WorldWideScience

Sample records for affect plasma cytokine

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

    DEFF Research Database (Denmark)

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

    2008-01-01

    -607, IFN-gamma+874, IL-6-174, IL-10-592 and IL-10-1082) and endotoxin-induced changes in plasma levels of TNF-alpha, IL-6 and IL-10. IL-18 levels were unaffected by endotoxin. In conclusion, the investigated SNPs did not affect endotoxin-induced low-grade cytokine production of TNF-alpha, IL-6, IL-18 or IL......The aim of this study was to investigate to what extent single nucleotide polymorphisms (SNPs) in promoter regions of genes of Toll-like receptor (TLR)-4, tumour necrosis factor (TNF)-alpha, interleukin (IL)-18, interferon (IFN)-gamma, IL-6 and IL-10 affect the cytokine response during a controlled...... low-grade inflammatory response in vivo. Two hundred healthy young male volunteers were genotyped, and cytokine levels were measured in response to a low-dose intravenous bolus of Escherichia coli endotoxin. No association was detected between SNPs (TLR-4299, TLR-4399, TNF-308, IL-18-137, IL-18...

  2. Dynamic and Static Exercises Differentially Affect Plasma Cytokine Content in Elite Endurance- and Strength-Trained Athletes and Untrained Volunteers

    Science.gov (United States)

    Kapilevich, Leonid V.; Zakharova, Anna N.; Kabachkova, Anastasia V.; Kironenko, Tatyana A.; Orlov, Sergei N.

    2017-01-01

    Extensive exercise increases the plasma content of IL-6, IL-8, IL-15, leukemia inhibitory factor (LIF), and several other cytokines via their augmented transcription in skeletal muscle cells. However, the relative impact of aerobic and resistant training interventions on cytokine production remains poorly defined. In this study, we compared effects of dynamic and static load on cytokine plasma content in elite strength- and endurance-trained athletes vs. healthy untrained volunteers. The plasma cytokine content was measured before, immediately after, and 30 min post-exercise using enzyme-linked immunosorbent assay. Pedaling on a bicycle ergometer increased IL-6 and IL-8 content in the plasma of trained athletes by about 4- and 2-fold, respectively. In contrast to dynamic load, weightlifting had negligible impact on these parameters in strength exercise-trained athletes. Unlike IL-6 and IL-8, dynamic exercise had no impact on IL-15 and LIF, whereas static load increases the content of these cytokines by ~50%. Two-fold increment of IL-8 content seen in athletes subjected to dynamic exercise was absent in untrained individuals, whereas the ~50% increase in IL-15 triggered by static load in the plasma of weightlifting athletes was not registered in the control group. Thus, our results show the distinct impact of static and dynamic exercises on cytokine content in the plasma of trained athletes. They also demonstrate that both types of exercises differentially affect cytokine content in plasma of athletes and untrained persons.

  3. Plasma cytokines in acute stroke

    DEFF Research Database (Denmark)

    Christensen, Hanne Krarup; Boysen, Gudrun; Christensen, Erik

    2011-01-01

    GOALS: The aim of this study was to test the relations between plasma cytokines and the clinical characteristics, course, and risk factors in acute stroke. PATIENTS AND METHODS: The analysis was based on 179 patients with acute stroke included within 24 hours of stroke onset. On inclusion and 3...... measured by enzyme-linked immunoassay (ELISA). FINDINGS: The levels of most cytokines were significantly different in acute stroke from the levels 3 months later; but only IL-10 was positively associated with stroke severity. C-reactive protein and white blood cell count were positively associated...... with the cytokine response. CONCLUSIONS: We found a substantial overall cytokine reaction that reflected the stroke incident. However, these results do not, at present, suggest a potential for clinical use, as they do not seem to add to the information obtained from the clinical workup of the individual patient....

  4. Unique Cytokine Signature in the Plasma of Patients with Fibromyalgia

    Directory of Open Access Journals (Sweden)

    Jamie Sturgill

    2014-01-01

    Full Text Available Fibromyalgia (FMS is a chronic pain syndrome with a complex but poorly understood pathogenesis affecting approximately 10 million adults in the United States. The lack of a clear etiology of FMS has limited the effective diagnosis and treatment of this debilitating condition. The objective of this secondary data analysis was to examine plasma cytokine levels in women with FMS using the Bio-Plex Human Cytokine 17-plex Assay. Post hoc analysis of plasma cytokine levels was performed to evaluate patterns that were not specified a priori. Upon examination, patients with FMS exhibited a marked reduction in TH2 cytokines such as IL-4, IL-5, and IL-13. The finding of this pattern of altered cytokine milieu not only supports the role of inflammation in FMS but also may lead to more definitive diagnostic tools for clinicians treating FMS. The TH2 suppression provides strong evidence of immune dysregulation in patients with FMS.

  5. Plasma cytokine levels and risks of abdominal aortic aneurysms

    DEFF Research Database (Denmark)

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

    2015-01-01

    BACKGROUND: Abdominal aortic aneurysm (AAA) is characterized by inflammatory cell accumulation in AAA lesions that produce inflammatory cytokines and advance its pathogenesis. Peripheral cytokines may predict the degree or risk of AAA. METHODS AND RESULTS: ELISA determined plasma interleukin-6 (I......-sectional AAA area, IL10 with AAA growth rate, and IL10 with IFN-γ and IL17A suggest combined Th1, Th2, and Th17 immune responses in human AAAs....

  6. Aggressive periodontitis and chronic arthritis: blood mononuclear cell gene expression and plasma protein levels of cytokines and cytokine inhibitors

    DEFF Research Database (Denmark)

    Sørensen, Lars K; Havemose-Poulsen, Anne; Bendtzen, Klaus

    2009-01-01

    BACKGROUND: Cytokines and cytokine inhibitors have been associated with many immunoinflammatory diseases. In the present study, we examined whether peripheral blood mononuclear cell (PBMC) gene expression mirrors the corresponding plasma levels of clinically important pro- and anti-inflammatory c......BACKGROUND: Cytokines and cytokine inhibitors have been associated with many immunoinflammatory diseases. In the present study, we examined whether peripheral blood mononuclear cell (PBMC) gene expression mirrors the corresponding plasma levels of clinically important pro- and anti...

  7. Plasma inflammatory cytokines correlate to the ovarian hyperstimulation syndrome.

    Science.gov (United States)

    Abramov, Y; Schenker, J G; Lewin, A; Friedler, S; Nisman, B; Barak, V

    1996-07-01

    The objective of this study was to follow the kinetics of four inflammatory cytokines in the plasma and ascitic fluid of seven patients who developed severe ovarian hyperstimulation syndrome (OHSS) after induction of ovulation for in-vitro fertilization. Blood samples were obtained from these patients at three different times: upon hospitalization; when significant clinical improvement was evident; and after complete resolution. Samples were analysed for interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-8 (IL-8) and tumour necrosis factor alpha (TNF-alpha). Ascitic fluid was obtained by therapeutic paracentesis from all study patients during the active phase and analysed for these cytokines. Two control groups were available: the first included 15 women undergoing controlled ovarian stimulation for in-vitro fertilization without developing OHSS, while the second consisted of 25 healthy women not undergoing ovulation induction or any other medical treatment. High concentrations of IL-1, IL-6 and TNF-alpha were detected in all individuals upon admission for severe OHSS. Concentrations dropped significantly along with clinical improvement, reaching normal values after complete resolution. A statistically significant correlation was found between plasma cytokine concentrations and certain biological characteristics of the syndrome such as leukocytosis, increased haematocrit, and elevated plasma 17-beta-oestradiol concentrations. Ascitic fluid obtained from the study patients contained high IL-6 and IL-8 concentrations, while other cytokines were unaltered. These results suggest close association between inflammatory cytokines and the pathophysiology of the ovarian hyperstimulation syndrome.

  8. Relationships among prenatal depression, plasma cortisol, and inflammatory cytokines.

    Science.gov (United States)

    Shelton, Melissa M; Schminkey, Donna L; Groer, Maureen W

    2015-05-01

    A secondary pilot study was carried out as part of a larger parent study of thyroid function in pregnancy and postpartum. All women in the parent study (N = 631) had blood samples, demographic data, and measures of perceived stress and dysphoric moods collected between 16 and 26 weeks' gestation. The current study was completed with a subset of 105 pregnant women to examine the relationships among perceived stress, depression, plasma cortisol, and cytokines during the second trimester of pregnancy. Stress was measured using Cohen's Perceived Stress Scale and dysphoric moods using the Profile of Mood States Depression/Dejection Scale. Cytokines were measured by a 12-plex analysis on a Luminex-200, and cortisol was measured by enzyme-linked immunosorbent assay on stored plasma samples. Stress and depression scores were highly correlated, and depressive symptoms were inversely correlated with 3 of the 12 cytokines: interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and IL-7. Cortisol was inversely correlated with proinflammatory cytokines (IL-1β and TNF-α) and anti-inflammatory cytokines (IL-4, IL-5, IL-10, and IL-13). These data support the new conceptualizations of normal pregnancy as an inflammatory state that is carefully regulated, as both excessive and inadequate inflammation are potentially hazardous to the health of the pregnancy and fetus.

  9. Plasma Cytokine Levels in Astronauts Before and after Spaceflight

    Science.gov (United States)

    Mehta, Satish K.; Aggarwal, Barat B.; Feiveson, Alan H.; Hammond, Dinne K.; Castro, Victoria A.; Stowe, Raymond; Pierson Duane L.

    2008-01-01

    Space flight is a unique experience and results in adverse effects on human physiology. Changes have been reported in various physiological systems, including musculoskeletal, neurovestibular, cardiovascular, endocrine, immunity and increased latent viral reactivation as well as others. The potential mechanisms behind these changes are not fully understood. Various cytokines such as IL-1, IL-6, TNF and chemokines have been linked to several of these changes, like muscle loss, bone loss, fatigue, sleep deprivation and viral reactivation. Eighteen astronauts (15 M and 3 F) from 8 spaceflights and 10 healthy age-matched adults (6 M, 4 F) were included in the present study. A panel of 21 plasma cytokines was analyzed with the Luminex 100 to measure the cytokines in these subjects 10 days before the flight (L-10), 2-3 hour after landing (R+0), 3 days after landing (R+3), and at their annual medical exam (AME). IL-10, IL-1, IFN-alpha, MCP-1 and IP-10 increased significantly at L-10 as compared with AME levels. IL-6 and IFN-alpha showed significant increases at R + 0 (P less than .05) over their baseline levels (AME). Cytokine levels at R+3 were not significantly different from R+0. IL-10 and IL-6 have been reported to increase in during viral reactivation. These data show that there was a shift from TH1 to TH2 cytokines L-10 and R+0. We also studied viral reactivation in 10 of the 18 subjects included in the present study before, during, and after space flight. Increased salivary varicella zoster virus (VZV) shedding in these subjects was found either during or after the mission. VZV shedding correlated with the increased levels of cytokines especially IL-10 and IL-6. Overall, our data suggests that cytokines may play an important role in regulating adverse changes in astronauts, and further studies are needed to fully understand the mechanism.

  10. Temporal reliability of cytokines and growth factors in EDTA plasma

    Directory of Open Access Journals (Sweden)

    Marrangoni Adele M

    2010-11-01

    Full Text Available Abstract Background Cytokines are involved in the development of chronic diseases, including cancer. It is important to evaluate the temporal reproducibility of cytokines in plasma prior to conducting epidemiologic studies utilizing these markers. Findings We assessed the temporal reliability of CRP, 22 cytokines and their soluble receptors (IL-1α, IL-1β, IL-1RA, IL-2, sIL-2R, IL-4, IL-5, IL-6, sIL-6R, IL-7, IL-8, IL-10, IL-12p40, IL-12p70, IL-13, IL-15, IL-17, TNFα, sTNF-R1, sTNF-R2, IFNα, IFNγ and eight growth factors (GM-CSF, EGF, bFGF, G-CSF, HGF, VEGF, EGFR, ErbB2 in repeated EDTA plasma samples collected an average of two years apart from 18 healthy women (age range: 42-62 enrolled in a prospective cohort study. We also estimated the correlation between serum and plasma biomarker levels using 18 paired clinical samples from postmenopausal women (age range: 75-86. Twenty-six assays were able to detect their analytes in at least 70% of samples. Of those 26 assays, we observed moderate to high intra-class correlation coefficients (ICCs(ranging from 0.53-0.89 for 22 assays, and low ICCs (0-0.47 for four assays. Serum and plasma levels were highly correlated (r > 0.6 for most markers, except for seven assays (r Conclusions For 22 of the 31 biomarkers, a single plasma measurement is a reliable estimate of a woman's average level over a two-year period.

  11. Plasma leptin, insulin and free tryptophan contribute to cytokine-induced anorexia.

    Science.gov (United States)

    Sato, Tomoi; Laviano, Alessandro; Meguid, Michael M; Rossi-Fanelli, Filippo

    2003-01-01

    Cytokines contribute to anorexia of diseases. Tumor Necrosis Factor (TNF) and/or interleukin-1 (IL-1) stimulate leptin release, but not insulin. Both affect hypothalamus to decrease food intake (FI). Hypothalamic serotonin (5HT) decreases FI. Its synthesis depends on brain availability of precursor, tryptophan (TRP), which depends on plasma free TRP. Purpose is to test involvement of plasma leptin, insulin, TRP, and thus hypothalamic 5HT in cytokine-induced anorexia in rats. In male rats, IL-1alpha (10 mg/kg/d; n=9), TNFalpha (30 mg/kg/d; n=9), Il-1alpha+TNFalpha (10:30 mg/kg/d; n=9), TRP (100 mg/kg/d, n=8) and saline (n=8; Control) were injected sc for 2 days. FI, BW, plasma free and total TRP, leptin and insulin, and body fat were measured. Data analyzed via ANOVA. IL-1alpha and IL-1alpha+TNFalpha vs others decreased FI and BW. TNFalpha and TRP did not change FI and BW. Plasma total TRP was higher in TRP vs IL-1alpha, TNFalpha, and IL-1alpha+TNFalpha. Plasma free TRP was higher in IL-1alpha and IL-1alpha+TNFalpha vs Control. IL-1alpha and IL-1alpha+TNFalpha decreased leptin and body fat. Insulin in Control was lower than others. Data suggest: i) IL-1alpha increases plasma free TRP, but not total TRP, thus increases hypothalamic 5HT synthesis, resulting in anorexia; ii) leptin does not mediate anorexia, but; iii) insulin may contribute to anorexia induced by cytokines.

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

    Directory of Open Access Journals (Sweden)

    Hopkins Stephen J

    2012-11-01

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

  13. Plasma cytokines do not reflect expression of pro- and anti-inflammatory cytokine mRNA at organ level after cardiopulmonary bypass in neonatal pigs

    DEFF Research Database (Denmark)

    Brix-Christensen, V.; Vestergaard, C.; Chew, M.

    2003-01-01

    Background: Plasma concentrations of inflammatory markers are increased in response to the trauma of cardiac surgery and cardiopulmonary bypass (CPB). It is, however, unknown whether the plasma cytokine levels and cytokine mRNA expression at organ level reflect each other. Methods: Twenty-six pig...... poorly reflected mRNA expression of the pro- and anti-inflammatory cytokines....

  14. Cytokines in Human Seminal Plasma and Their Effect on Male Fertility

    Institute of Scientific and Technical Information of China (English)

    Snje(z)ana (Z)idovec; Sanja Vujisi(c)

    2005-01-01

    Cytokines are a heterogeneous group of peptides that play an important role in intercellular communication, regulation of innate and specific immunity, hematopoiesis,interaction between the immune system and neuroendocrine network as well as in reproduction and development. Seminal plasma provides an immunological environment for the semen and contains important biological response mediators. Numerous studies investigated the presence of various cytokines in the seminal plasma and tried to correlate cytokine levels with sperm quality and male fertility. However, the pathophysiological significance of seminal cytokines in sperm function is still not completely understood. The purpose of this review is to provide a brief summary of the extensive literature dealing with cytokines in the seminal plasma and to discuss the contribution of local cytokine immunity to male fertility.

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

    Science.gov (United States)

    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.

  16. Plasma cytokine concentration and the cytokine producing ability of whole blood cell cultures from healthy females with pharmacologically induced hyperprolactinemia.

    Science.gov (United States)

    Rovenský, J; Lackovic, V; Veselková, Z; Horváthová, M; Koska, J; Blazícková, S; Vigas, M

    1999-01-01

    We investigated the in vitro effect of domperidone-induced hyperprolactinemia on plasma cytokine concentration and blood leukocyte cytokine production in healthy female volunteers. No changes were found in the plasma concentration of interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, interleukin (IL)-4, IL-10, IL-6 and IL-13 during hyperprolactinemia when compared with control values. Using unseparated blood leukocytes, we found that the spontaneous production of IL-6 (4-8 h) and transforming growth factor (TGF)-beta 1 (2-4 h) was significantly decreased and that the in vitro stimulated production of IFN-gamma (2-8 h) and TNF (4 h) was significantly increased compared with control. Our data concerning the increased IFN-gamma and TNF producing capacity of unseparated leukocytes during pharmacologically induced hyperprolactinemia strongly support the possibility that the lymphocyte production of these cytokines can be rapidly amplified by prolactin via a priming mechanism.

  17. Plasma Cytokine Levels During Long-Duration Spaceflight

    Science.gov (United States)

    Crucian, Brian E.; Zwart, Sara R.; Quiriarte, Heather A.; Smith, Scott M.; Sams, Clarence F.

    2012-01-01

    Determine the in-flight status of immunity, physiological stress, viral immunity/reactivation. Specific measurements include leukocyte distribution, T cell function, cytokine production profiles (mRNA, intracellular, secreted, plasma), virus-specific T cell number/function, latent herpesvirus reactivation, stress hormone levels. Determine the clinical risk related to immune dysregulation for exploration class spaceflight, as well as an appropriate monitoring strategy for spaceflight-associated immune dysfunction, that could be used for the evaluation of countermeasures. Specific Study Objectives: Determine the nutritional status of astronauts before, during, and after spaceflight ensure adequate intake of energy, protein, and vitamins during missions. The Clinical Nutritional Status Assessment measures dietary intake, body composition, protein, bone, iron, mineral, vitamin, and antioxidant status (60 total analytes). Currently, it is a medical requirement for U.S. crewmembers on-board the ISS. The results of data analysis are used both to understand the connections between nutrition and human health during space flight, and to develop effective dietary strategies to reduce adverse health impacts (including bone loss, loss of important vitamins and minerals, and increased genetic damage from radiation).

  18. Do bacterial vaginosis and chlamydial infection affect serum cytokine level?

    Directory of Open Access Journals (Sweden)

    Bogavac Mirjana

    2010-01-01

    Full Text Available Introduction. Serbia is the country with extremely low birth rate and a relatively high percentage of preterm deliveries (8%. With this in mind, discovering new diagnostic methods that could be used for the prediction of preterm delivery is of great importance. In this study we tried to determine whether bacterial vaginosis and chlamydial infection could provoke preterm delivery by activation of systemic cytokine network. Objective. The aim of this study was to determine serum levels of proinflammatory cytokines (IL-1β, IL-8, IFN-γ, IL-6 and TNF-α in pregnant women with symptoms of preterm delivery and to make correlation between these parameters and the presence of bacterial vaginosis or chlamydial infection. Method. In the serum of 35 pregnant women, which were divided in groups according to the presence or absence of bacterial vaginosis and chlamydial infection, commercial ELISA tests for proinflammatory cytokines were performed. Results. The serum level of IFN-γ was significantly increased in pregnant women having chlamydial infection, as well as the level of IL-1β in women with bacterial vaginosis. The levels of TNF-α, IL-6 and IL-8 were not significantly different between the investigated groups. Conclusion. The preliminary results obtained in this research point out the possibility that not only intrauterine or systemic infections, but also bacterial vaginosis and chlamydial infection can cause a partial activation of systemic cytokine network and contribute to the occurrence of preterm delivery.

  19. ALPK1 affects testosterone mediated regulation of proinflammatory cytokines production.

    Science.gov (United States)

    Kuo, Tzer-Min; Yeh, Kun-Tu; Hsu, Hui-Ting; Chiang, Shang-Lun; Chang, Jan-Gowth; Huang, Chung-Ming; Tu, Hung-Pin; Liu, Chiu-Shong; Ko, Ying-Chin

    2015-11-01

    Alpha-protein kinase 1, also known as alpha-kinase 1 (ALPK1), is associated with chronic kidney disease (CKD), myocardial infarction, gout and type 2 diabetes mellitus (DM). In addition to having an inductive effect on the proinflammatory cytokines in monocytic THP1 cells, ALPK1 is expressed abundantly in the mouse testes. Low testosterone levels are commonly associated with arthritis, CKD, type 2 DM, cardiovascular disease and inflammation. The testosterone's anti-inflammatory effect has been demonstrated to reduce proinflammatory cytokines and adhesion molecules. In this study, we found that ALPK1 transgenic mice showed lower levels of testosterone in both the testes and the serum. Decreasing endogenous ALPK1 enhanced testosterone levels and transcripts of testosterone-regulated genes (P450scc, 3beta-HSD, P450C17, 17beta-HSD, StAR, and INSL3) in TM3 Leydig cells. In contrast, increasing testosterone decreased ALPK1 in both TM3 and monocytic THP1 cells. This decrease was accompanied by a reduction of the proinflammatory cytokines. Increased ALPK1 levels attenuated the testosterone effects in THP1 cells. Finally, we also found that ALPK1 increased the release of TNF-alpha and TGF-beta1 in the human embryonic kidney 293 cells, while testosterone inhibited ALPK1 in the primary kidney cells. Taken together, this data suggests that the balance between ALPK1 and testosterone plays a critical role in the testosterone-mediated inhibition of proinflammatory cytokines.

  20. Exposure to Polycyclic Aromatic Hydrocarbons, Plasma Cytokines, and Heart Rate Variability.

    Science.gov (United States)

    Yang, Binyao; Deng, Qifei; Zhang, Wangzhen; Feng, Yingying; Dai, Xiayun; Feng, Wei; He, Xiaosheng; Huang, Suli; Zhang, Xiao; Li, Xiaohai; Lin, Dafeng; He, Meian; Guo, Huan; Sun, Huizhen; Yuan, Jing; Lu, Jiachun; Hu, Frank B; Zhang, Xiaomin; Wu, Tangchun

    2016-01-13

    Epidemiological studies have suggested associations between polycyclic aromatic hydrocarbons (PAHs) and heart rate variability (HRV). However, the roles of plasma cytokines in these associations are limited. In discovery stage of this study, we used Human Cytokine Antibody Arrays to examine differences in the concentrations of 280 plasma cytokines between 8 coke-oven workers and 16 community residents. We identified 19 cytokines with significant different expression (fold change ≥2 or ≤-2, and q-value cytokines were selected to validate in 489 coke-oven workers by enzyme-linked immunosorbent assays in validation stage. We found OH-PAHs were inversely associated with brain-derived neurotrophic factor (BDNF) (p 16% BDNF decreases. Additionally, OH-PAHs were positively associated with activated leukocyte cell adhesion molecule (ALCAM) and C-reactive protein (CRP) (p 20% increases in CRP. We also found significant associations between these cytokines and HRV (p 8% decreases in HRV. Our results indicated PAH exposure was associated with plasma cytokines, and higher cytokines were associated with decreased HRV, but additional human and potential mechanistic studies are needed.

  1. 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.

  2. Plasma from hemorrhaged mice activates CREB and increases cytokine expression in lung mononuclear cells through a xanthine oxidase-dependent mechanism.

    Science.gov (United States)

    Shenkar, R; Abraham, E

    1996-02-01

    Hemorrhage rapidly increases plasma xanthine oxidase levels as well as the expression of proinflammatory and immunoregulatory cytokines in the lungs. To determine the role of circulating xanthine oxidase (XO), as well as other plasma factors, in affecting pulmonary cytokine expression, we conducted studies in which plasma from hemorrhaged mice was transferred into unhemorrhaged recipient mice. Administration of posthemorrhage plasma to recipient mice increased the levels of mRNA for interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), and transforming growth factor-beta 1 (TGF-beta 1) in lung mononuclear cells. No enhancement of mRNA levels for these cytokines was found in the lungs of mice given allopurinol-treated posthemorrhage plasma or fed a tungsten-enriched, XO-depleting diet prior to transfer of posthemorrhage plasma. Among the nuclear transcriptional regulatory factors examined, only the cyclic AMP response-element binding protein (CREB) was activated in nuclear extracts from lung mononuclear cells of mice that were given posthemorrhage plasma. No activation of nuclear factor-kappa B (NF-kappa B), nuclear factor interleukin 6 (NF-IL6), activating protein-1 (AP-1), or serum protein-1 (SP-1) was found. These results suggest that the mechanism for hemorrhage-induced increases in pulmonary cytokine expression is by activation of the enhancer CREB through a tissue XO-dependent pathway initiated by plasma-borne mediators.

  3. Plasma cytokine levels in Tanzanian HIV-1-infected adults and the effect of antiretroviral treatment

    DEFF Research Database (Denmark)

    Haissman, J.M.; Vestergaard, L.S.; Sembuche, S.;

    2009-01-01

    OBJECTIVE: To evaluate the role immune activation leading to the production and circulation of cytokines has in the pathogenesis of HIV infection in sub-Saharan Africa and the effect of antiretroviral treatment (ART) on these parameters. METHODS: Plasma concentrations of tumor necrosis factor (TNF...... counts below 200 cells per microliter than individuals with CD4 cell counts above 200 cells per microliter. HIV RNA was the strongest predictor of all cytokine expression in multivariate analysis. ART leads to a decrease in all cytokines to levels close to those of HIV-uninfected individuals. CONCLUSIONS...

  4. Plasma Cytokine Levels During Long-Duration Spaceflight

    Science.gov (United States)

    Crucian, Brian E.; Zwart, Sara R.; Quiriarte, Heather A.; Smith, Scott M.; Sams, Clarence F.

    2011-01-01

    Reduced T cell, granulocyte, NK and monocyte function have all been reported following both long and short duration spaceflight, however these data indicate crews are generally not experiencing inflammatory or adaptive immune activation during spaceflight. There appear to be varied individual crew responses, and specific relationships between cytokines and markers of iron status and muscle turnover that warrant further evaluation. Increases in growth factors and chemokines may indicate other types of adaptation occurring during spaceflight, such as attempts to overcome diminished immunocyte function.

  5. Plasma cytokine expression after lower-limb compression in rats

    Directory of Open Access Journals (Sweden)

    Mauricio Wanderley Moral Sgarbi

    2015-02-01

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

  6. TLR-mediated NF-kB-dependent cytokine production is differently affected by HIV therapeutics

    DEFF Research Database (Denmark)

    Melchjorsen, Jesper; Paludan, Søren Riis; Mogensen, Trine

      Pathogen-recognizing Toll-like receptors 2 (TLR2) and TLR4 are known to recognize a number of pathogens, including E.Coli, S. Pneumonia and N. Meningococcus. We have studied whether a number of HIV therapeutics affect immediate proinflammatory cytokine responses in cell cultures. Preliminary...... results suggest an opposing effect of the drugs Tenofovir and Retrovir (AZT) on TLR-mediated production of NF-kappaB-dependent proinflammatory cytokines. We present data on the mechanisms behind the drug-mediated remodeling of innate immune activation and how the drugs effect early host...

  7. Inflammatory cytokines and plasma redox status responses in hypertensive subjects after heat exposure

    Directory of Open Access Journals (Sweden)

    S.F. Fonseca

    2016-03-01

    Full Text Available Hypertension is characterized by a pro-inflammatory status, including redox imbalance and increased levels of pro-inflammatory cytokines, which may be exacerbated after heat exposure. However, the effects of heat exposure, specifically in individuals with inflammatory chronic diseases such as hypertension, are complex and not well understood. This study compared the effects of heat exposure on plasma cytokine levels and redox status parameters in 8 hypertensive (H and 8 normotensive (N subjects (age: 46.5±1.3 and 45.6±1.4 years old, body mass index: 25.8±0.8 and 25.6±0.6 kg/m2, mean arterial pressure: 98.0±2.8 and 86.0±2.3 mmHg, respectively. They remained at rest in a sitting position for 10 min in a thermoneutral environment (22°C followed by 30 min in a heated environmental chamber (38°C and 60% relative humidity. Blood samples were collected before and after heat exposure. Plasma cytokine levels were measured using sandwich ELISA kits. Plasma redox status was determined by thiobarbituric acid reactive substances (TBARS levels and ferric reducing ability of plasma (FRAP. Hypertensive subjects showed higher plasma levels of IL-10 at baseline (P<0.05, although levels of this cytokine were similar between groups after heat exposure. Moreover, after heat exposure, hypertensive individuals showed higher plasma levels of soluble TNF receptor (sTNFR1 and lower TBARS (P<0.01 and FRAP (P<0.05 levels. Controlled hypertensive subjects, who use angiotensin-converting-enzyme inhibitor (ACE inhibitors, present an anti-inflammatory status and balanced redox status. Nevertheless, exposure to a heat stress condition seems to cause an imbalance in the redox status and an unregulated inflammatory response.

  8. 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.

  9. Obesity Related Alterations in Plasma Cytokines and Metabolic Hormones in Chimpanzees

    Directory of Open Access Journals (Sweden)

    Pramod Nehete

    2014-01-01

    Full Text Available Obesity is characterized by chronic low-grade inflammation and serves as a major risk factor for hypertension, coronary artery disease, dyslipidemias, and type-2 diabetes. The purpose of this study was to examine changes in metabolic hormones, inflammatory cytokines, and immune function, in lean, overweight, and obese chimpanzees in a controlled environment. We observed increased plasma circulating levels of proinflammatory TH-1 cytokines, Interferon gamma, interleukin-6, interleukin-12p40, tumor necrosis factor, soluble CD40 ligand, and Interleukin-1β and anti-inflammatory TH-2 cytokines, Interleukin-4, Interleukin-RA, Interleukin-10, and Interleukin-13 in overweight and obese chimpanzees. We also observed increased levels of metabolic hormones glucagon-like-peptide-1, glucagon, connecting peptide, insulin, pancreatic peptide YY3–36, and leptin in the plasma of overweight and obese chimpanzees. Chemokine, eotaxin, fractalkine, and monocyte chemoattractant protein-1 were higher in lean compared to obese chimpanzees, while chemokine ligand 8 increased in plasma of obese chimpanzees. We also observed an obesity-related effect on immune function as demonstrated by lower mitogen induced proliferation, and natural killer activity and higher production of IFN-γ by PBMC in Elispot assay, These findings suggest that lean, overweight, and obese chimpanzees share circulating inflammatory cytokines and metabolic hormone levels with humans and that chimpanzees can serve as a useful animal model for human studies.

  10. Cytokine Concentrations in Plasma from Children with Severe and Non-Severe Community Acquired Pneumonia.

    Directory of Open Access Journals (Sweden)

    Johanne Haugen

    Full Text Available Children in low and middle-income countries have a high burden of pneumonia. Measuring the cytokine responses may be useful to identify novel markers for diagnosing, monitoring, and treating pneumonia.To describe and compare a wide range of inflammatory mediators in plasma from children with WHO-defined severe and non-severe community acquired pneumonia (CAP, and explore to what extent certain mediators are associated with severity and viral detection.We collected blood samples from 430 children with severe (n = 43 and non-severe (n = 387 CAP. Plasma from these children were analysed for 27 different cytokines, and we measured the association with age, disease severity and viral detection.There were generally higher plasma concentrations of several cytokines with both pro-inflammatory and anti-inflammatory effects among children with severe CAP than in children with non-severe CAP. We found significantly higher concentrations of interleukin (IL-1, IL-4, IL-6, IL-8, IL-9, IL-15, eotaxin, basic fibroblast growth factor (b-FGF, granulocyte colony-stimulating factor (G-CSF, granulocyte-macrophage colony-stimulating factor (GM-CSF, and tumor necrosis factor-alpha (TNF-α in the group of severe CAP. Most of these associations persisted when adjusting for age in linear regression analyses. The cytokine response was strongly associated with age but to a lesser extent with viral etiology.The plasma concentrations of several cytokines, both with pro-inflammatory and anti-inflammatory effects, were higher among children with severe illness. In particular G-CSF and IL-6 reflected severity and might provide complementary information on the severity of the infection.ClinicalTrials.gov NCT00148733.

  11. Antibody Array Revealed PRL-3 Affects Protein Phosphorylation and Cytokine Secretion.

    Science.gov (United States)

    Yang, Yongyong; Lian, Shenyi; Meng, Lin; Qu, Like; Shou, Chengchao

    2017-01-01

    Phosphatase of regenerating liver 3 (PRL-3) promotes cancer metastasis and progression via increasing cell motility and invasiveness, however the mechanism is still not fully understood. Previous reports showed that PRL-3 increases the phosphorylation of many important proteins and suspected that PRL-3-enhanced protein phosphorylation may be due to its regulation on cytokines. To investigate PRL-3's impact on protein phosphorylation and cytokine secretion, we performed antibody arrays against protein phosphorylation and cytokines separately. The data showed that PRL-3 could enhance tyrosine phosphorylation and serine/threonine phosphorylation of diverse signaling proteins. Meanwhile, PRL-3 could affect the secretion of a subset of cytokines. Furthermore, we discovered the PRL-3-increased IL-1α secretion was regulated by NF-κB and Jak2-Stat3 pathways and inhibiting IL-1α could reduce PRL-3-enhanced cell migration. Therefore, our result indicated that PRL-3 promotes protein phosphorylation by acting as an 'activator kinase' and consequently regulates cytokine secretion.

  12. Tamm-Horsfall protein regulates circulating and renal cytokines by affecting glomerular filtration rate and acting as a urinary cytokine trap.

    Science.gov (United States)

    Liu, Yan; El-Achkar, Tarek M; Wu, Xue-Ru

    2012-05-11

    Although few organ systems play a more important role than the kidneys in cytokine catabolism, the mechanism(s) regulating this pivotal physiological function and how its deficiency affects systemic cytokine homeostasis remain unclear. Here we show that elimination of Tamm-Horsfall protein (THP) expression from mouse kidneys caused a marked elevation of circulating IFN-γ, IL1α, TNF-α, IL6, CXCL1, and IL13. Accompanying this were enlarged spleens with prominent white-pulp macrophage infiltration. Lipopolysaccharide (LPS) exacerbated the increase of serum cytokines without a corresponding increase in their urinary excretion in THP knock-out (KO) mice. This, along with the rise of serum cystatin C and the reduced inulin and creatinine clearance from the circulation, suggested that diminished glomerular filtration may contribute to reduced cytokine clearance in THP KO mice both at the baseline and under stress. Unlike wild-type mice where renal and urinary cytokines formed specific in vivo complexes with THP, this "trapping" effect was absent in THP KO mice, thus explaining why cytokine signaling pathways were activated in renal epithelial cells in such mice. Our study provides new evidence implicating an important role of THP in influencing cytokine clearance and acting as a decoy receptor for urinary cytokines. Based on these and other data, we present a unifying model that underscores the role of THP as a major regulator of renal and systemic immunity.

  13. Plasma Cytokine Concentrations in Workers Exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)

    NARCIS (Netherlands)

    Saberi Hosnijeh, F.; Boers, D.; Portengen, L.; Bueno-de-Mesquita, H.B.; Heederik, D.; Vermeulen, R.

    2012-01-01

    Objectives: Few epidemiological studies have studied the effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on blood cytokine levels. In this study we investigated changes in plasma levels of a large panel of cytokines, chemokines, and growth factors among workers from a Dutch historical cohort oc

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

    Science.gov (United States)

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

    2016-03-29

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

  15. The correlation between plasma cytokine levels in jaundice-free children with biliary atresia

    Institute of Scientific and Technical Information of China (English)

    Zhi-Hong Jian; Li-Ching Wang; Chieh-Chung Lin; Jiaan-Der Wang

    2015-01-01

    Background: T helper (Th) cell cytokines modulate inflammation and play a role in biliary atresia (BA). The aim of the study is a cross-sectional assessment of the levels of Th cytokines in the jaundice-free post Kasai procedure patients. Methods: There were 40 jaundice-free patients with BA and 28 normal controls enrolled. Patients were divided into 3 groups, including normal liver function, impaired liver function, and portal hypertension. Plasma concentration of Th1 [interferon-γ (INF-γ), interleukin (IL)-2], Th2 (IL-4, IL-10), Th3 [transforming growth factor-β1 (TGF-β1)], Th17 (IL-17) cytokines, and stromal cell-derived factor-1α (SDF-1α) were investigated. Results: The IFN-γ level was significantly higher in the BA patients with impaired liver function and portal hypertension than controls (P<0.0001 andP<0.0001, respectively). There was a signifi cantly increase of TGF-β1 in all BA groups compared with controls (P=0.003). The reduction of SDF-1α expression was found in BA groups (P<0.0001). IL-10 levels significantly correlated with aspartate aminotransferase to platelet ratio index (r=0.496, P=0.001). For the cytokine correlations, there were no correlations of Th1, Th2 and Th17 cytokine with the other measured cytokines, but TGF-β1 was negatively correlated with SDF-1α levels (r=-0.327,P=0.039). Conclusions: IFN-γ and IL-10 are likely to be involved in the disease progression in BA. Besides, TGF-β1 is found to be a suppression marker associated with SDF-1α levels and reduced production of TGF-β1 may be associated with the disease progression.

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

    Directory of Open Access Journals (Sweden)

    Lorraine V. Alves

    2015-10-01

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

  17. Adsorption properties of an activated carbon for 18 cytokines and HMGB1 from inflammatory model plasma.

    Science.gov (United States)

    Inoue, Satoru; Kiriyama, Kentaro; Hatanaka, Yoshihiro; Kanoh, Hirofumi

    2015-02-01

    The ability of an activated carbon (AC) to adsorb 18 different cytokines with molecular weights ranging from 8 kDa to 70 kDa and high mobility group box-1 (HMGB1) from inflammatory model plasma at 310 K and the mechanisms of adsorption were examined. Porosity analysis using N2 gas adsorption at 77K showed that the AC had micropores with diameters of 1-2 nm and mesopores with diameters of 5-20 nm. All 18 cytokines and HMGB1 were adsorbed on the AC; however, the shapes of the adsorption isotherms changed depending on the molecular weight. The adsorption isotherms for molecules of 8-10 kDa, 10-20 kDa, 20-30 kDa, and higher molecular weights were classified as H-2, L-3, S-3, and S-1 types, respectively. These results suggested that the adsorption mechanism for the cytokines and HMGB1 in the mesopores and on the surface of the AC differed as a function of the molecular weight. On the basis of these results, it can be concluded that AC should be efficient for cytokine adsorption.

  18. Changes in plasma cytokines after treatment of ascaris lumbricoides infection in individuals with HIV-1 infection.

    Science.gov (United States)

    Blish, Catherine A; Sangaré, Laura; Herrin, Bradley R; Richardson, Barbra A; John-Stewart, Grace; Walson, Judd L

    2010-06-15

    Albendazole treatment of individuals with human immunodeficiency virus type 1 (HIV-1) and Ascaris lumbricoides co-infection has led to significantly improved CD4(+) cell counts and a trend for lower plasma HIV-1 RNA levels in a previous randomized placebo-controlled trial. To define mechanisms by which deworming contributed to changes in markers of HIV-1 disease progression, plasma cytokine levels were evaluated. Albendazole treatment, compared with placebo, was associated with significantly decreased plasma interleukin (IL) 10 levels (P = .01)ot associated with significant changes in levels of IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-12p70, IL-13, interferon gamma, tumor necrosis factor alpha, or thymic stromal lymphopoietin. Treatment of A. lumbricoides co-infection may delay HIV-1 disease progression by reducing helminth-induced, IL-10-mediated immunosuppression.

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

    Directory of Open Access Journals (Sweden)

    Giovane Rodrigo Sousa

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

  20. Plasma cytokine concentration changes induced by the antitumor agents dipterinyl calcium pentahydrate (DCP) and related calcium pterins.

    Science.gov (United States)

    Moheno, Phillip; Pfleiderer, Wolfgang; Fuchs, Dietmar

    2009-01-01

    Analysis of plasma cytokine concentration changes determined that oral dosing with the antitumor agent (1:4 mol:mol) calcium pterin (CaPterin) increased plasma IL-10, decreased plasma IL-6, and decreased plasma IFN-gamma concentrations in nude mice with MDA-MB-231 xenograph tumors [Moheno, P., Pfleiderer, W., Dipasquale, A.G., Rheingold, A.L., Fuchs, D., 2008. Cytokine and IDO metabolite changes effected by calcium pterin during inhibition of MDA-MB-231 xenograph tumors in nude mice. Int. J. Pharm. 355, 238-248]. A further analysis, reported here, of plasma cytokine concentration changes in nude mice with the same tumor xenographs treated with dipterinyl calcium pentahydrate (DCP), (1:2 mol:mol) calcium pterin, and CaCl(2).2H(2)O has been carried out. The measured cytokines included: IL-1beta, IL-2, IL-4, IL-6, IL-10, IL-12, IFN-gamma, and TNF-alpha. The major preliminary findings from the analyses of these data are that (1) the overall relative tumor volumes for the treatments correlated significantly with a full study antitumor plasma cytokine pattern (fsAPCP), a composite measure consisting of decreased plasma IL-6 and increased IL-4 concentrations, and (2) DCP induces a significant threshold antitumor response strongly correlated to a derived DCP antitumor plasma cytokine pattern (DCP/APCP) consisting of plasma IL-12, IL-6, and IL-4 concentration changes. This DCP/APCP composite measure identifies plasma IL-12 concentration increases, plasma IL-6 concentration decreases, and plasma IL-4 concentration increases correlated to relative tumor volume decreases caused by DCP dosing. The finding that the novel calcium pterins and CaCl(2).2H(2)O treatments decrease plasma IL-6 concentrations corroborates the previous finding that CaPterin dosing decreases plasma IL-6 concentrations in this mouse/tumor system [Moheno, P., Pfleiderer, W., Dipasquale, A.G., Rheingold, A.L., Fuchs, D., 2008. Cytokine and IDO metabolite changes effected by calcium pterin during inhibition

  1. From the regulatory functions of B cells to the identification of cytokine-producing plasma cell subsets.

    Science.gov (United States)

    Dang, Van Duc; Hilgenberg, Ellen; Ries, Stefanie; Shen, Ping; Fillatreau, Simon

    2014-06-01

    B lymphocytes have a unique role as antibody-producing cells. Antibodies are key mediators of humoral immunity against infections, and are thought to account for the protection afforded by successful vaccines. B cells can also secrete cytokines and subsequently regulate immune responses mediated by T and innate cells. Remarkably, recent studies identified plasma blasts/plasma cells as the main types of activated B cells producing the cytokines interleukin (IL)-10, IL-35, tumor necrosis factor (TNF)-α, IL-17, and GM-CSF in various contexts in mice. Here, we discuss these observations, which suggest the existence of various subsets of plasma blast/plasma cells distinguishable through their cytokine expression pattern.

  2. Plasma Cytokine Concentrations Indicate In-vivo Hormonal Regulation of Immunity is Altered During Long-Duration Spaceflight

    Science.gov (United States)

    Crician, Brian E.; Zwart, Sara R.; Mehta, Satish; Uchakin, Peter; Quiriarte, Heather A.; Pierson, Duane; Sams, Clarence F.; Smith, Scott M.

    2013-01-01

    Background: Aspects of immune system dysregulation associated with long-duration spaceflight have yet to be fully characterized, and may represent a clinical risk to crewmembers during deep space missions. Plasma cytokine concentration may serve as an indicator of in vivo physiological changes or immune system mobilization. Methods: The plasma concentrations of 22 cytokines were monitored in 28 astronauts during long-duration spaceflight onboard the International Space Station. Blood samples were collected three times before flight, 3-5 times during flight (depending on mission duration), at landing and 30 days post-landing. Analysis was performed by bead array immunoassay. Results: With few exceptions, minimal detectable mean plasma levels (cytokines or adaptive regulatory cytokines, however IL-1ra and several chemokines were constitutively present. An increase in the plasma concentration IL-8, IL-1ra, Tpo, CCL4, CXCL5, TNF(alpha), GM-CSF and VEGF was observed associated with spaceflight. Significant post-flight increases were observed for IL-6 and CCL2. No significant alterations were observed during or following spaceflight for adaptive/T-regulatory cytokines (IL-2, IFN(gamma), IL-17, IL4, IL-5, IL-10). Conclusions: This pattern of cytokine dysregulation suggests multiple physiological adaptations persist during flight, including inflammation, leukocyte recruitment, angiogenesis and thrombocyte regulation.

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

    Directory of Open Access Journals (Sweden)

    Clarissa Gutierrez Carvalho

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

  4. Food contaminant zearalenone and its metabolites affect cytokine synthesis and intestinal epithelial integrity of porcine cells.

    Science.gov (United States)

    Marin, Daniela E; Motiu, Monica; Taranu, Ionelia

    2015-05-29

    The intestinal epithelium is the first barrier against food contaminants. Zearalenone (ZEN) is an estrogenic mycotoxin that was identified as a common contaminant of cereal grains and food and feedstuffs. In the present study, we have investigated the in vitro effects of ZEN and some of its metabolites (α-ZOL, β-ZOL) in concentrations of 10-100 µM on a swine epithelial cell line: Intestinal porcine epithelial cells (IPEC-1). We demonstrated that both ZEN metabolites were more toxic for IPEC cells as resulted from the XTT test, while for doses lower than 10 µM, only β-ZOL showed a more pronounced cytotoxicity versus epithelial cells as resulted from neutral red assay. ZEN has no effect on TER values, while α-ZOL significantly decreased the TER values, starting with day 4 of treatment. β-ZOL had a dual effect, firstly it induced a significant increase of TER, and then, starting on day 6, it induced a dramatic decrease of TER values as compared with on day 0. Concerning the cytokine synthesis, our results showed that ZEN has a tendency to increase the synthesis of IL-8 and IL-10. By contrast, α- and β-ZOL decreased the expression of both IL-8 and IL-10, in a dose dependent manner. In conclusion, our results showed that ZEN and its metabolites differently affected porcine intestinal cell viability, transepithelial resistance and cytokine synthesis with important implication for gut health.

  5. Autophagy gene polymorphism is associated with susceptibility to leprosy by affecting inflammatory cytokines.

    Science.gov (United States)

    Yang, Degang; Chen, Jia; Shi, Chao; Jing, Zhichun; Song, Ningjing

    2014-04-01

    Autophagy and inflammation closely interact with each other, and together, they play critical roles in bacterial infection. Leprosy is caused by the infection of Mycobacterium leprae (M. leprae). The objective of the study was to investigate the association between polymorphisms in IRGM, an autophagy gene, and susceptibility to leprosy, and identify possible functions of the polymorphism in the infection of M. leprae. Two polymorphisms in IRGM, rs4958842 and rs13361189, were tested in 412 leprosy cases and 432 healthy controls. Levels of inflammatory cytokines including interleukin 1 beta, IL-4, IL-6, and interferon gamma (INF-γ) were measured after the infection of M. leprae in the peripheral blood mononuclear cell (PBMC) of subjects with different genotypes of rs13361189. Data showed that prevalence of rs13361189TC and CC genotypes were significantly higher in leprosy patients than in healthy controls (odds ratio (OR) = 1.49, 95 % confidence interval (CI) 1.09-2.04, P = 0.012; OR = 2.58, 95 % CI 1.65-4.05, P autophagy gene polymorphism was associated with the increased risk of leprosy by affecting inflammatory cytokines.

  6. Influence of oxidative stress, diaphragm fatigue, and inspiratory muscle training on the plasma cytokine response to maximum sustainable voluntary ventilation.

    Science.gov (United States)

    Mills, Dean E; Johnson, Michael A; McPhilimey, Martin J; Williams, Neil C; Gonzalez, Javier T; Barnett, Yvonne A; Sharpe, Graham R

    2014-04-15

    The influence of oxidative stress, diaphragm fatigue, and inspiratory muscle training (IMT) on the cytokine response to maximum sustainable voluntary ventilation (MSVV) is unknown. Twelve healthy males were divided equally into an IMT or placebo (PLA) group, and before and after a 6-wk intervention they undertook, on separate days, 1 h of (1) passive rest and (2) MSVV, whereby participants undertook volitional hyperpnea at rest that mimicked the breathing and respiratory muscle recruitment patterns commensurate with heavy cycling exercise. Plasma cytokines remained unchanged during passive rest. There was a main effect of time (P ventilation and increases in plasma IL-6 concentration. In conclusion, increases in plasma IL-1β and IL-6 concentrations during MSVV were not due to diaphragm fatigue or DNA damage in PBMC. Increases in plasma IL-6 concentration during MSVV are attenuated following IMT, and the plasma IL-6 response is dependent upon the level of respiratory muscle work and minute ventilation.

  7. Predictive Value of Nuclear Factor κB Activity and Plasma Cytokine Levels in Patients with Sepsis

    Science.gov (United States)

    Arnalich, Francisco; Garcia-Palomero, Esther; López, Julia; Jiménez, Manuel; Madero, Rosario; Renart, Jaime; Vázquez, Juan José; Montiel, Carmen

    2000-01-01

    The relationship between fluctuating cytokine concentrations in plasma and the outcome of sepsis is complex. We postulated that early measurement of the activation of nuclear factor κB (NF-κB), a transcriptional regulatory protein involved in proinflammatory cytokine expression, may help to predict the outcome of sepsis. We determined NF-κB activation in peripheral blood mononuclear cells of 34 patients with severe sepsis (23 survivors and 11 nonsurvivors) and serial concentrations of inflammatory cytokines (interleukin-6, interleukin-1, and tumor necrosis factor) and various endogenous antagonists in plasma. NF-κB activity was significantly higher in nonsurvivors and correlated strongly with the severity of illness (APACHE II score), although neither was related to the cytokine levels. Apart from NF-κB activity, the interleukin-1 receptor antagonist was the only cytokine tested whose level in plasma was of value in predicting mortality by logistic regression analysis. These results underscore the prognostic value of early measurement of NF-κB activity in patients with severe sepsis. PMID:10722586

  8. The role of plasma coating on the permeation of cytokine-inducing substances through dialyser membranes.

    Science.gov (United States)

    Lonnemann, G; Schindler, R; Lufft, V; Mahiout, A; Shaldon, S; Koch, K M

    1995-01-01

    We studied the effects of coating of dialyser membranes with plasma proteins on the permeation of bacteria-derived cytokine-inducing substances (CIS). An in vitro dialysis circuit using polysulphone (PS) or modified cellulose triacetate (mCT) dialysers was used. Precoating of the dialysers was performed by recirculation of 10% normal human plasma for 30 min in the blood compartment and subsequent rinse with pyrogen-free saline. Samples from the blood compartment were tested for induction of interleukin-1 alpha (IL-1 alpha), interleukin-1 beta (IL-1 beta) and tumour necrosis factor (TNF alpha) at various time points after challenging the dialysate with sterile culture supernatants from Pseudomonas aeruginosa. Contamination of the dialysate resulted in the appearance of CIS in the blood compartment of both polysuphone modified cellulose triacetate (IL-1 alpha: PS, time 0: 81 +/- 11 pg/ml, time 60 min: 4747 +/- 1822 pg/ml, P < 0.05; mCT, time 0: 235 +/- 141 pg/ml, time 60 min: 1632 +/- 531 pg/ml, P < 0.05). The plasma protein layer reduced the penetration of CIS significantly only for polysulphone (IL-1 alpha: PS, time 60: 4747 +/- 1822 versus 880 +/- 525 pg/ml, P < 0.05; modified cellulose triacetate, time 60 min: 1632 +/- 531 pg/ml versus 930 +/- 326 pg/ml). Samples from the blood compartment contained < 6 pg/ml LAL-reactive material at all time points. We conclude that plasma coating of polysulphone dialysers reduces the permeability for CIS derived from Pseudomonas, either by reducing the effective pore size or by adsorption of proteins that bind CIS.(ABSTRACT TRUNCATED AT 250 WORDS)

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

    DEFF Research Database (Denmark)

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

    2008-01-01

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

  10. Eicosanoid and cytokine levels in plasma of patients during mesenteric infarction

    Directory of Open Access Journals (Sweden)

    N. Nathan

    1997-01-01

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

  11. Eicosanoid and cytokine levels in plasma of patients during mesenteric infarction.

    Science.gov (United States)

    Nathan, N; Denizot, Y; Feiss, P

    1997-01-01

    Multible organ failure (MOF) induced by mesenteric infarction is associated with a high mortality rate. This study reports eicosanoid and cytokine levels in the blood of three atherosclerotic patients who ultimately died from MOF induced by mesenteric infarction. High plasma levels of 6- keto-prostaglandin (PG) F(1alpha) (the stable metabolite of PGI(2)), interleukin (IL)-6 and IL-8 are observed whereas plasma tumour necrosis factor alpha (TNFalpha), TxB(2) (the stable metabolite of TxA(2)), PGE(2), leukotrienes (LT)B(4) and LTC(4), and whole blood platelet-activating factor levels are not different from values obtained in similarly severe atherosclerotic patients. This short report questioned the clinical involvement of TNFalpha during such a pathology where a persistent translocation of endotoxin has been observed through the gut endothelial barrier. Activation of phospholipase A(2) is suggested by the increase in the stable metabolite of PGI(2) and might be by itself or through lipidic metabolites, a major systemic stimulus of IL-6 and IL-8 production.

  12. Systemic inflammation affects human osteocyte-specific protein and cytokine expression

    NARCIS (Netherlands)

    Pathak, J.L.; Bakker, A.D.; Luyten, F.P.; Verschueren, P.; Lems, W.F.; Klein-Nulend, J.; Bravenboer, N.

    2016-01-01

    Bone remodeling can be disturbed in active rheumatoid arthritis (RA), possibly as a result of elevated levels of circulating inflammatory cytokines. Osteocyte-specific proteins and cytokines play a vital role in bone remodeling by orchestrating bone formation and/or bone resorption. Therefore, we ai

  13. Plasma levels of inflammatory cytokines in adult Nigerians with the metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Udenze Ifeoma Christiana

    2016-01-01

    Full Text Available Background: The aim of this study is to determine the plasma levels of interleukin 6 (IL-6, tumor necrotic factor alpha (TNF-α, and C-reactive protein (CRP in adult Nigerians with the metabolic syndrome and to determine the relationship between components of the metabolic syndrome and CRP in adult Nigerians. Subjects and Methods: This was a case–control study of fifty adult men and women with the metabolic syndrome, and fifty age- and sex-matched males and females without the metabolic syndrome. Metabolic syndrome was defined based on the National Cholesterol Education Programme-Adult Treatment Panel III criteria. Written informed consent was obtained from the participants. Blood pressure and anthropometry measurements were taken and venous blood was collected after an overnight fast. The Ethics Committee of the Lagos University Teaching Hospital, Lagos, Nigeria, approved the study protocol. Comparisons of continuous variables and categorical variables were done using the Student's t-test and Chi-square test, respectively. Regression analysis was used to determine the associations between variables. Statistical significance was set at P< 0.05. Results: The age- and sex-matched males and females with and without the metabolic syndrome did not differ in their sociodemographic characteristics. They however differed in some clinical and laboratory parameters such as diastolic blood pressure (P = 0.048, waist circumference (P = 0.002, body mass index (P = 0.012, waist/hip ratio (P = 0.023, high density lipoprotein (HDL (P = 0.012, and insulin resistance (IR (P = 0.042. There was a statistically significant increase in the inflammatory marker, CRP (P = 0.019, the cytokines, IL6 (P = 0.040, and TNF-α (P = 0.031 between the subjects with and without metabolic syndrome. There was also a significant association between CRP, waist circumference, IR, and HDL in the metabolic syndrome (P < 0.05. Conclusion: Plasma levels of inflammatory cytokines are

  14. Plasma cytokine response, lipid peroxidation and NF-κB activation in skeletal muscle following maximum progressive swimming

    Directory of Open Access Journals (Sweden)

    L.S. Cleto

    2011-06-01

    Full Text Available Our objective was to determine lipid peroxidation and nuclear factor-κB (NF-κB activation in skeletal muscle and the plasma cytokine profile following maximum progressive swimming. Adult male Swiss mice (N = 15 adapted to the aquatic environment were randomly divided into three groups: immediately after exercise (EX1, 3 h after exercise (EX2 and control. Animals from the exercising groups swam until exhaustion, with an initial workload of 2% of body mass attached to the tail. Control mice did not perform any exercise but were kept immersed in water for 20 min. Maximum swimming led to reactive oxygen species (ROS generation in skeletal muscle, as indicated by increased thiobarbituric acid reactive species (TBARS levels (4062.67 ±1487.10 vs 19,072.48 ± 8738.16 nmol malondialdehyde (MDA/mg protein, control vs EX1. Exercise also promoted NF-κB activation in soleus muscle. Cytokine secretion following exercise was marked by increased plasma interleukin-6 (IL-6 levels 3 h post-exercise (P < 0.05. Interleukin-10 (IL-10 levels were reduced following exercise and remained reduced 3 h post-exercise (P < 0.05. Plasma levels of other cytokines investigated, monocyte chemotactic protein-1 (MCP-1, tumor necrosis factor-alpha (TNF-α, interferon-gamma (IFN-γ and interleukin-12 (IL-12, were not altered by exercise. The present findings showed that maximum swimming, as well as other exercise models, led to lipid peroxidation and NF-κB activation in skeletal muscle and increased plasma IL-6 levels. The plasma cytokine response was also marked by reduced IL-10 levels. These results were attributed to exercise type and intensity.

  15. Tityus bahiensis scorpion venom injected to dams during pregnancy affects some cytokines of fetuses.

    Science.gov (United States)

    Dorce, Ana L C; Frare, Eduardo O; Paulo, Maria E F V; Dorce, Valquiria A C; Nencioni, Ana L A

    2015-09-01

    Due to the high incidence of scorpion stings in Brazil, pregnant women are among the possible victims. Cytokines are important during the pregnancy, and scorpion venoms can change their release. We evaluated the levels of some cytokines in the fetuses after the treatment of pregnant rats with the Tityus bahiensis scorpion venom. The concentration of some of them is altered and can be responsible for the effects previously observed on innate reflexes, and the physical and behavioral development of the offspring.

  16. Acute-phase proteins, oxidative stress biomarkers, proinflammatory cytokines, and cardiac troponin in Arabian mares affected with pyometra.

    Science.gov (United States)

    El-Bahr, S M; El-Deeb, W M

    2016-09-01

    New biomarkers are essential for diagnosis of pyometra in mares. In this context, 12 subfertile Arabian mares suffered from pyometra were admitted to the Veterinary Teaching Hospital. The basis for diagnosis of pyometra was positive findings of clinical examination and rectal palpation. Blood samples were collected from diseased animals and from five Arabian healthy mares, which were considered as control group. Acute-phase proteins (APP), oxidative stress biomarkers, proinflammatory cytokines, and cardiac troponin I were estimated in the harvested sera of both groups. Clinical examination revealed purulent yellowish fluid discharged from vagina of affected animals and rectal palpation of the reproductive tract revealed uterine distention. The biochemical analysis of the serum revealed significant increase in cardiac troponin I, creatin kinase, alkaline phosphatase, malondialdehyde, tumor necrosis factor α, interleukins 6, prostaglandin F2α, haptoglobin, and serum amyloid A and significant decrease in reduced glutathione, superoxide dismutase (SOD), total antioxidant capacity, and nitric oxide (NO) of mares affected with pyometra compare to control. Cardiac troponin I was positively correlated with aspartate aminotransferase, creatin kinase, malondialdehyde, alkaline phosphatase, tumor necrosis factor α, interleukins 6, prostaglandin F2α, haptoglobin and serum amyloid A and negatively correlated with glutathione, superoxide dismutase, total antioxidant capacity and nitric oxide in serum of mares affected with pyometra. Moreover, there was high positive correlation between proinflammatory cytokines and APP in serum of mares affected with pyometra. The present study suggests cardiac troponin I together with APP, proinflammatory cytokines, and oxidative stress parameters as biomarkers for pyometra in Arabian mares.

  17. Microglial cytokine gene induction after irradiation is affected by morphologic differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Hayakawa, Kazushige; Borchardt, P.E.; Sakuma, Shirou; Ijichi, Akihiro; Tofilon, P.J. [Univ. of Texas (United States). M. D. Anderson Cancer Center; Niibe, Hideo

    1997-11-01

    Microglia are known to play an important role in the CNS cytokine network, and their response after irradiation may be associated with the development of radiation-induced tissue damage. Radiation effects on this cytokine network have not yet been elucidated. We investigated the effect of {gamma}-irradiation on microglia stimulated with Zymosan A and lipopolysaccharide (LPS), which alone induce the expression of some cytokines and neurotoxic products by microglial cells. In the resting condition (ramified microglia), radiation had no effect on the mRNA level corresponding to cytokines such as ILl{beta} or IL-6, although TGF-{beta}l mRNA was minimally enhanced by irradiation. However, in the activated microglia (amoeboid microglia) stimulated with Zymosan A, radiation-induced IL-6 mRNA expression was increased about two-fold in comparison with non-irradiation. IL-l{beta} was slightly induced by 2 Gy irradiation, but was not induced by higher doses. TGF-{beta}l mRNA was not enhanced by radiation following Zymosan stimulation. In the LPS-stimulated condition, IL-6 mRNA was induced only by 2 Gy of irradiation, but no change in the expression of other genes was detected. These results suggested that radiation exerted different effects on cytokine gene transcription in microglia depending on their morphological state. (author)

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

    LENUS (Irish Health Repository)

    O'Brien, Sinead M

    2012-02-03

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

  19. Low frequency pulsed electromagnetic field affects proliferation, tissue-specific gene expression, and cytokines release of human tendon cells.

    Science.gov (United States)

    de Girolamo, L; Stanco, D; Galliera, E; Viganò, M; Colombini, A; Setti, S; Vianello, E; Corsi Romanelli, M M; Sansone, V

    2013-07-01

    Low frequency pulsed electromagnetic field (PEMF) has proven to be effective in the modulation of bone and cartilage tissue functional responsiveness, but its effect on tendon tissue and tendon cells (TCs) is still underinvestigated. PEMF treatment (1.5 mT, 75 Hz) was assessed on primary TCs, harvested from semitendinosus and gracilis tendons of eight patients, under different experimental conditions (4, 8, 12 h). Quantitative PCR analyses were conducted to identify the possible effect of PEMF on tendon-specific gene transcription (scleraxis, SCX and type I collagen, COL1A1); the release of pro- and anti-inflammatory cytokines and of vascular endothelial growth factor (VEGF) was also assessed. Our findings show that PEMF exposure is not cytotoxic and is able to stimulate TCs' proliferation. The increase of SCX and COL1A1 in PEMF-treated cells was positively correlated to the treatment length. The release of anti-inflammatory cytokines in TCs treated with PEMF for 8 and 12 h was significantly higher in comparison with untreated cells, while the production of pro-inflammatory cytokines was not affected. A dramatically higher increase of VEGF-A mRNA transcription and of its related protein was observed after PEMF exposure. Our data demonstrated that PEMF positively influence, in a dose-dependent manner, the proliferation, tendon-specific marker expression, and release of anti-inflammatory cytokines and angiogenic factor in a healthy human TCs culture model.

  20. Osteopathic manipulative therapy induces early plasma cytokine release and mobilization of a population of blood dendritic cells.

    Science.gov (United States)

    Walkowski, Stevan; Singh, Manindra; Puertas, Juan; Pate, Michelle; Goodrum, Kenneth; Benencia, Fabian

    2014-01-01

    It has been claimed that osteopathic manipulative treatment (OMT) is able to enhance the immune response of individuals. In particular, it has been reported that OMT has the capability to increase antibody titers, enhance the efficacy of vaccination, and upregulate the numbers of circulating leukocytes. Recently, it has been shown in human patients suffering chronic low back pain, that OMT is able to modify the levels of cytokines such as IL-6 and TNF-α in blood upon repeated treatment. Further, experimental animal models show that lymphatic pump techniques can induce a transient increase of cytokines in the lymphatic circulation. Taking into account all these data, we decided to investigate in healthy individuals the capacity of OMT to induce a rapid modification of the levels of cytokines and leukocytes in circulation. Human volunteers were subjected to a mixture of lymphatic and thoracic OMT, and shortly after the levels of several cytokines were evaluated by protein array technology and ELISA multiplex analysis, while the profile and activation status of circulating leukocytes was extensively evaluated by multicolor flow cytometry. In addition, the levels of nitric oxide and C-reactive protein (CRP) in plasma were determined. In this study, our results show that OMT was not able to induce a rapid modification in the levels of plasma nitrites or CRP or in the proportion or activation status of central memory, effector memory or naïve CD4 and CD8 T cells. A significant decrease in the proportion of a subpopulation of blood dendritic cells was detected in OMT patients. Significant differences were also detected in the levels of immune molecules such as IL-8, MCP-1, MIP-1α and most notably, G-CSF. Thus, OMT is able to induce a rapid change in the immunological profile of particular circulating cytokines and leukocytes.

  1. Osteopathic manipulative therapy induces early plasma cytokine release and mobilization of a population of blood dendritic cells.

    Directory of Open Access Journals (Sweden)

    Stevan Walkowski

    Full Text Available It has been claimed that osteopathic manipulative treatment (OMT is able to enhance the immune response of individuals. In particular, it has been reported that OMT has the capability to increase antibody titers, enhance the efficacy of vaccination, and upregulate the numbers of circulating leukocytes. Recently, it has been shown in human patients suffering chronic low back pain, that OMT is able to modify the levels of cytokines such as IL-6 and TNF-α in blood upon repeated treatment. Further, experimental animal models show that lymphatic pump techniques can induce a transient increase of cytokines in the lymphatic circulation. Taking into account all these data, we decided to investigate in healthy individuals the capacity of OMT to induce a rapid modification of the levels of cytokines and leukocytes in circulation. Human volunteers were subjected to a mixture of lymphatic and thoracic OMT, and shortly after the levels of several cytokines were evaluated by protein array technology and ELISA multiplex analysis, while the profile and activation status of circulating leukocytes was extensively evaluated by multicolor flow cytometry. In addition, the levels of nitric oxide and C-reactive protein (CRP in plasma were determined. In this study, our results show that OMT was not able to induce a rapid modification in the levels of plasma nitrites or CRP or in the proportion or activation status of central memory, effector memory or naïve CD4 and CD8 T cells. A significant decrease in the proportion of a subpopulation of blood dendritic cells was detected in OMT patients. Significant differences were also detected in the levels of immune molecules such as IL-8, MCP-1, MIP-1α and most notably, G-CSF. Thus, OMT is able to induce a rapid change in the immunological profile of particular circulating cytokines and leukocytes.

  2. Pro-inflammatory cytokines affect pancreatic carcinoma cell. Endothelial cell interactions

    NARCIS (Netherlands)

    M. ten Kate (Miranda); L.J. Hofland (Leo); P.M. van Koetsveld (Peter); J. Jeekel (Hans); C.H.J. van Eijck (Casper)

    2006-01-01

    textabstractOBJECTIVES: The potential role of surgery-induced pro-inflammatory cytokines on the development of tumor recurrence in pancreatic cancer was investigated. MAIN OUTCOME MEASURES: The adhesion of 3 human pancreatic carcinoma cell lines, PanC1, MiaPaCa and BxPC3 to monolay

  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. An Onion Byproduct Affects Plasma Lipids in Healthy Rats

    DEFF Research Database (Denmark)

    Roldan-Marin, E.; Jensen, R. I.; Krath, Britta

    2010-01-01

    lipids and on factors affecting cholesterol metabolism in healthy rats have been investigated. The OBP or its fractions did not significantly reduce cholesterol or down-regulate hepatic 3-hydroxy-3-methylglutaryl-coenzyme A reductase (Hmgcr) gene expression. The OR even had the effect of increasing...... plasma triacylglycerides (TAG) and cholesterol in the very low density lipoprotein (VLDL-C) fraction. Neither total bile acids nor total primary or secondary bile acids were significantly affected by feeding rats the OBP or its fractions. Principal component analysis combining all markers revealed...

  5. Trichuris suis ova therapy for allergic rhinitis does not affect allergen-specific cytokine responses despite a parasite-specific cytokine response

    DEFF Research Database (Denmark)

    Bourke, C.D.; Mutapi, F.; Nausch, N.;

    2012-01-01

    Parasitic helminths have been shown to reduce inflammation in most experimental models of allergic disease, and this effect is mediated via cytokine responses. However, in humans, the effects of controlled helminth infection on cytokine responses during allergy have not been studied....

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

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  7. Suppression of human anti-inflammatory plasma cytokines IL-10 and IL-1RA with elevation of proinflammatory cytokine IFN-gamma during the isolation of the Antarctic winter

    Science.gov (United States)

    Shearer, William T.; Lee, Bang-Ning; Cron, Stanley G.; Rosenblatt, Howard M.; Smith, E. O'Brian; Lugg, Desmond J.; Nickolls, Peter M.; Sharp, Robert M.; Rollings, Karl; Reuben, James M.

