; Vicente, Ana C P; Zanella, Louise; Puga, Marco Antonio Moreira; Tozetti, Inês Aparecida; Motta-Castro, Ana Rita Coimbra; da Cunha, Rivaldo Venâncio

    2017-01-01

    The lifetime risk of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) development differs among ethnic groups. To better understand these differences, this prospective cohort study was conducted to investigate the cytokine profile and the HTLV-1 proviral load (PVL) in Japanese and non-Japanese populations with HAM/TSP and asymptomatic carriers (ACs). The serum IL-2, IL-4, IL-6, IL-10, IL-17, TNF-α, and IFN-γ levels were quantified using the Cytometric Bead Array in 40 HTLV-1-infected patients (11 HAM/TSP and 29 ACs) and 18 healthy controls (HCs) in Brazil. Among ACs, 15 were Japanese descendants and 14 were non-Japanese. Of 11 patients with HAM/TSP, only one was a Japanese descendant. The HTLV-1 PVL was quantified by real-time PCR. The HTLV-1 PVL was 2.7-fold higher in HAM/TSP patients than ACs. Regardless of the clinical outcome, the PVL was significantly higher in patients younger than 60 years than older patients. The HAM/TSP and ACs had higher IL-10 serum concentrations than that of HCs. The ACs also showed higher IL-6 serum levels than those of HCs. According to age, the IL-10 and IL-6 levels were higher in ACs non-Japanese patients older than 60 years. HAM/TSP patients showed a positive correlation between IL-6 and IL-17 and a negative correlation between the PVL and IL-17 and IFN-γ. In the all ACs, a significant positive correlation was observed between IL-2 and IL-17 and a negative correlation was detected between IL-10 and TNF-α. Only 6.25% of the Japanese patients were symptomatic carriers, compared with 41.67% of the non-Japanese patients. In conclusion, this study showed that high levels of HTLV-1 PVL was intrinsicaly associated with the development of HAM/TSP. A higher HTLV-1 PVL and IL10 levels found in non-Japanese ACs over 60 years old, which compared with the Japanese group depicts that the ethnic background may interfere in the host immune status. More researches also need to be undertaken regarding the host genetic

  19. Placental oxygen transport estimated by the hyperoxic placental BOLD MRI response

    DEFF Research Database (Denmark)

    Sørensen, Anne Nødgaard; Sinding, Marianne; Peters, David A;

    2015-01-01

    cases of severe early onset FGR, placental BOLD MRI was performed in a 1.5 Tesla MRI system (TR:8000 msec, TE:50 msec, Flip angle:90). Placental histological examination was performed in the FGR cases. In normal pregnancies, the average hyperoxic placental BOLD response was 12.6 ± 5.4% (mean ± SD...

  20. Animal Models of Human Placentation - A Review

    DEFF Research Database (Denmark)

    Carter, Anthony Michael

    2007-01-01

    This review examines the strengths and weaknesses of animal models of human placentation and pays particular attention to the mouse and non-human primates. Analogies can be drawn between mouse and human in placental cell types and genes controlling placental development. There are, however...... and endometrium is similar in macaques and baboons, as is the subsequent lacunar stage. The absence of interstitial trophoblast cells in the monkey is an important difference from human placentation. However, there is a strong resemblance in the way spiral arteries are invaded and transformed in the macaque...

  1. Excess LIGHT contributes to placental impairment, increased secretion of vasoactive factors, hypertension, and proteinuria in preeclampsia.

    Science.gov (United States)

    Wang, Wei; Parchim, Nicholas F; Iriyama, Takayuki; Luo, Renna; Zhao, Cheng; Liu, Chen; Irani, Roxanna A; Zhang, Weiru; Ning, Chen; Zhang, Yujin; Blackwell, Sean C; Chen, Lieping; Tao, Lijian; Hicks, M John; Kellems, Rodney E; Xia, Yang

    2014-03-01

    Preeclampsia, a prevalent hypertensive disorder of pregnancy, is believed to be secondary to uteroplacental ischemia. Accumulating evidence indicates that hypoxia-independent mediators, including inflammatory cytokines and growth factors, are associated with preeclampsia, but it is unclear whether these signals directly contribute to placental damage and disease development in vivo. We report that LIGHT, a novel tumor necrosis factor superfamily member, is significantly elevated in the circulation and placentas of preeclamptic women compared with normotensive pregnant women. Injection of LIGHT into pregnant mice induced placental apoptosis, small fetuses, and key features of preeclampsia, hypertension and proteinuria. Mechanistically, using neutralizing antibodies specific for LIGHT receptors, we found that LIGHT receptors herpes virus entry mediator and lymphotoxin β receptor are required for LIGHT-induced placental impairment, small fetuses, and preeclampsia features in pregnant mice. Accordingly, we further revealed that LIGHT functions through these 2 receptors to induce secretion of soluble fms-like tyrosine kinase-1 and endothelin-1, 2 well-accepted pathogenic factors in preeclampsia, and thereby plays an important role in hypertension and proteinuria in pregnant mice. Lastly, we extended our animal findings to human studies and demonstrated that activation of LIGHT receptors resulted in increased apoptosis and elevation of soluble fms-like tyrosine kinase-1 secretion in human placental villous explants. Overall, our human and mouse studies show that LIGHT signaling is a previously unrecognized pathway responsible for placental apoptosis, elevated secretion of vasoactive factors, and subsequent maternal features of preeclampsia, and reveal new therapeutic opportunities for the management of the disease.

  2. ZnT8-Specific CD4+ T cells display distinct cytokine expression profiles between type 1 diabetes patients and healthy adults.

    Directory of Open Access Journals (Sweden)

    Daisuke Chujo

    Full Text Available Determination of antigen-specific T cell repertoires in human blood has been a challenge. Here, we show a novel integrated approach that permits determination of multiple parameters of antigen-specific T cell repertoires. The approach consists of two assays: the Direct assay and the Cytokine-driven assay. Briefly, human PBMCs are first stimulated with overlapping peptides encoding a given antigen for 48 hours to measure cytokine secretion (Direct assay. Peptide-reactive T cells are further expanded by IL-2 for 5 days; and after overnight starvation, expanded cells are stimulated with the same peptides from the initial culture to analyze cytokine secretion (Cytokine-driven assay. We first applied this integrated approach to determine the type of islet-antigen-specific T cells in healthy adults. Out of ten donors, the Direct assay identified GAD65-specific CD4(+ T cells in three adults and zinc transporter 8 (ZnT8-specific CD4(+ T cells in five adults. The intracytoplasmic cytokine staining assay showed that these islet-antigen-specific CD4(+ T cells belonged to the CD45RO(+ memory compartment. The Cytokine-driven assay further revealed that islet-antigen-specific CD4(+ T cells in healthy adults were capable of secreting various types of cytokines including type 1 and type 2 cytokines as well as IL-10. We next applied our integrated assay to determine whether the type of ZnT8-specific CD4(+ T cells is different between Type 1 diabetes patients and age/gender/HLA-matched healthy adults. We found that ZnT8-specific CD4(+ T cells were skewed towards Th1 cells in T1D patients, while Th2 and IL-10-producing cells were prevalent in healthy adults. In conclusion, the Direct assay and the Cytokine-driven assay complement each other, and the combination of the two assays provides information of antigen-specific T cell repertoires on the breadth, type, and avidity. This strategy is applicable to determine the differences in the quality of antigen-specific T

  3. Serum Cytokine Profile by ELISA in Patients with Echinococcal Cysts of the Liver: A Stage-Specific Approach to Assess Their Biological Activity

    Directory of Open Access Journals (Sweden)

    Luca Piccoli

    2012-01-01

    Full Text Available To investigate the usefulness of serum cytokine dosage in the clinical management of cystic echinococcosis (CE, we analyzed serum levels of Th1 and Th2 cytokines in patients with hepatic CE in different cyst stages, CE1-2 (active, CE3a-3b (transitional, and CE4-5 (inactive. Ex vivo assessment of Th1 (IFN-γ and Th2 (IL-4, IL-13, and IL-10 cytokines in sera was carried out using ELISA. IL-10 was undetectable in all serum samples of patients and controls, while a few sera contained measurable amounts of IFN-γ, IL-4, and IL-13. No statistically significant difference was found between the percentages of positive samples for each cytokine and the different groups analyzed (patients/controls, stage, number, location, and size of the cyst, serology, and sex of patients, with the exception of the association of IL-4 and IL-13 with the cyst stage. Overall, this investigation showed many limits of serum cytokine dosage as a marker of biological activity of echinococcal cysts. Because of low sensitivity and lack of specificity of this test, we believe that other ways to evaluate ex vivo biological activity of the cysts should be explored.

  4. The cumulative effect of assisted reproduction procedures on placental development and epigenetic perturbations in a mouse model.

    Science.gov (United States)

    de Waal, Eric; Vrooman, Lisa A; Fischer, Erin; Ord, Teri; Mainigi, Monica A; Coutifaris, Christos; Schultz, Richard M; Bartolomei, Marisa S

    2015-12-15

    Assisted reproductive technologies (ART) are associated with several complications including low birth weight, abnormal placentation and increased risk for rare imprinting disorders. Indeed, experimental studies demonstrate ART procedures independent of existing infertility induce epigenetic perturbations in the embryo and extraembryonic tissues. To test the hypothesis that these epigenetic perturbations persist and result in adverse outcomes at term, we assessed placental morphology and methylation profiles in E18.5 mouse concepti generated by in vitro fertilization (IVF) in two different genetic backgrounds. We also examined embryo transfer (ET) and superovulation procedures to ascertain if they contribute to developmental and epigenetic effects. Increased placental weight and reduced fetal-to-placental weight ratio were observed in all ART groups when compared with naturally conceived controls, demonstrating that non-surgical embryo transfer alone can impact placental development. Furthermore, superovulation further induced overgrowth of the placental junctional zone. Embryo transfer and superovulation defects were limited to these morphological changes, as we did not observe any differences in epigenetic profiles. IVF placentae, however, displayed hypomethylation of imprinting control regions of select imprinted genes and a global reduction in DNA methylation levels. Although we did not detect significant differences in DNA methylation in fetal brain or liver samples, rare IVF concepti displayed very low methylation and abnormal gene expression from the normally repressed allele. Our findings suggest that individual ART procedures cumulatively increase placental morphological abnormalities and epigenetic perturbations, potentially causing adverse neonatal and long-term health outcomes in offspring.

  5. Nickel-induced cytokine production from mononuclear cells in nickel-sensitive individuals and controls. Cytokine profiles in nickel-sensitive individuals with nickel allergy-related hand eczema before and after nickel challenge

    DEFF Research Database (Denmark)

    Borg, L; Christensen, J M; Kristiansen, J

    2000-01-01

    Exposure to nickel is a major cause of allergic contact dermatitis which is considered to be an inflammatory response induced by antigen-specific T cells. Here we describe the in vitro analysis of the nickel-specific T-cell-derived cytokine response of peripheral blood mononuclear cells from 35...... was somewhat of a surprise, since previous studies have suggested a Th1 response in nickel-mediated allergic contact dermatitis. Subsequently, the nickel-allergic individuals were randomized to experimental exposure to nickel or vehicle in a double-blind design. A daily 10-min exposure of one finger to 10 ppm...... nickel solution for 1 week followed by 100 ppm for an additional week evoked a clinical response of hand eczema in the nickel-exposed group. Blood samples were drawn on days 7 and 14 after the start of this exposure to occupationally relevant concentrations of nickel. No statistically significant...

  6. [Cytokines in bone diseases. What is cytokine?].

    Science.gov (United States)

    Murakami, Yousuke; Kohsaka, Hitoshi

    2010-10-01

    Cytokines have an essential role for cell-cell communication. They can regulate cell proliferation, differentiation, survival, and function. Interaction of cell surface receptor with cytokines is necessary for control of physiological responses. Activation of cytokine receptors transduces specific signal in the receptor-expressing cells, resulting that cytokines can regulate specific cell population. Thus, cytokines contribute directly or indirectly to morphogenesis, host defense and immune response, play critical roles for homeostasis and development.

  7. Gene expression profiles of inducible nitric oxide synthase and cytokines in Leishmania major-infected macrophage-like RAW 264.7 cells treated with gallic acid

    NARCIS (Netherlands)

    Radtke, O.A.; Kiderlen, A.F.; Kayser, Oliver; Kolodziej, H

    2004-01-01

    The effects of gallic acid on the gene expressions of inducible nitric oxide synthase (iNOS) and the cytokines interleukin (IL)-1, IL-10, IL-12, IL-18, TNF-alpha, and interferon (IFN)-gamma were investigated by reverse-transcription polymerase chain reaction (RT-PCR). The experiments were performed

  8. Combined exercise training reduces fatigue and modulates the cytokine profile of T-cells from multiple sclerosis patients in response to neuromediators.

    Science.gov (United States)

    Alvarenga-Filho, Helcio; Sacramento, Priscila M; Ferreira, Thais B; Hygino, Joana; Abreu, Jorge Eduardo Canto; Carvalho, Sonia Regina; Wing, Ana Cristina; Alvarenga, Regina Maria Papais; Bento, Cleonice A M

    2016-04-15

    Fatigue is a common and disabling symptom of multiple sclerosis (MS), a classical Th1- and Th17-mediated autoimmune disease. There is no effective pharmacological treatment for fatigue, but some reports point towards beneficial effects of physical activity on management of the fatigue in MS patients. As both MS and fatigue have been associated with dysregulated cytokine network production, the objective of the present study was to evaluate the impact of a physical activity program consisting of a 12-week series of combining Pilates and aerobic exercises on fatigue severity, determined by FSS, and cytokine production, quantified by ELISA, by T cells from MS patients (n=08) with low disability (EDSS≤2). The results showed decrease in FSSs in all patients at the end of physical activity intervention. Regarding the cytokines, a significant reduction of IL-22 release was observed in polyclonally-activated T cells form MS patients post-training follow-up. Interestingly, while the physical activity attenuated the ability of dopamine in up-regulating Th17-related cytokines, it enhanced the anti-inflammatory effects of serotonin, evidenced by high IL-10 production. In summary, all results suggest that programmed physical activity has beneficial effects on management of fatigue in MS patients, and it could be related, at least in part, to its ability in regulating neuroimmune parameters into T cell compartment.

  9. Maternal Outcomes According to Placental Position in Placental Previa

    Directory of Open Access Journals (Sweden)

    Dong Gyu Jang, Ji Sun We, Jae Un Shin, Yun Jin Choi, Hyun Sun Ko, In Yang Park, Jong Chul Shin

    2011-01-01

    Full Text Available Purpose: The purpose of this retrospective cohort study was to elucidate whether the location of placenta below uterine incision in cesarean section is important in the development of maternal complications in placenta previa patients.Methods: The study was conducted on 409 patients 414 parturition at 3 hospitals in affiliation with the Catholic Medical Center, Seoul, Korea from May 1999 to December 2009. The subjects were divided to two groups: the group whose placenta was located in the anterior portion of the uterus (anterior group and the group whose placenta was located in the posterior portion of the uterus (posterior group. And then they are compared to each other. Logistic regression was used to control for confounding factors.Results: In the anterior group, regardless of confounding factors, the incidence of excessive blood loss (OR 2.97; 95% CI: 1.64-5.37, massive transfusion (OR 3.31; 95% CI: 1.33-8.26, placental accreta (OR 2.60, 95% CI: 1.40-4.83, and hysterectomy (OR 3.47, 95% CI: 1.39-8.68 was higher.Conclusion: Sonographic determination of the placental position where its location beneath the uterine incision is very important to predict maternal outcomes in placenta previa patients, and such cases, close attention should be paid for massive hemorrhage.

  10. Microparasites and Placental Invasiveness in Eutherian Mammals.

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    Isabella Capellini

    Full Text Available Placental invasiveness-the number of maternal tissue layers separating fetal tissues from maternal blood-is variable across mammalian species. Although this diversity is likely to be functionally important, variation in placental invasiveness remains unexplained. Here we test the hypothesis that increased risk of transplacental transmission of pathogens from the mother to the fetus promotes the evolution of non-invasive placentation, the most likely derived condition in eutherian mammals. Specifically, we predict that non-invasive placentation is associated with increased microparasite species richness relative to more invasive placental types, based on the assumption that higher numbers of microparasites in a population reflects greater risk of transplacental transmission to fetuses. As predicted, higher bacteria species richness is associated with non-invasive placentation. Protozoa species richness, however, shows the opposite pattern. Because invasive placentae facilitate the transfer of maternal antibodies to the fetus, we propose that the ancestral condition of invasive placentation is retained under selection for protection of newborns from higher risk of postnatal protozoan infection. Hence, our findings suggest that a tradeoff exists between protection against bacterial infection prenatally and protozoan infection postnatally. Future studies are needed to investigate how maternal prevalence of infection and the relative pre- versus postnatal risk of fetal infection by different microparasite groups vary among mammalian hosts in relation to placental invasiveness.

  11. Placental urocortins and CRF in late gestation.

    NARCIS (Netherlands)

    Pepels, P.P.L.M.; Spaanderman, M.E.A.; Bulten, J.; Smits, P.; Hermus, A.R.M.M.; Lotgering, F.K.; Sweep, C.G.J.

    2009-01-01

    Placental corticotropin-releasing factor (CRF) are thought to induce labor via activation of CRF receptor type 1 (CRF-R1) leading to several feed forward mechanisms in the placental, fetal and maternal compartments. Recently, receptor type 2 (CRF-R2) selective ligands called urocortin 2 and 3 (Ucn

  12. Placental iron uptake and its regulation

    NARCIS (Netherlands)

    M. Bierings (Marc)

    1989-01-01

    textabstractIron transport in pregnancy is an active one-way process, from mother to fetus. Early in gestation fetal iron needs are low, and so is trans-placental transport, but as erythropoiesis develops, rising fetal iron needs are met by trans-placental iron transport. Apparently, the fetus is pr

  13. Gene Expression Profile of Endotoxin-stimulated Leukocytes of the Term New Born: Control of Cytokine Gene Expression by Interleukin-10

    Science.gov (United States)

    Davidson, Dennis; Zaytseva, Alla; Miskolci, Veronika; Castro-Alcaraz, Susana; Vancurova, Ivana; Patel, Hardik

    2013-01-01

    Introduction Increasing evidence now supports the association between the fetal inflammatory response syndrome (FIRS) with the pathogenesis of preterm labor, intraventricular hemorrhage and bronchopulmonary dysplasia. Polymorphonuclear leukocyte (PMNs) and mononuclear cell (MONOs) infiltration of the placenta is associated with these disorders. The aim of this study was to reveal cell-specific differences in gene expression and cytokine release in response to endotoxin that would elucidate inflammatory control mechanisms in the newly born. Methods PMNs and MONOs were separately isolated from the same cord blood sample. A genome-wide microarray screened for gene expression and related pathways at 4 h of LPS stimulation (n = 5). RT-qPCR and ELISA were performed for selected cytokines at 4 h and 18 h of LPS stimulation. Results Compared to PMNs, MONOs had a greater diversity and more robust gene expression that included pro-inflammatory (PI) cytokines, chemokines and growth factors at 4 h. Only MONOs had genes changing expression (all up regulated including interleukin-10) that were clustered in the JAK/STAT pathway. Pre-incubation with IL-10 antibody, for LPS-stimulated MONOs, led to up regulated PI and IL-10 gene expression and release of PI cytokines after 4 h. Discussion The present study suggests a dominant role of MONO gene expression in control of the fetal inflammatory response syndrome at 4 hrs of LPS stimulation. LPS-stimulated MONOs but not PMNs of the newborn have the ability to inhibit PI cytokine gene expression by latent IL-10 release. PMID:23326478

  14. Gene expression profile of endotoxin-stimulated leukocytes of the term new born: control of cytokine gene expression by interleukin-10.

