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

    The aim of this study was to investigate to what extent single nucleotide polymorphisms (SNPs) in promoter regions of genes of Toll-like receptor (TLR)-4, tumour necrosis factor (TNF)-alpha, interleukin (IL)-18, interferon (IFN)-gamma, IL-6 and IL-10 affect the cytokine response during a controlled......-607, IFN-gamma+874, IL-6-174, IL-10-592 and IL-10-1082) and endotoxin-induced changes in plasma levels of TNF-alpha, IL-6 and IL-10. IL-18 levels were unaffected by endotoxin. In conclusion, the investigated SNPs did not affect endotoxin-induced low-grade cytokine production of TNF-alpha, IL-6, IL-18 or IL...

  2. 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...... months later plasma levels of interleukin 1 beta (IL-1beta), tumor necrosis factor alpha (TNF-alpha), interleukin-1 receptor antagonist (IL-1RA), interleukin 6 (IL-6), interleukin 10 (IL-10), soluble tumor necrosis factor receptor 1 (sTNF-R1), and soluble tumor necrosis factor receptor 2 (sTNF-R2) were...

  3. 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.

  4. 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 Korsbæk Connor; Poulsen, Anne Havemose; 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...

  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 (IL6...... with systolic blood pressure, whereas CRP associated positively with diastolic blood pressure and body mass index. CRP was an independent AAA risk factor and correlated positively with aortic diameters before and after adjustments for other risk factors. IFN-γ, IL17A, and CRP correlated positively with cross...

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

    OpenAIRE

    Binyao Yang; Qifei Deng; Wangzhen Zhang; Yingying Feng; Xiayun Dai; Wei Feng; Xiaosheng He; Suli Huang; Xiao Zhang; Xiaohai Li; Dafeng Lin; Meian He; Huan Guo; Huizhen Sun; Jing Yuan

    2016-01-01

    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, an...

  7. 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.

  8. 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.

  9. Severe Traumatic Head Injury Affects Systemic Cytokine Expression

    Science.gov (United States)

    LaPar, Damien J; Rosenberger, Laura H; Walters, Dustin M; Hedrick, Traci L; Swenson, Brian R; Young, Jeffrey S; Dossett, Lesly A; May, Addison K; Sawyer, Robert G

    2012-01-01

    Background The neuroimmunologic effect of traumatic head injury remains ill-defined. This study aimed to characterize systemic cytokine profiles among traumatically injured patients to assess the effect of traumatic head injury on the systemic inflammatory response. Study Design Over five years, 1,022 patients were evaluated from a multi-institutional trauma immunomodulatory database (TIMD). Patients were stratified by presence of severe head injury (SHI, Head ISS ≥ 4, n=335) versus non-severe head injury (NHI, Head ISS ≤ 3, n=687). Systemic cytokine expression was quantified by ELISA within 72 hours of admission. Patient factors, outcomes, and cytokine profiles were compared by univariate analyses. Results SHI patients were more severely injured with higher mortality despite similar ICU infection and ventilator associated pneumonia (VAP) rates. Expression of early pro-inflammatory cytokines, IL-6 (p<0.001) and tumor necrosis factor (TNF)-α (p=0.02), were higher among NHI patients, while expression of immunomodulatory cytokines, interferon-γ (p=0.01) and IL-12 (p=0.003), was higher in SHI patients. High TNF-α levels in NHI patients were associated with mortality (p=0.01), increased mechanical ventilation (p=0.02), and development of VAP (p=0.01). Alternatively, among SHI patients, high IL-2 levels were associated with survival, decreased mechanical ventilation, and absence of VAP. Conclusions The presence of severe traumatic head injury significantly alters systemic cytokine expression and exerts an immunomodulatory effect. Early recognition of these profiles may allow for targeted intervention to reduce patient morbidity and mortality. PMID:22342787

  10. 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.

  11. Plasma Levels of the Anti-inflammatory Cytokine IL-10 and Inflammatory Cytokine IL-6 in Patients with Unstable Angina

    Institute of Scientific and Technical Information of China (English)

    HONG Mei; WEI Wenning; HU Yu; YANG Rui; YANG Yan

    2005-01-01

    The plasma levels of inflammatory cytokine interleukin-6 (IL-6) and anti-inflammatory cytokine interleukin-10 (IL-10) in the patients with unstable angina or stable angina were determined and compared. In 30 patients with unstable angina and 22 patients with stable angina, plasma levels of IL-10 and IL-6 were detected by ELISA and plasma lipid parameters by lipid research clinical methods respectively. The results showed plasma levels of IL-10 were significantly lower in unstable angina group than in stable angina group (P=0. 005), while those of IL-6 were significantly increased in unstable angina group as compared with those in stable angina group (P = 0. 039).There was a significantly negative correlation between IL-10 and IL-6 in patients with unstable angina (r=-0.41, P=0. 003). In the unstable angina group, IL-6 levels were obviously positively correlated with TC (r=0. 314, P=0. 023), but not with TG and HDL. There were no significant correlations between IL-10 and plasma lipid parameters. It was suggested that the decreased IL-10and increased IL-6 might be associated with the atheromatous plaque stability and progression of coronary heart diseases. IL-10 may play an important role in preventing coronary vascular lesions.

  12. 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...... poorly reflected mRNA expression of the pro- and anti-inflammatory cytokines....... increase in OI and increased plasma IL-8 and IL-10 concentrations in the CPB-pigs compared with the sham-pigs. Conclusion: The cytokine mRNA expression pattern was very different for the pigs killed already 0.5 h after the CPB procedure compared with the pigs killed 4 h post-CPB. The plasma cytokine levels...

  13. 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

    2016-01-01

    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 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. PMID:26758679

  14. 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. PMID:26950533

  15. 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

    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......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......)-alpha, interleukin (IL)-6, IL-8, monocyte chemotactic protein (MCP)-1, IL-10, and IL-1 receptor antagonist; plasma HIV RNA; hemoglobin concentration; and white blood cells were measured in 229 HIV-infected, 54 HIV-uninfected, and after 2 and 4 months, respectively, of ART in 35 eligible individuals in northeastern...

  16. 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...

  17. 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.

  18. 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.

  19. 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.

  20. Cytokines and migraine: increase of IL-5 and IL-4 plasma levels.

    Science.gov (United States)

    Munno, I; Centonze, V; Marinaro, M; Bassi, A; Lacedra, G; Causarano, V; Nardelli, P; Cassiano, M A; Albano, O

    1998-06-01

    Thirty-two patients suffering from migraine without aura were assessed during in interictal period to evaluate the contribution of cytokines to the pathophysiology of migraine. To this end, plasma levels of IFN-gamma, IL-4, IL-5, and IL-10 were measured by enzyme-linked immunosorbent assay (ELISA) techniques. Plasma levels of both IFN-gamma and IL-10 were not increased in the patients and did not differ significantly from healthy controls. Of interest, we observed a strong increase of IL-5 levels in 84.3% as well as increased IL-4 levels in 37.5% of patients with migraine without aura. These results suggests a preferential enhancement of some Th2-type cytokines, and may support the growing arguments of an immunoallergic mechanism in the pathophysiology of migraine. PMID:9664752

  1. 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

  2. Association of plasma endotoxin, inflammatory cytokines and risk of colorectal adenomas

    International Nuclear Information System (INIS)

    Recent studies suggest that bacterial endotoxins may be associated with various chronic diseases, including colorectal adenomas and cancer. Given the evidence linking inflammation and colorectal cancer, we sought to determine if plasma endotoxin concentrations are associated with indicators of systemic or local inflammation and colorectal adenomas. This cross-sectional study consisted of participants who underwent screening colonoscopies and included adenoma cases (n=138) and non-adenoma controls (n=324). Plasma concentrations of endotoxin were measured with Limulus Amebocyte Lysate (LAL) assay. We quantified concentrations of inflammatory cytokines, interleukin-4 (IL-4), IL-6, IL-8, IL-10, IL-12, tumor necrosis factor-alpha (TNF-α), and interferon-γ (IFN-γ) in plasma by ELISA and mRNA expression levels in rectal mucosal biopsies by quantitative RT-PCR. Interleukin-17 was evaluated only in the rectal mucosa. Compared to subjects with low plasma endotoxin concentrations, those with higher concentrations were more likely to have adenomas (OR 1.4, 95% CI 1.0-2.1). Among subjects with adenomas, those with villous histology were more likely to have higher endotoxin concentrations (5.4 vs. 4.1EU/mL, p=0.05) and lower plasma IFN-γ (0 vs. 1.64 pg/mL, p=0.02) compared to those with only tubular adenomas. Cases showed a trend of having higher plasma TNF-α levels than controls (p=0.06), but none of the other plasma or rectal mucosal cytokine levels differed between cases and controls. Elevated mucosal IL-12 levels were associated with having multiple adenomas (p=0.04). Higher concentrations of plasma endotoxin predicted increased plasma IL-12 levels (OR 1.5, 95% CI 1.0-2.2) and rectal mucosal IL-12 (OR 1.9, 95% CI 1.0-3.7) and IL-17 gene expression (OR 2.2, 95% CI 1.0-4.6). These findings suggest that interactions between elevated plasma endotoxin concentrations and inflammatory cytokines may be relevant to the development of colorectal adenomas

  3. 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.

  4. Impact of HIV co-infection on plasma level of cytokines and chemokines of pulmonary tuberculosis patients

    OpenAIRE

    Mihret, Adane; Abebe, Markos; Bekele, Yonas; Aseffa, Abraham; Walzl, Gerhard; Howe, Rawleigh

    2014-01-01

    Background The immunologic environment during HIV/M. tuberculosis co-infection is characterized by cytokine and chemokine irregularities that have been shown to increase immune activation, viral replication, and T cell dysfunction. Methods We analysed ex vivo plasma samples from 17 HIV negative and 16 HIV pulmonary tuberculosis co infected cases using Luminex assay to see impact of HIV co-infection on plasma level of cytokines and chemokines of pulmonary tuberculosis patients before and after...

  5. 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.

  6. Docosahexaenoic diet supplementation, exercise and temperature affect cytokine production by lipopolysaccharide-stimulated mononuclear cells.

    Science.gov (United States)

    Capó, Xavier; Martorell, Miquel; Sureda, Antoni; Batle, Juan Miguel; Tur, Josep Antoni; Pons, Antoni

    2016-09-01

    Acute exercise induces changes in peripheral mononuclear cells' (PBMCs) capabilities to produce cytokines. The aim was to investigate the effect of docosahexaenoic acid (DHA) diet supplementation on cytokine production, by lipopolysaccharide (LPS)-stimulated PBMCs after exercise, and the in vitro influence of temperature. Fifteen male soccer players were randomly assigned to a placebo or an experimental group. The experimental group consumed an almond-based beverage enriched with DHA (1.16 g DHA/day) for 8 weeks, whereas the placebo group consumed a similar non-enriched beverage. Blood samples were taken before and after the nutritional intervention in basal conditions and 2 h after acute exercise. Nutritional intervention significantly increased the DHA content in erythrocytes only in experimental group (from 34 ± 3.6 to 43 ± 3.6 nmols DHA/10(9) erythrocytes). Exercise significantly increased Toll-like receptor 4 (TLR4) in PBMCs but only in the placebo group (203 %). Exercise also significantly increased IL6, IL8, VEGF, INFγ, TNFα, IL1α, IL1β, MCP1, and EGG production rates by LPS-stimulated PBMCs, and this response was attenuated by DHA supplementation. Temperature but not DHA also affected the pattern of cytokine production increasing IL6, IL8, IL1β, and MCP1 synthesis. The higher change was evidenced in IL1β increasing the production rate at 39.5 °C from 3.19 ± 0.77 to 22.4 ± 6.1 pg/h 10(6) PBMC in placebo and from 2.36 ± 0.11 to 10.6 ± 0.38 pg/h 10(6) PBMC in the supplemented group. The profile of affected cytokines differs between temperature and exercise, suggesting a different PBMC activation pathway. DHA diet supplementation only attenuated cytokine production after exercise and not that induced by temperature. PMID:27139422

  7. 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.