    2002-01-01

    Cellular immune function has been shown to be decreased and latent virus shedding to be increased in human beings isolated during the Antarctic winter, a model used for assessing some effects of space flight. However, the balance of proinflammatory (IFN-gamma) and anti-inflammatory (IL-10 and IL-1RA) cytokines has not previously been evaluated. We therefore sought to determine whether isolation during the Antarctic winter would alter the proinflammatory and anti-inflammatory cytokine balance. Cytokine levels were measured with ELISA in monthly plasma samples from January through September 1999 in 21 study subjects in the Antarctic and 7 control subjects on Macquarie Island. There was a significant time-dependent increase in plasma IFN-gamma (P =.039) as well as decreases in IL-10 (P =.042) and IL-1RA (P =.053) in the study subjects compared with the control subjects. The study subjects also had significantly increased plasma IFN-gamma levels (P IL-10 and IL-1RA levels (P < or =.036) at individual time points of isolation. Isolation of human beings in the Antarctic appears to shift the plasma cytokine balance toward a proinflammatory profile. These observations are consistent with T-cell activation that might be due to activation of latent viruses, and they could hold importance for determining the risks of space flight.

  8. Plasma inflammatory and vascular homeostasis biomarkers increase during human pregnancy but are not affected by oily fish intake.

    Science.gov (United States)

    García-Rodríguez, Cruz E; Olza, Josune; Aguilera, Concepción M; Mesa, María D; Miles, Elizabeth A; Noakes, Paul S; Vlachava, Maria; Kremmyda, Lefkothea-Stella; Diaper, Norma D; Godfrey, Keith M; Calder, Philip C; Gil, Angel

    2012-07-01

    The Salmon in Pregnancy Study investigated whether the increased consumption of (n-3) long-chain PUFA (LC-PUFA) from farmed Atlantic salmon affects immune function during pregnancy and atopic disease in neonates compared with a habitual diet low in oily fish. In this context, because the ingestion of (n-3) LC-PUFA may lower the concentrations of inflammatory biomarkers, we investigated whether the consumption of oily fish affects the levels of inflammatory cytokines and vascular adhesion factors during pregnancy. Pregnant women (n = 123) were randomly assigned to continue their habitual diet (control group, n = 61), which was low in oily fish, or to consume two 150-g salmon portions/wk (salmon group, n = 62; providing 3.45 g EPA plus DHA) from 20 wk of gestation until delivery. Plasma inflammatory cytokines and vascular adhesion factors were measured in maternal plasma samples. Inflammatory biomarkers, including IL-8, hepatocyte growth factor, and monocyte chemotactic protein, increased over the course of pregnancy (P pregnancy progressed (P pregnancy, they are not affected by the increased intake of farmed salmon.

  9. PPAR-γ agonist pioglitazone affects rat gouty arthritis by regulating cytokines.

    Science.gov (United States)

    Wang, R-C; Jiang, D-M

    2014-08-28

    The objective was to study peroxisome proliferator-activated receptor gamma (PPARγ) agonist pioglitazone regulation effect and its mechanism of expression of cytokines on acute gouty arthritis synovial in rats. Rats with unilateral ankle were injected with artificial monosodium urate (MSU) crystals to make the acute gouty arthritis model. Taking the synovium 48 h after the injection of MSU and using RT-PCR, we assessed the effect of pioglitazone (20 mg·kg(-1)·day(-1), oral administration) on synovial expression, by detecting tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interferon-γ (IFN-γ). The pioglitazone treatment group showed synovial expression of TNF-α, and IFN-γ was significantly lower than in the control group; the inhibition rates were 78.5 and 60.4%. The IL-1 expression difference was not statistically significant between the two groups. Pioglitazone has anti-inflammatory effects on acute gouty arthritis by inhibiting the expression of TNF-α and IFN-γ.

  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. Association analysis of cytokine polymorphisms and plasma level in Northern Chinese Han patients with paroxysmal nocturnal hemoglobinuria

    Institute of Scientific and Technical Information of China (English)

    WANG Shu-ye; YANG Xi-jing; YANG Shan-shan; WANG Wei; TIAN Yao-yao; CAO Feng-lin; ZHOU Jin

    2012-01-01

    Background While the incidence of paroxysmal noctumalhemoglobinuria (PNH) is relatively high in Northern China,the exact mechanism of the disease remains unknown.Immunoregulatory cytokine polymorphisms can directly regulate the expression levels of cytokines,which play a crucial role in many diseases.The purpose of this study was to study cytokine gene single nucleotide polymorphisms (SNPs) and the correlated cytokine expression levels in relationship to the PNH pathogenesis.Methods Peripheral blood samples were collected from 30 PNH patients and 40 healthy donors; all of the samples were collected from the Han people of Northern China.Eight SNP loci in five cytokine genes,including tumor necrosis factor-alpha (TNF-α),interferon-gamma (IFN-γ),transforming growth factor-beta (TGF-β),interleukin-6 (IL-6),and IL-10,and aplastic anemia (AA) were assessed.TNF-α,TGF-β,IFN-γ,IL-6,and IL-10 were analyzed by sequence-specific primer polymerase chain reaction (PCR-SSP).The plasma protein levels of TNF-α,TGF-β,and IFN-γwere assessed by an ELISA.Results The PNH patients had a lower frequency of the TC/GG genotype of the TGF-I gene (P <0.01) and a higher frequency of the C allele in the TGF-β gene (+10) compared to the controls (P <0.05).The predominant genotype of the +874 locus of the IFN-γ gene was TA in the PNH patients,while that in the predominant genotype was AA in the control group and was statistically significant (P <0.001).The frequency of the T allele in the IFN-γ gene was dramatically higher in the PNH patients than in the controls (P <0.05).The PNH patients had a reduced frequency of the GC and CC genotypes,as well as the C allele at locus -174 of the IL-6 gene compared to the controls (P <0.01).In addition,the plasma concentrations of TNF-α,TGF-β,and IFN-γ were significantly higher in the PNH group compared to the control group (P <0.01). Conclusions Expression levels of the TNF-α,TGF-β,and IFN-γ cytokines play an important role in

  12. N-3 polyunsaturated fatty acids do not affect the cytokine response to strenuous exercise

    DEFF Research Database (Denmark)

    Toft, A.D.; Thorn, Mette; Ostrowski, Kenneth

    2000-01-01

    (PUFA), for 6 wk or to receive no supplementation (n = 10) before participating in The Copenhagen Marathon 1998. Blood samples were collected before the race, immediately after, and 1.5 and 3 h postexercise. The fatty acid composition in blood mononuclear cells (BMNC) differed between the fish oil......The aim of the present study was to investigate whether fish oil supplementation was able to modulate the acute-phase response to strenuous exercise. Twenty male runners were randomized to receive supplementation (n = 10) with 6.0 g fish oil daily, containing 3.6 g n-3 polyunsaturated fatty acids......-supplemented and the control group, showing incorporation of n-3 PUFA and less arachidonic acid in BMNC in the supplemented group. The plasma levels of tumor necrosis factor-alpha, interleukin-6, and transforming growth factor-beta(1) peaked immediately after the run, the increase being 3-, 92-, and 1.1-fold, respectively...

  13. Pretreatment plasma levels and diagnostic utility of hematopoietic cytokines in cervical cancer or cervical intraepithelial neoplasia patients.

    Science.gov (United States)

    Ławicki, Sławomir; Będkowska, Grażyna E; Gacuta-Szumarska, Ewa; Knapp, Paweł; Szmitkowski, Maciej

    2012-07-04

    In this study, we compared plasma levels and the diagnostic utility of hematopoietic growth factors (HGFs) with SCC-Ag in cervical cancer patients in relation to control groups and cervical intraepithelial neoplasia (CIN) patients and healthy subjects. Pretreatment plasma levels of HGFs (SCF, GM-CSF, G-CSF and M-CSF) were determined by the use of immunoenzyme assay (ELISA), and SCC-Ag by chemiluminescent microparticle immunoassay (CMIA). Significantly different concentrations of GM-CSF, G-CSF and M-CSF were observed in the group of patients with cervical cancer and CIN compared to the healthy controls. Significant differences in plasma levels of GM-CSF and M-CSF between cervical cancer and benign lesions patients were also found. The HGFs and SCC-Ag diagnostic specificities received high values. The diagnostic sensitivity and the predictive value of a positive and negative test result were higher for M-CSF than for antigen SCC in the cancer group. The M-CSF area under the ROC curve (AUC) was the largest from hematopoietic cytokines and SCC-Ag. These results suggest the potential utility of M-CSF as a good candidate for a marker of cervical cancer as well as benign lesions of this organ (CIN).

  14. 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.

  15. 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.

  16. Early application of nerve growth factor affects serum inflammatory cytokine levels in neonatal hypoxic ischemic encephalopathy

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    BACKGROUND: It has been demonstrated that there are changes of various cytokines, chemokines and adhesion factors in neonatal hypoxic ischemic encephalopathy (HIE). What are the changes of interleukin-6 and interleukin-18 in serum of HIE neonates.OBJECTIVE: To observe the dynamic changes of interleukin-6 and interleukin-18 in peripheral serum at different time after HIE in neonates, and analyze the possible therapeutic efficacy of early application of NGF.DESIGN: A non-randomized controlled observation synchronically.SETTING: Department of Neonatology, Sun Yat-sen Hospital affiliated to Sun Yat-sen University.PARTICIPANTS: Sixty neonates with HIE were selected from the Department of Neonatology, Sun Yat-sen Hospital affiliated to Sun Yat-sen University from January 2004 to October 2006, including 32 boys and 28 girls, who were all accorded with the diagnostic standards for moderate to severe HIE. The neonates were divided into two groups NGF-treated group (n =30), HIE group (n =30). The HIE neonates in the NGF-treated group were given routine treatment and intramuscular injection of NGF within 24 hours after birth. Those in the HIE group were given routine treatments. Meanwhile, 30 apneic normal neonates (17 boys and 13 girls) at the same period were selected as the control group. The gestational age was 37 - 42 weeks in all the three groups, the body mass at birth was 2 500 - 4 000 g. Informed contents were obtained from the relatives of all the enrolled neonates.METHODS: The HIE neonates in the NGF-treated group were given routine treatment and intramuscular injection of NGF (2 000 U) within 24 hours after birth, once a day, 10 days as a course. Those in the HIE group were given routine treatments. Blood samples (3 mL) were drawn from femoral vein in all the neonates 1, 3 and 7 days after birth. The levels of interleukin-6 and interleukin-18 in serum were detected with enzyme-linked immunoabsorbent assay (ELISA).MAIN OUTCOME MEASURES: Serum levels of interlenkin

  17. Cytokines TNF-α, IL-6, IL-17F, and IL-4 Differentially Affect Osteogenic Differentiation of Human Adipose Stem Cells

    Directory of Open Access Journals (Sweden)

    Angela P. Bastidas-Coral

    2016-01-01

    Full Text Available During the initial stages of bone repair, proinflammatory cytokines are released within the injury site, quickly followed by a shift to anti-inflammatory cytokines. The effect of pro- and anti-inflammatory cytokines on osteogenic differentiation of mesenchymal stem cells is controversial. Here, we investigated the effect of the proinflammatory cytokines TNF-α, IL-6, IL-8, and IL-17F and the anti-inflammatory cytokine IL-4 on proliferation and osteogenic differentiation of human adipose stem cells (hASCs. hASCs were treated with TNF-α, IL-6, IL-8, IL-17F, or IL-4 (10 ng/mL for 72 h mimicking bone repair. TNF-α reduced collagen type I gene expression but increased hASC proliferation and ALP activity. IL-6 also strongly enhanced ALP activity (18-fold, as well as bone nodule formation by hASCs. IL-8 did not affect proliferation or osteogenic gene expression but reduced bone nodule formation. IL-17F decreased hASC proliferation but enhanced ALP activity. IL-4 enhanced osteocalcin gene expression and ALP activity but reduced RUNX2 gene expression and bone nodule formation. In conclusion, all cytokines studied have both enhancing and reducing effects on osteogenic differentiation of hASCs, even when applied for 72 h only. Some cytokines, specifically IL-6, may be suitable to induce osteogenic differentiation of mesenchymal stem cells as a strategy for enhancing bone repair.

  18. Seminal plasma affects sperm sex sorting in boars.

    Science.gov (United States)

    Alkmin, Diego V; Parrilla, Inmaculada; Tarantini, Tatiana; Del Olmo, David; Vazquez, Juan M; Martinez, Emilio A; Roca, Jordi

    2016-04-01

    Two experiments were conducted in boar semen samples to evaluate how both holding time (24h) and the presence of seminal plasma (SP) before sorting affect sperm sortability and the ability of sex-sorted spermatozoa to tolerate liquid storage. Whole ejaculate samples were divided into three aliquots immediately after collection: one was diluted (1:1, v/v) in Beltsville thawing solution (BTS; 50% SP); the SP of the other two aliquots was removed and the sperm pellets were diluted with BTS + 10% of their own SP (10% SP) or BTS alone (0% SP). The three aliquots of each ejaculate were divided into two portions, one that was processed immediately for sorting and a second that was sorted after 24h storage at 15-17°C. In the first experiment, the ability to exhibit well-defined X- and Y-chromosome-bearing sperm peaks (split) in the cytometry histogram and the subsequent sorting efficiency were assessed (20 ejaculates). In contrast with holding time, the SP proportion influenced the parameters examined, as evidenced by the higher number of ejaculates exhibiting split and better sorting efficiency (P<0.05) in semen samples with 0-10% SP compared with those with 50% SP. In a second experiment, the quality (viability, total and progressive motility) and functionality (plasma membrane fluidity and intracellular generation of reactive oxygen species) of sex-sorted spermatozoa were evaluated after 0, 72 and 120h storage at 15-17°C (10 ejaculates). Holding time and SP proportion did not influence the quality or functionality of stored sex-sorted spermatozoa. In conclusion, a holding time as long as 24h before sorting did not negatively affect sex sorting efficiency or the ability of sorted boar spermatozoa to tolerate long-term liquid storage. A high proportion of SP (50%) in the semen samples before sorting reduced the number of ejaculates to be sorted and negatively influenced the sorting efficiency, but did not affect the ability of sex-sorted spermatozoa to tolerate liquid

  19. Vaccenic and elaidic acid modify plasma and splenocyte membrane phospholipids and mitogen-stimulated cytokine production in obese insulin resistant JCR: LA-cp rats.

    Science.gov (United States)

    Ruth, Megan R; Wang, Ye; Yu, Howe-Ming; Goruk, Susan; Reaney, Martin J; Proctor, Spencer D; Vine, Donna F; Field, Catherine J

    2010-02-01

    This study assessed the long-term effects of dietary vaccenic acid (VA) and elaidic acid (EA) on plasma and splenocyte phospholipid (PL) composition and related changes in inflammation and splenocyte phenotypes and cytokine responses in obese/insulin resistant JCR:LA-cp rats. Relative to lean control (Ctl), obese Ctl rats had higher serum haptoglobin and impaired T-cell-stimulated cytokine responses. VA and EA diets improved T-cell-stimulated cytokine production; but, only VA normalized serum haptoglobin. However, EA- and VA-fed rats had enhanced LPS-stimulated cytokine responses. The changes elicited by VA were likely due changes in essential fatty acid composition in PL; whereas EA-induced changes may due to direct incorporation into membrane PL.

  20. 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.

  1. Paraoxonase 1 polymorphism Q192R affects the pro-inflammatory cytokine TNF-alpha in healthy males

    Directory of Open Access Journals (Sweden)

    Rimbach Gerald

    2011-05-01

    Full Text Available Abstract Background Human paraoxonase 1 (PON1 is an HDL-associated enzyme with anti-oxidant/anti-inflammatory properties that has been suggested to play an important protective role against coronary heart diseases and underlying atherogenesis. The common PON1 Q192R polymorphism (rs662, A>G, a glutamine to arginine substitution at amino acid residue 192, has been analyzed in numerous association studies as a genetic marker for coronary heart diseases, however, with controversial results. Findings To get a better understanding about the pathophysiological function of PON1, we analyzed the relationships between the Q192R polymorphism, serum paraoxonase activity and serum biomarkers important for atherogenesis. Genotyping a cohort of 49 healthy German males for the Q192R polymorphism revealed an allele distribution of 0.74 and 0.26 for the Q and R allele, respectively, typical for Caucasian populations. Presence of the R192 allele was found to be associated with a significantly increased paraoxonase enzyme activity of 187.8 ± 11.4 U/l in comparison to the QQ192 genotype with 60.5 ± 4.9 U/l. No significant differences among the genotypes were found for blood pressure, asymmetric dimethylarginine, LDL, HDL, triglycerides, and cholesterol. As expected, MIP-2 alpha a cytokine rather not related to atherosclerosis is not affected by the PON1 polymorphism. In contrast to that, the pro-inflammatory cytokine TNF-alpha is enhanced in R192 carriers (163.8 ± 24.7 pg/ml vs 94.7 ± 3.2 pg/ml in QQ192 carriers. Conclusions Our findings support the hypothesis that the common PON1 R192 allele may be a genetic risk factor for atherogenesis by inducing chronic low-grade inflammation.

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

    Directory of Open Access Journals (Sweden)

    Noone Cariosa

    2013-01-01

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

  3. Receptor dimer stabilization by hierarchical plasma membrane microcompartments regulates cytokine signaling.

    Science.gov (United States)

    You, Changjiang; Marquez-Lago, Tatiana T; Richter, Christian Paolo; Wilmes, Stephan; Moraga, Ignacio; Garcia, K Christopher; Leier, André; Piehler, Jacob

    2016-12-01

    The interaction dynamics of signaling complexes is emerging as a key determinant that regulates the specificity of cellular responses. We present a combined experimental and computational study that quantifies the consequences of plasma membrane microcompartmentalization for the dynamics of type I interferon receptor complexes. By using long-term dual-color quantum dot (QD) tracking, we found that the lifetime of individual ligand-induced receptor heterodimers depends on the integrity of the membrane skeleton (MSK), which also proved important for efficient downstream signaling. By pair correlation tracking and localization microscopy as well as by fast QD tracking, we identified a secondary confinement within ~300-nm-sized zones. A quantitative spatial stochastic diffusion-reaction model, entirely parameterized on the basis of experimental data, predicts that transient receptor confinement by the MSK meshwork allows for rapid reassociation of dissociated receptor dimers. Moreover, the experimentally observed apparent stabilization of receptor dimers in the plasma membrane was reproduced by simulations of a refined, hierarchical compartment model. Our simulations further revealed that the two-dimensional association rate constant is a key parameter for controlling the extent of MSK-mediated stabilization of protein complexes, thus ensuring the specificity of this effect. Together, experimental evidence and simulations support the hypothesis that passive receptor confinement by MSK-based microcompartmentalization promotes maintenance of signaling complexes in the plasma membrane.

  4. Dietary zinc depletion and repletion affects plasma proteins: an analysis of the plasma proteome.

    Science.gov (United States)

    Grider, Arthur; Wickwire, Kathie; Ho, Emily; Chung, Carolyn S; King, Janet

    2013-02-01

    Zinc (Zn) deficiency is a problem world-wide. Current methods for assessing Zn status are limited to measuring plasma or serum Zn within populations suspected of deficiency. Despite the high prevalence of Zn deficiency in the human population there are no methods currently available for sensitively assessing Zn status among individuals. The purpose of this research was to utilize a proteomic approach using two-dimensional gel electrophoresis (2DE) and mass spectrometry to identify protein biomarkers that were sensitive to changes in dietary Zn levels in humans. Proteomic analysis was performed in human plasma samples (n = 6) obtained from healthy adult male subjects that completed a dietary Zn depletion/repletion protocol, current dietary zinc intake has a greater effect on fractional zinc absorption than does longer term zinc consumption in healthy adult men. Chung et al. (Am J Clin Nutr 87 (5):1224-1229, 2008). After a 13 day Zn acclimatization period where subjects consumed a Zn-adequate diet, the male subjects consumed a marginal Zn-depleted diet for 42 days followed by consumption of a Zn-repleted diet for 28 days. The samples at baseline, end of depletion and end of repletion were pre-fractionated through immuno-affinity columns to remove 14 highly abundant proteins, and each fraction separated by 2DE. Following staining by colloidal Coomassie blue and densitometric analysis, three proteins were identified by mass spectrometry as affected by changes in dietary Zn. Fibrin β and chain E, fragment double D were observed in the plasma protein fraction that remained bound to the immunoaffinity column. An unnamed protein that was related to immunoglobulins was observed in the immunodepleted plasma fraction. Fibrin β increased two-fold following the Zn depletion period and decreased to baseline values following the Zn repletion period; this protein may serve as a viable biomarker for Zn status in the future.

  5. Swimming exercise and diphenyl diselenide-supplemented diet affect the serum levels of pro- and anti-inflammatory cytokines differently depending on the age of rats.

    Science.gov (United States)

    Leite, Marlon R; Cechella, José L; Mantovani, Anderson C; Duarte, Marta M M F; Nogueira, Cristina W; Zeni, Gilson

    2015-01-01

    The increase in the inflammatory process is one of the main factors that contribute to aging. The aim of this study was to investigate the effects of a diphenyl diselenide (PhSe)2-supplemented diet (1p.p.m., 4weeks) and swimming exercise (3% of body weight, 20min per day, 4weeks) on the serum levels of cytokines in Wistar rats of different ages. The results demonstrated an increase in the levels of pro-inflammatory cytokines (IL-1β, IL-6, TNFα and INFγ) and a decrease in the levels of IL-10, an anti-inflammatory cytokine, with age. In middle-age rats, the swimming exercise and (PhSe)2-supplemented diet decreased serum levels of pro-inflammatory cytokines and increased the levels of IL-10. By contrast, in old rats the swimming exercise protocol increased the serum levels of pro-inflammatory cytokines and decreased the levels IL-10. Diet supplemented with (PhSe)2 did not alter the serum levels of cytokines in old rats. Middle-age and old rats subjected to swimming exercise and supplemented with (PhSe)2 in the diet had a decrease in the serum levels of pro-inflammatory cytokines and an increase in the levels of IL-10. This study demonstrated that swimming exercise and (PhSe)2-supplemented diet affect the serum levels of pro- and anti-inflammatory cytokines differently depending on the age of rats. (PhSe)2 supplemented in the diet had an anti-inflammatory effect, similar to that of induced by swimming exercise, in middle-age rats and reversed the pro-inflammatory effects of swimming exercise in old rats.

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    PURPOSE: To establish and validate a rapid, cost-effective and accurate screening assay for the simultaneous testing of human naturally occurring anti-cytokine autoantibodies (c-aAb) targeting interleukin-1α (IL-1α), interleukin-6 (IL-6), interleukin-10 (IL-10), granulocyte-macrophage colony...... plasma samples and pooled normal immunoglobulin preparations were used to validate the assay. Plasma samples from 98 transfusion recipients, half of whom presented with febrile reactions, were tested by the assay. RESULTS: The assay detected specific and saturable immunoglobulin G (IgG) binding to each...... cytokine autoantibodies quantities in the negative plasma samples ranged between 80% and 125%. The analytical intra- and inter-assay variations were 4% and 11%, respectively. Varying c-aAb levels were detectable in the transfusion recipients. There was no difference in c-aAb frequency between the patients...

  7. Splenic suppressor of cytokine signaling 3 transgene expression affects T cell responses and prevents development of collagen-induced arthritis.

    NARCIS (Netherlands)

    Veenbergen, S.; Bennink, M.B.; Hooge, A.S.K. de; Arntz, O.J.; Smeets, R.L.; Berg, W.B. van den; Loo, F.A.J. van de

    2008-01-01

    OBJECTIVE: Members of the suppressor of cytokine signaling (SOCS) family are key negative intracellular regulators of cytokine and growth factor responses, including those that regulate immune responses in autoimmune disorders, such as rheumatoid arthritis (RA). The aim of this study was to investig

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

    Directory of Open Access Journals (Sweden)

    Mirjam E Belderbos

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

  9. Effects of music therapy on autonomic nervous system activity, incidence of heart failure events, and plasma cytokine and catecholamine levels in elderly patients with cerebrovascular disease and dementia.

    Science.gov (United States)

    Okada, Kaoru; Kurita, Akira; Takase, Bonpei; Otsuka, Toshiaki; Kodani, Eitaro; Kusama, Yoshiki; Atarashi, Hirotsugu; Mizuno, Kyoichi

    2009-01-01

    Music therapy (MT) has been used in geriatric nursing hospitals, but there has been no extensive research into whether it actually has beneficial effects on elderly patients with cerebrovascular disease (CVD) and dementia. We investigated the effects of MT on the autonomic nervous system and plasma cytokine and catecholamine levels in elderly patients with CVD and dementia, since these are related to aging and chronic geriatric disease. We also investigated the effects of MT on congestive heart failure (CHF) events.Eighty-seven patients with pre-existing CVD were enrolled in the study. We assigned patients into an MT group (n = 55) and non-MT group (n = 32). The MT group received MT at least once per week for 45 minutes over 10 times. Cardiac autonomic activity was assessed by heart rate variability (HRV). We measured plasma cytokine and catecholamine levels in both the MT group and non-MT group. We compared the incidence of CHF events between these two groups. In the MT group, rMSSD, pNN50, and HF were significantly increased by MT, whereas LF/HF was slightly decreased. In the non-MT group, there were no significant changes in any HRV parameters. Among cytokines, plasma interleukin-6 (IL-6) in the MT group was significantly lower than those in the non-MT group. Plasma adrenaline and noradrenaline levels were significantly lower in the MT group than in the non-MT group. CHF events were less frequent in the MT group than in the non-MT group (P < 0.05). These findings suggest that MT enhanced parasympathetic activities and decreased CHF by reducing plasma cytokine and catecholamine levels.

  10. Preoperative plasma level of IL-10 but not of proinflammatory cytokines is an independent prognostic factor in patients with gastric cancer.

    Science.gov (United States)

    Szaflarska, Anna; Szczepanik, Antoni; Siedlar, Maciej; Czupryna, Antoni; Sierzega, Marek; Popiela, Tadeusz; Zembala, Marek

    2009-12-01

    There have been many discrepant observations on the serum levels of cytokines in cancer patients and their prognostic value. The purpose of this study was to determine the plasma levels of pro- and anti-inflammatory cytokines and their clinical significance in a large group of patients with gastric carcinoma. The levels of tumour necrosis factor alpha (TNF alpha), interleukin-12p40 (IL-12p40), IL-12p70, IL-18, IL-10 and soluble TNF receptors I and II sTNF-Rs were investigated in the plasma of 136 consecutive patients with biopsy proven gastric cancer using specific enzyme-linked immunoabsorbent assays (ELISA). Survival curves were estimated using the method of Kaplan and Meier and the differences in the survival rates were tested by the log-rank test. For multivariate analysis of prognostic factors, the Cox proportional hazard model was used. Proinflammatory cytokines and sTNF-Rs were higher in the whole group of patients in comparison to healthy volunteers. IL-10 was elevated mostly in advanced disease. The increased levels of IL-10 (>10 pg/ml) were associated with significantly poorer survival of patients, while the levels of the other cytokines and sTNF-Rs showed no correlation with prognosis. The increased level of IL-10 is an independent unfavorable prognostic factor in patients with gastric cancer.

  11. 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.

  12. Blood sampling and hemolysis affect concentration of plasma metabolites

    DEFF Research Database (Denmark)

    Theil, Peter Kappel; Pedersen, Lene Juul; Jensen, Margit Bak;

    2012-01-01

    , a subset of samples from 24 sows fed twice daily in Exp. 1 was combined with data obtained from 30 sows sampled using jugular vein catheters. All sows in Exp. 2 were fed twice daily (0800 h and 1500 h) and blood samples collected repeatedly 1, 4, 11, and 23 h after morning feeding (other conditions were......Two experiments were carried out to reveal and quantify plasma metabolites that are sensitive to hemolysis and animal stress due to the blood sampling procedure (vein puncture vs. catheter). In Exp. 1, 48 sows were fed 4 diets either once (0800 h) or twice daily (0800 h and 1500 h) in a crossover...... design and blood was collected after restraint via vein puncture 1, 4, 11, and 23 h after morning feeding. Plasma samples were categorized as without or with minor or major hemolysis [clear (n = 218), yellow (n = 97), or red (n = 37)] upon centrifugation. Plasma NEFA (P

  13. Plasma degradome affected by variable storage of human blood

    NARCIS (Netherlands)

    Kaisar, Maria; Van Dullemen, Leon F. A.; Thezenas, Marie-Laetitia; Akhtar, M. Zeeshan; Huang, Honglei; Rendel, Sandrine; Charles, Philip D.; Fischer, Roman; Ploeg, Rutger J.; Kessler, Benedikt M.

    2016-01-01

    Background: The successful application of-omics technologies in the discovery of novel biomarkers and targets of therapeutic interventions is facilitated by large collections of well curated clinical samples stored in bio banks. Mining the plasma proteome holds promise to improve our understanding o

  14. Plane of nutrition affects plasma ghrelin concentrations in neonatal calves

    Science.gov (United States)

    Investigating different planes of nutrition on appetite-related hormones could provide knowledge into the role of these hormones on growth performance in neonatal calves. The objective of the current study was to investigate the effects of feeding rates on ghrelin in plasma from preruminant calves....

  15. THE EFFECT OF TAPERING PERIOD ON PLASMA PRO-INFLAMMATORY CYTOKINE LEVELS AND PERFORMANCE IN ELITE MALE CYCLISTS

    Directory of Open Access Journals (Sweden)

    Peter M. Tiidus

    2009-12-01

    Full Text Available The aim of this study was to investigate the effect of two different tapering period lengths on the concentration of plasma interleukin- 6 (IL-6, interleukin (IL-1β and tumor necrosis factor-? (TNF-α and performance in elite male cyclists. To this end, after completing 8 weeks progressive endurance exercise, twenty four high-level endurance cyclists were randomly assigned to one of two groups: a control group of cyclists (n = 12 continued performing progressive weekly training volume for 3 weeks while a taper group of cyclists (n = 12 proceeded with a 50% reduction in weekly training volume relative to the control group. A simulated 40 min time trial (40TT performance ride was used as the criterion index of performance before and after the tapering period to evaluate the physiological and performance effects of each protocol. Blood samples were collected immediately post-40TT from all participants at the beginning of week 1, and the end of weeks 4, 8, 9 and 11. IL-1β, IL-6 and TNFα were assayed using a standard commercial ELISA kits (Quantikine; R & D Systems, Minneapolis, MN. The mean time to complete the 40TT in the taper group decreased significantly (p < 0.01 after both 1 and 3 weeks with reduced training volume relative to the control group. There were significant reductions in (p < 0.001 IL-1β, IL-6 and TNFα concentrations in the taper group relative to the control group at the end of the 3 week tapering period, but not at the end of the 1 week tapering period. These results demonstrate that both a 1 and a 3 week taper period will result in improved physical performance in trained cyclists but only a 3 week taper period will result in attenuation of post-exercise pro- inflammatory cytokines when compared to those continuing a more intense training regimen

  16. 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.

  17. Changes in Dietary Fat Content Rapidly Alters the Mouse Plasma Coagulation Profile without Affecting Relative Transcript Levels of Coagulation Factors.

    Directory of Open Access Journals (Sweden)

    Audrey C A Cleuren

    Full Text Available Obesity is associated with a hypercoagulable state and increased risk for thrombotic cardiovascular events.Establish the onset and reversibility of the hypercoagulable state during the development and regression of nutritionally-induced obesity in mice, and its relation to transcriptional changes and clearance rates of coagulation factors as well as its relation to changes in metabolic and inflammatory parameters.Male C57BL/6J mice were fed a low fat (10% kcal as fat; LFD or high fat diet (45% kcal as fat; HFD for 2, 4, 8 or 16 weeks. To study the effects of weight loss, mice were fed the HFD for 16 weeks and switched to the LFD for 1, 2 or 4 weeks. For each time point analyses of plasma and hepatic mRNA levels of coagulation factors were performed after overnight fasting, as well as measurements of circulating metabolic and inflammatory parameters. Furthermore, in vivo clearance rates of human factor (F VII, FVIII and FIX proteins were determined after 2 weeks of HFD-feeding.HFD feeding gradually increased the body and liver weight, which was accompanied by a significant increase in plasma glucose levels from 8 weeks onwards, while insulin levels were affected after 16 weeks. Besides a transient rise in cytokine levels at 2 weeks after starting the HFD, no significant effect on inflammation markers was present. Increased plasma levels of fibrinogen, FII, FVII, FVIII, FIX, FXI and FXII were observed in mice on a HFD for 2 weeks, which in general persisted throughout the 16 weeks of HFD-feeding. Interestingly, with the exception of FXI the effects on plasma coagulation levels were not paralleled by changes in relative transcript levels in the liver, nor by decreased clearance rates. Switching from HFD to LFD reversed the HFD-induced procoagulant shift in plasma, again not coinciding with transcriptional modulation.Changes in dietary fat content rapidly alter the mouse plasma coagulation profile, thereby preceding plasma metabolic changes, which

  18. Sex and storage affect cholinesterase activity in blood plasma of Japanese quail

    Science.gov (United States)

    Hill, E.F.

    1989-01-01

    Freezing at -25?C had confounding effects on cholinesterase (ChE) activity in blood plasma from breeding female quail, but did not affect ChE activity in plasma from males. Plasma ChE activity of control females increased consistently during 28 days of storage while both carbamate- and cidrotophos-inhibited ChE decreased. Refrigeration of plasma at 4?C for 2 days had little effect of ChE activity. Plasma ChE activity was averaged about 34% higher in breeding males than in females. Extreme caution should be exercised in use of blood plasma for evaluation of anti ChE exposure in free-living birds.

  19. N-Butanol Extract from Melilotus suaveolens Ledeb Affects Pro- and Anti-Inflammatory Cytokines and Mediators

    Directory of Open Access Journals (Sweden)

    Lei Zhao

    2010-01-01

    Full Text Available Melilotus suaveolens Ledeb is a traditional medicinal plant for treating inflammation-related disease. This explores the inner anti-inflammatory mechanism of n-butanol extract from M. suaveolens Ledeb. Inflammatory cellular model was established by lipopolysaccharide intervention on RAW264.7 cell line. Levels of secreted cytokines TNF-α, IL-1β, IL-6, NO and IL-10 in supernatant, mRNA expression of TNF-α, COX-2, iNOS and HO-1, protein expression of COX-2 and HO-1, activation of NF-κB and ingredients in the extract were assayed by ELISA, real time quantitative PCR, western blot, immunocytochemical test and HPLC fingerprint test, respectively. As a result, the extract could not only markedly reduce the production of pro-inflammatory mediators to different extents by blocking NF-κB activation but also promote the release of anti-inflammatory mediator HO-1 significantly. Each 1 g extract contained 0.023531 mg coumarin and another two high polar ingredients, probably saponins. It can be concluded that the extract has similar effects on antagonizing pro-inflammatory mediators and cytokines like Dexamethasone, and has effects on promoting the production of anti-inflammatory mediators.

  20. Plasma Interleukin-37 Is Elevated in Patients with Rheumatoid Arthritis: Its Correlation with Disease Activity and Th1/Th2/Th17-Related Cytokines

    Directory of Open Access Journals (Sweden)

    Ting Xia

    2015-01-01

    Full Text Available Interleukin- (IL- 37 is a novel anti-inflammatory cytokine that suppresses immune response and inflammation. This study was performed to determine whether IL-37 was elevated in patients with rheumatoid arthritis (RA and investigate the correlation between IL-37 level and disease activity and the concentration of Th1/Th2/Th17-related cytokines. Clinical parameters of disease activity, including the 28-joint disease activity score (DAS28 and C-reactive protein (CRP, were collected in 34 RA patients and 34 age- and sex-matched healthy controls. Plasma IL-37 was measured by ELISA. Plasma levels of TNF-α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-17, G-CSF, GM-CSF, IFN-γ, MCP-1, and MIP-1β were analyzed using the Bio-Plex suspension array system. It was found that IL-37 levels were elevated markedly in RA patients and almost undetectable in healthy controls. In addition, IL-37 levels in patients with active RA were significantly enhanced as compared with those in patients of remission. More importantly, IL-37 showed a significant correlation with disease activity (DAS28 and IL-4, IL-7, IL-10, IL-12, and IL-13 concentrations in RA patients. These findings suggest that IL-37 plays an important role in the pathogenesis of RA and may prove to be a potential biomarker of active RA.

  1. Evolutionary clade affects resistance of Clostridium difficile spores to Cold Atmospheric Plasma

    Science.gov (United States)

    Connor, Mairéad; Flynn, Padrig B.; Fairley, Derek J.; Marks, Nikki; Manesiotis, Panagiotis; Graham, William G.; Gilmore, Brendan F.; McGrath, John W.

    2017-02-01

    Clostridium difficile is a spore forming bacterium and the leading cause of colitis and antibiotic associated diarrhoea in the developed world. Spores produced by C. difficile are robust and can remain viable for months, leading to prolonged healthcare-associated outbreaks with high mortality. Exposure of C. difficile spores to a novel, non-thermal atmospheric pressure gas plasma was assessed. Factors affecting sporicidal efficacy, including percentage of oxygen in the helium carrier gas admixture, and the effect on spores from different strains representing the five evolutionary C. difficile clades was investigated. Strains from different clades displayed varying resistance to cold plasma. Strain R20291, representing the globally epidemic ribotype 027 type, was the most resistant. However all tested strains displayed a ~3 log reduction in viable spore counts after plasma treatment for 5 minutes. Inactivation of a ribotype 078 strain, the most prevalent clinical type seen in Northern Ireland, was further assessed with respect to surface decontamination, pH, and hydrogen peroxide concentration. Environmental factors affected plasma activity, with dry spores without the presence of organic matter being most susceptible. This study demonstrates that cold atmospheric plasma can effectively inactivate C. difficile spores, and highlights factors that can affect sporicidal activity.

  2. Plasma treatment of polystyrene thin films affects more than the surface.

    Science.gov (United States)

    Calchera, Angela R; Curtis, Alexander D; Patterson, James E

    2012-07-25

    Plasma treatment of polymer materials introduces chemical functionalities and modifies the material to make the native hydrophobic surface more hydrophilic. It is generally assumed that this process only affects the surface of the material. We used vibrationally resonant sum-frequency generation spectroscopy to observe changes in the orientation of phenyl groups in polystyrene (PS) thin films on various substrates before and after plasma treatment. VR-SFG selectively probes regions of broken symmetry, such as surfaces, but can also detect the emergence of anisotropy. On dielectric substrates, such as fused silica, the spectroscopic peak corresponding to the symmetric stretching (ν2) mode of the phenyl rings was undetectable after plasma treatment, showing that surface phenyl rings were altered. This peak also diminished on conducting substrates, but the intensity of another peak corresponding to the same mode in a bulklike environment increased significantly, suggesting that plasma treatment induces partial ordering of the bulk polymer. This ordering is seen on conducting substrates even when the polymer is not directly exposed to the plasma. Annealing reverses these effects on the polystyrene bulk; however, the surface phenyl rings do not return to the orientation observed for untreated films. These results call into question the assumption that the effects of plasma treatment are limited to the free surface and opens up other possibilities for material modification with low-temperature plasmas.

  3. Two Consecutive Days of Crossfit Training Affects Pro and Anti-inflammatory Cytokines and Osteoprotegerin without Impairments in Muscle Power.

    Science.gov (United States)

    Tibana, Ramires A; de Almeida, Leonardo M; Frade de Sousa, Nuno M; Nascimento, Dahan da Cunha; Neto, Ivo V de Sousa; de Almeida, Jeeser A; de Souza, Vinicius C; Lopes, Maria de Fátima T P L; Nobrega, Otávio de Tolêdo; Vieira, Denis C L; Navalta, James W; Prestes, Jonato

    2016-01-01

    The aim of this study was to investigate the effects of two consecutive Crossfit® training sessions (24 h apart) designed to enhance work-capacity that involved both cardiovascular and muscular exercises on cytokines, muscle power, blood lactate and glucose. Nine male members of the CrossFit® community (age 26.7 ± 6.6 years; body mass 78.8 ± 13.2 kg; body fat 13.5 ± 6.2%; training experience 2.5 ± 1.2 years) completed two experimental protocols (24 h apart): (1) strength and power exercises, (2) gymnastic movements, and (3) metabolic conditioning as follows: 10 min of as many rounds as possible (AMRAP) of 30 double-unders and 15 power snatches (34 kg). The same sequence as repeated on session 2 with the following metabolic conditioning: 12 min AMRAP of: row 250 m and 25 target burpees. Serum interleukin-6 (IL-6), IL-10, and osteoprotegerin were measured before, immediately post and 24 h after workout of the day (WOD) 1, immediately post, 24 and 48 h after WOD 2. Peak and mean power were obtained for each repetition (back squat with 50% of 1 repetition maximum) using a linear position transducer measured before, immediately post and 24 h after WOD 1, immediately post and 24 h after WOD 2. Blood lactate and glucose were measured pre and immediately post WOD 1 and 2. Although both sessions of exercise elicited an significant increase in blood lactate (1.20 ± 0.41 to 11.84 ± 1.34 vs. 0.94 ± 0.34 to 9.05 ± 2.56 mmol/l) and glucose concentration (81.59 ± 10.27 to 114.99 ± 12.52 vs. 69.47 ± 6.97 to 89.95 ± 19.26 mg/dL), WOD 1 induced a significantly greater increase than WOD 2 (p ≤ 0.05). The training sessions elicited significant changes (p ≤ 0.05) in IL-6, IL-10 and osteoprotegerin concentration over time. IL-6 displayed an increase immediately after training WOD 1 [197 ± 109%] (p = 0.009) and 2 [99 ± 58%] (p = 0.045). IL-10 displayed an increase immediately after only WOD 1 [44 ± 52%] (p = 0.046), and decreased 24 and 48 h following WOD 2 (~40%; p

  4. Plasma cytokine levels in young and elderly twins: genes versus environment and relation to in vivo insulin action

    DEFF Research Database (Denmark)

    Grunnet, L; Poulsen, P; Klarlund Pedersen, B;

    2006-01-01

    We studied the impact of genetic versus pre- and postnatal environmental factors on the plasma levels of IL6, TNF and the soluble TNF receptor superfamily, member 1A (TNFRSF1A, previously known as TNF receptor type1 [TNFR1]).......We studied the impact of genetic versus pre- and postnatal environmental factors on the plasma levels of IL6, TNF and the soluble TNF receptor superfamily, member 1A (TNFRSF1A, previously known as TNF receptor type1 [TNFR1])....

  5. Circulating cytokines and chemokines associated with plasma leakage and hepatic dysfunction in Brazilian children with dengue fever.

    Science.gov (United States)

    Ferreira, Ralph Antonio Xavier; de Oliveira, Solange Artimos; Gandini, Mariana; Ferreira, Laura da Cunha; Correa, Gladys; Abiraude, Fernanda Mattos; Reid, Mariana Mancebo; Cruz, Oswaldo Gonçalves; Kubelka, Claire Fernandes

    2015-09-01

    Dengue fever is usually a benign acute viral infection transmitted by arthropods but may evolve to severe clinical manifestations such as coagulation and/or hemodynamic disorders, caused mainly by an increase of vascular permeability. Deregulated circulating immunological factors have been associated with severity. In Brazil severe cases appeared in children only recently and we evaluated the profile of cytokine/chemokine kinetics in 134 hospitalized young patients during the epidemic in Rio de Janeiro in 2008. Inflammatory cytokines TNF and IFNγ were found elevated during the acute phase in children as well as the anti-inflammatory IL10 and chemokines MIF and CXCL10/IP10, all last three persisting longer during the recovery phase. Severe disease fitting the dengue hemorrhagic fever pattern (WHO, 1997) was associated with higher IL10 and CXCL10/IP10 circulating levels (peak levels at seven days with P<0.01 and P<0.001 respectively as compared to DF). These factors were higher in patients pulmonary effusion or ascites (P<0.05 for IL10 and P<0.01 for CXCL10/IP10). Both factors were also associated with liver changes such as AST increase correlated with CXCL10/IP10 (r=0.4300 with P<0.0001) and patients presenting painful hepatomegaly showed higher circulating levels of IL10 (P<0.01, at 7-9 days) and of CXCL10/IP10 (P<0.05, 4-6 days and P<0.001, 7-9 days) when compared to patients without apparent liver alterations. Most cases presented a history of prior infection (93%). This is the first study demonstrating cytokine and chemokine association with severity during dengue fever in Brazilian children. IL10 and CXCL10/IP10 play a role in the disease severity associated with induction of vascular leakage and a novel association with changes in liver dysfunction.

  6. Escitalopram reduces circulating pro-inflammatory cytokines and improves depressive behavior without affecting sleep in a rat model of post-cardiac infarct depression.

    Science.gov (United States)

    Bah, Thierno Madjou; Benderdour, Mohamed; Kaloustian, Sévan; Karam, Ramy; Rousseau, Guy; Godbout, Roger

    2011-11-20

    Myocardial infarction (MI) in rats is followed by a behavioral syndrome similar to human post-MI depression. We tested the effects of escitalopram, a selective serotonin reuptake inhibitor, on this syndrome. MI was induced in 19 Sprague-Dawley rats by occluding the left anterior descending coronary artery for 40min, followed by reperfusion. A sham-operated group of 20 rats was submitted to the same protocol without coronary artery occlusion. Fifteen minutes after the onset of reperfusion, escitalopram (10mg/kg/day, i.p.) or saline was infused continuously through osmotic minipumps. After 2weeks of treatment, the rats were tested for behavioral despair and anhedonia by the forced swimming and sucrose preference tests, respectively. They were then sacrificed, and blood levels of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), PGE(2) and corticosterone were measured. In a separate cohort of 24 rats, sleep was recorded after 2weeks of post-MI treatment with escitalopram or saline. In MI rats, behavioral despair and anhedonia were blocked by escitalopram but prolonged sleep latency, low total sleep time and short latency to paradoxical sleep (PS) were not; escitalopram decreased PS in sham controls. Plasma TNF-α, PGE(2), and corticosterone levels were higher in MI rats than in the controls. Escitalopram lowered TNF-α, IL-1β, and PGE(2) levels in both groups of rats while IL-6 showed no differences whatsoever. Escitalopram reverses post-MI behavioral syndrome in rats through a mechanism that could involve a reduction of pro-inflammatory cytokines and PGE(2). It has limited effects on sleep disorders in MI rats but reduces PS in control rats.

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

    Directory of Open Access Journals (Sweden)

    Seong-Beom Ahn

    2014-06-01

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

  8. The effects of ryanodine receptor (RYR1) mutation on natural killer cell cytotoxicity, plasma cytokines and stress hormones during acute intermittent exercise in pigs.

    Science.gov (United States)

    Ciepielewski, Z M; Stojek, W; Borman, A; Myślińska, D; Pałczyńska, P; Kamyczek, M

    2016-04-01

    Stress susceptibility has been mapped to a single recessive gene, the ryanodine receptor 1 (RYR1) gene or halothane (Hal) gene. Homozygous (Hal(nn)), mutated pigs are sensitive to halothane and susceptible to Porcine Stress Syndrome (PSS). Previous studies have shown that stress-susceptible RYR1 gene mutated homozygotes in response to restraint stress showed an increase in natural killer cell cytotoxicity (NKCC) accompanied by more pronounced stress-related hormone and anti-inflammatory cytokine changes. In order to determine the relationship of a RYR1 gene mutation with NKCC, plasma cytokines and stress-related hormones following a different stress model - exercise - 36 male pigs (representing different genotypes according to RYR1 gene mutation: NN, homozygous dominant; Nn, heterozygous; nn, homozygous recessive) were submitted to an intermittent treadmill walking. During the entire experiment the greatest level of NKCC and the greatest concentrations of interleukin (IL-) 6, IL-10, IL-12, interferon (IFN-)γ and tumor necrosis factor-α and stress-related hormones (adrenaline, prolactin, beta-endorphin) were observed in nn pigs, and the greatest concentration of IL-1 and growth hormone in NN pigs. Immunostimulatory effects of intermittent exercise on NKCC in nn pigs were concomitant with increases in IL-2, IL-12 and IFN-γ, the potent NKCC activators. Our findings suggest that stress-susceptible pigs RYR1 gene mutated pigs develop a greater level of NKCC and cytokine production in response to exercise stress. These results suggest that the heterogeneity of immunological and neuroendocrine response to exercise stress in pigs could be influenced by RYR1 gene mutation.

  9. Cytokines TNF-α, IL-6, IL-17F, and IL-4 differentially affect osteogenic differentiation of human adipose stem cells

    NARCIS (Netherlands)

    A.P. Bastidas-Coral; A.D. Bakker; B. Zandieh-Doulabi; C.J. Kleverlaan; N. Bravenboer; T. Forouzanfar; J. Klein-Nulend

    2016-01-01

    During the initial stages of bone repair, proinflammatory cytokines are released within the injury site, quickly followed by a shift to anti-inflammatory cytokines. The effect of pro- and anti-inflammatory cytokines on osteogenic differentiation of mesenchymal stem cells is controversial. Here, we i

  10. COMBINED PLASMA FILTRATION, SELECTIVE ADSORPTION OF CYTOKINES WITH HEMOFILTRATION AND PLASMA EXCHANGE IN THE CORRECTION OF PLATELET AND COAGULATION HEMOSTASIS IN PATIENTS WITH THE SYNDROME OF DISSEMINATED INTRAVASCULAR COAGULATION

    Directory of Open Access Journals (Sweden)

    L. V. Belskikh

    2015-01-01

    Full Text Available Aim. To improve the efficiency of treatment of the patients with pancreatic necrosis through correcting the platelet-coagulation potential by methods of combined plasma filtration, selective sorption of cytokines with hemofiltration and plasmapheresis. Methods. The effects of selective sorption of cytokines with hemofiltration and plasmapheresis upon coagulation potential were studied in 70 patients with acute pancreatitis. Plasmapheresis was performed on PCS 2 (Haemonetics, USA; selective sorption of cytokines with hemofiltration – on Lynda ® machine (Bellco, Italy. The method of computer laser phasemeter was used for vital assessing of platelet morphofunctional status. Results. In patients with pancreatic necrosis in the fermentation phase the percentage of resting platelets was 51.3%, which is 12% below the control numbers. The number of activated platelets increased: 25.1% of the cells were represented by platelets with low activation; 15.5% – highly activated cells. The number of degenerative-modified platelets increased by two times – up to 8.1%. In the phase of sequestration and suppurative complications the percentage of resting platelets was only 42.3%, which is 1.5 times lower than the control numbers. 34.2% of the cells were presented by platelets with low activation; 11.0% – highly activated cells. The number of degenerative-modified platelets exceeded 12.5%. The analysis of the morphological structure of the platelets population revealed that due to plasmapheresis inclusion into therapeutic complex in the phase of intoxication of pancreatic necrosis the normalization of platelet activation status of hemostasis was observed. In 5 (20% patients the normalization of average platelets morphometric parameters was shown after selective sorption of cytokines with hemofiltration and plasmapheresis. These patients demonstrated positive clinical dynamics. In 15 patients morphometric values of platelets either remained at the same

  11. Cytokines in bipolar disorder

    DEFF Research Database (Denmark)

    Munkholm, Klaus; Vinberg, Maj; Vedel Kessing, Lars

    2012-01-01

    BACKGROUND: Current research and hypothesis regarding the pathophysiology of bipolar disorder suggests the involvement of immune system dysfunction that is possibly related to disease activity. Our objective was to systematically review evidence of cytokine alterations in bipolar disorder according...... to affective state. METHODS: We conducted a systemtic review of studies measuring endogenous cytokine concentrations in patients with bipolar disorder and a meta-analysis, reporting results according to the PRISMA statement. RESULTS: Thirteen studies were included, comprising 556 bipolar disorder patients...

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

    DEFF Research Database (Denmark)

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

    2017-01-01

    Major overlaps of clinical characteristics and the limitations of conventional diagnostic tests render the initial diagnosis and clinical management of pulmonary disorders difficult. In this pilot study, we analyzed the predictive value of eotaxin, macrophage inflammatory protein 1 alpha (MIP-1α...... to predict the etiology and severity. Eotaxin and MCP-4 were significantly lower in patients with C-reactive protein ≥100, and MIP-1α was significantly higher in the patients with CURB-65 > 3, but the predictive power was low. In conclusion, further evaluation, including more patients, is required to assess...... the full potential of eotaxin, MCP-4, MIP-1α, and VEGF as biomarkers for LRTI because of their low predictive power and a high interindividual variation of cytokine levels....

  13. Short Hypoxia Does not Affect Plasma Leptin in Healthy Men under Euglycemic Clamp Conditions

    Directory of Open Access Journals (Sweden)

    Andre Schmoller

    2009-01-01

    Full Text Available Leptin is involved in the endocrine control of energy expenditure and body weight regulation. Previous studies emphasize a relationship between hypoxic states and leptin concentrations. The aim of this study was to investigate the effects of acute hypoxia on leptin concentrations in healthy subjects. We examined 14 healthy men. Hypoxic conditions were induced by decreasing oxygen saturation to 75% for 30 minutes. Plasma leptin concentrations were determined at baseline, after 3 hours of euglycemic clamping, during hypoxia, and repeatedly the following 2.5 hours thereafter. Our results show an increase of plasma leptin concentrations in the course of 6 hours of hyperinsulinemic-euglycemic clamping which may reflect diurnal rhythmicity. Notwithstanding, there was no difference between levels of leptin in the hypoxic and the normoxic condition (=.2. Since we did not find any significant changes in leptin responses upon hypoxia, plasma leptin levels do not seem to be affected by short hypoxic episodes of moderate degree.

  14. Ssh4, Rcr2 and Rcr1 affect plasma membrane transporter activity in Saccharomyces cerevisiae.

    Science.gov (United States)

    Kota, Jhansi; Melin-Larsson, Monika; Ljungdahl, Per O; Forsberg, Hanna

    2007-04-01

    Nutrient uptake in the yeast Saccharomyces cerevisiae is a highly regulated process. Cells adjust levels of nutrient transporters within the plasma membrane at multiple stages of the secretory and endosomal pathways. In the absence of the ER-membrane-localized chaperone Shr3, amino acid permeases (AAP) inefficiently fold and are largely retained in the ER. Consequently, shr3 null mutants exhibit greatly reduced rates of amino acid uptake due to lower levels of AAPs in their plasma membranes. To further our understanding of mechanisms affecting AAP localization, we identified SSH4 and RCR2 as high-copy suppressors of shr3 null mutations. The overexpression of SSH4, RCR2, or the RCR2 homolog RCR1 increases steady-state AAP levels, whereas the genetic inactivation of these genes reduces steady-state AAP levels. Additionally, the overexpression of any of these suppressor genes exerts a positive effect on phosphate and uracil uptake systems. Ssh4 and Rcr2 primarily localize to structures associated with the vacuole; however, Rcr2 also localizes to endosome-like vesicles. Our findings are consistent with a model in which Ssh4, Rcr2, and presumably Rcr1, function within the endosome-vacuole trafficking pathway, where they affect events that determine whether plasma membrane proteins are degraded or routed to the plasma membrane.

  15. Fresh frozen plasma transfusion does not affect outcomes following hepatic resection for hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Yoshito; Tomimaru; Hiroshi; Wada; Shigeru; Marubashi; Shogo; Kobayashi; Hidetoshi; Eguchi; Yutaka; Takeda; Masahiro; Tanemura; Takehiro; Noda; Koji; Umeshita; Yuichiro; Doki; Masaki; Mori; Hiroak; Nagano

    2010-01-01

    AIM:To investigate whether fresh frozen plasma (FFP) transfusion affects outcomes following hepatic resection for hepatocellular carcinoma (HCC) in terms of liver function,postoperative complications and cancer prognosis.METHODS:We retrospectively compared the incidence of postoperative complications between 204 patients who underwent hepatectomy for HCC with routine FFP transfusion in an early period (1983-1993,Group A) and 293 with necessity for FFP transfusion during a later period (1998-2006,Group B),an...

  16. Does Reactive Thrombocytosis Observed in Iron Deficiency Anemia Affect Plasma Viscosity?

    Directory of Open Access Journals (Sweden)

    Selami K. Toprak

    2012-09-01

    Full Text Available OBJECTIVE: The accompanying thrombocytosis is referred to as the major factor associated with thromboembolism in iron deficiency anemia (IDA. Increased viscosity may increase the risk of thrombosis. We hypothesized that increased platelet count -with reactive thrombocytosis- might also affect plasma viscosity. We planned to evaluate the influence of normal and high platelet count on plasma viscosity in IDA patients. METHODS: The patient population consisted of fifty-three newly diagnosed and untreated women aged between 18 and 62 years with IDA. Group 1 consisted of 33 patients, platelet levels below 400 x 109/L. Group 2 consisted of 20 patients, platelet levels above 400 x 109/L. Measurements of plasma viscosity were performed using Brookfield viscometer. RESULTS: Mean plasma viscosity was found as 1.05 ± 0.08 mPa.s. in Group 1, and 1.03 ± 0.06 mPa.s. in Group 2. Mean plasma viscosity was not statistically different. White blood cell count was significantly higher in Group 2. Vitamin B12 levels were significantly higher in Group 2, while folic acid levels were higher in Group 1 (p=0.011 and p=0.033. Plasma viscosity was correlated with erythrocyte sedimentation rate (r=0.512 p=0.002 in Group 1 and inversely correlated with vitamin B12 (r=−0.480 p=0.032 in Group 2. CONCLUSION: Despite the significant difference between groups in terms of platelet count, no significant difference was detected in plasma viscosity and this finding could be explained as the following; 1-These platelets were not thrombocythemic platelets; 2-Similar to the theory about leukocytes, higher platelet counts – even non-thrombocythemic – may increase plasma viscosity; 3-Evaluating platelet count alone is not sufficient and the associating red-cell deformability should also be taken into account; and 4-Although other diseases that could affect viscosity are excluded, some definitely proven literature criteria such as fibrinogen, hyperlipidemia, and the inflammatory

  17. The Liposuction-Induced Effects on Adiponectin and Selected Cytokines Are Not Affected by Exercise Training in Women

    Directory of Open Access Journals (Sweden)

    Marina Yazigi Solis

    2014-01-01

    Full Text Available It has been suggested that the abrupt liposuction-induced decrease in adipose tissue could affect adipokine secretion pattern. We hypothesized that exercise training could positively impact adipokine metabolism following liposuction. The aim of this study was to investigate the effects of liposuction on inflammation-related adipokines in women who were either exercise-trained or remained sedentary after surgery. Thirty-six healthy normal-weight women underwent an abdominal liposuction and two months after surgery were randomly allocated into two groups: trained (TR, n=18, four-month exercise program and nontrained (NT, n=18. Inflammation-related adipokine serum levels (TNF-α, IL-6, IL-10, and adiponectin and abdominal and thigh subcutaneous adipose tissue (scAT mRNA levels were assessed before (PRE and six months after surgery (POST6. TNF-α, IL-6, and IL-10 serum levels were unchanged in both groups. In contrast, TNF-α, IL-6, and IL-10 mRNA levels in scAT were increased, whereas adiponectin scAT mRNA and serum levels were decreased at POST6 (P<0.05, main effect for time. No changes were observed in mRNA levels of MCP-1, CD14, and CD68 in any of the groups. In conclusion, liposuction downregulates adiponectin scAT gene expression and serum levels and upregulates scAT gene expression of inflammation-related genes six months after surgery in normal-weight women, irrespective of exercise training.

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    in plasma and serum from 86 head and neck cancer patients and 33 controls were evaluated: EGFR, leptin, OPN, VEGFR-1, VEGFR-2, IL-2, IL-13, PDGF-bb, TNF, PAI-1, SDF-1a, IL-4, IL-6, IL-8, eotaxin, G-CSF, VEGF, GRO-a, and HGF. RESULTS: The correlation between measurements of the same samples analyzed...

  19. Genetic variants in ABCA1 promoter affect transcription activity and plasma HDL level in pigs.

    Science.gov (United States)

    Dang, Xiao-yong; Chu, Wei-wei; Shi, Heng-chuan; Yu, Shi-gang; Han, Hai-yin; Gu, Shu-Hua; Chen, Jie

    2015-01-25

    Excess accumulation of cholesterol in plasma may result in coronary artery disease. Numerous studies have demonstrated that ATP-binding cassette protein A1 (ABCA1) mediates the efflux of cholesterol and phospholipids to apolipoproteins, a process necessary for plasma high density lipoprotein (HDL) formation. Higher plasma levels of HDL are associated with lower risk for cardiovascular disease. Studies of human disease and animal models had shown that an increased hepatic ABCA1 activity relates to an enhanced plasma HDL level. In this study, we hypothesized that functional mutations in the ABCA1 promoter in pigs may affect gene transcription activity, and consequently the HDL level in plasma. The promoter region of ABCA1 was comparatively scanned by direct sequencing with pool DNA of high- and low-HDL groups (n=30 for each group). Two polymorphisms, c. - 608A>G and c. - 418T>A, were revealed with reverse allele distribution in the two groups. The two polymorphisms were completely linked and formed only G-A or A-T haplotypes when genotyped in a larger population (n=526). Furthermore, we found that the G-A/G-A genotype was associated with higher HDL and ABCA1 mRNA level than A-T/A-T genotype. Luciferase assay also revealed that G-A haplotype promoter had higher activity than A-T haplotype. Single-nucleotide mutant assay showed that c.-418T>A was the causal mutation for ABCA1 transcription activity alteration. Conclusively, we identified two completely linked SNPs in porcine ABCA1 promoter region which have influence on the plasma HDL level by altering ABCA1 gene transcriptional activity.

  20. Plasma Inflammatory Cytokine IL-4, IL-8, IL-10, and TNF-α Levels Correlate with Pulmonary Function in Patients with Asthma-Chronic Obstructive Pulmonary Disease (COPD) Overlap Syndrome.

    Science.gov (United States)

    Huang, Ai-Xia; Lu, Li-Wen; Liu, Wen-Juan; Huang, Mao

    2016-08-09

    BACKGROUND The aim of this study was to investigate the plasma inflammatory cytokine levels and their correlations with pulmonary function in patients with asthma-chronic obstructive pulmonary disease overlap syndrome (ACOS). MATERIAL AND METHODS Between January 2013 and December 2014, a total of 96 patients with asthma, acute exacerbation of chronic obstructive pulmonary disease (AECOPD), or ACOS were enrolled, and 35 healthy people were included as a control group. Fasting plasma interleukin (IL)-4, IL-8, IL-10, and tumor necrosis factor alpha (TNF-α) levels were detected using enzyme-linked immunosorbent assay (ELISA). Correlations between the plasma inflammatory cytokine levels and forced expiratory volume in 1 second (FEV1), FEV1/predicted value ratio (FEV1%pred), and FEV1/forced vital capacity (FVC) were analyzed. RESULTS IL-4 and IL-8 levels showed statistically significant differences among the 3 groups of patients (both PCOPD, and ACOS.

  1. Longitudinal instabilities affecting the moving critical layer laser-plasma ion accelerators

    CERN Document Server

    Sahai, Aakash Ajit

    2014-01-01

    In this work we analyze the longitudinal instabilities of propagating acceleration structures that are driven by a relativistically intense laser at the moving plasma critical layer [1]. These instabilities affect the energy-spectra of the accelerated ion-beams in propagating critical layer acceleration schemes [2][3]. Specifically, using analytical theory and PIC simulations we look into three fundamental physical processes and their interplay that are crucial to the understanding of energy spectral control by making the laser-plasma ion accelerators stable. The interacting processes are (i) Doppler-shifted ponderomotive bunching [1][4] (ii) potential quenching by beam-loading [2] and (iii) two-stream instabilities. These phenomenon have been observed in simulations analyzing these acceleration processes [5][6][7]. From the preliminary models and results we present in this work, we can infer measures by which these instabilities can be controlled [8] for improving the energy-spread of the beams.

  2. Age, segment, and horn disease affect expression of cytokines, growth factors, and receptors in the epidermis and dermis of the bovine claw.

    Science.gov (United States)

    Mills, J A; Zarlenga, D S; Habecker, P L; Dyer, R M

    2009-12-01

    The aim of this study was to examine changes in RNA expression for growth factors, cytokines, and receptors in epidermal-dermal tissues of the bovine claw relative to host age, claw segment, and disease state of the horn. Epidermal-dermal tissues were collected from the coronary, wall, sole, and bulb segments of 8- to 9-mo-old Holstein fetuses, normal adult cows, and adult cows with sole ulceration. Anatomic and pathologic characteristics were determined in tissues stained with eosin and hematoxylin, and RNA expression levels were evaluated using real-time, quantitative PCR. In normal tissues, certain RNA expression levels were clearly affected by host age: 290.0-, 610.0-, 53.4-, and 8.1-fold greater expression of granulocyte-macrophage colony stimulating factor was observed in fetal coronary, wall, sole, and bulb segment relative to adult tissues, respectively. A claw segment effect was also observed in that IL-1alpha expression was greater (1.59-fold) in the normal adult wall relative to the coronary segment, and IL-18 expression was greater (16.2-fold) in the normal adult sole compared with the coronary segment and 2.88 greater in the fetal sole relative to the bulb segment. Sole ulceration was associated with hemorrhage, thrombosis, inflammation, and striking increases in IL-1beta, IL-18, and inducible nitric oxide synthase, and with less dramatic, albeit measurable, changes in IL-1 type I receptor, IL-1 receptor antagonist, and tumor necrosis factor-alpha. Amidst striking increases in keratinocyte growth factor receptor (i.e., 21.0-fold, 10.4-fold, 0, and 21.6-fold in the coronary, wall, sole, and bulb segments, respectively), a concomitant decrease occurred in keratinocyte growth factor (i.e., 0.80-, 0.54-, 0.56-, and 0.72-fold, respectively). The results demonstrated changes in disease state and, to a lesser extent, claw segment and were accompanied by alterations in the RNA expression of several cytokines, growth factors, and receptors present in the normal

  3. Aircraft noise exposure affects rat behavior, plasma norepinephrine levels, and cell morphology of the temporal lobe

    Institute of Scientific and Technical Information of China (English)

    Guo-qing DI; Bing ZHOU; Zheng-guang; LI, Qi-li LIN

    2011-01-01

    In order to investigate the physiological effects of airport noise exposure on organisms,in this study,we exposed Sprague-Dawley rats in soundproof chambers to previously recorded aircraft-related noise for 65 d.For comparison,we also used unexposed control rats.Noise was arranged according to aircraft flight schedules and was adjusted to its weighted equivalent continuous perceived noise levels (LwEcPN) of 75 and 80 dB for the two experimental groups.We examined rat behaviors through an open field test and measured the concentrations of plasma norepinephrine (NE) by high performance liquid chromatography-fluorimetric detection (HPLC-FLD).We also examined the morphologies of neurons and synapses in the temporal lobe by transmission electron microscopy (TEM).Our results showed that rats exposed to airport noise of 80 dB had significantly lower line crossing number (P<0.05) and significantly longer center area duration (P<0.05) than control animals.After 29 d of airport noise exposure,the concentration of plasma NE of exposed rats was significantly higher than that of the control group (P<0.05).We also determined that the neuron and synapsis of the temporal lobe of rats showed signs of damage after aircraft noise of 80 dB exposure for 65 d.In conclusion,exposing rats to long-term aircraft noise affects their behaviors,plasma NE levels,and cell morphology of the temporal lobe.

  4. Aircraft noise exposure affects rat behavior, plasma norepinephrine levels, and cell morphology of the temporal lobe*

    Science.gov (United States)

    Di, Guo-qing; Zhou, Bing; Li, Zheng-guang; Lin, Qi-li

    2011-01-01

    In order to investigate the physiological effects of airport noise exposure on organisms, in this study, we exposed Sprague-Dawley rats in soundproof chambers to previously recorded aircraft-related noise for 65 d. For comparison, we also used unexposed control rats. Noise was arranged according to aircraft flight schedules and was adjusted to its weighted equivalent continuous perceived noise levels (L WECPN) of 75 and 80 dB for the two experimental groups. We examined rat behaviors through an open field test and measured the concentrations of plasma norepinephrine (NE) by high performance liquid chromatography-fluorimetric detection (HPLC-FLD). We also examined the morphologies of neurons and synapses in the temporal lobe by transmission electron microscopy (TEM). Our results showed that rats exposed to airport noise of 80 dB had significantly lower line crossing number (P<0.05) and significantly longer center area duration (P<0.05) than control animals. After 29 d of airport noise exposure, the concentration of plasma NE of exposed rats was significantly higher than that of the control group (P<0.05). We also determined that the neuron and synapsis of the temporal lobe of rats showed signs of damage after aircraft noise of 80 dB exposure for 65 d. In conclusion, exposing rats to long-term aircraft noise affects their behaviors, plasma NE levels, and cell morphology of the temporal lobe. PMID:22135145

  5. Ceylon cinnamon does not affect postprandial plasma glucose or insulin in subjects with impaired glucose tolerance.

    Science.gov (United States)

    Wickenberg, Jennie; Lindstedt, Sandra; Berntorp, Kerstin; Nilsson, Jan; Hlebowicz, Joanna

    2012-06-01

    Previous studies on healthy subjects have shown that the intake of 6 g Cinnamomum cassia reduces postprandial glucose and that the intake of 3 g C. cassia reduces insulin response, without affecting postprandial glucose concentrations. Coumarin, which may damage the liver, is present in C. cassia, but not in Cinnamomum zeylanicum. The aim of the present study was to study the effect of C. zeylanicum on postprandial concentrations of plasma glucose, insulin, glycaemic index (GI) and insulinaemic index (GII) in subjects with impaired glucose tolerance (IGT). A total of ten subjects with IGT were assessed in a crossover trial. A standard 75 g oral glucose tolerance test (OGTT) was administered together with placebo or C. zeylanicum capsules. Finger-prick capillary blood samples were taken for glucose measurements and venous blood for insulin measurements, before and at 15, 30, 45, 60, 90, 120, 150 and 180 min after the start of the OGTT. The ingestion of 6 g C. zeylanicum had no significant effect on glucose level, insulin response, GI or GII. Ingestion of C. zeylanicum does not affect postprandial plasma glucose or insulin levels in human subjects. The Federal Institute for Risk Assessment in Europe has suggested the replacement of C. cassia by C. zeylanicum or the use of aqueous extracts of C. cassia to lower coumarin exposure. However, the positive effects seen with C. cassia in subjects with poor glycaemic control would then be lost.