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    Dennis Davidson

    Full Text Available INTRODUCTION: Increasing evidence now supports the association between the fetal inflammatory response syndrome (FIRS with the pathogenesis of preterm labor, intraventricular hemorrhage and bronchopulmonary dysplasia. Polymorphonuclear leukocyte (PMNs and mononuclear cell (MONOs infiltration of the placenta is associated with these disorders. The aim of this study was to reveal cell-specific differences in gene expression and cytokine release in response to endotoxin that would elucidate inflammatory control mechanisms in the newly born. METHODS: PMNs and MONOs were separately isolated from the same cord blood sample. A genome-wide microarray screened for gene expression and related pathways at 4 h of LPS stimulation (n = 5. RT-qPCR and ELISA were performed for selected cytokines at 4 h and 18 h of LPS stimulation. RESULTS: Compared to PMNs, MONOs had a greater diversity and more robust gene expression that included pro-inflammatory (PI cytokines, chemokines and growth factors at 4 h. Only MONOs had genes changing expression (all up regulated including interleukin-10 that were clustered in the JAK/STAT pathway. Pre-incubation with IL-10 antibody, for LPS-stimulated MONOs, led to up regulated PI and IL-10 gene expression and release of PI cytokines after 4 h. DISCUSSION: The present study suggests a dominant role of MONO gene expression in control of the fetal inflammatory response syndrome at 4 hrs of LPS stimulation. LPS-stimulated MONOs but not PMNs of the newborn have the ability to inhibit PI cytokine gene expression by latent IL-10 release.

  15. Nomenclature and placental mammal phylogeny

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    Helgen Kristofer M

    2010-04-01

    Full Text Available Abstract An issue arising from recent progress in establishing the placental mammal Tree of Life concerns the nomenclature of high-level clades. Fortunately, there are now several well-supported clades among extant mammals that require unambiguous, stable names. Although the International Code of Zoological Nomenclature does not apply above the Linnean rank of family, and while consensus on the adoption of competing systems of nomenclature does not yet exist, there is a clear, historical basis upon which to arbitrate among competing names for high-level mammalian clades. Here, we recommend application of the principles of priority and stability, as laid down by G.G. Simpson in 1945, to discriminate among proposed names for high-level taxa. We apply these principles to specific cases among placental mammals with broad relevance for taxonomy, and close with particular emphasis on the Afrotherian family Tenrecidae. We conclude that no matter how reconstructions of the Tree of Life change in years to come, systematists should apply new names reluctantly, deferring to those already published and maximizing consistency with existing nomenclature.

  16. Cytokine profiles in peripheral blood mononuclear cells and lymph node cells from piglets infected in utero with porcine reproductive and respiratory syndrome virus

    DEFF Research Database (Denmark)

    Aasted, B.; Bach, P.; Nielsen, Jens;

    2002-01-01

    compared, the levels of cytokine expression at 4 weeks diverged from those at 2 and 6 weeks, in that there was a significant decrease in the numbers of lymphocytes producing gamma-IFN and TNF-alpha. This tendency was also observed among blood monocytes and lymph node macrophages. Possible reasons......The aim of the present study was to investigate at 2, 4, and 6 weeks after birth cytokine expression by peripheral blood mononuclear cells and bronchial lymph node cells from piglets infected in utero with porcine reproductive and respiratory syndrome virus (PRRSV). Technically, by flow cytometry...... we were able to measure gamma interferon (gamma-IFN), tumor necrosis factor alpha (TNF-alpha), interleukin-4 (IL-4), and IL-8 levels. In general, we found increases in the percentages of IL-4-, gamma-IFN-, and TNF-alpha-producing lymphocytes in the infected piglets compared to the percentages...

  17. Kinetics of serum and local cytokine profile in experimental intravaginal trichomoniasis induced with Trichomonas vaginalis isolates from symptomatic and asymptomatic women.

    Science.gov (United States)

    Malla, N; Yadav, M; Gupta, I

    2007-02-01

    Trichomoniasis, the most common non-viral sexually transmitted disease, is caused by infection with the protist Trichomonas vaginalis. The clinical spectrum varies from an asymptomatic to a severe symptomatic state. However, the exact factors leading to varied symptomatology have not been well elucidated. The role of cytokines in the pathogenesis of many microbial diseases has been reported. The present study reports the cytokine levels (IL-2, IL-4, IFN-gamma) on different days post infection (3rd, 7th, 14th, 21st and 28th d.p.i.) in serum and vaginal washes (VWs) of mice infected intravaginally with T. vaginalis isolates from 15 symptomatic and 15 asymptomatic women. Significantly higher production of IL-2 and IFN-gamma was observed on the 3rd to 28th d.p.i., and IL-4 on the 7th to 21st d.p.i., in infected as compared to uninfected mice. A significant increase in cytokine IL-2 and IFN-gamma was observed on the 3rd to 28th d.p.i. in serum and VWs of mice infected with T. vaginalis isolates from asymptomatic as compared to symptomatic women. IL-2 (P < 0.001) and IFN-gamma (P < 0.05) concentrations were significantly higher on the 14th d.p.i. in serum samples as compared to VWs of mice infected with T. vaginalis isolates from asymptomatic and symptomatic women, while no significant difference was observed in IL-4 concentration between the two groups of mice. The study indicates the involvement of a Th-1 (IL-2 and IFN-gamma) like response in mice infected with isolates from asymptomatic women as compared to symptomatic women and suggests that Th-1 type cytokines might be playing a role in maintaining low levels of infection.

  18. Cytokines and cytokine-specific therapy in asthma.

    Science.gov (United States)

    Desai, Dhananjay; Brightling, Christopher

    2012-01-01

    Asthma is increasing in prevalence worldwide. It is characterized by typical symptoms and variable airway obstruction punctuated with episodes of worsening symptoms known as exacerbations. Underlying this clinical expression of disease is airway inflammation and remodeling. Cytokines and their networks are implicated in the innate and adaptive immune responses driving airway inflammation in asthma and are modulated by host-environment interactions. Asthma is a complex heterogeneous disease, and the paradigm of Th2 cytokine-mediated eosinophilic inflammation as a consequence of allergic sensitization has been challenged and probably represents a subgroup of asthma. Indeed, as attention has switched to the importance of severe asthma, which represents the highest burden both to the patient and health care provider, there is an increasing recognition of inflammatory subphenotypes that are likely to be driven by different cytokine networks. Interestingly, these networks may be specific to aspects of clinical expression as well as inflammatory cell profiles and therefore present novel phenotype-specific therapeutic strategies. Here, we review the breadth of cytokines implicated in the pathogenesis of asthma and focus upon the outcomes of early clinical trials conducted using cytokines or cytokine-blocking therapies.

  19. Serum cytokine profiling and enrichment analysis reveal the involvement of immunological and inflammatory pathways in stable patients with chronic obstructive pulmonary disease

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    Bade G

    2014-08-01

    Full Text Available Geetanjali Bade,1 Meraj Alam Khan,2 Akhilesh Kumar Srivastava,1 Parul Khare,1 Krishna Kumar Solaiappan,1 Randeep Guleria,3 Nades Palaniyar,2 Anjana Talwar1 1Department of Physiology, All India Institute of Medical Sciences, New Delhi, India; 2Program in Physiology and Experimental Medicine, The Hospital for Sick Children, Department of Laboratory Medicine and Pathobiology, and Institute of Medical Sciences, Faculty of Medicine, University of Toronto, Toronto, ON, Canada; 3Department of Pulmonary Medicine and Sleep Disorders, All India Institute of Medical Sciences, New Delhi, India Abstract: Chronic obstructive pulmonary disease (COPD is a major global health problem. It results from chronic inflammation and causes irreversible airway damage. Levels of different serum cytokines could be surrogate biomarkers for inflammation and lung function in COPD. We aimed to determine the serum levels of different biomarkers in COPD patients, the association between cytokine levels and various prognostic parameters, and the key pathways/networks involved in stable COPD. In this study, serum levels of 48 cytokines were examined by multiplex assays in 30 subjects (control, n=9; COPD, n=21. Relationships between serum biomarkers and forced expiratory volume in 1 second, peak oxygen uptake, body mass index, dyspnea score, and smoking were assessed. Enrichment pathways and networks analyses were implemented, using a list of cytokines showing differential expression between healthy controls and patients with COPD by Cytoscape and GeneGo Metacore™ softwares (Thomson-Reuters Corporation, New York, NY, USA. Concentrations of cutaneous T-cell attracting chemokine, eotaxin, hepatocyte growth factor, interleukin 6 (IL-6, IL-16, and stem cell factor are significantly higher in COPD patients compared with in control patients. Notably, this study identifies stem cell factor as a biomarker for COPD. Multiple regression analysis predicts that cutaneous T

  20. Human placental lactogen levels in multiple pregnancies.

    Science.gov (United States)

    Spellacy, W N; Buhi, W C; Birk, S A

    1978-08-01

    Serum human placental lactogen (hPL) levels were measured in duplicate with a radioimmunoassay in 206 serum samples at 30 and 36 weeks' gestation from women with normal singleton pregnancies (75) or pregnancies with twins (37). One triplet pregnancy was also studied. The results show a significant elevation of hPL in the women with twin pregnancies at both the 30th (7.0 vs 6.0 microgram/ml) and the 36th (9.2 vs 7.4 microgram/ml) weeks. One-third of the twin pregnancies had values of hPL in excess of 8.0 microgram/ml at 30 weeks and more than half had values in excess of 9.0 microgram/ml at 36 weeks. The triplet pregnancy had an hPL value of 11.0 microgram/ml at 36 weeks' gestation. These data support the potential usefulness of serum hPL measurements in the screening profile for the detection of high-risk pregnancies.

  1. A stochastic model for early placental development.

    KAUST Repository

    Cotter, Simon L

    2014-08-01

    In the human, placental structure is closely related to placental function and consequent pregnancy outcome. Studies have noted abnormal placental shape in small-for-gestational-age infants which extends to increased lifetime risk of cardiovascular disease. The origins and determinants of placental shape are incompletely understood and are difficult to study in vivo. In this paper, we model the early development of the human placenta, based on the hypothesis that this is driven by a chemoattractant effect emanating from proximal spiral arteries in the decidua. We derive and explore a two-dimensional stochastic model, and investigate the effects of loss of spiral arteries in regions near to the cord insertion on the shape of the placenta. This model demonstrates that disruption of spiral arteries can exert profound effects on placental shape, particularly if this is close to the cord insertion. Thus, placental shape reflects the underlying maternal vascular bed. Abnormal placental shape may reflect an abnormal uterine environment, predisposing to pregnancy complications. Through statistical analysis of model placentas, we are able to characterize the probability that a given placenta grew in a disrupted environment, and even able to distinguish between different disruptions.

  2. Dengue-2 and yellow fever 17DD viruses infect human dendritic cells, resulting in an induction of activation markers, cytokines and chemokines and secretion of different TNF-α and IFN-α profiles

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    Mariana Gandini

    2011-08-01

    Full Text Available Flaviviruses cause severe acute febrile and haemorrhagic infections, including dengue and yellow fever and the pathogenesis of these infections is caused by an exacerbated immune response. Dendritic cells (DCs are targets for dengue virus (DENV and yellow fever virus (YF replication and are the first cell population to interact with these viruses during a natural infection, which leads to an induction of protective immunity in humans. We studied the infectivity of DENV2 (strain 16681, a YF vaccine (YF17DD and a chimeric YF17D/DENV2 vaccine in monocyte-derived DCs in vitro with regard to cell maturation, activation and cytokine production. Higher viral antigen positive cell frequencies were observed for DENV2 when compared with both vaccine viruses. Flavivirus-infected cultures exhibited dendritic cell activation and maturation molecules. CD38 expression on DCs was enhanced for both DENV2 and YF17DD, whereas OX40L expression was decreased as compared to mock-stimulated cells, suggesting that a T helper 1 profile is favoured. Tumor necrosis factor (TNF-α production in cell cultures was significantly higher in DENV2-infected cultures than in cultures infected with YF17DD or YF17D/DENV. In contrast, the vaccines induced higher IFN-α levels than DENV2. The differential cytokine production indicates that DENV2 results in TNF induction, which discriminates it from vaccine viruses that preferentially stimulate interferon expression. These differential response profiles may influence the pathogenic infection outcome.

  3. Dengue-2 and yellow fever 17DD viruses infect human dendritic cells, resulting in an induction of activation markers, cytokines and chemokines and secretion of different TNF-α and IFN-α profiles.

    Science.gov (United States)

    Gandini, Mariana; Reis, Sonia Regina Nogueira Ignacio; Torrentes-Carvalho, Amanda; Azeredo, Elzinandes Leal; Freire, Marcos da Silva; Galler, Ricardo; Kubelka, Claire Fernandes

    2011-08-01

    Flaviviruses cause severe acute febrile and haemorrhagic infections, including dengue and yellow fever and the pathogenesis of these infections is caused by an exacerbated immune response. Dendritic cells (DCs) are targets for dengue virus (DENV) and yellow fever virus (YF) replication and are the first cell population to interact with these viruses during a natural infection, which leads to an induction of protective immunity in humans. We studied the infectivity of DENV2 (strain 16681), a YF vaccine (YF17DD) and a chimeric YF17D/DENV2 vaccine in monocyte-derived DCs in vitro with regard to cell maturation, activation and cytokine production. Higher viral antigen positive cell frequencies were observed for DENV2 when compared with both vaccine viruses. Flavivirus-infected cultures exhibited dendritic cell activation and maturation molecules. CD38 expression on DCs was enhanced for both DENV2 and YF17DD, whereas OX40L expression was decreased as compared to mock-stimulated cells, suggesting that a T helper 1 profile is favoured. Tumor necrosis factor (TNF)-α production in cell cultures was significantly higher in DENV2-infected cultures than in cultures infected with YF17DD or YF17D/DENV. In contrast, the vaccines induced higher IFN-α levels than DENV2. The differential cytokine production indicates that DENV2 results in TNF induction, which discriminates it from vaccine viruses that preferentially stimulate interferon expression. These differential response profiles may influence the pathogenic infection outcome.

  4. Endocrine, paracrine, and autocrine placental mediators in labor.

    Science.gov (United States)

    Iliodromiti, Zoe; Antonakopoulos, Nikolaos; Sifakis, Stavros; Tsikouras, Panagiotis; Daniilidis, Angelos; Dafopoulos, Kostantinos; Botsis, Dimitrios; Vrachnis, Nikolaos

    2012-01-01

    Considering that preterm birth accounts for about 6-10% of all births in Western countries and of more than 65% of all perinatal deaths, elucidation of the particularly complicated mechanisms of labor is essential for determination of appropriate and effective therapeutic interventions. Labor in humans results from a complex interplay of fetal and maternal factors, which act upon the uterus to trigger pathways leading gradually to a coordinated cervical ripening and myometrial contractility. Although the exact mechanism of labor still remains uncertain, several components have been identified and described in detail. Based on the major role played by the human placenta in pregnancy and the cascade of labor processes activated via placental mediators exerting endocrine, paracrine, and autocrine actions, this review article has aimed at presenting the role of these mediators in term and preterm labor and the molecular pathways of their actions. Some of the aforementioned mediators are involved in myometrial activation and preparation and others in myometrial stimulation leading to delivery. In the early stages of pregnancy, myometrial molecules, like progesterone, nitric oxide, and relaxin, contribute to the retention of pregnancy. At late stages of gestation, fetal hypothalamus maturation signals act on the placenta causing the production of hormones, including CRH, in an endocrine manner; the signals then enhance paracrinically the production of more hormones, such as estrogens and neuropeptides, that contribute to cervical ripening and uterine contractility. These molecules act directly on the myometrium through specific receptors, while cytokines and multiple growth factors are also produced, additionally contributing to labor. In situations leading to preterm labor, as in maternal stress and fetal infection, cytokines trigger placental signaling sooner, thus leading to preterm birth.

  5. The evolution of epitheliochorial placentation.

    Science.gov (United States)

    Carter, Anthony M; Enders, Allen C

    2013-01-01

    Epitheliochorial placentation is a derived condition and has evolved separately in strepsirrhine primates and laurasiatherians (pangolins, whales, and hoofed mammals). Usually it is associated with a long gestation period, small litters, and precocial young. Oxygen transfer is facilitated by indenting of the uterine and trophoblast epithelia by maternal and fetal capillaries, respectively. Histotrophic nutrition is important, and adaptations include areolas and hemophagous regions. In pigs and horses, for example, iron is transported as uteroferrin secreted from the uterine glands and taken up by areolas. In the horse, invasive trophoblast cells form cups within the endometrium that are the source of equine chorionic gonadotropin. In ruminants, binucleate trophoblast cells fuse with uterine epithelial cells to form trinucleate cells or plaques that secrete pregnancy hormones. There is evidence of immunosuppression in connection with these more invasive types of trophoblasts. The epitheliochorial condition may be advantageous for long pregnancies in large animals.

  6. Oral supplementation of diabetic mice with propolis restores the proliferation capacity and chemotaxis of B and T lymphocytes towards CCL21 and CXCL12 by modulating the lipid profile, the pro-inflammatory cytokine levels and oxidative stress.