  8. 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

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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

    2015-06-01

    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. PMID:26035492

  14. 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.

  15. Cytokine-mediated regulation of plasma cell generation: IL-21 takes center stage

    Directory of Open Access Journals (Sweden)

    Stuart G Tangye

    2014-02-01

    Full Text Available During our life we are surrounded by continuous threats from a diverse range of invading pathogens. Our immune system has evolved multiple mechanisms to efficiently deal with these threats to prevent them causing disease. Differentiation of mature B cells into plasma cells (PC - the antibody (Ab secreting cells of the immune system - is critical for the generation of protective and long-lived humoral immune responses. Indeed, efficient production of antigen (Ag-specific Ab underlies the success of most currently available vaccines. The mature B cell pool is composed of several subsets, distinguished from one according to size, surface marker expression, location and Ag exposure, and they all have the capacity to differentiate into PCs. For a B cell to acquire the capacity to produce Abs, it must undergo an extensive differentiation process driven by changes in gene expression. Two broad categories of Ag exist that cause B cell activation and differentiation: T cell dependent (TD or T cell independent (TI. In addition to the B cell subset and nature of the Ag, it is important to consider the cytokine environment that also influences how B cell differentiation is achieved. Thus, while many cytokines can induce Ab secretion by B cells after activation with mimics of TD and TI stimuli in vitro, they can have different efficacies and specificities, and can often preferentially induce production of one Ig isotype over another. Here, we will provide an overview of in vitro studies (mouse and human origin that evaluated the role the different cytokines in inducing the differentiation of distinct B cell subsets to the PC lineage. We will place particular emphasis on IL-21, which has emerged as the most potent inducer of terminal B cell differentiation in humans. We will also focus on the role of IL-21 and defects in B-cell function and how these contribute to human immunopathologies such as primary immunodeficiencies and B-cell mediated autoimmune

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

    Directory of Open Access Journals (Sweden)

    Aline S Bossa

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

  17. 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

  18. A bioplex analysis of cytokines and chemokines in first trimester maternal plasma to screen for predictors of miscarriage.

    Directory of Open Access Journals (Sweden)

    Natalie J Hannan

    Full Text Available BACKGROUND: We have previously shown in two independent cohorts that circulating first trimester Macrophage Inhibitory Cytokine-1 (MIC-1 levels are lower in women in early pregnancy who are destined to miscarriage. While promising, the diagnostic performance of measuring MIC-1 alone was not sufficient for it to be a useful predictive test for miscarriage. Besides MIC-1, there are other cytokines, as well as chemokines, involved in facilitating early pregnancy. We reasoned that screening these factors in maternal plasma could uncover other predictive markers of miscarriage. METHODS: This was a nested case control study, of 78 women from a prospective study of 462 attending the Early Pregnancy Assessment Unit in the first trimester (EPAU with a threatened miscarriage; 34 of these subsequently miscarried (cases and 44 went on to have a normal delivery (controls Cytokines IL-1β, IL-6 and IL-10, and the chemokines, CXCL8, CCL2, CCL5, CCL7 and CX3CL1 were measured in plasma from our cohort. RESULTS: The cytokines IL-1β, IL-6, IL-10 and the chemokine CXCL8 were not detectable in first trimester plasma. The chemokines CCL2, CCL5, CCL7 and CX3CL1 were detectable in all samples but levels did not vary across 5-12 weeks of gestation among controls. Plasma levels of these chemokines were no different in the miscarriage cohort compared to controls. CONCLUSION: The chemokines CCL2, CCL5, CCL7 and CX3CL1 were detectable in plasma during the first trimester while IL-1β, IL-6, IL-10 and CXCL8 were not. However, none of the cytokines and chemokines screened were different in maternal plasma in cases or controls. These therefore do not appear to have potential for application as predictive biomarkers of miscarriage.

  19. 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....

  20. 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)

  1. 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 (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.

  2. 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.

  3. 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

  4. 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.......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....

  5. 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)

  6. 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. PMID:27177966

  7. Plasma cytokine concentrations in workers exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD

    Directory of Open Access Journals (Sweden)

    Fatemeh eSaberi Hosnijeh

    2012-04-01

    Full Text Available ObjectivesFew 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 occupationally exposed to chlorophenoxy herbicides and contaminants including TCDD.MethodsEighty-five workers who had been exposed to either high (n=47 or low (n=38 TCDD levels more than 30 years before serum collection were included in the current investigation. Plasma level of 16 cytokines, 10 chemokines and 6 growth factors were measured. Current plasma levels of TCDD (TCDDCurrent were determined by high resolution gas chromatography/isotope dilution high resolution mass spectrometry. TCDD blood levels at the time of last exposure (TCDDmax were estimated using a one-compartment first order kinetic model. ResultsBlood levels of most analytes had a negative association with current and estimated past maximum TCDD levels. These decreases reached formal statistical significance for fractalkine, transforming growth factor alpha (TGF-α and fibroblast growth factor 2 (FGF2 with increasing TCDD levels.ConclusionsOur study showed a general reduction in most analyte levels with the strongest effects for fractalkine, FGF2 and TGF-α. These findings suggest that TCDD exposure could suppress the immune system and that chemokine and growth factor-dependent cellular pathway changes by TCDD may play role in TCDD toxicity and associated health effects.

  8. 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.

  9. 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.

  10. 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.

  11. Evaluation of Plasma Cytokine Levels in Mesobuthus Eupeus (Scorpionida: Buthidae Scorpion Envenomation in Rats Treated With Polyvalent Antivenom

    Directory of Open Access Journals (Sweden)

    Razi Jalali

    2015-01-01

    Full Text Available Background Previous studies have demonstrated that scorpion venom increases blood levels of some cytokines, including Interleukin-1 (IL-1, Interleukin-6 (IL-6, and Tumor Necrosis Factor-alpha (TNF-α in experimental model of scorpion envenomation in laboratory animals. Objectives This study aimed to measure circulating cytokines levels in rats after envenomation with Mesobuthus Eupeus scorpion and to compare the findings in rats treated with polyvalent antivenom to evaluate the role of routine treatment in scorpion envenomation. Materials and Methods For the present research, the venom of Mesobuthus eupeus scorpion was extracted by electric shock and then intraperitoneally injected (1.5 mg/kg into 2 groups (V: venom group and AV: antivenom group of 36 Wistar rats each weighing 200 ± 10 g. Additional 36 rats were considered as control group (group C and were intraperitoneally (ip injected with 50 μL saline solution. Group AV were injected ip, with polyvalent antivenom 2.5 ml/kg, 30 minutes after envenomation. Heparinized blood samples were collected by heart puncture at different time periods (1, 3, 6, 12, 24, 48, and 72 hours after venom injection for determination of the levels of plasma cytokines, including IL-1α, IL-6, and TNF-α by Ray Biotech specific ELISA kits for rats. Results IL-1a, IL-6, and TNF-α levels were significantly increased in 3 hours after envenomation in both groups (V and AV, but the intensity of increase in AV group was less than the other group, i.e. moderate elevation of cytokines occurred after treatment with polyvalent antivenom. At next time points, gradually decreasing amounts of cytokines were seen. Conclusions Our data suggest that using polyvalent antivenom in short time after envenomation could reduce the inflammatory responses related to the systemic changes during the elevation of cytokines in scorpion envenomation.

  12. Clove (Syzygium aromaticum ingredients affect lymphocyte subtypes expansion and cytokine profile responses: An in vitro evaluation

    Directory of Open Access Journals (Sweden)

    Shaghayegh Pishkhan Dibazar

    2014-12-01

    Full Text Available Clove (Syzygium aromaticum has been used in folk medicine in many disorders. The present work aimed to investigate effects of clove essential oil as eugenol and water soluble ingredients on mouse splenocytes. Clove extracts were harvested and in different concentrations (0.001–1000 μg/mL were affected to splenocytes and also phytohemagglutinin (PHA = 5 μg/mL and lipopolysaccharide (LPS = 10 μg/mL activated splenocytes; then splenocytes proliferation assayed using the MTT ([3-(4, 5-dimethylthiazole-2-yl -2, 5-diphenyl tetrazolium bromide] method were done. On the culture supernatant interferon (IFN-γ, interleukin (IL-4, IL-10, and transforming growth factor (TGF-β cytokines were measured. Clove ingredients (100 μg/mL and 1000 μg/mL reduced PHA stimulated splenocytes proliferation and enhanced LPS stimulated cells expansion. Treated splenocytes showed suppression of IFN-γ release and induction of IL-4, IL-10, and TGF-β secretion (in the range of 0.1–1000 μg/mL. The results of this study suggest clove extracts could suppress the T cell cellular immunity and enhance humoral immune responses. In clove affection cytokine pattern shifted toward modulatory and Th2 responses and accelerator of humoral immunity cytokines.

  13. Environmental Levels of para-Nonylphenol Are Able to Affect Cytokine Secretion in Human Placenta

    OpenAIRE

    Bechi, Nicoletta; Ietta, Francesca; Romagnoli, Roberta; Jantra, Silke; Cencini, Marco; Galassi, Gianmichele; Serchi, Tommaso; Corsi, Ilaria; Focardi, Silvano; Paulesu, Luana

    2009-01-01

    Background para-Nonylphenol (p-NP) is a metabolite of alkylphenols widely used in the chemical industry and manufacturing. It accumulates in the environment, where it acts with estrogen-like activity. We previously showed that p-NP acts on human placenta by inducing trophoblast differentiation and apoptosis. Objective The aim of the present study was to investigate the effect of p-NP on cytokine secretion in human placenta. Methods In vitro cultures of chorionic villous explants from human pl...

  14. 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 < or =.045) but decreased 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.