  6. Plasma cytokines and future risk of non-Hodgkin lymphoma (NHL): a case-control study nested in the Italian European Prospective Investigation into Cancer and Nutrition.

    NARCIS (Netherlands)

    Saberi Hosnijeh, F.; Krop, E.J.M.; Scoccianti, C.; Krogh, V.; Palli, D.; Panico, S.; Tumino, R.; Sacredote, C.; Nawroly, N.; Portengen, L.; Linseisen, J.; Vineis, P.; Vermeulen, R.

    2010-01-01

    BACKGROUND: Recently, biological markers related to the immune system such as cytokines have been studied to further understand the etiology of non-Hodgkin Lymphoma (NHL). However, to date, there are no studies that have studied cytokine levels prospectively in relation to NHL risk in the general po

  7. The effects of honey supplementation on seminal plasma cytokines, oxidative stress biomarkers, and antioxidants during 8 weeks of intensive cycling training.

    Science.gov (United States)

    Tartibian, Bakhtyar; Maleki, Behzad Hajizadeh

    2012-01-01

    The purpose of this study was to examine the effects of natural honey supplementation on seminal plasma cytokines, oxidative stress biomarkers, and antioxidants during 8 weeks of intensive cycling training in male road cyclists. Thirty-nine healthy nonprofessional male road cyclists aged 18-28 years participated in this study. The participants were randomly assigned to exercise + supplement (E + S, n = 20) and exercise (E, n = 19) groups. All subjects participated in 8 weeks of intensive cycling training. Ninety minutes before each training session, subjects in the E + S group supplemented with 70 g of honey, whereas subjects in the E group received 70 g of an artificial sweetener. All subjects had an initial semen sampling at baseline (T(1)). The next 6 semen collections were collected immediately (T(2)) and 12 (T(3)) and 24 hours (T(4)) after the last training session in week 4, as well as immediately (T(5)) and 12 (T(6)) and 24 hours (T(7)) after the last training session in week 8, respectively. In the E group, 8 weeks of intensive cycling training significantly increased seminal interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor (TNF)-α, reactive oxygen species (ROS), and malondialdehyde (MDA) levels (P < .008) and significantly decreased the levels of seminal superoxide dismutase (SOD), catalase, and total antioxidant capacity (TAC) (P < .008). Significantly less elevation in seminal IL-1β, IL-6, IL-8, TNF-α, ROS, and MDA levels (P < .008) and significant increases in seminal SOD, catalase, and TAC concentrations were observed after the honey supplementation in the E + S group (P < .008). It may be possible that honey supplementation following long-term intensive cycling training would be effective in attenuating the probable aggravating effects of intensive cycling training on spermatogenesis and fertility capacity in road cyclists.

  8. Effects of cold atmospheric plasma (CAP on ß-defensins, inflammatory cytokines, and apoptosis-related molecules in keratinocytes in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Stephanie Arndt

    Full Text Available Cold atmospheric plasma (CAP has been gaining increasing interest as a new approach for the treatment of skin diseases or wounds. Although this approach has demonstrated promising antibacterial activity, its exact mechanism of action remains unclear. This study explored in vitro and in vivo whether CAP influences gene expression and molecular mechanisms in keratinocytes. Our results revealed that a 2 min CAP treatment using the MicroPlaSter ß in analogy to the performed clinical studies for wound treatment induces expression of IL-8, TGF-ß1, and TGF-ß2. In vitro and in vivo assays indicated that keratinocyte proliferation, migration, and apoptotic mechanisms were not affected by the CAP treatment under the applied conditions. Further, we observed that antimicrobial peptides of the ß-defensin family are upregulated after CAP treatment. In summary, our results suggest that a 2 min application of CAP induces gene expression of key regulators important for inflammation and wound healing without causing proliferation, migration or cell death in keratinocytes. The induction of ß-defensins in keratinocytes describes an absolutely new plasma strategy. Activation of antimicrobial peptides supports the well-known antibacterial effect of CAP treatment, whereas the mechanism of ß-defensin activation by CAP is not investigated so far.

  9. Effects of cold atmospheric plasma (CAP) on ß-defensins, inflammatory cytokines, and apoptosis-related molecules in keratinocytes in vitro and in vivo.

    Science.gov (United States)

    Arndt, Stephanie; Landthaler, Michael; Zimmermann, Julia L; Unger, Petra; Wacker, Eva; Shimizu, Tetsuji; Li, Yang-Fang; Morfill, Gregor E; Bosserhoff, Anja-Katrin; Karrer, Sigrid

    2015-01-01

    Cold atmospheric plasma (CAP) has been gaining increasing interest as a new approach for the treatment of skin diseases or wounds. Although this approach has demonstrated promising antibacterial activity, its exact mechanism of action remains unclear. This study explored in vitro and in vivo whether CAP influences gene expression and molecular mechanisms in keratinocytes. Our results revealed that a 2 min CAP treatment using the MicroPlaSter ß in analogy to the performed clinical studies for wound treatment induces expression of IL-8, TGF-ß1, and TGF-ß2. In vitro and in vivo assays indicated that keratinocyte proliferation, migration, and apoptotic mechanisms were not affected by the CAP treatment under the applied conditions. Further, we observed that antimicrobial peptides of the ß-defensin family are upregulated after CAP treatment. In summary, our results suggest that a 2 min application of CAP induces gene expression of key regulators important for inflammation and wound healing without causing proliferation, migration or cell death in keratinocytes. The induction of ß-defensins in keratinocytes describes an absolutely new plasma strategy. Activation of antimicrobial peptides supports the well-known antibacterial effect of CAP treatment, whereas the mechanism of ß-defensin activation by CAP is not investigated so far.

  10. Cytokines and T-lymphocyte subsets in healthy post-menopausal women: estrogen retards bone loss without affecting the release of IL-1 or IL-1ra

    DEFF Research Database (Denmark)

    Abrahamsen, Bo; Bendtzen, Klaus; Beck-Nielsen, H

    1997-01-01

    Interleukin (IL)-1 is a potent inducer of bone resorption, and an increased secretion of the IL-1 agonists IL-1 alpha and IL-1 beta relative to the IL-1 receptor antagonist (IL-1ra) has been proposed as a mechanism leading to post-menopausal osteoporosis. T-lymphocytes are capable of secreting bone...... resorptive cytokines and have also been linked with bone metabolism and the development of osteoporosis. Cytokine secretion from whole blood cell cultures was compared between two randomized groups of healthy early post-menopausal women (mean age 52.5 yrs, N = 91) and lymphocyte subsets were quantitated...... by flow cytometry. One group received cyclic estrogen-gestagen replacement therapy (ERT) while the other group was untreated. In spite of a significant bone maintaining effect of ERT, the basal and LPS-stimulated secretion of IL-1 alpha, IL-1 beta, and IL-1ra was identical in the two groups...

  11. [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.

  12. A high intake of industrial or ruminant trans fatty acids does not affect the plasma proteome in healthy men.

    Science.gov (United States)

    de Roos, Baukje; Wanders, Anne J; Wood, Sharon; Horgan, Graham; Rucklige, Garry; Reid, Martin; Siebelink, Els; Brouwer, Ingeborg A

    2011-10-01

    Consumption of industrial trans fat raises the risk of cardiovascular disease, but it is unclear whether cis9,trans11-conjugated linoleic acid (CLA)--a trans fatty acid in dairy products--modulates disease development. We investigated the effects of complete diets providing 7% of energy as industrial trans fat or cis9, trans11 CLA, compared with oleic acid, on regulation of plasma proteins in 12 healthy men. Diets were provided for 3 wk each, in random order. Plasma was collected at the end of each 3 wk intervention period, depleted of its 12 most abundant proteins and analyzed by 2-DE. Principal component analysis of protein spot intensity values revealed that the nature of the dietary intervention did not significantly affect the plasma proteome. The intervention provided in the 1st period produced a significant treatment effect compared with the interventions provided in the other two periods, and there was a significant subject effect. In conclusion, the nature of an extreme dietary intervention, i.e. 7% of energy provided by industrial trans fat or cis9,trans11 CLA, did not markedly affect the plasma proteome. Thus plasma proteomics using 2-DE appears, by and large, an unsuitable approach to detect regulation of plasma proteins due to changes in the diet.

  13. Cytokine-Leukotriene Receptor Interactions

    Directory of Open Access Journals (Sweden)

    Marek Rola-Pleszczynski

    2007-01-01

    Full Text Available Biochemical and pharmacological studies have identified the structure of leukotrienes, the pathways that lead to their synthesis, and the signaling events they trigger when they interact with their cognate receptors. A privileged interaction exists between these lipid mediators and another group of molecules essential for inflammation and immune modulation, namely, cytokines. Whereas leukotrienes can trigger the synthesis and release of selected cytokines in distinct cell populations, many cytokines can affect cellular responsiveness to leukotrienes by modulating leukotriene receptor expression. As we progressively begin to unravel these complex interactions, new areas of cell-cell communication and eventual therapeutic interventions will emerge.

  14. Correlation of plasma cytokine profiles with age, smoking and alcohol drinking behaviors%年龄和烟酒对血浆炎性因子水平的影响

    Institute of Scientific and Technical Information of China (English)

    杨蓬勃; 李捷; 李世超; 陈旭

    2013-01-01

    behaviors.Methods The concentrations of IL-6,IL-10,TNF-alpha and CRP in 350 healthy volunteers,60 cigarette smokers and 65 people with smoking and alcohol drinking behaviors were detected by ELISA.All subjects were grouped by age,gender,smoking and alcohol drinking behavior.The differences in the levels of plasma cytokine profiles among groups were analyzed by statistics software SPSS18.0.Results The concentrations of IL-6 and CRP in 25-39years,40-49 years,50-59 years and over 60 years groups were (1.1±0.7) ng/L,(1.5±0.1) ng/L,(1.7±0.2) ng/L,(2.1±0.1) ng/L and (3.1±1.0) mg/L,(4.4±±0.6) mg/L,(6.2±1.7) mg/L,(8.0±0.8) mg/L,respectively.The concentrations of IL-6 and CRP were significantly increased with age (F=1.60,7.50,P=0.012,0.043),while the concentrations of IL-10 and TNF-alpha were not correlated with age (F=4.20,4.80,P=0.178,0.421).There were no significant differences in the concentrations of IL-6,IL-10,TNF alpha and CRP between males and females (P>0.05).The plasma CRP level was higher in smoking group than in control group [(6.8±0.6) mg/L vs.(3.1± 0.4) mg/L] and was highest in smoking-alcohol group [(9.5±0.5) mg/L vs.(6.8±0.6) mg/L,(3.1±0.4) mg/L,F=8.40,P=0.046].Compared with the control group,IL-6 level was increased and IL-10 level was decreased in smoking group and smoking-alcohol group.There were no significant differences in levels of IL-6,IL-10 and TNF-a among the three groups (F=2.90,4.30,4.80,P=0.089,0.672,1.231).Conclusions The plasma levels of IL-6 and CRP are significantly increased with age,but the plasma levels of IL-10 and TNF-a have no correlations with age.The plasma levels of IL-6,IL-10,TNF-a and CRP are not affected by gender.CRP level is significantly influenced by smoking and alcohol drinking behaviors,which should be taken into consideration to establish the reference values.

  15. Heat Transfer Affected by Transverse Magnetic Field using 3D Modeling of Arc Plasma

    Science.gov (United States)

    Maeda, Yoshifumi; Tanaka, Tatsuro; Yamamoto, Shinji; Iwao, Toru

    2016-10-01

    Gas shielded metal arc welding is used to join the various metal because this is the high quality joining technology. Thus, this welding is used for a welding of large buildings such as bridges and LNG tanks. However, the welding defect caused by the heat transfer decrement may occur with increasing the wind velocity. This is because that the convection loss increases because the arc deflects to leeward side with increasing the wind velocity. In order to prevent from the arc deflection, it is used that the transverse magnetic field is applied to the arc. However, the arc deflection occurs with increasing the transverse magnetic field excessively. The energy balance of the arc is changed with increasing the convection loss caused by the arc deflection, and the heat transfer to the anode decreases. Therefore, the analysis including the arc and anode is necessary to elucidate the heat transfer to the anode. In this paper, the heat transfer affected by the transverse magnetic field using 3D modeling of the arc plasma is elucidated. The heat transfer to the anode is calculated by using the EMTF(electromagnetic thermal fluid) simulation with increasing the transverse magnetic field. As a result, the heat transfer decreased with increasing the transverse magnetic field.

  16. Plasma soluble (pro)renin receptor is independent of plasma renin, prorenin, and aldosterone concentrations but is affected by ethnicity.

    Science.gov (United States)

    Nguyen, Geneviève; Blanchard, Anne; Curis, Emmanuel; Bergerot, Damien; Chambon, Yann; Hirose, Takuo; Caumont-Prim, Aurore; Tabard, Sylvie Brailly; Baron, Stéphanie; Frank, Michael; Totsune, Kazuhito; Azizi, Michel

    2014-02-01

    A soluble (pro)renin receptor (sPRR) circulates in plasma and is able to bind renin and prorenin. It is not known whether plasma sPRR concentrations vary with the activity of the renin-angiotensin system. We measured plasma sPRR, renin, prorenin, and aldosterone concentrations in 121 white and 9 black healthy subjects, 40 patients with diabetes mellitus, 41 hypertensive patients with or without renin-angiotensin system blockers, 9 patients with primary aldosteronism, and 10 patients with Gitelman syndrome. Median physiological plasma sPRR concentration was 23.5 ng/mL (interquartile range, 20.9-26.5) under usual uncontrolled sodium diet. sPRR concentration in healthy subjects, unlike renin and prorenin, did not display circadian variation or dependence on age, sex, posture, or hormonal status. sPRR concentrations were ≈25% lower in black than in white subjects, whereas renin concentrations were ≈40% lower. Patients with diabetes mellitus (average renin-high prorenin levels) and with hypertension only (average renin-average prorenin levels) had sPRR concentrations similar to healthy subjects. Renin-angiotensin system blockade was associated with increase of sPRR concentration by ≈12%. sPRR in patients with primary aldosteronism (low renin-low prorenin) and Gitelman syndrome (high renin-high prorenin) were similar and ≈10% higher than in healthy subjects. There was no correlation between sPRR and renin or prorenin. In conclusion, our results show that plasma sPRR concentrations are dependent on ethnicity and independent of renin, prorenin, and aldosterone concentrations in healthy subjects and in patients with contrasted degrees of renin-angiotensin system activity.

  17. Dietary fructooligosaccharides and transgalactooligosaccharides can affect fermentation characteristics in gut contents and portal plasma of growing pigs

    NARCIS (Netherlands)

    Houdijk, J.G.M.; Verstegen, M.W.A.; Bosch, M.W.; Laere, van K.J.M.

    2002-01-01

    We studied whether dietary non-digestible oligosaccharides (NDOs) affected pH and volatile fatty acids (VFAs) in gastrointestinal contents and in portal plasma of young pigs. Five groups of five 57-day-old pigs received for 44 days either a corn-based control diet or this diet with 7.5 or 15 g/kg fr

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

    DEFF Research Database (Denmark)

    Bygbjerg, I C; Hansen, M B; Rønn, A M;

    1997-01-01

    The levels of coagulation factors II + VII + X and of blood platelets (thrombocytes) as well as of cytokines and soluble cytokine receptors were studied in the patients with malaria or meningococcal infections. The coagulation factors were decreased particularly in the meningococcal patients, while...... necrosis factor-I (sTNF-RI) in patients with malaria and meningococcal infections. Elevated sIL-2R and sTNF-RI levels and decreased coagulation factors reverted to normal within 3-5 days after initiation of therapy in P. falciparum patients followed consecutively. Estimation of coagulation factors may...

  19. RNAi-mediated downregulation of poplar plasma membrane intrinsic proteins (PIPs) changes plasma membrane proteome composition and affects leaf physiology.

    Science.gov (United States)

    Bi, Zhen; Merl-Pham, Juliane; Uehlein, Norbert; Zimmer, Ina; Mühlhans, Stefanie; Aichler, Michaela; Walch, Axel Karl; Kaldenhoff, Ralf; Palme, Klaus; Schnitzler, Jörg-Peter; Block, Katja

    2015-10-14

    Plasma membrane intrinsic proteins (PIPs) are one subfamily of aquaporins that mediate the transmembrane transport of water. To reveal their function in poplar, we generated transgenic poplar plants in which the translation of PIP genes was downregulated by RNA interference investigated these plants with a comprehensive leaf plasma membrane proteome and physiome analysis. First, inhibition of PIP synthesis strongly altered the leaf plasma membrane protein composition. Strikingly, several signaling components and transporters involved in the regulation of stomatal movement were differentially regulated in transgenic poplars. Furthermore, hormonal crosstalk related to abscisic acid, auxin and brassinosteroids was altered, in addition to cell wall biosynthesis/cutinization, the organization of cellular structures and membrane trafficking. A physiological analysis confirmed the proteomic results. The leaves had wider opened stomata and higher net CO2 assimilation and transpiration rates as well as greater mesophyll conductance for CO2 (gm) and leaf hydraulic conductance (Kleaf). Based on these results, we conclude that PIP proteins not only play essential roles in whole leaf water and CO2 flux but have important roles in the regulation of stomatal movement.

  20. Physical activity affects plasma coenzyme Q10 levels differently in young and old humans.

    Science.gov (United States)

    Del Pozo-Cruz, Jesús; Rodríguez-Bies, Elisabet; Ballesteros-Simarro, Manuel; Navas-Enamorado, Ignacio; Tung, Bui Thanh; Navas, Plácido; López-Lluch, Guillermo

    2014-04-01

    Coenzyme Q (Q) is a key lipidic compound for cell bioenergetics and membrane antioxidant activities. It has been shown that also has a central role in the prevention of oxidation of plasma lipoproteins. Q has been associated with the prevention of cholesterol oxidation and several aging-related diseases. However, to date no clear data on the levels of plasma Q during aging are available. We have measured the levels of plasmatic Q10 and cholesterol in young and old individuals showing different degrees of physical activity. Our results indicate that plasma Q10 levels in old people are higher that the levels found in young people. Our analysis also indicates that there is no a relationship between the degree of physical activity and Q10 levels when the general population is studied. However, very interestingly, we have found a different tendency between Q10 levels and physical activity depending on the age of individuals. In young people, higher activity correlates with lower Q10 levels in plasma whereas in older adults this ratio changes and higher activity is related to higher plasma Q10 levels and higher Q10/Chol ratios. Higher Q10 levels in plasma are related to lower lipoperoxidation and oxidized LDL levels in elderly people. Our results highlight the importance of life habits in the analysis of Q10 in plasma and indicate that the practice of physical activity at old age can improve antioxidant capacity in plasma and help to prevent cardiovascular diseases.

  1. Does Toxoplasma gondii Infection Affect the Levels of IgE and Cytokines (IL-5, IL-6, IL-10, IL-12, and TNF-alpha?

    Directory of Open Access Journals (Sweden)

    Joanna Matowicka-Karna

    2009-01-01

    Full Text Available In the study performed in a group of patients infected with T. gondii, we evaluated Th2 humoral response (IL-5, IL-6, IL-10 and Th1 cell response (IL-12, TNF-α. The study objective was to assess the effect of T. gondii on chosen indices of the immune response. The study involved 52 women infected with T. gondii (aged 18–42 years prior to antiparasitic treatment. In all the patients, we found IgM (index >0.7 and IgG which exceeded 300 IU/ml. The control group (C consisted of 40 healthy women aged 18–46 years. In the study group (T and in the control group (C, the levels of IgE, IL-5, IL-6, IL-10, IL-12, and TNF-α were determined. In our study, T. gondii patients had twofold higher levels of IL-5 and IL-6 as compared to healthy subjects, which seems to confirm the presence of an inflammatory state. We found the level of IL-10 to be fivefold higher in the course of toxoplasmosis than in healthy controls. The levels of IL-12 and TNF-α were comparable to those observed in healthy controls. The study has revealed that that patients infected with T. gondii show increased production of the humoral response cytokines, whereas the generation of the cell response cytokines remains unchanged.

  2. Seminal plasma applied post-thawing affects boar sperm physiology: a flow cytometry study.

    Science.gov (United States)

    Fernández-Gago, Rocío; Domínguez, Juan Carlos; Martínez-Pastor, Felipe

    2013-09-01

    Cryopreservation induces extensive biophysical and biochemical changes in the sperm. In the present study, we used flow cytometry to assess the capacitation-like status of frozen-thawed boar spermatozoa and its relationship with intracellular calcium, assessment of membrane fluidity, modification of thiol groups in plasma membrane proteins, reactive oxygen species (ROS) levels, viability, acrosomal status, and mitochondrial activity. This experiment was performed to verify the effect of adding seminal plasma on post-thaw sperm functions. To determine these effects after cryopreservation, frozen-thawed semen from seven boars was examined after supplementation with different concentrations of pooled seminal plasma (0%, 10%, and 50%) at various times of incubation from 0 to 4 hours. Incubation caused a decrease in membrane integrity and an increase in acrosomal damage, with small changes in other parameters (P > 0.05). Although 10% seminal plasma showed few differences with 0% (ROS increase at 4 hours, P boar spermatozoa, possibly through membrane changes and ROS increase. Although some effects were detrimental, the stimulatory effect of 50% seminal plasma could favor the performance of post-thawed boar semen, as showed in the field (García JC, Domínguez JC, Peña FJ, Alegre B, Gonzalez R, Castro MJ, Habing GG, Kirkwood RN. Thawing boar semen in the presence of seminal plasma: effects on sperm quality and fertility. Anim Reprod Sci 2010;119:160-5).

  3. Cytokines gene expression in newly diagnosed multiple sclerosis patients.

    OpenAIRE

    Seyed Javad Hasheminia; Sepideh Tolouei; Sayyed Hamid Zarkesh-Esfahani; Vahid Shaygannejad; Hedaiat Allah Shirzad; Reza Torabi; Morteza Hashem Zadeh Chaloshtory

    2015-01-01

    Multiple Sclerosis (MS) is characterized by multiple areas of inflammation, demyelination and neurodegeneration. Infiltrating Th1 CD4+ T cells secrete proinflammatory cytokines. They stimulate the release of some cytokines, expression of adhesion molecules and these cytokines may cause damage to the myelin sheath and axons. In this study, we analyzed plasma levels and gene expressions of five important cytokines in the new diagnosed MS Patients by ELISA and Real time PCR. PCR amplifications w...

  4. Thrombolytic therapy reduces red blood cell aggregation in plasma without affecting intrinsic aggregability.

    Science.gov (United States)

    Ben-Ami, R; Sheinman, G; Yedgar, S; Eldor, A; Roth, A; Berliner, A S; Barshtein, G

    2002-03-15

    Red blood cell (RBC) aggregation may contribute to occlusion of the coronary microcirculation during myocardial infarction. We studied the effect of thrombolytic therapy on RBC aggregation in patients with acute myocardial infarction (AMI). Compared with patients with myocardial infarction who did not receive thrombolytic therapy, those treated with systemic thrombolysis exhibited significantly reduced RBC aggregation, reduced plasma fibrinogen levels and increased plasma D-dimer levels. Using measurement of RBC aggregation in a standardized dextran-500 solution, reduction in RBC aggregation after thrombolysis was shown to be plasma dependent. Thrombolytic therapy had no direct effect on intrinsic RBC aggregability in patients with AMI. We conclude that thrombolytic therapy has rheologic consequences that may contribute to its overall efficacy. Inhibition of RBC aggregation by thrombolytic therapy may result from the degradation of fibrinogen, a key factor in the formation of RBC aggregates, and from the generation of fibrinogen degradation products capable of disaggregating RBCs.

  5. Proteomic analysis of seminal plasma from asthenozoospermia patients reveals proteins that affect oxidative stress responses and semen quality.

    Science.gov (United States)

    Wang, Jun; Wang, Jian; Zhang, Hua-Rong; Shi, Hui-Juan; Ma, Duan; Zhao, Hong-Xin; Lin, Biaoyang; Li, Run-Sheng

    2009-07-01

    Asthenozoospermia (AS) is a common cause of human male infertility. In one study, more than 80% of the samples from infertile men had reduced sperm motility. Seminal plasma is a mixture of secretions from the testis, epididymis and several male accessory glands, including the prostate, seminal vesicles and Cowper's gland. Studies have shown that seminal plasma contains proteins that are important for sperm motility. To further explore the pathophysiological character of AS, we separated the seminal plasma proteins from AS patients and healthy donors using sodium dodecyl sulfate polyacrylamide gel electrophoresis and in-gel digestion, and then subjected the proteins to liquid chromatography-mass spectrometry (LC-MS/MS) analysis. A total of 741 proteins were identified in the seminal plasma, with a false discovery rate of 3.3%. Using spectral counting, we found that 45 proteins were threefold upregulated and 56 proteins were threefold downregulated in the AS group when compared with the control. Most of these proteins originated from the epididymis and prostate. This study identified a rich source of biomarker candidates for male infertility and indicates that functional abnormalities of the epididymis and prostate can contribute to AS. We identified DJ-1-a protein that has been shown elsewhere to be involved in the control of oxidative stress (OS)-as a downregulated protein in AS seminal plasma. The levels of DJ-1 in AS seminal plasma were about half of those in the control samples. In addition, the levels of reactive oxygen species were 3.3-fold higher in the AS samples than in the controls. Taken together, these data suggest that downregulation of DJ-1 is involved in OS in semen, and therefore affects the quality of the semen.

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

    Directory of Open Access Journals (Sweden)

    Eliza Turlej

    2009-05-01

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

  7. Cold plasma inactivates salmonella on grape tomatoes in a commercial PET plastic container without affecting quality

    Science.gov (United States)

    Introduction: The number of outbreaks of foodborne illnesses associated with the consumption of fresh tomatoes has increased. Little research has been conducted on the effects of direct treatment of cold plasma (CP) on the microbial decontamination and preservation of bulk tomatoes packaged in comme...

  8. Phenylbutyrate reduces plasma leucine concentrations without affecting the flux of leucine

    Science.gov (United States)

    Phenylbutyrate (PB) has been used as an alternative pathway to excrete nitrogen in urea cycle disorder patients for the last 20 years. PB, after oxidation to phenylacetate, is conjugated with glutamine and excreted in the urine. A reduction in the plasma concentration of branched amino acids (BCAA) ...

  9. Cytokine Gene Polymorphisms support diagnostic monitoring of Romanian Multiple Myeloma patients

    OpenAIRE

    2011-01-01

    Introduction: cytokines and their receptor genes are very polymorphic. SNPs in the promotor region of the gene may influence the rate of cytokine secretion and may affect the biological activity of the encoded cytokine. A number of cytokines and cytokine receptors have been directly linked to the development of human cancers. The aim of our study was to determine the cytokine gene polymorphism in Romanian multiple myeloma patients. Material and methods: cytokine genotyping was performed in 80...

  10. Effects of peripheral blood stem cell apheresis on systemic cytokine levels in patients with multiple myeloma.

    Science.gov (United States)

    Akkök, Ciğdem Akalin; Hervig, Tor; Stamnesfet, Siren; Nesthus, Ingerid; Melve, Guro K; Lassalle, Philippe; Bruserud, Oystein

    2011-11-01

    BACKGROUND AIMS. Pro-angiogenic cytokines can affect myeloma cell proliferation directly and indirectly through stimulation of cancer-associated angiogenesis. METHODS. We investigated how peripheral blood stem cell (PBSC) collection affected plasma angioregulatory cytokine levels in 15 consecutive myeloma patients. RESULTS. Plasma levels of hepatocyte growth factor (HGF) were significantly increased prior to apheresis in patients compared with donors, and a further increase was detected immediately after PBSC apheresis. HGF levels decreased within 24 h, but were still higher than the levels in healthy donors, whose HGF levels were not altered by platelet apheresis. Pre-apheresis levels of other angioregulatory cytokines, angiopoietin-2 and vascular endothelial growth factor (VEGF), were also increased in patients, whereas angiopoietin-1, angiogenin and basic fibroblast growth factor levels did not differ from healthy controls. PBSC harvesting decreased angiopoietin-1 and VEGF levels, increased the microvascular endothelial cell marker endocan levels but did not affect the other mediators. CONCLUSIONS. Our results show that PBSC apheresis alters systemic angioregulatory profiles in myeloma patients. This cytokine modulation is not a general characteristic of all apheresis procedures and was not seen in healthy platelet donors.

  11. MHC class II super-enhancer increases surface expression of HLA-DR and HLA-DQ and affects cytokine production in autoimmune vitiligo.

    Science.gov (United States)

    Cavalli, Giulio; Hayashi, Masahiro; Jin, Ying; Yorgov, Daniel; Santorico, Stephanie A; Holcomb, Cherie; Rastrou, Melinda; Erlich, Henry; Tengesdal, Isak W; Dagna, Lorenzo; Neff, C Preston; Palmer, Brent E; Spritz, Richard A; Dinarello, Charles A

    2016-02-02

    Genetic risk for autoimmunity in HLA genes is most often attributed to structural specificity resulting in presentation of self-antigens. Autoimmune vitiligo is strongly associated with the MHC class II region. Here, we fine-map vitiligo MHC class II genetic risk to three SNPs only 47 bp apart, located within a predicted super-enhancer in an intergenic region between HLA-DRB1 and HLA-DQA1, localized by a genome-wide association study of 2,853 Caucasian vitiligo patients. The super-enhancer corresponds to an expression quantitative trait locus for expression of HLA-DR and HLA-DQ RNA; we observed elevated surface expression of HLA-DR (P = 0.008) and HLA-DQ (P = 0.02) on monocytes from healthy subjects homozygous for the high-risk SNP haplotype. Unexpectedly, pathogen-stimulated peripheral blood mononuclear cells from subjects homozygous for the high-risk super-enhancer haplotype exhibited greater increase in production of IFN-γ and IL-1β than cells from subjects homozygous for the low-risk haplotype. Specifically, production of IFN-γ on stimulation of dectin-1, mannose, and Toll-like receptors with Candida albicans and Staphylococcus epidermidis was 2.5- and 2.9-fold higher in high-risk subjects than in low-risk subjects, respectively (P = 0.007 and P = 0.01). Similarly, production of IL-1β was fivefold higher in high-risk subjects than in low-risk subjects (P = 0.02). Increased production of immunostimulatory cytokines in subjects carrying the high-risk haplotype may act as an "adjuvant" during the presentation of autoantigens, tying together genetic variation in the MHC with the development of autoimmunity. This study demonstrates that for risk of autoimmune vitiligo, expression level of HLA class II molecules is as or more important than antigen specificity.

  12. Suppressor of cytokine signaling 2 (SOCS2) negatively regulates the expression of antimicrobial peptides by affecting the Stat transcriptional activity in shrimp Marsupenaeus japonicus.

    Science.gov (United States)

    Sun, Jie-Jie; Lan, Jiang-Feng; Xu, Ji-Dong; Niu, Guo-Juan; Wang, Jin-Xing

    2016-09-01

    The suppressor of cytokine signaling (SOCS) family is a kind of negative regulators in the Janus kinase/signal transducer and activator of transcription (Jak/Stat) pathway in mammals and Drosophila. In kuruma shrimp, Marsupenaeus japonicus, SOCS2 is identified and its expression can be stimulated by peptidoglycan and polycytidylic acid. However, if SOCS2 participates in regulating Jak/Stat pathway in shrimp still needs further study. In this study, SOCS2 with Src homology 2 domain and SOCS box was identified in kuruma shrimp, M. japonicus. SOCS2 existed in hemocytes, heart, hepatopancreas, gills, stomach, and intestine, the expression of SOCS2 was upregulated significantly in the hemocytes and intestine of shrimp challenged with Vibrio anguillarum at 6 h. To analyze SOCS2 function in shrimp immunity, bacterial clearance and survival rate were analyzed after knockdown of SOCS2 in shrimp challenged with V. anguillarum. Results showed that bacterial clearance increased, and the survival rate improved significantly comparing with controls. The SOCS2 was expressed in Escherichia coli and the recombinant SOCS2 was injected into shrimp, and Stat phosphorylation and translocation were analyzed. The result showed that "overexpression" of SOCS2 declined Stat phosphorylation level and inhibited Stat translocation into the nucleus. After knockdown of SOCS2 in shrimp prior to V. anguillarum infection, the expression level of antimicrobial peptides, including anti-lipopolysaccharide factors C1, C2 and D1, and Crustin I was upregulated significantly, and the expression of the AMPs was declined after recombinant SOCS2 injection. The SOCS2 expression was also decreased in Stat-knockdown shrimp challenged by V. anguillarum at 6 and 12 h. Therefore, SOCS2 negatively regulates the AMP expression by inhibiting Stat phosphorylation and translocation into nucleus in shrimp, meanwhile, SOCS2 expression was also regulated by Jak/Stat pathway.

  13. Fish oil affects blood pressure and the plasma lipid profile in healthy Danish infants

    DEFF Research Database (Denmark)

    Damsgaard, C.T.; Schack-Nielsen, L.; Michaelsen, K.F.;

    2006-01-01

    Animal and epidemiologic studies indicate that early nutrition has lasting effects on metabolism and cardiovascular disease risk. In adults, (n-3) long-chain PUFA (LCPUFA) from fish oils improve blood pressure, the lipid profile, and possibly cardiovascular disease mortality. This randomized trial...... with an oscillometric device, and blood was sampled for analysis of erythrocyte fatty acid composition and the plasma lipid profile. This paper examines the effects of the fish oil supplement, with adjustment for the effects of the milk intervention when relevant. The fish oil intervention increased erythrocyte (n-3.......04) than infants not administered fish oil. Plasma triacylglycerol was inversely associated with the erythrocyte content of eicosapentaenoic acid (r = 0.34, P

  14. Long-term high fructose and saturated fat diet affects plasma fatty acid profile in rats

    Institute of Scientific and Technical Information of China (English)

    Fabrice TRANCHIDA; Léopold TCHIAKPE; Zo RAKOTONIAINA; Valérie DEYRIS; Olivier RAVION; Abel HIOL

    2012-01-01

    As the consumption of fructose and saturated fatty acids (FAs) has greatly increased in western diets and is linked with an increased risk of metabolic syndrome,the aim of this study was to investigate the effects of a moderate (10 weeks) and a prolonged (30 weeks) high fructose and saturated fatty acid (HFS) diet on plasma FA composition in rats.The effects of a few weeks of HFS diet had already been described,but in this paper we tried to establish whether these effects persist or if they are modified after 10 or 30 weeks.We hypothesized that the plasma FA profile would be altered between 10 and 30 weeks of the HFS diet.Rats fed with either the HFS or a standard diet were tested after 10 weeks and again after 30 weeks.After 10 weeks of feeding,HFS-fed rats developed the metabolic syndrome,as manifested by an increase in fasting insulinemia,total cholesterol and triglyceride levels,as well as by impaired glucose tolerance.Furthermore,the plasma FA profile of the HFS group showed higher proportions of monounsaturated FAs like palmitoleic acid [16:1(n-7)] and oleic acid [18:1(n-9)],whereas the proportions of some polyunsaturated n-6 FAs,such as linoleic acid [18:2(n-6)] and arachidonic acid [20:4(n-6)],were lower than those in the control group.After 30 weeks of the HFS diet,we observed changes mainly in the levels of 16:1(n-7) (decreased)and 20:4(n-6) (increased).Together,our results suggest that an HFS diet could lead to an adaptive response of the plasma FA profile over time,in association with the development of the metabolic syndrome.

  15. Robust computational method for fast calculations of multicharged ions lineshapes affected by a low-frequency electrostatic plasma turbulence

    Science.gov (United States)

    Dalimier, E.; Oks, E.

    2017-01-01

    Transport phenomena in plasmas, such as, e.g., resistivity, can be affected by electrostatic turbulence that frequently occurs in various kinds of laboratory and astrophysical plasmas. Transport phenomena are affected most significantly by a low-frequency electrostatic turbulence—such as, e.g., ion acoustic waves, also known as ionic sound—causing anomalous resistivity. In this case, for computing profiles of spectral lines, emitted by plasma ions, by any appropriate code for diagnostic purposes, it is necessary to calculate the distribution of the total quasistatic field. For a practically important situation, where the average turbulent field is much greater than the characteristic ion microfield, we develop a robust computational method valid for any appropriate distribution of the ion microfield at a charged point. We show that the correction to the Rayleigh distribution of the turbulent field is controlled by the behavior of the ion microfield distribution at large fields—in distinction to the opposite (and therefore, erroneous) result in the literature. We also obtain a universal analytical expression for the correction to the Rayleigh distribution based on the asymptotic of the ion microfield distribution at large fields at a charged point. By comparison with various known distributions of the ion microfield, we show that our asymptotic formula has a sufficiently high accuracy. Also exact computations are used to verify the high accuracy of the method. This robust approximate, but accurate method yields faster computational results than the exact calculations and therefore should be important for practical situations requiring simultaneous computations of a large number of spectral lineshapes (e.g., for calculating opacities)—especially for laser-produced plasmas.

  16. The amount of macrophages and activated plasma cells on wound healing process affected by spirulina

    Directory of Open Access Journals (Sweden)

    Regina Purnama Dewi Iskandar

    2015-12-01

    Full Text Available Background: Spirulina which grows abundantly in tropical seas have been investigated to enhance immune system. The administration of spirulina in tooth extraction sockets was expected to optimise the function of immunocompetent cells. Therefore, wound healing process would be improved. Purpose: The aim of this study was to prove that administration of spirulina could influence immune system in tooth extraction sockets. Method: There were 28 Cavia cobayas used in this study and were put in group of four. Mandibular left incisive were extracted from each of them. The basis made from mixture of polyethylene glycol (PEG 400 and PEG 4000 was administrated into each socket in control group (TG0. In addition, spirulina 12% was administrated into group TG1, spirulina 24% was administrated into group TG2, and spirulina 48% was administrated into group TG3. All of the Cavia cobaya were decapitated and the jaws were removed in day 5 after tooth extraction. The jaws were decalcified in EDTA solution, formed into paraffin block, processed for hematoxylin and eosin (H & E and immunohistochemistry staining afterwards. Datas were analysed statistically using Anova method. Result: There was an augmentation in the number of macrophages and activated plasma cells after spirulina application. The administration of higher concentrations of Spirulina leads to greater amount of macrophages and activated plasma cells in each groups. Conclusion: In conclusion, spirulina is able to increase the amount of macrophages and activated plasma cells which play important role in healing process.

  17. Cytokines as cellular communicators

    Directory of Open Access Journals (Sweden)

    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.

  18. No early effect of storage time of transfused red blood cells on fatigue and plasma cytokines in patients with anaemia from non-acute gastrointestinal bleeding

    DEFF Research Database (Denmark)

    Mynster, Tommie; Dziegiel, Morten H; Kofoed, Kristian

    2007-01-01

    Background: Fatigue in anaemia is empirically reduced by blood transfusion. Long storage time of red cells may be associated with immunomodulatory effects, and blood stored for a long time may cause tissue hypoxia upon transfusion. Patients and Methods: 22 patients admitted with haemoglobin ... (nsSL). Beside increase in haemoglobin the only significant change in blood parameters after transfusion was a decrease in thrombocyte count (nsSL). No significant differences were seen in concentrations of cytokines before and after transfusion. Conclusion: Transfusion of two units of red cells...... relieved self-estimated fatigue, independent of blood storage time. Thrombocyte count decreased after transfusion, probably due to dilution by transfused blood. Aged red cells may not, or only sparsely, directly trigger the interleukin cascade....

  19. The effect of recombinant erythropoietin on plasma brain derived neurotrophic factor levels in patients with affective disorders

    DEFF Research Database (Denmark)

    Vinberg, Maj; Miskowiak, Kamilla; Hoejman, Pernille

    2015-01-01

    UNLABELLED: The study aims to investigate the effect of repeated infusions of recombinant erythropoietin (EPO) on plasma brain derived neurotrophic factor (BDNF) levels in patients with affective disorders. In total, 83 patients were recruited: 40 currently depressed patients with treatment......-resistant depression (TRD) (Hamilton Depression Rating Scale-17 items (HDRS-17) score >17) (study 1) and 43 patients with bipolar disorder (BD) in partial remission (HDRS-17 and Young Mania Rating Scale (YMRS) ≤ 14) (study 2). In both studies, patients were randomised to receive eight weekly EPO (Eprex; 40,000 IU...

  20. Glycosaminoglycans affect the interaction of human plasma kallikrein with plasminogen, factor XII and inhibitors

    Directory of Open Access Journals (Sweden)

    Gozzo A.J.

    2003-01-01

    Full Text Available Human plasma kallikrein, a serine proteinase, plays a key role in intrinsic blood clotting, in the kallikrein-kinin system, and in fibrinolysis. The proteolytic enzymes involved in these processes are usually controlled by specific inhibitors and may be influenced by several factors including glycosaminoglycans, as recently demonstrated by our group. The aim of the present study was to investigate the effect of glycosaminoglycans (30 to 250 µg/ml on kallikrein activity on plasminogen and factor XII and on the inhibition of kallikrein by the plasma proteins C1-inhibitor and antithrombin. Almost all available glycosaminoglycans (heparin, heparan sulfate, bovine and tuna dermatan sulfate, chondroitin 4- and 6-sulfates reduced (1.2 to 3.0 times the catalytic efficiency of kallikrein (in a nanomolar range on the hydrolysis of plasminogen (0.3 to 1.8 µM and increased (1.9 to 7.7 times the enzyme efficiency in factor XII (0.1 to 10 µM activation. On the other hand, heparin, heparan sulfate, and bovine and tuna dermatan sulfate improved (1.2 to 3.4 times kallikrein inhibition by antithrombin (1.4 µM, while chondroitin 4- and 6-sulfates reduced it (1.3 times. Heparin and heparan sulfate increased (1.4 times the enzyme inhibition by the C1-inhibitor (150 nM.

  1. Factors affecting the microstructural stability and durability of thermal barrier coatings fabricated by air plasma spraying

    Energy Technology Data Exchange (ETDEWEB)

    Helminiak, M.A.; Yanar, N.M.; Pettit, F.S.; Meier, G.H. [National Energy Technology Laboratory, Pittsburgh, PA 15236 (United States); Department of Mechanical Engineering and Materials Science, University of Pittsburgh, 636 Benedum Hall, 3700 O& #x27; Hara Street, Pittsburgh, PA 15261 (United States); Taylor, T.A. [Praxair Surface Technologies, Inc., 1400 Polco Street, Indianapolis, IN 46224 (United States)

    2012-10-15

    The high-temperature behavior of high-purity, low-density (HP-LD) air plasma sprayed (APS) thermal barrier coatings (TBCs) with NiCoCrAlY bond coats deposited by argon-shrouded plasma spraying is described. The high purity yttria-stabilized zirconia resulted in top coats which are highly resistant to sintering and transformation from the metastable tetragonal phase to the equilibrium mixture of monoclinic and cubic phases. The thermal conductivity of the as-processed TBC is low but increases during high temperature exposure even before densification occurs. The porous topcoat microstructure also resulted in good spallation resistance during thermal cycling. The actual failure mechanisms of the APS coatings were found to depend on topcoat thickness, topcoat density, and the thermal cycle frequency. The failure mechanisms are described and the durability of the HP-LD coatings is compared with that of state-of-the-art electron beam physical vapor deposition TBCs. (Copyright copyright 2012 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  2. The impact of acute stress on hormones and cytokines, and how their recovery is affected by music-evoked positive mood.

    Science.gov (United States)

    Koelsch, Stefan; Boehlig, Albrecht; Hohenadel, Maximilian; Nitsche, Ines; Bauer, Katrin; Sack, Ulrich

    2016-03-29

    Stress and recovery from stress significantly affect interactions between the central nervous system, endocrine pathways, and the immune system. However, the influence of acute stress on circulating immune-endocrine mediators in humans is not well known. Using a double-blind, randomized study design, we administered a CO2 stress test to n = 143 participants to identify the effects of acute stress, and recovery from stress, on serum levels of several mediators with immune function (IL-6, TNF-α, leptin, and somatostatin), as well as on noradrenaline, and two hypothalamic-pituitary-adrenal axis hormones (ACTH and cortisol). Moreover, during a 1 h-recovery period, we repeatedly measured these serum parameters, and administered an auditory mood-induction protocol with positive music and a neutral control stimulus. The acute stress elicited increases in noradrenaline, ACTH, cortisol, IL-6, and leptin levels. Noradrenaline and ACTH exhibited the fastest and strongest stress responses, followed by cortisol, IL-6 and leptin. The music intervention was associated with more positive mood, and stronger cortisol responses to the acute stressor in the music group. Our data show that acute (CO2) stress affects endocrine, immune and metabolic functions in humans, and they show that mood plays a causal role in the modulation of responses to acute stress.

  3. 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.

  4. An apolipoprotein E4 fragment affects matrix metalloproteinase 9, tissue inhibitor of metalloproteinase 1 and cytokine levels in brain cell lines.

    Science.gov (United States)

    Dafnis, I; Tzinia, A K; Tsilibary, E C; Zannis, V I; Chroni, A

    2012-05-17

    Apolipoprotein (apo) E4 isoform, a major risk factor for Alzheimer disease (AD), is more susceptible to proteolysis than apoE2 and apoE3 isoforms. ApoE4 fragments have been found in AD patients' brain. In the present study, we examined the effect of full-length apoE4 and apoE4 fragments apoE4[Δ(186-299)] and apoE4[Δ(166-299)] on inflammation in human neuroblastoma SK-N-SH and human astrocytoma SW-1783 cells. Western blot and zymography analysis showed that treatment of SK-N-SH cells with apoE4[Δ(186-299)], but not full-length apoE4 or the shorter apoE4[Δ(166-299)] fragment, leads to increased extracellular levels of matrix metalloproteinase 9 (MMP9) and tissue inhibitor of metalloproteinase 1 (TIMP1). Real-time PCR showed that interleukin (IL)-1β gene expression is also increased in SK-N-SH cells treated with apoE4[Δ(186-299)]. Treatment of SK-N-SH cells with IL-1β leads to increased MMP9 and TIMP1 extracellular levels, suggesting that the induction of IL-1β may be the mechanism by which apoE4[Δ(186-299)] regulates MMP9 and TIMP1 levels in these cells. In contrast to SK-N-SH cells, treatment of SW-1783 cells with apoE4[Δ(186-299)], and to a lesser extent with apoE4, leads to increased TIMP1 extracellular levels without affecting MMP9 levels. Additionally, apoE4[Δ(186-299)] leads to decreased IL-10 gene expression in SK-N-SH cells, whereas both apoE4 and apoE4[Δ(186-299)] lead to decreased TNFα gene expression without affecting IL-1β and IL-10 gene expression in SW-1783 cells. Overall, our findings indicate that a specific apoE4 fragment (apoE4[Δ(186-299)]), with molecular mass similar that of apoE4 fragments detected in AD patients' brain, can influence the level of inflammatory molecules in brain cell lines. It is possible that these phenomena contribute to AD pathogenesis.

  5. Cheddar cheese ripening affects plasma nonesterified fatty acids and serum insulin concentrations in growing pigs

    DEFF Research Database (Denmark)

    Thorning, Tanja Kongerslev; Bendsen, Nathalie T; Jensen, Søren Krogh

    2015-01-01

    by means of a porcine model how cheeses with different ripening times affect blood glucose, insulin, and lipid concentrations and fecal-fat excretion. Methods: A parallel-arm randomized intervention study with 36 Landrace × Yorkshire × Duroc crossbred 3-mo-old female pigs was conducted. The pigs were fed...... resistance was lower in the 24-MRC diet group (0.030 ± 0.003) than in the 4-MRC diet group (0.041 ± 0.005; P growing pigs...

  6. The cytokines (IFN-gamma, IL-2, IL-4, IL-10, IL-17) and Treg cytokine (TGF-beta1) levels in adults with immune thrombocytopenia.

    Science.gov (United States)

    Ma, Liangliang; Liang, Yan; Fang, Meiyun; Guan, Yanchun; Si, Yang; Jiang, Feng; Wang, Fangting

    2014-09-01

    Previous studies have indicated that autoimmune diseases might be caused by an imbalance of T helper cells (Th), cytokines, and regulatory T cells (Treg) cytokines. We measured the plasma concentrations of Th1-associated cytokines (IFN-gamma, IL-2), Th2 -associated cytokines (IL-4, IL-10), Th17-associated cytokine (IL-17) and Treg -associated cytokine (TGF-beta1) in adult patients with immune thrombocytopenia (ITP) and evaluated their clinical relevance. Plasma IFN-gamma, IL-2, IL-4, IL-10, IL-17 and TGF-beta1 concentrations of 52 ITP patients and 30 age- and sex-matched healthy controls were measured by enzyme-linked immunosorbent assay method (ELISA). Concentration of Th2 cytokines (IL-4 and IL-10) were significantly higher in ITP patients compared to controls (P cytokines (IFN-gamma, IL-2), Th17 cytokine (IL-17) and Treg cytokine (TGF-beta1) were lower in ITP patients (P cytokine concentration among the other subgroups in ITP patients was found. Among the ITP patients, concentration of IFN-gamma correlated positively and significantly with PAIgG (r = 0.48, P = 0.02). A significant correlation was neither found between other cytokine levels and platelet count, nor between cytokine levels and megakaryocytes number, nor between cytokines levels and PAIgG or GPIIb/IIIa and/or GPIb/IX autoantibodies. The present study demonstrates that an imbalance of Th and Treg cytokines may mediate the pathogenesis of ITP.

  7. YKL-40 Gene Expression and Plasma Levels of CD30 are not Affected by Isoflurane or Propofol: Pilot Study

    Directory of Open Access Journals (Sweden)

    Shirin Lak

    2016-10-01

    Full Text Available Background: It has been hypothesized that the body's response to anesthesia techniques can increase risk of cancer recurrence and metastatic disease after surgery and also can modulate immune responses. Some acute inflammatory markers have been measured to survey the immunomodulatory effect of anesthesia, but in this research, we studied the plasma level of CD30 and YKL-40 gene expression which can present major changes of the immune system.Materials and Methods: Our study was a controlled before and after study. 34 women with biopsy-proven breast cancer were randomized to receive either propofol general anesthesia (n=17 or standard isoflurane general anesthesia (n=17. There were no significant differences between the two patient groups in age, body weight, and height, length of general anesthesia, operative time and group of surgery. The blood samples were collected in two different sets, before anesthesia and 72-h postoperatively. Soluble CD30 (sCD30 plasma level was measured by ELISA and YKL-40/CHI3L1 gene expression was evaluated by real-time-PCR.Results: The results showed that the anesthetics, propofol and isoflurane, have no effect on the expression of YKL-40. Despite increased in the expression of YKL-40 that was observed in patients receiving isoflurane, this increase was not statistically significant. There was no significant increase or decrease in plasma concentrations of sCD30.Conclusion: YKL-40 and sCD30 are not affected by isoflurane or propofol.  So, in immunological perspective, there is no preference in use of isoflurane or propofol in breast cancer patients.

  8. Eosinophil secretion of granule-derived cytokines

    Directory of Open Access Journals (Sweden)

    Lisa A Spencer

    2014-10-01

    Full Text Available Eosinophils are tissue-dwelling leukocytes, present in the thymus, and gastrointestinal and genitourinary tracts of healthy individuals at baseline, and recruited, often in large numbers, to allergic inflammatory foci and sites of active tissue repair. The biological significance of eosinophils is vast and varied. In health, eosinophils support uterine and mammary gland development, and maintain bone marrow plasma cells and adipose tissue alternatively activated macrophages, while in response to tissue insult eosinophils function as inflammatory effector cells, and, in the wake of an inflammatory response, promote tissue regeneration and wound healing. One common mechanism driving many of the diverse eosinophil functions is the regulated and differential secretion of a vast array of eosinophil-derived cytokines. Eosinophils are distinguished from most other leukocytes in that many, if not all, of the over three dozen eosinophil-derived cytokines are pre-synthesized and stored within intracellular granules, poised for very rapid, stimulus-induced secretion. Eosinophils engaged in cytokine secretion in situ utilize distinct pathways of cytokine release that include: classical exocytosis, whereby granules themselves fuse with the plasma membrane and release their entire contents extracellularly; piecemeal degranulation, whereby granule-derived cytokines are selectively mobilized into vesicles that emerge from granules, traverse the cytoplasm and fuse with the plasma membrane to release discrete packets of cytokines; and eosinophil cytolysis, whereby intact granules are extruded from eosinophils, and deposited within tissues. In this latter scenario, extracellular granules can themselves function as stimulus-responsive secretory-competent organelles within the tissue. Here we review the distinctive processes of differential secretion of eosinophil granule-derived cytokines.

  9. NK-like T cells and plasma cytokines, but not anti-viral serology, define immune fingerprints of resilience and mild disability in exceptional aging.

    Directory of Open Access Journals (Sweden)

    Abbe N Vallejo

    Full Text Available Exceptional aging has been defined as maintenance of physical and cognitive function beyond the median lifespan despite a history of diseases and/or concurrent subclinical conditions. Since immunity is vital to individual fitness, we examined immunologic fingerprint(s of highly functional elders. Therefore, survivors of the Cardiovascular Health Study in Pittsburgh, Pennsylvania, USA were recruited (n = 140; mean age = 86 years and underwent performance testing. Blood samples were collected and examined blindly for humoral factors and T cell phenotypes. Based on results of physical and cognitive performance testing, elders were classified as "impaired" or "unimpaired", accuracy of group assignment was verified by discriminant function analysis. The two groups showed distinct immune profiles as determined by factor analysis. The dominant immune signature of impaired elders consisted of interferon (IFN-γ, interleukin (IL-6, tumor necrosis factor-α, and T cells expressing inhibitory natural killer-related receptors (NKR CD158a, CD158e, and NKG2A. In contrast, the dominant signature of unimpaired elders consisted of IL-5, IL-12p70, and IL-13 with co-expression of IFN-γ, IL-4, and IL-17, and T cells expressing stimulatory NKRs CD56, CD16, and NKG2D. In logistic regression models, unimpaired phenotype was predicted independently by IL-5 and by CD4(+CD28(nullCD56(+CD57(+ T cells. All elders had high antibody titers to common viruses including cytomegalovirus. In cellular bioassays, T cell receptor (TCR-independent ligation of either CD56 or NKG2D elicited activation of T cells. Collectively, these data demonstrate the importance of immunological parameters in distinguishing between health phenotypes of older adults. NKR(+ T cells and cytokine upregulation indicate a unique physiologic environment in old age. Correlation of particular NKR(+ T cell subsets and IL-5 with unimpaired performance, and NKR-driven TCR-independent activation of T

  10. Cardiac tamponade as an independent condition affecting the relationship between the plasma B-type natriuretic peptide levels and cardiac function.

    Science.gov (United States)

    Minai, Kosuke; Komukai, Kimiaki; Arase, Satoshi; Nagoshi, Tomohisa; Matsuo, Seiichiro; Ogawa, Kazuo; Kayama, Yosuke; Inada, Keiichi; Tanigawa, Shin-Ichi; Takemoto, Tomoyuki; Sekiyama, Hiroshi; Date, Taro; Ogawa, Takayuki; Taniguchi, Ikuo; Yoshimura, Michihiro

    2013-07-01

    Plasma B-type natriuretic peptide (BNP) is finely regulated by the cardiac function and several extracardiac factors. Therefore, the relationship between the plasma BNP levels and the severity of heart failure sometimes seems inconsistent. The purpose of the present study was to investigate the plasma BNP levels in patients with cardiac tamponade and their changes after pericardial drainage. This study included 14 patients with cardiac tamponade who underwent pericardiocentesis. The cardiac tamponade was due to malignant diseases in 13 patients and uremia in 1 patient. The plasma BNP levels were measured before and 24-48 h after drainage. Although the patients reported severe symptoms of heart failure, their plasma BNP levels were only 71.2 ± 11.1 pg/ml before drainage. After appropriate drainage, the plasma BNP levels increased to 186.0 ± 22.5 pg/ml, which was significantly higher than that before drainage (P = 0.0002). In patients with cardiac tamponade, the plasma BNP levels were low, probably because of impaired ventricular stretching, and the levels significantly increased in response to the primary condition after drainage. This study demonstrates an additional condition that affects the relationship between the plasma BNP levels and cardiac function. If inconsistency is seen in the relationship between the plasma BNP levels and clinical signs of heart failure, the presence of cardiac tamponade should therefore be considered.

  11. The food matrix and sterol characteristics affect the plasma cholesterol lowering of phytosterol/phytostanol.

    Science.gov (United States)

    Cusack, Laura Kells; Fernandez, Maria Luz; Volek, Jeff S

    2013-11-01

    Foods with added phytosterols/phytostanols (PS) are recommended to lower LDL cholesterol (LDL-c) concentrations. Manufacturers have incorporated PS into a variety of common foods. Understanding the cholesterol-lowering impact of the food matrix and the PS characteristics would maximize their success and increase the benefit to consumers. This review systematically examines whether the PS characteristics and the fatty acid composition of foods with added PS affects serum LDL-c. A total of 33 studies published between the years 1998 and 2011 inclusive of 66 individual primary variables (strata) were evaluated. The functional food matrices included margarine, mayonnaise, yogurt, milk, cheese, meat, grain, juice, and chocolate. Consistently, ≥10% reductions in LDL-c were reported when the characteristics of the food matrix included poly- and monounsaturated fatty acids known to lower LDL-c. Also, >10% mean reductions in LDL-c were reported when β-sitostanol and campestanol as well as stanol esters were used. These characteristics allow both low-fat and high-fat foods to successfully incorporate PS and significantly lower LDL-c.

  12. Pre-Analytical Parameters Affecting Vascular Endothelial Growth Factor Measurement in Plasma: Identifying Confounders.

    Directory of Open Access Journals (Sweden)

    Johanna M Walz

    Full Text Available Vascular endothelial growth factor-A (VEGF-A is intensively investigated in various medical fields. However, comparing VEGF-A measurements is difficult because sample acquisition and pre-analytic procedures differ between studies. We therefore investigated which variables act as confounders of VEGF-A measurements.Following a standardized protocol, blood was taken at three clinical sites from six healthy participants (one male and one female participant at each center twice one week apart. The following pre-analytical parameters were varied in order to analyze their impact on VEGF-A measurements: analyzing center, anticoagulant (EDTA vs. PECT / CTAD, cannula (butterfly vs. neonatal, type of centrifuge (swing-out vs. fixed-angle, time before and after centrifugation, filling level (completely filled vs. half-filled tubes and analyzing method (ELISA vs. multiplex bead array. Additionally, intrapersonal variations over time and sex differences were explored. Statistical analysis was performed using a linear regression model.The following parameters were identified as statistically significant independent confounders of VEGF-A measurements: analyzing center, anticoagulant, centrifuge, analyzing method and sex of the proband. The following parameters were no significant confounders in our data set: intrapersonal variation over one week, cannula, time before and after centrifugation and filling level of collection tubes.VEGF-A measurement results can be affected significantly by the identified pre-analytical parameters. We recommend the use of CTAD anticoagulant, a standardized type of centrifuge and one central laboratory using the same analyzing method for all samples.

  13. Analysis of plasma cytokines and angiogenic factors in patients with pretreated urothelial cancer receiving Pazopanib: the role of circulating interleukin-8 to enhance the prognostic accuracy

    Science.gov (United States)

    Necchi, A; Pennati, M; Zaffaroni, N; Landoni, E; Giannatempo, P; Raggi, D; Schwartz, L H; Morosi, C; Crippa, F; Farè, E; Nicolai, N; Lanocita, R; Sava, T; Sacco, C; Messina, C; Ortega, C; De Braud, F G; Salvioni, R; Daidone, M G; Gianni, A M; Mariani, L

    2014-01-01

    Background: Pazopanib achieved the end point of clinical activity in pretreated patients with urothelial cancer in a single-group, phase 2 trial. The objective was to identify biological predictors of clinical benefit to pazopanib in these patients. Methods: EDTA blood samples were collected at baseline (T0) and after 4 weeks (T1) of treatment, together with radiological imaging in all 41 patients to analyse plasma circulating angiogenic factor levels by multiplex ELISA plates. Changes from T0 to T1 in marker levels were matched with response with the covariance analysis. Univariable and multivariable analyses evaluated the association with overall survival (OS), adjusted for prespecified clinical variables. Net reclassification improvement (NRI) tested the performance of the recognised Cox model. Results: Increasing IL8T1 level associated with lower response probability at covariance analysis (P=0.010). Both IL8T0 (P=0.019) and IL8T1 (P=0.004) associated with OS and the prognostic model, including clinical variables and IL8T1 best-predicted OS after backward selection. The NRI for this model was 39%. When analysed as a time-varying covariate, IL8T1 level<80 pg ml−1 portended significantly greater response (∼80%) and 6-month OS (∼60%) probability than level⩾80. Conclusion: IL8-level changes during pazopanib allowed for a prognostic improvement and were associated with response probability. PMID:24231947

  14. Elevated Systemic Levels of Inflammatory Cytokines in Older Women with Persistent Cervical HPV Infection1234

    Science.gov (United States)

    Kemp, Troy J.; Hildesheim, Allan; García-Piñeres, Alfonso; Williams, Marcus C.; Shearer, Gene M.; Rodriguez, Ana Cecilia; Schiffman, Mark; Burk, Robert; Freer, Enrique; Bonilla, Jose; Herrero, Rolando; Pinto, Ligia A.

    2010-01-01

    Background Defects in lymphoproliferative responses to mitogen/antigens in women >45 years old ith a persistent type-specific HPV infection have been reported. Methods To determine whether these defects were associated with altered cytokine profiles, plasma and PBMC culture supernatants from 50 cases (persistent HPV infection and weak lymphoproliferative responses) and 50 uninfected controls were examined for 24 cytokines using multiplexed bead-based immunoassays and enzyme-linked immunosorbent assay (ELISA). Results The following plasma cytokines were significantly increased from cases relative to controls: (cases vs. controls (median pg/ml); IL-6: 393.1 vs. 14.5, IL-8: 1128.5 vs. 43.9, TNF-α: 164.1 vs. 9.2, MIP-1α: 1368.9 vs. 25.5, GM-CSF: 13.8 vs. 7.3, IL-1β: 8.3 vs. 1.6, all p10) and highly statistically significant difference between cases and controls. Moreover, length of persistence or type of infection (high risk and low risk) did not affect these differences. IL-6, TNF-α, MIP-1α levels were increased in unstimulated PBMC culture supernatants from cases compared to controls (p <0.05), except for IL-8 (p=0.09). However, the cytokine levels from PHA-stimulated PBMC culture supernatants were significantly lower in the cases (p<0.0001). Conclusions Persistent HPV infection in older women with evidence of immune deficit is associated with an increase in systemic inflammatory cytokines. Impact Future studies are needed to determine whether the inflammatory profile is age dependent and to examine the role inflammatory cytokines play in HPV-induced progression from infection to cervical cancer. PMID:20647411

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

    DEFF Research Database (Denmark)

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

    2008-01-01

    BACKGROUND: Infusion of hypertonic saline provides early haemodynamic benefits and may affect the immune system. It is unknown if infusion of hypertonic saline affects plasma cytokines and stress hormones after surgery. METHODS: Sixty-two women undergoing abdominal hysterectomy were randomized...... factor-alpha. Serum cortisol and vasopressin were measured at these time points and 48 h after operation. Epinephrine and norepinephrine (n=26) were quantified at baseline, after infusion, 25 min after incision, 1, and 4 h after surgery. Finally, C-reactive protein was measured at baseline, 24, and 48 h...... with the other groups (Pstress...

  16. Treatment of Cancer Pain by Targeting Cytokines

    OpenAIRE

    Vendrell, I.; Macedo, D.; I. Alho; Dionísio, M. R.; Costa, L.

    2015-01-01

    Inflammation is one of the most important causes of the majority of cancer symptoms, including pain, fatigue, cachexia, and anorexia. Cancer pain affects 17 million people worldwide and can be caused by different mediators which act in primary efferent neurons directly or indirectly. Cytokines can be aberrantly produced by cancer and immune system cells and are of particular relevance in pain. Currently, there are very few strategies to control the release of cytokines that seems to be relate...

  17. Suprathermal electron energy spectrum and nonlocally affected plasma-wall interaction in helium/air micro-plasma at atmospheric pressure

    Science.gov (United States)

    Demidov, V. I.; Adams, S. F.; Miles, J. A.; Koepke, M. E.; Kurlyandskaya, I. P.

    2016-10-01

    Details of ground-state and excited-state neutral atoms and molecules in an atmospheric-pressure micro-discharge plasma may be obtained by plasma electron spectroscopy (PLES), based on a wall probe. The presence and transport of energetic (suprathermal) electrons, having a nonlocal origin, are responsible for electrostatic charging of the plasma boundary surfaces to potentials many times that associated with the ambient electron kinetic energy. The energy-flux distribution function is shown to be controllable for applications involving analysis of composition and processes taking place in a multiphase (plasma-gas-solid), chemically reactive, interaction region.

  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. Feed gas humidity: a vital parameter affecting a cold atmospheric-pressure plasma jet and plasma-treated human skin cells

    Science.gov (United States)

    Winter, J.; Wende, K.; Masur, K.; Iseni, S.; Dünnbier, M.; Hammer, M. U.; Tresp, H.; Weltmann, K.-D.; Reuter, S.

    2013-07-01

    In this study, the effect of feed gas humidity on the reactive component generation of an atmospheric-pressure argon plasma jet and its effect on human skin cells are investigated. Feed gas humidity is identified as one key parameter that strongly influences stability and reproducibility of plasma medical studies. The plasma jet is investigated by absorption spectroscopy in the ultraviolet and infrared spectral region for its ozone production depending on the humidity concentration in the feed gas. By optical emission spectroscopy the dependence of present excited plasma species such as hydroxyl radicals, molecular nitrogen, argon and atomic oxygen on the feed gas humidity is investigated. As an interface layer between the plasma jet effluent and the biological cell, a buffer solution is treated and the hydrogen peroxide (H2O2) production is studied with two independent colorimetric assays as a function of humidity admixture to the feed gas. Ultimately, the effect of varying feed gas humidity on the cell viability of indirect plasma treated adherent HaCAT cells is investigated. The highest viability is found for the driest feed gas condition. Furthermore, this work shows answers for the relevance of unwanted—or intended—feed gas humidity in plasma medical experiments and their comparatively large relevance with respect to ambient humidity. The findings will lead to more reproducible experiments in the field of plasma medicine.

  20. Effects of short-chain fatty acid-supplemented total parenteral nutrition on intestinal pro-inflammatory cytokine abundance.

    Science.gov (United States)

    Milo, L A; Reardon, K A; Tappenden, K A

    2002-09-01

    We examined the effect of short-chain fatty acid-supplemented total parenteral nutrition on proinflammatory cytokine levels in piglets. Piglets (N = 22) received either standard total parenteral nutrition or total parenteral nutrition supplemented with short-chain fatty acids. After seven days of continuous nutrient infusion, proinflammatory cytokine (TNF-alpha, IL-1beta, IL-6) abundance in plasma, jejunal, and ileal samples and small intestinal myeloperoxidase was determined using western blotting. No differences were seen in TNF-alpha small intestinal abundance. IL-1beta was higher in the small intestine of the short-chain fatty acid group (P short-chain fatty acids beneficially increase small intestinal abundance of IL-1beta and IL-6 during total parenteral nutrition administration, while not affecting systemic production of these cytokines or intestinal inflammation.

  1. 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.

  2. Unexpected depletion in plasma choline and phosphatidylcholine concentrations in a pregnant woman with bipolar affective disorder being treated with lithuim, haloperidol and benztropine: a case report

    OpenAIRE

    2008-01-01

    Abstract Introduction Patients with bipolar affective disorder can be effectively managed with pharmacological intervention. This case report describes a pregnant woman with a ten-year history of bipolar affective disorder that was being treated with lithium, haloperidol and benztropine. Case presentation The patient had a normal pregnancy, but developed an elevated blood pressure and started to lose weight at 36 weeks of gestation. During pregnancy, plasma concentrations of choline and phosp...