    Science.gov (United States)

    Al Ghamdi, Ahmad A; Badr, Gamal; Hozzein, Wael N; Allam, Ahmed; Al-Waili, Noori S; Al-Wadaan, Mohammed A; Garraud, Olivier

    2015-09-15

    Type 1 diabetes mellitus (T1D) is a chronic autoimmune disease caused by the selective destruction of pancreatic β cells, followed by hyperglycemia, oxidative stress and the subsequent extensive impairment of immune cell functions, a phenomenon responsible for the development of chronic diabetic complications. Propolis, a natural bee product that is extensively used in foods and beverages, significantly benefits human health. Specifically, propolis exerts antioxidant, anti-inflammatory and analgesic effects that may improve diabetic complications. To further elucidate the potential benefits of propolis, the present study investigated the effect of dietary supplementation with propolis on the plasma cytokine profiles, free radical levels, lipid profile and lymphocyte proliferation and chemotaxis in a streptozotocin (STZ)-induced type I diabetic mouse model. Thirty male mice were equally distributed into 3 experimental groups: group 1, non-diabetic control mice; group 2, diabetic mice; and group 3, diabetic mice supplemented daily with an ethanol-soluble derivative of propolis (100 mg/kg body weight) for 1 month. First, the induction of diabetes in mice was associated with hyperglycemia and significant decreases in the insulin level and the lymphocyte count. In this context, diabetic mice exhibited severe diabetic complications, as demonstrated by a significant decrease in the levels of IL-2, IL-4 and IL-7, prolonged elevation of the levels of pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) and reactive oxygen species (ROS) and altered lipid profiles compared with control non-diabetic mice. Moreover, antigen stimulation of B and T lymphocytes markedly reduced the proliferative capacity and chemotaxis of these cells towards CCL21 and CXCL12 in diabetic mice compared with control mice. Interestingly, compared with diabetes induction alone, treatment of diabetic mice with propolis significantly restored the plasma cytokine and ROS levels and the lipid profile to

  7. ULTRASONOGRAPHIC CORRELATION OF PLACENTAL THICKNESS WITH FETAL GESTATIONAL AGE AND GRADING OF PLACENTAL MATURIT

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    Nagesh

    2016-03-01

    Full Text Available AIMS AND OBJECTIVES Comparative correlation of placental thickness with foetal gestational age, and evaluation of placental maturity by ultrasonography. MATERIALS AND METHODS The study includes 100 normal singleton gestations between 10 to 40 weeks of gestation referred to our centre for routine antenatal ultrasound examination. All the women were evaluated by transabdominal ultrasonography. Foetal gestational age in weeks was determined by crown rump length, biparietal diameter, head circumference, abdominal circumference and femoral length. Placental thickness was measured in millimeters. All the placentae were graded using ultrasonographic grading system. RESULTS Our observations revealed that the placental thickness gradually increased from 11.8 mm at 12 weeks to 38.5 mm at 39 weeks. Placental thickness almost corresponds to advancing gestational age exhibiting a linear and direct growth. Progressive maturity changes were noted in placenta with advancing gestational age. CONCLUSION Placental thickness measured at cord insertion site can be used as one of the parameter for estimating foetal gestational age. Placental thickness measurement can also be used to differentiate certain abnormal conditions related to thick and thin placenta. Ultrasonographic placental grading helps to rule out certain conditions associated with premature or delayed placental maturation

  8. Cytokine profile, proliferation and phosphorylation of ERK1/2 and Akt in circulating mononuclear cells from individuals during the chronic intestinal phase of Schistosomiasis mansoni infection

    Directory of Open Access Journals (Sweden)

    Oliveira-Prado Roberta

    2012-12-01

    Full Text Available Abstract Background The immune response to Schistosoma mansoni is characterized by a granulomatous reaction around the parasite eggs that are trapped in the host liver, and this reaction modulates the immune response during the chronic phase of the disease. The typical peripheral blood mononuclear cell (PBMC response of patients during the chronic intestinal phase of infection is characterized by a decreased response to an S. mansoni soluble egg antigen. To obtain a greater understanding of Schistosoma infections, this study investigated the effects of the soluble egg antigen (SEA and soluble adult worm antigen (SWAP of S. mansoni on cellular proliferation, cytokine production, and ERK1/2 and Akt phosphorylation in PBMCs from infected (XTO and egg-negative (NI individuals living in the same endemic area. Methods The activation status was evaluated by cell immunophenotypic staining (cytometry. The cell proliferation assay was by CFSE method. Cytokine detection assay (Th1 and Th2 was by Cytometric Bead and Array phosphorylation status was by ELISA. Results The XTO, NI and BD (blood donor individuals from an area not endemic for schistosomiasis were compared. The CD4+ T lymphocyte proliferation rate was lower in the XTO group, but not the NI group, after SEA stimulation compared to the BD group. The CD8+ T cell proliferation rate was lower in the XTO group in the unstimulated cultures and after both SEA and SWAP stimulation compared to the BD group. Cytokine analysis after either SEA or SWAP stimulation showed a balanced cytokine pattern in the XTO and NI groups. ERK1/2 and Akt phosphorylation were only marginally detected in all groups; however, a decrease in ERK 1/2 phosphorylation was observed in the SWAP-stimulated XTO group compared to both the NI and BD groups. Conclusions The data indicate that SEA-stimulated CD4+ T cells from infected patients have a lower proliferation rate than the same cells from the NI group. Furthermore, we observed

  9. Overlap Chronic Placental Inflammation Is Associated with a Unique Gene Expression Pattern.

    Science.gov (United States)

    Raman, Kripa; Wang, Huaqing; Troncone, Michael J; Khan, Waliul I; Pare, Guillaume; Terry, Jefferson

    2015-01-01

    Breakdown of the balance between maternal pro- and anti-inflammatory pathways is thought to allow an anti-fetal maternal immune response that underlies development of chronic placental inflammation. Chronic placental inflammation is manifested by the influx of maternal inflammatory cells, including lymphocytes, histiocytes, and plasma cells, into the placental membranes, villi, and decidua. These infiltrates are recognized pathologically as chronic chorioamnionitis, chronic villitis of unknown etiology, and chronic deciduitis. Each of these histological entities is associated with adverse fetal outcomes including intrauterine growth restriction and preterm birth. Studying the gene expression patterns in chronically inflamed placenta, particularly when overlapping histologies are present, may lead to a better understanding of the underlying mechanism(s). Therefore, this study compared tissue with and without chronic placental inflammation, manifested as overlapping chronic chorioamnionitis, chronic villitis of unknown etiology, and chronic deciduitis. RNA expression profiling was conducted on formalin fixed, paraffin embedded placental tissue using Illumina microarrays. IGJ was the most significant differentially expressed gene identified and had increased expression in the inflamed tissue. In addition, IGLL1, CXCL13, CD27, CXCL9, ICOS, and KLRC1 had increased expression in the inflamed placental samples. These differentially expressed genes are associated with T follicular helper cells, natural killer cells, and B cells. Furthermore, these genes differ from those typically associated with the individual components of chronic placental inflammation, such as chronic villitis, suggesting that the inflammatory infiltrate associated with overlapping chronic chorioamnionitis, chronic villitis of unknown etiology, and chronic deciduitis differs is unique. To further explore and validate gene expression findings, we conducted immunohistochemical assessment of protein level

  10. SEX STEROIDS MODULATE UTERINE-PLACENTAL VASCULATURE: IMPLICATIONS FOR OBSTETRICS AND NEONATAL OUTCOMES

    Directory of Open Access Journals (Sweden)

    Manuel eMaliqueo

    2016-04-01

    Full Text Available Adequate blood supply to the uterine-placental region is crucial to ensure the transport of oxygen and nutrients to the growing fetus. Multiple factors intervene to achieve appropriate uterine blood flow and the structuring of the placental vasculature during the early stages of pregnancy. Among these factors, oxygen concentrations, growth factors, cytokines and steroid hormones are the most important. Sex steroids are present in extremely high concentrations in the maternal circulation and are important paracrine and autocrine regulators of a wide range of maternal and placental functions. In this regard, progesterone and estrogens act as modulators of uterine vessels and decrease the resistance of the spiral uterine arteries. On the other hand, androgens have the opposite effect, increasing the vascular resistance of the uterus. Moreover, progesterone and estrogens modulate the synthesis and release of angiogenic factors by placental cells, which regulates trophoblastic invasion and uterine artery remodeling. In this scenario, it is not surprising that women with pregnancy-related pathologies, such as early miscarriages, preterm delivery, preeclampsia and fetal growth restriction, exhibit altered sex steroid concentrations.

  11. Glucose, Insulin, and Oxygen Interplay in Placental Hypervascularisation in Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Silvija Cvitic

    2014-01-01

    Full Text Available The placental vasculature rapidly expands during the course of pregnancy in order to sustain the growing needs of the fetus. Angiogenesis and vascular growth are stimulated and regulated by a variety of growth factors expressed in the placenta or present in the fetal circulation. Like in tumors, hypoxia is a major regulator of angiogenesis because of its ability to stimulate expression of various proangiogenic factors. Chronic fetal hypoxia is often found in pregnancies complicated by maternal diabetes as a result of fetal hyperglycaemia and hyperinsulinemia. Both are associated with altered levels of hormones, growth factors, and proinflammatory cytokines, which may act in a proangiogenic manner and, hence, affect placental angiogenesis and vascular development. Indeed, the placenta in diabetes is characterized by hypervascularisation, demonstrating high placental plasticity in response to diabetic metabolic derangements. This review describes the major regulators of placental angiogenesis and how the diabetic environment in utero alters their expression. In the light of hypervascularized diabetic placenta, the focus was placed on proangiogenic factors.

  12. Hyperemesis gravidarum and placental dysfunction disorders

    NARCIS (Netherlands)

    Koudijs, Heleen M; Savitri, Ary I; Browne, Joyce L; Amelia, Dwirani; Baharuddin, Mohammad; Grobbee, Diederick E; Uiterwaal, Cuno S P M

    2016-01-01

    BACKGROUND: Evidence about the consequence of hyperemesis gravidarum (HG) on pregnancy outcomes is still inconclusive. In this study, we evaluated if occurrence of hyperemesis gravidarum is associated with placental dysfunction disorders and neonatal outcomes. METHODS: A prospective cohort study was

  13. Increased Survivorship and Altered Cytokine Profile from Treatment of Influenza A H1N1-Infected Mice with Ekybion: A Drug Complex of Natural Extracts and Inorganic Compounds

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    Christopher Lupfer

    2011-01-01

    Full Text Available Ekybion is a drug complex of 16 natural extracts and inorganic compounds designed to treat a variety of respiratory pathogens of bacterial and viral origin. It is licensed throughout Europe for the treatment of respiratory tract infections from equine parainfluenza type 3 and equine herpes virus type 1 in equine stables. The purpose of this paper was to test the efficacy of Ekybion on a well-developed animal model of influenza A infection and determine a mode of action. Experiments were performed with Balb/c mice infected with a lethal dose of influenza A/PR/8/34 H1N1 virus and treated with nebulized Ekybion every 8 h in a time-dependant or dose-dependant fashion. These experiments showed that mice treated prior to infection with Ekybion had a higher survival rates (~46% compared with untreated animals (~0%. Paradoxically, these mice showed no significant difference in lung virus titer or weight loss. There was, however, a decrease in the level of GM-CSF, IL-6, and G-CSF cytokines in the lungs of Ekybion-treated, infected mice. It is possible that decreases in proinflammatory cytokines may have contributed to increased survivorship in Ekybion-treated influenza-infected mice.

  14. Unique cytokine secretion profile in children with both type I diabetes and asthma distinct from that of solely diabetic or asthmatic children.

    Science.gov (United States)

    Kainonen, Essi; Rautava, Samuli; Korkeamäki, Mika; Isolauri, Erika

    2006-05-01

    Asthma and type I diabetes are major causes of chronic illness in childhood which, according to the current paradigm, have mutually antagonistic immunopathologies. Nonetheless, the disorders appear to preferably coexist both on population and individual levels. To assess whether children with asthma and type I diabetes might have a common immunoregulatory defect. The spontaneous and anti-CD3+ anti-CD28-stimulated cytokine production patterns by peripheral blood mononuclear cells of 13 children with both asthma and diabetes, nine children with diabetes, 11 children with asthma and nine healthy children were assessed using cytometric bead assay. The spontaneous production of IFN-gamma, TNF-alpha and IL-10 by mononuclear cells in children with both asthma and diabetes was elevated compared to the other study groups (p=0.02, p=0.001 and p=0.04, respectively). Stimulation in vitro increased IL-10 secretion in solely diabetic (p=0.008), asthmatic (p=0.008) and healthy children (p=0.01), but not in children with both diseases (p=0.22). Children suffering from both diabetes and asthma display a unique cytokine secretion pattern, distinct from those of solely diabetic, asthmatic and healthy children. In particular, these children appear to have a defect in regulation of IL-10 secretion.

  15. Extracellular vesicles from Leishmania-infected macrophages confer an anti-infection cytokine-production profile to naïve macrophages.

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    André Cronemberger-Andrade

    2014-09-01

    Full Text Available Extracellular vesicles (EVs are structures with phospholipid bilayer membranes and 100-1000 nm diameters. These vesicles are released from cells upon activation of surface receptors and/or apoptosis. The production of EVs by dendritic cells, mast cells, macrophages, and B and T lymphocytes has been extensively reported in the literature. EVs may express MHC class II and other membrane surface molecules and carry antigens. The aim of this study was to investigate the role of EVs from Leishmania-infected macrophages as immune modulatory particles.In this work it was shown that BALB/c mouse bone marrow-derived macrophages, either infected in vitro with Leishmania amazonensis or left uninfected, release comparable amounts of 50-300 nm-diameter extracellular vesicles (EVs. The EVs were characterized by flow cytometry and electron microscopy. The incubation of naïve macrophages with these EVs for 48 hours led to a statistically significant increase in the production of the cytokines IL-12, IL-1β, and TNF-α.EVs derived from macrophages infected with L. amazonensis induce other macrophages, which in vivo could be bystander cells, to produce the proinflammatory cytokines IL-12, IL-1β and TNF-α. This could contribute both to modulate the immune system in favor of a Th1 immune response and to the elimination of the Leishmania, leading, therefore, to the control the infection.

  16. Postpartum deaths: piglet, placental, and umbilical characteristics.

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    Rootwelt, V; Reksen, O; Farstad, W; Framstad, T

    2013-06-01

    The fetal growth of the piglet is highly dependent on its placenta, and the newborn piglet birth weight is highly associated with postpartum death. However, there is little information available in the literature on the assessment of the placenta in relation to postpartum death in piglets. The aim of this study was to evaluate the impact of the placental area and placental weight, status of the umbilical cord, and piglet birth characteristics, such as blood parameters, vitality score, and birth weight on postpartum death. All live born piglets in litters from 26 Landrace-Yorkshire sows were monitored during farrowing and the status of each was recorded, including placental area and placental weight and blood variables obtained from the piglets and umbilical veins. Out of the 386 live-born piglets, 16.8% died before weaning at 5 wk. Among these, 78.5% died within the first 3 d of life. Mean blood concentration of lactate was increased in piglets that did not survive to weaning (P = 0.003). Concentrations of hemoglobin and hematocrit were decreased (P Piglets born with a broken umbilical cord had a reduced vitality score vs. piglets born with an intact umbilical cord (P = 0.021), and they had an increased probability of dying before weaning (P = 0.050). Mean birth weight, body mass index, placental area (P piglets that died before weaning vs. those that survived. Birth weight and placental area were furthermore negatively associated with live litter size. Blood concentrations of IgG and albumin recorded at d 1 were decreased in piglets that died before weaning (P < 0.01), and blood concentration of albumin was positively associated with placental area (P < 0.001). We conclude that placental area and placental weight, status of the umbilical cord, birth weight, body mass index, blood concentrations of lactate, hemoglobin, and hematocrit recorded at birth, and blood concentrations of IgG and albumin recorded at d 1 were associated with postpartum death in this study

  17. Prediction of fetal acidemia in placental abruption

    OpenAIRE

    MATSUDA, Yoshio; OGAWA, Masaki; KONNO, Jun; MITANI, Minoru; MATSUI, Hideo

    2013-01-01

    Background To determine the major predictive factors for fetal acidemia in placental abruption. Methods A retrospective review of pregnancies with placental abruption was performed using a logistic regression model. Fetal acidemia was defined as a pH of less than 7.0 in umbilical artery. The severe abruption score, which was derived from a linear discriminant function, was calculated to determine the probability of fetal acidemia. Results Fetal acidemia was seen in 43 survivors (43/222, 19%)....

  18. Comparative aspects of trophoblast development and placentation

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    Enders Allen C

    2004-07-01

    Full Text Available Abstract Based on the number of tissues separating maternal from fetal blood, placentas are classified as epitheliochorial, endotheliochorial or hemochorial. We review the occurrence of these placental types in the various orders of eutherian mammals within the framework of the four superorders identified by the techniques of molecular phylogenetics. The superorder Afrotheria diversified in ancient Africa and its living representatives include elephants, sea cows, hyraxes, aardvark, elephant shrews and tenrecs. Xenarthra, comprising armadillos, anteaters and sloths, diversified in South America. All placentas examined from members of these two oldest superorders are either endotheliochorial or hemochorial. The superorder Euarchontoglires includes two sister groups, Glires and Euarchonta. The former comprises rodents and lagomorphs, which typically have hemochorial placentas. The most primitive members of Euarchonta, the tree shrews, have endotheliochorial placentation. Flying lemurs and all higher primates have hemochorial placentas. However, the lemurs and lorises are exceptional among primates in having epitheliochorial placentation. Laurasiatheria, the last superorder to arise, includes several orders with epitheliochorial placentation. These comprise whales, camels, pigs, ruminants, horses and pangolins. In contrast, nearly all carnivores have endotheliochorial placentation, whilst bats have endotheliochorial or hemochorial placentas. Also included in Laurasiatheria are a number of insectivores that have many conserved morphological characters; none of these has epitheliochorial placentation. Consideration of placental type in relation to the findings of molecular phylogenetics suggests that the likely path of evolution in Afrotheria was from endotheliochorial to hemochorial placentation. This is also a likely scenario for Xenarthra and the bats. We argue that a definitive epitheliochorial placenta is a secondary specialization and that it

  19. The distinct proteome of placental malaria parasites.

    Energy Technology Data Exchange (ETDEWEB)

    Fried, Michal; Hixson, Kim K.; Anderson, Lori; Ogata, Yuko; Mutabingwa, Theonest K.; Duffy, Patrick E.

    2007-09-01

    Malaria proteins expressed on the surface of Plasmodium falciparum infected erythrocytes (IE) mediate adhesion and are targeted by protective immune responses. During pregnancy, IE sequester in the placenta. Placental IE bind to the molecule chondroitin sulfate A (CSA) and preferentially transcribe the gene that encodes VAR2CSA, a member of the PfEMP1 variant surface antigen family. Over successive pregnancies women develop specific immunity to CSA-binding IE and antibodies to VAR2CSA. We used tandem mass spectrometry together with accurate mass and time tag technology to study IE membrane fractions of placental parasites. VAR2CSA peptides were detected in placental IE and in IE from children, but the MC variant of VAR2CSA was specifically associated with placental IE. We identified six conserved hypothetical proteins with putative TM or signal peptides that were exclusively expressed by the placental IE, and 11 such proteins that were significantly more abundant in placental IE. One of these hypothetical proteins, PFI1785w, is a 42kDa molecule detected by Western blot in parasites infecting pregnant women but not those infecting children.

  20. Perfil de citocinas da polipose nasossinusal na Fibrose Cística comparado com indivíduos sem doenças nasossinusais Cytokine profile in subjects with Cystic Fibrosis and nasal polyposis compared to patients with no nasal disorders

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    Flávio Barbosa Nunes

    2010-02-01

    Full Text Available Embora o perfil das citocinas na polipose nasossinusal seja bem documentado, pouco se sabe sobre estas proteínas quando associadas à Fibrose Cística. OBJETIVOS: Avaliar a expressão das citocinas IL¬4, IL¬5, IL¬6, IL¬8, GM¬C-SF e IFN--y analisada pela RT¬-PCR, nos pólipos de pacientes com Fibrose Cística. MATERIAL E MÉTODO: Estudo transversal, prospectivo, de 24 pacientes, 13 com Fibrose Cística e polipose nasossinusal (Grupo Fibrose Cística e 11 com exame otorrinolaringológico normal (Grupo Controle. A média de idade foi de 21 anos (3¬-57, 12 eram do sexo masculino e 12 do sexo feminino. O perfil das citocinas foi pesquisado nos fragmentos de mucosa (Grupo Controle ou pólipo nasal (Grupo Fibrose Cística através da RT-¬PCR. Foram estudadas as transcrições para as citocinas IL¬4, IL¬5, IL¬6, IL¬8, IFN¬y e GM¬-CSF ajustadas pelo valor da β¬ actina. RESULTADOS: As interleucinas 5, 6, 8 e GM¬-CSF foram semelhantes nos dois grupos (p>0,05. Menores valores de IFNy¬ (p=0,03 e forte tendência de aumento de IL¬4 (p=0,06 foram observados no grupo Fibrose Cística. CONCLUSÃO: As células inflamatórias e estruturais podem produzir RNA mensageiro para IL¬4, bloqueando a produção de outras citocinas com IFN-y¬, sugerindo a participação destes mecanismos na formação dos pólipos da Fibrose Cística.Although the cytokine profile in nasal polyposis is well documented, little is known about cytokines associated to cystic fibrosis. AIM: Assess the expression of cytokines IL¬4, IL¬5, IL¬6, IL¬8, GM¬-CSF and IFN¬-y, analyzed through RT-PCR, in the polyps of patients with cystic fibrosis. MATERIALS AND METHODS: A cross-sectional, prospective study was carried out with 24 patients, 13 of whom had cystic fibrosis and nasal polyposis (Cystic Fibrosis Group and 11 had normal otorhinolaryngological exams (Control Group. The average age was 21 years (3¬57; 12 participants were males and 12 were females. The cytokine

  1. Expression Profile of Cytokines and Enzymes mRNA in Blood Leukocytes of Dogs with Leptospirosis and Its Associated Pulmonary Hemorrhage Syndrome.