  15. Anticoagulants used in plasma collection affect adipokine multiplexed measurements.

    Science.gov (United States)

    Allione, Alessandra; Di Gaetano, Cornelia; Dani, Nadia; Barberio, Davide; Sieri, Sabina; Krogh, Vittorio; Matullo, Giuseppe

    2016-04-01

    Obesity is an important health problem worldwide. Adipose tissue acts as an endocrine organ that secretes various bioactive substances, called adipokines, including pro-inflammatory biomarkers such as TNF-α, IL-6, leptin and C-reactive protein (CRP) and anti-inflammatory molecules such as adiponectin. The deregulated production of adipokines in obesity is linked to the pathogenesis of various disease processes and monitoring their variation is critical to understand metabolic diseases. The aim of this study was to determine the plasma concentration of adipokines in healthy subjects by multiplexed measurements and the effect of anticoagulants on their levels. Plasma samples from 10 healthy donors were collected in two different anticoagulants (sodium citrate or heparin). All markers, excluding TNF-α, showed significantly higher concentrations in heparinized compared to citrate plasma. However, levels of adipokines in different plasma samples were highly correlated for most of these markers. We reported that different anticoagulants used in the preparation of the plasma samples affected the measurements of some adipokines. The importance of the present results in epidemiology is relevant when comparing different studies in which blood samples were collected with different anticoagulants. PMID:26945995

  16. Twelve-Month Antiretroviral Therapy Suppresses Plasma and Genital Viral Loads but Fails to Alter Genital Levels of Cytokines, in a Cohort of HIV-Infected Rwandan Women.

    Directory of Open Access Journals (Sweden)

    Pascale Ondoa

    Full Text Available Genital viral load (GVL is the main determinant of sexual transmission of human immune-deficiency virus (HIV. The effect of antiretroviral therapy (ART on local cervico-vaginal immunological factors associated with GVL is poorly described. We aimed to identify the risk factors of detectable GVL, and the impact of ART on HIV genital shedding and its correlates in a cohort of HIV-infected women, attending HIV care in Kigali, Rwanda.All participants were evaluated for GVL, plasma viral load (PVL, CD4 count, various sexually-transmitted infections (STIs at baseline and at month 12. Genital concentration of 19 cytokines and mRNA expression of APOBEC3G and BST2, two host HIV restriction factors, were evaluated at baseline in all participants. Cytokine levels were re-assessed at month 12 only in participants eligible for ART at baseline. Risk factors of GVL ≥ 40 copies/mL at baseline and month 12 were assessed using logistic regression. Effect of 12-month ART on various local and systemic immunological parameters was examined using a paired t-test and McNemar as appropriate.96 of the 247 women enrolled in the study were eligible for ART. After 12 months of ART, PVL and GVL decreased to undetectable level in respectively 74 and 88% of treated participants. ART did not affect cytokine levels. HIV genital shedding occurred only when PVL was detectable. At baseline, GVL was independently associated with IL-1β after controlling for PVL, age and N. gonorrhea infection (95% CI 1.32-2.15 and at month 12 with MIP-1β (95% CI 0.96-21.32 after controlling for baseline GVL, PVL and month 12 IL-8.Suppressive ART does not necessarily reduce genital level of immune activation. Minimizing all conditions favoring genital inflammation, including active detection and treatment of STIs, might reduce the risk of HIV transmission as supplement to the provision of potent ART.

  17. 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

  18. 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.

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

    Science.gov (United States)

    Bravenboer, Nathalie

    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 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.

  20. 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).

  1. 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.

  2. An Onion Byproduct Affects Plasma Lipids in Healthy Rats

    DEFF Research Database (Denmark)

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

    2010-01-01

    Onion may contribute to the health effects associated with high fruit and vegetable consumption. A considerable amount of onion production ends up as waste that might find use in foods. Onion byproduct has not yet been explored for potential health benefits. The aim of this study is to elucidate...... the safety and potential role of onion byproducts in affecting risk markers of cardiovascular disease (CVD). For that purpose, the effects of an onion byproduct, Allium cepa L. cepa 'Recas' (OBP), and its two derived fractions, an ethanolic extract (OE) and a residue (OR), on the distribution of plasma...

  3. Rapid formation of plasma protein corona critically affects nanoparticle pathophysiology

    Science.gov (United States)

    Tenzer, Stefan; Docter, Dominic; Kuharev, Jörg; Musyanovych, Anna; Fetz, Verena; Hecht, Rouven; Schlenk, Florian; Fischer, Dagmar; Kiouptsi, Klytaimnistra; Reinhardt, Christoph; Landfester, Katharina; Schild, Hansjörg; Maskos, Michael; Knauer, Shirley K.; Stauber, Roland H.

    2013-10-01

    In biological fluids, proteins bind to the surface of nanoparticles to form a coating known as the protein corona, which can critically affect the interaction of the nanoparticles with living systems. As physiological systems are highly dynamic, it is important to obtain a time-resolved knowledge of protein-corona formation, development and biological relevancy. Here we show that label-free snapshot proteomics can be used to obtain quantitative time-resolved profiles of human plasma coronas formed on silica and polystyrene nanoparticles of various size and surface functionalization. Complex time- and nanoparticle-specific coronas, which comprise almost 300 different proteins, were found to form rapidly (<0.5 minutes) and, over time, to change significantly in terms of the amount of bound protein, but not in composition. Rapid corona formation is found to affect haemolysis, thrombocyte activation, nanoparticle uptake and endothelial cell death at an early exposure time.

  4. 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.

  5. 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.

  6. 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...... 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...... of the present study was to screen for a broader spectrum of growth factors and inflammatory mediators and to compare the profiles in different subtypes of NHL in pediatric patients. Serum samples were collected at diagnosis from 31 pediatric patients diagnosed with NHL admitted at Rigshospitalet, Copenhagen...

  7. 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

  8. Kinetics of selected plasma cytokines during innate-adaptive immune response transition in adult cattle infected with the bovine ephemeral fever virus.

    Science.gov (United States)

    Barigye, R; Melville, L F; Davis, S; Walsh, S; Hunt, N; Hunt, R

    2016-04-15

    While virus neutralizing antibodies are known to be variably protective against bovine ephemeral fever (BEF) virus (BEFV) infections, the cytokine events that mediate the nascent adaptive immune response have not been defined in cattle. This study determined the plasma kinetics of IL-2, IFN-γ, IL-6, and IL-10 during the period of innate-immune response transition and evaluated the relationship between the virus neutralizing antibody response and viraemia in BEFV-infected cattle. Plasma from four virus-infected and uninfected negative control animals was tested by cytokine-specific immunoenzymatic assays, viraemia monitored by qRT-PCR, and virus neutralizing antibody titres determined using a standard protocol. Unlike the negative controls, plasma IL-6 and IL-10 were increased in all the virus-infected animals starting several days prior to initiation of viraemia. In one animal, plasma IL-2 and IFN-γ were consistently higher than in the other three virus-infected animals and the negative control mean. The animal with the strongest IL-2 and IFN-γ responses had the shortest viraemia while the heifer with the lowest IL-2/IFN-γ indices demonstrated the longest viraemia. Evidently, increase in plasma IL-6 and IL-10 precedes seroconversion during BEFV infections in cattle suggesting the two cytokines may influence immunological events that pave way to B-cell activation and seroconversion. While there is remarkable variability in IL-2 and IFN-γ expression amongst BEFV-infected animals, increased plasma levels of the two cytokines appear to be associated with a shorter viraemia. Ongoing studies will help define the precise role of T cells in anti-BEFV adaptive immune responses. PMID:27016765

  9. 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.

  10. 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. PMID:23255060

  11. 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.

  12. 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

  13. 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

  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. 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...... METHODS: The microsphere-based Luminex platform was used. Recombinant forms of human IL-1α, IL-6, IL-10, GM-CSF, and IFNα were gently coupled to MAG-PLEX beads. Plasma IgG binding was measured with phycoerythrin (PE)-labeled secondary antibodies. Previously confirmed c-aAb positive and negative donor...

  16. 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.

  17. MicroRNA-155 may affect allograft survival by regulating the expression of suppressor of cytokine signaling 1.

    Science.gov (United States)

    Zhang, Maomao; Zhang, Qi; Liu, Fang; Yin, Li; Yu, Bo; Wu, Jian

    2011-10-01

    Immune rejection of organ transplants has life-threatening implications. It is believed that allograft rejection is initiated by the activation of lymphocytes following recognition of donor antigens, leading to generation of effector T lymphocytes, alloantibody production, and graft infiltration by alloreactive cells. There is solid evidence that miRNAs are integral for maintaining immune homeostasis and self-tolerance. A deeper understanding of the regulation of the immune response by miRNAs could define new mechanisms for manipulating graft immunity and preventing rejection. The miRNA miR-155 is of particular interest due to its known roles in regulating the expression of genes relevant to allograft rejection and the induction of immune tolerance. Indeed, miR-155 has been shown to dramatically impact both innate and adaptive immune processes, including inflammation, antigen presentation, T-cell differentiation, cytokine production, and T regulatory cell (Treg) functions. The suppressor of cytokine signaling 1 (SOCS1) is a critical regulator of immune cell function and an evolutionarily conserved target of miR-155 in breast cancer cells. We propose that suppression of miR-155 could enhance SOCS1 expression in immune cells and suppress allograft rejection. Further studies on the specific role of miR-155 in allograft rejection may lead to the identification of new targets for therapeutic intervention. PMID:21802214

  18. Feeding a high dosage of zinc oxide affects suppressor of cytokine gene expression in Salmonella Typhimurium infected piglets.

    Science.gov (United States)

    Schulte, Jasper N; Brockmann, Gudrun A; Kreuzer-Redmer, Susanne

    2016-10-01

    Suppressor of cytokine signaling (SOCS) proteins play an important role in the regulation of the immune response by inhibiting cytokines. Here we investigated the effects of zinc oxide fed at three different dosages (LZN=57ppm, MZN=167ppm, HZN=2425ppm) to weaned piglets that were or were not orally infected with Salmonella enterica serovar Typhimurium DT 104. We detected higher expression of SOCS3 six days after weaning for all analyzed piglets, regardless of the infection or the zinc feeding, suggesting a stress induced immune response. Whereas, SOCS1 showed only higher transcript amounts in S. Typhimurium infected piglets, especially the LZN group. This might indicate an infection regulating effect of zinc oxide in the infection model. After 42days of infection, the expression of SOCS2, SOCS4, and SOCS7 was increased only in animals fed the highest concentrations of zinc oxide, while non-infected piglets at the age of 56days showed no regulation for these genes. The up-regulation of SOCS genes in the mesenteric lymph nodes of piglets fed a diet with a very high concentration of zinc over 6 weeks suggests that such treatments may impair the immune response. PMID:27496737

  19. Plasma PGE-2 levels and altered cytokine profiles in adherent peripheral blood mononuclear cells in non-small cell lung cancer (NSCLC

    Directory of Open Access Journals (Sweden)

    Hirschowitz Edward A

    2002-11-01

    Full Text Available Abstract Introduction PGE-2 is constitutively produced by many non-small cell lung cancers (NSCLC and its immunosuppressive effects have been linked to altered immune responses in lung cancer. We asked whether elevated levels of plasma PGE-2 correlated with monocyte IL10 production in the NSCLC environment. Looking for correlation in NSCLC patient blood we assayed plasma from NSCLC patients for PGE2 and IL10; we further evaluated production of IL10 by adherent mononuclear cells from a subset of these patients looking for an altered cytokine profile. Results Our initial in vitro experiments show that monocyte IL10 induction correlates with tumor cell PGE-2 production, confirming similar reports in the literature. Data show plasma PGE-2 levels in 38 NSCLC patients are elevated compared to normal controls. Plasma IL10 levels were not significantly elevated; however, adherent monocytes derived from NSCLC patient blood did produce significantly more IL10 in 24 hr primary culture than those from normal controls (p Conclusions Elevated plasma PGE-2 and monocyte IL10 production are associated with NSCLC. The biological significance to elevated PGE-2 levels in NSCLC are unclear. Further investigation of each as a nonspecific marker for NSCLC tumor is warranted.