  3. Post-glucose-load urinary C-peptide and glucose concentration obtained during OGTT do not affect oral minimal model-based plasma indices

    NARCIS (Netherlands)

    S. Jainandunsing (Sjaam); J.L.D. Wattimena (Josias); T. Rietveld (Trinet); J.N.I. van Miert (Joram); E.J.G. Sijbrands (Eric); F.W.M. de Rooij (Felix)

    2016-01-01

    textabstractThe purpose of this study was to investigate how renal loss of both C-peptide and glucose during oral glucose tolerance test (OGTT) relate to and affect plasma-derived oral minimal model (OMM) indices. All individuals were recruited during family screening between August 2007 and January

  4. Prerequisites for cytokine measurements in clinical trials with multiplex immunoassays

    Directory of Open Access Journals (Sweden)

    Rijkers Ger T

    2009-09-01

    Full Text Available Abstract Background Growing knowledge about cellular interactions in the immune system, including the central role of cytokine networks, has lead to new treatments using monoclonal antibodies that block specific components of the immune system. Systemic cytokine concentrations can serve as surrogate outcome parameters of these interventions to study inflammatory pathways operative in patients in vivo. This is now possible due to novel technologies such as multiplex immunoassays (MIA that allows detection of multiple cytokines in a single sample. However, apparently trivial underappreciated processes, (sample handling and storage, interference of endogenous plasma proteins can greatly impact the reliability and reproducibility of cytokine detection. Therefore we set out to investigate several processes that might impact cytokine profiles such as blood collecting tubes, duration of storage, and number of freeze thawing cycles. Results Since under physiological conditions cytokine concentrations normally are low or undetectable we spiked cytokines in the various plasma and serum samples. Overall recoveries ranged between 80-120%. Long time storage showed cytokines are stable for a period up to 2 years of storage at -80°C. After 4 years several cytokines (IL-1α, IL-1β, IL-10, IL-15 and CXCL8 degraded up to 75% or less of baseline values. Furthermore we show that only 2 out of 15 cytokines remained stable after several freeze-thawing cycles. We also demonstrate implementation of an internal control for multiplex cytokine immunoassays. Conclusion All together we show parameters which are essential for measurement of cytokines in the context of clinical trials.

  5. 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...

  6. Cytokines and Blastocyst Hatching.

    Science.gov (United States)

    Seshagiri, Polani B; Vani, Venkatappa; Madhulika, Pathak

    2016-03-01

    Blastocyst implantation into the uterine endometrium establishes early pregnancy. This event is regulated by blastocyst- and/or endometrium-derived molecular factors which include hormones, growth factors, cell adhesion molecules, cytokines and proteases. Their coordinated expression and function are critical for a viable pregnancy. A rate-limiting event that immediately precedes implantation is the hatching of blastocyst. Ironically, blastocyst hatching is tacitly linked to peri-implantation events, although it is a distinct developmental phenomenon. The exact molecular network regulating hatching is still unclear. A number of implantation-associated molecular factors are expressed in the pre-implanting blastocyst. Among others, cytokines, expressed by peri-implantation blastocysts, are thought to be important for hatching, making blastocysts implantation competent. Pro-inflammatory (IL-6, LIF, GM-CSF) and anti-inflammatory (IL-11, CSF-1) cytokines improve hatching rates; they modulate proteases (MMPs, tPAs, cathepsins and ISP1). However, functional involvement of cytokines and their specific mediation of hatching-associated proteases are unclear. There is a need to understand mechanistic roles of cytokines and proteases in blastocyst hatching. This review will assess the available knowledge on blastocyst-derived pro-inflammatory and anti-inflammatory cytokines and their role in potentially regulating blastocyst hatching. They have implications in our understanding of early embryonic loss and infertility in mammals, including humans.

  7. Effect of polymer-free sirolimus-eluting Nano stent implantation on plasma proinflammatory cytokines%Nano无载体药物支架对血清炎症因子的影响

    Institute of Scientific and Technical Information of China (English)

    成永霞; 邵芳; 周庆国

    2015-01-01

    目的:观察国产 Nano 无载体药物支架对血清炎症因子的影响,并探讨其对减少主要不良心脏事件的作用。方法选择2012年1月至2013年10月我院拟行经皮冠状动脉介入治疗(PCI)术的冠心病患者59例随机分为Partner组和Nano组,分别用ELISA法检测术前、术后24 h、1个月、3个月、6个月及12个月血清炎症因子高敏C反应蛋白(hsCRP)、白细胞介素-6(IL-6)、基质金属蛋白酶-9(MMP-9);术后1、3、6、10、12个月门诊或电话随访,观察有无主要不良心脏事件。结果25例患者成功置入Partner药物支架,34例置入Nano无载体药物支架。Partner组和Nano组术前基本情况无明显差异,术后24 h hsCRP、IL-6、MMP-9均达到最高值;术前、术后24 h、术后1、3个月两组间hsCRP、IL-6、MMP-9无明显差异(P>0.05);术后6个月Partner组IL-6、MMP-9明显高于Nano组(P<0.05),但两组间hsCRP无明显差异(P>0.05);术后12个月Partner组炎症因子hsCRP、IL-6、MMP-9均明显高于Nano组(P均<0.05)。随访期间Partner组发生主要不良心脏事件明显高于Nano组(P<0.05)。结论 Nano组较Partner组炎症反应更低,进一步减少支架置入术后主要不良心脏事件,考虑与去除载体有关。%ObjectiveTo study the effect of polymer-free sirolimus-eluting Nano stent implantation on plasma proinflammatory cytokines.MethodsFrom January 2012 to October 2013, 59 patients with coronary heart disease treated with primary percutaneous coronary intervention (PCI) were enroled and randomly divided into Partner and Nano group. Plasma proinflammatory cytokines high-sensitivity C-reactive protein (hsCRP), interleukin 6 (IL-6) and matrix metaloproteinases 9 (MMP-9) were detected by ELISA in the preoperative and postoperative 24 hours, 1 month, 3 months, 6 months and 12 months. All patients were folowed up in postoperative 1, 3, 6, 10, 12 months. The major adverse

  8. Three transcription factors and the way immune cells affected by different plasma change in opposite ways in the development of the syndrome of pre-eclampsia

    Institute of Scientific and Technical Information of China (English)

    Liang Zhou; Zhu Jing; Wang Yunfei; Wang You; Zhang Yu; Lin Jianhua; Di Wen

    2014-01-01

    Background How the transcriptional factors regulated the innate and adaptive immune system in pregnancy and preeclampsia are less understood.Nevertheless,what the plasma work in the development of this disease was not sure.The present study was design to evaluate what the transcriptional factors change in innate and adaptive immune system and what the plasma do in this filed.Methods Peripheral blood mononuclear cells (PBMC) from non-pregnant women (n=18),women with clinically normal pregnancies (n=23) and women with pre-eclampsia (n=20) were separated from peripheral blood to isolate monocytes and T cells.The purity of monocytes and T cells were analysed by flow cytometry.Monocytes and T cells were stimulated in either lipopolysaccharides (LPS) or phorbol-myristate-acetate (PMA),respectively.Transcription Factor Arrays were used to screen the transcription factors of interest in comparing of different groups.PBMC were isolated from another 8 nonpregnant samples were co-incubated with different groups of plasma.Polymerase chain reaction (PCR) was performed using whole cell extractions of the samples.Results Nuclear factor of activated T-cells-1 (NFAT-1),signal transducers and activators of transcription-1 (STAT-1) and activator protein-1 (AP-1) are up-regulated in monocytes in pregnancy and more so in pre-eclampsia.On the the contrary,NFAT-1,STAT-1 and AP-1 are down-regulated in T cells in pregnancy and more so in pre-eclampsia.A reduction was observed in interferon (IFN)-y,interleukin (IL)-12 and IL-4 expression in T cells incubated with pre-eclamptic plasma.An elevation was observed in tumor necrosis factor (TNF)-α,IL-1 and IL-12 expression in monocytes incubated with preeclamptic plasma.Conclusions Innate immunity is over activated and adaptive immunity is over suppressed in the development of preeclampsia.NFAT-1,STAT-1 and AP-1 might be the central transcription factors in the pathogenesis of pre-eclampsia.They induced some changes in plasma and "educate" the

  9. Patient age does not affect mefloquine concentrations in erythrocytes and plasma during the acute phase of falciparum malaria

    Directory of Open Access Journals (Sweden)

    José Luiz Fernandes Vieira

    Full Text Available Abstract Objective To evaluate whether patient age has a significant impact on mefloquine concentrations in the plasma and erythrocytes over the course of treatment for uncomplicated falciparum malaria. Methods A total of 20 children aged between 8 and 11 years and 20 adult males aged between 22 and 41 years with uncomplicated falciparum malaria were enrolled in the study. Mefloquine was administered to patients in both age groups at a dose of 20 mg kg−1. The steady-state drug concentrations were measured by reversed-phase high performance liquid chromatography. Results All patients had an undetectable mefloquine concentration on day 0. In adults, the plasma mefloquine concentrations ranged from 770 to 2930 ng mL−1 and the erythrocyte concentrations ranged from 2000 to 6030 ng mL−1. In children, plasma mefloquine concentrations ranged from 881 to 3300 ng mL−1 and erythrocyte concentrations ranged from 3000 to 4920 ng mL−1. There was no significant correlation between mefloquine concentrations in the plasma and erythrocytes in either adults or children. Conclusion In the present study, we observed no effect of patient age on the steady-state concentrations of mefloquine in the plasma and erythrocytes. We found that the mefloquine concentration in the erythrocytes was approximately 2.8-times higher than in the plasma. There were no significant correlations between mefloquine concentrations in the erythrocytes and plasma for either age group.

  10. [Cytokines and asthma].

    Science.gov (United States)

    Gani, F; Senna, G; Piglia, P; Grosso, B; Mezzelani, P; Pozzi, E

    1998-10-01

    Asthma is a chronic inflammatory lung disease in which eosinophils are one of the most important involved cells. These cells accumulate in the lung because of cytokines, which are able to regulate cellular responses. The role of cytokines is well known in allergic asthma: IL4, IL5, IL3, GMCSF are the principally cytokine involved. IL4 regulate IgE synthesis while IL5, (and IL3) cause the activation and accumulation of eosinophils. In non allergic asthma, whilst only IL5 seemed to be important recent data, shows that also IL4 plays an important role. Therefore nowadays no relevant difference seems to exist between allergic and non allergic asthma; instead the primer is different: the allergen in allergic asthma and often an unknown factor in the non allergic asthma. Recently other cytokines have been proved to play a role in the pathogenesis of asthma. IL8 is chemotactic not only for neutrophils but also for eosinophils and might cause chronic inflammation in severe asthma. IL13 works like IL4, while RANTES seems to be a more important chemotactic agent than IL5. Finally IL10, which immunoregulates T lymphocyte responses, may reduce asthma inflammation. In conclusion cytokine made us to learn more about the pathogenesis of asthma even if we do not yet know when and how asthma inflammation develops.

  11. Lactobacillus reuteri supplements do not affect salivary IgA or cytokine levels in healthy subjects: A randomized, double-blind, placebo-controlled cross-over trial

    DEFF Research Database (Denmark)

    Jørgensen, Mette Rose; Keller, Mette Kirstine; Kragelund, Camilla

    2016-01-01

    Objectives: To evaluate the effect of daily ingestion of probiotic lactobacilli on the levels of secretory IgA (sIgA) and selected cytokines in whole saliva of healthy young adults. Materials and methods: The study group consisted of 47 healthy adults (18–32 years) who volunteered for a randomize...

  12. A lignan complex isolated from flaxseed does not affect plasma lipid concentrations or antioxidant capacity in healthy postmenopausal women

    DEFF Research Database (Denmark)

    Hallund, Jesper; Ravn-Haren, Gitte; Bügel, S.;

    2006-01-01

    A lignan complex rich in the plant lignan secoisolariciresinol diglucoside (SDG) was isolated from flaxseed. SDG is metabolized by the colonic microflora to the mammalian lignans enterodiol (END) and enterolactone (ENL), and was hypothesized to reduce plasma lipid concentrations and improve...... (LDL-C), HDL cholesterol (HDL-C), triacylglycerol (TAG), serum lipoprotein oxidation lag time, plasma Trolox-equivalent antioxidant capacity (TEAC), and ferric reducing ability of plasma (FRAP) were measured at the beginning and end of each intervention period. ENL concentrations in serum (P

  13. VAMP-8 segregates mast cell-preformed mediator exocytosis from cytokine trafficking pathways.

    Science.gov (United States)

    Tiwari, Neeraj; Wang, Cheng-Chun; Brochetta, Cristiana; Ke, Gou; Vita, Francesca; Qi, Zeng; Rivera, Juan; Soranzo, Maria Rosa; Zabucchi, Giuliano; Hong, Wanjin; Blank, Ulrich

    2008-04-01

    Inflammatory responses by mast cells are characterized by massive exocytosis of prestored granular mediators followed by cytokine/chemokine release. The vesicular trafficking mechanisms involved remain poorly understood. Vesicular-associated membrane protein-8 (VAMP-8), a member of the soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein receptor (SNARE) family of fusion proteins initially characterized in endosomal and endosomal-lysosomal fusion, may also function in regulated exocytosis. Here we show that in bone marrow-derived mast cells (BMMCs) VAMP-8 partially colocalized with secretory granules and redistributed upon stimulation. This was associated with increased SNARE complex formation with the target t-SNAREs, SNAP-23 and syntaxin-4. VAMP-8-deficient BMMCs exhibited a markedly reduced degranulation response after IgE+ antigen-, thapsigargin-, or ionomycin-induced stimulation. VAMP-8-deficient mice also showed reduced plasma histamine levels in passive systemic anaphylaxis experiments, while cytokine/chemokine release was not affected. Unprocessed TNF accumulated at the plasma membrane where it colocalized with a VAMP-3-positive vesicular compartment but not with VAMP-8. The findings demonstrate that VAMP-8 segregates secretory lysosomal granule exocytosis in mast cells from cytokine/chemokine molecular trafficking pathways.

  14. Cytokines in Neuropathic Pain and Associated Depression.

    Science.gov (United States)

    Lees, Justin G; Fivelman, Brett; Duffy, Samuel S; Makker, Preet G S; Perera, Chamini J; Moalem-Taylor, Gila

    2015-01-01

    Neuropathic pain occurs as a result of lesion or disease affecting the somatosensory nervous system and is present in a diverse set of peripheral and central pathologies such as nerve trauma, diabetic neuropathy, post-herpetic neuralgia, chemotherapy-induced peripheral neuropathy, spinal cord injury and multiple sclerosis. Debilitating symptoms including allodynia, hyperalgesia and spontaneous pain have a substantial negative impact on patients' quality of life. The currently available therapeutic treatments are generally ineffective and characterised by poor response rates. Accumulating evidence suggests that neuroinflammation and cytokine signalling play a critical role in neuropathic pain. Numerous experimental studies have demonstrated that certain pro-inflammatory cytokines are elevated in neuropathic pain conditions, and administration of these cytokines can elicit pain hypersensitivity in the absence of injury or disease. This phenomenon is also apparent in the 'sickness response', which encompasses a broad inflammatory response to disease and injury and involves a series of physiological and behavioural changes including pain hypersensitivity. Interestingly, the 'sickness response' is also similar in nature to some of the defining characteristics of the depressed state of affective disorder. In this review, we explore links that may relate the co-existence of depression in neuropathic pain patients with the activity of cytokines and discuss the role of several key pro-inflammatory and anti-inflammatory cytokines in neuropathic pain.

  15. Lipid-based nutrient supplements do not affect efavirenz but lower plasma nevirapine concentrations in Ethiopian adult HIV patients

    DEFF Research Database (Denmark)

    Abdissa, A; Olsen, Mette Frahm; Yilma, D

    2015-01-01

    OBJECTIVES: Lipid-based nutrient supplements (LNSs) are increasingly used in HIV programmes in resource-limited settings. However, the possible effects of LNSs on the plasma concentrations of antiretroviral drugs have not been assessed. Here, we aimed to assess the effects of LNSs on plasma...... efavirenz and nevirapine trough concentrations in Ethiopian adult HIV-infected patients. METHODS: The effects of LNSs were studied in adults initiating antiretroviral therapy (ART) in a randomized trial. Patients with body mass index (BMI) > 17 kg/m(2) (n = 282) received daily supplementation of an LNS.......9; -0.9 μg/mL; P = 0.01), respectively, compared with the group not receiving supplements. There were no differences between groups with respect to efavirenz plasma concentrations. The CYP2B6 516 G>T polymorphism was associated with a 5 μg/mL higher plasma efavirenz concentration compared with the wild...

  16. Factors affecting ion kinetic temperature, number density, and containment time in the NASA Lewis bumpy-torus plasma

    Science.gov (United States)

    Roth, J. R.

    1977-01-01

    The degree of toroidal symmetry of the plasma, the number of midplane electrode rings, the configuration of electrode rings, and the location of the diagnostic instruments with respect to the electrode rings used to generate the plasma are discussed. Impurities were deliberately introduced into the plasma, and the effects of the impurity fraction on ion kinetic temperature and electron number density were observed. It is concluded that, if necessary precautions are taken, the plasma communicates extremely well along the magnetic field lines and displays a high degree of symmetry from sector to sector for a wide range of electrode ring configurations and operating conditions. Finally, some characteristic data taken under nonoptimized conditions are presented, which include the highest electron number density and the longest particle containment time (1.9 msec) observed. Also, evidence from a paired comparison test is presented which shows that the electric field acting along the minor radius of the toroidal plasma improves the plasma density and the calculated containment time more than an order of magnitude if the electric field points inward, relative to the values observed when it points (and pushes ions) radially outward.

  17. The T1405N carbamoyl phosphate synthetase polymorphism does not affect plasma arginine concentrations in preterm infants.

    Directory of Open Access Journals (Sweden)

    Rob M J Moonen

    Full Text Available BACKGROUND: A C-to-A nucleotide transversion (T1405N in the gene that encodes carbamoyl-phosphate synthetase 1 (CPS1 has been associated with changes in plasma concentrations of L-arginine in term and near term infants but not in adults. In preterm infants homozygosity for the CPS1 Thr1405 variant (CC genotype was associated with an increased risk of having necrotizing enterocolitis (NEC. Plasma L-arginine concentrations are decreased in preterm infants with NEC. AIM: To examine the putative association between the CPS1 T1405N polymorphism and plasma arginine concentrations in preterm infants. METHODS: Prospective multicenter cohort study. Plasma and DNA samples were collected from 128 preterm infants (<30 weeks between 6 and 12 hours after birth. Plasma amino acid and CPS1 T1405N polymorphism analysis were performed. RESULTS: Distribution of genotypes did not differ between the preterm (CC:CA:AA = 55.5%:33.6%:10.9%, n = 128 and term infants (CC:CA:AA = 54.2%:35.4%:10.4%, n = 96. There was no association between the CPS1 genotype and plasma L-arginine or L-citrulline concentration, or the ornithine to citrulline ratio, which varies inversely with CPS1 activity. Also the levels of asymmetric dimethylarginine, and symmetric dimethylarginine were not significantly different among the three genotypes. CONCLUSIONS: The present study in preterm infants did not confirm the earlier reported association between CPS1 genotype and L-arginine levels in term infants.

  18. Body Position Modulates Gastric Emptying and Affects the Post-Prandial Rise in Plasma Amino Acid Concentrations Following Protein Ingestion in Humans

    Directory of Open Access Journals (Sweden)

    Andrew M. Holwerda

    2016-04-01

    Full Text Available Dietary protein digestion and amino acid absorption kinetics determine the post-prandial muscle protein synthetic response. Body position may affect gastrointestinal function and modulate the post-prandial rise in plasma amino acid availability. We aimed to assess the impact of body position on gastric emptying rate and the post-prandial rise in plasma amino acid concentrations following ingestion of a single, meal-like amount of protein. In a randomized, cross-over design, eight healthy males (25 ± 2 years, 23.9 ± 0.8 kg·m−2 ingested 22 g protein and 1.5 g paracetamol (acetaminophen in an upright seated position (control and in a −20° head-down tilted position (inversion. Blood samples were collected during a 240-min post-prandial period and analyzed for paracetamol and plasma amino acid concentrations to assess gastric emptying rate and post-prandial amino acid availability, respectively. Peak plasma leucine concentrations were lower in the inversion compared with the control treatment (177 ± 15 vs. 236 ± 15 mmol·L−1, p < 0.05, which was accompanied by a lower plasma essential amino acid (EAA response over 240 min (31,956 ± 6441 vs. 50,351 ± 4015 AU; p < 0.05. Peak plasma paracetamol concentrations were lower in the inversion vs. control treatment (5.8 ± 1.1 vs. 10.0 ± 0.6 mg·L−1, p < 0.05. Gastric emptying rate and post-prandial plasma amino acid availability are significantly decreased after protein ingestion in a head-down tilted position. Therefore, upright body positioning should be considered when aiming to augment post-prandial muscle protein accretion in both health and disease.

  19. Post-glucose-load urinary C-peptide and glucose concentration obtained during OGTT do not affect oral minimal model-based plasma indices.

    Science.gov (United States)

    Jainandunsing, Sjaam; Wattimena, J L Darcos; Rietveld, Trinet; van Miert, Joram N I; Sijbrands, Eric J G; de Rooij, Felix W M

    2016-05-01

    The purpose of this study was to investigate how renal loss of both C-peptide and glucose during oral glucose tolerance test (OGTT) relate to and affect plasma-derived oral minimal model (OMM) indices. All individuals were recruited during family screening between August 2007 and January 2011 and underwent a 3.5-h OGTT, collecting nine plasma samples and urine during OGTT. We obtained the following three subgroups: normoglycemic, at risk, and T2D. We recruited South Asian and Caucasian families, and we report separate analyses if differences occurred. Plasma glucose, insulin, and C-peptide concentrations were analyzed as AUCs during OGTT, OMM estimate of renal C-peptide secretion, and OMM beta-cell and insulin sensitivity indices were calculated to obtain disposition indices. Post-glucose load glucose and C-peptide in urine were measured and related to plasma-based indices. Urinary glucose corresponded well with plasma glucose AUC (Cau r = 0.64, P oral (Cau r = -0.61, P indices in general nor in T2D patients (renal clearance range 0-2.1 %, with median 0.2 % of plasma glucose AUC). C-indices of urinary glucose to detect various stages of glucose intolerance were excellent (Cau 0.83-0.98; SA 0.75-0.89). The limited role of renal glucose secretion validates the neglecting of urinary glucose secretion in kinetic models of glucose homeostasis using plasma glucose concentrations. Both C-peptide and glucose in urine collected during OGTT might be used as non-invasive measures for endogenous insulin secretion and glucose tolerance state.

  20. Censored correlated cytokine concentrations

    DEFF Research Database (Denmark)

    Andersen, Andreas; Benn, Christine Stabell; Jørgensen, Mathias J;

    2013-01-01

    Interest in cytokines as markers for the function of the immune system is increasing. Methods quantifying cytokine concentrations are often subject to detection limits, which lead to non-detectable observations and censored distributions. When distributions are skewed, geometric mean ratios (GMRs...... for both homogeneous and inhomogeneous normal distributions. For skewed mixture and heavy-tailed distributions, they perform reasonably well if censoring is less than 30%. We recommend these methods to estimate GMRRs. At least one of the methods is available in Stata, R or SAS....

  1. Cytokiner og osteoporose

    DEFF Research Database (Denmark)

    Jørgensen, N R

    1997-01-01

    /testosterone, parathyroidhormone and 1,25(OH)2D3. Some of the cytokines primarily enhance osteoclastic bone resorption e.g. IL-1 (Interleukin-1), TNF (Tumor Necrosis Factor) and IL-6 (Interleukin-6), while others primarily stimulate bone formation e.g. TGF-beta (Transforming Growth Factor), IGF (Insulin-like Growth Factor......During the last few years, progress has been made towards the understanding of local regulation of bone remodelling especially in relation to osteoporosis. Cytokines have shown to be powerful regulators of bone resorption and formation, though under superior control from oestrogen...

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

    Science.gov (United States)

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

    2013-10-01

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

  3. Increasing levels of dietary crystalline methionine affect plasma methionine profiles, ammonia excretion, and the expression of genes related to the hepatic intermediary metabolism in rainbow trout (Oncorhynchus mykiss)

    DEFF Research Database (Denmark)

    Rolland, Marine; Skov, Peter Vilhelm; Larsen, Bodil Katrine;

    2016-01-01

    . The diets were fed in excess for six weeks before three sampling campaigns carried out successively to elucidate (i) the hepatic expression of selected genes involved in lipid, glucose and amino acid metabolism; (ii) the postprandial ammonia excretion; and (iii) the postprandial plasma methionine...... significantly affected by the increase in dietary methionine. Changes in gene expression reflected to some extent the decrease in ammonia excretion (P=0.022) and in the hepatosomatic index (HSI; P...

  4. Nitrite-induced methemoglobinaemia affects blood ionized and total magnesium level by hydrolysis of plasma adenosine triphosphate in rat.

    Science.gov (United States)

    Rahman, Md Mizanur; Kim, Shang-Jin; Kim, Gi-Beum; Hong, Chul-Un; Lee, Young-Up; Kim, Sung-Zoo; Kim, Jin-Shang; Kang, Hyung-Sub

    2009-11-01

    The objective of this study was to evaluate the effects of sodium nitrite (NaNO(2))-induced methemoglobinaemia on plasma ATP (adenosine triphosphate) and corresponding changes of blood-ionized magnesium (iMg(2+)) as well as total magnesium (tMg(2+)) in a time-dependent manner. This study was performed on male Sprague-Dawley rats to which NaNO(2) was injected (10 mg/kg i.p.) to induce methemoglobinaemia. Methemoglobin (MetHb) in blood was measured before (0 min.) and after 10, 30, 60 and 120 min. of NaNO(2) injection. At respective time points, the tMg(2+), blood ions and gases were measured by atomic absorption spectrometry and ion selective electrode, respectively. Haematological parameters were checked by automatic blood cell count, and blood films were observed under light microscope. Plasma ATP was measured by bioluminescence assay using a luminometer, and plasma proteins were measured by an automatic analyser. Blood cell count (RBC, WBC and platelet), haematocrit, and haemoglobin were found to be decreased with the advancement of MetHb concentration. With the gradual increase of MetHb concentration, the plasma ATP decreased and blood iMg(2+) and plasma tMg(2+) increased significantly as time passed by in comparison with the pre-drug values. A significant decrease of the ratio of ionized calcium to iMg(2+), Na(+) and increase of K(+) was observed. In conclusion, NaNO(2)-induced methemoglobinaemia is a cause of hydrolysis of plasma ATP which is responsible for the increase of blood iMg(2+) and plasma tMg(2+) in rats.

  5. Cytokines in Sjogren's syndrome

    NARCIS (Netherlands)

    N. Roescher; P.P. Tak; G.G. Illei

    2009-01-01

    Cytokines play a central role in the regulation of immunity and are often found to be deregulated in autoimmune diseases. Sjogren's syndrome is a chronic autoimmune disease characterized by inflammation and loss of secretory function of the salivary and lachrymal glands. This review highlights the c

  6. Behavior and pro-inflammatory cytokine variations among submissive and dominant mice engaged in aggressive encounters: moderation by corticosterone reactivity.

    Directory of Open Access Journals (Sweden)

    Marie-Claude Audet

    2010-08-01

    Full Text Available Psychosocial stressors contribute to the pathophysiology of affective disorders and variations of cytokine functioning have been implicated in this process. The present investigation demonstrated, in mice, the impact of stressful aggressive encounters on activity levels, plasma corticosterone and cytokine concentrations, and on cytokine mRNA expression within the prefrontal cortex (PFC and hippocampus. As glucocorticoids have been tied to cytokine variations, mice were subdivided into low or high corticosterone responders, defined in terms of circulating hormone levels 75 min post-confrontation. Interestingly, stressor-induced effects among low and high responders varied as a function of whether mice were submissive or dominant during the aggressive bout. Agonistic encounters elicited subsequent hyperactivity, particularly among low corticosterone responders and among dominant mice. Plasma levels of corticosterone and interleukin (IL-6 concomitantly increased after aggressive encounters and varied with dominance status and with the low versus high corticosterone response. Among the low responders corticosterone and IL-6 increases were modest and only apparent among submissive mice, whereas among high responders these elevations were more pronounced and comparable in submissive and dominant mice. Aggressive episodes also increased IL-1B and IL-6 mRNA brain expression. The IL-1B rise was greater in the PFC and hippocampus of submissive mice that were low responders. Among high responders IL-1B and IL-6 increased in both groups, although in the PFC this effect was specific to dominant mice. The data are discussed in terms of their relevance to the impact of aggressive encounters on affective behaviors, and to the role that cytokines might play in this regard.

  7. Plasma nesfatin-1 is not affected by long-term food restriction and does not predict rematuration among iteroparous female rainbow trout (Oncorhynchus mykiss.

    Directory of Open Access Journals (Sweden)

    Lucius K Caldwell

    Full Text Available The metabolic peptide hormone nesfatin-1 has been linked to the reproductive axis in fishes. The purpose of this study was to determine how energy availability after spawning affects plasma levels of nesfatin-1, the metabolic peptide hormone ghrelin, and sex steroid hormones in rematuring female rainbow trout (Oncorhynchus mykiss. To limit reproductive maturation, a group of female trout was food-restricted after spawning and compared with a control group that was fed a standard broodstock ration. The experiment was conducted twice, once using two-year-old trout (second-time spawners and once using three-year-old trout (third-time spawners. During monthly sampling, blood was collected from all fish, and a subset of fish from each treatment was sacrificed for pituitaries. Pituitary follicle-stimulating hormone-beta (fsh-β mRNA expression was analyzed with q-RT-PCR; plasma hormone levels were quantified by radioimmunoassay (17β-estradiol and ghrelin and enzyme-linked immunosorbent assay (11-keto-testosterone and nesfatin-1. Although plasma nesfatin-1 levels increased significantly in the months immediately after spawning within both feeding treatments, plasma nesfatin-1 did not differ significantly between the two treatments at any point. Similarly, plasma ghrelin levels did not differ significantly between the two treatments at any point. Food restriction arrested ovarian development by 15-20 weeks after spawning, shown by significantly lower plasma E2 levels among restricted-ration fish. Pituitary fsh-β mRNA levels were higher among control-ration fish than restricted-ration fish starting at 20 weeks, but did not differ significantly between treatment groups until 30 weeks after spawning. Within both treatment groups, plasma 11-KT was elevated immediately after spawning and rapidly decreased to and persisted at low levels; starting between 20 and 25 weeks after spawning, plasma 11-KT was higher among control-ration fish than restricted

  8. Ageing and long-term smoking affects KL-6 levels in the lung, induced sputum and plasma

    Directory of Open Access Journals (Sweden)

    Horimasu Yasushi

    2011-05-01

    Full Text Available Abstract Background KL-6 is a high-molecular-weight glycoprotein classified as a human MUC1 mucin. It was hypothesized that KL-6 could be detectable in the circulating blood and especially in airway secretions in lung diseases associated with mucus production such as chronic obstructive pulmonary disease (COPD. Additional aims of this study were to investigate whether the levels of KL-6 in plasma and sputum are related to ageing and smoking history. Methods The concentrations of KL-6 in plasma and induced sputum supernatants from young and/or middle aged/elderly non-smokers, smokers and patients with COPD were assayed by ELISA (n = 201. The subjects were classified into five groups according to age, smoking status and presence of COPD. In addition, KL-6 expression in control and diseased lung i.e. samples from patients with COPD (n = 28, were analyzed by immunohistochemistry and digital image analysis. Results The plasma levels of KL-6 increased with age both in non-smokers and smokers. Among middle aged/elderly subjects, plasma KL-6 levels in all smokers regardless of COPD were significantly higher than in non-smokers, whereas sputum levels of KL-6 were significantly higher in COPD compared not only to non-smokers but also to smokers. KL-6 was more prominently expressed in the bronchiolar/alveolar epithelium in COPD than in the control lungs. Plasma and sputum KL-6 levels correlated inversely with obstruction and positively with smoking history and ageing. The linear multiple regression analysis confirmed that age and cigarette smoking had independent effects on plasma KL-6. Conclusions KL-6 increases with ageing and chronic smoking history, but prospective studies will be needed to elucidate the significance of KL-6 in chronic airway diseases.

  9. Treatment of Cancer Pain by Targeting Cytokines.

    Science.gov (United States)

    Vendrell, I; Macedo, D; Alho, I; Dionísio, M R; Costa, L

    2015-01-01

    Inflammation is one of the most important causes of the majority of cancer symptoms, including pain, fatigue, cachexia, and anorexia. Cancer pain affects 17 million people worldwide and can be caused by different mediators which act in primary efferent neurons directly or indirectly. Cytokines can be aberrantly produced by cancer and immune system cells and are of particular relevance in pain. Currently, there are very few strategies to control the release of cytokines that seems to be related to cancer pain. Nevertheless, in some cases, targeted drugs are available and in use for other diseases. In this paper, we aim to review the importance of cytokines in cancer pain and targeted strategies that can have an impact on controlling this symptom.

  10. The role of cytokines in immune changes induced by spaceflight

    Science.gov (United States)

    Sonnenfeld, G.; Miller, E. S.

    1993-01-01

    It has become apparent that spaceflight alters many immune responses. Among the regulatory components of the immune response that have been shown to be affected by spaceflight is the cytokine network. Spaceflight, as well as model systems of spaceflight, have been shown to affect the production and action of various cytokines including interferons, interleukins, colony stimulating factors, and tumor necrosis factors. These changes have been shown not to involve a general shutdown of the cytokine network but, rather, to involve selective alterations of specific cytokine functions by spaceflight. The full breadth of changes in cytokines induced by spaceflight, as well as mechanisms, duration, adaptation, reversibility, and significance to resistance to infection and neoplastic diseases, remains to be established.

  11. Cytokines in bipolar disorder vs. healthy control subjects

    DEFF Research Database (Denmark)

    Munkholm, Klaus; Braüner, Julie Vestergaard; Kessing, Lars Vedel

    2013-01-01

    Bipolar disorder may be associated with peripheral immune system dysfunction; however, results in individual studies are conflicting. Our aim was to systematically review evidence of peripheral cytokine alterations in bipolar disorder integrating findings from various affective states....

  12. Autophagy and cytokines.

    Science.gov (United States)

    Harris, James

    2011-11-01

    Autophagy is a highly conserved homoeostatic mechanism for the lysosomal degradation of cytosolic constituents, including long-lived macromolecules, organelles and intracellular pathogens. Autophagosomes are formed in response to a number of environmental stimuli, including amino acid deprivation, but also by both host- and pathogen-derived molecules, including toll-like receptor ligands and cytokines. In particular, IFN-γ, TNF-α, IL-1, IL-2, IL-6 and TGF-β have been shown to induce autophagy, while IL-4, IL-10 and IL-13 are inhibitory. Moreover, autophagy can itself regulate the production and secretion of cytokines, including IL-1, IL-18, TNF-α, and Type I IFN. This review discusses the potentially pivotal roles of autophagy in the regulation of inflammation and the coordination of innate and adaptive immune responses.

  13. Cytokines and anti-cytokines as therapeutics--an update.

    Science.gov (United States)

    Tayal, Vandana; Kalra, Bhupinder Singh

    2008-01-28

    Cytokines which comprise of a family of proteins--interleukins, lymphokines, monokines, interferons, and chemokines, are important components of the immune system. They act in concert with specific cytokine inhibitors and soluble cytokine receptors to regulate the human immune response. Their physiologic role in inflammation and pathologic role in systemic inflammatory states are now well recognized. An imbalance in cytokine production or cytokine receptor expression and/or dysregulation of a cytokine process contributes to various pathological disorders. Research is progressing rapidly in the area of cytokines and their therapeutic targets, the two major therapeutic modalities being the administration of purified recombinant cytokines and the use of their antagonists in various inflammatory disorders. However, given the large number of cytokines, it is disappointing that only relatively few can be used clinically. In the present article, we have made an attempt to review and present a glimpse of the history as well as up to date information that is pertinent to cytokines and anti-cytokine therapies in the treatment of cancer, autoimmune disorders and various other related diseases.

  14. Coordinate cytokine regulatory sequences

    Science.gov (United States)

    Frazer, Kelly A.; Rubin, Edward M.; Loots, Gabriela G.

    2005-05-10

    The present invention provides CNS sequences that regulate the cytokine gene expression, expression cassettes and vectors comprising or lacking the CNS sequences, host cells and non-human transgenic animals comprising the CNS sequences or lacking the CNS sequences. The present invention also provides methods for identifying compounds that modulate the functions of CNS sequences as well as methods for diagnosing defects in the CNS sequences of patients.

  15. Chemical modification of extracellular matrix by cold atmospheric plasma-generated reactive species affects chondrogenesis and bone formation.

    Science.gov (United States)

    Eisenhauer, Peter; Chernets, Natalie; Song, You; Dobrynin, Danil; Pleshko, Nancy; Steinbeck, Marla J; Freeman, Theresa A

    2016-09-01

    The goal of this study was to investigate whether cold plasma generated by dielectric barrier discharge (DBD) modifies extracellular matrices (ECM) to influence chondrogenesis and endochondral ossification. Replacement of cartilage by bone during endochondral ossification is essential in fetal skeletal development, bone growth and fracture healing. Regulation of this process by the ECM occurs through matrix remodelling, involving a variety of cell attachment molecules and growth factors, which influence cell morphology and protein expression. The commercially available ECM, Matrigel, was treated with microsecond or nanosecond pulsed (μsp or nsp, respectively) DBD frequencies conditions at the equivalent frequencies (1 kHz) or power (~1 W). Recombinant human bone morphogenetic protein-2 was added and the mixture subcutaneously injected into mice to simulate ectopic endochondral ossification. Two weeks later, the masses were extracted and analysed by microcomputed tomography. A significant increase in bone formation was observed in Matrigel treated with μsp DBD compared with control, while a significant decrease in bone formation was observed for both nsp treatments. Histological and immunohistochemical analysis showed Matrigel treated with μsp plasma increased the number of invading cells, the amount of vascular endothelial growth factor and chondrogenesis while the opposite was true for Matrigel treated with nsp plasma. In support of the in vivo Matrigel study, 10 T1/2 cells cultured in vitro on μsp DBD-treated type I collagen showed increased expression of adhesion proteins and activation of survival pathways, which decreased with nsp plasma treatments. These results indicate DBD modification of ECM can influence cellular behaviours to accelerate or inhibit chondrogenesis and endochondral ossification. Copyright © 2016 John Wiley & Sons, Ltd.

  16. Early social instability affects plasma testosterone during adolescence but does not alter reproductive capacity or measures of stress later in life.

    Science.gov (United States)

    Siegeler, Katja; Wistuba, Joachim; Damm, Oliver S; von Engelhardt, Nikolaus; Sachser, Norbert; Kaiser, Sylvia

    2013-08-15

    The social environment plays an important role in modulating processes of the hormonal and behavioural profile of an animal in a variety of group-living species. In wild cavies for instance, unstable social environmental conditions during pregnancy and lactation lead to an infantilised biobehavioural profile of the male offspring. In the present study, the influence of the social environment during pregnancy and lactation on the male wild cavy offsprings' plasma testosterone development, reproductive capacity and stress system activity was investigated. To this purpose, 12 sons whose mothers had lived in an unstable social environment during pregnancy and lactation were compared with 12 sons whose mothers had lived in a stable social environment during the same time. Plasma testosterone (T) and plasma cortisol (C) concentrations were determined from days 20 to 107 of age. Adrenal tyrosine hydroxylase (TH) activity and different parameters of reproductive capacity (weights of testes, epididymides and accessory sex glands, cellular composition of the testes, DNA fragmentation indices and sperm motility parameters) were analysed at day 107 of age. TH activity and plasma C were unaffected by different social environmental conditions early in life. The developmental time course of T concentrations, however, was significantly different: Sons whose mothers had lived in an unstable social environment during pregnancy and lactation showed a delayed increase in T concentrations around adolescence compared to controls. In contrast, no reproduction-related parameters measured within this study differed significantly between the two groups. Thus, early social instability affects plasma testosterone development during adolescence in a significant way but does not alter reproductive capacity or measures of stress later in life.

  17. Cytokine Therapies in Neurological Disease.

    Science.gov (United States)

    Azodi, Shila; Jacobson, Steven

    2016-07-01

    Cytokines are a heterogeneous group of glycoproteins that coordinate physiological functions. Cytokine deregulation is observed in many neurological diseases. This article reviews current research focused on human clinical trials of cytokine and anticytokine therapies in the treatment of several neurological disease including stroke, neuromuscular diseases, neuroinfectious diseases, demyelinating diseases, and neurobehavioral diseases. This research suggests that cytokine therapy applications may play an important role in offering new strategies for disease modulation and treatment. Further, this research provides insights into the causal link between cytokine deregulation and neurological diseases.

  18. Detection of autoantibodies to cytokines

    DEFF Research Database (Denmark)

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

    2000-01-01

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

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

    Science.gov (United States)

    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.

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

    DEFF Research Database (Denmark)

    Pankratova, S.; 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...... explain that NEC lesions, via changes in CSF cytokine levels, may affect neurodevelopment in preterm neonates...

  1. Wheat Bran Does Not Affect Postprandial Plasma Short-Chain Fatty Acids from 13C-inulin Fermentation in Healthy Subjects

    Science.gov (United States)

    Deroover, Lise; Verspreet, Joran; Luypaerts, Anja; Vandermeulen, Greet; Courtin, Christophe M.; Verbeke, Kristin

    2017-01-01

    Wheat bran (WB) is a constituent of whole grain products with beneficial effects for human health. Within the human colon, such insoluble particles may be colonized by specific microbial teams which can stimulate cross-feeding, leading to a more efficient carbohydrate fermentation and an increased butyrate production. We investigated the extent to which WB fractions with different properties affect the fermentation of other carbohydrates in the colon. Ten healthy subjects performed four test days, during which they consumed a standard breakfast supplemented with 10 g 13C-inulin. A total of 20 g of a WB fraction (unmodified WB, wheat bran with a reduced particle size (WB RPS), or de-starched pericarp-enriched wheat bran (PE WB)) was also added to the breakfast, except for one test day, which served as a control. Blood samples were collected at regular time points for 14 h, in order to measure 13C-labeled short-chain fatty acid (SCFA; acetate, propionate and butyrate) concentrations. Fermentation of 13C-inulin resulted in increased plasma SCFA for about 8 h, suggesting that a sustained increase in plasma SCFA can be achieved by administering a moderate dose of carbohydrates, three times per day. However, the addition of a single dose of a WB fraction did not further increase the 13C-SCFA concentrations in plasma, nor did it stimulate cross-feeding (Wilcoxon signed ranks test). PMID:28117694

  2. [Cytokines and hematopoiesis].

    Science.gov (United States)

    Mannoni, P

    1993-03-01

    The identification and purification of haemopoietic growth regulators have resulted in a better understanding of control mechanisms. Cloning and expression of the corresponding genes have shown that most of the activities observed correspond to specific glycoproteins produced by cells from numerous tissues, including those of bone marrow stroma and immune system. These cytokines activate the responsive cells through specific receptors expressed on their membranes. They exert an accurate control of haematopoiesis in a network of synergistic and antagonistic factors. The exact identification of their biological activities, together with the possibility of producing them in large amounts by genetic recombination, have already resulted in their therapeutic use with, in certain cases, a remarkable efficiency.

  3. The inflammatory cytokines: molecular biomarkers for major depressive disorder?

    Science.gov (United States)

    Martin, Charlotte; Tansey, Katherine E; Schalkwyk, Leonard C; Powell, Timothy R

    2015-01-01

    Cytokines are pleotropic cell signaling proteins that, in addition to their role as inflammatory mediators, also affect neurotransmitter systems, brain functionality and mood. Here we explore the potential utility of cytokine biomarkers for major depressive disorder. Specifically, we explore how genetic, transcriptomic and proteomic information relating to the cytokines might act as biomarkers, aiding clinical diagnosis and treatment selection processes. We advise future studies to investigate whether cytokine biomarkers might differentiate major depressive disorder patients from other patient groups with overlapping clinical characteristics. Furthermore, we invite future pharmacogenetic studies to investigate whether early antidepressant-induced changes to cytokine mRNA or protein levels precede behavioral changes and act as longer-term predictors of clinical antidepressant response.

  4. Chronic fatigue syndrome and circulating cytokines: A systematic review.

    Science.gov (United States)

    Blundell, S; Ray, K K; Buckland, M; White, P D

    2015-11-01

    There has been much interest in the role of the immune system in the pathophysiology of chronic fatigue syndrome (CFS), as CFS may develop following an infection and cytokines are known to induce acute sickness behaviour, with similar symptoms to CFS. Using the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-analyses) guidelines, a search was conducted on PubMed, Web of Science, Embase and PsycINFO, for CFS related-terms in combination with cytokine-related terms. Cases had to meet established criteria for CFS and be compared with healthy controls. Papers retrieved were assessed for both inclusionary criteria and quality. 38 papers met the inclusionary criteria. The quality of the studies varied. 77 serum or plasma cytokines were measured without immune stimulation. Cases of CFS had significantly elevated concentrations of transforming growth factor-beta (TGF-β) in five out of eight (63%) studies. No other cytokines were present in abnormal concentrations in the majority of studies, although insufficient data were available for some cytokines. Following physical exercise there were no differences in circulating cytokine levels between cases and controls and exercise made no difference to already elevated TGF-β concentrations. The finding of elevated TGF-β concentration, at biologically relevant levels, needs further exploration, but circulating cytokines do not seem to explain the core characteristic of post-exertional fatigue.

  5. [Cytokines in bone diseases. Cytokine and postmenopausal osteoporosis].

    Science.gov (United States)

    Inada, Masaki; Miyaura, Chisato

    2010-10-01

    Bone resorption is regulated by various cytokines. In postmenopausal osteoporosis, bone loss due to estrogen deficiency is closely related to the production of bone-resorbing cytokine. Especially, the increased production of IL-1, IL-6 and TNF-α could induce the expression of RANKL in bone tissues to enhance osteoclastogenesis. Relationship between estrogen deficiency and various cytokines is important to clarify the pathogenesis of postmenopausal osteoporosis.

  6. Arsenic exposure affects plasma insulin-like growth factor 1 (IGF-1 in children in rural Bangladesh.

    Directory of Open Access Journals (Sweden)

    Sultan Ahmed

    Full Text Available BACKGROUND: Exposure to inorganic arsenic (As through drinking water during pregnancy is associated with lower birth size and child growth. The aim of the study was to assess the effects of As exposure on child growth parameters to evaluate causal associations. METHODOLOGY/FINDINGS: Children born in a longitudinal mother-child cohort in rural Bangladesh were studied at 4.5 years (n=640 as well as at birth (n=134. Exposure to arsenic was assessed by concurrent and prenatal (maternal urinary concentrations of arsenic metabolites (U-As. Associations with plasma concentrations of insulin-like growth factor 1 (IGF-1, calcium (Ca, vitamin D (Vit-D, bone-specific alkaline phosphatase (B-ALP, intact parathyroid hormone (iPTH, and phosphate (PO4 were evaluated by linear regression analysis, adjusted for socioeconomic factor, parity and child sex. Child U-As (per 10 µg/L was significantly inversely associated with concurrent plasma IGF-1 (β=-0.27; 95% confidence interval: -0.50, -0.0042 at 4.5 years. The effect was more obvious in girls (β=-0.29; -0.59, 0.021 than in boys, and particularly in girls with adequate height (β=-0.491; -0.97, -0.02 or weight (β=-0.47; 0.97, 0.01. Maternal U-As was inversely associated with child IGF-1 at birth (r=-0.254, P=0.003, but not at 4.5 years. There was a tendency of positive association between U-As and plasma PO4 in stunted boys (β=0.27; 0.089, 0.46. When stratified by % monomethylarsonic acid (MMA, arsenic metabolite (median split at 9.7%, a much stronger inverse association between U-As and IGF-1 in the girls (β=-0.41; -0.77, -0.03 was obtained above the median split. CONCLUSION: The results suggest that As-related growth impairment in children is mediated, at least partly, through suppressed IGF-1 levels.

  7. Periconceptional undernutrition affects in utero methyltransferase expression and steroid hormone concentrations in uterine flushings and blood plasma during the peri-implantation period in domestic pigs.

    Science.gov (United States)

    Franczak, A; Zglejc, K; Waszkiewicz, E; Wojciechowicz, B; Martyniak, M; Sobotka, W; Okrasa, S; Kotwica, G

    2016-08-18

    Female undernutrition during early pregnancy may affect the physiological pattern of genomic DNA methylation. We hypothesised that in utero DNA methylation may be impaired in females fed a restrictive diet in early pregnancy. In this study we evaluated whether poor maternal nutritional status, induced by applying a restricted diet during the peri-conceptional period, may influence: (1) the potential for in utero DNA methylation, expressed as changes in the mRNA expression and protein abundance of methyltransferases: DNA methyltransferase 1 (DNMT1) and DNMT3a in the endometrium and the myometrium, (2) the intrauterine microenvironment, measured as oestradiol 17β (E2) and progesterone (P4) concentrations in uterine flushings and (3) plasma concentration of E2 and P4 during the peri-implantation period. Our results indicate that maternal peri-conceptional undernutrition affects maintenance and de novo DNA methylation in the endometrium, de novo methylation in the myometrium and a results in a decrease in intrauterine E2 concentration during the peri-implantation period. The intrauterine concentration of P4 and plasma concentrations of E2 and P4 did not change. These findings suggest that undernutrition during the earliest period of pregnancy, and perhaps the pre-pregnancy period, may create changes in epigenetic mechanisms in the uterus and intrauterine milieu of E2 during the peri-implantation period.

  8. Effects of intermittent hemofiltration on the protein levels of plasma inflammatory cytokines of severe acute panreatitis patients%间断短时血液滤过对重症急性胰腺炎患者血浆炎性细胞因子的影响

    Institute of Scientific and Technical Information of China (English)

    白云

    2011-01-01

    Severe acute pancreatitis (SAP) is a severe disease, a threat to patients' life.During SAP, large amounts of inflammatory cytokines are released to the blood plasma, which subsequently cause systemic inflammatory response syndrome in patients.It has been shown that high flow hemofiltration strategy is beneficial to clear up the blood inflammatory cytokines.In this study, we try a new strategy, intermittent hemofiltration, to observe the efficiency of the clearance of blood inflammatory cytokines in SAP patients by measuring TNF-α, IL-6 and IL-8 by ELISA assay.We found that patients treated with intermittent hemofiltration method had significantly lower levels of TNF-α and IL-8 in plasma at 4 days post treatment, and markedly lower levels of TNF-α, IL-6 and IL-8 levels at day 10 post treatment, as compared with control group.Results indicate that this new strategy has an advantage over the currently established methods on the clearance of inflammatory cytokines in SAP patients, and suggest its potential extended application in the future.%目的 观察间断短时血液滤过对重症急性胰腺炎血浆炎性细胞因子的影响.方法 重症胰腺炎病人经过短时、重复血液滤过后,酶联免疫吸附法测定血浆TNF-α、IL-6和IL-8水平.结果 血滤组与非血滤组住院第4天TNF-α及IL-8评分差异有统计学意义(P<0.05或P<0.01),住院第10天2组IL-6、IL-8及A队CHEⅡ差异均有统计学意义(P<0.01).结论 间断血液滤过治疗在控制病情、减轻或缩短SIRS上较非血滤组优越,提示该方法 有推广应用潜力.

  9. Cytokines and immune surveillance in humans

    Science.gov (United States)

    Sonnenfeld, Gerald

    1994-01-01

    Evidence from both human and rodent studies has indicated that alterations in immunological parameters occur after space flight. Among the parameters shown, by us and others, to be affected is the production of interferons. Interferons are a family of cytokines that are antiviral and play a major role in regulating immune responses that control resistance to infection. Alterations in interferon and other cytokine production and activity could result in changes in immunity and a possible compromise of host defenses against both opportunistic and external infections. The purpose of the present study is to explore further the effects of space flight on cyotokines and cytokine-directed immunological function. Among the tests carried out are interferon-alpha production, interferon-gamma production, interleukin-1 and -2 production, signal transduction in neutrophils, signal transduction in monocytes, and monocyte phagocytic activity. The experiments will be performed using peripheral blood obtained from human subjects. It is our intent to eventually carry out these experiments using astronauts as subjects to determine the effects of space flight on cytokine production and activity. However, these subjects are not currently available. Until they become available, we will carry out these experiments using subjects maintained in the bed-rest model for microgravity.

  10. Type 2 diabetes mellitus interacts with obesity and common variations in PLTP to affect plasma phospholipid transfer protein activity

    NARCIS (Netherlands)

    Dullaart, R. P. F.; Vergeer, M.; de Vries, R.; Kappelle, Paul J.W.H.; Dallinga-Thie, G. M.

    2012-01-01

    Dullaart RPF, Vergeer M, de Vries R, Kappelle PJWH, Dallinga-Thie GM (University Medical Center Groningen, University of Groningen, Groningen; and Academic Medical Center Amsterdam, Amsterdam; The Netherlands). Type 2 diabetes mellitus interacts with obesity and common variations in PLTP to affect p

  11. Circulating levels of platelet α-granule cytokines in trauma patients

    DEFF Research Database (Denmark)

    Windeløv, Nis Agerlin; Ostrowski, Sisse Rye; Johansson, Per Ingemar

    2015-01-01

    OBJECTIVE AND DESIGN: To elucidate whether platelets differentiate cytokine release following trauma, we prospectively measured three major platelet-derived cytokines in 213 trauma patients on hospital arrival. METHODS: We measured plasma levels of the anti-inflammatory β-thromboglobulins (β...

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

    DEFF Research Database (Denmark)

    Goegebeur, Yuri; Psiosik, Zofia; Klitkou, Louise

    2013-01-01

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

  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. Cytokines, cytokine gene polymorphisms and Helicobacter pylori infection: friend or foe?

    Science.gov (United States)

    Figueiredo, Camila A; Marques, Cintia Rodrigues; Costa, Ryan dos Santos; da Silva, Hugo Bernardino F; Alcantara-Neves, Neuza M

    2014-05-14

    Helicobacter pylori (H. pylori) is a flagellated, spiral-shaped, microaerophilic Gram-negative bacillus that colonises the gastric mucosa of more than 50% of the human population. Infection is a risk factor for gastritis, ulcer disease and stomach cancer. Immunity against H. pylori is mainly related to Th1/Th17 skewing, and the activation of regulatory T cells is the main strategy used to limit inflammatory responses, which can result in the pathogen persistence and can lead to chronic gastrointestinal diseases, including cancer. Furthermore, host genetic factors that affect cytokines may determine differences in the susceptibility to many diseases. In this review, we present the cytokine profiles and the main cytokine gene polymorphisms associated with resistance/susceptibility to H. pylori and discuss how such polymorphisms may influence infection/disease outcomes.

  15. Pivotal Advance: Th-1 cytokines inhibit, and Th-2 cytokines promote fibrocyte differentiation.

    Science.gov (United States)

    Shao, Diane D; Suresh, Rahul; Vakil, Varsha; Gomer, Richard H; Pilling, Darrell

    2008-06-01

    CD14+ peripheral blood monocytes can differentiate into fibroblast-like cells called fibrocytes, which are associated with and are at least partially responsible for wound healing and fibrosis in multiple organ systems. Signals regulating fibrocyte differentiation are poorly understood. In this study, we find that when added to human PBMCs cultured in serum-free medium, the profibrotic cytokines IL-4 and IL-13 promote fibrocyte differentiation without inducing fibrocyte or fibrocyte precursor proliferation. We also find that the potent, antifibrotic cytokines IFN-gamma and IL-12 inhibit fibrocyte differentiation. In our culture system, IL-1beta, IL-3, IL-6, IL-7, IL-16, GM-CSF, M-CSF, fetal liver tyrosine kinase 3, insulin growth factor 1, vascular endothelial growth factor, and TNF-alpha had no significant effect on fibrocyte differentiation. IL-4, IL-13, and IFN-gamma act directly on monocytes to regulate fibrocyte differentiation, and IL-12 acts indirectly, possibly through CD16-positive NK cells. We previously identified the plasma protein serum amyloid P (SAP) as a potent inhibitor of fibrocyte differentiation. When added together, the fibrocyte-inhibitory activity of SAP dominates the profibrocyte activities of IL-4 and IL-13. The profibrocyte activities of IL-4 and IL-13 and the fibrocyte-inhibitory activities of IFN-gamma and IL-12 counteract each other in a concentration-dependent manner. These results indicate that the complex mix of cytokines and plasma proteins present in inflammatory lesions, wounds, and fibrosis will influence fibrocyte differentiation.

  16. Poststroke Depression as a Factor Adversely Affecting the Level of Oxidative Damage to Plasma Proteins during a Brain Stroke

    Directory of Open Access Journals (Sweden)

    Natalia Cichoń

    2015-01-01

    Full Text Available Poststroke depression, the second most serious psychosomatic complication after brain stroke, leads to delay of the rehabilitation process and is associated with an increased disability and cognitive impairment along with increase in term mortality. Research into the biochemical changes in depression is still insufficiently described. The aim of our study was therefore to evaluate the possible association between plasma protein oxidative/nitrative damages and the development of poststroke depression. We evaluated oxidative/nitrative modifications of specific proteins by measurement of 3-nitrotyrosine and carbonyl groups levels using ELISA test. Additionally, we checked differences in proteins thiol groups by spectrophotometric assay based on reaction between DTNB and thiols. We also evaluated catalase activity in erythrocytes measured as ability to decompose H2O2. Correlation analysis was performed using Spearman’s rank. We observed significant (P<0.001 differences in all oxidative/nitrative stress parameters in brain stroke patients compared to healthy group. Our research shows that oxidative damage of proteins is correlated with the degree of poststroke depression, while nitrative changes do not show any relationship. We demonstrate a positive correlation between the concentration of carbonyl groups and the Geriatric Depression Scale and a negative correlation between the degree of depression and the concentration of -SH groups or catalase activity.

  17. Poststroke depression as a factor adversely affecting the level of oxidative damage to plasma proteins during a brain stroke.

    Science.gov (United States)

    Cichoń, Natalia; Bijak, Michał; Miller, Elżbieta; Niwald, Marta; Saluk, Joanna

    2015-01-01

    Poststroke depression, the second most serious psychosomatic complication after brain stroke, leads to delay of the rehabilitation process and is associated with an increased disability and cognitive impairment along with increase in term mortality. Research into the biochemical changes in depression is still insufficiently described. The aim of our study was therefore to evaluate the possible association between plasma protein oxidative/nitrative damages and the development of poststroke depression. We evaluated oxidative/nitrative modifications of specific proteins by measurement of 3-nitrotyrosine and carbonyl groups levels using ELISA test. Additionally, we checked differences in proteins thiol groups by spectrophotometric assay based on reaction between DTNB and thiols. We also evaluated catalase activity in erythrocytes measured as ability to decompose H2O2. Correlation analysis was performed using Spearman's rank. We observed significant (P stroke patients compared to healthy group. Our research shows that oxidative damage of proteins is correlated with the degree of poststroke depression, while nitrative changes do not show any relationship. We demonstrate a positive correlation between the concentration of carbonyl groups and the Geriatric Depression Scale and a negative correlation between the degree of depression and the concentration of -SH groups or catalase activity.

  18. Glycation sites of human plasma proteins are affected to different extents by hyperglycemic conditions in type 2 diabetes mellitus.

    Science.gov (United States)

    Frolov, Andrej; Blüher, Matthias; Hoffmann, Ralf

    2014-09-01

    Glucose can modify proteins in human blood, forming early glycation products (e.g., Amadori compounds), which can slowly degrade to advanced glycation endproducts (AGEs). AGEs contribute significantly to complications of diabetes mellitus and, thus, represent markers of advanced disease stages. They are, however, currently unsuitable for early diagnosis and therapeutic monitoring. Here, we report sensitive strategies to identify and relatively quantify protein glycation sites in human plasma samples obtained from type 2 diabetes mellitus (T2DM) patients and age-matched nondiabetic individuals using a bottom-up approach. Specifically, Amadori peptides were enriched from tryptic digests by boronic acid affinity chromatography, separated by reversed-phase chromatography, and analyzed on-line by high-resolution mass spectrometry. Among the 52 Amadori peptides studied here were 20 peptides resembling 19 glycation sites in six human proteins detected at statistically significantly higher levels in T2DM than in the normoglycemic controls. Four positions appeared to be unique for T2DM within the detection limit. All 19 glycation sites represent promising new biomarker candidates for early diagnosis of T2DM and adequate therapeutic control, as they may indicate early metabolic changes preceding T2DM.

  19. Transport of maternal cholesterol to the fetus is affected by maternal plasma cholesterol concentrations in the golden Syrian hamster.

    Science.gov (United States)

    Burke, Katie T; Colvin, Perry L; Myatt, Leslie; Graf, Gregory A; Schroeder, Friedhelm; Woollett, Laura A

    2009-06-01

    The fetus has a high requirement for cholesterol and synthesizes cholesterol at elevated rates. Recent studies suggest that fetal cholesterol also can be obtained from exogenous sources. The purpose of the current study was to examine the transport of maternal cholesterol to the fetus and determine the mechanism responsible for any cholesterol-driven changes in transport. Studies were completed in pregnant hamsters with normal and elevated plasma cholesterol concentrations. Cholesterol feeding resulted in a 3.1-fold increase in the amount of LDL-cholesterol taken up by the fetus and a 2.4-fold increase in the amount of HDL-cholesterol taken up. LDL-cholesterol was transported to the fetus primarily by the placenta, and HDL-cholesterol was transported by the yolk sac and placenta. Several proteins associated with sterol transport and efflux, including those induced by activated liver X receptor, were expressed in hamster and human placentas: NPC1, NPC1L1, ABCA2, SCP-x, and ABCG1, but not ABCG8. NPC1L1 was the only protein increased in hypercholesterolemic placentas. Thus, increasing maternal lipoprotein-cholesterol concentrations can enhance transport of maternal cholesterol to the fetus, leading to 1) increased movement of cholesterol down a concentration gradient in the placenta, 2) increased lipoprotein secretion from the yolk sac (shown previously), and possibly 3) increased placental NPC1L1 expression.

  20. Zinc and Regulation of Inflammatory Cytokines: Implications for Cardiometabolic Disease

    Directory of Open Access Journals (Sweden)

    Samir Samman

    2012-07-01

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

  1. The effect of recombinant erythropoietin on plasma brain derived neurotrophic factor levels in patients with affective disorders: a randomised controlled study.

    Directory of Open Access Journals (Sweden)

    Maj Vinberg

    Full Text Available The study aims to investigate the effect of repeated infusions of recombinant erythropoietin (EPO on plasma brain derived neurotrophic factor (BDNF levels in patients with affective disorders. In total, 83 patients were recruited: 40 currently depressed patients with treatment-resistant depression (TRD (Hamilton Depression Rating Scale-17 items (HDRS-17 score >17 (study 1 and 43 patients with bipolar disorder (BD in partial remission (HDRS-17 and Young Mania Rating Scale (YMRS ≤ 14 (study 2. In both studies, patients were randomised to receive eight weekly EPO (Eprex; 40,000 IU or saline (0.9% NaCl infusions in a double-blind, placebo-controlled, parallel--group design. Plasma BDNF levels were measured at baseline and at weeks 5, 9 and at follow up, week 14. In contrast with our hypothesis, EPO down regulated plasma BDNF levels in patients with TRD (mean reduction at week 9 (95% CI: EPO 10.94 ng/l (4.51-21.41 ng/l; mean increase at week 9: Saline 0.52 ng/l, p=0.04 (-5.88-4.48 ng/l p=0.04, partial ŋ2=0.12. No significant effects were found on BDNF levels in partially remitted patients with BD (p=0.35. The present effects of EPO on BDNF levels in patients with TRD point to a role of neurotrophic factors in the potential effects of EPO seen in TRD and BD. The neurobiological mechanisms underlying these effects and the interaction between EPO and peripheral levels on BDNF need to be further elucidated in human studies including a broad range of biomarkers.ClinicalTrials.gov: NCT00916552.

  2. Psoralen and Ultraviolet A Light Treatment Directly Affects Phosphatidylinositol 3-Kinase Signal Transduction by Altering Plasma Membrane Packing.

    Science.gov (United States)

    Van Aelst, Britt; Devloo, Rosalie; Zachée, Pierre; t'Kindt, Ruben; Sandra, Koen; Vandekerckhove, Philippe; Compernolle, Veerle; Feys, Hendrik B

    2016-11-18

    Psoralen and ultraviolet A light (PUVA) are used to kill pathogens in blood products and as a treatment of aberrant cell proliferation in dermatitis, cutaneous T-cell lymphoma, and graft-versus-host disease. DNA damage is well described, but the direct effects of PUVA on cell signal transduction are poorly understood. Because platelets are anucleate and contain archetypal signal transduction machinery, they are ideally suited to address this. Lipidomics on platelet membrane extracts showed that psoralen forms adducts with unsaturated carbon bonds of fatty acyls in all major phospholipid classes after PUVA. Such adducts increased lipid packing as measured by a blue shift of an environment-sensitive fluorescent probe in model liposomes. Furthermore, the interaction of these liposomes with lipid order-sensitive proteins like amphipathic lipid-packing sensor and α-synuclein was inhibited by PUVA. In platelets, PUVA caused poor membrane binding of Akt and Bruton's tyrosine kinase effectors following activation of the collagen glycoprotein VI and thrombin protease-activated receptor (PAR) 1. This resulted in defective Akt phosphorylation despite unaltered phosphatidylinositol 3,4,5-trisphosphate levels. Downstream integrin activation was furthermore affected similarly by PUVA following PAR1 (effective half-maximal concentration (EC50), 8.4 ± 1.1 versus 4.3 ± 1.1 μm) and glycoprotein VI (EC50, 1.61 ± 0.85 versus 0.26 ± 0.21 μg/ml) but not PAR4 (EC50, 50 ± 1 versus 58 ± 1 μm) signal transduction. Our findings were confirmed in T-cells from graft-versus-host disease patients treated with extracorporeal photopheresis, a form of systemic PUVA. In conclusion, PUVA increases the order of lipid phases by covalent modification of phospholipids, thereby inhibiting membrane recruitment of effector kinases.

  3. Cytokine receptors and hematopoietic differentiation.

    Science.gov (United States)

    Robb, L

    2007-10-15

    Colony-stimulating factors and other cytokines signal via their cognate receptors to regulate hematopoiesis. In many developmental systems, inductive signalling determines cell fate and, by analogy with this, it has been postulated that cytokines, signalling via their cognate receptors, may play an instructive role in lineage specification in hematopoiesis. An alternative to this instructive hypothesis is the stochastic or permissive hypothesis. The latter proposes that commitment to a particular hematopoietic lineage is an event that occurs independently of extrinsic signals. It predicts that the role of cytokines is to provide nonspecific survival and proliferation signals. In this review, we look at the role of cytokine receptor signalling in hematopoiesis and consider the evidence for both hypotheses. Data from experiments that genetically manipulate receptor gene expression in vitro or in vivo are reviewed. Experiments in which cytokine receptors were installed in multipotential cells showed that, in some cases, stimulation with the cognate ligand could lead to alterations in lineage output. The creation of genetically manipulated mouse strains demonstrated that cytokine receptors are required for expansion and survival of single lineages but did not reveal a role in lineage commitment. We conclude that hematopoietic differentiation involves mainly stochastic events, but that cytokine receptors also have some instructive role.

  4. 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.

  5. Understanding the role of cytokines in the pathogenesis of rheumatoid arthritis.

    Science.gov (United States)

    Mateen, Somaiya; Zafar, Atif; Moin, Shagufta; Khan, Abdul Qayyum; Zubair, Swaleha

    2016-04-01

    Rheumatoid arthritis (RA) is a chronic, inflammatory autoimmune disease of unknown etiology. It is characterized by the presence of rheumatoid factor and anti-citrullinated peptide antibodies. Initial phase of RA involves the activation of both T and B cells. Cytokines have a crucial role in the pathophysiology of RA as pro-inflammatory cytokines such as TNFα, IL-1, IL-17 stimulates inflammation and degradation of bone and cartilage. There occurs an imbalance between the pro- and anti-inflammatory cytokine activities which leads to multisystem immune complications. There occurs a decline in the number of Treg cells which may also play an important role in pathophysiology of the disease. In RA patients, serum or plasma level of cytokines may indicate the severity of disease. Cytokine gene polymorphism could be used as markers of susceptibility and severity of RA. Anti-cytokine agents seem to emerge as potent drug molecules to treat RA. Many clinical trials are ongoing and several positive results have been obtained. There is a need to develop potential anti-cytokine agents that target numerous pathways involved in the pathogenesis of RA. This review article describes the effector functions of pro- and anti-inflammatory cytokines and the role of cytokine gene polymorphism in the pathogenesis of RA. Anti-cytokine agents that are currently available and those that are still in clinical trials have also been summarized.

  6. B cells responses and cytokine production are regulated by their immune microenvironment.

    Science.gov (United States)

    Vazquez, Monica I; Catalan-Dibene, Jovani; Zlotnik, Albert

    2015-08-01

    The adaptive immune system consists of two types of lymphocytes: T and B cells. These two lymphocytes originate from a common precursor, yet are fundamentally different with B cells mediating humoral immunity while T cells mediate cell mediated immunity. In cytokine production, naïve T cells produce multiple cytokines upon activation while naïve activated B cells do not. B cells are capable of producing cytokines, but their cytokine production depends on their differentiation state and activation conditions. Hence, unlike T cells that can produce a large amount of cytokines upon activation, B cells require specific differentiation and activation conditions to produce cytokines. Many cytokines act on B cells as well. Here, we discuss several cytokines and their effects on B cells including: Interleukins, IL-7, IL-4, IL-6, IL-10, and Interferons, IFN-α, IFN-β, IFN-γ. These cytokines play important roles in the development, survival, differentiation and/or proliferation of B cells. Certain chemokines also play important roles in B cell function, namely antibody production. As an example, we discuss CCL28, a chemokine that directs the migration of plasma cells to mucosal sites. We conclude with a brief overview of B cells as cytokine producers and their likely functional consequences on the immune response.