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    Carla A Maissen-Villiger

    Full Text Available Dogs with leptospirosis show similar organ manifestations and disease course as human patients, including acute kidney injury and pulmonary hemorrhage, making this naturally-occurring infection a good animal model for human leptospirosis. Expression patterns of cytokines and enzymes have been correlated with disease manifestations and clinical outcome in humans and animals. The aim of this study was to describe mRNA expression of pro- and anti-inflammatory mediators in canine leptospirosis and to compare it with other renal diseases to identify patterns characterizing the disease and especially its pulmonary form.The mRNA abundance of cytokines (IL-1α, IL-1β, IL-8, IL-10, TNF-α, TGF-β and enzymes (5-LO, iNOS was measured prospectively in blood leukocytes from 34 dogs with severe leptospirosis and acute kidney injury, including 22 dogs with leptospirosis-associated pulmonary hemorrhages. Dogs with leptospirosis were compared to 14 dogs with acute kidney injury of other origin than leptospirosis, 8 dogs with chronic kidney disease, and 10 healthy control dogs. Canine leptospirosis was characterized by high 5-LO and low TNF-α expression compared to other causes of acute kidney injury, although the decreased TNF-α expression was also seen in chronic kidney disease. Leptospirosis-associated pulmonary hemorrhage was not characterized by a specific pattern, with only mild changes noted, including increased IL-10 and decreased 5-LO expression on some days in affected dogs. Fatal outcome from pulmonary hemorrhages was associated with low TNF-α, high IL-1β, and high iNOS expression, a pattern possibly expressed also in dogs with other forms of acute kidney injury.The patterns of cytokine and enzyme expression observed in the present study indicate a complex pro- and anti-inflammatory response to the infection with leptospires. The recognition of these signatures may be of diagnostic and prognostic relevance for affected individuals and they may

  2. Tissue-specific transcription profile of cytokine and chemokine genes associated with flavivirus control and non-lethal neuropathogenesis in rabbits.

    Science.gov (United States)

    Suen, Willy W; Uddin, Muhammad Jasim; Prow, Natalie A; Bowen, Richard A; Hall, Roy A; Bielefeldt-Ohmann, Helle

    2016-07-01

    We previously showed that New Zealand White (NZWRs) and cottontail rabbits (CTRs) are a suitable model for studying immune mechanisms behind virus control and non-lethal neuropathogenesis associated with West Nile virus (WNV) and Murray Valley encephalitis virus (MVEV) infections. In the current study, we observed that MVEV infection induced high IFNα, TNFα, IL6, and CXCL10 transcript levels in the brains of weanling NZWRs, unlike infection with the less virulent WNVNSW2011. These transcript levels also correlated with encephalitis severity. Widespread STAT1 protein expression in brain with moderate neuropathology suggests that IFN-I signaling is crucial for limiting neural infection and mediating non-lethal neuropathogenesis. Unlike NZWRs, CTRs limit neuroinvasion without upregulation of many cytokine/chemokine transcripts, suggesting a species-dependent virus control mechanism. However, the common IFNγ, TNFα and IL6 transcript upregulation in specific lymphoid organs suggest some conserved elements in the response against flaviviruses, unique to all rabbits.

  3. Cytokine and chemokine mRNA expression profiles in BALF cells isolated from pigs single infected or co-infected with swine influenza virus and Bordetella bronchiseptica.

    Science.gov (United States)

    Kowalczyk, Andrzej; Pomorska-Mól, Małgorzata; Kwit, Krzysztof; Pejsak, Zygmunt; Rachubik, Jarosław; Markowska-Daniel, Iwona

    2014-06-01

    Pigs serve as a valuable animal experimental model for several respiratory pathogens, including Swine Influenza Virus (SIV) and Bordetella bronchiseptica (Bbr). To investigate the effect of SIV and Bbr coinfection on cytokine and viral RNA expression, we performed a study in which pigs were inoculated with SIV, Bbr or both pathogens (SIV/Bbr). Our results indicate that Bbr infection alters SIV clearance. Pulmonary lesions in the SIV/Bbr group were more severe when compared to SIV or Bbr groups and Bbr did not cause significant lesions. Broncho-alveolar lavage fluid (BALF) was examined for inflammatory mediators by qPCR. Interferon (IFN)-α, interleukin IL-8, IL-1 peaked in BALF at 2 DPI, while the virus titres and severity of clinical signs were maximal at the same time. Despite its increased expression in co-infected pigs, interferon-α did not enhance SIV clearance, since the viral replication was detected at the same day as the highest IFN levels. The mRNA levels for IFN-α, IL-1β and IL-8 were significantly higher in BALF of co-infected pigs and correlated with enhanced viral RNA titers in lungs, trachea and nasal swabs. Transcription of mRNA for IL-1β was stable in SIV and SIV/Bbr groups throughout all the study. In Bbr group, the levels of mRNAs for IL-1β were significantly higher at 2, 4 and 9 DPI. The mean levels of mRNAs for TNF-α were lower than the levels of other chemokines and cytokines in all infected groups. Transcript levels of IL-10 and IL-4 did not increase at each time points. Overall, SIV replication was increased by Bbr presence and the enhanced production of pro-inflammatory mediators could contribute to the exacerbated pulmonary lesions.

  4. The placental exposome: Placental determinants of fetal adiposity and postnatal body composition

    NARCIS (Netherlands)

    R.M. Lewis (R.); H. Demmelmair (Hans); R. Gaillard (Romy); N. Godfrey; S. Hauguel-De Mouzon (S.); B. Huppertz (B.); E. Larque (E.); R. Saffery (R.); M.E. Symonds (M.); G. Desoye (G.)

    2013-01-01

    textabstractOffspring of obese and diabetic mothers are at increased risk of being born with excess adiposity as a consequence of their intrauterine environment. Excessive fetal fat accretion reflects additional placental nutrient transfer, suggesting an effect of the maternal environment on placent

  5. The placental exposome: Placental determinants of fetal adiposity and postnatal body composition

    NARCIS (Netherlands)

    R.M. Lewis (R.); H. Demmelmair (Hans); R. Gaillard (Romy); N. Godfrey; S. Hauguel-De Mouzon (S.); B. Huppertz (B.); E. Larque (E.); R. Saffery (R.); M.E. Symonds (M.); G. Desoye (G.)

    2013-01-01

    textabstractOffspring of obese and diabetic mothers are at increased risk of being born with excess adiposity as a consequence of their intrauterine environment. Excessive fetal fat accretion reflects additional placental nutrient transfer, suggesting an effect of the maternal environment on placent

  6. The placental RCAS1 expression during stillbirth

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    Tetlak Tomasz

    2005-06-01

    Full Text Available Abstract Background Independently of the fetal death cause the beginning and course of stillbirth is closely related with the growing cytotoxic activity at the maternal-fetal interface. RCAS1 participates in the inhibition of maternal immune response during pregnancy. The alterations of RCAS1 protein expression in placental cells seem to determine the beginning of the labor and participate in the placental abruption. The aim of the present study was to investigate RCAS1 expression in placentas obtained following stillbirths or normal term births. Methods: RCAS1 expression was evaluated by Western blot method with the use of monoclonal anti-RCAS1 antibody in 67 placental tissue samples. Pregnant women were divided into four groups according to the mode of labor onset – spontaneous or induced, and the type of labor, stillbirth or labor at term. Placental beta-Actin expression was chosen as a control protein. Relative amounts of placental RCAS1 were compared with the use of Student's t-test, whereas beta-Actin control data were compared with the use of Mann-Whitney U test. Results: The average relative amount of RCAS1 was significantly lower in women with induced stillbirths than in women with induced labor at term. Similarly, significantly lower RCAS1 placental levels were observed in patients with spontaneous stillbirths than in women with spontaneous labor at term. Significant differences in RCAS1 expression were also observed with the respect to the beginning of the stillbirth: spontaneous and induced. Lowest RCAS1 placental levels were observed in women with spontaneous stillbirth. Conclusions: These preliminary results indicate that the alterations of RCAS1 expression in the human placenta may be involved in the changes of maternal immune system that take place during stillbirth.

  7. Natural killer cell activity, lymphocyte proliferation, and cytokine profile in tumor-bearing mice treated with MAPA, a magnesium aggregated polymer from Aspergillus oryzae.

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    Justo, G Z; Durán, N; Queiroz, M L S

    2003-08-01

    The present study examined the effects of MAPA, an antitumor aggregated polymer of protein magnesium ammonium phospholinoleate-palmitoleate anhydride, isolated from Aspergillus oryzae, on concanavalin A (Con A)-induced spleen cell proliferation, cytokine production and on natural killer (NK) cell activity in Ehrlich ascites tumor-bearing mice. The Ehrlich ascites tumor (EAT) growth led to diminished mitogen-induced expansion of spleen cell populations and total NK activity. This was accompanied by striking spleen enlargement, with a marked increase in total cell counts. Moreover, a substantial enhancement in IL-10 levels, paralleled by a significant decrease in IL-2 was observed, while production of IL-4 and interferon-gamma (IFN-gamma) was not altered. Treatment of mice with 5 mg/kg MAPA for 7 days promoted spleen cell proliferation, IL-2 production and NK cell activity regardless of tumor outgrowth. In addition, MAPA treatment markedly enhanced IFN-gamma levels and reduced IL-10 production relative to EAT mice. A 35% reduction in splenomegaly with normal number of nucleated cells was also found. Altogether, our results suggest that MAPA directly and/or indirectly modulates immune cell activity, and probably disengages tumor-induced suppression of these responses. Clearly, MAPA has an impact and may delay tumor outgrowth through immunotherapeutic mechanisms.

  8. Mast cell depletion in the preclinical phase of collagen-induced arthritis reduces clinical outcome by lowering the inflammatory cytokine profile.

    Science.gov (United States)

    van der Velden, Daniël; Lagraauw, H Maxime; Wezel, Anouk; Launay, Pierre; Kuiper, Johan; Huizinga, Tom W J; Toes, René E M; Bot, Ilze; Stoop, Jeroen N

    2016-06-13

    Rheumatoid arthritis (RA) is a multifactorial autoimmune disease, which is characterized by inflammation of synovial joints leading to the destruction of cartilage and bone. Infiltrating mast cells can be found within the inflamed synovial tissue, however their role in disease pathogenesis is unclear. Therefore we have studied the role of mast cells during different phases of experimental arthritis. We induced collagen-induced arthritis (CIA), the most frequently used animal model of arthritis, in an inducible mast cell knock-out mouse and determined the effect of mast cell depletion on the development and severity of arthritis. Depletion of mast cells in established arthritis did not affect clinical outcome. However, depletion of mast cells during the preclinical phase resulted in a significant reduction in arthritis. This reduction coincided with a decrease in circulating CD4(+) T cells and inflammatory monocytes but not in the collagen-specific antibody levels. Mast cell depletion resulted in reduced levels of IL-6 and IL-17 in serum. Furthermore, stimulation of splenocytes from mast cell-depleted mice with collagen type II resulted in reduced levels of IL-17 and enhanced production of IL-10. Here we show that mast cells contribute to the preclinical phase of CIA. Depletion of mast cells before disease onset resulted in an altered collagen-specific T cell and cytokine response. These data may suggest that mast cells play a role in the regulation of the adaptive immune response during the development of arthritis.

  9. 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.

  10. Relation between utero-placental and feto-placental circulations: a longitudinal study.

    Science.gov (United States)

    Flo, Kari; Wilsgaard, Tom; Acharya, Ganesh

    2010-10-01

    To explore the relation between total utero-placental (TQ(uta)) and feto-placental (Q(uv)) blood flows and establish longitudinal reference ranges for the TQ(uta)/Q(uv) ratio and the mean uterine artery and umbilical artery pulsatility (UtaPI/UAPI) and resistance index (UtaRI/UARI) ratios. Prospective longitudinal observational study. University hospital in Norway. Fifty-three low-risk pregnant women. Uterine artery and umbilical vein blood flow was measured using Doppler ultrasonography at 4-weekly intervals from 22(+0) to 39(+6) weeks of gestation. Ratios between utero-placental and feto-placental volume blood flows and between indices of uterine and umbilical artery impedance. The TQ(uta)/Q(uv) ratio had a significant association with the gestational age (p feto-placental circulations do not appear to be affected by each other under physiological conditions. We have established longitudinal reference ranges for the utero-placental and feto-placental blood flow and impedance ratios during the second half of pregnancy.

  11. Adipocytokine profile, cytokine levels and foxp3 expression in multiple sclerosis: a possible link to susceptibility and clinical course of disease.

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    Solaleh Emamgholipour

    Full Text Available BACKGROUND: Adipocytokines may be involved in multiple sclerosis (MS as well as other autoimmune and inflammatory-related diseases. This study aims to compare levels of resistin, visfatin and leptin in three subgroups of MS patients with healthy subjects and also to study their relationship with Foxp3 expression and levels of several pro-inflammatory mediators such as interleukine-1 β(IL-1 β,tumor necrosis factor-α (TNF-α and human sensitive C-reactive protein (hs-CRP. METHODS: A total of 391 subjects including 200 healthy controls and 191 MS patients were recruited for this case-control study. Circulating adipocytokines and inflammatory mediators were measured using immunoassay methods. Foxp3 gene expression in peripheral blood mononuclear cells (PBMC was determined by quantitative real-time PCR. Fat tissue mass was evaluated by using dual energy X-ray absorptiometery (DEXA. RESULTS: A significant difference was observed in levels of inflammatory mediators, adipocytokines, Foxp3 gene expression and adipose tissue mass between MS patients and healthy controls. All adipocytokines were positively correlated with levels of inflammatory mediators and negatively correlated with Foxp3 expression in MS patients. In controls, there were positive correlations between circulating leptin and resistin with TNF-α and IL-1β in subgroup analysis, the highest levels of TNF-α, IL-1β, hs-CRP, resistin and leptin were observed in primary progressive-MS (PP-MS patients. Also, expression of Foxp3 and levels of visfatin in relapsing remitting-MS(RR-MS patients were higher compared with the other subgroups. CONCLUSIONS: Our findings suggest the potential role of adipocytokines in pathogenesis and severity of MS. Notably, the relationship of adipocytokines levels with inflammatory cytokines as well as clinical features of MS could be considerable in translational medicine and biomarker studies.

  12. PPAR Signaling in Placental Development and Function.

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    Barak, Yaacov; Sadovsky, Yoel; Shalom-Barak, Tali

    2008-01-01

    With the major attention to the pivotal roles of PPARs in diverse aspects of energy metabolism, the essential functions of PPARgamma and PPARbeta/delta in placental development came as a surprise and were often considered a nuisance en route to their genetic analysis. However, these findings provided an opportune entrée into placental biology. Genetic and pharmacological studies, primarily of knockout animal models and cell culture, uncovered networks of PPARgamma and PPARdelta, their heterodimeric RXR partners, associated transcriptional coactivators, and target genes, that regulate various aspects of placental development and function. These studies furnish both specific information about trophoblasts and the placenta and potential hints about the functions of PPARs in other tissues and cell types. They reveal that the remarkable versatility of PPARs extends beyond the orchestration of metabolism to the regulation of cellular differentiation, tissue development, and trophoblast-specific functions. This information and its implications are the subject of this review.

  13. Confined placental mosaicism in short term culture

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    Petrović Bojana

    2016-01-01

    Full Text Available Finding of fetal chromosomal mosaicism complicates genetic counseling, as well as pregnancy management. The aim of this study was to determine the risk of confined placental mosaicism in short term culture of chorionic villous samples. We conducted a retrospective review of karyotype analysis results obtained after chorionic villous sampling (CVS in two years period. A 420 samples of chorionic villi were taken transabdominally and obtained by a semidirect method (overnight incubating culture. All fetuses with CVS mosaicism were under the intensive perinatal care. In all cases of chromosome mosaicism the additional karyotyping was performed from fetal blood samples after 22nd gestational week in order to exclude true fetal mosaicism. After delivery newborns were examined by experienced pediatrician. From 420 analyzed samples in 11 (2,6% cases we found placental mosaicism. No anomalies were seen in genetic sonogram of this fetuses and mosaicism was confirmed only in one case. Confined placental mosaicism (CPM was found in 2,1% (9/420 of all analyzed cases, and it made 90% of all placental mosaicism. In 60% (6/10 of placental mosaicism cases we found mosaicism with single aberrant cell. Trisomy 21 mosaicism was the most frequent aberration found in 30% of cases. Finding of mosaicism in chorionic villi sample is at special importance for genetic counseling, because every case has to be reveled individually regarding the type and level of mosaicism. Anyway, in every case of placental mosaicism intensive antenatal monitoring is necessary, with additional chromosome analysis from different tissue in consideration of previous findings.

  14. Cytokines in Drosophila immunity.

    Science.gov (United States)

    Vanha-Aho, Leena-Maija; Valanne, Susanna; Rämet, Mika

    2016-02-01

    Cytokines are a large and diverse group of small proteins that can affect many biological processes, but most commonly cytokines are known as mediators of the immune response. In the event of an infection, cytokines are produced in response to an immune stimulus, and they function as key regulators of the immune response. Cytokines come in many shapes and sizes, and although they vary greatly in structure, their functions have been well conserved in evolution. The immune signaling pathways that respond to cytokines are remarkably conserved from fly to man. Therefore, Drosophila melanogaster, provides an excellent platform for studying the biology and function of cytokines. In this review, we will describe the cytokines and cytokine-like molecules found in the fly and discuss their roles in host immunity.

  15. Placental ontogeny in Tasmanian snow skinks (genus Niveoscincus) (Lacertilia: Scincidae).

    Science.gov (United States)

    Stewart, James R; Thompson, Michael B

    2009-04-01

    Lizards of the viviparous genus Niveoscincus contributed importantly to a classic model for the evolution of placentation of squamate reptiles. This model predicts that: (1) placental function is correlated with placental structural complexity and (2) the type of chorioallantoic placenta attributed to three species of Niveoscincus (N. metallicus, N. ocellatus, N. pretiosus) is intermediate in complexity to a highly placentotrophic type of placenta. Recent studies of two of these species (N. metallicus, N. ocellatus) revealed additional variation in placental structure, as well as variation in the level of placentotrophy; N. metallicus is predominantly lecithotrophic, while N. ocellatus is highly placentotrophic. We used light microscopy to study placental ontogeny in two biennially reproducing species of Niveoscincus (N. greeni, N. microlepidotus) and placental morphology in late stage embryos of N. pretiosus. These data, in combination with prior studies, provide descriptions of placental structure for six of the eight species assigned to this lineage. The genus Niveoscincus has greater variation in placental structure than any other squamate lineage. We recognize four distinct groupings among these six species based on placental structure. The most highly placentotrophic species, N. ocellatus, has a complex placental morphology, yet shares these structures with a predominantly lecithotrophic species, N. microlepidotus. Thus, among species of Niveoscincus, placental structural complexity is not an infallible predictor of overall placental function.