  20. Blueberry, blackberry, and blackcurrant differentially affect plasma lipids and pro-inflammatory markers in diet-induced obesity mice

    Science.gov (United States)

    Kim, Bohkyung; Lee, Sang Gil; Park, Young-Ki; Ku, Chai Siah; Pham, Tho X.; Wegner, Casey J.; Yang, Yue; Koo, Sung I.; Chun, Ock K.

    2016-01-01

    BACKGROUND/OBJECTIVES Evidence indicates that berry anthocyanins are anti-atherogenic, antioxidant, and anti-inflammatory. However, berries differ vastly in their anthocyanin composition and thus potentially in their biological and metabolic effects. The present study compared hypolipidemic, antioxidant, and anti-inflammatory properties of blueberry (BB), blackberry (BK), and blackcurrant (BC) in a diet-induced obesity (DIO) mouse model. MATERIALS/METHODS Male C57BL/6J mice were fed a high fat (HF; 35% fat, w/w) control diet or a HF diet supplemented with freeze-dried 5% BB, 6.3% BK or 5.7% BC for 12 weeks (10 mice/group) to achieve the same total anthocyanin content in each diet. Plasma lipids, antioxidant status and pro-inflammatory cytokines were measured. The expression of genes involved in antioxidant defense, inflammation, and lipid metabolism was determined in the liver, epididymal adipose tissue, proximal intestine, and skeletal muscle. Histological analysis was performed to identify crown-like structure (CLS) in epididymal fat pads to determine macrophage infiltration. RESULTS No differences were noted between the control and any berry-fed groups in plasma levels of liver enzymes, insulin, glucose, ferric reducing antioxidant power, superoxide dismutase, and tumor necrosis factor α. However, BK significantly lowered plasma triglyceride compared with the HF control and other berries, whereas BC significantly reduced F4/80 mRNA and the number of CLS in the epididymal fat pad, indicative of less macrophage infiltration. CONCLUSIONS The present study provides evidence that BB, BK and BC with varying anthocyanin composition differentially affect plasma lipids and adipose macrophage infiltration in DIO mice, but with no differences in their antioxidant capacity and anti-inflammatory potential.

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

    International Nuclear Information System (INIS)

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

  2. 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.

  3. 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 Phistory 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. PMID:25944351

  4. 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

  5. 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

  6. 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...

  7. 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.

  8. 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

  9. 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])....

  10. 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.

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

    OpenAIRE

    Marina Yazigi Solis; Guilherme Giannini Artioli; Eduardo Montag; Vitor de Salles Painelli; Fábio Lopes Saito; Fernanda Rodrigues Lima; Hamilton Roschel; Bruno Gualano; Antonio Herbert Lancha Junior; Fabiana Braga Benatti

    2014-01-01

    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...

  12. Clove (Syzygium aromaticum) ingredients affect lymphocyte subtypes expansion and cytokine profile responses: An in vitro evaluation

    OpenAIRE

    Shaghayegh Pishkhan Dibazar; Shirin Fateh; Saeed Daneshmandi

    2014-01-01

    Clove (Syzygium aromaticum) has been used in folk medicine in many disorders. The present work aimed to investigate effects of clove essential oil as eugenol and water soluble ingredients on mouse splenocytes. Clove extracts were harvested and in different concentrations (0.001–1000 μg/mL) were affected to splenocytes and also phytohemagglutinin (PHA = 5 μg/mL) and lipopolysaccharide (LPS = 10 μg/mL) activated splenocytes; then splenocytes proliferation assayed using the MTT ([3-(4, 5-dimethy...

  13. 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.

  14. Effects of adacolumn selective leukocytapheresis on plasma cytokines during active disease in patients with active ulcerative colitis

    Institute of Scientific and Technical Information of China (English)

    Hiroyuki Hanai; Yasushi Iwaoka; Akiko Nakamura; Kazuhisa Hirayama; Abby R Saniabadi; Fumitoshi Watanabe; Takayuki Iida; Masami Yamada; Yoshihiko Sato; Ken Takeuchi; Tatsuo Tanaka; Kenji Kondo; Masataka Kikuyama; Yasuhiko Maruyama

    2006-01-01

    AIM: To investigate the relationship between ulcerative colitis (UC) clinical activity index (CAI) and circulating levels of IL-1ra, IL-10, IL-6 and IL-18.METHODS: Blood levels of IL-1ra, IL-10, IL-6 and IL-18 were measured in 31 patients with active UC, the mean CAI was 11.1, ranging from 5-25; and 12 healthy individuals as controls. Patients were given granulocyte and monocyte adsorptive apheresis (GMA) with Adacolumn. Leucocytes which bear the FcyR and complement receptors were adsorbed to the column leucocytapheresis carriers. Each patient could receive up to 11 GMA sessions over 8 wk.RESULTS: We found strong correlations between CAI and IL-10 (r = 0.827, P < 0.001), IL-6 (r = 0.785, P <0.001) and IL-18 (r = 0.791, P < 0.001). IL-1ra was not correlated with CAI. Following GMA therapy, 24 of the 31 patients achieved remission and the levels of all 4 cytokines fell to the levels in healthy controls. Further,blood levels of IL-1ra and IL-10 increased at the column outflow and inflow at 60 min suggesting release from leucocytes that adhered to the carriers.CONCLUSION: Elevated blood levels of IL-6 and IL-18 together with peripheral blood granulocytes and monocytes/macrophages in patients with active UC show activative behaviour and increased survival time can be proinflammatory and the targets of GMA therapy.

  15. The effects of mind-body training on stress reduction, positive affect, and plasma catecholamines.

    Science.gov (United States)

    Jung, Ye-Ha; Kang, Do-Hyung; Jang, Joon Hwan; Park, Hye Yoon; Byun, Min Soo; Kwon, Soo Jin; Jang, Go-Eun; Lee, Ul Soon; An, Seung Chan; Kwon, Jun Soo

    2010-07-26

    This study was designed to assess the association between stress, positive affect and catecholamine levels in meditation and control groups. The meditation group consisted of 67 subjects who regularly engaged in mind-body training of "Brain-Wave Vibration" and the control group consisted of 57 healthy subjects. Plasma catecholamine (norepinephrine (NE), epinephrine (E), and dopamine (DA)) levels were measured, and a modified form of the Stress Response Inventory (SRI-MF) and the Positive Affect and Negative Affect Scale (PANAS) were administered. The meditation group showed higher scores on positive affect (p=.019) and lower scores on stress (pmeditation (p=.031) than in the control group. The control group demonstrated a negative correlation between stress and positive affects (r=-.408, p=.002), whereas this correlation was not observed in the meditation group. The control group showed positive correlations between somatization and NE/E (r=.267, p=.045) and DA/E (r=.271, p=.042) ratios, whereas these correlations did not emerge in the meditation group. In conclusion, these results suggest that meditation as mind-body training is associated with lower stress, higher positive affect and higher plasma DA levels when comparing the meditation group with the control group. Thus, mind-body training may influence stress, positive affect and the sympathetic nervous system including DA activity.

  16. Studies on Factors Affecting Plasma PIVKA-II Levels in Hepatocellular Carcinoma

    OpenAIRE

    Soga, Kenji; Arai, Futoshi; Tsuruya, Takashi; Aikawa, Keiko; Toshima, Muneatsu; Shibasaki, Koichi; Aoyagi, Yutaka

    1993-01-01

    In order to diagnose hepatocellular carcinoma (HCC), plasma levels of protein induced by vitamin K absence or antagonist-II (PIVKA-II) were determined by an enzyme-linked immunosorbent assay (ELISA). Positive reaction was noted in 34 (68%) of 50 patients with HCC, with PIVKA-II serving as an useful tumor marker in the estimation of HCC staging. On the other hand, the administration of vitamin K and the presence of jaundice were found to be important factors that affect plasma PIVKA-II levels....

  17. 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

    OBJECTIVE: To assess the usability of archived plasma and serum by multiplex (Luminex) analysis of circulating proteins (analytes) by evaluating the day to day variation, the effect of several freeze-thaw cycles, and the influence of the media and choice of anticoagulant. METHODS: Nineteen analyt...

  18. 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.

  19. Reflex sympathetic dystrophy: the significance of differing plasma catecholamine concentrations in affected and unaffected limbs.

    Science.gov (United States)

    Drummond, P D; Finch, P M; Smythe, G A

    1991-10-01

    In 26 patients with features of reflex sympathetic dystrophy, venous blood was collected from painful and unaffected limbs. Levels of plasma adrenaline, noradrenaline and its intracellular metabolite, 3,4-dihydroxyphenylethyleneglycol (DHPG), were measured by combined gas chromatography/mass spectrometry. Plasma DHPG was lower on the painful side. Concentration of plasma noradrenaline was also lower on the painful side in patients with widespread allodynia, and in those with hyperhidrosis in the affected hand or foot. These findings do not support the widely held view that autonomic disturbances in reflex sympathetic dystrophy are due to sympathetic overactivity. Rather, they suggest that sweating and changes in peripheral blood flow result from supersensitivity to sympathetic neurotransmitters. After injury, supersensitivity to noradrenaline may also contribute to spontaneous pain and allodynia by disrupting efferent sympathetic modulation of sensation. This would explain why pain and allodynia are relieved by sympathetic blockade, and why noradrenaline rekindles pain in sympathectomized skin. PMID:1933231

  20. Therapeutic control of plasma concentrations and long-term effect of nortriptyline in recurrent affective disorders.

    Science.gov (United States)

    Kragh-Sørensen; Hansen, C E; Baastrup, P C; Hvidberg, E F

    1976-07-01

    Based on the evidence that therapeutic plasma concentration range in fact exists for the tricyclic antidepressant drug, Nortriptyline (range 50-150 ng/ml), three different investigations were under taken in order to clarify some clinical pharmacological problems during long-term treatment with this drug. The possible prophlactic effect of the drug in recurrent affective disorders was specially examined in a group of patients with a high risk of episodes in their unipolar manic-depressive disease. The results highly demonstrate the value of monitoring plasma levels in achieving therapeutic control. Depressive relapses during treatment, for months and years, were only related to therapeutic insufficient plasma levels of the drug. PMID:981330

  1. 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.

  2. 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...

  3. 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 cycling training would be effective in attenuating the probable aggravating effects of intensive cycling training on spermatogenesis and fertility capacity in road cyclists.

  4. 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

  5. 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.