  7. Leucocytes, cytokines and satellite cells

    DEFF Research Database (Denmark)

    Paulsen, Gøran; Mikkelsen, Ulla Ramer; Raastad, Truls

    2012-01-01

    -damaging exercise', primarily eccentric exercise. We review the evidence for the notion that the degree of muscle damage is related to the magnitude of the cytokine response. In the third and final section, we look at the satellite cell response to a single bout of eccentric exercise, as well as the role...... variation in individual responses to a given exercise should, however be expected. The link between cytokine and satellite cell responses and exercise-induced muscle damage is not so clear The systemic cytokine response may be linked more closely to the metabolic demands of exercise rather than muscle...... damage. With the exception of IL-6, the sources of systemic cytokines following exercise remain unclear The satellite cell response to severe muscle damage is related to regeneration, whereas the biological significance of satellite cell proliferation after mild damage or non-damaging exercise remains...

  8. Oxyntomodulin increases the concentrations of insulin and glucose in plasma but does not affect ghrelin secretion in Holstein cattle under normal physiological conditions.

    Science.gov (United States)

    ThanThan, S; Zhao, H; Yannaing, S; Ishikawa, T; Kuwayama, H

    2010-10-01

    Ghrelin, the natural ligand of the growth hormone secretagogue receptor (GHS-R1a), has been shown to stimulate growth hormone (GH) secretion. Regulation of ghrelin secretion in ruminants is not well studied. We investigated the effects of oxyntomodulin (OXM) and secretin on the secretions of ghrelin, insulin, glucagon, glucose, and nonesterified fatty acids (NEFA) in pre-ruminants (5 wk old) and ruminants (10 wk old) under normal physiological (feeding) conditions. Eight male Holstein calves (pre-ruminants: 52 +/- 1 kg body weight [BW]; and ruminants: 85 +/- 1 kg BW) were injected intravenously with 30 microg of OXM/kg BW, 50 microg of secretin/kg BW, and vehicle (0.1% bovine serum albumin [BSA] in saline as a control) in random order. Blood samples were collected, and plasma hormones and metabolites were analyzed using a double-antibody radioimmunoassay system and commercially available kits, respectively. We found that OXM increased the concentrations of insulin and glucose but did not affect the concentrations of ghrelin in both pre-ruminants and ruminants and that there was no effect of secretin on the concentrations of ghrelin, insulin, and glucose in these calves. We also investigated the dose-response effects of OXM on the secretion of insulin and glucose in 8 Holstein steers (401 +/- 1 d old, 398 +/- 10 kg BW). We found that OXM increased the concentrations of insulin and glucose even at physiological plasma concentrations, with a minimum effective dose of 0.4 microg/kg for the promotion of glucose secretion and 2 microg/kg for the stimulation of insulin secretion. These findings suggest that OXM takes part in glucose metabolism in ruminants.

  9. Th2 cytokines inhibit lymphangiogenesis.

    Directory of Open Access Journals (Sweden)

    Ira L Savetsky

    Full Text Available Lymphangiogenesis is the process by which new lymphatic vessels grow in response to pathologic stimuli such as wound healing, inflammation, and tumor metastasis. It is well-recognized that growth factors and cytokines regulate lymphangiogenesis by promoting or inhibiting lymphatic endothelial cell (LEC proliferation, migration and differentiation. Our group has shown that the expression of T-helper 2 (Th2 cytokines is markedly increased in lymphedema, and that these cytokines inhibit lymphatic function by increasing fibrosis and promoting changes in the extracellular matrix. However, while the evidence supporting a role for T cells and Th2 cytokines as negative regulators of lymphatic function is clear, the direct effects of Th2 cytokines on isolated LECs remains poorly understood. Using in vitro and in vivo studies, we show that physiologic doses of interleukin-4 (IL-4 and interleukin-13 (IL-13 have profound anti-lymphangiogenic effects and potently impair LEC survival, proliferation, migration, and tubule formation. Inhibition of these cytokines with targeted monoclonal antibodies in the cornea suture model specifically increases inflammatory lymphangiogenesis without concomitant changes in angiogenesis. These findings suggest that manipulation of anti-lymphangiogenic pathways may represent a novel and potent means of improving lymphangiogenesis.

  10. Cytokines and soluble tumour necrosis factor I receptor levels during pretransplant conditioning in allogeneic stem-cell transplantation

    DEFF Research Database (Denmark)

    Andersen, Johnny; Heilmann, Carsten; Jacobsen, Niels;

    2005-01-01

    The inflammatory response induced by the conditioning regime may be related to the outcome in allogeneic stem-cell transplantation (SCT). However, previous statements concerning the prognostic significance of cytokine measurements during conditioning have not been conclusive. We investigated...... a broad range of cytokines in plasma samples drawn daily immediately before start of pretransplant conditioning and during the conditioning. The presented data indicate that single-day measurements of inflammatory cytokines during conditioning may lead to unreliable conclusions concerning their prognostic...

  11. Increase of plasma IL-9 and decrease of plasma IL-5, IL-7, and IFN-γ in patients with chronic heart failure

    Directory of Open Access Journals (Sweden)

    Liuzzo Giovanna

    2011-03-01

    Full Text Available Abstract Background Several cytokines are associated with the development and/or progression of chronic heart failure (CHF. Our aim was to look more closely at the cytokine networks involved in CHF, and to assess whether disease etiology affects cytokine expression. The study population was comprised of a 69 patients with stable CHF, New York Heart Association (NYHA II/IV classes, secondary to ischaemic (ICM and non ischaemic dilated (NIDCM cardiomyopathy and b 16 control subjects. We analyzed and compared the plasma levels of 27 pro- and anti-inflammatory mediators, in the study population and assessed for any possible correlation with echocardiographic parameters and disease duration. Methods 27 cytokines and growth factors were analyzed in the plasma of ICM- (n = 42 and NIDCM (n = 27 NYHA class II-IV patients vs age- and gender-matched controls (n = 16 by a beadbased multiplex immunoassay. Statistical analysis was performed by ANOVA followed by Tukey post-hoc test for multiple comparison. Results Macrophage inflammatory protein (MIP-1β, Vascular endothelial growth factor (VEGF, interleukin (IL-9, Monocyte chemotactic protein (MCP-1, and IL-8 plasma levels were increased in both ICM and NIDCM groups vs controls. In contrast, IL-7, IL-5, and Interferon (IFN-γ were decreased in both ICM and NIDCM groups as compared to controls. Plasma IL-6 and IL-1 β were increased in ICM and decreased in NIDCM, vs controls, respectively. IL-9 levels inversely correlated, in ICM patients, with left ventricular ejection fraction (LVEF while IL-5 plasma levels inversely correlated with disease duration, in NYHA III/IV ICM patients. This is the first time that both an increase of plasma IL-9, and a decrease of plasma IL-5, IL-7 and IFN-γ have been reported in ICM as well as in NIDCM groups, vs controls. Interestingly, such cytokines are part of a network of genes whose expression levels change during chronic heart failure. The altered expression levels of MIP-1

  12. Cytokines in Sjogren's syndrome: potential therapeutic targets

    NARCIS (Netherlands)

    Roescher, N.; Tak, P.P.; Illei, G.G.

    2010-01-01

    The dysregulated cytokine network in Sjogren's Syndrome (SS) is reflected by local and systemic overexpression of pro-inflammatory cytokines and absent or low levels of anti-inflammatory cytokines. To date, the use of cytokine based therapies in SS has been disappointing. Oral administration of low

  13. Circadian Rhythm in Cytokines Administration.

    Science.gov (United States)

    Trufakin, Valery A; Shurlygina, Anna V

    2016-01-01

    In recent times, a number of diseases involving immune system dysfunction have appeared. This increases the importance of research aimed at finding and developing optimized methods for immune system correction. Numerous studies have found a positive effect in using cytokines to treat a variety of diseases, yet the clinical use of cytokines is limited by their toxicity. Research in the field of chronotherapy, aimed at designing schedules of medicine intake using circadian biorhythms of endogenous production of factors, and receptors' expression to the factors on the target cells, as well as chronopharmacodynamics and chronopharmacokinetics of medicines may contribute to the solution of this problem. Advantages of chronotherapy include a greater effectiveness of treatment, reduced dose of required drugs, and minimized adverse effects. This review presents data on the presence of circadian rhythms of spontaneous and induced cytokine production, as well as the expression of cytokine receptors in the healthy body and in a number of diseases. The article reviews various effects of cytokines, used at different times of the day in humans and experimental animals, as well as possible mechanisms underlying the chronodependent effects of cytokines. The article presents the results of chronotherapeutic modes of administering IL-2, interferons, G-CSF, and GM-CSF in treatment of various types of cancer as well as in experimental models of immune suppression and inflammation, which lead to a greater effectiveness of therapy, the possibility of reducing or increasing the dosage, and reduced drug toxicity. Further research in this field will contribute to the effectiveness and safety of cytokine therapy.

  14. Neuroinflammation and cytokine abnormality in major depression: Cause or consequence in that illness?

    Science.gov (United States)

    Jeon, Sang Won; Kim, Yong Ku

    2016-01-01

    Depression results from changes in the central nervous system (CNS) that may result from immunological abnormalities. The immune system affects the CNS through cytokines, which regulate brain activities and emotions. Cytokines affect two biological systems that are most associated with the pathophysiology of depression: The hypothalamic-pituitary-adrenal axis and the catecholamine/sympathetic nervous system. Neuroinflammation and cytokines affect the brain signal patterns involved in the psychopathology of depression and the mechanisms of antidepressants, and they are associated with neurogenesis and neural plasticity. These observations suggest that neuroinflammation and cytokines might cause and/or maintain depression, and that they might be useful in the diagnosis and prognosis of depression. This psychoneuroimmunologic perspective might compensate for some of the limitations of the monoamine theory by suggesting that depression is a result of a failure to adapt to stress and that inflammatory responses and cytokines are involved in this process. In this review, the interactions of cytokines with the CNS, neuroendocrine system, neurotransmitters, neurodegeneration/neurogenesis, and antidepressants are discussed. The roles of cytokines in the etiology and psychopathology of depression are examined. The use of cytokine inhibitors or anti-inflammatory drugs in depression treatment is explored. Finally, the significance and limitations of the cytokine hypothesis are discussed. PMID:27679767

  15. Neuroinflammation and cytokine abnormality in major depression: Cause or consequence in that illness?

    Science.gov (United States)

    Jeon, Sang Won; Kim, Yong Ku

    2016-09-22

    Depression results from changes in the central nervous system (CNS) that may result from immunological abnormalities. The immune system affects the CNS through cytokines, which regulate brain activities and emotions. Cytokines affect two biological systems that are most associated with the pathophysiology of depression: The hypothalamic-pituitary-adrenal axis and the catecholamine/sympathetic nervous system. Neuroinflammation and cytokines affect the brain signal patterns involved in the psychopathology of depression and the mechanisms of antidepressants, and they are associated with neurogenesis and neural plasticity. These observations suggest that neuroinflammation and cytokines might cause and/or maintain depression, and that they might be useful in the diagnosis and prognosis of depression. This psychoneuroimmunologic perspective might compensate for some of the limitations of the monoamine theory by suggesting that depression is a result of a failure to adapt to stress and that inflammatory responses and cytokines are involved in this process. In this review, the interactions of cytokines with the CNS, neuroendocrine system, neurotransmitters, neurodegeneration/neurogenesis, and antidepressants are discussed. The roles of cytokines in the etiology and psychopathology of depression are examined. The use of cytokine inhibitors or anti-inflammatory drugs in depression treatment is explored. Finally, the significance and limitations of the cytokine hypothesis are discussed.

  16. Endotoxin and cytokines in patients with gastrointestinal tract perforation

    Directory of Open Access Journals (Sweden)

    S. Endo

    1992-01-01

    Full Text Available Plasma levels of endotoxin and various cytokines were assessed in 70 patients with gastrointestinal tract perforation. Sepsis developed in 29 of them, and eight of these (27.6% had on admission endotoxin levels higher than 9.8 pg ml-1. The clinical outcome correlated with the level of tumour necrosis factor α (TNFα, rather than with the endotoxin level. The high interleukin 6 (IL-6 level was shown in septic patients and no correlation was observed between the IL-6 level and the clinical outcome. Plasma TNFα levels tended to change independently from endotoxin levels, suggesting that TNFα may have been locally produced in inflammatory lesions.

  17. 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.

  18. 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.

  19. Plasma fatty acid ratios affect blood gene expression profiles--a cross-sectional study of the Norwegian Women and Cancer Post-Genome Cohort.

    Science.gov (United States)

    Olsen, Karina Standahl; Fenton, Christopher; Frøyland, Livar; Waaseth, Marit; Paulssen, Ruth H; Lund, Eiliv

    2013-01-01

    High blood concentrations of n-6 fatty acids (FAs) relative to n-3 FAs may lead to a "physiological switch" towards permanent low-grade inflammation, potentially influencing the onset of cardiovascular and inflammatory diseases, as well as cancer. To explore the potential effects of FA ratios prior to disease onset, we measured blood gene expression profiles and plasma FA ratios (linoleic acid/alpha-linolenic acid, LA/ALA; arachidonic acid/eicosapentaenoic acid, AA/EPA; and total n-6/n-3) in a cross-section of middle-aged Norwegian women (n = 227). After arranging samples from the highest values to the lowest for all three FA ratios (LA/ALA, AA/EPA and total n-6/n-3), the highest and lowest deciles of samples were compared. Differences in gene expression profiles were assessed by single-gene and pathway-level analyses. The LA/ALA ratio had the largest impact on gene expression profiles, with 135 differentially expressed genes, followed by the total n-6/n-3 ratio (125 genes) and the AA/EPA ratio (72 genes). All FA ratios were associated with genes related to immune processes, with a tendency for increased pro-inflammatory signaling in the highest FA ratio deciles. Lipid metabolism related to peroxisome proliferator-activated receptor γ (PPARγ) signaling was modified, with possible implications for foam cell formation and development of cardiovascular diseases. We identified higher expression levels of several autophagy marker genes, mainly in the lowest LA/ALA decile. This finding may point to the regulation of autophagy as a novel aspect of FA biology which warrants further study. Lastly, all FA ratios were associated with gene sets that included targets of specific microRNAs, and gene sets containing common promoter motifs that did not match any known transcription factors. We conclude that plasma FA ratios are associated with differences in blood gene expression profiles in this free-living population, and that affected genes and pathways may influence the

  20. Plasma fatty acid ratios affect blood gene expression profiles--a cross-sectional study of the Norwegian Women and Cancer Post-Genome Cohort.

    Directory of Open Access Journals (Sweden)

    Karina Standahl Olsen

    Full Text Available High blood concentrations of n-6 fatty acids (FAs relative to n-3 FAs may lead to a "physiological switch" towards permanent low-grade inflammation, potentially influencing the onset of cardiovascular and inflammatory diseases, as well as cancer. To explore the potential effects of FA ratios prior to disease onset, we measured blood gene expression profiles and plasma FA ratios (linoleic acid/alpha-linolenic acid, LA/ALA; arachidonic acid/eicosapentaenoic acid, AA/EPA; and total n-6/n-3 in a cross-section of middle-aged Norwegian women (n = 227. After arranging samples from the highest values to the lowest for all three FA ratios (LA/ALA, AA/EPA and total n-6/n-3, the highest and lowest deciles of samples were compared. Differences in gene expression profiles were assessed by single-gene and pathway-level analyses. The LA/ALA ratio had the largest impact on gene expression profiles, with 135 differentially expressed genes, followed by the total n-6/n-3 ratio (125 genes and the AA/EPA ratio (72 genes. All FA ratios were associated with genes related to immune processes, with a tendency for increased pro-inflammatory signaling in the highest FA ratio deciles. Lipid metabolism related to peroxisome proliferator-activated receptor γ (PPARγ signaling was modified, with possible implications for foam cell formation and development of cardiovascular diseases. We identified higher expression levels of several autophagy marker genes, mainly in the lowest LA/ALA decile. This finding may point to the regulation of autophagy as a novel aspect of FA biology which warrants further study. Lastly, all FA ratios were associated with gene sets that included targets of specific microRNAs, and gene sets containing common promoter motifs that did not match any known transcription factors. We conclude that plasma FA ratios are associated with differences in blood gene expression profiles in this free-living population, and that affected genes and pathways may

  1. Effects of treatment with melatonin and tryptophan on liver enzymes, parameters of fat metabolism and plasma levels of cytokines in patients with non-alcoholic fatty liver disease--14 months follow up.

    Science.gov (United States)

    Celinski, K; Konturek, P C; Slomka, M; Cichoz-Lach, H; Brzozowski, T; Konturek, S J; Korolczuk, A

    2014-02-01

    levels of pro-inflammatory cytokines and improve some parameters of fat metabolism in patients with NAFLD. In few patients with NASH melatonin and tryptophan reduced the inflammation in liver. We conclude that melatonin is worth considering for the therapy of NAFLD, particularly in patients with impaired fat metabolism accompanied by hypertriglyceridemia and hyper-LDL cholesterolemia.

  2. Cytokine profile in murine toxoplasmosis

    Institute of Scientific and Technical Information of China (English)

    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.

  3. Cytokines, STATs and Liver Disease

    Institute of Scientific and Technical Information of China (English)

    BinGao

    2005-01-01

    The Janus kinase-signal transducers and activators of transcription (JAK-STAT) signaling pathway, activated by more than 50 cytokines or growth factors, plays critical roles in a wide variety of cellular functions in the hematopoietic, immune, neuronal and hepatic systems. In the liver, this signaling pathway, activated by more than 20 cytokines, growth factors, hormones, and hepatitis viral proteins, plays critical roles in antiviral defense, acute phase response, hepatic injury, repair, inflammation, transformation, and hepatitis. This article reviews the biological significance of STAT1, 2, 3, 4, 5, 6 in hepatic functions and diseases. Cellular & Molecular Immunology. 2005;2(2):92-100.

  4. Cytokines, STATs and Liver Disease

    Institute of Scientific and Technical Information of China (English)

    Bin Gao

    2005-01-01

    The Janus kinase-signal transducers and activators of transcription (JAK-STAT) signaling pathway, activated by more than 50 cytokines or growth factors, plays critical roles in a wide variety of cellular functions in the hematopoietic, immune, neuronal and hepatic systems. In the liver, this signaling pathway, activated by more than 20 cytokines, growth factors, hormones, and hepatitis viral proteins, plays critical roles in antiviral defense, acute phase response, hepatic injury, repair, inflammation, transformation, and hepatitis. This article reviews the biological significance of STAT1, 2, 3, 4, 5, 6 in hepatic functions and diseases. Cellular & Molecular Immunology.2005;2(2):92-100.

  5. Cytokine crowdsourcing: multicellular production of TH17-associated cytokines.

    Science.gov (United States)

    Busman-Sahay, Kathleen O; Walrath, Travis; Huber, Samuel; O'Connor, William

    2015-03-01

    In the 2 decades since its discovery, IL-17A has become appreciated for mounting robust, protective responses against bacterial and fungal pathogens. When improperly regulated, however, IL-17A can play a profoundly pathogenic role in perpetuating inflammation and has been linked to a wide variety of debilitating diseases. IL-17A is often present in a composite milieu that includes cytokines produced by TH17 cells (i.e., IL-17F, IL-21, IL-22, and IL-26) or associated with other T cell lineages (e.g., IFN-γ). These combinatorial effects add mechanistic complexity and more importantly, contribute differentially to disease outcome. Whereas TH17 cells are among the best-understood cell types that secrete IL-17A, they are frequently neither the earliest nor dominant producers. Indeed, non-TH17 cell sources of IL-17A can dramatically alter the course and severity of inflammatory episodes. The dissection of the temporal regulation of TH17-associated cytokines and the resulting net signaling outcomes will be critical toward understanding the increasingly intricate role of IL-17A and TH17-associated cytokines in disease, informing our therapeutic decisions. Herein, we discuss important non-TH17 cell sources of IL-17A and other TH17-associated cytokines relevant to inflammatory events in mucosal tissues.

  6. Ca2+- and Mg2+-ATPase activities in winter wheat root plasma membranes as affected by NaCl stress during growth

    NARCIS (Netherlands)

    Mansour, MMF; van Hasselt, PR; Kuiper, PJC

    1998-01-01

    Winter wheat seedlings were grown in Hoagland nutrient solution with or without 100 mmol/L NaCl added. Plasma membranes from root cells were prepared by aqueous polymer two phase partitioning and the stimulation of plasma membrane ATPase activity by Mg2+ and Ca2+ was investigated. The enzyme was act

  7. The Role of Cytokines and Chemokines in Filovirus Infection

    Directory of Open Access Journals (Sweden)

    Sandra L. Bixler

    2015-10-01

    Full Text Available Ebola- and marburgviruses are highly pathogenic filoviruses and causative agents of viral hemorrhagic fever. Filovirus disease is characterized by a dysregulated immune response, severe organ damage, and coagulation abnormalities. This includes modulation of cytokines, signaling mediators that regulate various components of the immune system as well as other biological processes. Here we examine the role of cytokines in filovirus infection, with an emphasis on understanding how these molecules affect development of the antiviral immune response and influence pathology. These proteins may present targets for immune modulation by therapeutic agents and vaccines in an effort to boost the natural immune response to infection and/or reduce immunopathology.

  8. Malaria: toxins, cytokines and disease

    DEFF Research Database (Denmark)

    Jakobsen, P H; Bate, C A; Taverne, J;

    1995-01-01

    In this review the old concept of severe malaria as a toxic disease is re-examined in the light of recent discoveries in the field of cytokines. Animal studies suggest that the induction of TNF by parasite-derived molecules may be partly responsible for cerebral malaria and anemia, while hypoglyc...

  9. Cytokines in human lung fibrosis.

    Science.gov (United States)

    Martinet, Y; Menard, O; Vaillant, P; Vignaud, J M; Martinet, N

    1996-01-01

    Fibrosis is a pathological process characterized by the replacement of normal tissue by mesenchymal cells and the extracellular matrix produced by these cells. The sequence of events leading to fibrosis of an organ involves the subsequent processes of injury with inflammation and disruption of the normal tissue architecture, followed by tissue repair with accumulation of mesenchymal cells in the area of derangement. The same sequence of events occurs in wound healing with normal granulation tissue and scar formation, but, while normal scar formation is very localized and transient, in contrast, in fibrosis, the repair process is exaggerated and usually widespread and can be chronic. Inflammatory cells (mainly mononuclear phagocytes), platelets, endothelial cells, and type II pneumocytes play a direct and indirect role in tissue injury and repair. The evaluation of three human fibrotic lung diseases, two diffuse [idiopathic pulmonary fibrosis (IPF), and the adult respiratory distress syndrome (ARDS)], and one focal (tumor stroma in lung cancer), has shown that several cytokines participate to the local injury and inflammatory reaction [interleukin-1 (IL-1), interleukin-8 (IL-8), monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-alpha)], while other cytokines are involved in tissue repair and fibrosis [platelet-derived growth factor (PDGF), insulin-like growth factor-1 (IGF-1), transforming growth factor-beta (TGF-beta), and basic-fibroblast growth factor (b-FGF)]. A better understanding of the cytokines and cytokine networks involved in lung fibrosis leads to the possibility of new therapeutic approaches.

  10. Anesthesiology and the cytokine network

    Directory of Open Access Journals (Sweden)

    Barbara Lisowska

    2013-08-01

    Full Text Available The immune response is a highly specific reaction carried out by means of specialized cells that belong to the immune system. There are two types of immune response mechanisms aimed towards pathogens: non-specific, innate reactions, and specific, acquired reactions. Acquired immunity, characterized by its specificity, is comprised of lymphocytes, including both T cell and B cell populations. The role of B lymphocytes is not limited to the humoral response, though the cellular immune response is carried out mainly by various T lymphocyte subpopulations. The reactions of the humoral and cellular responses complement and stimulate one another mutually – cytokines are their common linking element. The attachment of cytokines to their specific receptors activates a sequence of signals – either intracellular or between the cells of various systems. This organization of respective connections and reactions, including the functional relations between cells of the immune response, in its complexity, is best described as a cytokine network. The response of the immune system to surgical trauma can be looked at from both a local and a general perspective. Not only surgical trauma caused by tissue damage, however, influences the functioning of the immune system, but also the drugs and techniques used during anesthesia. Our article is a presentation of the effects of medications used in anesthesia with respect to their influence on the cytokine network.

  11. Formulation and stability of cytokine therapeutics.

    Science.gov (United States)

    Lipiäinen, Tiina; Peltoniemi, Marikki; Sarkhel, Sanjay; Yrjönen, Teijo; Vuorela, Heikki; Urtti, Arto; Juppo, Anne

    2015-02-01

    Cytokines are messenger proteins that regulate the proliferation and differentiation of cells and control immune responses. Interferons, interleukins, and growth factors have applications in cancer, autoimmune, and viral disease treatment. The cytokines are susceptible to chemical and physical instability. This article reviews the structure and stability issues of clinically used cytokines, as well as formulation strategies for improved stability. Some general aspects for identifying most probable stability concerns, selecting excipients, and developing stable cytokine formulations are presented. The vast group of cytokines offers possibilities for new biopharmaceuticals. The formulation approaches of the current cytokine products could facilitate development of new biopharmaceuticals.

  12. Cytokine responses during chronic denervation

    Directory of Open Access Journals (Sweden)

    Olsson Tomas

    2005-11-01

    Full Text Available Abstract Background The aim of the present study was to examine inflammatory responses during Wallerian degeneration in rat peripheral nerve when the regrowth of axons was prevented by suturing. Methods Transected rat sciatic nerve was sutured and ligated to prevent reinnervation. The samples were collected from the left sciatic nerve distally and proximally from the point of transection. The endoneurium was separated from the surrounding epi- and perineurium to examine the expression of cytokines in both of these compartments. Macrophage invasion into endoneurium was investigated and Schwann cell proliferation was followed as well as the expression of cytokines IL-1β, IL-10, IFN-γ and TNF-α mRNA. The samples were collected from 1 day up to 5 weeks after the primary operation. Results At days 1 to 3 after injury in the epi-/perineurium of the proximal and distal stump, a marked expression of the pro-inflammatory cytokines TNF-α and IL-1β and of the anti-inflammatory cytokine IL-10 was observed. Concurrently, numerous macrophages started to gather into the epineurium of both proximal and distal stumps. At day 7 the number of macrophages decreased in the perineurium and increased markedly in the endoneurium of both stumps. At this time point marked expression of TNF-α and IFN-γ mRNA was observed in the endo- and epi-/perineurium of the proximal stump. At day 14 a marked increase in the expression of IL-1β could be noted in the proximal stump epi-/perineurium and in the distal stump endoneurium. At that time point many macrophages were observed in the longitudinally sectioned epineurium of the proximal 2 area as well as in the cross-section slides from the distal stump. At day 35 TNF-α, IL-1β and IL-10 mRNA appeared abundantly in the proximal epi-/perineurium together with macrophages. Conclusion The present studies show that even during chronic denervation there is a cyclic expression pattern for the studied cytokines. Contrary to the

  13. Consumption of soy isoflavone enriched bread in men with prostate cancer is associated with reduced proinflammatory cytokines and immunosuppressive cells.

    Science.gov (United States)

    Lesinski, Gregory B; Reville, Patrick K; Mace, Thomas A; Young, Gregory S; Ahn-Jarvis, Jennifer; Thomas-Ahner, Jennifer; Vodovotz, Yael; Ameen, Zeenath; Grainger, Elizabeth; Riedl, Kenneth; Schwartz, Steven; Clinton, Steven K

    2015-11-01

    We hypothesized that soy phytochemicals may have immunomodulatory properties that may affect prostate carcinogenesis and progression. A randomized, phase II trial was conducted in 32 patients with prostate cancer with asymptomatic biochemical recurrence but no measurable disease on standard staging studies. Patients were randomized to two slices of soy bread (34 mg isoflavones/slice) or soy bread containing almond powder daily as a source of β-glucosidase. Flow cytometry and bioplex assays were used to measure cytokines or immune cell phenotype in blood at baseline (day 0) and following intervention (day 56). Adequate blood samples were available at enrollment and day 56 and evaluated. Multiple plasma cytokines and chemokines were significantly decreased on day 56 versus baseline. Subgroup analysis indicated reduced TH1 (P = 0.028) and myeloid-derived suppressor cell (MDSC)-associated cytokines (P = 0.035). TH2 and TH17 cytokines were not significantly altered. Phenotypic analysis revealed no change in CD8(+) or CD4(+) T cells but showed increased CD56(+) natural killer (NK) cells (P = 0.038). The percentage of cells with a T regulatory cell phenotype (CD4(+)CD25(+)FoxP3(+)) was significantly decreased after 56 days of soy bread (P = 0.0136). Significantly decreased monocytic (CD33(+)HLADR(neg)CD14(+)) MDSC were observed in patients consuming soy bread (P = 0.0056). These data suggest that soy bread modulates systemic soluble and cellular biomarkers consistent with limiting inflammation and suppression of MDSCs. Additional studies to elucidate impact on the carcinogenic process or as a complement to immune-based therapy are required.

  14. Therapeutic modulation of growth factors and cytokines in regenerative medicine.

    Science.gov (United States)

    Ioannidou, Effie

    2006-01-01

    Regeneration that takes place in the human body is limited throughout life. Therefore, when organs are irreparably damaged, they are usually replaced with an artificial device or donor organ. The term "regenerative medicine" covers the restoration or replacement of cells, tissues, and organs. Stem cells play a major role in regenerative medicine by providing the way to repopulate organs damaged by disease. Stem cells have the ability to self renew and to regenerate cells of diverse lineages within the tissue in which they reside. Stem cells could originate from embryos or adult tissues. Growth factors are proteins that may act locally or systemically to affect the growth of cells in several ways. Various cell activities, including division, are influenced by growth factors. Cytokines are a family of low-molecular-weight proteins that are produced by numerous cell types and are responsible for regulating the immune response, inflammation, tissue remodeling and cellular differentiation. Target cells of growth factors and cytokines are mesenchymal, epithelial and endothelial cells. These molecules frequently have overlapping activities and can act in an autocrine or paracrine fashion. A complex network of growth factors and cytokines guides cellular differentiation and regeneration in all organs and tissues. The aim of this paper is to review the role of growth factors and cytokines in different organs or systems and explore their therapeutic application in regenerative medicine. The role of stem cells combined with growth factors and cytokines in the regeneration of vascular and hematopoietic, neural, skeletal, pancreatic, periodontal, and mucosal tissue is reviewed. There is evidence that supports the use of growth factors and cytokines in the treatment of neurological diseases, diabetes, cardiovascular disease, periodontal disease, cancer and its complication, oral mucositis. After solving the ethical issues and establishing clear and reasonable regulations

  15. Altered sodium intake affects plasma concentrations of BNP but not proBNP in healthy individuals and patients with compensated heart failure

    DEFF Research Database (Denmark)

    Damgaard, Morten; Goetze, Jens Peter; Norsk, Peter

    2007-01-01

    AIMS: Plasma B-type natriuretic peptide (BNP) and proBNP are promising markers for treatment of heart failure (HF), but the intra-individual biological variation is high. We investigated whether changes in sodium intake and posture contribute to this variation. METHODS AND RESULTS: A total of 12...... has a considerable effect on plasma BNP and therefore contributes to the intra-individual variability. We suggest dietary sodium intake to be standardized at least 3 days prior to blood sampling for the determination of plasma BNP....

  16. Inflammatory cytokines in pediatric obstructive sleep apnea

    Science.gov (United States)

    Huang, Yu-Shu; Guilleminault, Christian; Hwang, Fang-Ming; Cheng, Chuan; Lin, Cheng-Hui; Li, Hsueh-Yu; Lee, Li-Ang

    2016-01-01

    Abstract Pediatric obstructive sleep apnea (OSA) is associated with chronic systemic inflammation and with cognitive impairments. This study aimed to investigate the status of proinflammatory cytokines, particularly interleukin 17 (IL-17) and interleukin 23 (IL-23) and cognition in pediatric OSA. Controls and OSA children participated in the study. Exclusion criteria were adenotonsillectomy, heart, neurological and severe psychiatric diseases, craniofacial syndromes, and obesity. Polysomnogram was followed by serum testing for inflammatory markers and neurocognitive tests such as continuous performance task (CPT) and Wisconsin card sorting test, questionnaires, analyses of plasma high-sensitivity C-reactive protein (HS-CRP), tumor necrosis factor alpha (TNF-α), interleukin 1 (IL-1), interleukin 6 (IL-6), IL-17, and IL-23. Seventy-nine, 4 to 12-year-old subjects in 2 groups ended the study: 47 nonobese OSA children (mean age = 7.84 ± 0.56 years, body mass index [BMI] = 16.95 ± 0.47 kg/m2, BMI z-score = 0.15 ± 0.21, and mean apnea–hypopnea index [AHI] = 9.13 ± 1.67 events/h) and 32 healthy control children (mean age = 7.02 ± 0.65 years, with BMI = 16.55 ± 0.58 kg/m2, BMI z-score = −0.12 ± 0.27, and mean AHI = 0.41 ± 0.07 event/h) were enrolled. Serum cytokine analyses showed significantly higher levels of HS-CRP, IL-17, and IL-23 in OSA children (P = 0.002, P = 0.024, and P = 0.047). Regression test showed significant influence of HS-CRP, TNF-α, IL-6, IL-17, and specifically IL-23, with the continuous performance test and Wisconsin card sorting test. OSA children have abnormal levels of IL-17, an interleukin related to T helper 17 cells, a T helper cell involved in development of autoimmunity and inflammation. This high expression level may contribute to the complications of pediatric OSA; we also found a significant influence of inflammatory cytokines, particularly IL-23, on abnormal neurocognitive testing. PMID

  17. Targeting the binding interface on a shared receptor subunit of a cytokine family enables the inhibition of multiple member cytokines with selectable target spectrum.

    Science.gov (United States)

    Nata, Toshie; Basheer, Asjad; Cocchi, Fiorenza; van Besien, Richard; Massoud, Raya; Jacobson, Steven; Azimi, Nazli; Tagaya, Yutaka

    2015-09-11

    The common γ molecule (γc) is a shared signaling receptor subunit used by six γc-cytokines. These cytokines play crucial roles in the differentiation of the mature immune system and are involved in many human diseases. Moreover, recent studies suggest that multiple γc-cytokines are pathogenically involved in a single disease, thus making the shared γc-molecule a logical target for therapeutic intervention. However, the current therapeutic strategies seem to lack options to treat such cases, partly because of the lack of appropriate neutralizing antibodies recognizing the γc and, more importantly, because of the inherent and practical limitations in the use of monoclonal antibodies. By targeting the binding interface of the γc and cytokines, we successfully designed peptides that not only inhibit multiple γc-cytokines but with a selectable target spectrum. Notably, the lead peptide inhibited three γc-cytokines without affecting the other three or non-γc-cytokines. Biological and mutational analyses of our peptide provide new insights to our current understanding on the structural aspect of the binding of γc-cytokines the γc-molecule. Furthermore, we provide evidence that our peptide, when conjugated to polyethylene glycol to gain stability in vivo, efficiently blocks the action of one of the target cytokines in animal models. Collectively, our technology can be expanded to target various combinations of γc-cytokines and thereby will provide a novel strategy to the current anti-cytokine therapies against immune, inflammatory, and malignant diseases.

  18. Nociceptive neurons detect cytokines in arthritis

    OpenAIRE

    Schaible, Hans-Georg

    2014-01-01

    Proinflammatory cytokines are major mediators in the pathogenesis of diseases of joints such as rheumatoid arthritis and osteoarthritis. This review emphasizes that proinflammatory cytokines such as tumor necrosis factor-alpha, interleukin-1beta, interleukin-6 and interleukin-17 are also mediators of pain by directly acting on the nociceptive system. Proportions of nociceptive sensory neurons express receptors for these cytokines, and the application of cytokines rapidly changes the excitabil...

  19. Leukocyte inclusion within a platelet rich plasma-derived fibrin scaffold stimulates a more pro-inflammatory environment and alters fibrin properties.

    Science.gov (United States)

    Anitua, Eduardo; Zalduendo, Mar; Troya, María; Padilla, Sabino; Orive, Gorka

    2015-01-01

    One of the main differences among platelet-rich plasma (PRP) products is the inclusion of leukocytes that may affect the biological efficacy of these autologous preparations. The purpose of this study was to evaluate whether the addition of leukocytes modified the morphological, biomechanical and biological properties of PRP under normal and inflammatory conditions. The release of pro-inflammatory cytokines from plasma rich in growth factors (PRGF) and leukocyte-platelet rich plasma (L-PRP) scaffolds was determined by enzyme-linked immunosorbent assay (ELISA) and was significantly increased under an inflammatory condition when leukocytes were included in the PRP. Fibroblasts and osteoblasts treated with L-PRP, under an inflammatory situation, underwent a greater activation of NFĸB pathway, proliferated significantly less and secreted a higher concentration of pro-inflammatory cytokines. These cellular events were assessed through Western blot and fluorimetric and ELISA methods, respectively. Therefore, the inclusion of leukocytes induced significantly higher pro-inflammatory conditions.

  20. Avian cytokines in health and disease

    Directory of Open Access Journals (Sweden)

    P Wigley

    2003-04-01

    Full Text Available Cytokines are proteins secreted by cells that play an important role in the activation and regulation of other cells and tissues during inflammation and immune responses. Although well described in several mammalian species, the role of cytokines and other related proteins is poorly understood in avian species. Recent advances in avian genetics and immunology have begun to allow the exploration of cytokines in health and disease. Cytokines may be classified in a number of ways, but may be conveniently arranged into four broad groups on the basis of their function. Proinflammatory cytokines such as interleukin-6 and interleukin-1beta play a role in mediating inflammation during disease or injury. Th1 cytokines, including interleukin-12 and interferon-gamma, are involved in the induction of cell-mediated immunity, whereas Th2 cytokines such as interleukin-4 are involved in the induction of humoral immunity. The final group Th3 or Tr cytokines play a role in regulation of immunity. The role of various cytokines in infectious and non-infectious diseases of chickens and turkeys is now being investigated. Although there are only a few reliable ELISAs or bioassays developed for avian cytokines, the use of molecular techniques, and in particular quantitative RT-PCR (Taqman has allowed investigation of cytokine responses in a number of diseases including salmonellosis, coccidiosis and autoimmune thyroiditis. In addition the use of recombinant cytokines as therapeutic agents or as vaccine adjuvants is now being explored.

  1. Cytokines and perinatal brain injury.

    Science.gov (United States)

    Silverstein, F S; Barks, J D; Hagan, P; Liu, X H; Ivacko, J; Szaflarski, J

    1997-01-01

    A rapidly expanding body of data provides support for the hypothesis that pro-inflammatory cytokines including interleukin-1 beta (IL-1 beta), and tumor necrosis factor-alpha (TNF-alpha) are expressed acutely in injured brain and contribute to progressive neuronal damage. Little is known about the pathogenetic role of these cytokines in perinatal brain injury. Recent experimental studies have incorporated two closely related in vivo perinatal rodent brain injury models to evaluate the role(s) of pro-inflammatory cytokines in the progression of neuronal injury: a perinatal stroke model, elicited by unilateral carotid artery ligation and subsequent timed exposure to 8% oxygen in 7-day-old rats, and a model of excitotoxic injury, elicited by stereotactic intra-cerebral injection of the selective excitatory amino acid agonist NMDA. Each of these lesioning methods results in reproducible, quantifiable focal forebrain injury at this developmental stage. Acute brain injury, evoked by cerebral hypoxia-ischemia or excitotoxin lesioning, results in transient marked increases in expression of IL-1 beta, and TNF-alpha mRNA in brain regions susceptible to irreversible injury, and there is evidence that pharmacological antagonism of IL-1 receptors can attenuate injury in both models. Recent studies also suggest that complementary strategies, based on pharmacological antagonism of platelet activating factor and on neutrophil depletion can also limit the extent of irreversible injury. In summary, current data suggest that pro-inflammatory cytokines contribute to the progression of perinatal brain injury, and that these mediators are important targets for neuroprotective interventions in the acute post-injury period.

  2. International movement of plasma and plasma contracting.

    Science.gov (United States)

    Farrugia, A

    2005-01-01

    Plasma fractionation is a global business characterised by technological stability, increasing consolidation and a high level of regulatory oversight. All these factors affect the ease with which plasma derivatives can be accessed in the world market. As domestic regulatory measures in the first world blood economies become increasingly resonant to the precautionary approach, the availability of plasma as a raw material, as well as its cost, become an increasingly significant component in the cost of the final product. This decreases the amount of plasma which fractionators are able to allocate for export activities. Also, regulatory standards in the country of manufacture will reflect priorities in that country which may not be similar to those in export markets, but which will affect entry to those markets. While many countries possess a fractionation capacity, the limiting factor in supply worldwide is the amount of plasma available, and nationalistic drivers for each country to have its own plant are inimical to product safety and supply. Rather, the provision of sufficient supplies of domestic plasma should be the focus of resource allocation, with a choice of an appropriate contract fractionator. However, contract fractionation too may be affected by domestic considerations unrelated to the needs of the country of plasma origin. This chapter will review the global plasma market and the influences on plasma and plasma product movement across national borders. Problems in ensuring adequate safety and supply will be identified, and some tentative approaches to the amelioration of current barriers to the provision of plasma derivatives will be outlined.

  3. Caffeine suppresses amyloid-beta levels in plasma and brain of Alzheimer's disease transgenic mice.

    Science.gov (United States)

    Cao, Chuanhai; Cirrito, John R; Lin, Xiaoyang; Wang, Li; Wang, Lilly; Verges, Deborah K; Dickson, Alexander; Mamcarz, Malgorzata; Zhang, Chi; Mori, Takashi; Arendash, Gary W; Holtzman, David M; Potter, Huntington

    2009-01-01

    Recent epidemiologic studies suggest that caffeine may be protective against Alzheimer's disease (AD). Supportive of this premise, our previous studies have shown that moderate caffeine administration protects/restores cognitive function and suppresses brain amyloid-beta (Abeta) production in AD transgenic mice. In the present study, we report that acute caffeine administration to both young adult and aged AD transgenic mice rapidly reduces Abeta levels in both brain interstitial fluid and plasma without affecting Abeta elimination. Long-term oral caffeine treatment to aged AD mice provided not only sustained reductions in plasma Abeta, but also decreases in both soluble and deposited Abeta in hippocampus and cortex. Irrespective of caffeine treatment, plasma Abeta levels did not correlate with brain Abeta levels or with cognitive performance in individual aged AD mice. Although higher plasma caffeine levels were strongly associated with lower plasma Abeta1-40 levels in aged AD mice, plasma caffeine levels were also not linked to cognitive performance. Plasma caffeine and theophylline levels were tightly correlated, both being associated with reduced inflammatory cytokine levels in hippocampus. Our conclusion is two-fold: first, that both plasma and brain Abeta levels are reduced by acute or chronic caffeine administration in several AD transgenic lines and ages, indicating a therapeutic value of caffeine against AD; and second, that plasma Abeta levels are not an accurate index of brain Abeta levels/deposition or cognitive performance in aged AD mice.

  4. A whole blood in vitro cytokine release assay with aqueous monoclonal antibody presentation for the prediction of therapeutic protein induced cytokine release syndrome in humans.

    Science.gov (United States)

    Wolf, Babette; Morgan, Hannah; Krieg, Jennifer; Gani, Zaahira; Milicov, Adriana; Warncke, Max; Brennan, Frank; Jones, Stewart; Sims, Jennifer; Kiessling, Andrea

    2012-12-01

    The administration of several monoclonal antibodies (mAbs) to humans has been associated with acute adverse events characterized by clinically significant release of cytokines in the blood. The limited predictive value of toxicology species in this field has triggered intensive research to establish human in vitro assays using peripheral blood mononuclear cells or blood to predict cytokine release in humans. A thorough characterization of these assays is required to understand their predictive value for hazard identification and risk assessment in an optimal manner, and to highlight potential limitations of individual assay formats. We have characterized a whole human blood cytokine release assay with only minimal dilution by the test antibodies (95% v/v blood) in aqueous presentation format, an assay which has so far received less attention in the scientific world with respect to the evaluation of its suitability to predict cytokine release in humans. This format was compared with a human PBMC assay with immobilized mAbs presentation already well-characterized by others. Cytokine secretion into plasma or cell culture supernatants after 24h incubation with the test mAbs (anti-CD28 superagonist TGN1412-like material (TGN1412L), another anti-CD28 superagonistic mAb (ANC28.1), a T-cell depleting mAb (Orthoclone™), and a TGN1412 isotype-matched control (Tysabri™) not associated with clinically-relevant cytokine release) was detected by a multiplex assay based on electrochemiluminescent excitation. We provide proof that this whole blood assay is a suitable new method for hazard identification of safety-relevant cytokine release in the clinic based on its ability to detect the typical cytokine signatures found in humans for the tested mAbs and on a markedly lower assay background and cytokine release with the isotype-matched control mAb Tysabri™ - a clear advantage over the PBMC assay. Importantly, quantitative and qualitative differences in the relative cytokine

  5. Cytokines as effectors and predictors of responses in the treatment of bladder cancer by bacillus Calmette-Guérin.

    Science.gov (United States)

    Liu, Xiaoxuan; Dowell, Alexander C; Patel, Prashant; Viney, Richard P; Foster, Michael C; Porfiri, Emilio; James, Nicholas D; Bryan, Richard T

    2014-06-01

    The most effective intravesical treatment of non-muscle-invasive bladder cancer is instillation of live Mycobacterium bovis bacillus Calmette-Guérin (BCG). BCG stimulates the release of cytokines, contributing directly or indirectly to its effectiveness. However, the function of specific cytokines is not well understood. We have undertaken a nonsystematic review of primary evidence regarding cytokine detection, activation and response in BCG patients. Cytokines IL-2, IL-8 and TNF-α appear to be essential for effective BCG therapy and nonrecurrence, while IL-10 may have an inhibitory effect on BCG responses. IL-2, IL-8, TRAIL and TNF-α are potentially predictive of response to BCG. Alterations in genes encoding cytokines may also affect responses. There are significant data showing the association of certain cytokines with successful BCG treatment, and which may be useful predictive markers. Isolating those cytokines mediating efficacy may hold the key to ameliorating BCG's side effects and improving efficacy and patient compliance.

  6. Discovery of potential new gene variants and inflammatory cytokine associations with fibromyalgia syndrome by whole exome sequencing.

    Directory of Open Access Journals (Sweden)

    Jinong Feng

    Full Text Available Fibromyalgia syndrome (FMS is a chronic musculoskeletal pain disorder affecting 2% to 5% of the general population. Both genetic and environmental factors may be involved. To ascertain in an unbiased manner which genes play a role in the disorder, we performed complete exome sequencing on a subset of FMS patients. Out of 150 nuclear families (trios DNA from 19 probands was subjected to complete exome sequencing. Since >80,000 SNPs were found per proband, the data were further filtered, including analysis of those with stop codons, a rare frequency (<2.5% in the 1000 Genomes database, and presence in at least 2/19 probands sequenced. Two nonsense mutations, W32X in C11orf40 and Q100X in ZNF77 among 150 FMS trios had a significantly elevated frequency of transmission to affected probands (p = 0.026 and p = 0.032, respectively and were present in a subset of 13% and 11% of FMS patients, respectively. Among 9 patients bearing more than one of the variants we have described, 4 had onset of symptoms between the ages of 10 and 18. The subset with the C11orf40 mutation had elevated plasma levels of the inflammatory cytokines, MCP-1 and IP-10, compared with unaffected controls or FMS patients with the wild-type allele. Similarly, patients with the ZNF77 mutation have elevated levels of the inflammatory cytokine, IL-12, compared with controls or patients with the wild type allele. Our results strongly implicate an inflammatory basis for FMS, as well as specific cytokine dysregulation, in at least 35% of our FMS cohort.

  7. Novel Flow Cytometry Analyses of Boar Sperm Viability: Can the Addition of Whole Sperm-Rich Fraction Seminal Plasma to Frozen-Thawed Boar Sperm Affect It?

    Science.gov (United States)

    Díaz, Rommy; Boguen, Rodrigo; Martins, Simone Maria Massami Kitamura; Ravagnani, Gisele Mouro; Leal, Diego Feitosa; Oliveira, Melissa de Lima; Muro, Bruno Bracco Donatelli; Parra, Beatriz Martins; Meirelles, Flávio Vieira; Papa, Frederico Ozanan; Dell’Aqua, José Antônio; Alvarenga, Marco Antônio; Moretti, Aníbal de Sant’Anna; Sepúlveda, Néstor

    2016-01-01

    Boar semen cryopreservation remains a challenge due to the extension of cold shock damage. Thus, many alternatives have emerged to improve the quality of frozen-thawed boar sperm. Although the use of seminal plasma arising from boar sperm-rich fraction (SP-SRF) has shown good efficacy; however, the majority of actual sperm evaluation techniques include a single or dual sperm parameter analysis, which overrates the real sperm viability. Within this context, this work was performed to introduce a sperm flow cytometry fourfold stain technique for simultaneous evaluation of plasma and acrosomal membrane integrity and mitochondrial membrane potential. We then used the sperm flow cytometry fourfold stain technique to study the effect of SP-SRF on frozen-thawed boar sperm and further evaluated the effect of this treatment on sperm movement, tyrosine phosphorylation and fertility rate (FR). The sperm fourfold stain technique is accurate (R2 = 0.9356, p > 0.01) for simultaneous evaluation of plasma and acrosomal membrane integrity and mitochondrial membrane potential (IPIAH cells). Centrifugation pre-cryopreservation was not deleterious (p > 0.05) for any analyzed variables. Addition of SP-SRF after cryopreservation was able to improve total and progressive motility (p 0.05) or improve IPIAH cells (p > 0.05). FR was not (p > 0.05) statistically increased by the addition of seminal plasma, though females inseminated with frozen-thawed boar semen plus SP-SRF did perform better than those inseminated with sperm lacking seminal plasma. Thus, we conclude that sperm fourfold stain can be used to simultaneously evaluate plasma and acrosomal membrane integrity and mitochondrial membrane potential, and the addition of SP-SRF at thawed boar semen cryopreserved in absence of SP-SRF improve its total and progressive motility. PMID:27529819

  8. Secretion of immunoregulatory cytokines by mesenchymal stem cells

    Institute of Scientific and Technical Information of China (English)

    Dobroslav; Kyurkchiev; Ivan; Bochev; Ekaterina; Ivanova-Todorova; Milena; Mourdjeva; Tsvetelina; Oreshkova; Kalina; Belemezova; Stanimir; Kyurkchiev

    2014-01-01

    According to the minimal criteria of the International Society of Cellular Therapy, mesenchymal stem cells(MSCs) are a population of undifferentiated cells defined by their ability to adhere to plastic surfaces when cultured under standard conditions, express a certain panel of phenotypic markers and can differentiate into osteogenic, chondrogenic and adipogenic lineages when cultured in specific inducing media. In parallel with their major role as undifferentiated cell reserves, MSCs have immunomodulatory functions which are exerted by direct cell-to-cell contacts, secretion of cytokines and/or by a combination of both mechanisms. There are no convincing data about a principal difference in the profile of cytokines secreted by MSCs isolated from different tissue sources, although some papers report some quantitative but not qualitative differences in cytokine secretion. The present review focuses on the basic cytokines secreted by MSCs as described in the literature by which the MSCs exert immunodulatory effects. It should be pointed out that MSCs themselves are objects of cytokine regulation. Hypothetical mechanisms by which the MSCs exert their immunoregulatory effects are also discussed in this review. These mechanisms may either influence the target immune cells directly or indirectly by affecting the activities of predominantly dendritic cells. Chemokines are also discussed as participants in this process by recruiting cells of the immune systems and thus making them targets of immunosuppression. This review aims to present and discuss the published data and the personal experience of the authors regarding cytokines secreted by MSCs and their effects on the cells of the immune system.

  9. The Effect of a Prophylactic Dose of Ibuprofen on Plasma Level of Interleukin 1, Interleukin 6 and Tumor Necrosis Factor-Alpha in a 1500 m Running Practice

    Directory of Open Access Journals (Sweden)

    Gholamreza Sepehri

    2011-01-01

    Full Text Available Problem statement: there are controversies about the effects of anti-inflammatory drugs on exercised induced changes on plasma cytokines in untrained male athletes, so the primary purpose of this study was to measure the influence of a prophylactic dose of ibuprofen use on plasma cytokines during a 1500 m running race. Approach: Subjects were 10 untrained male Medical University students who consumed 400 mg ibuprofen two hours before the 1500 m running practice and 10 controls that competed in the race but avoided ibuprofen and all other medications. Blood samples were collected before, 1h and 24 h following the 1500 m exercise bout to measure plasma concentrations of interleukin-1 beta (IL-1β , interleukin-6(IL-6 and tumor necrosis factor alpha (TNF- α . Results: There were not any significant differences between plasma concentration of IL-1β, IL-6 and TNF- α during the study period. Also the data showed that there were not any significant differences between plasma level of IL-1β, IL-6 and TNF- α in ibuprofen and control group during the study period. Conclusions/Recommendation: Our result showed that a prophylactic dose of ibuprofen did not affect acute inflammatory cytokines levels (IL-1β, IL-6 and TNF- α in untrained healthy young males. So the etiology of the muscle soreness in athletes actively participating in sport races seems to be independent of inflammatory processes.

  10. CYP7A1 A-278C polymorphism affects the response of plasma lipids after dietary cholesterol and cafestol interventions in humans.

    NARCIS (Netherlands)

    Hofman, M.K.; Weggemans, R.M.; Zock, P.L.; Schouten, E.G.; Katan, M.B.; Princen, H.M.G.

    2004-01-01

    The response of plasma lipids to dietary cholesterol and fat varies among individuals. Variations in genes involved in cholesterol metabolism can be important in these interindividual differences. The rate-limiting enzyme in the conversion of cholesterol into bile acids is cholesterol 7-hydroxylase

  11. Different environmental temperatures affect amino acid metabolism in the eurytherm teleost Senegalese sole (Solea senegalensis Kaup, 1858) as indicated by changes in plasma metabolites.

    NARCIS (Netherlands)

    Costas, B.; Aragao, C.; Ruiz-Jarabo, I.; Vargas-Chacoff, L.; Arjona, F.J.; Mancera, J.M.; Dinis, M.T.; Conceicao, L.E.

    2012-01-01

    Senegalese sole (Solea senegalensis) is a eurytherm teleost that under natural conditions can be exposed to annual water temperature fluctuations between 12 and 26 degrees C. This study assessed the effects of temperature on sole metabolic status, in particular in what concerns plasma free amino aci

  12. A low-saturated-fat, low-cholesterol diet decreases plasma CETP activity and pre beta-HDL formation but does not affect cellular cholesterol efflux to plasma from type 1 diabetic patients

    NARCIS (Netherlands)

    De Vries, R; Beusekamp, BJ; Kerstens, MN; Groen, AK; Van Tol, A; Dullaart, RPF

    2005-01-01

    The aim of this study was to evaluate the effect of a low-saturated-fat, low-cholesterol diet on plasma lipopoproteins, pre beta-high density lipoprotein (HDL) formation, lecithin: cholesterol acyltransferase (LCAT), cholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP)

  13. Depressive-like behavior, its sensitization, social buffering, and altered cytokine responses in rhesus macaques moved from outdoor social groups to indoor housing.

    Science.gov (United States)

    Hennessy, Michael B; Chun, Katie; Capitanio, John P

    2017-02-01

    Psychosocial stressors appear to promote the onset of depressive illness through activation and sensitization of inflammatory mechanisms. Here, adult male rhesus monkeys brought from large outdoor social groups to indoor housing for 8 days reliably exhibited a hunched, depressive-like posture. When rehoused indoors a second 8 days about 2 weeks later, monkeys housed alone, but not those with an affiliative partner, showed sensitization of the depressive-like hunched posture. Housing indoors also affected circulating pro-inflammatory cytokines: IL-1β showed increased responsiveness to immune challenge, and IL-1β and TNF-α showed reduced suppression by dexamethasone. Sensitivity of the anti-inflammatory cytokine IL-10 to immune challenge exhibited a relative increase from the first to the second round of indoor housing in animals housed in pairs, and a relative decrease in animals housed alone. Cytokine levels during indoor housing were positively correlated with duration of depressive-like behavior. Plasma cortisol levels increased but did not differentiate housing conditions or rounds. Results demonstrate a rapid induction and sensitization of depressive-like behavior to indoor individual housing, social buffering of sensitization, and associated inflammatory responses. This paradigm may provide a practical nonhuman primate model for examining inflammatory-mediated consequences of psychosocial stressors on depression and possible social buffering of these effects.

  14. Gender, but not CYP7A1 or SLCO1B1 polymorphism, affects the fasting plasma concentrations of bile acids in human beings.

    Science.gov (United States)

    Xiang, Xiaoqiang; Backman, Janne T; Neuvonen, Pertti J; Niemi, Mikko

    2012-03-01

    Cholesterol 7α-hydroxylase (CYP7A1) is the rate-limiting enzyme of bile acid production in human beings, and organic anion-transporting polypeptide 1B1 (OATP1B1) may influence bile acid hepatic uptake and cholesterol and bile acid synthesis rate. Our purpose was to investigate the effects of gender and CYP7A1 and SLCO1B1 polymorphisms on the fasting plasma concentrations of bile acids, bile acid synthesis marker and total cholesterol in a Finnish population. Fasting plasma concentrations of 16 endogenous bile acids, their synthesis marker (7α-hydroxy-4-cholesten-3-one) and total cholesterol were measured in 243 samples from 143 healthy volunteers. The volunteers were genotyped for 6 haplotype-tagging single-nucleotide polymorphisms (SNPs) of CYP7A1 and two functionally relevant SNPs in SLCO1B1. The mean plasma concentrations of chenodeoxycholic acid, glycochenodeoxycholic acid, ursodeoxycholic acid and glycoursodeoxycholic acid were 61-111% higher in men than in women (P ≤ 0.001). Accordingly, the mean concentration of total bile acids was 51% higher in men than in women (P = 0.001). The CYP7A1 rs8192879 and rs1023652 SNPs were associated with deoxycholic acid and hyodeoxycholic acid concentrations, respectively, but the associations were not significant after correction for multiple testing. None of the six CYP7A1 SNPs was associated with the plasma concentrations of cholesterol or 7α-hydroxy-4-cholesten-3-one. SLCO1B1 genotype was associated with total plasma cholesterol concentration only, but the association was not significant after correction for multiple testing. In general, the gender contributes substantially more to variation in fasting plasma bile acid concentrations than CYP7A1 or SLCO1B1 polymorphism do. Common genetic variability in CYP7A1 is unlikely to play a significant role in cholesterol metabolism and bile acid homeostasis under normal physiological conditions.

  15. Plasma dynamo

    CERN Document Server

    Rincon, F; Schekochihin, A A; Valentini, F

    2015-01-01

    Magnetic fields pervade the entire Universe and, through their dynamical interactions with matter, affect the formation and evolution of astrophysical systems from cosmological to planetary scales. How primordial cosmological seed fields arose and were further amplified to $\\mu$Gauss levels reported in nearby galaxy clusters, near equipartition with kinetic energy of plasma motions and on scales of at least tens of kiloparsecs, is a major theoretical puzzle still largely unconstrained by observations. Extragalactic plasmas are weakly collisional (as opposed to collisional magnetohydrodynamic fluids), and whether magnetic-field growth and its sustainment through an efficient dynamo instability driven by chaotic motions is possible in such plasmas is not known. Fully kinetic numerical simulations of the Vlasov equation in a six-dimensional phase space necessary to answer this question have until recently remained beyond computational capabilities. Here, we show by means of such simulations that magnetic-field a...

  16. 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...

  17. FUNDAMENTAL IMMUNOBIOLOGY OF PRO-INFLAMMATORY CYTOKINES AND MIF

    Directory of Open Access Journals (Sweden)

    A. P. Suslov

    2006-01-01

    Full Text Available Fundamental immunobiology of proinflammatory cytokines and MIFThere are a lot of similarity as well as differences when we compare cytokines with MIF according their biological properties. MIF characteristics are unique structure, organs and tissues ubiquity, extremely wide variety of functions (proinflammatory cytokine, enzyme, hormone, ability to be induced by glucocorticoid hormones and affects as their immunosuppressive effects antagonist. MIF exists in preformed condition in lymphocytes, macrophages and endothelium cells. It secrets by these cells and operates as a mobilizing defense system factor in the first minutes of foreign invasion. MIF exhibits the properties of super-ligand binding with many biologically important molecules. This factor carries out the functions that are important for cell activation, proliferation and death, using a variety of intracellular signaling pathways. Some of MIF homologues exists in plants and bacteria earlier than innate and adaptive immune systems appears in evolution. In ontogenesis MIF appears at the stage of firsts cell divisions. MIF has a lot of functions, variety of ligand bindings, many effector pathways, it appears early in ontogeny and phylogeny. MIF takes part into protective reactions at any levels – from cell up to whole organism. All these MIF features taking together into account make it possible to possess it as a particular type of cytokine – eocytokine (from Greek word “eo” – early. It is assumed that MIF may function as some kind of cells and organisms "natural stability" key factor.

  18. Effects of prebiotics on immune system and cytokine expression.

    Science.gov (United States)

    Shokryazdan, Parisa; Faseleh Jahromi, Mohammad; Navidshad, Bahman; Liang, Juan Boo

    2017-02-01

    Nowadays, use of prebiotics as feed and food additives has received increasing interest because of the beneficial effects of prebiotics on the health of animals and humans. One of the beneficial effects of prebiotics is stimulation of immune system, which can be direct or indirect through increasing population of beneficial microbes or probiotics, especially lactic acid bacteria and bifidobacteria, in the gut. An important mechanism of action of probiotics and prebiotics, by which they can affect the immune system, is changing the expression of cytokines. The present review tried to summarize the findings of studies that investigated the effects of prebiotics on immune system with focusing on their effects on cytokine expression. Generally, most of reviewed studies indicated beneficial effects for prebiotics in terms of improving immune system, by increasing the expression of anti-inflammatory cytokines, while reducing the expressions of proinflammatory cytokines. However, most of studies mainly considered the indirect effects of prebiotics on the immune system (through changing the composition and population of gut microbiota), and their direct effects still need to be further studied using prebiotics with different degree of polymerization in different hosts.

  19. PCTAIRE1-knockdown sensitizes cancer cells to TNF family cytokines.

    Directory of Open Access Journals (Sweden)

    Teruki Yanagi

    Full Text Available While PCTAIRE1/PCTK1/Cdk16 is overexpressed in malignant cells and is crucial in tumorigenesis, its function in apoptosis remains unclear. Here we investigated the role of PCTAIRE1 in apoptosis, especially in the extrinsic cell death pathway. Gene-knockdown of PCTAIRE1 sensitized prostate cancer PPC1 and Du145 cells, and breast cancer MDA-MB-468 cells to TNF-family cytokines, including TNF-related apoptosis-inducing ligand (TRAIL. Meanwhile, PCTAIRE1-knockdown did not sensitize non-malignant cells, including diploid fibroblasts IMR-90 and the immortalized prostate epithelial cell line 267B1. PCTAIRE1-knockdown did not up-regulate death receptor expression on the cell surface or affect caspase-8, FADD and FLIP expression levels. PCTAIRE1-knockdown did promote caspase-8 cleavage and RIPK1 degradation, while RIPK1 mRNA knockdown sensitized PPC1 cells to TNF-family cytokines. Furthermore, the kinase inhibitor SNS-032, which inhibits PCTAIRE1 kinase activity, sensitized PPC1 cells to TRAIL-induced apoptosis. Together these results suggest that PCTAIRE1 contributes to the resistance of cancer cell lines to apoptosis induced by TNF-family cytokines, which implies that PCTAIRE1 inhibitors could have synergistic effects with TNF-family cytokines for cytodestruction of cancer cells.

  20. PCTAIRE1-knockdown sensitizes cancer cells to TNF family cytokines.

    Science.gov (United States)

    Yanagi, Teruki; Shi, Ranxin; Aza-Blanc, Pedro; Reed, John C; Matsuzawa, Shu-ichi

    2015-01-01

    While PCTAIRE1/PCTK1/Cdk16 is overexpressed in malignant cells and is crucial in tumorigenesis, its function in apoptosis remains unclear. Here we investigated the role of PCTAIRE1 in apoptosis, especially in the extrinsic cell death pathway. Gene-knockdown of PCTAIRE1 sensitized prostate cancer PPC1 and Du145 cells, and breast cancer MDA-MB-468 cells to TNF-family cytokines, including TNF-related apoptosis-inducing ligand (TRAIL). Meanwhile, PCTAIRE1-knockdown did not sensitize non-malignant cells, including diploid fibroblasts IMR-90 and the immortalized prostate epithelial cell line 267B1. PCTAIRE1-knockdown did not up-regulate death receptor expression on the cell surface or affect caspase-8, FADD and FLIP expression levels. PCTAIRE1-knockdown did promote caspase-8 cleavage and RIPK1 degradation, while RIPK1 mRNA knockdown sensitized PPC1 cells to TNF-family cytokines. Furthermore, the kinase inhibitor SNS-032, which inhibits PCTAIRE1 kinase activity, sensitized PPC1 cells to TRAIL-induced apoptosis. Together these results suggest that PCTAIRE1 contributes to the resistance of cancer cell lines to apoptosis induced by TNF-family cytokines, which implies that PCTAIRE1 inhibitors could have synergistic effects with TNF-family cytokines for cytodestruction of cancer cells.

  1. Bioanalytical chemistry of cytokines--a review.

    Science.gov (United States)

    Stenken, Julie A; Poschenrieder, Andreas J

    2015-01-01

    Cytokines are bioactive proteins produced by many different cells of the immune system. Due to their role in different inflammatory disease states and maintaining homeostasis, there is enormous clinical interest in the quantitation of cytokines. The typical standard methods for quantitation of cytokines are immunoassay-based techniques including enzyme-linked immusorbent assays (ELISA) and bead-based immunoassays read by either standard or modified flow cytometers. A review of recent developments in analytical methods for measurements of cytokine proteins is provided. This review briefly covers cytokine biology and the analysis challenges associated with measurement of these biomarker proteins for understanding both health and disease. New techniques applied to immunoassay-based assays are presented along with the uses of aptamers, electrochemistry, mass spectrometry, optical resonator-based methods. Methods used for elucidating the release of cytokines from single cells as well as in vivo collection methods are described.

  2. Respiratory mechanics and plasma levels of tumor necrosis factor alpha and interleukin 6 are affected by gas humidification during mechanical ventilation in dogs.

    Directory of Open Access Journals (Sweden)

    Claudia Hernández-Jiménez

    Full Text Available The use of dry gases during mechanical ventilation has been associated with the risk of serious airway complications. The goal of the present study was to quantify the plasma levels of TNF-alpha and IL-6 and to determine the radiological, hemodynamic, gasometric, and microscopic changes in lung mechanics in dogs subjected to short-term mechanical ventilation with and without humidification of the inhaled gas. The experiment was conducted for 24 hours in 10 dogs divided into two groups: Group I (n = 5, mechanical ventilation with dry oxygen dispensation, and Group II (n = 5, mechanical ventilation with oxygen dispensation using a moisture chamber. Variance analysis was used. No changes in physiological, hemodynamic, or gasometric, and radiographic constants were observed. Plasma TNF-alpha levels increased in group I, reaching a maximum 24 hours after mechanical ventilation was initiated (ANOVA p = 0.77. This increase was correlated to changes in mechanical ventilation. Plasma IL-6 levels decreased at 12 hours and increased again towards the end of the study (ANOVA p>0.05. Both groups exhibited a decrease in lung compliance and functional residual capacity values, but this was more pronounced in group I. Pplat increased in group I (ANOVA p = 0.02. Inhalation of dry gas caused histological lesions in the entire respiratory tract, including pulmonary parenchyma, to a greater extent than humidified gas. Humidification of inspired gases can attenuate damage associated with mechanical ventilation.

  3. Respiratory mechanics and plasma levels of tumor necrosis factor alpha and interleukin 6 are affected by gas humidification during mechanical ventilation in dogs.