  16. Quality assessment of a placental perfusion protocol

    DEFF Research Database (Denmark)

    Mathiesen, Line; Mose, Tina; Mørck, Thit Juul;

    2010-01-01

    the placental perfusion model in Copenhagen including control substances. The positive control substance antipyrine shows no difference in transport regardless of perfusion media used or of terms of delivery (n=59, pmarked dextran correspond with leakage criteria (...mlh(-1) from the fetal reservoir) when adding 2 (n=7) and 20mg (n=9) FITC-dextran/100ml fetal perfusion media. Success rate of the Copenhagen placental perfusions is provided in this study, including considerations and quality control parameters. Three checkpoints suggested to determine success rate...

  17. Human CD4+ T-cell response to hepatitis delta virus: identification of multiple epitopes and characterization of T-helper cytokine profiles.

    Science.gov (United States)

    Nisini, R; Paroli, M; Accapezzato, D; Bonino, F; Rosina, F; Santantonio, T; Sallusto, F; Amoroso, A; Houghton, M; Barnaba, V

    1997-01-01

    The T-cell-mediated immune response plays a crucial role in defense against hepatotropic viruses as well as in the pathogenesis of viral chronic hepatitides. However, very little is known about the role of specific T cells during hepatitis delta virus (HDV) infection in humans. In this study, the T-cell response to HDV in chronic hepatitis B virus (HBV) carriers with HDV superinfection was investigated at different levels. Analysis of peripheral blood mononuclear cell (PBMC) proliferation in response to a recombinant form of large hepatitis delta antigen (HDAg) revealed that 8 of 30 patients studied (27%) specifically responded to HDAg. By employing synthetic peptides spanning the entire HDAg sequence, we found that T-cell recognition was directed against different antigenic determinants, with patient-to-patient variation in the pattern of response to peptides. Interestingly, all responders had signs of inactive HDV-induced disease, while none of the patients with active disease and none of the control subjects showed any significant proliferation. More accurate information about the specific T-cell response was obtained at the clonal level. A panel of HDAg-specific CD4+ T-cell clones from three HDV-infected individuals and fine-specificity analysis revealed that the clones tested individually recognized four epitopes corresponding to amino acids (aa) 26 to 41, 50 to 65, 66 to 81, or 106 to 121 of HDAg sequence. The study of human leukocyte antigen (HLA) restriction revealed that peptides 50 to 65 and 106 to 121 were presented to specific T cells in association with multiple class II molecules. In addition, peptide 26 to 41 was efficiently generated after processing of HDAg through the endogenous processing pathway. Cytokine secretion analysis showed that all the CD4+ T-cell clones assayed were able to produce high levels of gamma interferon (IFN-gamma), belonging either to T helper-1 (Th1) or Th0 subsets and that some of them were cytotoxic in a specific assay

  18. Immunosuppressive and angiogenic cytokine profile associated with Bartonella bacilliformis infection in post-outbreak and endemic areas of Carrion's disease in Peru.

    Directory of Open Access Journals (Sweden)

    Maria J Pons

    2017-06-01

    Full Text Available Analysis of immune responses in Bartonella bacilliformis carriers are needed to understand acquisition of immunity to Carrion's disease and may allow identifying biomarkers associated with bacterial infection and disease phases. Serum samples from 144 healthy subjects from 5 villages in the North of Peru collected in 2014 were analyzed. Four villages had a Carrion's disease outbreak in 2013, and the other is a traditionally endemic area. Thirty cytokines, chemokines and growth factors were determined in sera by fluorescent bead-based quantitative suspension array technology, and analyzed in relation to available data on bacteremia quantified by RT-PCR, and IgM and IgG levels measured by ELISA against B. bacilliformis lysates. The presence of bacteremia was associated with low concentrations of HGF (p = 0.005, IL-15 (p = 0.002, IL-6 (p = 0.05, IP-10 (p = 0.008, MIG (p = 0.03 and MIP-1α (p = 0.03. In multi-marker analysis, the same and further TH1-related and pro-inflammatory biomarkers were inversely associated with infection, whereas angiogenic chemokines and IL-10 were positively associated. Only EGF and eotaxin showed a moderate positive correlation with bacteremia. IgM seropositivity, which reflects a recent acute infection, was associated with lower levels of eotaxin (p = 0.05, IL-6 (p = 0.001, and VEGF (p = 0.03. Only GM-CSF and IL-10 concentrations were positively associated with higher levels of IgM (p = 0.01 and p = 0.007. Additionally, IgG seropositivity and levels were associated with high levels of angiogenic markers VEGF (p = 0.047 and eotaxin (p = 0.006, respectively. Our findings suggest that B. bacilliformis infection causes immunosuppression, led in part by overproduction of IL-10. This immunosuppression probably contributes to the chronicity of asymptomatic infections favoring B. bacilliformis persistence in the host, allowing the subsequent transmission to the vector. In addition, angiogenic markers associated with bacteremia

  19. Cytokines: Names and Numbers You Should Care About.

    Science.gov (United States)

    Holdsworth, Stephen R; Gan, Poh-Yi

    2015-12-07

    Cytokines play an important role in host defense against microorganisms. They orchestrate innate immunity by inducing protective local inflammation and systemic acute phase responses. Cytokines are important in initiating, amplifying, directing, mediating, and regulating adaptive immunity. Unfortunately, they may also direct tissue damage if excessive responses occur or if they are involved in directing and mediating autoimmunity. Under these circumstances, cytokines are potential therapeutic targets. Over the last 20 years, we have seen the successful development and clinical implementation of biologic strategies that target key cytokines in specific inflammatory diseases with efficacy, specificity, and toxicity profiles challenging conventional drug therapies. These therapies are finding new applications and many new agents show promise. Unfortunately, these new cytokine-based therapies have had little effect on renal disease. This review provides evidence that common renal diseases, including those causing AKI and the autoimmune proliferative and crescentic forms of GN, have cytokine mediation profiles that suggest they would be susceptible to cytokine-targeting therapeutic strategies.

  20. Cytokines in bipolar disorder

    DEFF Research Database (Denmark)

    Munkholm, Klaus; Vinberg, Maj; Vedel Kessing, Lars

    2012-01-01

    and 767 healthy controls, evaluating 15 different cytokines-, cytokine receptors- or cytokine antagonists. The levels of tumor necrosis factor-α (TNF-α), the soluble tumor necrosis factor receptor type 1 (sTNF-R1) and the soluble inlerleukin-2 receptor (sIL-2R) were elevated in manic patients compared...

  1. Administration of a Multi-Strain Probiotic Product to Women in the Perinatal Period Differentially Affects the Breast Milk Cytokine Profile and May Have Beneficial Effects on Neonatal Gastrointestinal Functional Symptoms. A Randomized Clinical Trial

    Directory of Open Access Journals (Sweden)

    Maria Elisabetta Baldassarre

    2016-10-01

    Full Text Available Background: Probiotic supplementation to women during pregnancy and lactation can modulate breast milk composition, with immune benefits being transferred to their infants. Aim: The aim of the study was to evaluate the effect of high-dose probiotic supplementation to women during late pregnancy and lactation on cytokine profile and secretory IgA (sIgA in breast milk and thus to study if differences in breast milk composition can affect lactoferrin and sIgA levels in stool samples of newborns. The safety of maternal probiotic administration on neonatal growth pattern and gastrointestinal symptoms were also evaluated. Methods: In a double-blind, placebo-controlled, randomized trial, 66 women took either the probiotic (n = 33 or a placebo (n = 33 daily. Levels of interleukins (IL-6, IL-10 and IL-1β, transforming growth factor-β1 (TGF-β1, and sIgA in breast milk; and the level of sIgA and lactoferrin in newborn stool samples were analyzed at birth and then again at one month of life. Antropometrical evaluation and analysis of gastrointestinal events in newborns was also performed. Results: Probiotic maternal consumption had a significant impact on IL6 mean values in colostrum and on IL10 and TGF-β1 mean values in mature breast milk. Fecal sIgA mean values were higher in newborns whose mothers took the probiotic product than in the control group. Probiotic maternal supplementation seems to decrease incidence of infantile colic and regurgitation in infants. Conclusion: High-dose multi-strain probiotic administration to women during pregnancy influences breast milk cytokines pattern and sIgA production in newborns, and seems to improve gastrointestinal functional symptoms in infants.

  2. Placental lesions and outcome in preterm born children : the relation between placental lesions, neonatal morbidity and neurological development

    NARCIS (Netherlands)

    Roescher, Annemiek

    2014-01-01

    The placenta is the link between the mother and her fetus during pregnancy and plays a crucial role in fetal growth and development. A less than optimal placental function as a result of placental lesions, may lead to maternal and or fetal problems. It is known that placental lesions are an importan

  3. Cytokine balance and cytokine-driven natural killer cell dysfunction in systemic juvenile idiopathic arthritis.

    Science.gov (United States)

    Avau, Anneleen; Put, Karen; Wouters, Carine H; Matthys, Patrick

    2015-02-01

    Systemic juvenile idiopathic arthritis (sJIA) is a severe inflammatory childhood disorder, characterized by a specific pattern of systemic features and a typical cytokine profile. Patients are at risk to develop macrophage activation syndrome (MAS), an acute life-threatening condition defined by excessive proliferation and activation of macrophages and T cells. Defects of unknown cause in the natural killer (NK) cell cytotoxic capacity are presumed to underlie the pathogenesis of MAS and have been detected in sJIA patients. Here, we provide an overview of the cytokine profiles in sJIA and related mouse models. We discuss the influence of cytokines on NK cell function, and hypothesize that NK cell dysfunction in sJIA is caused by altered cytokine profiles.

  4. Compartmentalized Cytokine Responses in Hidradenitis Suppurativa.

    Directory of Open Access Journals (Sweden)

    Theodora Kanni

    Full Text Available Favorable treatment outcomes with TNF blockade led us to explore cytokine responses in hidradenitis suppurativa (HS.Blood monocytes of 120 patients and 24 healthy volunteers were subtyped by flow cytometry. Isolated blood mononuclear cells (PBMCs were stimulated for cytokine production; this was repeated in 13 severe patients during treatment with etanercept. Cytokines in pus were measured.CD14brightCD16dim inflammatory monocytes and patrolling monocytes were increased in Hurley III patients. Cytokine production by stimulated PBMCs was low compared to controls but the cytokine gene copies did not differ, indicating post-translational inhibition. The low production of IL-17 was restored, when cells were incubated with adalimumab. In pus, high concentrations of pro-inflammatory cytokines were detected. Based on the patterns, six different cytokine profiles were discerned, which are potentially relevant for the choice of treatment. Clinical improvement with etanercept was predicted by increased production of IL-1β and IL-17 by PBMCs at week 8.Findings indicate compartmentalized cytokine expression in HS; high in pus but suppressed in PBMCs. This is modulated through blockade of TNF.

  5. Placental Development in Ongoing Pregnancy and Miscarriage

    NARCIS (Netherlands)

    A.D. Reus (Averil)

    2015-01-01

    markdownabstract__Abstract__ In this thesis three-dimensional ultrasound, three-dimensional power Doppler ultrasound, virtual reality and histologic examination of the chorionic villous vascularization were used to investigate early placental development in normal ongoing pregnancy as well as misca

  6. A RADIOIMMUNOASSAY FOR PLACENTAL PROTEIN PP5

    Institute of Scientific and Technical Information of China (English)

    WANGShui-Long; DUGuo-Guang; ZHENGShu-Rong; LIUXin-Jun; YANRen-Ying

    1989-01-01

    A radioimmunoasay of high sendtivity end smbility was developed For placental proteinPP5 (PP5), a syncytiotrophoblast product oF the human placenta. We measured 94 samples from 17 normal nonpregnant women, 47 normal pregnant women, and 30 samples

  7. Placental specializations in lecithotrophic viviparous squamate reptiles.

    Science.gov (United States)

    Stewart, James R

    2015-09-01

    Squamate reptiles have been thought to be predisposed to evolution of viviparity because embryos of most oviparous species undergo considerable development in the uterus prior to oviposition. A related hypothesis proposes that prolonged intrauterine gestation, an intermediate condition leading to viviparity, requires little or no physiological adjustment, other than reduction in thickness of the eggshell. This logical framework is often accompanied by an assumption that mode of parity (oviparity, viviparity) and pattern of embryonic nutrition (lecithotrophy, placentotrophy) are independent traits that evolve in sequence. Thus, specializations for viviparity should be absent in some lecithotrophic viviparous species. Studies of species of lizards with geographic variation in mode of parity challenge this scenario by demonstrating that placental specializations are correlated with viviparity. Uterine specializations for placental transport of calcium to viviparous embryos alter uterine physiology compared to oviparous females. In addition, comparative studies of oviparous and viviparous species, i.e., in which gene flow is disrupted, reveal that both uterine and embryonic structural modifications are commonly associated with viviparity, suggesting relatively rapid evolution of placental specializations. Studies of squamate reproductive biology support two hypotheses: 1) evolution of viviparity requires physiological adjustments of the uterine environment, and 2) evolution of viviparity promotes relatively rapid adaptations for placentation. Models for the evolution of viviparity from oviparity, or for reversals from viviparity to oviparity, should reflect current understanding of squamate reproductive biology and future studies should be designed to challenge these models.

  8. Pregnancy Complications: Placental Accreta, Increta and Percreta

    Science.gov (United States)

    ... Being 35 or older Being pregnant before Having placenta previa How can you reduce your risk for placental conditions? One way to reduce your chances for having these ... In some cases, the placenta doesn’t develop correctly or work as well ...

  9. Placental Malaria: From Infection to Malfunction

    OpenAIRE

    2013-01-01

    Malaria during pregnancy is a major factor in infant morbidity and mortality. In this issue of Cell Host and Microbe, Conroy et al. (2013) propose that C5a, a product of complement cascade activation, counteracts the placental vascular remodeling response induced by Plasmodium infection and contributes to fetal growth restriction. Fundação para a Ciência e Tecnologia.

  10. Placental Mesenchymal Dysplasia: A Case Report

    Directory of Open Access Journals (Sweden)

    Rachna Agarwal

    2012-01-01

    Full Text Available Introduction. A rare case of histologically proven placental mesenchymal dysplasia (PMD with fetal omphalocele in a 22-year-old patient is reported. Material and Methods. Antenatal ultrasound of this patient showed hydropic placenta with a live fetus of 17 weeks period of gestation associated with omphalocele. Cordocentesis detected the diploid karyotype of the fetus. Patient, when prognosticated, choose to terminate the pregnancy in view of high incidence of fetal and placental anomalies. Subsequent histopathological examination of placenta established the diagnosis to be placental mesenchymal dysplasia. Conclusion. On clinical and ultrasonic grounds, suspicion of P.M.D. arises when hydropic placenta with a live fetus presents in second trimester of pregnancy. Cordocentesis can detect the diploid karyotype of the fetus in such cases. As this condition is prognostically better than triploid partial mole, continuation of pregnancy can sometimes be considered after through antenatal screening and patient counseling. However, a definite diagnosis of P.M.D. is made only on placental histology by absence of trophoblast hyperplasia and trophoblastic inclusions.

  11. Evolution of factors affecting placental oxygen transfer

    DEFF Research Database (Denmark)

    Carter, A M

    2009-01-01

    states, are more amenable to analysis. This is exemplified by factors contributing, respectively, to blood oxygen affinity and placental diffusing capacity. Comparative genomics has given fresh insight into the evolution of the beta-globin gene complex. In higher primates, duplication of an embryonic...

  12. Recent progress towards understanding the role of DNA methylation in human placental development

    Science.gov (United States)

    Mayne, Benjamin T; Buckberry, Sam; Breen, James; Rodriguez Lopez, Carlos M; Roberts, Claire T

    2016-01-01

    Epigenetic modifications, and particularly DNA methylation, have been studied in many tissues, both healthy and diseased, and across numerous developmental stages. The placenta is the only organ that has a transient life of 9 months and undergoes rapid growth and dynamic structural and functional changes across gestation. Additionally, the placenta is unique because although developing within the mother, its genome is identical to that of the foetus. Given these distinctive characteristics, it is not surprising that the epigenetic landscape affecting placental gene expression may be different to that in other healthy tissues. However, the role of epigenetic modifications, and particularly DNA methylation, in placental development remains largely unknown. Of particular interest is the fact that the placenta is the most hypomethylated human tissue and is characterized by the presence of large partially methylated domains (PMDs) containing silenced genes. Moreover, how and why the placenta is hypomethylated and what role DNA methylation plays in regulating placental gene expression across gestation are poorly understood. We review genome-wide DNA methylation studies in the human placenta and highlight that the different cell types that make up the placenta have very different DNA methylation profiles. Summarizing studies on DNA methylation in the placenta and its relationship with pregnancy complications are difficult due to the limited number of studies available for comparison. To understand the key steps in placental development and hence what may be perturbed in pregnancy complications requires large-scale genome-wide DNA methylation studies coupled with transcriptome analyses. PMID:27026712

  13. Differential Gene Expression Profiles and Selected Cytokine Protein Analysis of Mediastinal Lymph Nodes of Horses with Chronic Recurrent Airway Obstruction (RAO Support an Interleukin-17 Immune Response.

    Directory of Open Access Journals (Sweden)

    Alexandra Korn

    Full Text Available Recurrent airway obstruction (RAO is a pulmonary inflammatory condition that afflicts certain mature horses exposed to organic dust particulates in hay. Its clinical and pathological features, manifested by reversible bronchoconstriction, excessive mucus production and airway neutrophilia, resemble the pulmonary alterations that occur in agricultural workers with occupational asthma. The immunological basis of RAO remains uncertain although its chronicity, its localization to a mucosal surface and its domination by a neutrophilic, non-septic inflammatory response, suggest involvement of Interleukin-17 (IL-17. We examined global gene expression profiles in mediastinal (pulmonary-draining lymph nodes isolated from RAO-affected and control horses. Differential expression of > 200 genes, coupled with network analysis, supports an IL-17 response centered about NF-κB. Immunohistochemical analysis of mediastinal lymph node sections demonstrated increased IL-17 staining intensity in diseased horses. This result, along with the finding of increased IL-17 concentrations in lymph node homogenates from RAO-affected horses (P = 0.1 and a down-regulation of IL-4 gene and protein expression, provides additional evidence of the involvement of IL-17 in the chronic stages of RAO. Additional investigations are needed to ascertain the cellular source of IL-17 in this equine model of occupational asthma. Understanding the immunopathogenesis of this disorder likely will enhance the development of therapeutic interventions beneficial to human and animal pulmonary health.

  14. Imbalance of placental regulatory T cell and Th17 cell population dynamics in the FIV-infected pregnant cat

    Directory of Open Access Journals (Sweden)

    Boudreaux Crystal E

    2012-05-01

    Full Text Available Abstract Background An appropriate balance in placental regulatory T cells (Tregs, an immunosuppressive cell population, and Th17 cells, a pro-inflammatory cell population, is essential in allowing tolerance of the semi-allogeneic fetus. TGF-β and IL-6 are cytokines that promote differentiation of Tregs and Th17 cells from a common progenitor; aberrant expression of the cytokines may perturb the balance in the two cell populations. We previously reported a pro-inflammatory placental environment with decreased levels of FoxP3, a Treg marker, and increased levels of IL-6 in the placentas of FIV-infected cats at early pregnancy. Thus, we hypothesized that FIV infection in the pregnant cat causes altered placental Treg and Th17 cell populations, possibly resulting in placental inflammation. Methods We examined the effect of FIV infection on Treg and Th17 populations in placentas at early pregnancy using quantitative confocal microscopy to measure FoxP3 or RORγ, a Th17 marker, and qPCR to quantify expression of the key cytokines TGF-β and IL-6. Results FoxP3 and RORγ were positively correlated in FIV-infected placentas at early pregnancy, but not placentas from normal cats, indicating virus-induced alteration in the balance of these cell populations. In control cats the expression of IL-6 and RORγ was positively correlated as predicted, but this relationship was disrupted in infected animals. TGF-β was reduced in infected queens, an occurrence that could dysregulate both Treg and Th17 cell populations. Co-expression analyses revealed a highly significant positive correlation between IL-6 and TGF-β expression in control animals that did not occur in infected animals. Conclusion Collectively, these data point toward potential disruption in the balance of Treg and Th17 cell populations that may contribute to FIV-induced inflammation in the feline placenta.