  6. Zinc and copper levels in the plasma of Nubian goat as affected by the physiological status

    International Nuclear Information System (INIS)

    This study is undertaken directed to determine the blood concentration of micro (trace) minerals, particularly zinc (Zn) and copper (Cu), in dairy goats as affected by the different physiological status. Animals selected were the Nubian goats as an important dairy breed in sudan. The animals were divided into eight groups as follows: Young animals (4-6 month old), adult animals (9-12 month old), up to 50 days after first kidding, up to 50 days after second kidding, up to 50 days after third kidding, low yielder, high yielder. Each of the above groups consisted of 5 animals. The analysis was carried by using the spectrophotometer technique and the results revealed that, plasma Zn concentration decreased with increase of age while that of Cu increased with the increase of age. The plasma Zn level showed continuous increase through first pregnancy, after first kidding, after second kidding and after third kidding. It increased in the lactating animals. The plasma Cu concentration fluctuated throughout the groups with different physiological status, it showed the same levels in the pregnant group, up to 50 days after second kidding, and up to 50 days after third kidding groups, while it showed a marked decrease in the group of up to 50 days after first kidding. No significant differences were observed between the low lactating and the high lactating groups. (Author)

  7. 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.

  8. Some factors affecting the dynamics of a plasma-wall interaction simulator

    International Nuclear Information System (INIS)

    Isotope mixing and thermal desorption from samples exposed in a glow discharge apparatus were used to study the factors affecting hydrogen recycle and wall inventory. Conditions were chosen to be similar to those expected at the walls in today's experimental fusion devices. The size and nature of the hydrogen reservoir in the wall after plasma pulses was investigated by thermal desorption techniques. Large amounts of deuterium, i.e., 5 x 1015 D cm-2 remain in the sample 4 min after a single 200 ms plasma pulse. While this result may be explained by a model using bulk diffusion and traps, it is suggested that either a spectrum of desorption energies, or a concentration dependent recombination coefficient, may also be useful in describing the thermal desorption processes. Experiments with various pumping conditions show that readsorption of molecular hydrogen isotopes on the wall should be considered in modeling hydrogen recycle and isotope changeover processes. HD formation without plasmas confirms the role readsorption plays. (orig.)

  9. 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......, and there was no effect of ERT on lymphocyte subsets. The number of CD3+ CD56+ T-cells showed a highly significant negative correlation with femoral and lumbar bone density in untreated women (r = -0.42, p

  10. 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.

  11. 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

    2011-12-01

    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 (Paircraft 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

  12. 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.

  13. Affectivity

    OpenAIRE

    Stenner, Paul; Greco, Monica

    2013-01-01

    The concept of affectivity has assumed central importance in much recent scholarship, and many in the social sciences and humanities now talk of an ‘affective turn’. The concept of affectivity at play in this ‘turn’ remains, however, somewhat vague and slippery. Starting with Silvan Tomkins’ influential theory of affect, this paper will explore the relevance of the general assumptions (or ‘utmost abstractions’) that inform thinking about affectivity. The technological and instrumentalist char...

  14. 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...... be used to monitor the course of these common and potentially life-threatening infections....

  15. Macrophage-stimulating protein differently affects human alveolar macrophages from smoker and non-smoker patients: evaluation of respiratory burst, cytokine release and NF-kappaB pathway.

    Science.gov (United States)

    Gunella, Gabriele; Bardelli, Claudio; Amoruso, Angela; Viano, Ilario; Balbo, Piero; Brunelleschi, Sandra

    2006-06-01

    Macrophage activation is a key feature of inflammatory reactions occurring during bacterial infections, immune responses and tissue injury. We previously demonstrated that human macrophages of different origin express the tyrosine kinase receptor recepteur d'origine nantaise, the human receptor for MSP (RON) and produce superoxide anion (O(2)(-)) when challenged with macrophage-stimulating protein (MSP), the endogenous ligand for RON. This study was aimed to evaluate the role of MSP in alveolar macrophages (AM) isolated from healthy volunteers and patients with interstitial lung diseases (sarcoidosis, idiopathic pulmonary fibrosis), either smokers or non-smokers, by evaluating the respiratory burst, cytokine release and nuclear factor-kappa B (NF-kappaB) activation. MSP effects were compared with those induced by known AM stimuli, for example, phorbol myristate acetate, N-formyl-methionyl-leucyl-phenylalanine, lipopolysaccharide.MSP evokes O(2)(-) production, cytokine release and NF-kappaB activation in a concentration-dependent manner. By evaluating the respiratory burst, we demonstrate a significantly increased O(2)(-) production in AM from healthy smokers or smokers with pulmonary fibrosis, as compared to non-smokers, thus suggesting MSP as an enhancer of cigarette smoke toxicity. Besides inducing interleukin-1 beta (IL-1beta) and interleukin-10 (IL-10) production, MSP triggers an enhanced tumor necrosis factor-alpha release, especially in healthy and pulmonary fibrosis smokers. On the contrary, MSP-induced IL-10 release is higher in AM from healthy non-smokers. MSP activates the transcription factor NF-kappaB; this effect is more potent in healthy and fibrosis smokers (2.5-fold increase in p50 subunit translocation). This effect is receptor-mediated, as it is prevented by a monoclonal anti-human MSP antibody. The higher effectiveness of MSP in AM from healthy smokers and patients with pulmonary fibrosis is suggestive of its role in these clinical conditions

  16. Effect of space flight on cytokine production

    Science.gov (United States)

    Sonnenfeld, Gerald

    Space flight has been shown to alter many immunological responses. Among those affected are the production of cytokines, Cytokines are the messengers of the immune system that facilitate communication among cells that allow the interaction among cells leading to the development of immune responses. Included among the cytokines are the interferons, interleukins, and colony stimulating factors. Cytokines also facilitate communication between the immune system and other body systems, such as the neuroendocrine and musculoskeletal systems. Some cytokines also have direct protective effects on the host, such as interferon, which can inhibit the replication of viruses. Studies in both humans and animals indicate that models of space flight as well as actual space flight alter the production and action of cytokines. Included among these changes are altered interferon production, altered responsiveness of bone marrow cells to granulocyte/monocyte-colony stimulating factor, but no alteration in the production of interleukin-3. This suggests that there are selective effects of space flight on immune responses, i.e. not all cytokines are affected in the same fashion by space flight. Tissue culture studies also suggest that there may be direct effects of space flight on the cells responsible for cytokine production and action. The results of the above study indicate that the effects of space flight on cytokines may be a fundamental mechanism by which space flight not only affects immune responses, but also other biological systems of the human.

  17. 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.

  18. 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. PMID:26248320

  19. 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.

  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. 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

    2016-02-01

    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.

  2. 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.

  3. Vitamin E and omega-3 fatty acids independently attenuate plasma concentrations of proinflammatory cytokines and prostaglandin E3 in Escherichia coli lipopolysaccharide-challenged growing-finishing pigs.

    Science.gov (United States)

    Upadhaya, S D; Kim, J C; Mullan, B P; Pluske, J R; Kim, I H

    2015-06-01

    This study tested the hypothesis that vitamin E (Vit E) and omega-3 fatty acids will additively attenuate the production of proinflammatory cytokines and PGE2 in immune system–stimulated growing–finishing pigs. A total of 80 mixed sex pigs weighing 50.7 ± 0.76 kg (mean ± SE) were blocked and stratified based on sex and BW to a 2 × 2 factorial design with the respective factors being 1) without and with 300 IU Vit E and 2) without and with 25% replacement of tallow to linseed oil as a source of n-3 fatty acids. Each treatment consisted of 4 replicate pens with 5 pigs (3 barrows and 2 gilts) per pen. All pigs were challenged with an intramuscular injection of Escherichia coli lipopolysaccharide (LPS; O111:B4) twice weekly over the 6-wk experiment. After LPS challenge, pigs fed a diet supplemented with n-3 fatty acids had fewer (P fatty acids reduced (P fatty acids; however, the extent of the reduction was greater (P fatty acid–supplemented diet. However, there were no additive effects of the combined supplementation of Vit E and n-3 fatty acids on serum concentrations of proinflammatory cytokines and PGE2. The results suggest that n-3 fatty acids independently attenuate production of TNF-α and PGE2 in immune system–stimulated growing–finishing pigs. PMID:26115279

  4. Cytokines and brain excitability

    OpenAIRE

    Galic, Michael A.; Riazi, Kiarash; Pittman, Quentin J.

    2011-01-01

    Cytokines are molecules secreted by peripheral immune cells, microglia, astrocytes and neurons in the central nervous system. Peripheral or central inflammation is characterized by an upregulation of cytokines and their receptors in the brain. Emerging evidence indicates that pro-inflammatory cytokines modulate brain excitability. Findings from both the clinical literature and from in vivo and in vitro laboratory studies suggest that cytokines can increase seizure susceptibility and may be in...

  5. Plasma taurine levels are not affected by vigabatrin in pediatric patients.

    Science.gov (United States)

    Spelbrink, Emily M; Mabud, Tarub S; Reimer, Richard; Porter, Brenda E

    2016-08-01

    Vigabatrin is a highly effective antiseizure medication, but its use is limited due to concerns about retinal toxicity. One proposed mechanism for this toxicity is vigabatrin-mediated reduction of taurine. Herein we assess plasma taurine levels in a retrospective cohort of children with epilepsy, including a subset receiving vigabatrin. All children who underwent a plasma amino acid analysis as part of their clinical evaluation between 2006 and 2015 at Stanford Children's Health were included in the analysis. There were no significant differences in plasma taurine levels between children taking vigabatrin (n = 16), children taking other anti-seizure medications, and children not taking any anti-seizure medication (n = 556) (analysis of variance [ANOVA] p = 0.841). There were, however, age-dependent decreases in plasma taurine levels. Multiple linear regression revealed no significant association between vigabatrin use and plasma taurine level (p = 0.87) when controlling for age. These results suggest that children taking vigabatrin maintain normal plasma taurine levels, although they leave unanswered whether taurine supplementation is necessary or sufficient to prevent vigabatrin-associated visual field loss. They also indicate that age should be taken into consideration when evaluating taurine levels in young children. PMID:27344989

  6. 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). PMID:23756043

  7. Cytokines and the Skin Barrier

    Directory of Open Access Journals (Sweden)

    Jens Malte Baron

    2013-03-01

    Full Text Available The skin is the largest organ of the human body and builds a barrier to protect us from the harmful environment and also from unregulated loss of water. Keratinocytes form the skin barrier by undergoing a highly complex differentiation process that involves changing their morphology and structural integrity, a process referred to as cornification. Alterations in the epidermal cornification process affect the formation of the skin barrier. Typically, this results in a disturbed barrier, which allows the entry of substances into the skin that are immunologically reactive. This contributes to and promotes inflammatory processes in the skin but also affects other organs. In many common skin diseases, including atopic dermatitis and psoriasis, a defect in the formation of the skin barrier is observed. In these diseases the cytokine composition within the skin is different compared to normal human skin. This is the result of resident skin cells that produce cytokines, but also because additional immune cells are recruited. Many of the cytokines found in defective skin are able to influence various processes of differentiation and cornification. Here we summarize the current knowledge on cytokines and their functions in healthy skin and their contributions to inflammatory skin diseases.