    Science.gov (United States)

    Hernández-Jiménez, Claudia; García-Torrentera, Rogelio; Olmos-Zúñiga, J Raúl; Jasso-Victoria, Rogelio; Gaxiola-Gaxiola, Miguel O; Baltazares-Lipp, Matilde; Gutiérrez-González, Luis H

    2014-01-01

    The use of dry gases during mechanical ventilation has been associated with the risk of serious airway complications. The goal of the present study was to quantify the plasma levels of TNF-alpha and IL-6 and to determine the radiological, hemodynamic, gasometric, and microscopic changes in lung mechanics in dogs subjected to short-term mechanical ventilation with and without humidification of the inhaled gas. The experiment was conducted for 24 hours in 10 dogs divided into two groups: Group I (n = 5), mechanical ventilation with dry oxygen dispensation, and Group II (n = 5), mechanical ventilation with oxygen dispensation using a moisture chamber. Variance analysis was used. No changes in physiological, hemodynamic, or gasometric, and radiographic constants were observed. Plasma TNF-alpha levels increased in group I, reaching a maximum 24 hours after mechanical ventilation was initiated (ANOVA p = 0.77). This increase was correlated to changes in mechanical ventilation. Plasma IL-6 levels decreased at 12 hours and increased again towards the end of the study (ANOVA p>0.05). Both groups exhibited a decrease in lung compliance and functional residual capacity values, but this was more pronounced in group I. Pplat increased in group I (ANOVA p = 0.02). Inhalation of dry gas caused histological lesions in the entire respiratory tract, including pulmonary parenchyma, to a greater extent than humidified gas. Humidification of inspired gases can attenuate damage associated with mechanical ventilation.

  4. 老年情感障碍患者SSRIs类药物治疗前后血清细胞因子、皮质醇及认知功能的变化%Changes of serum cytokines, cortisol levels and cognitive function in elderly patients with affective disorders before and after SSRIs treatment

    Institute of Scientific and Technical Information of China (English)

    崔莹; 单培彦; 侯桂华; 麻琳; 冯永平

    2011-01-01

    Objective To explore changes of serum cytokines, cortisol (Cor) levels and cognitive function of patients with affective disorders in the elderly before and after selective serotonin reuptake inhibitors (SSRIs) treatment.Methods 50 elderly patients with affective disorder ( the patient group) and 45 normal elderly subjects ( the control group) were enrolled. Blood samples were used for determining serum macrophage migration inhibitory factor (MIF) by enzyme linked immunosorbent assay and IL-1β, IL-6 and Cor levels by radioimmunoassay. The patient group was tested by neuropsychology scales before and after SSRIs treatment. Results ① Before treatment, MIF, IL-1β, IL-6 and Cor levels were higher in the patient group than those in the controls and those after treatment(P <0.05). There was a positive correlation( P <0.01 ) of MIF, IL-1β, IL-6 and Cor levels with the score of the 24 item Hamilton Depression Scale( HAMD24 ) and Pittsburgh sleep quality index (PQSI) . The score of the 14 item Hamilton Anxiety Scale (HAMA14) positively correlated with levels of MIF and IL-6( P < 0. 05 ). ② Patients with affective disorder made improvements in scores of neuropsychological tests after treatment( P <0.01 ). ③ The score in sleeping disturbance symptom was negatively correlated to the improvement in visuospatial and executive ability( r = -0. 251, P <0.01 ), verbal ability(r= -0.326, P<0.01), and delay memory(r= -0. 296, P<0.01), and the score in anxiety/somatization was negatively correlated to the improvement in visuospatial and executive ability ( r = - 0. 204, P < 0.01 ), verbal ability( r = - 0. 398, P < 0.01 ) , abstract( r = - 0. 307, P < 0.01 ) and delay memory( r = - 0. 236, P < 0.05 ). Conclusion Increasing of serum cytokines and Cor levels in patients with affective disorder in the elderly is related to the severity of anxiety and depression. SSRIs can inhibit expressions of inflammatory factors to improve cognitive function of patients

  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. CYTOKINE REGULATION OF ULCEROGENESIS IN GASTRODUODENAL MUCOSA

    Directory of Open Access Journals (Sweden)

    L. V. Matveeva

    2013-01-01

    Full Text Available Ulcerogenesis in gastroduodenal mucosa area is a complex multistep process. Its, phases arecontrolled by interaction and activation of pro­ and antiinflammatory cytokine cascade. Present review article summarizes scientific data on impact of cytokines upon ulcerative and reparatory processes, a variety of their diagnostic and therapeutic options is defined. Evaluation of cytokine status, or, in some cases, cytokine genotyping in patients with stomach and duodenal ulcers, may predict clinical course of the disease, as well as efficiency of basic and eradication therapy, correction of the treatment.

  7. Low- and high-dose plant and marine (n-3) fatty acids do not affect plasma inflammatory markers in adults with metabolic syndrome.

    Science.gov (United States)

    Dewell, Antonella; Marvasti, Farshad Fani; Harris, William S; Tsao, Philip; Gardner, Christopher D

    2011-12-01

    Chronic inflammation is considered to play a role in the development of cardiovascular disease. Various (n-3) fatty acids (FA) have been reported to have antiinflammatory effects, but there is a lack of consensus in this area, particularly in regard to optimal source(s) and dose(s). This study aimed to determine the effects of high and low doses of (n-3) FA from plant and marine sources on plasma inflammatory marker concentrations. One-hundred adults with metabolic syndrome were randomly assigned to a low or high dose of plant- (2.2 or 6.6 g/d α-linolenic acid) or marine- (1.2 or 3.6 g/d EPA and DHA) derived (n-3) FA or placebo for 8 wk, using a parallel arm design (n = 20/arm). Fasting blood samples collected at 0, 4, and 8 wk were analyzed for concentrations of monocyte chemotactic protein-1 (MCP-1), IL-6, and soluble intercellular adhesion molecule-1 (sICAM-1) and for cardiovascular risk factors. Baseline concentrations across all 5 groups combined were (mean ± SD) 103 ± 32 ng/L for MCP-1, 1.06 ± 0.56 ng/L for IL-6, and 0.197 ± 0.041 ng/L for sICAM-1. There were no significant differences in 8-wk changes in plasma inflammatory marker concentrations among the 5 groups. Plasma TG and blood pressure decreased significantly more and the LDL cholesterol concentration increased more in the high-dose fish oil group compared to the 8-wk changes in some of the other 4 groups (P ≤ 0.04). In conclusion, no beneficial effects were detected for any of the 3 inflammatory markers investigated in response to (n-3) FA in adults with metabolic syndrome regardless of dose or source.

  8. Changes in the electro-physical properties of MCT epitaxial films affected by a plasma volume discharge induced by an avalanche beam in atmospheric-pressure air

    Science.gov (United States)

    Grigoryev, D. V.; Voitsekhovskii, A. V.; Lozovoy, K. A.; Tarasenko, V. F.; Shulepov, M. A.

    2015-11-01

    In this paper the influence of the plasma volume discharge of nanosecond duration formed in a non-uniform electric field at atmospheric pressure on samples of epitaxial films HgCdTe (MCT) films are discussed. The experimental data show that the action of pulses of nanosecond volume discharge in air at atmospheric pressure leads to changes in the electrophysical properties of MCT epitaxial films due to formation of a near-surface high- conductivity layer of the n-type conduction. The preliminary results show that it is possible to use such actions in the development of technologies for the controlled change of the properties of MCT.

  9. Cortisol, Cytokines, and Hippocampal Volume in the Elderly

    Directory of Open Access Journals (Sweden)

    Keith Daniel Sudheimer

    2014-07-01

    Full Text Available Separate bodies of literature report that elevated pro-inflammatory cytokines and cortisol negatively affect hippocampal structure and cognitive functioning, particularly in older adults. Although interactions between cytokines and cortisol occur through a variety of known mechanisms, few studies consider how their interactions affect brain structure. In this preliminary study, we assess the impact of interactions between circulating levels of IL-1Beta, IL-6, IL-8, IL-10, IL-12, TNF-alpha, and waking cortisol on hippocampal volume. Twenty-eight community-dwelling older adults underwent blood draws for quantification of circulating cytokines and saliva collections to quantify the cortisol awakening response. Hippocampal volume measurements were made using structural magnetic resonance imaging. Elevated levels of waking cortisol in conjunction with higher concentrations of IL-6 and TNF-alpha were associated with smaller hippocampal volumes. In addition, independent of cortisol, higher levels of IL-1beta and TNF-alpha were also associated with smaller hippocampal volumes. These data provide preliminary evidence that higher cortisol, in conjunction with higher IL-6 and TNF-alpha, are associated with smaller hippocampal volume in older adults. We suggest that the dynamic balance between the hypothalamic-pituitary adrenal axis and inflammation processes may explain hippocampal volume reductions in older adults better than either set of measures do in isolation.

  10. Synergistic Communication between CD4+ T Cells and Monocytes Impacts the Cytokine Environment

    Science.gov (United States)

    Schrier, Sarah B.; Hill, Abby S.; Plana, Deborah; Lauffenburger, Douglas A.

    2016-01-01

    Physiological cytokine environments arise from factors produced by diverse cell types in coordinated concert. Understanding the contributions of each cell type in the context of cell-cell communication is important for effectively designing disease modifying interventions. Here, we present multi-plexed measurement of 48 cytokines from a coculture system of primary human CD4+ T cells and monocytes across a spectrum of stimuli and for a range of relative T cell/monocyte compositions, coupled with corresponding measurements from PBMCs and plasma from the same donors. Computational analysis of the resulting data-sets elucidated communication-independent and communication-dependent contributions, including both positive and negative synergies. We find that cytokines in cell supernatants were uncorrelated to those found in plasma. Additionally, as an example of positive synergy, production levels of CXCR3 cytokines IP-10 and MIG, depend non-linearly on both IFNγ and TNFα levels in cross-talk between T cells and monocytes. Overall, this work demonstrates that communication between cell types can significantly impact the consequent cytokine environment, emphasizing the value of mixed cell population studies. PMID:27721433

  11. Cytokines and organ failure in acute pancreatitis

    DEFF Research Database (Denmark)

    Malmstrøm, Marie Louise; Hansen, Mark Berner; Andersen, Anders Møller

    2012-01-01

    We aimed at synchronously examining the early time course of 4 proinflammatory cytokines as predictive factors for development of organ failure in patients with acute pancreatitis (AP).......We aimed at synchronously examining the early time course of 4 proinflammatory cytokines as predictive factors for development of organ failure in patients with acute pancreatitis (AP)....

  12. Cytokines and mood in healthy young adults

    NARCIS (Netherlands)

    Jansen, J.; Fernstrand, A.M.; Van De Loo, A.J.A.E.|info:eu-repo/dai/nl/369403649; Garssen, J.|info:eu-repo/dai/nl/086369962; Verster, J.C.|info:eu-repo/dai/nl/241442702

    2015-01-01

    Purpose: A link between chronic inflammation and neuropsychiatric disorders has been demonstrated previously. For example, pro- and anti-inflammatory cytokines have shown to impact neurocircuits relevant to mood regulation. Elevated levels of inflammatory cytokines have been associated with the deve

  13. Cytokines in clinical and experimental transplantation

    NARCIS (Netherlands)

    A.C.Th.M. Vossen (Ann); H.F.J. Savelkoul (Huub)

    1994-01-01

    textabstractAllograft rejection is a complex process, which requires interactions between different cell types and a variety of soluble factors, such as cytokines. In this review we discuss the role of cytokines in the induction and effector phases of the rejection process and in the induction and m

  14. Polymorphisms at Cytokine Genes May Determine the Effect of Vitamin E on Cytokine Production in the Elderly1–3

    Science.gov (United States)

    Belisle, Sarah E.; Leka, Lynette S.; Delgado-Lista, Javier; Jacques, Paul F.; Ordovas, Jose M.; Meydani, Simin Nikbin

    2009-01-01

    Vitamin E has been shown to affect cytokine production. However, individual response to vitamin E supplementation varies. Previous studies indicate that cytokine production is heritable and common single nucleotide polymorphisms (SNP) may explain differences in cytokine production between individuals. We hypothesize that the differential response to the immunomodulatory actions of vitamin E reflects genetic differences among individuals, including SNP at cytokine genes that modulate cytokine production. We used data from a double-blind, placebo-controlled 1-y vitamin E (182 mg d,l-α-tocopherol) intervention study in elderly men and women (mean age 83 y) to test this hypothesis (vitamin E, n = 47; placebo, n = 63). We found that the effect of vitamin E on tumor necrosis factor (TNF)-α production in whole blood stimulated for 24 h with lipopolysaccharide (1.0 mg/L) is dependent on TNFα -308G > A. Participants with the A/A and A/G genotypes at TNFα -308G > A who were treated with vitamin E had lower TNFα production than those with the A allele treated with placebo. These observations suggest that individual immune responses to vitamin E supplementation are in part mediated by genetic factors. Because the A allele at TNFα has been previously associated with higher TNFα levels in whole blood and isolated immune cells, our observations suggest that the antiinflammatory effect of vitamin E is specific to those genetically predisposed to higher inflammation. Further studies are needed to determine the biological mechanism driving the interaction between vitamin E treatment and TNFα -308G > A and its implications for disease resistance. PMID:19710156

  15. 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.

  16. Chronic Inflammation and Cytokines in the Tumor Microenvironment

    Science.gov (United States)

    Landskron, Glauben; De la Fuente, Marjorie; Thuwajit, Peti; Thuwajit, Chanitra; Hermoso, Marcela A.

    2014-01-01

    Acute inflammation is a response to an alteration induced by a pathogen or a physical or chemical insult, which functions to eliminate the source of the damage and restore homeostasis to the affected tissue. However, chronic inflammation triggers cellular events that can promote malignant transformation of cells and carcinogenesis. Several inflammatory mediators, such as TNF-α, IL-6, TGF-β, and IL-10, have been shown to participate in both the initiation and progression of cancer. In this review, we explore the role of these cytokines in important events of carcinogenesis, such as their capacity to generate reactive oxygen and nitrogen species, their potential mutagenic effect, and their involvement in mechanisms for epithelial mesenchymal transition, angiogenesis, and metastasis. Finally, we will provide an in-depth analysis of the participation of these cytokines in two types of cancer attributable to chronic inflammatory disease: colitis-associated colorectal cancer and cholangiocarcinoma. PMID:24901008

  17. Chronic Inflammation and Cytokines in the Tumor Microenvironment

    Directory of Open Access Journals (Sweden)

    Glauben Landskron

    2014-01-01

    Full Text Available Acute inflammation is a response to an alteration induced by a pathogen or a physical or chemical insult, which functions to eliminate the source of the damage and restore homeostasis to the affected tissue. However, chronic inflammation triggers cellular events that can promote malignant transformation of cells and carcinogenesis. Several inflammatory mediators, such as TNF-α, IL-6, TGF-β, and IL-10, have been shown to participate in both the initiation and progression of cancer. In this review, we explore the role of these cytokines in important events of carcinogenesis, such as their capacity to generate reactive oxygen and nitrogen species, their potential mutagenic effect, and their involvement in mechanisms for epithelial mesenchymal transition, angiogenesis, and metastasis. Finally, we will provide an in-depth analysis of the participation of these cytokines in two types of cancer attributable to chronic inflammatory disease: colitis-associated colorectal cancer and cholangiocarcinoma.

  18. Cytokines in juvenile rheumatoid arthritis (JRA).

    Science.gov (United States)

    Mangge, H; Schauenstein, K

    1998-06-01

    Juvenile rheumatoid arthritis (JRA), unlike rheumatoid arthritis of adulthood (RA), is a heterogenous disease comprising at least five subtypes that differ in clinical course and prognosis, and require different therapeutical approaches. As compared to RA, the production of local and systemic cytokines in JRA have not yet been as extensively investigated. In this article we review the available literature on cytokine expression in serum and synovial fluid in all five different subtypes of JRA. Even though the data are still fragmentary, the evidence so far suggests that the determination of serum cytokines yields relevant information as to clinical subtype and inflammatory activity of the disease. Furthermore, the cytokine data suggest that the pathogenesis of JRA may even by more heterogenous than defined by the clinical subtypes. Finally, future directions of research in this area are proposed, and-based on the latest results-arguments for (anti)cytokine therapies in JRA are critically discussed.

  19. Interactions between Autophagy and Inhibitory Cytokines.

    Science.gov (United States)

    Wu, Tian-Tian; Li, Wei-Min; Yao, Yong-Ming

    2016-01-01

    Autophagy is a degradative pathway that plays an essential role in maintaining cellular homeostasis. Most early studies of autophagy focused on its involvement in age-associated degeneration and nutrient deprivation. However, the immunological functions of autophagy have become more widely studied in recent years. Autophagy has been shown to be an intrinsic cellular defense mechanism in the innate and adaptive immune responses. Cytokines belong to a broad and loose category of proteins and are crucial for innate and adaptive immunity. Inhibitory cytokines have evolved to permit tolerance to self while also contributing to the eradication of invading pathogens. Interactions between inhibitory cytokines and autophagy have recently been reported, revealing a novel mechanism by which autophagy controls the immune response. In this review, we discuss interactions between autophagy and the regulatory cytokines IL-10, transforming growth factor-β, and IL-27. We also mention possible interactions between two newly discovered cytokines, IL-35 and IL-37, and autophagy.

  20. Interactions between Autophagy and Inhibitory Cytokines

    Science.gov (United States)

    Wu, Tian-tian; Li, Wei-Min; Yao, Yong-Ming

    2016-01-01

    Autophagy is a degradative pathway that plays an essential role in maintaining cellular homeostasis. Most early studies of autophagy focused on its involvement in age-associated degeneration and nutrient deprivation. However, the immunological functions of autophagy have become more widely studied in recent years. Autophagy has been shown to be an intrinsic cellular defense mechanism in the innate and adaptive immune responses. Cytokines belong to a broad and loose category of proteins and are crucial for innate and adaptive immunity. Inhibitory cytokines have evolved to permit tolerance to self while also contributing to the eradication of invading pathogens. Interactions between inhibitory cytokines and autophagy have recently been reported, revealing a novel mechanism by which autophagy controls the immune response. In this review, we discuss interactions between autophagy and the regulatory cytokines IL-10, transforming growth factor-β, and IL-27. We also mention possible interactions between two newly discovered cytokines, IL-35 and IL-37, and autophagy. PMID:27313501

  1. Cytokine signalling in embryonic stem cells

    DEFF Research Database (Denmark)

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

    2006-01-01

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

  2. Cytokines and Immune Responses in Murine Atherosclerosis.

    Science.gov (United States)

    Kusters, Pascal J H; Lutgens, Esther

    2015-01-01

    Atherosclerosis is an inflammatory disease of the vessel wall characterized by activation of the innate immune system, with macrophages as the main players, as well as the adaptive immune system, characterized by a Th1-dominant immune response. Cytokines play a major role in the initiation and regulation of inflammation. In recent years, many studies have investigated the role of these molecules in experimental models of atherosclerosis. While some cytokines such as TNF or IFNγ clearly had atherogenic effects, others such as IL-10 were found to be atheroprotective. However, studies investigating the different cytokines in experimental atherosclerosis revealed that the cytokine system is complex with both disease stage-dependent and site-specific effects. In this review, we strive to provide an overview of the main cytokines involved in atherosclerosis and to shed light on their individual role during atherogenesis.

  3. Proinflammatory cytokines and their membrane-bound receptors are altered in the lymphocytes of schizophrenia patients.

    Science.gov (United States)

    Pandey, Ghanshyam N; Ren, Xinguo; Rizavi, Hooriyah S; Zhang, Hui

    2015-05-01

    Abnormalities of protein levels of proinflammatory cytokines and their soluble receptors have been reported in the plasma/serum of schizophrenia (SZ) patients. To examine if SZ is also associated with the abnormal gene expression of cytokines and their membrane-bound receptors, we studied mRNA expression of proinflammatory cytokines and their receptors in lymphocytes of SZ patients and normal control (NC) subjects. We determined the protein and mRNA expression of proinflammatory cytokines and mRNA expression of their receptors in lymphocytes from 30 SZ patients and 30 drug-free NC subjects. The subjects were diagnosed according to DSM-IV criteria. Protein levels of cytokines were determined by ELISA, and mRNA levels in lymphocytes were determined by the qPCR method. We found that the mRNA levels of IL-6, TNF-α, IL-1R1, TNFR1, and TNFR2, but not IL-1β, IL-1R2, IL-1RA, IL-6R, or GP130 were significantly increased in lymphocytes of SZ patients compared with NC subjects. We also found that the protein expression of IL-6 and TNF-α, but not IL-1β, was also significantly increased in SZ patients compared with NC subjects. These studies suggest that in addition to the reported abnormalities of proinflammatory cytokines and their soluble receptors in the plasma of SZ patients, an abnormal gene expression of these cytokines and their membrane-bound receptors may be involved in the pathogenesis of SZ.

  4. Neither plasma progesterone concentrations nor exogenous eCG affects rates of ovulation or pregnancy in fixed-time artificial insemination (FTAI) protocols for puberal Nellore heifers.

    Science.gov (United States)

    Pegorer, M Figueira; Ereno, R L; Satrapa, R A; Pinheiro, V G; Trinca, L A; Barros, C M

    2011-01-01

    The objective was to evaluate the effects of plasma progesterone (P4) concentrations and exogenous eCG on ovulation and pregnancy rates of pubertal Nellore heifers in fixed-time artificial insemination (FTAI) protocols. In Experiment 1 (Exp. 1), on Day 0 (7 d after ovulation), heifers (n = 15) were given 2 mg of estradiol benzoate (EB) im and randomly allocated to receive: an intravaginal progesterone-releasing device containing 0.558 g of P4 (group 0.5G, n = 4); an intravaginal device containing 1 g of P4 (group 1G, n = 4); 0.558 g of P4 and PGF(2α) (PGF; 150 μg d-cloprostenol, group 0.5G/PGF, n = 4); or 1 g of P4 and PGF (group 1G/PGF, n = 3). On Day 8, PGF was given to all heifers and intravaginal devices removed; 24 h later (Day 9), all heifers were given 1 mg EB im. In Exp. 2, pubertal Nellore heifers (n = 292) were treated as in Exp. 1, with FTAI on Day 10 (30 to 36 h after EB). In Exp. 3, pubertal heifers (n = 459) received the treatments described for groups 0.5G/PGF and 1G/PGF and were also given 300 IU of eCG im (groups 0.5G/PGF/eCG and 1G/PGF/eCG) at device removal (Day 8). In Exp. 1, plasma P4 concentrations were significantly higher in heifers that received 1.0 vs 0.588 g P4, and were significantly lower in heifers that received PGF on Day 0. In Exp. 2 and 3, there were no significant differences among groups in rates of ovulation (65-77%) or pregnancy (Exp. 2: 26-33%; Exp. 3: 39-43%). In Exp. 3, diameter of the dominant ovarian follicle on Day 9 was larger in heifers given 0.558 g vs 1.0 g P4 (10.3 ± 0.2 vs 9.3 ± 0.2 mm; P decreased plasma P4 from Days 1 to 8 and increased diameter of the dominant follicle on Day 9. However, neither of these nor 300 IU of eCG on Day 8 significantly increased rates of ovulation or pregnancy.

  5. A comparison of cytokine responses during prolonged cycling in normal and hot environmental conditions

    Directory of Open Access Journals (Sweden)

    Ludmila M Cosio-Lima

    2011-01-01

    Full Text Available Ludmila M Cosio-Lima, Bhargav V Desai, Petra B Schuler, Lesley Keck, Logan ScheelerDepartment of Health, Leisure, and Exercise Science, University of West Florida, Pensacola, FL, USAPurpose: Components of immune function are affected by physical activity in an adverse environment. The purpose of this study was to compare plasma differences in inflammatory cytokines including tumor necrosis factor α (TNF-α and interleukin 6 (IL-6, in addition to the stress hormone cortisol, during prolonged cycling under normal and hot environmental conditions in elite cyclists.Methods and design: Six trained elite male cyclists (27 ± 8 years; 75.5 ± 4 kg; maximum oxygen uptake [VO2max] = 66 ± 6 mL/kg/min, mean ± SD. The cyclists biked for 2.5 h at their prescribed 60% maximum exercise workload (Wmax or 75% VO2max either in an environmental chamber set at 15°C and 40% relative humidity (NEUTRAL or at 35°C and 40% relative humidity (HOT. The cyclists were given 4 mL of water/kg body weight every 15 min under both conditions.Results: Total cortisol concentrations were elevated (P < 0.05 immediately postexercise and 12 h postexercise in both the NEUTRAL and HOT conditions. TNF-α concentrations were only significantly (P = 0.045 elevated postexercise in HOT conditions. During the HOT conditions, a significant (P = 0.006 and 0.007, respectively difference in IL-6 was seen immediately after and 12 h postexercise. During the NEUTRAL condition, IL-6 was only significantly elevated postexercise (P < 0.05.Conclusions: Heat exposure during a long bout of exercise is sufficient to elicit stress response in elite cyclists. However, the degree of release of anti-inflammatory and proinflammatory cytokines might be related to several factors that include the athlete’s fitness level, hydration status, exercise intensity, and length of exposure to hot environments.Keywords: cytokines, inflammation, heat, exercise, performance 

  6. Role of proinflammatory cytokines on lipopolysaccharide-induced phase shifts in locomotor activity circadian rhythm.

    Science.gov (United States)

    Leone, M Juliana; Marpegan, Luciano; Duhart, José M; Golombek, Diego A

    2012-07-01

    We previously reported that early night peripheral bacterial lipopolysaccharide (LPS) injection produces phase delays in the circadian rhythm of locomotor activity in mice. We now assess the effects of proinflammatory cytokines on circadian physiology, including their role in LPS-induced phase shifts. First, we investigated whether differential systemic induction of classic proinflammatory cytokines could explain the time-specific behavioral effects of peripheral LPS. Induction levels for plasma interleukin (IL)-1α, IL-1β, IL-6, or tumor necrosis factor (TNF)-α did not differ between animals receiving a LPS challenge in the early day or early night. We next tested the in vivo effects of central proinflammatory cytokines on circadian physiology. We found that intracerebroventricular (i.c.v.) delivery of TNF-α or interleukin IL-1β induced phase delays on wheel-running activity rhythms. Furthermore, we analyzed if these cytokines mediate the LPS-induced phase shifts and found that i.c.v. administration of soluble TNF-α receptor (but not an IL-1β antagonistic) prior to LPS stimulation inhibited the phase delays. Our work suggests that the suprachiasmatic nucleus (SCN) responds to central proinflammatory cytokines in vivo, producing phase shifts in locomotor activity rhythms. Moreover, we show that the LPS-induced phase delays are mediated through the action of TNF-α at the central level, and that systemic induction of proinflammatory cytokines might be necessary, but not sufficient, for this behavioral outcome.

  7. Interleukin-6: a cytokine to forget.

    Science.gov (United States)

    Balschun, D; Wetzel, W; Del Rey, A; Pitossi, F; Schneider, H; Zuschratter, W; Besedovsky, H O

    2004-11-01

    It is known that proinflammatory cytokines such as interleukin-6 (IL-6) are expressed in the central nervous system (CNS) during disease conditions and affect several brain functions including memory and learning. In contrast to these effects observed during pathological conditions, here we describe a physiological function of IL-6 in the "healthy" brain in synaptic plasticity and memory consolidation. During long-term potentiation (LTP) in vitro and in freely moving rats, IL-6 gene expression in the hippocampus was substantially increased. This increase was long lasting, specific to potentiation, and was prevented by inhibition of N-methyl-D-aspartate receptors with (+/-)-2-amino-5-phosphonopentanoic acid (AP-5). Blockade of endogenous IL-6 by application of a neutralizing anti-IL-6 antibody 90 min after tetanus caused a remarkable prolongation of LTP. Consistently, blockade of endogenous IL-6, 90 min after hippocampus-dependent spatial alternation learning resulted in a significant improvement of long-term memory. In view of the suggested role of LTP in memory formation, these data implicate IL-6 in the mechanisms controlling the kinetics and amount of information storage.

  8. Plasma dipeptidyl peptidase-IV activity in patients with type-2 diabetes mellitus correlates positively with HbAlc levels, but is not acutely affected by food intake

    DEFF Research Database (Denmark)

    Ryskjaer, Jakob; Deacon, Carolyn F.; Carr, Richard D;

    2006-01-01

    a standard meal test (566 kcal) was estimated. RESULTS: Mean fasting plasma DPP-IV activity (expressed as degradation of GLP-1) was significantly higher in this patient group compared with the control subjects (67.5 +/- 1.9 vs 56.8 +/- 2.2 fmol GLP-1/h (mean +/- s.e.m.); P=0.001). In the type-2 diabetic...... patients and control subjects. DESIGN: The study included two protocols. Protocol one involved 40 fasting type-2 diabetic patients (28 men); age 61 +/- 1.4 (mean +/- s.e.m.) years; body mass index (BMI) 31 +/- 0.6 kg/m(2); HbAlc 7.2 +/- 0.2%; and 20 matched control subjects (14 men) were studied. Protocol...

  9. Influence of acute hyperglycemia in human sepsis on inflammatory cytokine and counterregulatory hormone concentrations

    Institute of Scientific and Technical Information of China (English)

    Wen-Kui Yu; Wei-Qin Li; Ning Li; Jie-Shou Li

    2003-01-01

    AIM: In human sepsis, a prominent component of the hypermetabolite is impaired glucose tolerance (IGT) and hyperglycemia. Elevations in plasma glucose concentration impair immune function by altering cytokine production from macrophages. We assessed the role of glucose in the regulation of circulating levels of insulin, glucagon, cortisol,IL-6 and TNF-α in human sepsis with normal or impaired glucose tolerance.METHODS: According to the results of intravenous glucose tolerance test, forty patients were classified into two groups: control group (n=20) and IGT group (n=20).Plasma glucose levels were acutely raised in two groups and maintained at 15 mmol/L for 3 hours. Plasma insulin,glucagon and cortisol levels were measured by radioimmunoassay, the levels of TNF-α and IL-6 were detected by ELISA.RESULTS: In IGT group, the fasting concentrations of plasma glucose, insulin, glucagon, cortisol, IL-6 and TNFα levels were significantly higher than those in control group (P<0.05). During clamp, the control group had a higher average amount of dextrose infusion than the IGT group (P<0.01). In control group, plasma insulin levels rose from a basal value to a peak at an hour (P<0.05) and maintained at high levels. Plasma glucagon levels descended from a basal value to the lowest level within an hour (P<0.01)and low levels were maintained throughout the clamp. In IGT group, plasma insulin was more significantly elevated (P<0.01), and plasma glucagon levels were not significantly declined. Plasma cortisol levels were not significantly changed in two groups. In control group, plasma IL-6 and TNF-α levels rose (P<0.01) within 2 hours of the clamp and returned to basal values at 3 hours. In IGT group, increased levels of plasma cytokine lasted longer than in control group (3 hours vs. 2 hours, P<0.05), and the cytokine peaks of IGT group were higher (P<0.05) than those of control group.CONCLUSION: Acute hyperglycemia pricks up hyperinsulinemia and increases

  10. Cytokine production in patients with papillary thyroid cancer and associated autoimmune Hashimoto thyroiditis.

    Science.gov (United States)

    Zivancevic-Simonovic, Snezana; Mihaljevic, Olgica; Majstorovic, Ivana; Popovic, Suzana; Markovic, Slavica; Milosevic-Djordjevic, Olivera; Jovanovic, Zorica; Mijatovic-Teodorovic, Ljiljana; Mihajlovic, Dusan; Colic, Miodrag

    2015-08-01

    Hashimoto thyroiditis (HT) is the most frequent thyroid autoimmune disease, while papillary thyroid cancer (PTC) is one of the most common endocrine malignancies. A few patients with HT also develop PTC. The aim of this study was to analyze cytokine profiles in patients with PTC accompanied with autoimmune HT in comparison with those in patients with PTC alone or HT alone and healthy subjects. Cytokine levels were determined in supernatants obtained from phytohemagglutinin (PHA)-stimulated whole blood cultures in vitro. The concentrations of selected cytokines: Th1-interferon gamma (IFN-γ); Th2-interleukin 4 (IL-4), interleukin 5 (IL-5), interleukin 6 (IL-6), interleukin 10 (IL-10) and interleukin 13 (IL-13); Th9-interleukin 9 (IL-9); and Th17-interleukin 17 (IL-17A) were measured using multiplex cytokine detection systems for human Th1/Th2/Th9/Th17/Th22. We found that PTC patients with HT produced significantly higher concentrations of IL-4, IL-6, IL-9, IL-13 and IFN-γ than PTC patients without HT. In conclusion, autoimmune HT affects the cytokine profile of patients with PTC by stimulating secretion of Th1/Th2/Th9 types of cytokines. Th1/Th2 cytokine ratios in PTC patients with associated autoimmune HT indicate a marked shift toward Th2 immunity.

  11. Photonic crystal enhanced cytokine immunoassay.

    Science.gov (United States)

    Mathias, Patrick C; Ganesh, Nikhil; Cunningham, Brian T

    2009-01-01

    Photonic crystal surfaces are demonstrated as a means for enhancing the detection sensitivity and resolution for assays that use a fluorescent tag to quantify the concentration of an analyte protein molecule in a liquid test sample. Computer modeling of the spatial distribution of resonantly coupled electromagnetic fields on the photonic crystal surface are used to estimate the magnitude of enhancement factor compared to performing the same fluorescent assay on a plain glass surface, and the photonic crystal structure is fabricated and tested to experimentally verify the performance using a sandwich immunoassay for the protein Tumor Necrosis Factor-alpha (TNF-alpha). The demonstrated photonic crystal fabrication method utilizes a nanoreplica molding technique that allows for large-area inexpensive fabrication of the structure in a format that is compatible with confocal microarray laser scanners. The signal-to-noise ratio for fluorescent spots on the photonic crystal is increased by at least five-fold relative to the glass slide, allowing a TNF-alpha concentration of 1.6 pg/ml to be distinguished from noise on a photonic crystal surface. In addition, the minimum quantitative limit of detection on the photonic crystal surface is one-third the limit on the glass slide - a decrease from 18 pg/ml to 6 pg/ml. The increased performance of the immunoassay allows for more accurate quantitation of physiologically relevant concentrations of TNF-alpha in a protein microarray format that can be expanded to multiple cytokines.

  12. Surface plasma functionalization influences macrophage behavior on carbon nanowalls

    Energy Technology Data Exchange (ETDEWEB)

    Ion, Raluca [University of Bucharest, Department of Biochemistry and Molecular Biology, 91-95 Spl. Independentei, 050095 Bucharest (Romania); Vizireanu, Sorin [National Institute for Laser, Plasma and Radiation Physics, 409 Atomistilor, PO Box MG-36, 077125, Magurele, Bucharest (Romania); Stancu, Claudia Elena [National Institute for Laser, Plasma and Radiation Physics, 409 Atomistilor, PO Box MG-36, 077125, Magurele, Bucharest (Romania); Leibniz Institute for Plasma Science and Technology (INP Greifswald), Felix-Hausdorff-Str. 2, 17489 Greifswald (Germany); Luculescu, Catalin [National Institute for Laser, Plasma and Radiation Physics, 409 Atomistilor, PO Box MG-36, 077125, Magurele, Bucharest (Romania); Cimpean, Anisoara, E-mail: anisoara.cimpean@bio.unibuc.ro [University of Bucharest, Department of Biochemistry and Molecular Biology, 91-95 Spl. Independentei, 050095 Bucharest (Romania); Dinescu, Gheorghe [National Institute for Laser, Plasma and Radiation Physics, 409 Atomistilor, PO Box MG-36, 077125, Magurele, Bucharest (Romania)

    2015-03-01

    The surfaces of carbon nanowall samples as scaffolds for tissue engineering applications were treated with oxygen or nitrogen plasma to improve their wettability and to functionalize their surfaces with different functional groups. X-ray photoelectron spectroscopy and water contact angle results illustrated the effective conversion of the carbon nanowall surfaces from hydrophobic to hydrophilic and the incorporation of various amounts of carbon, oxygen and nitrogen functional groups during the treatments. The early inflammatory responses elicited by un-treated and modified carbon nanowall surfaces were investigated by quantifying tumor necrosis factor-alpha and macrophage inflammatory protein-1 alpha released by attached RAW 264.7 macrophage cells. Scanning electron microscopy and fluorescence studies were employed to investigate the changes in macrophage morphology and adhesive properties, while MTT assay was used to quantify cell proliferation. All samples sustained macrophage adhesion and growth. In addition, nitrogen plasma treatment was more beneficial for cell adhesion in comparison with un-modified carbon nanowall surfaces. Instead, oxygen plasma functionalization led to increased macrophage adhesion and spreading suggesting a more activated phenotype, confirmed by elevated cytokine release. Thus, our findings showed that the chemical surface alterations which occur as a result of plasma treatment, independent of surface wettability, affect macrophage response in vitro. - Highlights: • N{sub 2} and O{sub 2} plasma treatments alter the CNW surface chemistry and wettability. • Cells seeded on CNW scaffolds are viable and metabolically active. • Surface functional groups, independent of surface wettability, affect cell response. • O{sub 2} plasma treatment of CNW leads to a more activated macrophage phenotype.

  13. Rapid Detection of Neutrophil Oxidative Burst Capacity is Predictive of Whole Blood Cytokine Responses.

    Directory of Open Access Journals (Sweden)

    Philip J Vernon

    Full Text Available Maladaptive immune responses, particularly cytokine and chemokine-driven, are a significant contributor to the deleterious inflammation present in many types of injury and infection. Widely available applications to rapidly assess individual inflammatory capacity could permit identification of patients at risk for exacerbated immune responses and guide therapy. Here we evaluate neutrophil oxidative burst (NOX capacity measured by plate reader to immuno-type Rhesus Macaques as an acute strategy to rapidly detect inflammatory capacity and predict maladaptive immune responses as assayed by cytokine array.Whole blood was collected from anesthetized Rhesus Macaques (n = 25 and analyzed for plasma cytokine secretion (23-plex Luminex assay and NOX capacity. For cytokine secretion, paired samples were either unstimulated or ex-vivo lipopolysaccharide (LPS-stimulated (100μg/mL/24h. NOX capacity was measured in dihydrorhodamine-123 loaded samples following phorbol 12-myristate 13-acetate (PMA/ionomycin treatment. Pearson's test was utilized to correlate NOX capacity with cytokine secretion, p<0.05 considered significant.LPS stimulation induced secretion of the inflammatory molecules G-CSF, IL-1β, IL-1RA, IL-6, IL-10, IL-12/23(p40, IL-18, MIP-1α, MIP-1β, and TNFα. Although values were variable, several cytokines correlated with NOX capacity, p-values≤0.0001. Specifically, IL-1β (r = 0.66, IL-6 (r = 0.74, the Th1-polarizing cytokine IL-12/23(p40 (r = 0.78, and TNFα (r = 0.76 were strongly associated with NOX.NOX capacity correlated with Th1-polarizing cytokine secretion, indicating its ability to rapidly predict inflammatory responses. These data suggest that NOX capacity may quickly identify patients at risk for maladaptive immune responses and who may benefit from immuno-modulatory therapies. Future studies will assess the in-vivo predictive value of NOX in animal models of immune-mediated pathologies.

  14. Fish oil in combination with high or low intakes of linoleic acid lowers plasma triacylglycerols but does not affect other cardiovascular risk markers in healthy men

    DEFF Research Database (Denmark)

    Damsgaard, Camilla T.; Frøkiær, Hanne; Andersen, Anders D.

    2008-01-01

    with a high- or low-LA intake affects overall CVD risk profile. Healthy men (n = 64) were randomized to 5 mL/d fish oil capsules (FO) [mean intake 3.1 g/d (n-3) LCPUFA] or olive oil capsules (control) and to oils and spreads with either a high (S/B) or a low (R/K) LA content, resulting in a 7.3 g/d higher LA...

  15. A novel compound C12 inhibits inflammatory cytokine production and protects from inflammatory injury in vivo.

    Directory of Open Access Journals (Sweden)

    Yi Wang

    Full Text Available Inflammation is a hallmark of many diseases. Although steroids and cyclooxygenase inhibitors are main anti-inflammatory therapeutical agents, they may cause serious side effects. Therefore, developing non-steroid anti-inflammatory agents is urgently needed. A novel hydrosoluble compound, C12 (2,6-bis(4-(3-(dimethylamino-propoxybenzylidenecyclohexanone, has been designed and synthesized as an anti-inflammatory agent in our previous study. In the present study, we investigated whether C12 can affect inflammatory processes in vitro and in vivo. In mouse primary peritoneal macrophages, C12 potently inhibited the production of the proinflammatory gene expression including TNF-α, IL-1β, IL-6, iNOS, COX-2 and PGE synthase. The activity of C12 was partly dependent on inhibition of ERK/JNK (but p38 phosphorylation and NF-κB activation. In vivo, C12 suppressed proinflammatory cytokine production in plasma and liver, attenuated lung histopathology, and significantly reduced mortality in endotoxemic mice. In addition, the pre-treatment with C12 reduced the inflammatory pain in the acetic acid and formalin models and reduced the carrageenan-induced paw oedema and acetic acid-increased vascular permeability. Taken together, C12 has multiple anti-inflammatory effects. These findings, coupled with the low toxicity and hydrosolubility of C12, suggests that this agent may be useful in the treatment of inflammatory diseases.

  16. Inflammatory cytokines suppress arylamine N-acetyltransferase 1 in cholangiocarcinoma cells

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To evaluate the effect of inflammatory cytokines on arylamine N-acetyltransferase 1 (NAT1), which is a phase-Ⅱ enzyme involved in the biotransformation of aromatic and heterocyclic amines found in food, drugs and the environment.METHODS: Human cholangiocarcinoma KKU-100 cells were treated with a mixture of proinflammatory cytokines (interferon-y, interleukin-1β and tumor necrosis factor-α)for 48 h, and the effect on NAT1 activity was assessed by high performance liquid chromatography, while NAT1 expression was determined by reverse-transcription polymerase chain reaction. The oxidative stress on the cells was examined by the formation of nitric oxide,superoxide anion and glutathione (GSH) levels. The cells were also treated with S-nitroso-glutathione (GSNO), a nitric oxide donor, to see if the responses were similar to those obtained with the inflammatory cytokines.RESULTS: Cytokines suppressed NAT1 activity,reducing the Vmax without affecting the Km. Cytokines also had a significant impact on the induction of nitric oxide production and in reducing the redox ratios of glutathione (GSH) and GSH disulfide. Treatment with GSNO for 2-48 h reduced NAT1 activity without affecting the GSH ratio. Moreover, inflammatory cytokines and GSNO suppressed NAT1 mRNA expression.CONCLUSION: These findings indicate an association between inflammation and suppression of NAT1, which perhaps contributes to chemical-mediated toxicity and carcinogenesis.

  17. Haplotypes in the APOA1-C3-A4-A5 gene cluster affect plasma lipids in both humans and baboons

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Qian-fei; Liu, Xin; O' Connell, Jeff; Peng, Ze; Krauss, Ronald M.; Rainwater, David L.; VandeBerg, John L.; Rubin, Edward M.; Cheng, Jan-Fang; Pennacchio, Len A.

    2003-09-15

    Genetic studies in non-human primates serve as a potential strategy for identifying genomic intervals where polymorphisms impact upon human disease-related phenotypes. It remains unclear, however, whether independently arising polymorphisms in orthologous regions of non-human primates leads to similar variation in a quantitative trait found in both species. To explore this paradigm, we studied a baboon apolipoprotein gene cluster (APOA1/C3/A4/A5) for which the human gene orthologs have well established roles in influencing plasma HDL-cholesterol and triglyceride concentrations. Our extensive polymorphism analysis of this 68 kb gene cluster in 96 pedigreed baboons identified several haplotype blocks each with limited diversity, consistent with haplotype findings in humans. To determine whether baboons, like humans, also have particular haplotypes associated with lipid phenotypes, we genotyped 634 well characterized baboons using 16 haplotype tagging SNPs. Genetic analysis of single SNPs, as well as haplotypes, revealed an association of APOA5 and APOC3 variants with HDL cholesterol and triglyceride concentrations, respectively. Thus, independent variation in orthologous genomic intervals does associate with similar quantitative lipid traits in both species, supporting the possibility of uncovering human QTL genes in a highly controlled non-human primate model.

  18. Cytokine medicines in clinical practice: current issues.

    Science.gov (United States)

    Barnes, Theresa; Moots, Robert J; Goodacre, John

    2005-10-21

    Cytokine medicines have been licensed for the treatment of rheumatoid arthritis since 2000. The rheumatology community has accrued a large amount of experience in the use of these medications. This experience has led to the development of guidelines for their use that include ongoing vigilance for long term adverse events and efficacy using the Biologics Register. Delivery of these expensive therapies has prompted extensive system developments within rheumatology. The cytokine medicines have provided important tools to probe the pathogenesis of rheumatoid and other inflammatory diseases. Further cytokine medicines, in various stages of development, are on the horizon and continue to stimulate excitement within this fast expanding field.

  19. Possible Impact of Salivary Influence on Cytokine Analysis in Exhaled Breath Condensate

    Directory of Open Access Journals (Sweden)

    T. Ichikawa

    2007-01-01

    Full Text Available Background: Exhaled breath condensate (EBC is thought to contain substances of the lower airway epithelial lining fluid (ELF aerosolized by turbulent flow. However, contamination by saliva may affect the EBC when collected orally.Objective: The purpose of this study was to compare the cytokine expression levels in EBC with those in saliva, and to clarify the influence of saliva on cytokine measurements of EBC.Methods: EBC and saliva samples were obtained from 10 adult subjects with stable asthma. To estimate differences in the contents of substances between EBC and saliva, the total protein concentration of each sample was measured. Further, we also measured the total protein concentration of ELF obtained from another patient group with suspected lung cancer using a micro sampling probe during bronchoscopic examination and roughly estimated the dilution of EBC by comparing the total protein concentration of EBC and ELF from those two patient groups. The cytokine expression levels of EBC and saliva from asthmatic group were assessed by a cytokine protein array.Results: The mean total protein concentrations in EBC, saliva and ELF were 4.6 μg/ml, 2,398 μg/ml and 14,111 μg/ml, respectively. The dilution of EBC could be estimated as 1:3000. Forty cytokines were analyzed by a cytokine protein array and each cytokine expression level of EBC was found to be different from that of saliva. Corrected by the total protein concentration, all cytokine expression levels of EBC were significantly higher than those of saliva.Conclusion: These results suggest that the salivary influence on the cytokine assessment in EBC may be negligible.

  20. Circulating T lymphocyte subsets, cytokines, and immune checkpoint inhibitors in patients with bipolar II or major depression: a preliminary study

    Science.gov (United States)

    Wu, Wei; Zheng, Ya-li; Tian, Li-ping; Lai, Jian-bo; Hu, Chan-chan; Zhang, Peng; Chen, Jing-kai; Hu, Jian-bo; Huang, Man-li; Wei, Ning; Xu, Wei-juan; Zhou, Wei-hua; Lu, Shao-jia; Lu, Jing; Qi, Hong-li; Wang, Dan-dan; Zhou, Xiao-yi; Duan, Jin-feng; Xu, Yi; Hu, Shao-hua

    2017-01-01

    This study aimed to investigate the less known activation pattern of T lymphocyte populations and immune checkpoint inhibitors on immunocytes in patients with bipolar II disorder depression (BD) or major depression (MD). A total of 23 patients with BD, 22 patients with MD, and 20 healthy controls (HCs) were recruited. The blood cell count of T lymphocyte subsets and the plasma level of cytokines (IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ) were selectively investigated. The expression of T-cell immunoglobulin and mucin-domain containing-3 (TIM-3), programmed cell death protein 1 (PD-1) and its ligands, PD-L1 and PD-L2, on T lymphocytes and monocytes, was detected. In results, blood proportion of cytotoxic T cells significantly decreased in BD patients than in either MD patients or HCs. The plasma level of IL-6 increased in patients with BD and MD. The expression of TIM-3 on cytotoxic T cells significantly increased, whereas the expression of PD-L2 on monocytes significantly decreased in patients with BD than in HCs. These findings extended our knowledge of the immune dysfunction in patients with affective disorders. PMID:28074937

  1. Pregnancy associated plasma protein A2 (PAPP-A2) affects bone size and shape and contributes to natural variation in postnatal growth in mice.

    Science.gov (United States)

    Christians, Julian Kenneth; de Zwaan, Devin Rhys; Fung, Sunny Ho Yeung

    2013-01-01

    Pregnancy associated plasma protein A2 (PAPP-A2) is a protease of insulin-like growth factor binding protein 5 and is receiving increasing attention for its roles in pregnancy and postnatal growth. The goals of the present study were to characterize the effects of PAPP-A2 deletion on bone size and shape in mice at 10 weeks of age, and to determine whether Pappa2 is the gene responsible for a previously-identified quantitative trait locus (QTL) contributing to natural variation in postnatal growth in mice. Mice homozygous for constitutive PAPP-A2 deletion were lighter than wild-type littermates, and had smaller mandible dimensions and shorter skull, humerus, femur, tibia, pelvic girdle, and tail bone. Furthermore, PAPP-A2 deletion reduced mandible dimensions and the lengths of the skull, femur, pelvic girdle, and tail bone more than would be expected due to the effect on body mass. In addition to its effects on bone size, PAPP-A2 deficiency also altered the shape of the mandible and pelvic girdle, as assessed by geometric morphometrics. Mice homozygous for the PAPP-A2 deletion had less deep mandibles, and pelvic girdles with a more feminine shape. Using a quantitative complementation test, we confirmed that Pappa2 is responsible for the effects of the previously-identified QTL, demonstrating that natural variation in the Pappa2 gene contributes to variation in postnatal growth in mice. If similar functional variation in the Pappa2 gene exists in other species, effects of this variation on the shape of the pelvic girdle might explain the previously-reported associations between Pappa2 SNPs and developmental dysplasia of the hip in humans, and birthing in cattle.

  2. Rheumatoid Factor and Its Interference with Cytokine Measurements: Problems and Solutions

    Directory of Open Access Journals (Sweden)

    Else Marie Bartels

    2011-01-01

    Full Text Available Use of cytokines as biomarkers for disease is getting more widespread. Cytokines are conveniently determined by immunoassay, but interference from present antibodies is known to cause problems. In rheumatoid arthritis (RA, interference of rheumatoid factor (RF may be problematic. RF covers a group of autoantibodies from immunoglobulin subclasses and is present in 65–80% of RA patients. Partly removal of RF is possible by precipitation. This study aims at determining the effects of presence of RF in blood and synovial fluid on cytokine measurements in samples from RA patients and finding possible solutions for recognized problems. IL-1β, IL-4, IL-6, and IL-8 were determined with multiplex immunoassays (MIA in samples from RA patients prior to and after polyethylene glycol (PEG 6000 precipitation. Presence of RF does interfere with MIA. PEG 6000 precipitation abolishes this RF interference. We recommend PEG precipitation for all immunoassay measurements of plasma samples from RA patients.

  3. Dynamical Systems, Cytokine Storms, and Blood Filtration

    Science.gov (United States)

    Foster, Glenn; Hubler, Alfred

    2008-03-01

    Various infections and non-infectious diseases can trigger immune cells and the proteins (cytokines) the cells use to communicate with each other to be caught in a positive feedback loop; this ``cytokine storm'' is frequently fatal. By examining the network of cytokine-immune cell interactions we will illustrate why anti-mediator drugs have been generally ineffective in stopping this feedback. A more effective approach may be to try and reduce interactions by dampening many signals at once by filtering the cytokines out of the blood directly (think dialysis). We will argue that feedback on an out of control nonlinear dynamical system is easier to understand than its normal healthy state and apply filtration to a toy model of immune response.

  4. Cytokines and HCV-Related Disorders

    Directory of Open Access Journals (Sweden)

    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.

  5. Cytokine orchestration in post-operative peritoneal adhesion formation.

    LENUS (Irish Health Repository)

    Cahill, Ronan A

    2012-02-03

    Peritoneal adhesions are a near inevitable occurrence after laparotomy and a major cause of both patient and physician misery. To date, clinical attempts at their amelioration have concentrated on manipulating the physical factors that affect their development despite a wealth of experimental data elucidating the molecular mechanisms that underlie their initiation, development and maturation. However, the advent of targeted, specific anti-cytokine agents as directed therapy for inflammatory and neoplastic conditions raises the prospect of a new era for anti-adhesion strategies. To harness this potential will require considerable cross-disciplinary collaboration and that surgeon-scientists propel themselves to the forefront of this emerging field.

  6. Rapidly alternating photoperiods disrupt central and peripheral rhythmicity and decrease plasma glucose, but do not affect glucose tolerance or insulin secretion in sheep.

    Science.gov (United States)

    Varcoe, Tamara J; Gatford, Kathryn L; Voultsios, Athena; Salkeld, Mark D; Boden, Michael J; Rattanatray, Leewen; Kennaway, David J

    2014-09-01

    Disrupting circadian rhythms in rodents perturbs glucose metabolism and increases adiposity. To determine whether these effects occur in a large diurnal animal, we assessed the impact of circadian rhythm disruption upon metabolic function in sheep. Adult ewes (n = 7) underwent 3 weeks of a control 12 h light-12 h dark photoperiod, followed by 4 weeks of rapidly alternating photoperiods (RAPs) whereby the time of light exposure was reversed twice each week. Measures of central (melatonin secretion and core body temperature) and peripheral rhythmicity (clock and metabolic gene expression in skeletal muscle) were obtained over 24 h in both conditions. Metabolic homeostasis was assessed by glucose tolerance tests and 24 h glucose and insulin profiles. Melatonin and core body temperature rhythms resynchronized within 2 days of the last photoperiod shift. High-amplitude Bmal1, Clock, Nr1d1, Cry2 and Per3 mRNA rhythms were apparent in skeletal muscle, which were phase advanced by up to 3.5 h at 2 days after the last phase shift, whereas Per1 expression was downregulated at this time. Pparα, Pgc1α and Nampt mRNA were constitutively expressed in both conditions. Nocturnal glucose concentrations were reduced following chronic phase shifts (zeitgeber time 0, -5.5%; zeitgeber time 12, -2.9%; and zeitgeber time 16, -5.7%), whereas plasma insulin, glucose tolerance and glucose-stimulated insulin secretion were not altered. These results demonstrate that clock gene expression within ovine skeletal muscle oscillates over 24 h and responds to changing photoperiods. However, metabolic genes which link circadian and metabolic clocks in rodents were arrhythmic in sheep. Differences may be due to the ruminant versus monogastric digestive organization in each species. Together, these results demonstrate that despite disruptions to central and peripheral rhythmicity following exposure to rapidly alternating photoperiods, there was minimal impact on glucose homeostasis in

  7. Radiolabelled cytokines for imaging chronic inflammation

    Directory of Open Access Journals (Sweden)

    Alberto Signore

    2002-09-01

    Full Text Available Diagnosis and particularly follow-up of chronic inflammatory disorders could be often difficult in clinical practice. Indeed, traditional radiological techniques reveal only structural tissue alterations and are not able to monitor functional changes occurring in tissues affected by chronic inflammation. The continuous advances in the knowledge of the pathophysioloy of chronic disorders, combined with the progress of radiochemistry, led to the development of new specific radiolabelled agents for the imaging of chronic diseases. In this scenario, cytokines, due to their pivotal role in such diseases, represent good candidates as radiopharmaceuticals.O diagnóstico, e particularmente o acompanhamento das doenças inflamatórias crônicas, pode ser freqüentemente muito difícil na prática clínica. As técnicas radiológicas tradicionais revelam somente as alterações teciduais estruturas, não sendo capazes de monitorar as alterações funcionais que ocorrem nesses tecidos afetados pela inflamação crônica. O contínuo avanço no conhecimento da fisiopatologia dessas doenças, combinado com o progresso da radioquímica, levou ao desenvolvimento de novos agentes radiomarcados para a obtenção de imagens de doenças crônicas. Nesse cenário, as citocinas, devido ao papel primordial em tais doenças, apresentam-se como fortes candidatas a radiofármacos.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    Guiyu Lou

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

  10. A genetic contribution to circulating cytokines and obesity in children

    Science.gov (United States)

    Cytokines are considered to be involved in obesity-related metabolic diseases. Study objectives are to determine the heritability of circulating cytokine levels, to investigate pleiotropy between cytokines and obesity traits, and to present genome scan results for cytokines in 1030 Hispanic children...

  11. Inflammatory cytokine expression in the quadriceps of rats with posttraumatic knee stiffness: A preliminary study.

    Science.gov (United States)

    Liu, Kemin; Wang, Fei; Cui, Zhigang; Liu, Sihai; Han, Xinzuo

    2015-06-01

    The primary purpose of this study was to investigate cytokine expression in the quadriceps of rats with posttraumatic knee stiffness (PTKS) and to determine the effect of exercise training on these cytokines at different follow-up time points. The PTKS rats were randomly assigned into two even groups. The treatment group received exercise training, while the control group received no treatment. Quadriceps specimens were harvested randomly from each group at 8, 12, 16, and 20 weeks. RT-qPCR and immunohistochemical analyses were used to assess the protein and mRNA expression levels of the cytokines IL-1, IL-2, TNF-α, COX-1, and COX-2. TNF-α immunostaining did not differ between the treated and control group tissues, whereas weak immunostaining was observed for all other cytokines in the specimens from the treatment group compared with those from the control group at approximately 12 and 20 weeks. The cytokine levels decreased at approximately 8 weeks in the treatment group, whereas these levels remained elevated or plateaued in the control group. These differences were statistically significant (pcytokines IL-1, IL-2, COX-1, and COX-2 increased in the quadriceps of rats with PTKS and that exercise training affected the observed profile trends of these cytokines.

  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. Cigarette smoking affects sperm plasma membrane integrity%流式细胞术检测吸烟对精子质膜完整性的影响

    Institute of Scientific and Technical Information of China (English)

    李卫巍; 李娜; 吴秋月; 夏欣一; 崔英霞; 黄宇烽; 姚勤

    2012-01-01

    To detect sperm plasma membrane integrity (PMI) of cigarette smoking infertile males using SYBR-14/ PI fluorescent staining and flow cytometry and investigate its clinical significance. Methods: We collected semen samples from 132 cigarette smoking infertile men and 70 normal fertile controls, the former divided into a heavy-smoker group ( > 20 cigarettes a day, n = 68) and a light-smoker group ( ≤20 cigarettes a day, n = 64). We performed computer-assisted semen analysis of the semen samples , and determined sperm PMI by flow cytometry after rinsing with PBS and staining by SYBR-14/PI, the sperm with normal PMI indicated as the percentage of those emitting green fluorescence ( SYBR-14 + /PI- %) , dead sperm as the percentage of those emitting red (SYBR-14 - /PI+ ) , and moribund sperm as the percentage of those emitting both green and red (SYBR-14 + /PI + ). Results: Both the heavy- and light-smoker groups showed significant differences in SYBR-14 -/PI +% and SYBR-14+/PI - % from the normal controls (P<0.01 or P<0.05). SYBR-14 +/PI- % was remarkably lower, while SYBR-14-/PI+ % markedly higher in the heavy-smoker than in the light-smoker group (P<0.05). There was a significant correlation between SYBR-14+ /PI-'% and sperm motility (r = 0.938, P = 0.000). Conclusion: SYBR-14/PI fluorescent staining and flow cytometry analysis could quickly and exactly detect sperm PMI. Cigarette smoking reduces sperm PMI and consequently sperm motility, which might be an important factor of male infertility.%目的:应用荧光染料SYBR-14/PI双色标记法进行流式细胞术检测不育患者精子质膜完整性,分析吸烟对精子质膜完整性的影响并探讨其临床意义. 方法:收集202例男性精液标本,其中132例为本院就诊男性不育患者,分为大烟量组(n=68)与小烟量组(n=64),正常生育男性为正常对照组(n=70).通过计算机辅助精液分析系统进行精液常规分析.精液标本经PBS洗涤处理后用荧光染料SYBR-14/碘

  14. PATHOGENETIC ROLE OF CYTOKINES IN CHILDHOOD ROTAVIRUS INFECTION

    Directory of Open Access Journals (Sweden)

    S. N. Benyova

    2007-01-01

    Full Text Available Abstract. Results of cytokine network studies system in children with rotavirus infection are presented. Concentrations of cytokines were determined at both local and systemic levels. Analysis of cytokine levels was performed at initial terms (day 1 to 3, and in the course of disease (day 7 to 10. It was revealed that mild and mid-severe cases of rotavirus infection in the children are characterized by early increase in proinflammatory cytokines with restricted overshoot of proinflammatory cytokines at early recovery period. Meanwhile, the patients with severe forms of viral gastroenteritis exhibited high levels of proinflammatory cytokines. However, this balance was shifted towards anti-inflammatory cytokines during early reconvalescence.

  15. Correlation between endothelia cells activation and imbalance of cytokines in pulmonary hypertension of congenital heart disease

    Institute of Scientific and Technical Information of China (English)

    师桃; 吕毅; 耿希刚; 李兆志

    2007-01-01

    Objective To explore the correlation between endothelia cells activation and cytokines (ET-1, NO) levels in patients with pulmonary hypertension (PH), and to discuss their roles in the development of PH. Methods Twenty patients with simple ventricular septal defect (VSD) were chosen as controls, and 30 patients with PH were studied. Plasma levels of ET-1 and NO were measured by radioimmunoassay or colorimetric method. Before cardiopulmonary bypass was established, the specimens from right lung were fixed wi...

  16. Th1 cytokine-based immunotherapy for cancer

    Institute of Scientific and Technical Information of China (English)

    Hong-Mei Xu

    2014-01-01

    Cytokine-based immunotherapy is executed by harnessing cytokines to activate the immune system to suppress tumors. Th1-type cytokines including IL-1, IL-2, IL-12 and granulocyte-macrophage colony-stimulating factor are potent stimulators of Th1 differentiation and Th1-based antitumor response. Many preclinical studies demonstrated the antitumor effects of Th1 cytokines but their clinical efficacy is limited. Multiple factors influence the efficacy of immunotherapy for tumors. For instance immunosuppressive cells in the tumor microenvironment can produce inhibitory cytokines which suppress antitumor immune response. Most studies on cytokine immunotherapy focused on how to boost Th1 response; many studies combined cytokine-based therapy with other treatments to reverse immunosuppression in tumor microenvironment. In addition, cytokines have pleiotropic functions and some cytokines show paradoxical activities under different settings. Better understanding the physiological and pathological functions of cytokines helps clinicians to design Th1-based cancer therapy in clinical practice.

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

    Science.gov (United States)

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

    2014-10-01

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

  18. Magnetic resonance imaging determined visceral fat reduction associates with enhanced IL-10 plasma levels in calorie restricted obese subjects.

    Directory of Open Access Journals (Sweden)

    Gloria Formoso

    Full Text Available BACKGROUND: Obesity is characterized by a low grade chronic inflammation state. Indeed circulating pro-inflammatory cytokines, such as TNF-α and IL-6, are elevated in obese subjects, while anti-inflammatory cytokines, such as IL-10, appear to be reduced. Cytokines profile improves after weight loss, but how visceral or subcutaneous fat loss respectively affect pro- or anti-inflammatory cytokines plasma levels has not been precisely assessed. Therefore in the present study we correlated changes in circulating cytokine profile with quantitative changes in visceral and subcutaneous adipose tissue depots measured by an ad hoc Magnetic Resonance Imaging (MRI protocol before and after weight loss. MATERIALS AND METHODS: In 14 obese subjects, MRI determination of visceral and subcutaneous fat and plasma glucose, insulin, TNF-α IL-6, and IL-10 measurements were performed before and after a caloric restriction induced weight loss of at least 5% of the original body weight. RESULTS: Weight loss improved insulin sensitivity (QUICKI Index: 0.35±0.03 vs 0.37±0.04; P<0.05, increased IL-10 (3.4±1.9 vs 4.6±1.0 pg/mL; P<0.03, and reduced TNF-α and IL-6 plasma levels (2.5±1.3 vs 1.6±1.5 pg/mL, P<0.0015, 2.3±0.4 vs 1.6±0.6 pg/mL, P<0.02 respectively. A significant correlation was observed between the amount of visceral fat loss and the percentage reduction in both TNF-α (r = 0.56, p<0.05 and IL-6 (r = 0.19 p<0.05 plasma levels. In a multiple regression analysis, the amount of visceral fat loss independently correlated with the increase in IL-10 plasma levels. CONCLUSION: The reduction in visceral adipose tissue is the main driver of the improved inflammatory profile induced by weight loss.

  19. Cytokines in rheumatoid arthritis and osteoarthrosis

    Directory of Open Access Journals (Sweden)

    Petrović-Rackov Ljiljana

    2005-01-01

    Full Text Available The aim of this research was to determine the clinical significance of tumor necrosis factor-alpha (TNF-alpha, IL-12, IL-15 and IL-18 in evaluation of the activity of rheumatoid arthritis. Cytokine concentrations in serum samples and synovial fluid were measured by immnnoenzymatic methods using kits for human interleukins and the Disease Activity Score 28 in 64 patients with active disease. The control group consisted of 25 subjects with arthritis of the knee and osteoarthrosis. Patients with rheumatoid arthritis have significantly high (p<0.01 concentrations of examined cytokines in relation to patients with osteoarthritis. By comparing concentrations in 30 patients with high, 14 patients with moderate and 20 patients with mild activity of rheumatoid arthritis, it was established that patients with high degree of disease activity have significantly high (p<0.01; p<0.05 concentrations of examined cytokines in the blood and synovial fluid in relation to patients with moderate and mild disease. We have concluded that cytokine concentrations are good indicators of the degree of rheumatoid arthritis activity. This research is a contribution to understanding the insufficiently known pathogenetic mechanisms of cytokines, especially IL-18, in active disease. .

  20. Methodological issues in cytokine measurement in schizophrenia

    Directory of Open Access Journals (Sweden)

    Maju Mathew Koola

    2016-01-01

    Full Text Available There is mounting evidence that inflammation is a major factor in the pathophysiology of schizophrenia. Inflammatory status is commonly ascertained by measuring peripheral cytokine concentrations. An issue concerning research on inflammation and schizophrenia relates to assay methodology. Enzyme-linked immunosorbent assay (ELISA is the most widely used and the gold standard method used to measure cytokine concentrations. ELISA has a number of limitations. Both ELISA and multiplex are limited by not being able to distinguish between bioactive and inactive molecules and the matrix and heterophilic (auto- antibody interference. Multiplex assays when combined with gene expression analysis and flow cytometry techniques such as fluorescence-activated cell sorting may be useful to detect abnormalities in specific immune pathways. Peripheral blood mononuclear cells cultures, to evaluate in vitro lipopolysaccharide-induced cytokine production, may be a better technology than measuring cytokines in the serum. The purpose of this paper is to shed light on major methodological issues that need to be addressed in order to advance the study of cytokines in schizophrenia. We make a few recommendations on how to address these issues.

  1. Regulation of human cytokines by Cordyceps militaris

    Directory of Open Access Journals (Sweden)

    Yong Sun

    2014-12-01

    Full Text Available Cordyceps (Cordyceps militaris exhibits many biological activities including antioxidant, inhibition of inflammation, cancer prevention, hypoglycemic, and antiaging properties, etc. However, a majority of studies involving C. militaris have focused only on in vitro and animal models, and there is a lack of direct translation and application of study results to clinical practice (e.g., health benefits. In this study, we investigated the regulatory effects of C. militaris micron powder (3 doses on the human immune system. The study results showed that administration of C. militaris at various dosages reduced the activity of cytokines such as eotaxin, fibroblast growth factor-2, GRO, and monocyte chemoattractant protein-1. In addition, there was a significant decrease in the activity of various cytokines, including GRO, sCD40L, and tumor necrosis factor-α, and a significant downregulation of interleukin-12(p70, interferon-γ inducible protein 10, and macrophage inflammatory protein-1β activities, indicating that C. militaris at all three dosages downregulated the activity of cytokines, especially inflammatory cytokines and chemokines. Different dosages of C. militaris produced different changes in cytokines.

  2. The diverse applications of plasma

    Energy Technology Data Exchange (ETDEWEB)

    Sharma, Mukul, E-mail: mukulsharma@acropolis.edu.in; Darwhekar, Gajanan, E-mail: gdarwhekar@acropolis.edu.in [Acropolis Institute of Pharmaceutical Education & Research, Indore MP India (India); Dubey, Shivani, E-mail: dubeyshivani08@rediffmail.com [Mata Gujri College of Professional Studies, Indore MP India (India); Jain, Sudhir Kumar, E-mail: sudhirkjain1@rediffmail.com [School of Studies in Microbiology, Vikram University, Ujjain MP India (India)

    2015-07-31

    Plasma being the fourth state of matter has always been an attraction for Physicists and Chemists. With the advent of time, plasma energy has been recognized in having widening horizons in the field of Biomedical Sciences. Plasma medicine can be subdivided into three main fields; Non-thermal atmospheric-pressure direct plasma for medical therapy; Plasma-assisted modification of bio-relevant surfaces and Plasma-based bio-decontamination and sterilization. The basis of the research is that as it has free carrier molecules, it has the ability to target specific cells and regulate functions like wound healing. Plasma does not harm healthy human cells but can kill bacteria and possibly even cancer cells to help treat various diseases. Nosocomial infection control, prevention and containment of contagious diseases, disinfection of medical devices, surface treatment (heat and UV sensitive surfaces) are research of interest. Recent success in generating plasma at very low temperature ie. Cold plasma makes the therapy painless. It has the ability to activate cellular responses and important mechanisms in the body. They target specific molecules such as prothrombin for blood coagulation, cytokines for killing bacteria, and angiogenesis for tissue regeneration. Plasma has bactericidal, fungicidal and virucidal properties. Plasma technology has flourishing future in diverse fields like Textiles, Nanofabrication, Automotives, Waste management, Microbiology, Food Hygiene, Medical Science like Skin treatments, sterilisation of wounds, Hand disinfection, Dental treatments etc. Food hygiene using plasma can be achieved in disinfection of food containers, food surface disinfection, hygiene in food handling, preparation and packaging. Therefore Plasma is most promising field for budding Scientist for fluorishing research in Biological Sciences.