  15. The placental membrane microbiome is altered among subjects with spontaneous preterm birth with and without chorioamnionitis.

    Science.gov (United States)

    Prince, Amanda L; Ma, Jun; Kannan, Paranthaman S; Alvarez, Manuel; Gisslen, Tate; Harris, R Alan; Sweeney, Emma L; Knox, Christine L; Lambers, Donna S; Jobe, Alan H; Chougnet, Claire A; Kallapur, Suhas G; Aagaard, Kjersti M

    2016-05-01

    Preterm birth (PTB) is a leading cause of neonatal morbidity and mortality and is not uncommonly associated with chorioamnionitis. We recently have demonstrated that the placenta harbors a unique microbiome with similar flora to the oral community. We also have shown an association of these placental microbiota with PTB, history of antenatal infection, and excess maternal weight gain. On the basis of these previous observations, we hypothesized that the placental membranes would retain a microbiome community that would vary in association with preterm birth and chorioamnionitis. In the current study, we aimed to examine the differences in the placental membrane microbiome in association with PTB in both the presence and absence of chorioamnionitis and/or funisitis using state-of-the-science whole-genome shotgun metagenomics. This was a cross-sectional analysis with 6 nested spontaneous birth cohorts (n = 9-15 subjects/cohort): Term gestations without chorioamnionitis, term with chorioamnionitis, preterm without chorioamnionitis, preterm with mild chorioamnionitis, preterm with severe chorioamnionitis, and preterm with chorioamnionitis and funisitis. Histologic analysis was performed with Redline's criteria, and inflammatory cytokines were analyzed in the cord blood. DNA from placental membranes was extracted from sterile swabs collected at delivery, and whole-genome shotgun sequencing was performed on the Illumina HiSeq platform. Filtered microbial DNA sequences were annotated and analyzed with MG-RAST (ie, Metagenomic Rapid Annotations using Subsystems Technology) and R. Subjects were assigned to cohorts on the basis of gestational age at delivery and independent scoring of histologic chorioamnionitis. We found that preterm subjects with severe chorioamnionitis and funisitis had increases in cord blood inflammatory cytokines. Of interest, although the placental membrane microbiome was altered in association with severity of histologic chorioamnionitis

  16. Long term NSAID treatment inhibits COX‐2 synthesis in the knee synovial membrane of patients with osteoarthritis: differential proinflammatory cytokine profile between celecoxib and aceclofenac

    Science.gov (United States)

    Álvarez‐Soria, M A; Largo, R; Santillana, J; Sánchez‐Pernaute, O; Calvo, E; Hernández, M; Egido, J; Herrero‐Beaumont, G

    2006-01-01

    Objective To compare the effect of celecoxib with that of a classic non‐steroidal anti‐inflammatory drug (NSAID) on synovial inflammation and on the synovial expression of proinflammatory genes in patients with knee osteoarthritis (OA). Methods 30 patients with severe knee OA scheduled for total knee replacement surgery were included in a 3 month clinical trial. They were randomised to two groups: patients treated with celecoxib (CBX) (200 mg/24 h) and patients treated with aceclofenac (ACF) (100 mg/12 h). Those patients with OA who did not want to be treated with NSAIDs served as a control group. During knee surgery, synovial fluid (SF) and synovial membrane (SM) were collected. A SM specimen was fixed and embedded in paraffin and another part was frozen for molecular biology studies. Results At the end of study both CBX and ACF treated patients showed a significant improvement in pain and knee function compared with controls. Both drugs significantly reduced prostaglandin E2 (PGE2) SF concentration and down regulated COX‐2 mRNA and protein expression at the SM. However, synovial macrophage infiltration (CD68 antigen staining) and expression of proinflammatory mediators, such as interleukin 1β and tumour necrosis factor α, were decreased only by CBX treatment. Conclusion Both drugs improved joint pain and function, inhibited SF PGE2 concentration, and induced a decrease in synovial COX‐2 expression and synthesis not related to the tissue inflammatory status. These data suggest that PGE2 blocking agents may decrease PGE2 production not only by direct COX‐2 inhibition but also by down regulating COX‐2 expression and synthesis. However, CBX and ACF appear to have different anti‐inflammatory profiles in controlling OA synovial macrophage infiltration and proinflammatory expression. PMID:16476713

  17. Global gene expression profiling of a mouse model of ovarian clear cell carcinoma caused by ARID1A and PIK3CA mutations implicates a role for inflammatory cytokine signaling

    Directory of Open Access Journals (Sweden)

    Ronald L. Chandler

    2015-09-01

    Full Text Available Ovarian clear-cell carcinoma (OCCC is an aggressive form of epithelial ovarian cancer (EOC. OCCC represents 5–25% of all EOC incidences and is the second leading cause of death from ovarian cancer (Glasspool and McNeish, 2013 [1]. A recent publication by Chandler et al. reported the first mouse model of OCCC that resembles human OCCC both genetically and histologically by inducing a localized deletion of ARID1A and the expression of the PIK3CAH1047R substitution mutation (Chandler et al., 2015 [2]. We utilized Affymetrix Mouse Gene 2.1 ST arrays for the global gene expression profiling of mouse primary OCCC tumor samples and animal-matched normal ovaries to identify cancer-dependent gene expression. We describe the approach used to generate the differentially expressed genes from the publicly available data deposited at the Gene Expression Omnibus (GEO database under the accession number GSE57380. These data were used in cross-species comparisons to publically available human OCCC gene expression data and allowed the identification of coordinately regulated genes in both mouse and human OCCC and supportive of a role for inflammatory cytokine signaling in OCCC pathogenesis (Chandler et al., 2015 [2].

  18. PLACENTAL PATHOLOGY IN INTRA UTERINE GROWTH RETARDATION

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    Vijaya Sheela

    2015-04-01

    Full Text Available INTRODUCTION: The placental development is an essential step in developing effective strategies or the prediction of various maternal and fetal medical and developmental problems . Oxygen transfer and nutrients to the fetus will be actively regulated by the placenta . AIM AND OBJECTIVE: To study morphological changes of placenta in Intrauterine growth Retardation and to correlate morphological changes of placenta with fetal outcome . MATERIALS AND METHODS: Placental tissue samples were obtained from 50 pregnancies complicated by IUGR and 50 normal uncomplicated pregnancies with gestational age between 28 to 42 weeks attending King George hospital Visakhapatnam . INCLUSIVE CRITERIA : An IUGR fetuses whose estimated fetal weight less than those in 10 th percentile are included in the study . Birth weight percentiles were determined by previously published normal curves . EXCLUSIVE CRITERIA: fetuses with known syndromes , chromosomal anomalies and twins . For all patients included in the data set gestational age was estimated from the last menstrual period or early ultra - sonogram before the 12 th week of gestation . The final data set was composed of 50pregnancies complicated by IUGR and APGAR scores . Because preeclampsia is an important maternal factor associated with IUGR , these cases were further divided into t wo subgroups according to presence of hypertension . Samples were taken both from vaginal deliveries and caesarean sections . All the placentas were examined by pathologists . The placentas were weighed . For each case one or two samples from the umbilical cor ds , extra placental membrane , and parenchyma were taken . Gross pathological findings were confirmed by histology . Histological data included are ischemic necrosis , decidual vascularity , acute chorioamni oni tis , fibrinoid necrosis and choriangiosis . Appropriate statistical parameters were used . Chi - square test was conducted to compare placental pathological changes

  19. The Ovine Fetal and Placental Inflammatory Response to Umbilical Cord Occlusions With Worsening Acidosis.

    Science.gov (United States)

    Xu, Alex; Matushewski, Brad; Cao, Mingju; Hammond, Robert; Frasch, Martin G; Richardson, Bryan S

    2015-11-01

    We hypothesized that repetitive umbilical cord occlusions (UCOs) leading to severe acidemia will stimulate a placental and thereby fetal inflammatory response which will be exacerbated by chronic hypoxemia and low-grade bacterial infection. Chronically instrumented fetal sheep served as controls or underwent repetitive UCOs for up to 4 hours or until fetal arterial pH was 55% and pH approaching 7.00 for all 3 UCO groups. Neutrophils, while unchanged within the cotyledon fetal and intermediate zones, were ∼2-fold higher within the zona intima for all 3 UCO groups. However, no differences were observed in macrophage counts among the treatment groups and no cotyledon mast cells were seen. Fetal plasma and amniotic fluid cytokines remained little changed post-UCOs and/or at 1 and 48 hours of recovery in the normoxic-UCO and hypoxic-UCO groups but increased several fold in the LPS-UCO group with IL-6 plasma values at 1 hour recovery highly correlated with the nadir pH attained (r = -.97). As such, repetitive UCOs with severe acidemia can induce a placental inflammatory response and more so with simulated low-grade infection and likely contributing to cytokine release in the umbilical circulation.

  20. Obesity during pregnancy disrupts placental morphology, cell proliferation, and inflammation in a sex-specific manner across gestation in the mouse.

    Science.gov (United States)

    Kim, Dong Won; Young, Sarah L; Grattan, David R; Jasoni, Christine L

    2014-06-01

    It is well-accepted that maternal obesity affects fetal development to elevate the risk of offspring disease, but how this happens is unclear. Understanding placental alterations during gestation as a consequence of maternal obesity is critical to understanding the impact of maternal obesity on fetal programming. Here, we used histological criteria, flow cytometry, quantitative PCR, and multiplex cytokine assays to examine changes in cell proliferation and inflammation in the placenta during gestation in a mouse model of maternal high-fat diet-induced obesity. We focused on mouse mid- to late gestation (approximately human late first and third trimester) because previous literature has indicated that this is when important regulators of metabolism, including that of the brain and endocrine pancreas, are forming. These studies were undertaken in order to understand how maternal obesity changes the placenta during this period, which might suggest a causal link to later-life metabolic dysfunction. We found that labyrinth thickness and cell proliferation were decreased at both pregnancy stages in obese compared to normal weight pregnancies. Inflammation was also altered in late pregnancy with increased macrophage activation and elevated cytokine gene expression in the placenta as well as increased abundance of some cytokines in the fetal circulation in obese compared to normal weight pregnancies. These changes in macrophage activation and cytokine gene expression were of greater magnitude and significance in placentas accompanying male fetuses. These data provide insight into placental changes in obesity and identify potential links between placental inflammation and programming of offspring disease by maternal obesity.

  1. Doppler indicates of uterine artery Doppler velocimetry by placental location

    Energy Technology Data Exchange (ETDEWEB)

    Han, Sung Shik; Park, Yong Won; Cho, Jae Sung; Kwon, Hye Kyeung; Kim, Jae Wook [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2001-09-15

    Our purpose was to investigate the relation between the vascular resistance of uterine artery and placental location and to establish the reference value of Doppler index in uterine artery by placental location. Placental location and flow velocity waveforms of both uterine arteries in 7,016 pregnant women after 18 weeks gestation were examined using color Doppler ultrasonography. Placental location was classified as central and lateral placental and the uterine artery with lateral placental were divided into ipsilateral uterine artery (same side of the placental) and contralateral uterine artery (opposite side of the placenta). The uterine artery with central placental was classified as the central uterine artery. Systolic-Diastolic ratio (S/D ratio) of uterine arteries by gestational weeks were calculated and compared with the placental location and perinatal outcomes. In the lateral placental group, the S/D ratio of the contralateral uterine artery was higher than the ipsilateral one (mean=2.08+0.34 vs 1.89+0.34, p=0.0001). S/D ratio of the uterine artery decreased during second trimester and the ratio after 27 weeks was a tendency to have a constant values(ipsilateral: 1.85+ 0.34, central : 1.96+ 0.40, contralateral: 2.01+0.54). S/D ratio of the uterine artery was affected by placental location. So when we evaluate Doppler spectrum of uterine artery, placental location should be considered and we established the reference value of Doppler index of uterine artery by placental location.

  2. Bioactive factors in uteroplacental and systemic circulation link placental ischemia to generalized vascular dysfunction in hypertensive pregnancy and preeclampsia.

    Science.gov (United States)

    Shah, Dania A; Khalil, Raouf A

    2015-06-15

    Preeclampsia is a pregnancy-associated disorder characterized by hypertension, and could lead to maternal and fetal morbidity and mortality; however, the pathophysiological mechanisms involved are unclear. Predisposing demographic, genetic and environmental risk factors could cause localized abnormalities in uteroplacental cytoactive factors such as integrins, matrix metalloproteinases, cytokines and major histocompatibility complex molecules leading to decreased vascular remodeling, uteroplacental vasoconstriction, trophoblast cells apoptosis, and abnormal development of the placenta. Defective placentation and decreased trophoblast invasion of the myometrium cause reduction in uteroplacental perfusion pressure (RUPP) and placental ischemia/hypoxia, an important event in preeclampsia. RUPP could stimulate the release of circulating bioactive factors such as the anti-angiogenic factors soluble fms-like tyrosine kinase-1 and soluble endoglin that cause imbalance with the pro-angiogenic factors vascular endothelial growth factor and placental growth factor, or cause the release of inflammatory cytokines, reactive oxygen species, hypoxia-induced factor-1 and AT1 angiotensin receptor agonistic autoantibodies. The circulating bioactive factors target endothelial cells causing generalized endotheliosis, endothelial dysfunction, decreased vasodilators such as nitric oxide and prostacyclin and increased vasoconstrictors such as endothelin-1 and thromboxane A2, leading to increased vasoconstriction. The bioactive factors also stimulate the mechanisms of VSM contraction including Ca(2+), protein kinase C, and Rho-kinase and induce extracellular matrix remodeling leading to further vasoconstriction and hypertension. While therapeutic options are currently limited, understanding the underlying mechanisms could help design new interventions for management of preeclampsia.

  3. Cytokines and HCV-Related Disorders

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    Poupak Fallahi

    2012-01-01

    However, HCV interferes with cytokines at various levels and escapes immune response by inducing a T-helper (Th2/T cytotoxic 2 cytokine profile. Inability to control infection leads to the recruitment of inflammatory infiltrates into the liver parenchyma by interferon (IFN-gamma-inducible CXC chemokine ligand (CXCL-9, -10, and -11 chemokines, which results in sustained liver damage and eventually in liver cirrhosis. The most important systemic HCV-related extrahepatic diseases—mixed cryoglobulinemia, lymphoproliferative disorders, thyroid autoimmune disorders, and type 2 diabetes—are associated with a complex dysregulation of the cytokine/chemokine network, involving proinflammatory and Th1 chemokines. The therapeutical administration of cytokines such as IFN-alpha may result in viral clearance during persistent infection and reverts this process.

  4. 甲基乙二醛对Jurkat细胞氧化应激及分泌细胞因子的影响%Effects of methylglyoxal on oxidative stress and cytokine profiles in cultured Jurkat cells

    Institute of Scientific and Technical Information of China (English)

    游捷; 余洪根; 彭雪峰; 刘晓红; 刘礼斌

    2011-01-01

    Objective:To investigate the effects of mthylglyoxal(MGO) on oxidative stress and cytokine profiles in cultured Jurkat cells for understanding more about the mechanism of diabetes accelerated athevosclerosis.Method:Jurkat cell which pre-stimulated by PHA were incubated with MGO for 24h.The cells survial rate was detected by MTT.ROS was quantitated by flow cytometry.Total and phosphory-lated p38 and JNK were assessed using Western blot.After incubation with MGO,the expression of TNFF-α and IFN-γ were tested by ELISA.Results:No changes in cells viability was observed when Jurkat cells were treated with 0-60 μmol/1cytokines.Conclusion:These data demonstrate that MGO in-duced the release of TNF-α and IFN-γ in Jurkat cells viaoxidative stress,p38,JNK signaling pathway.%目的:探讨甲基乙二醛(MGO)对Jurkat细胞氧化应激及分泌细胞因子的影响.方法:不同浓度MGO作用PHA预刺激的Jurkat细胞,MTT检测细胞生长,流式细胞检测细胞内活性氧(ROS),Western blot检测p38 MAPK、JNK磷酸化水平,ELISA检测TNF-α、IFN-γ.结果:15~60 μmol/L MGO对Jurkat细胞生长无影响,但能使ROS呈浓度依赖性升高;N-乙酰-L-半胱氨酸(NAC)和氨基胍(AG)能明显抑制此作用.MGO作用30分钟,pp38/p38、pJNK/JNK明显升高.MGO诱导Jurkat细胞分泌TNF-α、IFN-γ;P38、JNK抑制剂及NAC能降低TNF-α、IFN-γ的分泌.结论:MGO能诱导Jurkat分泌TNF-α、IFN-γ;其机制可能通过氧化应激、P38、JNK信号通路.

  5. Human cytomegalovirus-induces cytokine changes in the placenta with implications for adverse pregnancy outcomes.

    Directory of Open Access Journals (Sweden)

    Stuart T Hamilton

    Full Text Available Human cytomegalovirus (CMV infection of the developing fetus can result in adverse pregnancy outcomes including death in utero. Fetal injury results from direct viral cytopathic damage to the CMV-infected fetus, although evidence suggests CMV placental infection may indirectly cause injury to the fetus, possibly via immune dysregulation with placental dysfunction. This study investigated the effects of CMV infection on expression of the chemokine MCP-1 (CCL2 and cytokine TNF-α in placentae from naturally infected stillborn babies, and compared these changes with those found in placental villous explant histocultures acutely infected with CMV ex vivo. Tissue cytokine protein levels were assessed using quantitative immunohistochemistry. CMV-infected placentae from stillborn babies had significantly elevated MCP-1 and TNF-α levels compared with uninfected placentae (p = 0.001 and p = 0.007, which was not observed in placentae infected with other microorganisms (p = 0.62 and p = 0.71 (n = 7 per group. Modelling acute clinical infection using ex vivo placental explant histocultures showed infection with CMV laboratory strain AD169 (0.2 pfu/ml caused significantly elevated expression of MCP-1 and TNF-α compared with uninfected explants (p = 0.0003 and p<0.0001 (n = 25 per group. Explant infection with wild-type Merlin at a tenfold lower multiplicity of infection (0.02 pfu/ml, caused a significant positive correlation between increased explant infection and upregulation of MCP-1 and TNF-α expression (p = 0.0001 and p = 0.017. Cytokine dysregulation has been associated with adverse outcomes of pregnancy, and can negatively affect placental development and function. These novel findings demonstrate CMV infection modulates the placental immune environment in vivo and in a multicellular ex vivo model, suggesting CMV-induced cytokine modulation as a potential initiator and/or exacerbator of placental and fetal injury.