  8. 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

    2016-01-01

    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. PMID:27020850

  9. 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

    2016-01-01

    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. PMID:27020850

  10. HAEMATOLOGICAL VALUES AND PLASMA CHOLESTEROL AS AFFECTED BY MOULTING IN NICK CHICK LAYING HENS

    OpenAIRE

    Bashir Mahmood Bhatti and Tanzeela Talat

    2001-01-01

    This study was conducted to examine effect of moulting on haematological values and plasma cholesterol levels of 86 weeks old Nick Chick laying hens. Washington and California moulting methods were used. Young laying hens, 40 weeks old served as control group. There were 408 hens in each group. There was no significant (P

  11. Plasma membrane lipid-protein interactions affect signaling processes in sterol-biosynthesis mutants of Arabidopsis thaliana

    Directory of Open Access Journals (Sweden)

    Henrik eZauber

    2014-03-01

    Full Text Available The plasma membrane is an important organelle providing structure, signaling and transport as major biological functions. Being composed of lipids and proteins with different physicochemical properties, the biological functions of membranes depend on specific protein-protein and protein-lipid interactions. Interactions of proteins with their specific sterol and lipid environment were shown to be important factors for protein recruitment into sub-compartmental structures of the plasma membrane. System-wide implications of altered endogenous sterol levels for membrane functions in living cells were not studied in higher plant cells. In particular, little is known how alterations in membrane sterol composition affect protein and lipid organization and interaction within membranes. Here, we conducted a comparative analysis of the plasma membrane protein and lipid composition in Arabidopsis sterol-biosynthesis mutants smt1 and ugt80A2;B1. smt1 shows general alterations in sterol composition while ugt80A2;B1 is significantly impaired in sterol glycosylation. By systematically analyzing different cellular fractions and combining proteomic with lipidomic data we were able to reveal contrasting alterations in lipid-protein interactions in both mutants, with resulting differential changes in plasma membrane signaling status.

  12. 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.

  13. Therapeutic potential for cytokine antagonists: Thalidomide and pentoxifylline in Hansen’s disease

    OpenAIRE

    1995-01-01

    Cytokine antagonists are a group of drugs defined by their actions on specific cytokines. Cytokine antagonists can inhibit action of cytokines by acting directly on receptors, by affecting production of cytokines or by binding to cytokines and preventing their subsequent action. Recent evidence suggests that Hansen’s disease, which is characterized by reactional states, is associated with elevated serum levels of tumour necrosis factor-α (tnf-α) and interleukin-1β during these reactional stat...

  14. The Matrigel Cytokine Assay

    OpenAIRE

    sprotocols

    2015-01-01

    Authors: Ole Audun Haabeth, Bjarne Bogen & Alexandre Corthay ### Abstract Cytokines represent a diverse group of soluble proteins that play a key role in a number of physiological processes, including regulation of both the innate and adaptive immune responses. Cytokines are generally secreted in small amounts, and are relatively unstable. Therefore, detection and measurement of cytokine local concentrations in a tissue extracellular matrix can be challenging. To investigate cytok...

  15. Inhibition of sphingomyelin synthase (SMS) affects intracellular sphingomyelin accumulation and plasma membrane lipid organization

    OpenAIRE

    Li, Zhiqiang; Hailemariam, Tiruneh K.; Zhou, Hongwen; Li, Yan; Duckworth, Dale C.; Peake, David A.; Zhang, Youyan; Kuo, Ming-Shang; Cao, Guoqing; Jiang, Xian-Cheng

    2007-01-01

    Sphingomyelin plays a very important role both in cell membrane formation that may well have an impact on the development of diseases like atherosclerosis and diabetes. However, the molecular mechanism that governs intracellular and plasma membrane SM levels is largely unknown. Recently, two isoforms of sphingomyelin synthase (SMS1 and SMS2), the last enzyme for SM de novo synthesis, have been cloned. We have hypothesized that SMS1 and SMS2 are the two most likely candidates responsible for t...

  16. 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.

  17. Plasma Procalcitonin Concentration in Healthy Horses and Horses Affected by Systemic Inflammatory Response Syndrome

    OpenAIRE

    Bonelli, F.; Meucci, V.; Divers, T.J.; Jose‐Cunilleras, E.; Corazza, M; Tognetti, R; Guidi, G.; Intorre, L.; Sgorbini, M.

    2015-01-01

    Background The diseases most frequent associated with SIRS in adult horses are those involving the gastrointestinal tract. An early diagnosis should be the goal in the management of horses with SIRS. Objective The objective of this study was to evaluate the plasma procalcitonin (PCT) concentration in healthy and SIRS horses to assess differences between the two groups. Animals Seventy‐eight horses (30 healthy and 48 SIRS). Methods Prospective in vivo multicentric study. Horses were classified...

  18. 孟鲁司特对过敏性紫癜患儿血浆细胞因子水平的疗效观察%The Efficacy of Montelukast in Children with Allergic Purpura of Plasma Cytokines Levels

    Institute of Scientific and Technical Information of China (English)

    刘芳; 钟日英; 涂燕青; 周莲珠; 王景香

    2015-01-01

    Objective:To study the clinical efficacy of montelukast in children with allergic purpura of plasma cytokine levels .Method:100 children with allergic purpura were selected in our hospital as research subjects,and were randomly divided into two groups,the control group of children were given anti-histamine drugs,anti-infective drugs and calcium,vitamin C and other conventional drugs.The observation group was treated with montelukast chewable tablets treatment on the basis of conventional therapy. In two weeks for a course of treatment,the clinical effect of plasma cytokine levels in patients before and after treatment were compared and observed.Result:IL-6,IL-8 and TNF-αexpression levels observed before the treatment,two groups of patients showed no significant difference(P>0.05);after treatment,the expression levels of three indicators had decreased significantly,and compared with before the treatment,the differences were statistically significant(P0.05);治疗后,三项指标的表达水平都有显著降低,且与治疗前相比差异均有统计学意义(P<0.05);观察组患者各项指标的下降程度超过对照组患者,两组比较差异具有统计意义(P<0.05)。观察组和对照组患者的临床治疗总有效率分别是96.0%和78.0%,两组比较差异有统计学意义(P<0.05)。结论:孟鲁司特治疗儿童过敏性紫癜具有临床疗效确切、安全性好的优点,可以对患儿血浆内的细胞因子进行调节,促进患儿免疫功能的改善,值得临床推广应用。

  19. Treatment of Cancer Pain by Targeting Cytokines

    OpenAIRE

    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 relate...

  20. 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

  1. 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......) 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...

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    BACKGROUND: Meta-analyses of observational studies found cheese consumption to be inversely associated with risk of type 2 diabetes and metabolic syndrome. This may be attributed to the bioactive compounds produced during cheese ripening. OBJECTIVE: The objective of this study was to investigate...... a 21-d butter-rich run-in diet (143 g of butter/kg diet), followed by a 14-d intervention with 1 of 3 isocaloric diets: 4-mo ripened cheddar (4-MRC) diet, 14-mo ripened cheddar (14-MRC) diet, or 24-mo ripened cheddar (24-MRC) diet (350 g of cheese/kg diet). Serum cholesterol, triglyceride, HDL...... cholesterol, LDL cholesterol, insulin, plasma nonesterified fatty acid (NEFA), glucose, fecal-fat excretion, and body weight were measured. RESULTS: Plasma NEFA was lower in the 24-MRC (201 ± 26 μEq/L) and in the 14-MRC (171 ± 19 μEq/L) diet groups than in the 4-MRC diet group (260 ± 27 μEq/L; P = 0.044 and P...

  3. The MICA-129Met/Val dimorphism affects plasma membrane expression and shedding of the NKG2D ligand MICA.

    Science.gov (United States)

    Isernhagen, Antje; Schilling, Daniela; Monecke, Sebastian; Shah, Pranali; Elsner, Leslie; Walter, Lutz; Multhoff, Gabriele; Dressel, Ralf

    2016-02-01

    The MHC class I chain-related molecule A (MICA) is a ligand for the activating natural killer (NK) cell receptor NKG2D. A polymorphism causing a valine to methionine exchange at position 129 affects binding to NKG2D, cytotoxicity, interferon-γ release by NK cells and activation of CD8(+) T cells. It is known that tumors can escape NKG2D-mediated immune surveillance by proteolytic shedding of MICA. Therefore, we investigated whether this polymorphism affects plasma membrane expression (pmMICA) and shedding of MICA. Expression of pmMICA was higher in a panel of tumor (n = 16, P = 0.0699) and melanoma cell lines (n = 13, P = 0.0429) carrying the MICA-129Val/Val genotype. MICA-129Val homozygous melanoma cell lines released more soluble MICA (sMICA) by shedding (P = 0.0015). MICA-129Met or MICA-129Val isoforms differing only in this amino acid were expressed in the MICA-negative melanoma cell line Malme, and clones with similar pmMICA expression intensity were selected. The MICA-129Met clones released more sMICA (P = 0.0006), and a higher proportion of the MICA-129Met than the MICA-129Val variant was retained in intracellular compartments (P = 0.0199). The MICA-129Met clones also expressed more MICA messenger RNA (P = 0.0047). The latter phenotype was also observed in mouse L cells transfected with the MICA expression constructs (P = 0.0212). In conclusion, the MICA-129Met/Val dimorphism affects the expression density of MICA on the plasma membrane. More of the MICA-129Met variants were retained intracellularly. If expressed at the cell surface, the MICA-129Met isoform was more susceptible to shedding. Both processes appear to limit the cell surface expression of MICA-129Met variants that have a high binding avidity to NKG2D.

  4. [Cytokines and osteogenesis].

    Science.gov (United States)

    Fujiwara, Makoto; Ozono, Keiichi

    2014-06-01

    Many cytokines associate with proliferation, differentiation and activation of osteoblasts which have an important role in osteogenesis. TGF-β, BMP, IGF, FGF, Hedgehog, Notch, IL and WNT signaling pathways and their inhibitors have been revealed to correlate to osteogenesis, and those gene mutations have been shown to cause various bone disorders. It has been suggested that there are common pathways or crosstalk in these cytokine signaling each other, but mechanism of their complicated regulation on osteogenesis has been unclear. It was expected that the knowledge about these cytokines will apply to clinical therapies of bone diseases. PMID:24870835

  5. Platelet Concentration in Platelet-Rich Plasma Affects Tenocyte Behavior In Vitro

    Directory of Open Access Journals (Sweden)

    Ilaria Giusti

    2014-01-01

    Full Text Available Since tendon injuries and tendinopathy are a growing problem, sometimes requiring surgery, new strategies that improve conservative therapies are needed. Platelet-rich plasma (PRP seems to be a good candidate by virtue of its high content of growth factors, most of which are involved in tendon healing. This study aimed to evaluate if different concentrations of platelets in PRP have different effects on the biological features of normal human tenocytes that are usually required during tendon healing. The different platelet concentrations tested (up to 5 × 106 plt/µL stimulated differently tenocytes behavior; intermediate concentrations (0.5 × 106, 1 × 106 plt/µL strongly induced all tested processes (proliferation, migration, collagen, and MMPs production if compared to untreated cells; on the contrary, the highest concentration had inhibitory effects on proliferation and strongly reduced migration abilities and overall collagen production but, at the same time, induced increasing MMP production, which could be counterproductive because excessive proteolysis could impair tendon mechanical stability. Thus, these in vitro data strongly suggest the need for a compromise between extremely high and low platelet concentrations to obtain an optimal global effect when inducing in vivo tendon healing.