  3. Plasma turbulence

    Energy Technology Data Exchange (ETDEWEB)

    Horton, W. [Univ. of Texas, Austin, TX (United States). Inst. for Fusion Studies; Hu, G. [Globalstar LP, San Jose, CA (United States)

    1998-07-01

    The origin of plasma turbulence from currents and spatial gradients in plasmas is described and shown to lead to the dominant transport mechanism in many plasma regimes. A wide variety of turbulent transport mechanism exists in plasmas. In this survey the authors summarize some of the universally observed plasma transport rates.

  4. Changes of inflammation-associated cytokine expressions during early phase of experimental endotoxic shock in macaques

    Institute of Scientific and Technical Information of China (English)

    Xiao-Hui Ji; Ke-Yi Sun; Yan-Hong Feng; Guo-Qing Yin

    2004-01-01

    AIM: To study changes of inflammation-associated cytokine expressions during early phase of endotoxic shock in macague.METHODS: Experiments were performed in Macaque mulatta treated with LPS 2.8 mg/kg in shock model group or with normal saline in control group. Blood samples were collected before, or 60 min, or 120 min after LPS injection,respectively. Liver and spleen tissues were obtained at 120 min after LPS injection. The plasma levels of TNF-α,IL-1 β, IL-10 and IL-12P40 were determined by doubleantibody sandwich ELISA with antibodies against human cytokines. The mRNA levels of TNF-α, IL-1 β, and IL-18 in peripheral blood mononuclear cells (PBMCs), liver and spleen were examined by real-time fluorescence semi-quantitative RT-PCR with the primers based on human genes.RESULTS: Mean systemic arterial pressure (MAP), systemic vascular resistance index (SVRI) and left ventricular work index (LVWI) of macaques were significant declined in shock model group on average 60 min after LPS injection. The plasma levels of TNF-α and IL-10 were significantly increased 60 min after LPS injection and then decreased.The plasma levels of IL-1 β and IL-12P40 were significantly increased at 120 min after LPS injection. The mRNA levels of TNF-α and IL-1 β were significantly increased 60 min after LPS stimulation in PBMCs and 120 min after LPS stimulation in livers. The mRNA level of IL-18 was significantly increased 120 min after LPS stimulation in PBMCs and livers. But in spleen, only TNF-α mRNA level in LPS group was significantly higher 120 min after LPS stimulation, compared with that in control group.CONCLUSION: An endotoxic shock model of Macaque mulatta was successfully established. Both antibodies for ELISA and PCR primers based on human cytokine assays were successfully applied to detect macaque cytokines. In the model, inflammatory cytokines, such as TNF-α, IL-1 β,IL-12 and IL-18 as well as anti-inflammation cytokine IL-10,were released at very early phase of

  5. Fish oil affects immune function in 9 to 12 month old infants

    DEFF Research Database (Denmark)

    Damsgaard, Camilla Trab; Lauritzen, Lotte; Kjær, Tanja;

    Background - n-3 Polyunsaturated fatty acids (PUFA) are thought to affect immune function and may affect immune maturation in early life. Objective - To examine if fish oil supplementation in late infancy could modify immune function. Design - A 2×2 intervention with fish oil (3.4 ± 1.1 ml....../day) or no fish oil and cow’s milk or infant formula from 9 to 12 month of age in 64 healthy Danish infants. Before and after the intervention we measured the fatty acid composition of erythrocyte (RBC) membranes, plasma IgE levels, C-reactive protein and soluble IL-2 receptors (sIL-2R) as well as cytokine...... production in whole-blood cultures stimulated with lipopolysaccharide (LPS)/phytohaemaglutinin (PHA) or Lactobacillus paracasei for 22 h. IgA was measured in feces at 10 months of age. Results - Fish oil supplementation effectively raised RBC n-3 PUFA (p...

  6. Using cluster analysis of cytokines to identify patterns of inflammation in hospitalized patients with community-acquired pneumonia: a pilot study

    Science.gov (United States)

    Wiemken, Timothy L; Kelley, Robert R; Fernandez-Botran, Rafael; Mattingly, William A.; Arnold, Forest W.; Furmanek, Stephen P; Restrepo, Marcos I; Chalmers, James D; Peyrani, Paula; Cavallazzi, Rodrigo; Bordon, Jose; Aliberti, Stefano; Ramirez, Julio A.

    2017-01-01

    Introduction Patients with severe community-acquired pneumonia (CAP) are believed to have an exaggerated inflammatory response to bacterial infection. Therapies aiming to modulate the inflammatory response have been largely unsuccessful, perhaps reflecting that CAP is a heterogeneous disorder that cannot be modulated by a single anti-inflammatory approach. We hypothesize that the host inflammatory response to pneumonia may be characterized by distinct cytokine patterns, which can be harnessed for personalized therapies. Methods Here, we use hierarchical cluster analysis of cytokines to examine if patterns of inflammatory response in 13 hospitalized patients with CAP can be defined. This was a secondary data analysis of the Community-Acquired Pneumonia Inflammatory Study Group (CAPISG) database. The following cytokines were measured in plasma and sputum on the day of admission: interleukin (IL)-1β, IL-1 receptor antagonist (IL-1ra), IL-6, CXCL8 (IL-8), IL-10, IL-12p40, IL-17, interferon (IFN)γ, tumor necrosis factor (TNF)α, and CXCL10 (IP-10). Hierarchical agglomerative clustering algorithms were used to evaluate clusters of patients within plasma and sputum cytokine determinations. Results A total of thirteen patients were included in this pilot study. Cluster analysis identified distinct inflammatory response patterns of cytokines in the plasma, sputum, and the ratio of plasma to sputum. Conclusions Inflammatory response patterns in plasma and sputum can be identified in hospitalized patients with CAP. Characterization of the local and systemic inflammatory response may help to better discriminate patients for enrollment into clinical trials of immunomodulatory therapies.

  7. A multiplex panel of plasma markers of immunity and inflammation in classical kaposi sarcoma.

    Science.gov (United States)

    Aka, Peter V; Kemp, Troy J; Rabkin, Charles S; Shiels, Meredith S; Polizzotto, Mark N; Lauria, Carmela; Vitale, Francesco; Pinto, Ligia A; Goedert, James J

    2015-01-15

    Kaposi sarcoma (KS) risk is affected by perturbed immunity. Herein, we compared plasma from 15 human immunodeficiency virus (HIV)-negative classic KS cases to plasma from 29 matched controls, using a multiplex panel of immunity markers. Of 70 markers, CXCL10 (IP-10), sIL-1RII, sIL-2RA, and CCL3 (MIP-1A) were strongly and significantly associated with KS, after adjustment for age and smoking status. These and previous observations are consistent with a tumor-promoting role for these cytokines, particularly CXCL10, but the small sample size and case-control design preclude firm conclusions on KS risk or pathogenesis. Larger, well-designed prospective studies are needed to better assess the association of these markers with KS.

  8. Cytokines and Pancreatic β-Cell Apoptosis

    DEFF Research Database (Denmark)

    Berchtold, L A; Prause, M; Størling, J

    2016-01-01

    The discovery 30 years ago that inflammatory cytokines cause a concentration, activity, and time-dependent bimodal response in pancreatic β-cell function and viability has been a game-changer in the fields of research directed at understanding inflammatory regulation of β-cell function and survival...... and the causes of β-cell failure and destruction in diabetes. Having until then been confined to the use of pathophysiologically irrelevant β-cell toxic chemicals as a model of β-cell death, researchers could now mimic endocrine and paracrine effects of the cytokine response in vitro by titrating concentrations...... to gene expressional changes, endoplasmic reticulum stress, and triggering of mitochondrial dysfunction. Preclinical studies have shown preventive effects of cytokine antagonism in animal models of diabetes, and clinical trials demonstrating proof of concept are emerging. The full clinical potential...

  9. The role of cytokines in postmenopausal osteoporosis.

    Science.gov (United States)

    Brincat, S D; Borg, M; Camilleri, G; Calleja-Agius, J

    2014-08-01

    Postmenopausal osteoporosis is a silent systemic progressive disease characterised by a decrease in bone mass per unit volume. This condition compromises the physical strength of the skeleton and increases the susceptibility to fractures on minor trauma. The imbalance between bone formation and bone resorption is known to be responsible for postmenopausal bone loss. Estrogen deficiency contributes to bone loss by increasing the production of pro-inflammatory cytokines by bone marrow and bone cells. Clinical and molecular evidence indicates that estrogen-regulated cytokines exert regulatory effects on bone turnover implicating their role as being the primary mediators of the accelerated bone loss at menopause. The current perspective on the role and interaction of cytokines such as IL-1, IL-4, IL-6, IL-17, TNF, IFN-γ and TGF-β in bone loss linked with estrogen deficiency is reviewed. Current treatment options and emerging drug therapies in the management of postmenopausal osteoporosis are also evaluated.

  10. Th1/Th2 Cytokines in Psoriasis

    Directory of Open Access Journals (Sweden)

    Z Jadali

    2007-08-01

    Full Text Available Background: The aim of this study was to determine the Th1 and Th2 serum cytokines, in patients with psoriasis and to com¬pare their cytokine levels with those of normal control subjects. Methods: Serum levels of Interferon-gamma (IFN-γ, Interleukin-2 (IL-2, Interleukin-4 (IL-4, and Interleukin-10 (IL-10 were measured by enzyme linked immunosorbent assay in 40 patients with psoriasis and in 40 normal controls. Results: Compared with control subjects, patients with psoriasis had elevated levels of IFN-γ and IL-2 (P<0.001. In addi¬tion a positive correlation was found between the levels of IFN-γ, IL-2 and disease severity. Conclusion: Th1 secreting inflammatory cytokines may contribute to the pathogenesis of psoriasis.

  11. Cytokine production associated with smallpox vaccine responses.

    Science.gov (United States)

    Simon, Whitney L; Salk, Hannah M; Ovsyannikova, Inna G; Kennedy, Richard B; Poland, Gregory A

    2014-01-01

    Smallpox was eradicated 34 years ago due to the success of the smallpox vaccine; yet, the vaccine continues to be studied because of its importance in responding to potential biological warfare and the adverse events associated with current smallpox vaccines. Interindividual variations in vaccine response are observed and are, in part, due to genetic variation. In some cases, these varying responses lead to adverse events, which occur at a relatively high rate for the smallpox vaccine compared with other vaccines. Here, we aim to summarize the cytokine responses associated with smallpox vaccine response to date. Along with a description of each of these cytokines, we describe the genetic and adverse event data associated with cytokine responses to smallpox vaccination.

  12. Cytokine and lipid mediator networks in tuberculosis.

    Science.gov (United States)

    Mayer-Barber, Katrin D; Sher, Alan

    2015-03-01

    A major approach for immunologic intervention in tuberculosis involves redirecting the outcome of the host immune response from the induction of disease to pathogen control. Cytokines and lipid mediators known as eicosanoids play key roles in regulating this balance and as such represent important targets for immunologic intervention. While the evidence for cytokine/eicosanoid function derives largely from the investigation of murine and zebrafish experimental infection models, clinical studies have confirmed the existence of many of the same pathways in tuberculosis patients. Here, we summarize new data that reveal important intersections between the cytokine and eicosanoid networks in the host response to mycobacteria and discuss how targeting this crosstalk can promote resistance to lethal Mycobacterium tuberculosis infection. This approach could lead to new host-directed therapies to be used either as an adjunct for improving the efficacy of standard antibiotic treatment or for the management of drug-resistant infections.

  13. Modulation of pro- and anti-inflammatory cytokines in active and latent tuberculosis by coexistent Strongyloides stercoralis infection.

    Science.gov (United States)

    George, Parakkal Jovvian; Pavan Kumar, Nathella; Jaganathan, Jeeva; Dolla, Chandrakumar; Kumaran, Paul; Nair, Dina; Banurekha, Vaithilingam V; Shen, Kui; Nutman, Thomas B; Babu, Subash

    2015-12-01

    Helminth infections are known to induce modulation of both innate and adaptive immune responses in active and latent tuberculosis (TB). However, the role of helminth infections in modulating systemic cytokine responses in active and latent tuberculosis (LTB) is not known. To define the systemic cytokine levels in helminth-TB coinfection, we measured the circulating plasma levels of Type 1, Type 2, Type 17, other pro-inflammatory and regulatory cytokines in individuals with active TB (ATB) with or without coexistent Strongyloides stercoralis (Ss) infection by multiplex ELISA. Similarly, we also measured the same cytokine levels in individuals with LTB with or without concomitant Ss infection in a cross-sectional study. Our data reveal that individuals with ATB or LTB and coexistent Ss infection have significantly lower levels of Type 1 (IFNγ, TNFα and IL-2) and Type 17 (IL-17A and IL-17F) cytokines compared to those without Ss infection. In contrast, those with ATB and LTB with Ss infection have significantly higher levels of the regulatory cytokines (IL-10 and TGFβ), and those with LTB and Ss infection also have significantly higher levels of Type 2 cytokines (IL-4, IL-5 and IL-13) as well. Finally, those with LTB (but not ATB) exhibit significantly lower levels of other pro-inflammatory cytokines (IFNα, IFNβ, IL-6, IL-12 and GM-CSF). Our data therefore reveal a profound effect of Ss infection on the systemic cytokine responses in ATB and LTB and indicate that coincident helminth infections might influence pathogenesis of TB infection and disease.

  14. Cytokine inhibition in the treatment of COPD

    Directory of Open Access Journals (Sweden)

    Caramori G

    2014-04-01

    Full Text Available Gaetano Caramori,1 Ian M Adcock,2,3 Antonino Di Stefano,4 Kian Fan Chung2,3 1Dipartimento di Scienze Mediche, Centro Interdipartimentale per lo Studio delle Malattie Infiammatorie delle Vie Aeree e Patologie Fumo-correlate (CEMICEF; formerly Centro di Ricerca su Asma e BPCO, Sezione di Medicina Interna e Cardiorespiratoria, Università di Ferrara, Ferrara, Italy; 2Airway Diseases Section, National Heart and Lung Institute, Imperial College London, UK; 3Biomedical Research Unit, Royal Brompton and Harefield NHS Trust, London, UK; 4Divisione di Pneumologia e Laboratorio di Citoimmunopatologia dell'Apparato Cardio-Respiratorio, Fondazione Salvatore Maugeri, IRCCS, Veruno, Italy Abstract: Cytokines play an important part in many pathobiological processes of chronic obstructive pulmonary disease (COPD, including the chronic inflammatory process, emphysema, and altered innate immune response. Proinflammatory cytokines of potential importance include tumor necrosis factor (TNF-α, interferon-γ, interleukin (IL-1β, IL-6, IL-17, IL-18, IL-32, and thymic stromal lymphopoietin (TSLP, and growth factors such as transforming growth factor-β. The current objectives of COPD treatment are to reduce symptoms, and to prevent and reduce the number of exacerbations. While current treatments achieve these goals to a certain extent, preventing the decline in lung function is not currently achievable. In addition, reversal of corticosteroid insensitivity and control of the fibrotic process while reducing the emphysematous process could also be controlled by specific cytokines. The abnormal pathobiological process of COPD may contribute to these fundamental characteristics of COPD, and therefore targeting cytokines involved may be a fruitful endeavor. Although there has been much work that has implicated various cytokines as potentially playing an important role in COPD, there have been very few studies that have examined the effect of specific cytokine blockade in

  15. Complement factor H interferes with Mycobacterium bovis BCG entry into macrophages and modulates the pro-inflammatory cytokine response.

    Science.gov (United States)

    Abdul-Aziz, Munirah; Tsolaki, Anthony G; Kouser, Lubna; Carroll, Maria V; Al-Ahdal, Mohammed N; Sim, Robert B; Kishore, Uday

    2016-09-01

    Mycobacterium tuberculosis is an accomplished intracellular pathogen, particularly within the macrophage and this is of the utmost importance in the host-pathogen stand-off observed in the granuloma during latent tuberculosis. Contact with innate immune molecules is one of the primary interactions that can occur with the pathogen M. tuberculosis once inhaled. Complement proteins may play a role in facilitating M. tuberculosis interactions with macrophages. Here, we demonstrate that factor H, a complement regulatory protein that down-regulates complement alternative pathway activation, binds directly to the model organism M. bovis BCG. Binding of factor H reaches saturation at 5-10μg of factor H/ml, well below the plasma level. C4 binding protein (C4BP) competed with factor H for binding to mycobacteria. Factor H was also found to inhibit uptake of M. bovis BCG by THP-1 macrophage cells in a dose-dependent manner. Real-time qPCR analysis showed stark differential responses of pro- and anti-inflammatory cytokines during the early stages of phagocytosis, as evident from elevated levels of TNF-α, IL-1β and IL-6, and a concomitant decrease in IL-10, TGF-β and IL-12 levels, when THP-1:BCG interaction took place in the presence of factor H. Our results suggest that factor H can interfere with mycobacterial entry into macrophages and modulate inflammatory cytokine responses, particularly during the initial stages of infection, thus affecting the extracellular survival of the pathogen. Our results offer novel insights into complement activation-independent functions of factor H during the host-pathogen interaction in tuberculosis.

  16. 精子脂质过氧化反应与致炎细胞因子%Sperm lipid peroxidation and pro-inflammatory cytokines

    Institute of Scientific and Technical Information of China (English)

    P.Martinez; F.Proverbio; M.I.Camejo

    2007-01-01

    Aim:To investigate if interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), interferon-gamma (IFN-γ) or tumor necrosis factor-alpha (TNF-α) are able to stimulate the level of lipid peroxidation of sperm membranes, either alone or in the presence of leukocytes. Methods: Semen samples from normozoospermic donors were prepared by density gradient. The sperms were exposed to the indicated cytokines, at physiological and infection-inflammation concentrations, in the absence or presence of leukocytes. Lipid peroxidation of the sperm membranes was determined by measuring malondialdehyde (MDA) and 4-hydroxialkenals (HAE) formation. Results: TNF-α, IL-8 and IFN-γ increased the level of sperm membrane lipid peroxidation when tested at physiological concentrations. At infectioninflammation concentrations, only IL-8 was able to produce a higher effect. When assayed in the presence of leucocytes,IL-8 and TNF-α showed a higher effect at infection-inflammation concentrations than at physiological concentrations.Finally, IL-8 showed a higher effect in the presence of leukocytes than in their absence at both physiological and infection-inflammation concentrations. TNF-α also showed a higher effect when assayed in the presence of leukocytes than in their absence, but only at infection-inflammation concentrations. There was no effect of IL-6 or IL- 10 in any of the tested conditions. Conclusion: Several pro-inflammatory cytokines at physiological concentrations increase the level of lipid peroxidation of sperm membranes, which could be important for the sperm fecundation process. However, infection-inflammation concentrations of some cytokines, such as IL-8 and TNF-α, either alone or in the presence of leukocytes, could drive the lipid peroxidation of the spermatozoa plasma membrane to levels that can affect the sperm fertility capacity.

  17. Plasma harmonics

    CERN Document Server

    Ganeev, Rashid A

    2014-01-01

    Preface; Why plasma harmonics? A very brief introduction Early stage of plasma harmonic studies - hopes and frustrations New developments in plasma harmonics studies: first successes Improvements of plasma harmonics; Theoretical basics of plasma harmonics; Basics of HHG Harmonic generation in fullerenes using few-cycle pulsesVarious approaches for description of observed peculiarities of resonant enhancement of a single harmonic in laser plasmaTwo-colour pump resonance-induced enhancement of odd and even harmonics from a tin plasmaCalculations of single harmonic generation from Mn plasma;Low-o

  18. 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.

  19. 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.

  20. Divergent effects of Tenofovir and Retrovir (AZT) on TLR-mediated cytokine production

    DEFF Research Database (Denmark)

    Melchjorsen, Jesper; Tolstrup, Martin; Paludan, Søren Riis

      Pathogen-recognizing Toll-like receptors 2 (TLR2) and TLR4 are known to recognize a number of pathogens, including E.Coli, S. Pneumoniae and N. Meningitidis. We have studied whether a number of HIV therapeutics affect immediate proinflammatory cytokine responses in cell cultures. Preliminary...... results suggest an opposing effect of the drugs Tenofovir and Retrovir (AZT) on TLR-mediated proinflammatory cytokine production. We present data on the mechanisms behind the drug-mediated remodeling of innate immune activation and how the drugs effect early host-pathogen interactions....

  1. Cytokines and Chemokines as Regulators of Skeletal Muscle Inflammation: Presenting the Case of Duchenne Muscular Dystrophy

    Directory of Open Access Journals (Sweden)

    Boel De Paepe

    2013-01-01

    Full Text Available Duchenne muscular dystrophy is a severe inherited muscle disease that affects 1 in 3500 boys worldwide. Infiltration of skeletal muscle by inflammatory cells is an important facet of disease pathophysiology and is strongly associated with disease severity in the individual patient. In the chronic inflammation that characterizes Duchenne muscle, cytokines and chemokines are considered essential activators and recruiters of inflammatory cells. In addition, they provide potential beneficiary effects on muscle fiber damage control and tissue regeneration. In this review, current knowledge of cytokine and chemokine expression in Duchenne muscular dystrophy and its relevant animal disease models is listed, and implications for future therapeutic avenues are discussed.

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

    Directory of Open Access Journals (Sweden)

    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.

  3. Bone mineral density and circulating cytokines in patients with acromegaly.

    Science.gov (United States)

    Longobardi, S; Di Somma, C; Di Rella, F; Angelillo, N; Ferone, D; Colao, A; Merola, B; Lombardi, G

    1998-11-01

    Acromegalic patients present an increase of osteoblastic and osteoclastic activity, showing a different effect on the axial and appendicular skeletal structures. At this regard controversial data about bone mineral density (BMD) have been published in literature. In fact an increase of BMD levels in femoral neck and Ward's triangle without any difference in lumbar spine has been described. On the other hand normal BMD levels at forearm and reduced BMD levels at lumbar spine were found. These patients seem to have a reduction of trabecular BMD similar to postmenopausal osteoporotic patients despite normal or slightly elevated cortical BMD. Recently, it has been described that cytokines, in particular tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1), are implicated in the pathogenetic mechanism of postmenopausal osteoporosis. Taking into account that growth hormone (GH) can increase TNF-alpha and IL-1 secretion by mononuclear blood cells, the evaluation of possible relationship between the reduced BMD at lumbar spine and circulating cytokines levels was carried out in acromegalic patients. In addition we evaluated the effect of acute octreotide administration on serum TNF-alpha and IL-I concentrations. Eleven patients with active acromegaly and eleven healthy age-, sex-, weight- and heightmatched subjects were enrolled in this study. BMD was significantly reduced at lumbar spine (0.80 +/- 0.29 g/cm2 vs 1.02 +/- 0.11 g/cm2; p affect bone turnover inducing an increase of cytokines acting by a paracrine/autocrine mechanism cannot be ruled out.

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

    Science.gov (United States)

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

    2015-03-01

    The potential influence of leukocyte incorporation in the kinetic release of growth factors from platelet-rich plasma (PRP) may explain the conflicting efficiency of leukocyte platelet-rich plasma (L-PRP) scaffolds in tissue regeneration. To assess this hypothesis, leukocyte-free (PRGF-Endoret) and L-PRP fibrin scaffolds were prepared, and both morphogen and proinflammatory cytokine release kinetics were analyzed. Clots were incubated with culture medium to monitor protein release over 8 days. Furthermore, the different fibrin scaffolds were morphologically characterized. Results show that leukocyte-free fibrin matrices were homogenous while leukocyte-containing ones were heterogeneous, loose and cellular. Leukocyte incorporation produced a significant increase in the contents of proinflammatory cytokines interleukin (IL)-1β and IL-16 but not in the platelet-derived growth factors release (<1.5-fold). Surprisingly, the availability of vascular endothelial growth factor suffered an important decrease after 3 days of incubation in the case of L-PRP matrices. While the release of proinflammatory cytokines was almost absent or very low from PRGF-Endoret, the inclusion of leukocytes induced a major increase in these cytokines, which was characterized by the presence of a latent period. The PRGF-Endoret matrices were stable during the 8 days of incubation. The inclusion of leukocytes alters the growth factors release profile and also increased the dose of proinflammatory cytokines.

  5. Recombinant human interleukin-1 receptor antagonist promotes M1 microglia biased cytokines and chemokines following human traumatic brain injury.

    Science.gov (United States)

    Helmy, Adel; Guilfoyle, Mathew R; Carpenter, Keri Lh; Pickard, John D; Menon, David K; Hutchinson, Peter J

    2016-08-01

    Interleukin-1 receptor antagonist (IL1ra) has demonstrated efficacy in a wide range of animal models of neuronal injury. We have previously published a randomised controlled study of IL1ra in human severe TBI, with concomitant microdialysis and plasma sampling of 42 cytokines and chemokines. In this study, we have used partial least squares discriminant analysis to model the effects of drug administration and time following injury on the cytokine milieu within the injured brain. We demonstrate that treatment with rhIL1ra causes a brain-specific modification of the cytokine and chemokine response to injury, particularly in samples from the first 48 h following injury. The magnitude of this response is dependent on the concentration of IL1ra achieved in the brain extracellular space. Chemokines related to recruitment of macrophages from the plasma compartment (MCP-1) and biasing towards a M1 microglial phenotype (GM-CSF, IL1) are increased in patient samples in the rhIL1ra-treated patients. In control patients, cytokines and chemokines biased to a M2 microglia phenotype (IL4, IL10, MDC) are relatively increased. This pattern of response suggests that a simple classification of IL1ra as an 'anti-inflammatory' cytokine may not be appropriate and highlights the importance of the microglial response to injury.

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

    Directory of Open Access Journals (Sweden)

    Kirsi Alestalo

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

  7. Differential DNA methylation regions in cytokine and transcription factor genomic loci associate with childhood physical aggression.

    Directory of Open Access Journals (Sweden)

    Nadine Provençal

    Full Text Available BACKGROUND: Animal and human studies suggest that inflammation is associated with behavioral disorders including aggression. We have recently shown that physical aggression of boys during childhood is strongly associated with reduced plasma levels of cytokines IL-1α, IL-4, IL-6, IL-8 and IL-10, later in early adulthood. This study tests the hypothesis that there is an association between differential DNA methylation regions in cytokine genes in T cells and monocytes DNA in adult subjects and a trajectory of physical aggression from childhood to adolescence. METHODOLOGY/PRINCIPAL FINDINGS: We compared the methylation profiles of the entire genomic loci encompassing the IL-1α, IL-6, IL-4, IL-10 and IL-8 and three of their regulatory transcription factors (TF NFkB1, NFAT5 and STAT6 genes in adult males on a chronic physical aggression trajectory (CPA and males with the same background who followed a normal physical aggression trajectory (control group from childhood to adolescence. We used the method of methylated DNA immunoprecipitation with comprehensive cytokine gene loci and TF loci microarray hybridization, statistical analysis and false discovery rate correction. We found differentially methylated regions to associate with CPA in both the cytokine loci as well as in their transcription factors loci analyzed. Some of these differentially methylated regions were located in known regulatory regions whereas others, to our knowledge, were previously unknown as regulatory areas. However, using the ENCODE database, we were able to identify key regulatory elements in many of these regions that indicate that they might be involved in the regulation of cytokine expression. CONCLUSIONS: We provide here the first evidence for an association between differential DNA methylation in cytokines and their regulators in T cells and monocytes and male physical aggression.

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

    Directory of Open Access Journals (Sweden)

    Raquel M Gonçalves

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

  9. Role of cytokines in inflammatory bowel disease

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC), rep- resents a group of chronic disorders characterized by inflammation of the gastrointestinal tract, typically with a relapsing and remitting clinical course. Mucosal mac- rophages play an important role in the mucosal im- mune system, and an increase in the number of newly recruited monocytes and activated macrophages has been noted in the inflamed gut of patients with IBD. Activated macrophages are thought to be major con- tributors to the production of inflammatory cytokines in the gut, and imbalance of cytokines is contributing to the pathogenesis of IBD. The intestinal inflammation in IBD is controlled by a complex interplay of innate and adaptive immune mechanisms. Cytokines play a key role in IBD that determine T cell differentiation of Th1, Th2, T regulatory and newly described Th17 cells. Cytokines levels in time and space orchestrate the development, recurrence and exacerbation of theinflammatory process in IBD. Therefore, several cyto- kine therapies have been developed and tested for the treatment of IBD patients.

  10. Cytokines and Organ Failure in Acute Pancreatitis

    DEFF Research Database (Denmark)

    Malmstrøm, Marie Louise; Hansen, Mark Berner; Andersen, Anders Møller

    2012-01-01

    Objectives: We aimed at synchronously examining the early time course of 4 proinflammatory cytokines as predictive factors for development of organ failure in patients with acute pancreatitis (AP). Methods: Interleukin (IL) 6, IL-8, IL-18, and tumor necrosis factor > were measured on admission...

  11. Murine cytokine patterns following rubella vaccination.

    Science.gov (United States)

    Farzaneh, Parvarich; Ebtekar, Massoumeh; Hassan, Z M; Rafati, Sima

    2003-06-01

    Although thorough studies on the immune reponse to rubella have been performed, less attention has been given to the cellular mechanism and mediators that shape the process. Specifically, information concerning the nature ofcytokine patterns involved in the immune response to Rubella vaccination is not avaliable. This study deals with cytokine production patterns of spleen cells from Balb/c mice following vaccination with the Takahashi strain of Rubella vaccine. Mice were injected intraperitonealy with Rubella virus and PBS and 7, 10 or 14 days later, spleen cells were separated and cultured with varying doses of virus, con A or only the medium. ELISA assays were performed on supernatants for measurement of IL-4, INF-gamma and IL-5. LTT (Lymphocyte Transformation Test) was also performed. The data indicate variation in cytokine patterns during the time periods after vaccination. On day 7 a type 1 pattern was observed. The LTT response was also indicative of CMI (Cell Mediated Immunity) response on the 7th and 14th days while a transient suppression on day 10 was observed. These results indicate a time dependent cytokine response with variation ultimately leading o a dominant type 1 (Ti) cytokine response.

  12. Cytokines in atherosclerosis: an intricate balance

    NARCIS (Netherlands)

    Boshuizen, M.C.S.

    2016-01-01

    Atherosclerosis is the underlying pathology in the majority of clinical manifestations of cardiovascular diseases, which are nowadays the main global cause of mortality. Atherosclerosis is a lipid-driven chronic inflammatory disease of the arterial wall. This inflammatory response, with cytokines as

  13. IFN-gamma: Novel antiviral cytokines

    DEFF Research Database (Denmark)

    Ank, Nina; West, Hans; Paludan, Søren Riis

    2006-01-01

    and adaptive immune responses. Recently, a novel class of cytokines was discovered and named IFN-lambda (alternatively type III IFN or interleukin-28/29 [IL- 28/29]), based on IFN-like antiviral activity and induction of typical IFN-inducible genes. Here, we review the literature on IFN-lambda and discuss...

  14. During the long way to Mars: effects of 520 days of confinement (Mars500 on the assessment of affective stimuli and stage alteration in mood and plasma hormone levels.

    Directory of Open Access Journals (Sweden)

    Yue Wang

    Full Text Available For future interplanetary manned spaceflight, mental issues, as well as physiological problems, must inevitably be considered and solved. Mars500 is a high-fidelity ground simulation experiment that involved 520 days of confined isolation for six multinational crewmembers. This experiment provided a good opportunity to perform psycho-physiological and psycho-social researches on such missions. To investigate emotional responses and psychological adaptation over long-term confinement, the International Affective Pictures System (IAPS was selected as the visual emotional stimuli in this study. Additional data collected and analyzed included the Profile of Mood States (POMS questionnaire and the levels of four types of plasma hormones: cortisol, 5-hydroxy tryptamine, dopamine, and norepinephrine. The results demonstrated an obvious bias on valence rating for unpleasant stimuli with time (p<0.05, and the correlation between psychological and biochemical data was identified (p<0.05. Overall, we concluded that the confined crew tended to assign positive ratings to negative pictures with time, which might be driven by a defensive system. There was a stage-changing pattern of psychological adaptation of the Mars500 crew, which is similar to the third-quarter phenomenon.

  15. Neuropathic pain and cytokines: current perspectives

    Directory of Open Access Journals (Sweden)

    Clark AK

    2013-11-01

    Full Text Available Anna K Clark, Elizabeth A Old, Marzia Malcangio Wolfson Centre for Age Related Diseases, King's College London, London, UK Abstract: Neuropathic pain represents a major problem in clinical medicine because it causes debilitating suffering and is largely resistant to currently available analgesics. A characteristic of neuropathic pain is abnormal response to somatic sensory stimulation. Thus, patients suffering peripheral neuropathies may experience pain caused by stimuli which are normally nonpainful, such as simple touching of the skin or by changes in temperature, as well as exaggerated responses to noxious stimuli. Convincing evidence suggests that this hypersensitivity is the result of pain remaining centralized. In particular, at the first pain synapse in the dorsal horn of the spinal cord, the gain of neurons is increased and neurons begin to be activated by innocuous inputs. In recent years, it has become appreciated that a remote damage in the peripheral nervous system results in neuronal plasticity and changes in microglial and astrocyte activity, as well as infiltration of macrophages and T cells, which all contribute to central sensitization. Specifically, the release of pronociceptive factors such as cytokines and chemokines from neurons and non-neuronal cells can sensitize neurons of the first pain synapse. In this article we review the current evidence for the role of cytokines in mediating spinal neuron–non-neuronal cell communication in neuropathic pain mechanisms following peripheral nerve injury. Specific and selective control of cytokine-mediated neuronal–glia interactions results in attenuation of the hypersensitivity to both noxious and innocuous stimuli observed in neuropathic pain models, and may represent an avenue for future therapeutic intervention. Keywords: anti-inflammatory cytokines, proinflammatory cytokines, microglia, astrocytes, first pain synapse

  16. Porphyromonas Gingivalis and E-coli induce different cytokine production patterns in pregnant women.

    Directory of Open Access Journals (Sweden)

    Marijke M Faas

    Full Text Available OBJECTIVE: Pregnant individuals of many species, including humans, are more sensitive to various bacteria or their products as compared with non-pregnant individuals. Pregnant individuals also respond differently to different bacteria or their products. Therefore, in the present study, we evaluated whether the increased sensitivity of pregnant women to bacterial products and their heterogeneous response to different bacteria was associated with differences in whole blood cytokine production upon stimulation with bacteria or their products. METHODS: Blood samples were taken from healthy pregnant and age-matched non-pregnant women and ex vivo stimulated with bacteria or LPS from Porphyromonas Gingivalis (Pg or E-coli for 24 hrs. TNFα, IL-1ß, IL-6, IL-12 and IL-10 were measured using a multiplex Luminex system. RESULTS: We observed a generally lower cytokine production after stimulation with Pg bacteria or it's LPS as compared with E-coli bacteria. However, there was also an effect of pregnancy upon cytokine production: in pregnant women the production of IL-6 upon Pg stimulation was decreased as compared with non-pregnant women. After stimulation with E-coli, the production of IL-12 and TNFα was decreased in pregnant women as compared with non-pregnant women. CONCLUSION: Our results showed that cytokine production upon bacterial stimulation of whole blood differed between pregnant and non-pregnant women, showing that the increased sensitivity of pregnant women may be due to differences in cytokine production. Moreover, pregnancy also affected whole blood cytokine production upon Pg or E-coli stimulation differently. Thus, the different responses of pregnant women to different bacteria or their products may result from variations in cytokine production.

  17. High multi-cytokine levels are not a predictive marker of alloimmunization in transfused sickle cell disease patients.

    Science.gov (United States)

    Tatari-Calderone, Zohreh; Fasano, Ross M; Miles, Megan R; Pinto, Ligia A; Luban, Naomi L C; Vukmanovic, Stanislav

    2014-07-01

    Patients with sickle cell disease (SCD) receive multiple red blood cell (RBC) transfusions for both prevention of and therapy for disease-related complications. In some patients, transfusion results in development of both allo- and auto-antibodies to RBC antigens. What precipitates the antibody formation is currently unclear. It has been hypothesized that a pro-inflammatory state preceding the therapeutic transfusion may be a predisposing factor. Plasma levels of ten cytokines were evaluated upon recruitment to the study of 83 children with SCD undergoing therapeutic RBC transfusions. The levels of cytokines were correlated with development of anti-RBC antibodies prior, or during seven years post recruitment. Twelve subjects displayed significantly higher levels of all cytokines examined, with pro-, as well as anti-inflammatory properties. Surprisingly, the elevated levels of cytokines were preferentially found in patients without anti-RBC allo- and/or auto-antibodies. Further, presence of high cytokine levels was not predictive of anti-RBC antibody development during the subsequent seven year follow up. These data suggest that the increased concentration of multiple cytokines is not a biomarker of either the presence of or susceptibility to the development of RBC alloimmunization.

  18. 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.

  19. Dusty plasmas

    Energy Technology Data Exchange (ETDEWEB)

    Fortov, Vladimir E; Khrapak, Aleksei G; Molotkov, Vladimir I; Petrov, Oleg F [Institute for High Energy Densities, Associated Institute for High Temperatures, Russian Academy of Sciences, Moscow (Russian Federation); Khrapak, Sergei A [Max-Planck-Institut fur Extraterrestrische Physik, Garching (Germany)

    2004-05-31

    The properties of dusty plasmas - low-temperature plasmas containing charged macroparticles - are considered. The most important elementary processes in dusty plasmas and the forces acting on dust particles are investigated. The results of experimental and theoretical investigations of different states of strongly nonideal dusty plasmas - crystal-like, liquid-like, gas-like - are summarized. Waves and oscillations in dusty plasmas, as well as their damping and instability mechanisms, are studied. Some results on dusty plasma investigated under microgravity conditions are presented. New directions of experimental research and potential applications of dusty plasmas are discussed. (reviews of topical problems)

  20. Interplay between pro-inflammatory cytokines and growth factors in depressive illnesses

    Directory of Open Access Journals (Sweden)

    Marie-Claude eAudet

    2013-05-01

    Full Text Available The development of depressive disorders had long been attributed to monoamine variations, and pharmacological treatment strategies likewise focused on methods of altering monoamine availability. However, the limited success achieved by treatments that altered these processes spurred the search for alternative mechanisms and treatments. Here we provide a brief overview concerning a possible role for pro-inflammatory cytokines and growth factors in major depression, as well as the possibility of targeting these factors in treating this disorder. The data suggest that focusing on one or another cytokine or growth factor might be counterproductive, especially as these factors may act sequentially or in parallel in affecting depressive disorders. It is also suggested that cytokines and growth factors might be useful biomarkers for individualized treatments of depressive illnesses.

  1. All Plasma Products Are Not Created Equal: Characterizing Differences Between Plasma Products

    Science.gov (United States)

    2015-06-01

    products that may affect efficacy and safety. METHODS: Four different plasma products were analyzed to include fresh frozen plasma (FFP), liquid plasma...have come onto the market. FFP, plasma frozen at 24 hours (PF-24), and liquid plasma (LP) are single-donor products pre- pared by separating plasma from...Transfusion. 2004;44(11):1674Y1675. 2. American Association of Blood Banks . Standards for Blood Banks and Transfusion Services. 26th ed. Bethesda, MD

  2. Inhibition of adenosine deaminase attenuates endotoxin-induced release of cytokines in vivo in rats.

    Science.gov (United States)

    Tofovic, S P; Zacharia, L; Carcillo, J A; Jackson, E K

    2001-09-01

    The purpose of this study was to investigate in vivo the effects of modulating the adenosine system on endotoxin-induced release of cytokines and changes in heart performance and neurohumoral status in early, profound endotoxemia in rats. Time/pressure variables of heart performance and blood pressure were recorded continuously, and plasma levels of tumor necrosis factor alpha (TNFalpha), interleukin 1-beta (IL-1beta), plasma renin activity (PRA), and catecholamines were determined before and 90 min after administration of endotoxin (30 mg/kg of lipopolysaccharide, i.v.). Erythro-9[2-hydroxyl-3-nonyl] adenine (EHNA; an adenosine deaminase inhibitor) had no effects on measured time-pressure variables of heart performance under baseline conditions and during endotoxemia, yet significantly attenuated endotoxin-induced release of cytokines and PRA. Pretreatment with the non-selective adenosine receptor antagonist DPSPX not only prevented the effects of EHNA but also increased the basal release of cytokines and augmented PRA. At baseline, caffeine (a non-selective adenosine receptor antagonist) increased HR, +dP/dtmax, heart rate x ventricular pressure product (HR x VPSP) and +dP/dtmax normalized by pressure (+dP/dtmax/VPSP), and these changes persisted during endotoxemia. Caffeine attenuated endotoxin-induced release of cytokines and augmented endotoxin-induced increases in plasma catecholamines and PRA. Pretreatment with propranolol abolished the effects of caffeine on heart performance and neurohumoral activation during the early phase of endotoxemia. 6N-cyclopentyladenosine (CPA; selective A1 adenosine receptor agonist) induced bradicardia and negative inotropic effects, reduced work load (i.e., decreased HR, VPSP, +dP/dtmax, +dP/dtmax/VPSP and HR x VPSP) and inhibited endotoxin-induced tachycardia and renin release. CGS 21680 (selective A2A adenosine receptor agonist) decreased blood pressure under basal condition but did not potentiate decreases in blood pressure

  3. Cytokine-Mediated Bone Destruction in Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Seung Min Jung

    2014-01-01

    Full Text Available Bone homeostasis, which involves formation and resorption, is an important process for maintaining adequate bone mass in humans. Rheumatoid arthritis (RA is an autoimmune disease characterized by inflammation and bone loss, leading to joint destruction and deformity, and is a representative disease of disrupted bone homeostasis. The bone loss and joint destruction are mediated by immunological insults by proinflammatory cytokines and various immune cells. The connection between bone and immunity has been intensely studied and comprises the emerging field of osteoimmunology. Osteoimmunology is an interdisciplinary science investigating the interplay between the skeletal and the immune systems. The main contributors in osteoimmunology are the bone effector cells, such as osteoclasts or osteoblasts, and the immune cells, particularly lymphocytes and monocytes. Physiologically, osteoclasts originate from immune cells, and immune cells regulate osteoblasts and vice versa. Pathological conditions such as RA might affect these interactions, thereby altering bone homeostasis, resulting in the unfavorable outcome of bone destruction. In this review, we describe the osteoclastogenic roles of the proinflammatory cytokines and immune cells that are important in the pathophysiology of RA.

  4. Effect of Malnutrition on the Expression of Cytokines Involved in Th1 Cell Differentiation

    Directory of Open Access Journals (Sweden)

    Leonor Rodríguez

    2013-02-01

    Full Text Available Malnutrition is a common cause of secondary immune deficiency and has been linked to an increased susceptibility to infection in humans. Malnutrition specifically affects T-cell-mediated immune responses. The aim of this study was to assess in lymphocytes from malnourished children the expression levels of IL-12, IL-18 and IL-21, molecules that induce the differentiation of T cells related to the immunological cellular response (Th1 response and the production of cytokines related to the immunological cellular response (Th1 cytokines. We found that the expression levels of IL-12, IL-18 and IL-21 were significantly diminished in malnourished children compared to well-nourished children and were coincident with lower plasmatic levels of IL-2 and IFN-γ (Th1 cytokines. In this study, we show for the first time that the gene expression and intracellular production of cytokines responsible for Th1 cell differentiation (IL-12, IL-18 and IL-21 are diminished in malnourished children. As expected, this finding was related to lower plasmatic levels of IL-2 and IFN-γ. The decreased expression of Th1 cytokines observed in this study may contribute to the deterioration of the immunological Type 1 (cellular response. We hypothesize that the decreased production of IL-12, IL-18 and IL-21 in malnourished children contributes to their inability to eradicate infections.

  5. Effect of malnutrition on the expression of cytokines involved in Th1 cell differentiation.

    Science.gov (United States)

    González-Torres, Cristina; González-Martínez, Haydeé; Miliar, Angel; Nájera, Oralia; Graniel, Jaime; Firo, Verónica; Alvarez, Catalina; Bonilla, Edmundo; Rodríguez, Leonor

    2013-02-19

    Malnutrition is a common cause of secondary immune deficiency and has been linked to an increased susceptibility to infection in humans. Malnutrition specifically affects T-cell-mediated immune responses. The aim of this study was to assess in lymphocytes from malnourished children the expression levels of IL-12, IL-18 and IL-21, molecules that induce the differentiation of T cells related to the immunological cellular response (Th1 response) and the production of cytokines related to the immunological cellular response (Th1 cytokines). We found that the expression levels of IL-12, IL-18 and IL-21 were significantly diminished in malnourished children compared to well-nourished children and were coincident with lower plasmatic levels of IL-2 and IFN-γ (Th1 cytokines). In this study, we show for the first time that the gene expression and intracellular production of cytokines responsible for Th1 cell differentiation (IL-12, IL-18 and IL-21) are diminished in malnourished children. As expected, this finding was related to lower plasmatic levels of IL-2 and IFN-γ. The decreased expression of Th1 cytokines observed in this study may contribute to the deterioration of the immunological Type 1 (cellular) response. We hypothesize that the decreased production of IL-12, IL-18 and IL-21 in malnourished children contributes to their inability to eradicate infections.

  6. Melatonin enhances pro-inflammatory cytokine levels and protects against Chagas disease.

    Science.gov (United States)

    Santello, Fabricia Helena; Frare, Eduardo Osório; Caetano, Leony Cristina; AlonsoToldo, Míriam Paula; do Prado, José Clóvis

    2008-08-01

    Pro-inflammatory and modulatory cytokines have an essential role in host defense against human and murine Trypanosoma cruzi infection. Control of T. cruzi parasitism during the acute phase of infection is considered to be critically dependent on direct macrophage activation by cytokines. Melatonin has been proposed to regulate the immune system by affecting cytokine production in immunocompetent cells, enhancing the production of several T helper (Th)1 cytokines. The aims of this work were to evaluate in rats, the influences of exogenous melatonin treatment on T. cruzi-infected host's immune responses. With this in mind, several immunological parameters were analyzed, including tumor necrosis factor-alpha, gamma-interferon, interleukin-12, nitric oxide (NO) and macrophage count. The melatonin therapy was provided in one of two different treatment regimens, that is, either beginning 7 days prior to infection or concomitant with the infection. Both treatments triggered an up-regulation of the immune response, with the concomitant treatment being more effective; in this case all cytokines studied, with exception of NO, displayed enhanced concentrations and there was a higher number of peritoneal macrophages, which displayed reduced concentrations under melatonin therapy. We conclude that melatonin plays a pivotal role in up-regulating the Th1 immune response thus controlling parasite replication.

  7. Recent research on the growth plate: Impact of inflammatory cytokines on longitudinal bone growth.

    Science.gov (United States)

    Sederquist, Bettina; Fernandez-Vojvodich, Paola; Zaman, Farasat; Sävendahl, Lars

    2014-08-01

    Children with inflammatory diseases usually display abnormal growth patterns as well as delayed puberty. This is a result of several factors related to the disease itself, such as malnutrition, hypercortisolism, and elevated levels of pro-inflammatory cytokines. These factors in combination with glucocorticoid treatment contribute to growth retardation during chronic inflammation by systemically affecting the major regulator of growth, the GH/IGF1 axis. However, recent studies have also shown evidence of a direct effect of these factors at the growth plate level. In conditions of chronic inflammation, pro-inflammatory cytokines are upregulated and released into the circulation. The most abundant of these, tumor necrosis factor α, interleukin 1β (IL1β), and IL6, are all known to directly act on growth plate cartilage to induce apoptosis and thereby suppress bone growth. Both clinical and experimental studies have shown that growth retardation can partly be rescued when these cytokines are blocked. Therefore, therapy modulating the local actions of these cytokines may be effective for preventing growth failure in patients with chronic inflammatory disorders. In this review, we report the current knowledge of inflammatory cytokines and their role in regulating bone growth.

  8. Effect of Malnutrition on the Expression of Cytokines Involved in Th1 Cell Differentiation

    Science.gov (United States)

    González-Torres, Cristina; González-Martínez, Haydeé; Miliar, Angel; Nájera, Oralia; Graniel, Jaime; Firo, Verónica; Alvarez, Catalina; Bonilla, Edmundo; Rodríguez, Leonor

    2013-01-01

    Malnutrition is a common cause of secondary immune deficiency and has been linked to an increased susceptibility to infection in humans. Malnutrition specifically affects T-cell-mediated immune responses. The aim of this study was to assess in lymphocytes from malnourished children the expression levels of IL-12, IL-18 and IL-21, molecules that induce the differentiation of T cells related to the immunological cellular response (Th1 response) and the production of cytokines related to the immunological cellular response (Th1 cytokines). We found that the expression levels of IL-12, IL-18 and IL-21 were significantly diminished in malnourished children compared to well-nourished children and were coincident with lower plasmatic levels of IL-2 and IFN-γ (Th1 cytokines). In this study, we show for the first time that the gene expression and intracellular production of cytokines responsible for Th1 cell differentiation (IL-12, IL-18 and IL-21) are diminished in malnourished children. As expected, this finding was related to lower plasmatic levels of IL-2 and IFN-γ. The decreased expression of Th1 cytokines observed in this study may contribute to the deterioration of the immunological Type 1 (cellular) response. We hypothesize that the decreased production of IL-12, IL-18 and IL-21 in malnourished children contributes to their inability to eradicate infections. PMID:23429441

  9. Serum Fatty Acids Are Correlated with Inflammatory Cytokines in Ulcerative Colitis.

    Directory of Open Access Journals (Sweden)

    Dawn M Wiese

    Full Text Available Ulcerative colitis (UC is associated with increased dietary intake of fat and n-6 polyunsaturated fatty acids (PUFA. Modification of fat metabolism may alter inflammation and disease severity. Our aim was to assess differences in dietary and serum fatty acid levels between control and UC subjects and associations with disease activity and inflammatory cytokines.Dietary histories, serum, and colonic tissue samples were prospectively collected from 137 UC subjects and 38 controls. Both histologic injury and the Mayo Disease Activity Index were assessed. Serum and tissue cytokines were measured by Luminex assay. Serum fatty acids were obtained by gas chromatography.UC subjects had increased total fat and oleic acid (OA intake, but decreased arachidonic acid (AA intake vs controls. In serum, there was less percent saturated fatty acid (SFA and AA, with higher monounsaturated fatty acids (MUFA, linoleic acid, OA, eicosapentaenoic acid (EPA, and docosapentaenoic acid (DPA in UC. Tissue cytokine levels were directly correlated with SFA and inversely correlated with PUFA, EPA, and DPA in UC subjects, but not controls. 5-aminosalicylic acid therapy blunted these associations.In summary, we found differences in serum fatty acids in UC subjects that correlated with pro-inflammatory tissue cytokines. We propose that fatty acids may affect cytokine production and thus be immunomodulatory in UC.

  10. Assessment of cytokine levels and hs-CRP in bipolar I disorder before and after treatment.

    Science.gov (United States)

    Uyanik, Vesile; Tuglu, Cengiz; Gorgulu, Yasemin; Kunduracilar, Hakan; Uyanik, Mehmet Sevki

    2015-08-30

    We aimed to assess the relationship between cytokine levels and the severity of the manic period in medication free patients. 30 Medication free patients and 28 healthy subjects (HS) were recruited. Plasma levels of pro-inflammatory, anti-inflammatory, inflammatory cytokines, and hs-CRP levels were investigated upon hospital admission, after six weeks follow up in bipolar disease manic episode and the results were compared to HS. The severity of the manic episodes was assessed according to the Young mania rating scale. TNF-α, INF-γ, IL-6 and hs-CRP levels were significantly higher in patients with manic episode of bipolar I disorder before treatment than HS. After treatment the levels of TNF-α, INF-γ, IL-6 and hs-CRP were observed to be significantly decreased. There was no difference between the levels of anti-inflammatory cytokines in patients before or after treatment of bipolar disorder and HS. hs-CRP was observed to be the only parameter correlated with clinical response. The most significant outcome of this study is the correlation between clinical outcome and hs-CRP levels in treatment naive manic episode bipolar type I patients. hs-CRP is the most consistent indicator according to pro-inflammatory, inflammatory and anti-inflammatory cytokines, in predicting treatment outcomes.

  11. Therapeutic antibodies that target inflammatory cytokines in autoimmune diseases.

    Science.gov (United States)

    Lai, Yuping; Dong, Chen

    2016-04-01

    Inflammatory cytokines are key regulators of immune responses. Persistent and excessive production of inflammatory cytokines underscores the development of autoimmune diseases. Therefore, neutralizing inflammatory cytokines or antagonizing their receptor function is considered as a useful therapeutic strategy to treat autoimmune diseases. To achieve the success of such a strategy, understanding of the complex actions of these cytokines and cytokine networks is required. In this review we focus on four inflammatory cytokines--tumor necrosis factor α (TNFα), interleukin-6 (IL-6), IL-23 and IL-17--and dissect how the dysregulation of these cytokines regulates autoimmune diseases. On the basis of pre-clinical and clinical data, we specifically discuss the therapeutic rationale for targeting these cytokines and describe the potential adverse effects.

  12. Cytokine activation during embryonic development and in hen ovary and vagina during reproductive age and Salmonella infection.

    Science.gov (United States)

    Anastasiadou, M; Michailidis, G

    2016-12-01

    Salmonellosis is one of the most important zoonotic diseases and is usually associated with consumption of Salmonella Enteritidis (SE) contaminated poultry meat or eggs. Contamination with SE is usually the result of infection of the digestive tract, or reproductive organs, especially the ovary and vagina. Thus, knowledge of endogenous innate immune mechanisms operating in the ovary and vagina of hen is an emerging aspect of reproductive physiology. Cytokines are key factors for triggering the immune response and inflammation in chicken to Salmonella infection. The aim of this study was to investigate the expression profile of 11 proinflammatory cytokines in the chicken embryos during embryonic development, as well as in the hen ovary and vagina in vivo, to investigate whether sexual maturation affects their ovarian and vaginal mRNA abundance and to determine whether cytokine expression was constitutive or induced in the ovary and vagina as a response to SE infection. RT-PCR analysis revealed that several cytokines were expressed in the chicken embryos, and in the ovary and vagina of healthy birds. Expression of various cytokines during sexual maturation appeared to be developmentally regulated. In addition, a significant up-regulation of several cytokines in the ovary and vagina of sexually mature SE infected birds compared to healthy birds of the same age was observed. These results suggest a cytokine-mediated immune response mechanism against Salmonella infection in the hen reproductive organs.

  13. Heroin use is associated with suppressed pro-inflammatory cytokine response after LPS exposure in HIV-infected individuals.

    Directory of Open Access Journals (Sweden)

    Hinta Meijerink

    Full Text Available Opioid use is associated with increased incidence of infectious diseases. Although experimental studies have shown that opioids affect various functions of immune cells, only limited data are available from human studies. Drug use is an important risk factor for HIV transmission; however no data are available whether heroin and/or methadone modulate immune response. Therefore, we examined the effect of heroin and methadone use among HIV-infected individuals on the production of cytokines after ex vivo stimulation with various pathogens.Treatment naïve HIV-infected individuals from Indonesia were recruited. Several cohorts of individuals were recruited: 1 using heroin 2 receiving methadone opioid substitution 3 using heroin over 1 year ago and 4 controls (never used opioids. Whole blood was stimulated with Mycobacterium tuberculosis, Candida albicans and LPS for 24 to 48 hours. Cytokine production (IL-1 β, IL-6, IL-10, IFN-α, IFN-γ and TNF-α was determined using multiplex beads assay.Among 82 individuals, the cytokine levels in unstimulated samples did not differ between groups. Overall, heroin users had significantly lower cytokine response after exposure to LPS (p<0.05. After stimulation with either M. tuberculosis or C. albicans the cytokine production of all groups were comparable.The cytokine production after exposure to LPS is significantly down-regulated in HIV-infected heroin users. Interesting, methadone use did not suppress cytokine response, which could have implications guidelines of opioid substitution.

  14. Inhibition of Cholesterol Esterification Influences Cytokine Exspression in Lypopolisaccharide-activated P388D1 Macrophages

    Directory of Open Access Journals (Sweden)

    Rosa Rita Bonatesta

    2007-01-01

    Full Text Available Several in vivo and in vitro studies have demonstrated the involvement of infectious agents in the development of atherosclerosis. However, the mechanisms by which micro-organisms induce and/or aggravate atherosclerosis, are so far unclear. Accumulation of cholesterol esters and lipid laden cell formation are hallmark of the atherogenesis, however, the possible relationship between cholesterol esterification and the signal-transducing component of LPS recognition complex inducing cytokine secretion has not been yet investigated. In the present study, we investigated the effect of mevinolin, the ACAT inhibitor, Sandoz 58035, and plasma from statin-treated hypercholesterolemic patients on cholesterol metabolism and cytokine expression in LPS activated P388D1 macrophages. In P388D1 macrophages cholesterol synthesis and uptake, as well as cholesterol ester synthesis, were unchanged following LPS-activation. When cells were grown in presence of serum from patients under statin therapy, cholesterol esterification was lower compared to cells grown with plasma from healthy subjects, independently from the type of statin used. This effect was accompanied by inhibition of IL-1β expression in LPS activated cells. The ACAT inhibitor, Sandoz 58035, which completely blocked cholesterol esterification in normal and LPS-activated macrophages, prevented IL-1β and IL-6 over-expression in LPS activated cells. Although preliminary, these data point to a possible relationship between cholesterol esterification and cytokine production in macrophages, prospecting new possible mechanisms by which microbial or inflammatory agents may induce and/or accelerate the atherosclerotic process.

  15. Mechanism of cytokine modulation of epithelial tight junction barrier

    OpenAIRE

    Al-Sadi, Rana; Boivin, Michel; Ma, Thomas

    2009-01-01

    Cytokines play a crucial role in the modulation of inflammatory response in the gastrointestinal tract. Pro-inflammatory cytokines including tumor necrosis factor-α, interferon-γ, interleukin-1β (IL-1β), and interleukin-12 are essential in mediating the inflammatory response, while anti-inflammatory cytokines including interleukin-10 and transforming growth factor-β are important in the attenuation or containment of inflammatory process. It is increasingly recognized that cytokines have an im...

  16. The role of the Th17 cytokines IL-17 and IL-22 in Rheumatoid Arthritis pathogenesis and developments in cytokine immunotherapy.

    Science.gov (United States)

    Roeleveld, Debbie M; Koenders, Marije I

    2015-07-01

    Over the past few years, the importance of Interleukin (IL)-17 and T helper (Th)17 cells in the pathology of Rheumatoid Arthritis (RA) has become apparent. RA is a systemic autoimmune disease that affects up to 1% of the population worldwide. It is characterized by an inflamed, hyperplastic synovium with pannus formation, leading to bone and cartilage destruction in the joints. By the production of effector cytokines like IL-17 and IL-22, the T helper 17 subset protects the host against bacterial and fungal infections, but it can also promote the development of various autoimmune diseases like RA. Hence, the Th17 pathway recently became a very interesting target in RA treatment. Up to now, several therapies targeting the Th17 cells or its effector cytokines have been tested, or are currently under investigation. This review clarifies the role of Th17 cells and its cytokines in the pathogenesis of RA, and provides an overview of the clinical trials using immunotherapy to target this particular T helper subset or the two main effector cytokines by which the Th17 cells exert their function, IL-17 and IL-22.

  17. Proinflammatory and anti-inflammatory cytokines in meningococcal disease.

    OpenAIRE

    Riordan, F A; Marzouk, O; Thomson, A. P.; Sills, J A; Hart, C. A.

    1996-01-01

    Interleukin-10 (IL-10), an anti-inflammatory cytokine, was measured in 131 children with meningococcal disease. IL-10 concentrations were significantly higher in children who died and correlated positively with proinflammatory cytokines. Children who die from meningococcal disease have high IL-10 concentrations, which do not suppress proinflammatory cytokines.

  18. Intragraft Cytokine mRNA Expression After Clinical Organ Transplantation

    NARCIS (Netherlands)

    C.C. Baan (Carla)

    1998-01-01

    textabstractAs the knowledge of the cytokine network in experimental transplant models grows, we need to understand how and to what extent cytokines mediate the various donordirected immune events in clinical situations. This overview on clinical cytokine measurements shows that specific intragraft

  19. Screening the cytokines for diagnosis of tuberculous meningitis

    Institute of Scientific and Technical Information of China (English)

    王丽豪

    2014-01-01

    Objective To select cytokines for diagnosis of tuber-culous meningitis.Methods One hundred and twenty kinds of cytokines were detected with protein chips among two tuberculous meningitis cases,two viral meningitis cases and two noninfectious neurologic disease cases.The results were compared among different disease groups to select the differential cytokines,which were

  20. Cytokines: muscle protein and amino acid metabolism

    DEFF Research Database (Denmark)

    van Hall, Gerrit

    2012-01-01

    raises TNF-α and IL-6 to moderate levels, has only identified IL-6 as a potent cytokine, decreasing systemic amino acid levels and muscle protein metabolism. The marked decrease in circulatory and muscle amino acid concentrations was observed with a concomitant reduction in both the rates of muscle...... protein synthesis and breakdown, that is, reduced turnover with a minor increase in net muscle degradation. Very similar observations have been made in models of acute inflammation, induced by high-dose endotoxin injection. However, these changes were suggested not to be attributed to a direct effect...... of IL-6 on the regulation of muscle protein metabolism but indirectly via IL-6 reducing amino acid availability. SUMMARY: Recent studies suggest that the best described cytokines TNF-α and IL-6 are unlikely to be the major direct mediators of muscle protein loss in inflammatory diseases. However...

  1. Cytokine orchestration in post-operative peritoneal adhesion formation

    Institute of Scientific and Technical Information of China (English)

    Ronan A Cahill; H Paul Redmond

    2008-01-01

    Peritoneal adhesions are a near inevitable occurrence after laparotomy and a major cause of both patient and physician misery.To date,clinical attempts at their amelioration have concentrated on manipulating the physical factors that affect their development despite a wealth of experimental data elucidating the molecular mechanisms that underlie their initiation,development and maturation.However,the advent of targeted,specific anti-cytokine agents as directed therapy for inflammatory and neoplastic conditions raises the prospect of a new era for anti-adhesion strategies.To harness this potential will require considerable cross-disciplinary collaboration and that surgeon-scientists propel themselves to the forefront of this emerging field.

  2. Effects of hemorrhage on cytokine gene transcription.

    Science.gov (United States)

    Shenkar, R; Abraham, E

    1993-08-01

    Injury and blood loss are often followed by infection and the rapid development of organ system dysfunction, frequently involving mucosal sites, such as the lung and intestine. To examine possible mechanisms contributing to these conditions, we used semiquantitative polymerase chain reactions to determine cytokine mRNA expression among cellular populations isolated from mucosal and systemic anatomic sites of mice at predetermined time points following 30% blood volume hemorrhage with resuscitation 1 hr later. Within 1 hr after hemorrhage, significant increases were observed in mRNA levels for IL-1 alpha, IL-1 beta, IL-5, and TGF-beta in intraparenchymal pulmonary mononuclear cells. The levels of TGF-beta transcripts among alveolar macrophages were increased 1 hr following blood loss, and increase in IL-1 alpha transcripts was found starting 2 hr posthemorrhage. Cells from Peyer's patches showed significant increases in mRNA levels for IL-1 beta, IL-2, IL-5, IL-6, IFN-gamma, and TGF-beta during the 4 hr following hemorrhage. Significant increases in mRNA levels for IL-1 beta, TNF-alpha, and TGF-beta were present within 4 hr of blood loss among cells isolated from mesenteric lymph nodes. The expression of mRNA for most cytokines was not significantly altered in splenocytes or peripheral blood mononuclear cells at any time point following hemorrhage. These experiments demonstrate that blood loss, even if resuscitated, produces significant increases in proinflammatory and immunoregulatory cytokine gene transcription as early as 1 hr following hemorrhage. These posthemorrhage alterations in cytokine mRNA expression were particularly prominent at mucosal sites, suggesting a mechanism for the increased incidence of pulmonary and intestinal involvement in organ system failure following severe blood loss and injury.

  3. Acute pancreatitis and fibromyalgia: Cytokine link

    Directory of Open Access Journals (Sweden)

    Sadat Muzammil

    2011-01-01

    Full Text Available Context: Fibromyalgia is a widespread musculoskeletal pain disorder found in 2% of the general population and with a preponderance of 85% in females, and has both genetic and environmental contribution. Acute pancreatitis is a severe condition and in most cases gallstones disease represents approximately half of the cases of acute pancreatitis, and 20-25% are related to alcohol abuse. Small numbers of cases are caused by a variety of other reasons but a few cases have no obvious cause, referred to as ′idiopathic′. Here we present a case where fibromyalgia might be linked to acute pancreatitis. We believe this has not been reported in this context in literature. Case Report: Fibromyalgia is a widespread musculoskeletal pain disorder found in 2% of the general population and with a preponderance of 85% in females, and has both genetic and environmental contribution. Patient had a cholecystectomy eight years previously. Patient feels tired almost all the time due to her fibromyalgia and requires family support for daily routine. Patient′s blood results showed alanine transaminase 527 IU/L, alkaline phosphatase 604 IU/L, bilirubin 34 μmol/L, amylase 2257 IU/L, C-reactive protein 19 mg/L, Gamma-Glutamyl transpeptidase 851 IU/L, renal function and electrolytes were within normal limits. The patient was admitted to the high dependency unit with a diagnosis of acute pancreatitis. Conclusion: There is a known increase in levels of cytokines in patients with fibromyalgia. Part of the pathophysiology of acute pancreatitis is related to raised cytokines and immune deregulations. We hypothesize that elevated levels of cytokines in fibromyalgia has led to acute pancreatitis in our patient. Further epidemiological research on the incidence of pancreatitis in cytokine mediated conditions such as fibromyalgia is required.

  4. Plasma astrophysics

    CERN Document Server

    Kaplan, S A; ter Haar, D

    2013-01-01

    Plasma Astrophysics is a translation from the Russian language; the topics discussed are based on lectures given by V.N. Tsytovich at several universities. The book describes the physics of the various phenomena and their mathematical formulation connected with plasma astrophysics. This book also explains the theory of the interaction of fast particles plasma, their radiation activities, as well as the plasma behavior when exposed to a very strong magnetic field. The text describes the nature of collective plasma processes and of plasma turbulence. One author explains the method of elementary

  5. Plasma waves

    CERN Document Server

    Swanson, DG

    1989-01-01

    Plasma Waves discusses the basic development and equations for the many aspects of plasma waves. The book is organized into two major parts, examining both linear and nonlinear plasma waves in the eight chapters it encompasses. After briefly discussing the properties and applications of plasma wave, the book goes on examining the wave types in a cold, magnetized plasma and the general forms of the dispersion relation that characterize the waves and label the various types of solutions. Chapters 3 and 4 analyze the acoustic phenomena through the fluid model of plasma and the kinetic effects. Th

  6. Cytokines as Biomarkers in Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Agata Burska

    2014-01-01

    Full Text Available RA is a complex disease that develops as a series of events often referred to as disease continuum. RA would benefit from novel biomarker development for diagnosis where new biomarkers are still needed (even if progresses have been made with the inclusion of ACPA into the ACR/EULAR 2010 diagnostic criteria and for prognostic notably in at risk of evolution patients with autoantibody-positive arthralgia. Risk biomarkers for rapid evolution or cardiovascular complications are also highly desirable. Monitoring biomarkers would be useful in predicting relapse. Finally, predictive biomarkers for therapy outcome would allow tailoring therapy to the individual. Increasing numbers of cytokines have been involved in RA pathology. Many have the potential as biomarkers in RA especially as their clinical utility is already established in other diseases and could be easily transferable to rheumatology. We will review the current knowledge’s relation to cytokine used as biomarker in RA. However, given the complexity and heterogeneous nature of RA, it is unlikely that a single cytokine may provide sufficient discrimination; therefore multiple biomarker signatures may represent more realistic approach for the future of personalised medicine in RA.

  7. Cytokine-Induced Modulation of Colorectal Cancer.

    Science.gov (United States)

    Mager, Lukas F; Wasmer, Marie-Hélène; Rau, Tilman T; Krebs, Philippe

    2016-01-01

    The emergence of novel immunomodulatory cancer therapies over the last decade, above all immune checkpoint blockade, has significantly advanced tumor treatment. For colorectal cancer (CRC), a novel scoring system based on the immune cell infiltration in tumors has greatly improved disease prognostic evaluation and guidance to more specific therapy. These findings underline the relevance of tumor immunology in the future handling and therapeutic approach of malignant disease. Inflammation can either promote or suppress CRC pathogenesis and inflammatory mediators, mainly cytokines, critically determine the pro- or anti-tumorigenic signals within the tumor environment. Here, we review the current knowledge on the cytokines known to be critically involved in CRC development and illustrate their mechanisms of action. We also highlight similarities and differences between CRC patients and murine models of CRC and point out cytokines with an ambivalent role for intestinal cancer. We also identify some of the future challenges in the field that should be addressed for the development of more effective immunomodulatory therapies.