  6. Human placental lactogen and intrauterine growth retardation.

    Science.gov (United States)

    Spellacy, W N; Buhi, W C; Birk, S A

    1976-04-01

    Serum human placental lactogen levels were measured after 36 weeks' gestation in 264 serum samples from 109 women with normal pregnancies and in 137 serum samples from 70 women with pregnancies complicated by fetal intrauterine growth retardation (IGR). The fetal and placental weights were significantly lower in the IGR groups while the maternal ages were not different. There was a significantly lower hPL value at each week from 36 to 41 (except for the 39th) in the IGR group. Sixty percent of the women with IGR had hPL values less than 6 mug/ml, and 18.6% were less than 4 mug/ml. It is suggested that a low serum hPL value obtained during the last month of pregnancy should alert the physician to the possibility of intrauterine problems, including IGR.

  7. Neurotrophins: Role in Placental Growth and Development.

    Science.gov (United States)

    Sahay, A S; Sundrani, D P; Joshi, S R

    2017-01-01

    Neurotrophins, a family of closely related proteins, were originally identified as growth factors for survival, development, and function of neurons in both the central and peripheral nervous systems. Subsequently, neurotrophins have been shown to have functions in immune and reproductive systems. Neurotrophins like nerve growth factor and brain-derived neurotrophic factor (BDNF) are known to play an important role during pregnancy in the process of placental angiogenesis and maturation. Several studies have demonstrated the presence of neurotrophins in the human placenta. The current chapter reviews studies demonstrating the role of neurotrophins during pregnancy particularly in placental development. This chapter also focuses on the regional changes in neurotrophins in the human placenta and its interactions with other growth factors. Future research is needed to understand the mechanisms through which neurotrophins influence the growth and development of the placenta and pregnancy outcome.

  8. Placentation in the Amazonian manatee (Trichechus inunguis)

    DEFF Research Database (Denmark)

    Carter, A M; Miglino, M A; Ambrosio, C E;

    2008-01-01

    Evidence from several sources supports a close phylogenetic relationship between elephants and sirenians. To explore whether this was reflected in similar placentation, we examined eight delivered placentae from the Amazonian manatee using light microscopy and immunohistochemistry. In addition......, the fetal placental circulation was described by scanning electron microscopy of vessel casts. The manatee placenta was zonary and endotheliochorial, like that of the elephant. The interhaemal barrier comprised maternal endothelium, cytotrophoblasts and fetal endothelium. We found columnar trophoblast...... beneath the chorionic plate and lining lacunae in this region, but there was no trace in the term placenta of haemophagous activity. The gross anatomy of the cord and fetal membranes was consistent with previous descriptions and included a four-chambered allantoic sac, as also found in the elephant...

  9. How does Chinese medicine target cytokine imbalance in rheumatoid arthritis?

    Science.gov (United States)

    Liu, Jian; Sun, Yue

    2013-11-01

    Rheumatoid arthritis (RA) manifests as an imbalance between pro- and anti-inflammatory cytokines. Cytokine imbalance is suggested to play critical roles in the development of RA. Currently, various treatments for RA, including biological agents such as antibodies against inflammation mediators, or Chinese herbal medicines, intervene the disease by restoring the balance of cytokines. Chinese medicine (CM) can not only suppress the expression of pro-inflammatory cytokines, but also induce the expression of cytokines with anti-inflammatory and immunomodulatory effects. Thus, Chinese medicine can effectively reduce inflammatory cell infiltration into synovial tissue, pannus formation, and degradation of the extracellular matrix surrounding cartilage cells, thereby reducing subchondral bone damage. This paper reviews the changes of cytokine profiling during development of RA and discuss the mechanisms by which Chinese medicine restores the cytokine balance.

  10. Adenoviral-mediated placental gene transfer of IGF-1 corrects placental insufficiency via enhanced placental glucose transport mechanisms.

    Directory of Open Access Journals (Sweden)

    Helen N Jones

    Full Text Available Previous work in our laboratory demonstrated that over-expression of human insulin-like growth factor -1 (hIGF-1 in the placenta corrects fetal weight deficits in mouse, rat, and rabbit models of intrauterine growth restriction without changes in placental weight. The underlying mechanisms of this effect have not been elucidated. To investigate the effect of intra-placental IGF-1 over-expression on placental function we examined glucose transporter expression and localization in both a mouse model of IUGR and a model of human trophoblast, the BeWo Choriocarcinoma cell line.At gestational day 18, animals were divided into four groups; sham-operated controls, uterine artery branch ligation (UABL, UABL+Ad-hIGF-1 (10(8 PFU, UABL+Ad-LacZ (10(8 PFU. At gestational day 20, pups and placentas were harvested by C-section. For human studies, BeWo choriocarcinoma cells were grown in F12 complete medium +10%FBS. Cells were incubated in serum-free control media ± Ad-IGF-1 or Ad-LacZ for 48 hours. MOIs of 10∶1 and 100∶1 were utilized. The RNA, protein expression and localization of glucose transporters GLUT1, 3, 8, and 9 were analyzed by RT-PCR, Western blot and immunohistochemistry.In both the mouse placenta and BeWo, GLUT1 regulation was linked to altered protein localization. GLUT3, localized to the mouse fetal endothelial cells, was reduced in placental insufficiency but maintained with Ad-I GF-1 treatment. Interestingly, GLUT8 expression was reduced in the UABL placenta but up-regulated following Ad-IGF-1 in both mouse and human systems. GLUT9 expression in the mouse was increased by Ad-IGF-1 but this was not reflected in the BeWo, where Ad-IGF-1 caused moderate membrane relocalization.Enhanced GLUT isoform transporter expression and relocalization to the membrane may be an important mechanism in Ad-hIGF-1mediated correction of placental insufficiency.

  11. Preeclampsia, biomarkers, syncytiotrophoblast stress, and placental capacity.

    Science.gov (United States)

    Redman, Christopher W G; Staff, Anne Cathrine

    2015-10-01

    The maternal syndrome of preeclampsia is mediated by dysfunctional syncytiotrophoblast (STB). When this is stressed by uteroplacental malperfusion, its signaling to the mother changes, as part of a highly coordinated stress response. The STB signals are both proinflammatory and dysangiogenic such that the preeclamptic mother has a stronger vascular inflammatory response than normal, with an antiangiogenic bias. Angiogenic factors have limitations as preeclampsia biomarkers, especially for prediction and diagnosis of preeclampsia at term. However, if they are recognized as markers of STB stress, their physiological changes at term demonstrate that STB stress develops in all pregnancies. The biomarkers reveal that the duration of pregnancies is restricted by placental capacity, such that there is increasing placental dysfunction, at and beyond term. This capacity includes limitations imposed by the size of the uterus, the capacity of the uteroplacental circulation and, possibly, the supply of villous progenitor trophoblast cells. Limited placental capacity explains the increasing risks of postmaturity, including preeclampsia. Early-onset preeclampsia is predictable because STB stress and changes in its biomarkers are intrinsic to poor placentation, an early pregnancy pathology. Prediction of preeclampsia at term is not good because there is no early STB pathology. Moreover, biomarkers cannot accurately diagnose term preeclampsia against a background of universal STB dysfunction, which may or may not be clinically revealed before spontaneous or induced delivery. In this sense, postterm pregnancy is, at best, a pseudonormal state. However, the markers may prove useful in screening for women with more severe problems of postmaturity. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Placental lactogen levels in rhesus isoimmunization.

    Science.gov (United States)

    Ward, R H; Letchworth, A T; Niven, P A; Chard, T

    1974-03-02

    A prospective study of the plasma levels of human placental lactogen (HPL) in pregnancies complicated by rhesus isoimmunization showed that in mild and moderately affected cases the levels were normal, while in severely affected cases they were raised. Serial levels of HPL before the 26th week provide a valuable indication of fetal outcome, and we suggest that this estimation should be used routinely as an adjunct to other tests in the management of rhesus isoimmunization.

  13. Placentation in mammals once grouped as insectivores.

    Science.gov (United States)

    Carter, Anthony M; Enders, Allen C

    2010-01-01

    Interest in insectivoran grade mammals has been reawakened by taxonomic changes that place tenrecs and golden moles in a new order and separate hedgehogs from moles, shrews and solenodons. This survey of their placentation shows there is great variation even within families. As an example three subfamilies of tenrec have been examined. The interhemal region is cellular hemomonochorial in Echinops and Microgale but endotheliochorial in Micropotamogale. Golden moles, which are placed in the same order, have hemodichorial placentation. Many insectivores have complex arrangements for histotrophic nutrition involving columnar trophoblast cells. These range from areolae in moles through complexly folded hemophagous regions in tenrecs to the trophoblastic annulus in shrews. Of these placental characters, few offer support to current phylogenies. However, the case for placing hedgehogs and gymnures in a separate order (Erinaceomorpha) is bolstered by the presence of interstitial implantation, amniogenesis by cavitation, a hemochorial barrier and a prominent spongy zone; these features do not occur in shrews, moles or solenodons (Soricomorpha). Three insectivoran grade mammals deserve close attention as they have been selected for genome sequencing. One of these, the European hedgehog (Erinaceus europaeus), has not been studied with current methodology and renewed investigation of this or the closely related genus Atelerix should be a priority.

  14. PLACENTAL PATHOLOGY IN PREGNANCY INDUCED HYPERTENSION

    Directory of Open Access Journals (Sweden)

    Sreechithra

    2014-08-01

    Full Text Available BACKGROUND: Hypertensive disorders complicating pregnancy are common and form one of the deadly triad along with hemorrhage and infection, that results in a large number of maternal deaths and there of fetal deaths. Since all anabolites needed for foetal metabolism come from the mothers blood and foetal catabolites are passed back into the mothers circulation through the placenta, the examination of placenta gives a clear idea of what had happened with it, when it was in the mother, s womb and what is going to happen with the foetus in future. With this objective the present study was carried out. MATERIALS AND METHODS: Retrospective study was done for a period of 21 months from April1st 2008 to December 31st 2009..Fifty mothers with uncomplicated pregnancy (control group and 100 mothers (test group diagnosed as having pregnancy induced hypertension were selected from patients of our institution of the age range from 20-40 years, and parity –primi, para2 and 3.Placental morphometric parameters, gross and histopathological features were examined in both test and control groups. STATISTICAL ANALYSIS USED: Fishers exact test RESULTS: Placental morphometric parameters were significantly reduced in the control group. Acute atherosis, endothelial proliferation and fibrinoid necrosis were the significant histological findings noted in our study. CONCLUSION: Placental findings can be confirmatory of PIH, but its absence does not exclude the diseases. These findings will become more evident only when there is significant reduction in the uteroplacental bloodflow

  15. Placental dysfunction and fetal programming: the importance of placental size, shape, histopathology, and molecular composition.

    Science.gov (United States)

    Longtine, Mark S; Nelson, D Michael

    2011-05-01

    Normal function of the placenta is pivotal for optimal fetal growth and development. Fetal programming commonly is associated with placental dysfunction that predisposes to obstetric complications and suboptimal fetal outcomes. We consider several clinical phenotypes for placental dysfunction that likely predispose to fetal programming. Some of these reflect abnormal development of the chorioallantoic placenta in size, shape, or histopathology. Others result when exogenous stressors in the maternal environment combine with maladaptation of the placental response to yield small placentas with limited reserve, as typical of early-onset intrauterine growth restriction and preeclampsia. Still others reflect epigenetic changes, including altered expression of imprinted genes, altered enzymatic activity, or altered efficiencies in nutrient transport. Although the human placenta is a transient organ that persists only 9 months, the effects of this organ on the offspring remain for a lifetime.

  16. The placental mammal ancestor and the post-K-Pg radiation of placentals.

    Science.gov (United States)

    O'Leary, Maureen A; Bloch, Jonathan I; Flynn, John J; Gaudin, Timothy J; Giallombardo, Andres; Giannini, Norberto P; Goldberg, Suzann L; Kraatz, Brian P; Luo, Zhe-Xi; Meng, Jin; Ni, Xijun; Novacek, Michael J; Perini, Fernando A; Randall, Zachary S; Rougier, Guillermo W; Sargis, Eric J; Silcox, Mary T; Simmons, Nancy B; Spaulding, Michelle; Velazco, Paúl M; Weksler, Marcelo; Wible, John R; Cirranello, Andrea L

    2013-02-01

    To discover interordinal relationships of living and fossil placental mammals and the time of origin of placentals relative to the Cretaceous-Paleogene (K-Pg) boundary, we scored 4541 phenomic characters de novo for 86 fossil and living species. Combining these data with molecular sequences, we obtained a phylogenetic tree that, when calibrated with fossils, shows that crown clade Placentalia and placental orders originated after the K-Pg boundary. Many nodes discovered using molecular data are upheld, but phenomic signals overturn molecular signals to show Sundatheria (Dermoptera + Scandentia) as the sister taxon of Primates, a close link between Proboscidea (elephants) and Sirenia (sea cows), and the monophyly of echolocating Chiroptera (bats). Our tree suggests that Placentalia first split into Xenarthra and Epitheria; extinct New World species are the oldest members of Afrotheria.

  17. Placental Protein 13 (PP13 – a placental immunoregulatory galectin protecting pregnancy

    Directory of Open Access Journals (Sweden)

    Nandor Gabor Than

    2014-08-01

    Full Text Available Galectins are glycan-binding proteins that regulate innate and adaptive immune responses, and some confer maternal-fetal immune tolerance in eutherian mammals. A chromosome 19 cluster of galectins has emerged in anthropoid primates, species with deep placentation and long gestation. Three of the five human cluster galectins are solely expressed in the placenta, where they may confer additional immunoregulatory functions to enable deep placentation. One of these is galectin-13, also known as Placental Protein 13 (PP13. It has a jelly-roll fold, carbohydrate-recognition domain and sugar-binding preference resembling to other mammalian galectins. PP13 is predominantly expressed by the syncytiotrophoblast and released from the placenta into the maternal circulation. Its ability to induce apoptosis of activated T cells in vitro, and to divert and kill T cells as well as macrophages in the maternal decidua in situ suggests important immune functions. Indeed, mutations in the promoter and an exon of LGALS13 presumably leading to altered or non-functional protein expression are associated with a higher frequency of preeclampsia and other obstetrical syndromes, which involve immune dysregulation. Moreover, decreased placental expression of PP13 and its low first trimester maternal serum concentrations are associated with elevated risk of preeclampsia. Indeed, PP13 turned to be a good early biomarker to assess maternal risk for the subsequent development of pregnancy complications caused by impaired placentation. Due to the ischemic placental stress in preterm preeclampsia, there is an increased trophoblastic shedding of PP13 immunopositive microvesicles starting in the second trimester, which leads to high maternal blood PP13 concentrations. Our meta-analysis suggests that this phenomenon may enable the potential use of PP13 in directing patient management near to or at the time of delivery. Recent findings on the beneficial effects of PP13 on decreasing

  18. Insights into cytokine-receptor interactions from cytokine engineering.

    Science.gov (United States)

    Spangler, Jamie B; Moraga, Ignacio; Mendoza, Juan L; Garcia, K Christopher

    2015-01-01

    Cytokines exert a vast array of immunoregulatory actions critical to human biology and disease. However, the desired immunotherapeutic effects of native cytokines are often mitigated by toxicity or lack of efficacy, either of which results from cytokine receptor pleiotropy and/or undesired activation of off-target cells. As our understanding of the structural principles of cytokine-receptor interactions has advanced, mechanism-based manipulation of cytokine signaling through protein engineering has become an increasingly feasible and powerful approach. Modified cytokines, both agonists and antagonists, have been engineered with narrowed target cell specificities, and they have also yielded important mechanistic insights into cytokine biology and signaling. Here we review the theory and practice of cytokine engineering and rationalize the mechanisms of several engineered cytokines in the context of structure. We discuss specific examples of how structure-based cytokine engineering has opened new opportunities for cytokines as drugs, with a focus on the immunotherapeutic cytokines interferon, interleukin-2, and interleukin-4.

  19. Elevated placental adenosine signaling contributes to the pathogenesis of preeclampsia.

    Science.gov (United States)

    Iriyama, Takayuki; Sun, Kaiqi; Parchim, Nicholas F; Li, Jessica; Zhao, Cheng; Song, Anren; Hart, Laura A; Blackwell, Sean C; Sibai, Baha M; Chan, Lee-Nien L; Chan, Teh-Sheng; Hicks, M John; Blackburn, Michael R; Kellems, Rodney E; Xia, Yang

    2015-02-24

    Preeclampsia is a prevalent hypertensive disorder of pregnancy and a leading cause of maternal and neonatal morbidity and mortality worldwide. This pathogenic condition is speculated to be caused by placental abnormalities that contribute to the maternal syndrome. However, the specific factors and signaling pathways that lead to impaired placentas and maternal disease development remain elusive. Using 2 independent animal models of preeclampsia (genetically engineered pregnant mice with elevated adenosine exclusively in placentas and a pathogenic autoantibody-induced preeclampsia mouse model), we demonstrated that chronically elevated placental adenosine was sufficient to induce hallmark features of preeclampsia, including hypertension, proteinuria, small fetuses, and impaired placental vasculature. Genetic and pharmacological approaches revealed that elevated placental adenosine coupled with excessive A₂B adenosine receptor (ADORA2B) signaling contributed to the development of these features of preeclampsia. Mechanistically, we provided both human and mouse evidence that elevated placental CD73 is a key enzyme causing increased placental adenosine, thereby contributing to preeclampsia. We determined that elevated placental adenosine signaling is a previously unrecognized pathogenic factor for preeclampsia. Moreover, our findings revealed the molecular basis underlying the elevation of placental adenosine and the detrimental role of excess placental adenosine in the pathophysiology of preeclampsia, and thereby, we highlight novel therapeutic targets. © 2014 American Heart Association, Inc.

  20. Placental localization by scanning with indium 113m

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Seung Wook; Choe, Yong Kyu; Choi, Byung Sook [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    1972-09-15

    The application of radioactive tracers for placental localization has been introduced as the worthwhile diagnostic method in placenta previa. Recently {sup 113m}In has been applied as the broad spectrum agent for the visualization of various organs. The advantage of {sup 113m}In are a short half-life with 1.7 hours and no beta particle emission. During the period from May 1970 to August 1971, the placental scanning with {sup 113m}In was carried out at Yonsei Medical Center on 19 cases of Korean pregnant females who had painless vaginal bleeding with suspicious placenta previa or other placental lesions, clinically. Followings are the results of placental scanning with Indium-113m. 1) Eight cases out of 19 cases were suggested as placenta previa and the remaining 11 cases were turned out to be normal placental location. 2) Among these 8 case of positive scanning, placenta previa totalis was 6 cases, placental previa partialis was 1 case and placenta previa marginalis was also 1 case. 3) Among 11 cases of normal placental localization, right side placenta was 7 cases and left side, 4 cases. The placental scanning with Indium-113m is thought to be one of the simple, safe and rapid method with high accuracy for clinical diagnosis of the placenta previa and placental localization.

  1. Placental Abnormalities and Preeclampsia in Trisomy 13 Pregnancies

    Directory of Open Access Journals (Sweden)

    Chih-Ping Chen

    2009-03-01

    Full Text Available Women who are carrying a trisomy 13 fetus are prone to have an abnormal placenta as well as to develop preeclampsia in the second and third trimesters. This article provides a comprehensive review of placental abnormalities, such as small placental volume, reduced placental vascularization, a partial molar appearance of the placenta and placental mesenchymal dysplasia, and preeclampsia associated with trisomy 13 pregnancies. The candidate preeclampsia-causing genes on chromosome 13, such as sFlt1, COL4A2 and periostin, are discussed.