  6. Nanosecond electric pulses affect a plant-specific kinesin at the plasma membrane.

    Science.gov (United States)

    Kühn, Sebastian; Liu, Qiong; Eing, Christian; Frey, Wolfgang; Nick, Peter

    2013-12-01

    Electric pulses with high field strength and durations in the nanosecond range (nsPEFs) are of considerable interest for biotechnological and medical applications. However, their actual cellular site of action is still under debate--due to their extremely short rise times, nsPEFs are thought to act mainly in the cell interior rather than at the plasma membrane. On the other hand, nsPEFs can induce membrane permeability. We have revisited this issue using plant cells as a model. By mapping the cellular responses to nsPEFs of different field strength and duration in the tobacco BY-2 cell line, we could define a treatment that does not impinge on short-term viability, such that the physiological responses to the treatment can be followed. We observe, for these conditions, a mild disintegration of the cytoskeleton, impaired membrane localization of the PIN1 auxin-efflux transporter and a delayed premitotic nuclear positioning followed by a transient mitotic arrest. To address the target site of nsPEFs, we made use of the plant-specific KCH kinesin, which can assume two different states with different localization (either near the nucleus or at the cell membrane) driving different cellular functions. We show that nsPEFs reduce cell expansion in nontransformed cells but promote expansion in a line overexpressing KCH. Since cell elongation and cell widening are linked to the KCH localized at the cell membrane, the inverted response in the KCH overexpressor provides evidence for a direct action of nsPEFs, also at the cell membrane. PMID:24062185

  7. Amniotic fluid inflammatory cytokines

    DEFF Research Database (Denmark)

    Abdallah, Morsi; Larsen, Nanna; Grove, Jakob;

    2013-01-01

    The aim of the study was to analyze cytokine profiles in amniotic fluid (AF) samples of children developing autism spectrum disorders (ASD) and controls, adjusting for maternal autoimmune disorders and maternal infections during pregnancy.......The aim of the study was to analyze cytokine profiles in amniotic fluid (AF) samples of children developing autism spectrum disorders (ASD) and controls, adjusting for maternal autoimmune disorders and maternal infections during pregnancy....

  8. 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...

  9. 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.

  10. Dietary fat affects plasma prolactin in female F344 rats under conditions of ether stress.

    Science.gov (United States)

    Bosland, M C; Bunnik, G S; Wilbrink, B; de Bie, B T; Floor, B

    1994-01-01

    The influence of amount and type of dietary fat on circulating concentrations of prolactin and estradiol-17 beta in female F344 rats from which blood was sampled by decapitation under ether anesthesia was compared with that in rats from which blood was collected without anesthesia. The animals were fed isonutrient (adjusted for differences in energy density) semipurified diets containing 5% or 20% (by weight) sunflower seed oil or lard. Blood was sampled by decapitation with or without standardized ether anesthesia during the afternoon of proestrus-estrus or the morning of metestrus-diestrus, as determined by examination of vaginal smears. Plasma hormone concentrations were measured by radioimmunoassay. Prolactin levels were lower during proestrus-estrus in rats fed a low-fat diet than in animals fed a high-fat diet, statistically independent of the type of dietary fat, but only when blood was sampled by decapitation under ether anesthesia [p = 0.0384, 2-way analysis of variance (ANOVA)]. No such difference was found in rats decapitated without anesthesia. This effect of amount of dietary fat on prolactin in proestrus-estrus animals anesthetized with ether was predominantly present in animals fed polyunsaturated fat (p rats fed saturated fat diets. During metestrus-diestrus, prolactin levels were significantly lower in animals fed a high-saturated fat diet than in those fed low-saturated fat, low-unsaturated fat, or high-unsaturated fat diets, independent of the blood sampling conditions (p conversion efficiency was lower in animals fed low-fat diets than in those fed high-fat diets. This study confirms the hypothesis that effects of dietary fat, particularly polyunsaturated fat, on circulating prolactin occur only during (ether) stress. Because stress is a frequent and normal phenomenon, this observation implies that the mammary glands of animals with a high dietary intake of polyunsaturated fat are frequently exposed to higher circulating prolactin concentrations

  11. 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.

  12. Infusion of hypertonic saline before elective hysterectomy: effects on cytokines and stress hormonesTumor necrosis factor-alpha binding capacity and anti-infliximab antibodies measured by fluid-phase radioimmunoassays as predictors of clinical efficacy of infliximab in Crohn's disease

    DEFF Research Database (Denmark)

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

    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 in a...... with the other groups (P<0.05). No other differences were found between the groups. CONCLUSIONS: Infusion of a clinically relevant dose of hypertonic saline before hysterectomy appears to have limited effect on the postoperative concentration of selected plasma cytokines and the hormonal stress...

  13. 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.

  14. 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....

  15. 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.

  16. 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

  17. Cytokines and antitumor immunity.

    Science.gov (United States)

    Müller, Ludmila; Pawelec, Graham

    2003-06-01

    Currently, the notion of immunosurveillance against tumors is enjoying something of a renaissance. Even if we still refuse to accept that tumors arising in the normal host are unable to trigger an immune response because of the lack of initiation ("danger") signals, there is no doubt that the immune system can be manipulated experimentally and by implication therapeutically to exert anti-tumor effects. For this activity to be successful, the appropriate cytokine milieu has to be provided, making cytokine manipulation central to immunotherapy. On the other hand, the major hurdle currently preventing successful immunotherapy is the ability of tumors to evolve resistant variants under the pressure of immune selection. Here, too, the cytokine milieu plays an essential role. The purpose of this brief review is to consider the current status of the application of cytokines in facilitating antitumor immunity, as well their role in inhibiting responses to tumors. Clearly, encouraging the former but preventing the latter will be the key to the effective clinical application of cancer immunotherapy. PMID:12779349

  18. Cytokines and signaling molecules predict clinical outcomes in sepsis.

    Directory of Open Access Journals (Sweden)

    Christopher D Fjell

    Full Text Available INTRODUCTION: Inflammatory response during sepsis is incompletely understood due to small sample sizes and variable timing of measurements following the onset of symptoms. The vasopressin in septic shock trial (VASST compared the addition of vasopressin to norepinephrine alone in patients with septic shock. During this study plasma was collected and 39 cytokines measured in a 363 patients at both baseline (before treatment and 24 hours. Clinical features relating to both underlying health and the acute organ dysfunction induced by the severe infection were collected during the first 28 days of admission. HYPOTHESIS: Cluster analysis of cytokines identifies subgroups of patients at differing risk of death and organ failure. METHODS: Circulating cytokines and other signaling molecules were measured using a Luminex multi-bead analyte detection system. Hierarchical clustering was performed on plasma values to create patient subgroups. Enrichment analysis identified clinical outcomes significantly different according to these chemically defined patient subgroups. Logistic regression was performed to assess the importance of cytokines for predicting patient subgroups. RESULTS: Plasma levels at baseline produced three subgroups of patients, while 24 hour levels produced two subgroups. Using baseline cytokine data, one subgroup of 47 patients showed a high level of enrichment for severe septic shock, coagulopathy, renal failure, and risk of death. Using data at 24 hours, a larger subgroup of 81 patients that largely encompassed the 47 baseline subgroup patients had a similar enrichment profile. Measurement of two cytokines, IL2 and CSF2 and their product were sufficient to classify patients into these subgroups that defined clinical risks. CONCLUSIONS: A distinct pattern of cytokine levels measured early in the course of sepsis predicts disease outcome. Subpopulations of patients have differing clinical outcomes that can be predicted accurately from

  19. 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

  20. 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.

  1. Cytokines in acute chikungunya.

    Directory of Open Access Journals (Sweden)

    Anuradha Venugopalan

    Full Text Available Acute chikungunya (CHIKV is predominantly an acute onset of excruciatingly painful, self-limiting musculoskeletal (MSK arbovirus illness and this was further reported by us during the 2006 Indian epidemic [Chopra et al. Epidemiol Infect 2012]. Selected serum cytokines profile in subjects within one month of onset of illness is being presented.Out of 509 clinical CHIKV cases (43% population identified during a rural population survey, 225 subjects consented blood investigations. 132 examined within 30 days of febrile onset are the study cohort. Anti-CHIKV IgM and IgG antibodies tested by immunochromatography and indirect immunofluorescence respectively. Interferons (IFN-α, -β and -γ, Interferon Gamma-Induced Protein-10 (CXCL-10/IP-10, Tumor Necrosis Factor-α (TNF-α, Interleukin-1β (IL-1β, Interleukin-6 (IL-6, Interleukin-13 (IL-13, Monocyte Chemoattractant Protein-1 (MCP-1, Interleukin-4 (IL-4 and Interleukin-10 (IL-10 performed by ELISA. Samples collected from neighboring community a year prior to the epidemic used as healthy controls.Seropositivity for anti-CHIKV IgM and IgG was 65% and 52% respectively. IFN-α, IFN-β, IFN-γ, CXCL10/IP-10 and IL-1β showed intense response in early acute phase. Cytokines (particularly TNF-α, MCP-1, IL-4, IL-6 and IL-10 was maximum in extended symptomatic phase and remained elevated in recovered subjects. Higher (p<0.05 IFN and IL-4 seen in patients seropositive for anti-CHIKV IgG. Elderly cases (≥65 years showed elevated cytokines (except IFN and anti-CHIKV antibodies near similar to younger subjects. Significant correlations (p<0.05 found between cytokines and clinical features (fatigue, low back ache, myalgia and anti-CHIKV antibodies.An intense cytokine milieu was evident in the early and immediate persistent symptomatic phase and in recovered subjects. Early persistent IgM and lower IgG to anti-CHKV and intense Th2 cytokine phenotype seem to be associated with delay in resolution of MSK symptoms

  2. 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....

  3. 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.

  4. Plant cytokine or phytocytokine

    OpenAIRE

    Luo, Li

    2012-01-01

    Peptide hormones play an important role in plant growth and development. Some of them are secreted by stem cells and also regulate plant immunity through cell-cell communication and reprogramming the expression of immune related genes, such as CLAVATA3p (CLV3p) and phytosulfokine (PSK). These peptides play similar roles as cytokines in plant innate immunity. As explosive progress of plant omics, more and more such functional peptides will be discovered. I recommend that they should be named a...

  5. Interactions between genetic variants of folate metabolism genes and lifestyle affect plasma homocysteine concentrations in the Boston Puerto Rican Population

    Science.gov (United States)

    Results of studies investigating relationships between lifestyle factors and elevated plasma homocysteine (Hcy), an independent risk factor for cardiovascular disease, are conflicting. The objective of this study was to investigate genetic and lifestyle factors and their interactions on plasma Hcy c...

  6. 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

  7. 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...

  8. Plasma membrane lipid–protein interactions affect signaling processes in sterol-biosynthesis mutants in Arabidopsis thaliana

    OpenAIRE

    Zauber, Henrik; Burgos, Asdrubal; Garapati, Prashanth; Schulze, Waltraud X.