  8. Cytokines as biomarkers in rheumatoid arthritis.

    Science.gov (United States)

    Burska, Agata; Boissinot, Marjorie; Ponchel, Frederique

    2014-01-01

    RA is a complex disease that develops as a series of events often referred to as disease continuum. RA would benefit from novel biomarker development for diagnosis where new biomarkers are still needed (even if progresses have been made with the inclusion of ACPA into the ACR/EULAR 2010 diagnostic criteria) and for prognostic notably in at risk of evolution patients with autoantibody-positive arthralgia. Risk biomarkers for rapid evolution or cardiovascular complications are also highly desirable. Monitoring biomarkers would be useful in predicting relapse. Finally, predictive biomarkers for therapy outcome would allow tailoring therapy to the individual. Increasing numbers of cytokines have been involved in RA pathology. Many have the potential as biomarkers in RA especially as their clinical utility is already established in other diseases and could be easily transferable to rheumatology. We will review the current knowledge's relation to cytokine used as biomarker in RA. However, given the complexity and heterogeneous nature of RA, it is unlikely that a single cytokine may provide sufficient discrimination; therefore multiple biomarker signatures may represent more realistic approach for the future of personalised medicine in RA.

  9. The feeding route (enteral or parenteral) affects the plasma response of the dipetide Ala-Gln and the amino acids glutamine, citrulline and arginine, with the administration of Ala-Gln in preoperative patients.

    Science.gov (United States)

    Melis, Gerdien C; Boelens, Petra G; van der Sijp, Joost R M; Popovici, Theodora; De Bandt, Jean-Pascal; Cynober, Luc; van Leeuwen, Paul A M

    2005-07-01

    Enhancement of depressed plasma concentrations of glutamine and arginine is associated with better clinical outcome. Supplementation of glutamine might be a way to provide the patient with glutamine, and also arginine, because glutamine provides the kidney with citrulline, from which the kidney produces arginine when plasma levels of arginine are low. The aim of the present study was to investigate the parenteral and enteral response of the administered dipeptide Ala-Gln, glutamine, citrulline and arginine. Therefore, seven patients received 20 g Ala-Gln, administered over 4 h, parenterally or enterally, on two separate occasions. Arterial blood samples were taken before and during the administration of Ala-Gln. ANOVA and a paired t test were used to test differences (Pglutamine was observed with parenteral infusion of the dipeptide, although enteral infusion also significantly increased plasma levels of glutamine. The highest plasma response of citrulline was observed with the enteral administration of the dipeptide, although parenteral administration also increased plasma levels of citrulline. Plasma arginine increased significantly with parenteral infusion, but not with enteral administration of Ala-Gln. In conclusion, administrations of Ala-Gln, parenteral or enteral, resulted in an increased plasma glutamine response, as compared with baseline. Interestingly, in spite of the high availability of citrulline with enteral administration of the dipeptide, only parenteral infusion of Ala-Gln increased plasma arginine concentration.

  10. Pro-Inflammatory Cytokine-Mediated Anemia: Regarding Molecular Mechanisms of Erythropoiesis

    Directory of Open Access Journals (Sweden)

    F. Morceau

    2009-01-01

    Full Text Available Anemia of cancer and chronic inflammatory diseases is a frequent complication affecting quality of life. For cancer patients it represents a particularly bad prognostic. Low level of erythropoietin is considered as one of the causes of anemia in these pathologies. The deficiency in erythropoietin production results from pro-inflammatory cytokines effect. However, few data is available concerning molecular mechanisms involved in cytokine-mediated anemia. Some recent publications have demonstrated the direct effect of pro-inflammatory cytokines on cell differentiation towards erythroid pathway, without erythropoietin defect. This suggested that pro-inflammatory cytokine-mediated signaling pathways affect erythropoietin activity. They could interfere with erythropoietin-mediated signaling pathways, inducing early apoptosis and perturbing the expression and regulation of specific transcription factors involved in the control of erythroid differentiation. In this review we summarize the effect of tumor necrosis factor (TNFα, TNF-related apoptosis-inducing ligand (TRAIL, and interferon (IFN-γ on erythropoiesis with a particular interest for molecular feature.

  11. 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

  12. Plasma Levels of Monocyte Chemotactic Protein 3 and Beta-Nerve Growth Factor Increase with Amnestic Mild Cognitive Impairment

    Institute of Scientific and Technical Information of China (English)

    Kang Soo Lee; Ji Hyung Chung; Kyung Hye Lee; Min-Jeong Shin; Byoung Hoon Oh; Soo Hyung Lee; Chang Hyung Hong

    2009-01-01

    A number of studies have investigated peripheral inflammatory indices, including plasma cytokines and related molecules according to subtypes of dementia, but not in mild cognitive impairment (MCI). In this study, we used multiplex cytokine assay to assess the plasma levels of 22 cytokines in patients with MCI subtyped as amnestic and non-amnestic, according to cognitive features. When comparing the levels of plasma growth factors, chemokines and cytokines, plasma levels of monocyte chemotactic protein 3 (MCP-3), and beta-nerve growth factor (β-NGF) in these two groups, they were found to be significantly higher in amnestic MCI patients than in non-amnestic MCI patients, after adjusting for age and gender. This suggests that plasma MCP-3 and β-NGF may be useful in differentiating subtypes of MCI. Cellular & Molecular Immunology.

  13. Stress downregulates lipopolysaccharide-induced expression of proinflammatory cytokines in the spleen, pituitary, and brain of mice.

    Science.gov (United States)

    Goujon, E; Parnet, P; Laye, S; Combe, C; Kelley, K W; Dantzer, R

    1995-12-01

    Mice injected with LPS (10 mu g/mouse, sc) or saline were submitted to a 15-min restraint stress and sacrificed 1 or 2 h later to assess the effect of stress on the induction of interleukin-1beta (IL-1beta) and other proinflammatory cytokines (IL-1alpha, IL-1ra, IL-6, and tumor necrosis factor-alpha) in the spleen, pituitary, hypothalamus, hippocampus, and striatum. LPS-induced cytokine gene expression, as determined by comparative RT-PCR, was lower in stressed than in nonstressed mice. LPS increased plasma and tissue levels of IL-1beta, as determined by ELISA, but this effect was less marked in stressed than in nonstressed mice. These results are discussed in relation to the modulatory effects of glucocorticoids on cytokine production.

  14. Rheumatoid arthritis pathophysiology: update on emerging cytokine and cytokine-associated cell targets.

    Science.gov (United States)

    Furst, Daniel E; Emery, Paul

    2014-09-01

    Biologic therapies that target pathogenic cytokines such as TNF, IL-1β or IL-6 have greatly improved the treatment of RA. Unfortunately, not all RA patients respond to current biologic therapies and responses are not always maintained, suggesting that there are alternative drivers of RA pathogenesis that might serve as promising therapeutic targets. Discovery of the new Th17 subset of Th cells, and their role in autoimmune disease development, has implicated the proinflammatory IL-12 and IL-17 families of cytokines in RA disease pathogenesis. Members of these cytokine families are elevated in the blood and joints of RA patients and have been shown to remain elevated in patients who do not respond to current biologics. In addition, these cytokines have been shown to play roles in joint destruction and erosion. A new subclass of biologics that target the IL-12 and/or IL-17 signalling pathways are under development. Here we review evidence for a role of Th17 cells as well as IL-12 and IL-17 cytokines in RA pathogenesis as the rationale for a subsequent discussion of the ongoing and completed clinical trials of newly emerging biologic therapies directed at IL-12 or IL-17 pathway inhibition.

  15. Regulation of cytokines by small RNAs during skin inflammation

    Directory of Open Access Journals (Sweden)

    Mikkelsen Jacob G

    2010-07-01

    Full Text Available Abstract Intercellular signaling by cytokines is a vital feature of the innate immune system. In skin, an inflammatory response is mediated by cytokines and an entwined network of cellular communication between T-cells and epidermal keratinocytes. Dysregulated cytokine production, orchestrated by activated T-cells homing to the skin, is believed to be the main cause of psoriasis, a common inflammatory skin disorder. Cytokines are heavily regulated at the transcriptional level, but emerging evidence suggests that regulatory mechanisms that operate after transcription play a key role in balancing the production of cytokines. Herein, we review the nature of cytokine signaling in psoriasis with particular emphasis on regulation by mRNA destabilizing elements and the potential targeting of cytokine-encoding mRNAs by miRNAs. The proposed linkage between mRNA decay mediated by AU-rich elements and miRNA association is described and discussed as a possible general feature of cytokine regulation in skin. Moreover, we describe the latest attempts to therapeutically target cytokines at the RNA level in psoriasis by exploiting the cellular RNA interference machinery. The applicability of cytokine-encoding mRNAs as future clinical drug targets is evaluated, and advances and obstacles related to topical administration of RNA-based drugs targeting the cytokine circuit in psoriasis are described.

  16. Cytokines: The Good, the Bad, and the Deadly.

    Science.gov (United States)

    Ramani, Thulasi; Auletta, Carol S; Weinstock, Daniel; Mounho-Zamora, Barbara; Ryan, Patricia C; Salcedo, Theodora W; Bannish, Gregory

    2015-01-01

    Over the past 30 years, the world of pharmaceutical toxicology has seen an explosion in the area of cytokines. An overview of the many aspects of cytokine safety evaluation currently in progress and evolving strategies for evaluating these important entities was presented at this symposium. Cytokines play a broad role to help the immune system respond to diseases, and drugs which modulate their effect have led to some amazing therapies. Cytokines may be "good" when stimulating the immune system to fight a foreign pathogen or attack tumors. Other "good" cytokine effects include reduction of an immune response, for example interferon β reduction of neuron inflammation in patients with multiple sclerosis. They may be "bad" when their expression causes inflammatory diseases, such as the role of tumor necrosis factor α in rheumatoid arthritis or asthma and Crohn's disease. Therapeutic modulation of cytokine expression can help the "good" cytokines to generate or quench the immune system and block the "bad" cytokines to prevent damaging inflammatory events. However, care must be exercised, as some antibody therapeutics can cause "ugly" cytokine release which can be deadly. Well-designed toxicology studies should incorporate careful assessment of cytokine modulation that will allow effective therapies to treat unmet needs. This symposium discussed lessons learned in cytokine toxicology using case studies and suggested future directions.

  17. 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.

  18. 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.

  19. Early cytokine release in response to live Borrelia burgdorferi Sensu Lato Spirochetes is largely complement independent.

    Directory of Open Access Journals (Sweden)

    Kerstin Sandholm

    Full Text Available AIM: Here we investigated the role of complement activation in phagocytosis and the release of cytokines and chemokines in response to two clinical isolates: Borrelia afzelii K78, which is resistant to complement-mediated lysis, and Borrelia garinii LU59, which is complement-sensitive. METHODS: Borrelia spirochetes were incubated in hirudin plasma, or hirudin-anticoagulated whole blood. Complement activation was measured as the generation of C3a and sC5b-9. Binding of the complement components C3, factor H, C4, and C4BP to the bacterial surfaces was analyzed. The importance of complement activation on phagocytosis, and on the release of cytokines and chemokines, was investigated using inhibitors acting at different levels of the complement cascade. RESULTS: 1 Borrelia garinii LU59 induced significantly higher complement activation than did Borrelia afzelii K78. 2 Borrelia afzelii K78 recruited higher amounts of factor H resulting in significantly lower C3 binding. 3 Both Borrelia strains were efficiently phagocytized by granulocytes and monocytes, with substantial inhibition by complement blockade at the levels of C3 and C5. 4 The release of the pro-inflammatory cytokines and chemokines IL-1β, IL-6, TNF, CCL20, and CXCL8, together with the anti-inflammatory IL-10, were increased the most (by>10-fold after exposure to Borrelia. 5 Both strains induced a similar release of cytokines and chemokines, which in contrast to the phagocytosis, was almost totally unaffected by complement blockade. CONCLUSIONS: Our results show that complement activation plays an important role in the process of phagocytosis but not in the subsequent cytokine release in response to live Borrelia spirochetes.

  20. Environmental mold and mycotoxin exposures elicit specific cytokine and chemokine responses.

    Directory of Open Access Journals (Sweden)

    Jamie H Rosenblum Lichtenstein

    Full Text Available Molds can cause respiratory symptoms and asthma. We sought to use isolated peripheral blood mononuclear cells (PBMCs to understand changes in cytokine and chemokine levels in response to mold and mycotoxin exposures and to link these levels with respiratory symptoms in humans. We did this by utilizing an ex vivo assay approach to differentiate mold-exposed patients and unexposed controls. While circulating plasma chemokine and cytokine levels from these two groups might be similar, we hypothesized that by challenging their isolated white blood cells with mold or mold extracts, we would see a differential chemokine and cytokine release.Peripheral blood mononuclear cells (PBMCs were isolated from blood from 33 patients with a history of mold exposures and from 17 controls. Cultured PBMCs were incubated with the most prominent Stachybotrys chartarum mycotoxin, satratoxin G, or with aqueous mold extract, ionomycin, or media, each with or without PMA. Additional PBMCs were exposed to spores of Aspergillus niger, Cladosporium herbarum and Penicillium chrysogenum. After 18 hours, cytokines and chemokines released into the culture medium were measured by multiplex assay. Clinical histories, physical examinations and pulmonary function tests were also conducted. After ex vivo PBMC exposures to molds or mycotoxins, the chemokine and cytokine profiles from patients with a history of mold exposure were significantly different from those of unexposed controls. In contrast, biomarker profiles from cells exposed to media alone showed no difference between the patients and controls.These findings demonstrate that chronic mold exposures induced changes in inflammatory and immune system responses to specific mold and mycotoxin challenges. These responses can differentiate mold-exposed patients from unexposed controls. This strategy may be a powerful approach to document immune system responsiveness to molds and other inflammation-inducing environmental agents.

  1. Sex differences in psychiatric comorbidity and plasma biomarkers for cocaine addiction in abstinent cocaine-addicted subjects in outpatient settings

    Directory of Open Access Journals (Sweden)

    MARIA ePEDRAZ

    2015-02-01

    Full Text Available There are sex differences in the progression of drug addiction, relapse and response to therapies. Because biological factors participate in these differences, they should be considered when using biomarkers for addiction. In the current study, we evaluated the sex differences in psychiatric comorbidity and the concentrations of plasma mediators that have been reported to be affected by cocaine.Fifty-five abstinent cocaine-addicted subjects diagnosed with lifetime cocaine use disorders (40 men and 15 women and 73 healthy controls (48 men and 25 women were clinically assessed with the diagnostic interview ‘Psychiatric Research Interview for Substance and Mental Disorders’. Plasma concentrations of chemokines, cytokines, N-acyl-ethanolamines and 2-acyl-glycerols were analyzed according to history of cocaine addiction and sex.The results showed that the chemokine concentrations of CCL2/MCP-1 and CXCL12/SDF-1 were only affected by history of cocaine addiction. The plasma concentrations of IL-1β, IL-6, IL-10 and TNFα were higher in control women relative to men, but these concentrations were reduced in cocaine-addicted women. Cytokine concentrations were unaltered in addicted men. Regarding fatty acid derivatives, history of cocaine addiction had a main effect on the concentration of each acyl derivative; whereas N-acyl-ethanolamines were increased overall in the cocaine group, 2-acyl-glycerols were decreased. Interestingly, POEA was only increased in cocaine-addicted women.Regarding psychiatric comorbidity in the cocaine group, women had lower incidence rates of comorbid substance use disorders than did men. For example, alcohol use disorders were found in 80% of men and 40% of women. In contrast, the addicted women had increased prevalences of comorbid psychiatric disorders (mood, anxiety and psychosis disorders.These results demonstrate the existence of a sex influence on plasma biomarkers for cocaine addiction and on the presence of

  2. Influence of phthalates on cytokine production in monocytes and macrophages: a systematic review of experimental trials.

    Directory of Open Access Journals (Sweden)

    Juliana Frohnert Hansen

    Full Text Available Phthalates are a group of endocrine disrupting chemicals suspected to influence the immune system. The aim of this systematic review is to summarise the present knowledge on the influence of phthalates on monocyte and macrophage production and secretion of cytokines, an influence which could affect both pro- and anti-inflammatory abilities of these cells.A systematic search was performed in Medline, Embase and Toxline in June 2013, last updated 3rd of August 2014. Criteria used to select studies were described and published beforehand online on Prospero (http://www.crd.york.ac.uk/NIHR_PROSPERO, registration number CRD42013004236. In vivo, ex vivo and in vitro studies investigating the influence of phthalates on cytokine mRNA expression and cytokine secretion in animals and humans were included. A total of 11 reports, containing 12 studies, were found eligible for inclusion. In these, a total of four different phthalate diesters, six primary metabolites (phthalate monoesters and seven different cytokines were investigated. Though all studies varied greatly in study design and species sources, four out of five studies that investigated di-2-ethylhexyl phthalate found an increased tumour necrosis factor-α secretion/production from monocytes or macrophages. A summary of cytokine measurements was not possible since few studies were comparable in study design and due to insufficient reporting of raw data for most of the included studies.Results from this review have suggested that at least one phthalate (di-2-ethylhexyl phthalate has the ability to enhance tumour necrosis factor-α production/secretion from monocytes/macrophages in vitro, but also observed ex vivo. Influence of other phthalates on other cytokines has only been investigated in few studies. Thus, in vitro studies on primary human monocytes/macrophages as well as more in vivo studies are needed to confirm or dispute these findings.

  3. Local cytokine changes in complex regional pain syndrome type I (CRPS I) resolve after 6 months.

    Science.gov (United States)

    Lenz, Melanie; Uçeyler, Nurcan; Frettlöh, Jule; Höffken, Oliver; Krumova, Elena K; Lissek, Silke; Reinersmann, Annika; Sommer, Claudia; Stude, Philipp; Waaga-Gasser, Ana M; Tegenthoff, Martin; Maier, Christoph

    2013-10-01

    There is evidence that inflammatory processes are involved in at least the early phase of complex regional pain syndrome (CRPS). We compared a panel of pro- and antiinflammatory cytokines in skin blister fluids and serum from patients with CRPS and patients with upper-limb pain of other origin (non-CRPS) in the early stage (< 1 year) and after 6 months of pain treatment. Blister fluid was collected from the affected and contralateral nonaffected side. We used a multiplex-10 bead array cytokine assay and Luminex technology to measure protein concentrations of the cytokines interleukin-1 receptor antagonist (IL-1RA), IL-2, IL-6, IL-8, IL-10, IL-12p40, and tumor necrosis factor-alpha (TNF-α) and the chemokines eotaxin, monocyte chemotactic protein-1 (MCP-1), and macrophage inflammatory protein-1β (MIP-1β). We found bilaterally increased proinflammatory TNF-α and MIP-1β and decreased antiinflammatory IL-1RA protein levels in CRPS patients compared to non-CRPS patients. Neither group showed side differences. After 6 months under analgesic treatment, protein levels of all measured cytokines in CRPS patients, except for IL-6, significantly changed bilaterally to the level of non-CRPS patients. These changes were not related to treatment outcome. In serum, only IL-8, TNF-α, eotaxin, MCP-1, and MIP-1β were detectable without intergroup differences. Blister fluid of CRPS patients showed a bilateral proinflammatory cytokine profile. This profile seems to be relevant only at the early stage of CRPS. Almost all measured cytokine levels were comparable to those of non-CRPS patients after 6 months of analgesic treatment and were not related to treatment outcome.

  4. Tacaribe virus but not junin virus infection induces cytokine release from primary human monocytes and macrophages.

    Directory of Open Access Journals (Sweden)

    Allison Groseth

    Full Text Available The mechanisms underlying the development of disease during arenavirus infection are poorly understood. However, common to all hemorrhagic fever diseases is the involvement of macrophages as primary target cells, suggesting that the immune response in these cells may be of paramount importance during infection. Thus, in order to identify features of the immune response that contribute to arenavirus pathogenesis, we have examined the growth kinetics and cytokine profiles of two closely related New World arenaviruses, the apathogenic Tacaribe virus (TCRV and the hemorrhagic fever-causing Junin virus (JUNV, in primary human monocytes and macrophages. Both viruses grew robustly in VeroE6 cells; however, TCRV titres were decreased by approximately 10 fold compared to JUNV in both monocytes and macrophages. Infection of both monocytes and macrophages with TCRV also resulted in the release of high levels of IL-6, IL-10 and TNF-α, while levels of IFN-α, IFN-β and IL-12 were not affected. However, we could show that the presence of these cytokines had no direct effect on growth of either TCRV of JUNV in macrophages. Further analysis also showed that while the production of IL-6 and IL-10 are dependent on viral replication, production of TNF-α also occurs after exposure to UV-inactivated TCRV particles and is thus independent of productive virus infection. Surprisingly, JUNV infection did not have an effect on any of the cytokines examined indicating that, in contrast to other viral hemorrhagic fever viruses, macrophage-derived cytokine production is unlikely to play an active role in contributing to the cytokine dysregulation observed in JUNV infected patients. Rather, these results suggest that an early, controlled immune response by infected macrophages may be critical for the successful control of infection of apathogenic viruses and prevention of subsequent disease, including systemic cytokine dysregulation.

  5. Herpesvirus saimiri encodes a new cytokine, IL-17, which binds to a novel cytokine receptor.

    Science.gov (United States)

    Yao, Zhengbin; Fanslow, William C; Seldin, Michael F; Rousseau, Anne-Marie; Painter, Sally L; Comeau, Michael R; Cohen, Jeffrey I; Spriggs, Melanie K

    2011-11-01

    Herpesvirus Saimiri gene 13 (HVS13) exhibits 57% identity with the predicted sequence of a T cell-derived molecule termed CTLA8. Recombinant HVS13 and CTLA8 stimulate transcriptional factor NF-kappaB activity and Interleukin-6 (IL-6) secretion in fibroblasts, and costimulate T cell proliferation. An HVS13.Fc fusion protein was used to isolate a cDNA encoding a novel receptor that also binds CTLA8. This receptor is unrelated to previously identified cytokine receptor families. A recombinant soluble receptor inhibited T cell proliferation and IL-2 production induced by PHA, concanavalin A (conA), and anti-TCR MAb. These results define CTLA8 and HVS13 as novel cytokines that bind to a novel cytokine receptor. We propose to call these molecules IL-17, vIL-17, and IL-17R, respectively.

  6. 脑缺血再灌注大鼠血浆炎性细胞因子与脾脏质量指数的相关性%Correction of plasma inflammatory cytokines with the spleen weight index following cerebral ischemia-reperfusion in rats

    Institute of Scientific and Technical Information of China (English)

    张金华; 闫福岭

    2012-01-01

    目的 探讨脑梗死大鼠外周细胞免疫功能改变与脾脏质量指数和组织学变化的关系.方法 成年雄性大鼠制作大脑中动脉闭塞(middle cerebral artery occlusion,MCAO)模型,检测外周血细胞因子水平、脾脏质量指数和组织学变化.结果 大鼠血清促炎细胞因子白细胞介素(int erleukin,IL)-1β和干扰素(interferon,INF)-γ水平分别在模型制作后6h和12 h升高,24 h时开始回落,72 h时降至最低,较假手术组存在显著统计学差异(P<0.01);相反,抗炎细胞因子IL-10水平则在模型制作后6h时降低,12 h时回升,72 h时达高峰,较假手术组存在显著统计学差异(P<0.01).MCAO组大鼠脾脏质量指数在模型制作后6h显著降低(P<0.01),12 h时回升,但仍低于假手术组(P<0.01),随后逐渐下降,72 h时降至最低(P<0.01).HE染色显示,MCAO后72 h大鼠脾脏的生发中心明显缩小,且轮廓显示欠清晰.相关分析显示,促炎细胞因子IL-1β( r=0.304,P=0.002)和INF-γ水平(r=0.644,P=0.000)与脾脏质量指数均呈显著正相关,而抗炎性细胞因子IL-10水平与脾脏质量指数呈显著负相关(r=-0.492,P=0.000).结论 MCAO大鼠外周细胞免疫功能处于抑制状态,脾脏变化可能在卒中后免疫抑制的发生过程中起着重要作用.%Objective To investigate the relationship between the changes of peripheral cellular immune function and the spleen weight index and the spleen histopathological changes following cerebral ischemiareperfusion in rats.Methods A model of middle cerebral artery occlusion (MCAO) of adult male rats was induced.The peripheral blood cytokine levels,spleen weight index and the spleen histopathological changes were evaluated.Results The serum proinflammatory cytokine interleukin (IL) -1β and interferon (INF) -γ levels in rats increased at 6 and 12 hours respectively after modeling.They began to decrease at 24 hours and decreased to the lowest at 72 hours.Compared to the sham operation

  7. Plasma Science Committee (PLSC)

    Science.gov (United States)

    1990-12-01

    The Plasma Science Committee (PLSC) is a standing committee under the auspices of the Board on Physics and Astronomy, Commission on Physical Sciences, Mathematics, and Applications of the National Academy of Sciences - National Research Council. Plasma sciences represent a broad and diverse field. The PLSC has accepted the responsibility of monitoring the continuing development and assessing the general health of the field as whole. Although select advisory bodies have been created to address specific issues that affect plasma science, such as the Fusion Policy Advisory Committee (FPAC), the PLSC provides a focus for the plasma science community that is unique and essential. The membership of the PLSC is drawn from research laboratories in universities, industry, and government. Areas of expertise on the committee include accelerators and beams, space physics, astrophysics, computational physics and applied mathematics, fusion plasmas, fundamental experiments and theory, radiation sources, low temperature plasmas, and plasma-surface interactions. The PLSC is well prepared to respond to requests for studies on specific issues.

  8. Plasmodium genetic loci linked to host cytokine and chemokine responses.

    Science.gov (United States)

    Pattaradilokrat, S; Li, J; Wu, J; Qi, Y; Eastman, R T; Zilversmit, M; Nair, S C; Huaman, M C; Quinones, M; Jiang, H; Li, N; Zhu, J; Zhao, K; Kaneko, O; Long, C A; Su, X-z

    2014-01-01

    Both host and parasite factors contribute to disease severity of malaria infection; however, the molecular mechanisms responsible for the disease and the host-parasite interactions involved remain largely unresolved. To investigate the effects of parasite factors on host immune responses and pathogenesis, we measured levels of plasma cytokines/chemokines (CCs) and growth rates in mice infected with two Plasmodium yoelii strains having different virulence phenotypes and in progeny from a genetic cross of the two parasites. Quantitative trait loci (QTL) analysis linked levels of many CCs, particularly IL-1β, IP-10, IFN-γ, MCP-1 and MIG, and early parasite growth rate to loci on multiple parasite chromosomes, including chromosomes 7, 9, 10, 12 and 13. Comparison of the genome sequences spanning the mapped loci revealed various candidate genes. The loci on chromosomes 7 and 13 had significant (P<0.005) additive effects on IL-1β, IL-5 and IP-10 responses, and the chromosome 9 and 12 loci had significant (P=0.017) interaction. Infection of knockout mice showed critical roles of MCP-1 and IL-10 in parasitemia control and host mortality. These results provide important information for a better understanding of malaria pathogenesis and can be used to examine the role of these factors in human malaria infection.

  9. Alterations in cytokines and haematological parameters during the acute and convalescent phases of Plasmodium falciparum and Plasmodium vivax infections

    Directory of Open Access Journals (Sweden)

    Rodrigo Nunes Rodrigues-da-Silva

    2014-04-01

    Full Text Available Haematological and cytokine alterations in malaria are a broad and controversial subject in the literature. However, few studies have simultaneously evaluated various cytokines in a single patient group during the acute and convalescent phases of infection. The aim of this study was to sequentially characterise alterations in haematological patters and circulating plasma cytokine and chemokine levels in patients infected with Plasmodium vivax or Plasmodium falciparum from a Brazilian endemic area during the acute and convalescent phases of infection. During the acute phase, thrombocytopaenia, eosinopaenia, lymphopaenia and an increased number of band cells were observed in the majority of the patients. During the convalescent phase, the haematologic parameters returned to normal. During the acute phase, P. vivax and P. falciparum patients had significantly higher interleukin (IL-6, IL-8, IL-17, interferon-γ, tumour necrosis factor (TNF-α, macrophage inflammatory protein-1β and granulocyte-colony stimulating factor levels than controls and maintained high levels during the convalescent phase. IL-10 was detected at high concentrations during the acute phase, but returned to normal levels during the convalescent phase. Plasma IL-10 concentration was positively correlated with parasitaemia in P. vivax and P. falciparum-infected patients. The same was true for the TNF-α concentration in P. falciparum-infected patients. Finally, the haematological and cytokine profiles were similar between uncomplicated P. falciparum and P. vivax infections.

  10. Affective Urbanism

    DEFF Research Database (Denmark)

    Samson, Kristine

    Urban design and architecture are increasingly used as material and affective strategies for setting the scene, for manipulation and the production of urban life: The orchestration of atmospheres, the framing and staging of urban actions, the programming for contemplation, involvement, play, expe...... affects can be choreographed and designed intentionally or whether it arises from unpredictable circumstances within urbanity itself....

  11. Affective Maps

    DEFF Research Database (Denmark)

    Salovaara-Moring, Inka

    of environmental knowledge production. It uses InfoAmazonia, the databased platform on Amazon rainforests, as an example of affective geo-visualization within information mapping that enhances embodiment in the experience of the information. Amazonia is defined as a digitally created affective (map)space within...

  12. Solution assembly of cytokine receptor ectodomain complexes

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Zining; Ciardelli, T.L. [Dartmouth Medical School, Hanover, NH (United States). Dept. of Pharmacology and Toxicology; Johnson, K.W. [Chiron Corp., Emeryville, CA (United States)] [and others

    1995-09-01

    For the majority of single transmembrane-spanning cell surface receptors, signal transmission across the lipid bilayer barrier involves several discrete components of molecular recognition. The interaction between ligand and the extracellular segment of its cognate receptor (ectodomain) initiates either homomeric or heteromeric association of receptor subunits. Specific recognition among these subunits may then occur between ectodomain regions, within the membrane by interhelical contact or inside the cell between cytoplasmic domains. Any or all of these interactions may contribute to the stability of the signaling complex. It is the characteristics of ligand binding by the ectodomains of these receptors that controls the heteromeric or homomeric nature and the stoichiometry of the complex. Cytokines and their receptors belong to a growing family of macromolecular systems that exhibit these functional features and share many structural similarities as well. Interleukin-2 is a multifunctional cytokine that represents, perhaps, the most complex example to date of ligand recognition among the hematopoietin receptor family. It is the cooperative binding of IL-2 by all three proteins on the surface of activated T-lymphocytes, however, that ultimately results in crosslinking of the {beta}- and {gamma}-subunits and signaling via association of their cytoplasmic domains. Although the high-affinity IL-2R functions as a heterotrimer, heterodimers of the receptor subunits are also physiologically important. The {alpha}/{beta} heterodimer or {open_quotes}pseudo-high affinity{close_quotes} receptor captures IL-2 as a preformed cell surface complex while the {beta}/{gamma} intermediate affinity site exists, in the absence of the {alpha} subunit, on the majority of natural killer cells. We have begun to study stable complexes of cytokine receptor ectodomains of defined composition and that mimic the ligand binding characteristics of the equivalent cell surface receptor sites.

  13. Type 2 diabetes - Tuberculosis co-morbidity is associated with diminished circulating levels of IL-20 subfamily of cytokines.

    Science.gov (United States)

    Kumar, Nathella Pavan; Banurekha, Vaithilingam V; Nair, Dina; Kumaran, Paul; Dolla, Chandra Kumar; Babu, Subash

    2015-12-01

    IL-20 subfamily of cytokines play an important role in both host defense mechanisms and glucose metabolism. Since, the interaction between tuberculosis (TB) and diabetes (DM) involves both of the above processes, we examined the association of IL-20 subfamily of cytokines in TB-DM co-morbidity. We examined circulating plasma cytokine levels in individuals with active TB with (PTB-DM) or without (PTB) diabetes and also those with latent TB with (LTB-DM) or without (LTB) diabetes. PTB-DM is characterized by diminished circulating levels of IL-19, IL-20, IL-22 and IL-24 but increased levels of IL-10. Similarly, LTB-DM was also characterized by diminished circulating levels of IL-10, IL-19, IL-20 and IL-24 but increased levels of IL-22. Moreover, there was a significant negative correlation of IL-10, IL-19, IL-20, IL-22 and IL-24 levels with hemoglobin A1C (HbA1c) levels in both PTB and/or LTB individuals. Finally, PTB is characterized by diminished levels of IL-19, IL-20, IL-22 and IL-24 in comparison to LTB individuals. Our data reveal that coincident diabetes in either PTB or LTB is characterized by decreased production of the IL-20 subfamily of cytokines and suggest that these cytokines might play an important role in pathogenesis or protection.

  14. Standardization of cytokine flow cytometry assays

    Directory of Open Access Journals (Sweden)

    Cox Josephine

    2005-06-01

    Full Text Available Abstract Background Cytokine flow cytometry (CFC or intracellular cytokine staining (ICS can quantitate antigen-specific T cell responses in settings such as experimental vaccination. Standardization of ICS among laboratories performing vaccine studies would provide a common platform by which to compare the immunogenicity of different vaccine candidates across multiple international organizations conducting clinical trials. As such, a study was carried out among several laboratories involved in HIV clinical trials, to define the inter-lab precision of ICS using various sample types, and using a common protocol for each experiment (see additional files online. Results Three sample types (activated, fixed, and frozen whole blood; fresh whole blood; and cryopreserved PBMC were shipped to various sites, where ICS assays using cytomegalovirus (CMV pp65 peptide mix or control antigens were performed in parallel in 96-well plates. For one experiment, antigens and antibody cocktails were lyophilised into 96-well plates to simplify and standardize the assay setup. Results (CD4+cytokine+ cells and CD8+cytokine+ cells were determined by each site. Raw data were also sent to a central site for batch analysis with a dynamic gating template. Mean inter-laboratory coefficient of variation (C.V. ranged from 17–44% depending upon the sample type and analysis method. Cryopreserved peripheral blood mononuclear cells (PBMC yielded lower inter-lab C.V.'s than whole blood. Centralized analysis (using a dynamic gating template reduced the inter-lab C.V. by 5–20%, depending upon the experiment. The inter-lab C.V. was lowest (18–24% for samples with a mean of >0.5% IFNγ + T cells, and highest (57–82% for samples with a mean of Conclusion ICS assays can be performed by multiple laboratories using a common protocol with good inter-laboratory precision, which improves as the frequency of responding cells increases. Cryopreserved PBMC may yield slightly more

  15. Cytokines in the modulation of eosinophilia

    Directory of Open Access Journals (Sweden)

    Faccioli Lúcia H

    1997-01-01

    Full Text Available In this review we discuss our recently results showing interleukin 5 (IL-5 involvement in eosinophil migration and in the maintenance of eosinophilia in blood, bone marrow, lung and peritoneal cavity, in a visceral larva migrans syndrome model using guinea-pigs infected with Toxocara canis. We also describe the sequential release of TNF-alpha and IL-8 during the course of infection, and the interaction between these cytokines and IL-5 during infection. Finally we propose a new biological role for IL-5, at least in our model, as a modulator of IL-8 release and secretion.

  16. AUTOPHAGY AND IL-1 FAMILY CYTOKINES

    Directory of Open Access Journals (Sweden)

    James Harris

    2013-01-01

    Full Text Available Autophagy is an important intracellular homeostatic mechanism for the targeting of cytosolic constituents, including organelles, for lysosomal degradation. Autophagy plays roles in numerous physiological processes, include immune cell responses to endogenous and exogenous pathogenic stimuli. Moreover, autophagy has a potentially pivotal role in the regulation of inflammatory responses. In particular, autophagy regulates endogenous inflammasome activators, as well as inflammasome components and pro-IL-1β. This review focuses specifically on the role autophagy plays in regulating the production, processing and secretion of IL-1 family cytokines.

  17. Chronic pain: cytokines, lymphocytes and chemokines.

    Science.gov (United States)

    de Miguel, Marcia; Kraychete, Durval Campos; Meyer Nascimento, Roberto Jose

    2014-01-01

    Chronic pain is a debilitating condition and, in most cases, difficult to treat. A prominent example of this is neuropathic pain. Understanding pathophysiological mechanisms of pain and, therefore, making this knowledge into an effective treatment is still a challenge to experts. Pain can now be considered as a neuro-immune disorder, since recent data indicate critical involvement of innate and adaptive immune responses following injury, and this interaction plays an important role in the onset and perpetuation of chronic pain. The aim of this article is to review the relationship between immune system and chronic pain, especially about neuropathic pain, and focusing on cytokines, chemokines and lymphocytes.

  18. Cytokines and Pancreatic β-Cell Apoptosis.

    Science.gov (United States)

    Berchtold, L A; Prause, M; Størling, J; Mandrup-Poulsen, T

    The discovery 30 years ago that inflammatory cytokines cause a concentration, activity, and time-dependent bimodal response in pancreatic β-cell function and viability has been a game-changer in the fields of research directed at understanding inflammatory regulation of β-cell function and survival and the causes of β-cell failure and destruction in diabetes. Having until then been confined to the use of pathophysiologically irrelevant β-cell toxic chemicals as a model of β-cell death, researchers could now mimic endocrine and paracrine effects of the cytokine response in vitro by titrating concentrations in the low to the high picomolar-femtomolar range and vary exposure time for up to 14-16h to reproduce the acute regulatory effects of systemic inflammation on β-cell secretory responses, with a shift to inhibition at high picomolar concentrations or more than 16h of exposure to illustrate adverse effects of local, chronic islet inflammation. Since then, numerous studies have clarified how these bimodal responses depend on discrete signaling pathways. Most interest has been devoted to the proapoptotic response dependent upon mainly nuclear factor κ B and mitogen-activated protein kinase activation, leading to gene expressional changes, endoplasmic reticulum stress, and triggering of mitochondrial dysfunction. Preclinical studies have shown preventive effects of cytokine antagonism in animal models of diabetes, and clinical trials demonstrating proof of concept are emerging. The full clinical potential of anticytokine therapies has yet to be shown by testing the incremental effects of appropriate dosing, timing, and combinations of treatments. Due to the considerable translational importance of enhancing the precision, specificity, and safety of antiinflammatory treatments of diabetes, we review here the cellular, preclinical, and clinical evidence of which of the death pathways recently proposed in the Nomenclature Committee on Cell Death 2012

  19. The mechanism of bifidobacterium vinegar affecting the plasma lipid of rats fed with high-fat diet%双歧醋对高脂饮食大鼠血脂影响的机制探讨

    Institute of Scientific and Technical Information of China (English)

    李金玲; 张德纯; 刘永云; 陈翠竹; 王春耀

    2012-01-01

    Objective To discuss the prophylactic antiobesity effect of bifidobacterium vinegar and its possible mechanism. Methods 48 SD rats were randomly divided into 6 groups; bifidobacterium vinegar groups of three different doses, ordinary vineger group, high-fat model group and basic group. The possible mechanism of bifidobacterium vinegar affecting the plasma lipid of rats fed with high-fat diet was observed. The lipidoses in liver were measured; mRNA expression of LDLR and HMGCoA reductase in liver tissue were detected by immunohistochemistry and RT-PCR. Results The levels of HMGCoA re-ductase of bifidobacterium vinegar groups were depressed obviously compared with that of high-fat model group. Conclusion Bifidobacterium vinegar can prevent the occurance of high-fat in rats through adjusting the LDLR and HMGCoA reductase in liver to some degree.%目的 探讨双歧醋对高脂饮食大鼠血脂的影响机制.方法 48只SD大鼠被随机分成双歧醋低剂量组[1.8 mL/(kg·BW)]、中剂量组[3.4 mL/(kg· BW)]、高剂量组[6.8 mL/(kg·BW)]和市售醋组[3.4 mL/(kg·BW)]、高脂模型组以及基础对照组,观察双歧醋对高脂饮食大鼠血脂的影响作用机制,测定指标包括大鼠肝脏脂质、大鼠LDLR的免疫组化分析,HMGCoA还原酶和LDLR的RT-PCR分析.结果 双歧醋各组对于HMGCoA还原酶表达有抑制作用,但可以上调LDLR的基因和蛋白质表达.结论 双歧醋可以通过调节HMGCoA还原酶和LDLR的表达预防高脂饮食大鼠高血脂的发生.

  20. Expression of acute phase proteins and inflammatory cytokines in mouse mammary gland following Staphylococcus aureus challenge and in response to milk accumulation

    DEFF Research Database (Denmark)

    Nazemi, Sasan; Aalbæk, Bent; Kjelgaard-Hansen, Mads

    2014-01-01

    We used a mouse model of pathogenic (Staphylococcus aureus) and non-pathogenic (teat sealing) mammary inflammation to investigate mRNA expression of several inflammatory cytokines and acute phase proteins (APP) in mammary tissue and liver, and the appearance of some of these factors in plasma...... in combination might provide a tool for diagnostic discrimination between mastitis caused by pathogenic invasion and milk accumulation, and hence allow for better targeting of antibiotic therapy. In comparison with mammary expression, expression of cytokines in liver tissue was up-regulated to a similar...... or lesser extent, whilst expression of APP was up-regulated to a much greater extent. The first appearance of increased cytokine and APP concentrations in plasma and of milk amyloid A (MAA) in milk occurred in advance of the measurable up-regulation of expression, hence their origin cannot be stated...

  1. Differential expression of cytokines in subcutaneous and marrow fat of aging C57BL/6J mice.

    Science.gov (United States)

    Gasparrini, Marco; Rivas, Daniel; Elbaz, Alexandre; Duque, Gustavo

    2009-09-01

    Increasing marrow adipogenesis plays a causative role in the pathogenesis of age-related bone loss that could be associated with high cytokine production. In this study, we characterized the age-related changes in cytokine expression by bone marrow (BM) adipocytes as compared with subcutaneous (SC) fat. BM and SC adipocytes were isolated from young (4 months) and old (24 months) male C57BL/6J. Total proteins were extracted and proteomic analysis of 96 cytokines was performed using a cytokine antibody array. Proteins showing a significant change were grouped according with their known function in bone. We found a significant age-induced difference in the expression of 53 cytokines. As compared with SC adipocytes, aging BM adipocytes showed a more pro-adipogenic, anti-osteoblastogenic and pro-apoptotic phenotype. These data suggest that, with aging, BM adipocytes become significantly more toxic than SC adipocytes. These cytokines, if secreted, could play a role in the pathogenesis of age-related bone loss by affecting other cells within the marrow milieu.

  2. Specific siRNA Downregulated TLR9 and Altered Cytokine Expression Pattern in Macrophage after CpG DNA Stimulation

    Institute of Scientific and Technical Information of China (English)

    BinQiao; BaohuaLi; XiuliYang; HongyongZhang; YiweiChu; YingWang; SidongXiong

    2005-01-01

    Bacterial CpG DNA or synthetic oligonucleotides (ODNs) that contain unmethylated CpG motifs (CpG ODN) can directly activate antigen-presenting cells (APCs) to secrete various cytokines through the intraceilular receptor TL R9. Cytokine profiles elicited by the actions of stimulatory CpG DNA on TLR9 expressed APCs are crucial to the subsequent immune responses. To date, cytokine profiles in APCs upon CpG ODN stimulation in vitro are not fully investigated. In the present study, vector-based siRNA was used to downregulate TLR9 expression. Cytokine profiles were observed in murine macrophage cell line RAW264.7 transfected with TLR9-siRNA plasmid uponCpG ODN stimulation. We found that not all the cytokine expressions by the macrophage were decreased whileTLR9 was downregulated. IL-12, TNF-α, IFN-γ and IL-1β expressions were significantly decreased, but IL-6, IFN-β and IL-10 expressions were not affected. Interestingly, the level of IFN-α was even increased. This alteration of cytokines produced by TLR9-downregulated APCs upon CpG ODN stimulation might indicate that the role of CpG DNA is more complicated in the pathogenesis and prevention of diseases. Cellular & Molecular Immunology. 2005;2(2):130-135.

  3. Specific siRNA Downregulated TLR9 and Altered Cytokine Expression Pattern in Macrophage after CpG DNA Stimulation

    Institute of Scientific and Technical Information of China (English)

    Bin Qiao; Baohua Li; Xiuli Yang; Hongyong Zhang; Yiwei Chu; Ying Wang; Sidong Xiong

    2005-01-01

    Bacterial CpG DNA or synthetic oligonucleotides (ODNs) that contain unmethylated CpG motifs (CpG ODN) can directly activate antigen-presenting cells (APCs) to secrete various cytokines through the intracellular receptor TLR9. Cytokine profiles elicited by the actions of stimulatory CpG DNA on TLR9 expressed APCs are crucial to the subsequent immune responses. To date, cytokine profiles in APCs upon CpG ODN stimulation in vitro are not fully investigated. In the present study, vector-based siRNA was used to downregulate TLR9 expression. Cytokine profiles were observed in murine macrophage cell line RAW264.7 transfected with TLR9-siRNA plasmid upon CpG ODN stimulation. We found that not all the cytokine expressions by the macrophage were decreased while TLR9 was downregulated. IL-12, TNF-α, IFN-γ and IL-1β expressions were significantly decreased, but IL-6,IFN-β and IL-10 expressions were not affected. Interestingly, the level of IFN-α was even increased. This alteration of cytokines produced by TLR9-downregulated APCs upon CpG ODN stimulation might indicate that the role of CpG DNA is more complicated in the pathogenesis and prevention of diseases. Cellular & Molecular Immunology.2005;2(2):130-135.

  4. Cytokines and growth factors cross-link heparan sulfate

    Science.gov (United States)

    Migliorini, Elisa; Thakar, Dhruv; Kühnle, Jens; Sadir, Rabia; Dyer, Douglas P.; Li, Yong; Sun, Changye; Volkman, Brian F.; Handel, Tracy M.; Coche-Guerente, Liliane; Fernig, David G.; Lortat-Jacob, Hugues; Richter, Ralf P.

    2015-01-01

    The glycosaminoglycan heparan sulfate (HS), present at the surface of most cells and ubiquitous in extracellular matrix, binds many soluble extracellular signalling molecules such as chemokines and growth factors, and regulates their transport and effector functions. It is, however, unknown whether upon binding HS these proteins can affect the long-range structure of HS. To test this idea, we interrogated a supramolecular model system, in which HS chains grafted to streptavidin-functionalized oligoethylene glycol monolayers or supported lipid bilayers mimic the HS-rich pericellular or extracellular matrix, with the biophysical techniques quartz crystal microbalance (QCM-D) and fluorescence recovery after photobleaching (FRAP). We were able to control and characterize the supramolecular presentation of HS chains—their local density, orientation, conformation and lateral mobility—and their interaction with proteins. The chemokine CXCL12α (or SDF-1α) rigidified the HS film, and this effect was due to protein-mediated cross-linking of HS chains. Complementary measurements with CXCL12α mutants and the CXCL12γ isoform provided insight into the molecular mechanism underlying cross-linking. Fibroblast growth factor 2 (FGF-2), which has three HS binding sites, was also found to cross-link HS, but FGF-9, which has just one binding site, did not. Based on these data, we propose that the ability to cross-link HS is a generic feature of many cytokines and growth factors, which depends on the architecture of their HS binding sites. The ability to change matrix organization and physico-chemical properties (e.g. permeability and rigidification) implies that the functions of cytokines and growth factors may not simply be confined to the activation of cognate cellular receptors. PMID:26269427

  5. Chemokine and cytokine levels in inflammatory bowel disease patients.

    Science.gov (United States)

    Singh, Udai P; Singh, Narendra P; Murphy, E Angela; Price, Robert L; Fayad, Raja; Nagarkatti, Mitzi; Nagarkatti, Prakash S

    2016-01-01

    Crohn's disease (CD) and ulcerative colitis (UC), two forms of inflammatory bowel disease (IBD), are chronic, relapsing, and tissue destructive lesions that are accompanied by the uncontrolled activation of effector immune cells in the mucosa. Recent estimates indicate that there are 1.3 million annual cases of IBD in the United States, 50% of which consists of CD and 50% of UC. Chemokines and cytokines play a pivotal role in the regulation of mucosal inflammation by promoting leukocyte migration to sites of inflammation ultimately leading to tissue damage and destruction. In recent years, experimental studies in rodents have led to a better understanding of the role played by these inflammatory mediators in the development and progression of colitis. However, the clinical literature on IBD remains limited. Therefore, the aim of this study was to evaluate systemic concentrations of key chemokines and cytokines in forty-two IBD patients with a range of disease activity compared to levels found in ten healthy donors. We found a significant increase in an array of chemokines including macrophage migration factor (MIF), CCL25, CCL23, CXCL5, CXCL13, CXCL10, CXCL11, MCP1, and CCL21 in IBD patients as compared to normal healthy donors (Pcytokines IL-16, IFN-γ, IL-1β and TNF-α in IBD patients when compared to healthy donors (Pcytokines that are known to modulate systemic level through immune cells results in affecting local intestinal inflammation and tissue damage in IBD patients. Blockade of these inflammatory mediators should be explored as a mechanism to alleviate or even reverse symptoms of IBD.

  6. Association between Prediagnostic Allergy-Related Serum Cytokines and Glioma.

    Directory of Open Access Journals (Sweden)

    Judith Schwartzbaum

    Full Text Available Allergy is inversely related to glioma risk. To determine whether prediagnostic allergy-related serum proteins are associated with glioma, we conducted a nested case-control study of seven cytokines (IL4, IL13, IL5, IL6, IL10, IFNG, TGFB2, two soluble cytokine receptors (sIL4RA, sIL13RA2 and three allergy-related transcription factors (FOXP3, STAT3, STAT6 using serum specimens from the Janus Serum Bank Cohort in Oslo, Norway. Blood donors subsequently diagnosed with glioma (n = 487 were matched to controls (n = 487 on age and date of blood draw and sex. We first estimated individual effects of the 12 serum proteins and then interactions between IL4 and IL13 and their receptors using conditional logistic regression. We next tested equality of case-control inter-correlations among the 12 serum proteins. We found that TGFB2 is inversely related to glioblastoma (Odds Ratio (OR = 0.87, 95% Confidence Interval (CI = 0.76, 0.98. In addition, ≤ 5 years before diagnosis, we observed associations between IL4 (OR = 0.82, 95% CI = 0.66, 1.01, sIL4RA (OR = 0.80, 95% CI = 0.65, 1.00, their interaction (OR = 1.06, 95% CI = 1.01, 1.12 and glioblastoma. This interaction was apparent > 20 years before diagnosis (IL4-sIL4RA OR = 1.20, 95% CI = 1.05, 1.37. Findings for glioma were similar. Case correlations were different from control correlations stratified on time before diagnosis. Five years or less before diagnosis, correlations among case serum proteins were weaker than were those among controls. Our findings suggest that IL4 and sIL4RA reduce glioma risk long before diagnosis and early gliomagenesis affects circulating immune function proteins.

  7. Moxonidine modulates cytokine signalling and effects on cardiac cell viability.

    Science.gov (United States)

    Aceros, Henry; Farah, Georges; Noiseux, Nicolas; Mukaddam-Daher, Suhayla

    2014-10-05

    Regression of left ventricular hypertrophy and improved cardiac function in SHR by the centrally acting imidazoline I1-receptor agonist, moxonidine, are associated with differential actions on circulating and cardiac cytokines. Herein, we investigated cell-type specific I1-receptor (also known as nischarin) signalling and the mechanisms through which moxonidine may interfere with cytokines to affect cardiac cell viability. Studies were performed on neonatal rat cardiomyocytes and fibroblasts incubated with interleukin (IL)-1β (5 ng/ml), tumor necrosis factor (TNF)-α (10 ng/ml), and moxonidine (10(-7) and 10(-5) M), separately and in combination, for 15 min, and 24 and 48 h for the measurement of MAPKs (ERK1/2, JNK, and p38) and Akt activation and inducible NOS (iNOS) expression, by Western blotting, and cardiac cell viability/proliferation and apoptosis by flow cytometry, MTT assay, and Live/Dead assay. Participation of imidazoline I1-receptors and the signalling proteins in the detected effects was identified using imidazoline I1-receptor antagonist and signalling protein inhibitors. The results show that IL-1β, and to a lower extent, TNF-α, causes cell death and that moxonidine protects against starvation- as well as IL-1β -induced mortality, mainly by maintaining membrane integrity, and in part, by improving mitochondrial activity. The protection involves activation of Akt, ERK1/2, p38, JNK, and iNOS. In contrast, moxonidine stimulates basal and IL-1β-induced fibroblast mortality by mechanisms that include inhibition of JNK and iNOS. Thus, apart from their actions on the central nervous system, imidazoline I1-receptors are directly involved in cardiac cell growth and death, and may play an important role in cardiovascular diseases associated with inflammation.

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

    Directory of Open Access Journals (Sweden)

    Bruno de Paulo Ribeiro

    2016-03-01

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

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

    Science.gov (United States)

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

    2016-03-01

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

  10. Cytokine response to pregnancy-associated recrudescence of Plasmodium berghei infection in mice with pre-existing immunity to malaria

    DEFF Research Database (Denmark)

    Megnekou, Rosette; Staalsoe, Trine; Hviid, Lars

    2013-01-01

    During childhood, residents of areas with stable transmission of Plasmodium falciparum parasites acquire substantial protective immunity to malaria, and adults therefore rarely experience clinical disease episodes. However, susceptibility to infection reappears in pregnant women, particularly...... primigravidae. This is due to appearance of antigenic parasite variants that are restricted to pregnancy. Variant-specific immunity also governs pregnancy-associated recrudescence of Plasmodium berghei infection in pregnant mice. Pregnancy-related changes in the plasma cytokine levels of mice with immunity...

  11. Effects of partial sleep deprivation on proinflammatory cytokines, growth hormone, and steroid hormone concentrations during repeated brief sprint interval exercise.

    Science.gov (United States)

    Abedelmalek, Salma; Souissi, Nizar; Chtourou, Hamdi; Denguezli, Meriam; Aouichaoui, Chirine; Ajina, Monia; Aloui, Asma; Dogui, Mohamed; Haddouk, Samy; Tabka, Zouhair

    2013-05-01

    The purpose of this study was to evaluate the effects of partial sleep deprivation (PSD) on circulating concentrations of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in relation to the secretory profiles of growth hormone (GH), cortisol, and testosterone during a repeated brief sprint interval exercise. Thirty healthy football players (mean age: 21.1 [range: 18-24] years; body mass index [BMI]: 22.6 [range: 18.47-24.46] Kg/m(2)) completed two test sessions at 08:00 h, one scheduled after a baseline night (bedtime: from 22:30 to 07:00 h) and the other after a PSD night caused by an early awakening (bedtime: from 22:30 to 03:00 h). During each session, participants performed 4 × 250-m run on a treadmill at a constant intensity of 80% of the personal maximal speed with a 3-min recovery in between. Tests session were performed at 08:00 h. Blood samples were collected before, immediately after the first and the fourth 250-m run, and 60 min after the exercise. The results showed that cortisol concentrations were not affected by the PSD. However, GH and testosterone concentrations were higher (p exercise during PSD in comparison with baseline. Likewise, plasma concentrations of IL-6 and TNF-α were higher (p exercise (i.e., the first and the fourth run) and remained elevated during the recovery period (i.e., 60 min after the exercise). In conclusion, these results showed that sleep restriction increases the proinflammatory cytokine, GH, and testosterone concentrations after physical exercise but did not affect the cortisol responses.

  12. Chronic alcohol use affects therapeutic steady state plasma drug concentrations of stavudine, lamivudine and nevirapine in HIV-infected patients during 9 months follow up period: WHO AUDIT tool application

    Directory of Open Access Journals (Sweden)

    Godfrey S. Bbosa

    2013-10-01

    Full Text Available Chronic alcohol consumption is a common problem among the HIV-infected patients on HAART. The study determined the effect of chronic alcohol use on steady state plasma drug concentrations of stavudine (d4T, lamivudine (3TC and nevirapine (NVP in HIV-infected patients during the 9 months follow up period. It also determined whether there were some patients with undetectable plasma drug concentrations in their plasma during the follow up. A case control using repeated measures design with serial measurements model, where plasma drug concentrations were measured at 3 month intervals was used. Chronic alcohol-use using WHO AUDIT tool was used to screen patients. A total of 41 patients (21 alcohol group and 20 control group were followed up for 9 months with blood sampling done at 3 month intervals. The Shimadzu Class-VPTM HPLC Chromatography data system version 6.1 equipment with UV detector was used to measure the plasma drug concentrations. Data was analyzed using SAS 2003 version 9.1 statistical package with repeated measures fixed the model and means were compared using the student t-test. The mean steady state plasma concentration of both d4T and 3TC in chronic alcohol use group were lower than in the control group all throughout the 9 months period of follow-up. The mean steady state plasma drug concentrations of NVP were higher in the alcohol group at 0 and 3 months and lower in the 6 and 9 months as compared to the control group. The mean total plasma NVP concentration was higher in the chronic alcohol group as compared to the control group and the difference was statistically significant (p≤0.05. However some patients had undetectable plasma drug concentrations despite of having ≥ 95 % adherence rate. Chronic alcohol use by the HIV-infected patients lowers the steady state plasma drug concentrations of d4T, 3TC and NVP in patients. [Int J Basic Clin Pharmacol 2013; 2(5.000: 507-516

  13. Cytokine production by leukocytes of military personnel with depressive symptoms after deployment to a combat-zone: a prospective, longitudinal study.

    Directory of Open Access Journals (Sweden)

    Mirjam van Zuiden

    -zone affects the capacity of T-cells and monocytes to produce cytokines and chemokines until at least 6 months after return.

  14. Phagosomal Acidification Prevents Macrophage Inflammatory Cytokine Production to Malaria, and Dendritic Cells Are the Major Source at the Early Stages of Infection: IMPLICATION FOR MALARIA PROTECTIVE IMMUNITY DEVELOPMENT.

    Science.gov (United States)

    Wu, Xianzhu; Gowda, Nagaraj M; Gowda, D Channe

    2015-09-18

    Inflammatory cytokines produced at the early stages of malaria infection contribute to shaping protective immunity and pathophysiology. To gain mechanistic insight into these processes, it is important to understand the cellular origin of cytokines because both cytokine input and cytokine-producing cells play key roles. Here, we determined cytokine responses by monocytes, macrophages, and dendritic cells (DCs) to purified Plasmodium falciparum and Plasmodium berghei ANKA, and by spleen macrophages and DCs from Plasmodium yoelii 17NXL-infected and P. berghei ANKA-infected mice. The results demonstrate that monocytes and macrophages do not produce inflammatory cytokines to malaria parasites and that DCs are the primary source early in infection, and DC subsets differentially produce cytokines. Importantly, blocking of phagosomal acidification by inhibiting vacuolar-type H(+)-ATPase enabled macrophages to elicit cytokine responses. Because cytokine responses to malaria parasites are mediated primarily through endosomal Toll-like receptors, our data indicate that the inability of macrophages to produce cytokines is due to the phagosomal acidification that disrupts endosomal ligand-receptor engagement. Macrophages efficiently produced cytokines to LPS upon simultaneously internalizing parasites and to heat-killed Escherichia coli, demonstrating that phagosomal acidification affects endosomal receptor-mediated, but not cell surface receptor-mediated, recognition of Toll-like receptor agonists. Enabling monocytes/macrophages to elicit immune responses to parasites by blocking endosomal acidification can be a novel strategy for the effective development of protective immunity to malaria. The results have important implications for enhancing the efficacy of a whole parasite-based malaria vaccine and for designing strategies for the development of protective immunity to pathogens that induce immune responses primarily through endosomal receptors.

  15. Relationship of cytokines and cytokine signaling to immunodeficiency disorders in the mouse

    Directory of Open Access Journals (Sweden)

    Morawetz R.A.

    1998-01-01

    Full Text Available The contributions of cytokines to the development and progression of disease in a mouse model of retrovirus-induced immunodeficiency (MAIDS are controversial. Some studies have indicated an etiologic role for type 2 cytokines, while others have emphasized the importance of type 1 cytokines. We have used mice deficient in expression of IL-4, IL-10, IL-4 and IL-10, IFN-g, or ICSBP - a transcriptional protein involved in IFN signaling - to examine their contributions to this disorder. Our results demonstrate that expression of type 2 cytokines is an epiphenomenon of infection and that IFN-g is a driving force in disease progression. In addition, exogenously administered IL-12 prevents many manifestations of disease while blocking retrovirus expression. Interruption of the IFN signaling pathways in ICSBP-/- mice blocks induction of MAIDS. Predictably, ICSBP-deficient mice exhibit impaired responses to challenge with several other viruses. This immunodeficiency is associated with impaired production of IFN-g and IL-12. Unexpectedly, however, the ICSBP-/- mice also develop a syndrome with many similarities to chronic myelogenous leukemia in humans. The chronic phase of this disease is followed by a fatal blast crisis characterized by clonal expansions of undifferentiated cells. ICSBP is thus an important determinant of hematopoietic growth and differentiation as well as a prominent signaling molecule for IFNs

  16. Boswellia carterii extract inhibits TH1 cytokines and promotes TH2 cytokines in vitro.

    Science.gov (United States)

    Chevrier, Marc R; Ryan, Abigail E; Lee, David Y-W; Zhongze, Ma; Wu-Yan, Zhang; Via, Charles S

    2005-05-01

    Traditional herbal formulas used to treat inflammatory arthritis in China and India include Boswellia carterii or Boswellia serrata. They both contain boswellic acids (BAs) which have been shown to exhibit anti-inflammatory and antiarthritic properties. This study tests the hypothesis that mixtures of BAs derived from B. carterii have immunomodulatory properties. B. carterii plant resin obtained from China was prepared as an ethanol extract, and the presence of seven BAs was confirmed by column chromatography, high-performance liquid chromatography, and UV laser desorption/ionization tandem mass spectroscopy. The extract was then tested for its ability to alter in vitro production of TH1 cytokines (interleukin-2 [IL-2] and gamma interferon) and TH2 cytokines (IL-4 and IL-10) by murine splenocytes. Delivery of the resin extract using ethanol as a solvent resulted in significant cellular toxicity not seen with the addition of ethanol alone. By contrast, delivery of the resin extract using a sesame oil solvent resulted in a dose-dependent inhibition of TH1 cytokines coupled with a dose-dependent potentiation of TH2 cytokines. These results indicate that a purified mixture of BAs from B. carterii plant resin exhibits carrier-dependent immunomodulatory properties in vitro.

  17. The changes of inflammatory cytokines and their clinical significance in patients of inferior ST-segment elevation acute myocardial infarction with anterior ST-segment depression

    Institute of Scientific and Technical Information of China (English)

    叶明

    2014-01-01

    Objective To investigate the level of Hs-CRP,Fib,IL-6,TNF-α,MDA,SOD,and analyze the correlation between the level of plasma inflammatory cytokines and clinical significance in patients with anterior ST-segment depression.Methods We chose 360 patients with inferior ST Segment elavation acute myocardial infarction from May 2007 to Sep 2012 in emergency department of

  18. 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.

  19. Pro- and Anti-Inflammatory Cytokines Release in Mice Injected with Crotalus durissus terrificus Venom

    Directory of Open Access Journals (Sweden)

    A. Hernández Cruz

    2008-01-01

    Full Text Available The effects of Crotalus durissus terrificus venom (Cdt were analyzed with respect to the susceptibility and the inflammatory mediators in an experimental model of severe envenomation. BALB/c female mice injected intraperitoneally presented sensibility to Cdt, with changes in specific signs, blood biochemical and inflammatory mediators. The venom induced reduction of glucose and urea levels and an increment of creatinine levels in serum from mice. Significant differences were observed in the time-course of mediator levels in sera from mice injected with Cdt. The maximum levels of IL-6, NO, IL-5, TNF, IL-4 and IL-10 were observed 15 min, 30 min, 1, 2 and 4 hours post-injection, respectively. No difference was observed for levels of IFN-γ. Taken together, these data indicate that the envenomation by Cdt is regulated both pro- and anti-inflammatory cytokine responses at time-dependent manner. In serum from mice injected with Cdt at the two first hours revealed of pro-inflammatory dominance. However, with an increment of time an increase of anti-inflammatory cytokines was observed and the balance toward to anti-inflammatory dominance. In conclusion, the observation that Cdt affects the production of pro- and anti-inflammatory cytokines provides further evidence for the role played by Cdt in modulating pro/anti-inflammatory cytokine balance.

  20. Leptin enhances the release of cytokines by peripheral blood mononuclear cells from acute multiple sclerosis patients

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Objective To explore the effect of leptin on cytokine production by PBMCs obtained from MS patients either in acute (relapse) or in stable (nonrelapse) phase of disease. Methods PBMCs were collected from 25 untreated acute MS patients, 11 stable MS patients and 20 healthy controls. PBMCs were cultured either with RPMI-1640 alone or with leptin (1.25 nmol/ml), phytohemagglutinin (PHA) ( 100 μg/ml), and leptin + PHA. 72 h later the supernate of the culture medium were collected and stored at -70℃. The pro-inflammatory cytokine (IFN-γ) concentration were determined using an enzyme-linked immunosorbent assay ( ELISA), and the anti-inflammatory cytokine (IL-4) concentration were investigated by radioimmunity methods. Results Our data showed that leptin induced IFN-γproduction by PBMCs of patients in an acute phase of disease but not in a stable phase or in healthy controls. Moreover, we found that PHA induced IL-4 production by PBMCs of patients in an acute phase of disease, but leptin inhibited this ability of PHA. Conclusion Leptin can affect on pro- and anti-inflammatory cytokine production by PBMCs collected from MS patients, may be this connected with leptin increase the susceptiveness of MS.

  1. Th1/Th2 cytokines and their genotypes as predictors ofhepatitis B virus related hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Hepatocellular carcinoma (HCC), the predominant typeof primary liver cancer, is one of the most serious lifethreateningmalignancies, worldwide. In majority ofthe cases, HCC develops after prolonged and persistentchronic liver disease. hepatitis B virus (HBV) or HCVinfection is prominent etiological factors, attributing to this condition. It has been well documented that HBV,being the inducer of chronic inflammation, is the maincausative agent in causing HCC, particularly in Asiancountries. The HBV infection leads to a wide range ofclinical symptoms from carrier state to malignancy.Cytokines being immune-modulatory molecules, arethe key mediators in the defense mechanism againstviral infection. In this regard, this review will detail thesubstantial role of key Th1: interleukin 1 (IL-1), IL-2,IL-12, tumor necrosis factor-α, interferon-γ; Th2: IL-4,IL-10 and non Th1/Th2: IL-6, transforming growthfactor-β1 cytokines genotypes in analyzing the variabilityin the clinical manifestations in an HBV-afflicted individual,which might finally, culminates into HCC. Since cytokineproduction is regulated genetically, the cytokine promoterregion single-nucleotide polymorphisms induced changes,greatly affects the cytokine production, thus resulting intodifferential outcome of immune balance.

  2. Impaired Cytokine Responses to Epstein-Barr Virus Antigens in Systemic Lupus Erythematosus Patients

    Directory of Open Access Journals (Sweden)

    Anette Holck Draborg

    2016-01-01

    Full Text Available We analyzed cytokine responses against latent and lytic Epstein-Barr virus (EBV antigens in systemic lupus erythematosus (SLE patients and healthy controls (HCs to obtain an overview of the distinctive immune regulatory response in SLE patients and to expand the previously determined impaired EBV-directed T-cell response. The concentrations of 14 cytokines (IL2, IL4, IL5, IL6, IL10, IL12, IL17, IL18, IL1β, IFNγ, TNFα, TNFβ, TGFβ, and GM-CSF were quantified upon stimulation of whole blood with latent state antigen EBNA1, lytic cycle antigen EBV-EA/D, and the superantigen SEB. To avoid results affected by lack of lymphocytes, we focused on SLE patients with normal levels. Decreased induction of IL12, IFNγ, IL17, and IL6 upon EBNA1 stimulation and that of IFNγ, IL6, TNFβ, IL1β, and GM-CSF upon EBV-EA/D stimulation were detected in SLE patients compared to HCs. IFNγ responses, especially, were shown to be reduced. Induction of several cytokines was furthermore impaired in SLE patients upon SEB stimulation, but no difference was observed in basic levels. Results substantiate the previously proposed impaired regulation of the immune response against latent and lytic cycle EBV infection in SLE patients without lymphopenia. Furthermore, results indicate general dysfunction of leukocytes and their cytokine regulations in SLE patients.

  3. Changes in proinflammatory cytokines and white matter in chronically stressed rats

    Directory of Open Access Journals (Sweden)

    Yang P

    2015-03-01

    Full Text Available Ping Yang,1 Zhenyong Gao,1 Handi Zhang,1 Zeman Fang,1 Cairu Wu,1 Haiyun Xu,1,2 Qing-Jun Huang1 1Mental Health Center, 2Department of Anatomy, Shantou University Medical College, Shantou, Guangdong, People’s Republic of China Abstract: Although the pathogenesis of depression, an incapacitating psychiatric ailment, remains largely unknown, previous human and animal studies have suggested that both proinflammatory cytokines and altered oligodendrocytes play important roles in the condition. This study examined these two factors in the brains of rats following unpredictable chronic mild stress for 4 weeks, with the hypothesis that chronic stress may affect oligodendrocytes and elevate proinflammatory cytokines in the brain. After suffering unpredictable stressors for 4 weeks, the rats showed depression-like behaviors, including decreased locomotion in the open field, increased immobility time in the forced swim test, and decreased sucrose consumption and less sucrose preference when compared with controls. Immunohi