  2. Cesarean Delivery for a Life-threatening Preterm Placental Abruption

    Science.gov (United States)

    Okafor, II; Ugwu, EO

    2015-01-01

    Placental abruption is one of the major life-threatening obstetric conditions. The fetomaternal outcome of a severe placental abruption depends largely on prompt maternal resuscitation and delivery. A case of severe preterm placental abruption with intrauterine fetal death. Following a failed induction of labor with a deteriorating maternal condition despite resuscitation, emergency cesarean delivery was offered with good maternal outcome. Cesarean delivery could avert further disease progression and possible maternal death in cases of severe preterm placental abruption where vaginal delivery is not imminent. However, further studies are necessary before this could be recommended for routine clinical practice. PMID:27057388

  3. Clinical development of placental malaria vaccines and immunoassays harmonization

    DEFF Research Database (Denmark)

    Chêne, Arnaud; Houard, Sophie; Nielsen, Morten A;

    2016-01-01

    Placental malaria caused by Plasmodium falciparum infection constitutes a major health problem manifesting as severe disease and anaemia in the mother, impaired fetal development, low birth weight or spontaneous abortion. Prevention of placental malaria currently relies on two key strategies...... that are losing efficacy due to spread of resistance: long-lasting insecticide-treated nets and intermittent preventive treatment during pregnancy. A placental malaria vaccine would be an attractive, cost-effective complement to the existing control tools. Two placental malaria vaccine candidates are currently...

  4. Circulating placental proteins in pregnancies complicated by RH isoimmunization.

    Science.gov (United States)

    Lee, J N; Huang, S C; Ouyang, P C; Chard, T

    1984-07-01

    Nine pregnant women with Rh isoimmunization who delivered newborns with hydrops fetalis were studied. The placental proteins, pregnancy specific beta 1-glycoprotein (SP1), human placental lactogen, and placental protein 5 (PP5) were measured in maternal serum by radioimmunoassays. The results indicate that both the serum human placental lactogen and PP5 levels were significantly higher than those observed in normal pregnancy. The strikingly higher circulating PP5 levels found in all nine patients with Rh isoimmunization studied suggests that serum PP5 may be specifically elevated in pregnant patients with Rh isoimmunization and hydrops fetalis.

  5. Prevention of Defective Placentation and Pregnancy Loss by Blocking Innate Immune Pathways in a Syngeneic Model of Placental Insufficiency.

    Science.gov (United States)

    Gelber, Shari E; Brent, Elyssa; Redecha, Patricia; Perino, Giorgio; Tomlinson, Stephen; Davisson, Robin L; Salmon, Jane E

    2015-08-01

    Defective placentation and subsequent placental insufficiency lead to maternal and fetal adverse pregnancy outcome, but their pathologic mechanisms are unclear, and treatment remains elusive. The mildly hypertensive BPH/5 mouse recapitulates many features of human adverse pregnancy outcome, with pregnancies characterized by fetal loss, growth restriction, abnormal placental development, and defects in maternal decidual arteries. Using this model, we show that recruitment of neutrophils triggered by complement activation at the maternal/fetal interface leads to elevation in local TNF-α levels, reduction of the essential angiogenic factor vascular endothelial growth factor, and, ultimately, abnormal placentation and fetal death. Blockade of complement with inhibitors specifically targeted to sites of complement activation, depletion of neutrophils, or blockade of TNF-α improves spiral artery remodeling and rescues pregnancies. These data underscore the importance of innate immune system activation in the pathogenesis of placental insufficiency and identify novel methods for treatment of pregnancy loss mediated by abnormal placentation.

  6. Profiling cytokines in temporal lobe epilepsy

    NARCIS (Netherlands)

    Kan, A.A.

    2012-01-01

    Temporal lobe epilepsy (TLE) is one of the most common types of partial epilepsy. Because about 30% of the TLE patients poorly respond to medication, identification of new drug targets to treat TLE is imperative. This requires detailed knowledge of the pathophysiology of TLE . The aim of this thesis

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

    Science.gov (United States)

    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.

  8. Hofbauer cells of M2a, M2b and M2c polarization may regulate feto-placental angiogenesis.

    Science.gov (United States)

    Loegl, J; Hiden, U; Nussbaumer, E; Schliefsteiner, C; Cvitic, S; Lang, I; Wadsack, C; Huppertz, B; Desoye, G

    2016-11-01

    The human placenta comprises a special type of tissue macrophages, the Hofbauer cells (HBC), which exhibit M2 macrophage phenotype. Several subtypes of M2-polarized macrophages (M2a, M2b and M2c) exist in almost all tissues. Macrophage polarization depends on the way of macrophage activation and leads to the expression of specific cell surface markers and the acquisition of specific functions, including tissue remodeling and the promotion of angiogenesis. The placenta is a highly vascularized and rapidly growing organ, suggesting a role of HBC in feto-placental angiogenesis. We here aimed to characterize the specific polarization and phenotype of HBC and investigated the role of HBC in feto-placental angiogenesis. Therefore, HBC were isolated from third trimester placentas and their phenotype was determined by the presence of cell surface markers (FACS analysis) and secretion of cytokines (ELISA). HBC conditioned medium (CM) was analyzed for pro-angiogenic factors, and the effect of HBC CM on angiogenesis, proliferation and chemoattraction of isolated primary feto-placental endothelial cells (fpEC) was determined in vitro Our results revealed that isolated HBC possess an M2 polarization, with M2a, M2b and M2c characteristics. HBC secreted the pro-angiogenic molecules VEGF and FGF2. Furthermore, HBC CM stimulated the in vitro angiogenesis of fpEC. However, compared with control medium, chemoattraction of fpEC toward HBC CM was reduced. Proliferation of fpEC was not affected by HBC CM. These findings demonstrate a paracrine regulation of feto-placental angiogenesis by HBC in vitro Based on our collective results, we propose that the changes in HBC number or phenotype may affect feto-placental angiogenesis. © 2016 Society for Reproduction and Fertility.

  9. Cytokines and Liver Diseases

    Directory of Open Access Journals (Sweden)

    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.

  10. Placental Inflammatory Changes and Bacterial Infection in Premature Neonates with Respiratory Failure

    Directory of Open Access Journals (Sweden)

    S. A. Perepelitsa

    2012-01-01

    Full Text Available Objective: to reveal a relationship of placental inflammatory changes to bacterial infection in premature neonates with respiratory failure. Material and methods. Bronchoalveolar aspirate was bacteriologically studied in 157 premature neonates with respiratory distress syndrome (NRDS; the total and differential leukocyte counts were measured in their peripheral blood. The levels of the cytokines IL-1^3, IL-4, IL-6, and TNF-a were studied in different biological fluids of mothers and their babies; the placentas were also morphologically examined. Results. An analysis of bacterial cultures from the tracheobronchial tree revealed no growth of bacterial microflora in 61.8% of cases, Enterococcus faecalis and Staphylococcus epidermidis were isolated in 6.4 and 8.3% of the infants, respectively; Staphylococcus haemolyticus, Staphylococcus capitis, Enterobacter agglomerans, and hemolytic group A Streptococcus were seen in 1.9% each; moreover, 1.3% of the newborn infants were found to have Bacillus spp., Staphylococcus aureus, Escherichia coli, Acinetobacter spp., and Serratia marcescens. Other microorganisms and a microbial association were encountered in 8.9% of cases. Placental morphological examination revealed different inflammatory changes concurrent with chronic and acute placental insufficiency. The investigation demonstrated that the maternal peripheral plasma levels of IL-1^, IL-4, IL-6, and TNF-a were within the physiological range at the end of the first period of delivery. The amniotic fluid displayed elevated IL-6 and TNF-a concentrations and normal IL-4 and IL-1e levels, suggesting that there was an intrauterine inflammatory process. Conclusion. Premature birth is associated with various placental inflammatory changes, which causes intrauterine stimulation of macrophages in the chorionic villi. Specific immune defense mechanisms that prevent the development of a fetal infectious process, i.e. the maternal infectious process, may induce

  11. Inflammatory cytokine responses in a pregnant mouse model of Chlamydophila abortus infection.

    Science.gov (United States)

    Kerr, Karen; Wheelhouse, Nicholas; Livingstone, Morag; Anderson, Ian E; Entrican, Gary; McKeever, Declan; Longbottom, David

    2010-08-26

    Chlamydophila abortus (C. abortus) is the aetiological agent of ovine enzootic abortion (OEA). The highly elevated expression of the pro-inflammatory cytokine tumour necrosis factor-alpha (TNFalpha) and low-level expression of interferon-gamma (IFNgamma) that are detected in C. abortus-infected placentas have been implicated in the pathogenesis of OEA. Late-term abortions similar to those occurring in sheep have also been observed in mouse models of C. abortus infection. Since mouse studies have contributed significantly to our understanding of the immunological responses to chlamydial infections and serve as a good model for rapidly assessing candidate vaccines for OEA, we investigated local expression of TNFalpha and IFNgamma in infected mice. At various time points over the course of infection mice were sacrificed, serum samples obtained for serum antibody and cytokine analyses, and livers and placental tissues were removed and fixed to determine C. abortus colonisation and cytokine expression. Immunostaining for C. abortus was significantly greater in placenta compared to liver (P<0.001), whereas local IFNgamma expression was lower and TNFalpha expression was absent in the placenta compared with the liver across all time points. Serum concentrations of both IFNgamma and TNFalpha increased throughout pregnancy in infected mice. These data suggest that a protective systemic inflammatory immune response controls maternal C. abortus infection but not placental/fetal infection in mice. In contrast to sheep, murine placental TNFalpha expression does not correlate with C. abortus infection, suggesting that the immunopathogenesis of chlamydial abortion differs in these species.

  12. The placental exposome: Placental determinants of fetal adiposity and postnatal body composition

    NARCIS (Netherlands)

    R.M. Lewis (R.); H. Demmelmair (Hans); R. Gaillard (Romy); N. Godfrey; S. Hauguel-De Mouzon (S.); B. Huppertz (B.); E. Larque (E.); R. Saffery (R.); M.E. Symonds (M.); G. Desoye (G.)

    2013-01-01

    textabstractOffspring of obese and diabetic mothers are at increased risk of being born with excess adiposity as a consequence of their intrauterine environment. Excessive fetal fat accretion reflects additional placental nutrient transfer, suggesting an effect of the maternal environment on

  13. Prenatal endotoxemia and placental drug transport in the mouse: placental size-specific effects.

    Directory of Open Access Journals (Sweden)

    Enrrico Bloise

    Full Text Available Lipopolysaccharide (LPS in high doses inhibits placental multidrug resistance P-glycoprotein (P-gp--Abcb1a/b and breast cancer resistance protein (BCRP--Abcg2. This potentially impairs fetal protection against harmful factors in the maternal circulation. However, it is unknown whether LPS exposure, at doses that mimic sub-lethal clinical infection, alters placental multidrug resistance. We hypothesized that sub-lethal (fetal LPS exposure reduces placental P-gp activity. Acute LPS (n = 19;150 µg/kg; ip or vehicle (n = 19 were given to C57BL/6 mice at E15.5 and E17.5. Placentas and fetal-units were collected 4 and 24 h following injection. Chronic LPS (n = 6; 5 µg/kg/day; ip or vehicle (n = 5 were administered from E11.5-15.5 and tissues were collected 4 h after final treatment. P-gp activity was assessed by [³H]digoxin accumulation. Placental Abcb1a/b, Abcg2, interleukin-6 (Il-6, Tnf-α, Il-10 and toll-like receptor-4 (Tlr-4 mRNA were measured by qPCR. Maternal plasma IL-6 was determined. At E15.5, maternal IL-6 was elevated 4 h after single (p<0.001 and chronic (p<0.05 LPS, but levels had returned to baseline by 24 h. Placental Il-6 mRNA was also increased after acute and chronic LPS treatments (p<0.05, whereas Abcb1a/b and Abcg2 mRNA were unaffected. However, fetal [³H]digoxin accumulation was increased (p<0.05 4 h after acute LPS, and maternal [³H]digoxin myocardial accumulation was increased (p<0.05 in mice exposed to chronic LPS treatments. There was a negative correlation between fetal [³H]digoxin accumulation and placental size (p<0.0001. Acute and chronic sub-lethal LPS exposure resulted in a robust inflammatory response in the maternal systemic circulation and placenta. Acute infection decreased placental P-gp activity in a time- and gestational age-dependent manner. Chronic LPS decreased P-gp activity in the maternal myocardium and there was a trend for fetuses with smaller placentas to accumulate more P

  14. Recombinant Cytokines from Plants

    OpenAIRE

    Patrycja Redkiewicz; Anna Góra-Sochacka; Tomas Vaněk; Agnieszka Sirko

    2011-01-01

    Plant-based platforms have been successfully applied for the last two decades for the efficient production of pharmaceutical proteins. The number of commercialized products biomanufactured in plants is, however, rather discouraging. Cytokines are small glycosylated polypeptides used in the treatment of cancer, immune disorders and various other related diseases. Because the clinical use of cytokines is limited by high production costs they are good candidates for plant-made pharmaceuticals. S...

  15. Placental glucose dehydrogenase polymorphism in Koreans.

    Science.gov (United States)

    Kim, Y J; Paik, S G; Park, H Y

    1994-12-01

    The genetic polymorphism of placental glucose dehydrogenase (GDH) was investigated in 300 Korean placentae using horizontal starch gel electrophoresis. The allele frequencies for GDH1, GDH2 and GDH3 were 0.537, 0.440 and 0.005, respectively, which were similar to those in Japanese. We also observed an anodal allele which was similar to the GDH4 originally reported in Chinese populations at a low frequency of 0.015. An additional new cathodal allele (named GDH6) was observed in the present study with a very low frequency of 0.003.

  16. Hans Strahl's pioneering studies in comparative placentation

    DEFF Research Database (Denmark)

    Carter, Anthony Michael; Mess, A

    2010-01-01

    and relationship to maternal tissues. This greatly influenced the work of Otto Grosser, who became better known in part because his work was more accessible to other scientists and clinicians. Strahl described the development of the fetal membranes across a broad range of mammalian orders extending his...... observations beyond parturition to the post partum involution of the uterus. He paid close attention to structures designed for histotrophic nutrition including the areolae of moles, haemophagous organs of carnivores and tenrecs and chorionic vesicles of lemurs and lorises. We here provide a summary of some...... of the most important findings made by Strahl including work on placentation in carnivores and higher primates that remains unsurpassed....

  17. Placentation in mammals once grouped as insectivores

    DEFF Research Database (Denmark)

    Carter, Anthony; Enders, Allen

    2009-01-01

    Interest in insectivoran grade mammals has been reawakened by taxonomic changes that place tenrecs and golden moles in a new order and separate hedgehogs from moles, shrews and solenodons. This survey of their placentation shows there is great variation even within families. As an example three...... in a separate order (Erinaceomorpha) is bolstered by the presence of interstitial implantation, amniogenesis by cavitation, a hemochorial barrier and a prominent spongy zone; these features do not occur in shrews, moles or solenodons (Soricomorpha). Three insectivoran grade mammals deserve close attention...

  18. Placental characteristics in women with polycystic ovary syndrome

    NARCIS (Netherlands)

    Koster, Maria P H; de Wilde, Marlieke A; Veltman-Verhulst, Susanne M; Houben, ML; Nikkels, Peter G J; van Rijn, Bas B; Fauser, Bart C J M

    2015-01-01

    STUDY QUESTION: Are macroscopic and microscopic placental characteristics in a heterogeneous group of women diagnosed with polycystic ovary syndrome (PCOS) different from those of a low-risk general population? SUMMARY ANSWER: Women with PCOS have significantly different microscopic placental charac

  19. Placental vascular responses are dependent on surrounding tissue

    DEFF Research Database (Denmark)

    Brøgger, Torbjørn Halle

    Background: The placenta is the base for the exchange of nutrients, oxygen and waste products for the fetus. The placental vessels hold a crucial role in regulation the blood flow, and a compromised placental function leads to serious complications such as fetal death or growth retardation. An in...

  20. Placental vascular responses are dependent on surrounding tissue

    DEFF Research Database (Denmark)

    Brøgger, Torbjørn Halle

    Background. The placenta is the base for the exchange of nutrients, oxygen and waste products for the fetus.The placental vessels hold a crucial role in regulation the blood flow, and a compromised placental function leads to serious complications such as fetal death or growth retardation...

  1. Placental transport and in vitro effects of Bisphenol A

    DEFF Research Database (Denmark)

    Mørck, Thit J; Sorda, Giuseppina; Bechi, Nicoletta

    2010-01-01

    Bisphenol A (BPA), an estrogen-like chemical, leaches from consumer products potentially causing human exposure. To examine the effects of BPA exposure during pregnancy, we performed studies using the BeWo trophoblast cell line, placental explant cultures, placental perfusions and skin diffusion...

  2. Of mice and women: rodent models of placental malaria

    DEFF Research Database (Denmark)

    Hviid, Lars; Marinho, Claudio R F; Staalsoe, Trine

    2010-01-01

    Pregnant women are at increased malaria risk. The infections are characterized by placental accumulation of infected erythrocytes (IEs) with adverse consequences for mother and baby. Placental IE sequestration in the intervillous space is mediated by variant surface antigens (VSAs) selectively ex...

  3. Arrangement of collagen fibers in human placental stem villi

    NARCIS (Netherlands)

    Sati, Leyla; Demir, Ayse Yasemin; Sarikcioglu, Levent; Demir, Ramazan

    2008-01-01

    The aim of the study was to investigate the arrangements and related localization patterns of different collagen types in the stroma of placental stem villi by immunohistochemistry and electron microscopy. A total of 14 normal human term placental tissue samples were studied. Immunohistochemistry wa

  4. Arrangement of collagen fibers in human placental stem villi

    NARCIS (Netherlands)

    Sati, Leyla; Demir, Ayse Yasemin; Sarikcioglu, Levent; Demir, Ramazan

    2008-01-01

    The aim of the study was to investigate the arrangements and related localization patterns of different collagen types in the stroma of placental stem villi by immunohistochemistry and electron microscopy. A total of 14 normal human term placental tissue samples were studied. Immunohistochemistry

  5. Providing a Placental Transfusion in Newborns Who Need Resuscitation

    Science.gov (United States)

    Katheria, Anup C.; Brown, Melissa K.; Rich, Wade; Arnell, Kathy

    2017-01-01

    Over the past decade, there have been several studies and reviews on the importance of providing a placental transfusion to the newborn. Allowing a placental transfusion to occur by delaying the clamping of the umbilical cord is an extremely effective method of enhancing arterial oxygen content, increasing cardiac output, and improving oxygen delivery. However, premature and term newborns who require resuscitation have impaired transitional hemodynamics and may warrant different methods to actively provide a placental transfusion while still allowing for resuscitation. In this review, we will provide evidence for providing a placental transfusion in these circumstances and methods for implementation. Several factors including cord clamping time, uterine contractions, umbilical blood flow, respirations, and gravity play an important role in determining placental transfusion volumes. Finally, while many practitioners agree that a placental transfusion is beneficial, it is not always straightforward to implement and can be performed using different methods, making this basic procedure important to discuss. We will review three placental transfusion techniques: delayed cord clamping, intact umbilical cord milking, and cut-umbilical cord milking. We will also review resuscitation with an intact cord and the evidence in term and preterm newborns supporting this practice. We will discuss perceived risks versus benefits of these procedures. Finally, we will provide key straightforward concepts and implementation strategies to ensure that placental-to-newborn transfusion can become routine practice at any institution. PMID:28180126

  6. Longitudinal study of serum placental GH in 455 normal pregnancies