    2014-01-01

    The plasma membrane is an important organelle providing structure, signaling and transport as major biological functions. Being composed of lipids and proteins with different physicochemical properties, the biological functions of membranes depend on specific protein-protein and protein-lipid interactions. Interactions of proteins with their specific sterol and lipid environment were shown to be important factors for protein recruitment into sub-compartmental structures of the plasma membrane...

  9. 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.

  10. 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.

  11. The Effect of Recombinant Erythropoietin on Plasma Brain Derived Neurotrophic Factor Levels in Patients with Affective Disorders: A Randomised Controlled Study

    OpenAIRE

    Maj Vinberg; Kamilla Miskowiak; Pernille Hoejman; Maria Pedersen; Lars Vedel Kessing

    2015-01-01

    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) (...

  12. Involvement of cytokines in slow wave sleep

    OpenAIRE

    Krueger, James M.; Clinton, James M.; Winters, Bradley D.; Zielinski, Mark R.; Taishi, Ping; Jewett, Kathryn A.; Davis, Christopher J.

    2011-01-01

    Cytokines such as tumor necrosis factor alpha (TNFα) and interleukin-1 beta (IL1β) play a role in sleep regulation in health and disease. TNFα or IL1β injection enhances non-rapid eye movement sleep. Inhibition of TNFα or IL1β reduces spontaneous sleep. Mice lacking TNFα or IL1β receptors sleep less. In normal humans and in multiple disease states, plasma levels of TNFα covary with EEG slow wave activity (SWA) and sleep propensity. Many of the symptoms induced by sleep loss, for example, slee...

  13. Cytokine levels as biomarkers for leptospirosis patients.

    Science.gov (United States)

    Chirathaworn, C; Supputtamongkol, Y; Lertmaharit, S; Poovorawan, Y

    2016-09-01

    Inflammatory mediators were suggested to be biomarkers for prediction of disease severity. In this study, we investigated the levels of IL-6, IL-8, IL-10 and TNF-α in leptospirosis patients with mild or severe illnesses. Sera samples were divided into two groups. The OI group and NOI groups included sera from patients with and without organ involvement, respectively. Each group consisted of 20 pairs of sera. Twenty-five sera from healthy individuals were included as controls. Cytokine levels were compared. Although IL-6, IL-8 and IL-10 levels in acute sera from the OI group were significantly higher than NOI group, only IL-8 level was significantly higher in the OI group when cytokine levels in convalescent sera were compared. TNF-α, an inflammatory cytokine widely studied in leptospirosis was not significantly different between two groups of patients. Our data suggested that IL-6, IL-8 and IL-10 were involved in disease severity. However, time of specimen collection could affect the significant levels of cytokines especially as biomarkers for monitoring disease severity. PMID:27295614

  14. 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

  15. 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.

  16. Cytokines and therapeutic oligonucleotides.

    Science.gov (United States)

    Hartmann, G; Bidlingmaier, M; Eigler, A; Hacker, U; Endres, S

    1997-12-01

    Therapeutic oligonucleotides - short strands of synthetic nucleic acids - encompass antisense and aptamer oligonucleotides. Antisense oligonucleotides are designed to bind to target RNA by complementary base pairing and to inhibit translation of the target protein. Antisense oligonucleotides enable specific inhibition of cytokine synthesis. In contrast, aptamer oligonucleotides are able to bind directly to specific proteins. This binding depends on the sequence of the oligonucleotide. Aptamer oligonucleotides with CpG motifs can exert strong immunostimulatory effects. Both kinds of therapeutic oligonucleotides - antisense and aptamer oligonucleotides - provide promising tools to modulate immunological functions. Recently, therapeutic oligonucleotides have moved towards clinical application. An antisense oligonucleotide directed against the proinflammatory intercellular adhesion molecule 1 (ICAM-1) is currently being tested in clinical trials for therapy of inflammatory disease. Immunostimulatory aptamer oligonucleotides are in preclinical development for immunotherapy. In the present review we summarize the application of therapeutic oligonucleotides to modulate immunological functions. We include technological aspects as well as current therapeutic concepts and clinical studies. PMID:9740353

  17. 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

  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 difficul...

  19. Does Cold Plasma Affect Breaking Dormancy and Seed Germination? A Study on Seeds of Lamb's Quarters (Chenopodium album agg.)

    International Nuclear Information System (INIS)

    Low-pressure discharge is applied for stimulation of germination of two seed lots of Lamb's Quarters (Chenopodium album agg.) with different starting germinations (17%, 8%) and in different stages of dormancy. Different exposition durations with cold plasma treatment were applied. The variable of the ratio cumulative germination was calculated. The Richards' equation was used for curve-fitting and simulation of the growth curves. Population parameters, namely Vi - viability, Me - time, Qu - dispersion, and Sk - skewness, counted from the curves described the germination rate well. Significant differences among Qu confirmed the erratic dormancy and gradual germination of Lamb's Quarters. No difference in the Me parameter was found between two tested seed lots, and no interspecies characteristics were changed using low-pressure discharge. The results suggested that plasma treatment changed seed germination in Lamb's Quarters seeds.

  20. Does overnight normalization of plasma glucose by insulin infusion affect assessment of glucose metabolism in Type 2 diabetes?

    DEFF Research Database (Denmark)

    Staehr, P; Højlund, Kurt; Hother-Nielsen, O;

    2003-01-01

    turnover rates were quantified by adjusted primed-constant 3-3H-glucose infusions, and insulin action was assessed in 4-h euglycaemic, hyperinsulinaemic (40 mU m-2 min-1) clamp studies using labelled glucose infusates (Hot-GINF). RESULTS: Basal plasma glucose levels (mean +/- sd) were 5.5 +/- 0.5 and 10...... from basal rates of Rd, assessment of glucose turnover rates in euglycaemic clamp studies of Type 2 diabetic patients is not dependent on the method by which plasma glucose levels are lowered........7 +/- 2.9 mmol/l in the + ON and - ON studies, respectively, and were clamped at -5.5 mmol/l. Basal rates of glucose production (GP) were similar in the + ON and - ON studies, 83 +/- 13 vs. 85 +/- 14 mg m-2 min-1 (NS), whereas basal rates of glucose disappearance (Rd) were lower in the + ON than in the...

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

    OpenAIRE

    Horimasu Yasushi; Rönty Mikko; Vuopala Katri; Toljamo Tuula; Mazur Witold; Ishikawa Nobuhisa; Kohno Nobuoki; Kinnula Vuokko L

    2011-01-01

    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 plas...

  2. 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.

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

    DEFF Research Database (Denmark)

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

    2013-01-01

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

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

    Science.gov (United States)

    Costas, Benjamín; Aragão, Cláudia; Ruiz-Jarabo, Ignacio; Vargas-Chacoff, Luis; Arjona, Francisco J; Mancera, Juan M; Dinis, Maria T; Conceição, Luís E C

    2012-07-01

    Senegalese sole (Solea senegalensis) is a eurytherm teleost that under natural conditions can be exposed to annual water temperature fluctuations between 12 and 26°C. This study assessed the effects of temperature on sole metabolic status, in particular in what concerns plasma free amino acid changes during thermal acclimation. Senegalese sole maintained at 18°C were acclimated to either cold (12°C) or warm (26°C) environmental temperatures for 21 days. Fish maintained at 18°C served as control. Plasma concentrations of cortisol, glucose, lactate, triglycerides, proteins, and free amino acids were assessed. Cold acclimation influenced interrenal responses of sole by increasing cortisol release. Moreover, plasma glucose and lactate concentrations increased linearly with temperature, presumably reflecting a higher metabolic activity of sole acclimated to 26°C. Acclimation temperature affected more drastically plasma concentrations of dispensable than that of indispensable amino acids, and different acclimation temperatures induced different responses. Asparagine, glutamine and ornithine seem to be of particular importance for ammonia detoxification mechanisms, synthesis of triglycerides that may be used during homeoviscous adaptation and, to a lesser extent, as energetic substrates in specimens acclimated to 12°C. When sole is acclimated to 26°C taurine, glutamate, GABA and glycine increased, which may suggest important roles as antioxidant defences, in osmoregulatory processes and/or for energetic purposes at this thermal regimen. In conclusion, acclimation to different environmental temperatures induces several metabolic changes in Senegalese sole, suggesting that amino acids may be important for thermal acclimation. PMID:21947601

  5. 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...

  6. Vasculogenic Cytokines in Wound Healing

    Directory of Open Access Journals (Sweden)

    Victor W. Wong

    2013-01-01

    Full Text Available Chronic wounds represent a growing healthcare burden that particularly afflicts aged, diabetic, vasculopathic, and obese patients. Studies have shown that nonhealing wounds are characterized by dysregulated cytokine networks that impair blood vessel formation. Two distinct forms of neovascularization have been described: vasculogenesis (driven by bone-marrow-derived circulating endothelial progenitor cells and angiogenesis (local endothelial cell sprouting from existing vasculature. Researchers have traditionally focused on angiogenesis but defects in vasculogenesis are increasingly recognized to impact diseases including wound healing. A more comprehensive understanding of vasculogenic cytokine networks may facilitate the development of novel strategies to treat recalcitrant wounds. Further, the clinical success of endothelial progenitor cell-based therapies will depend not only on the delivery of the cells themselves but also on the appropriate cytokine milieu to promote tissue regeneration. This paper will highlight major cytokines involved in vasculogenesis within the context of cutaneous wound healing.

  7. 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.

  8. Radiolabelled cytokines for imaging chronic inflammation

    International Nuclear Information System (INIS)

    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 pathophysiology of chronic disorders, combine 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 candidate as radiopharmaceuticals. (author)

  9. The concentration of plasma metabolites varies throughout reproduction and affects offspring number in wild brown trout (Salmo trutta).

    Science.gov (United States)

    Gauthey, Zoé; Freychet, Marine; Manicki, Aurélie; Herman, Alexandre; Lepais, Olivier; Panserat, Stéphane; Elosegi, Arturo; Tentelier, Cédric; Labonne, Jacques

    2015-06-01

    In wild populations, measuring energy invested in the reproduction and disentangling investment in gametes versus investment in reproductive behavior (such as intrasexual competition or intersexual preference) remain challenging. In this study, we investigated the energy expenditure in brown trout reproductive behavior by using two proxies: variation in weight and variation of plasma metabolites involved in energy production, over the course of reproductive season in a semi natural experimental river. We estimated overall reproductive success using genetic assignment at the end of the reproductive season. Results show that triglycerides and free fatty acid concentrations vary negatively during reproduction, while amino-acids and glucose concentrations remain stable. Decrease in triglyceride and free fatty acid concentrations during reproduction is not related to initial concentration levels or to weight variation. Both metabolite concentration variations and weight variations are correlated to the number of offspring produced, which could indicate that gametic and behavioral reproductive investments substantially contribute to reproductive success in wild brown trout. This study opens a path to further investigate variations in reproductive investment in wild populations. PMID:25666363

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

    NARCIS (Netherlands)

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

    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

  11. 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.

  12. 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. PMID:27679767

  13. 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

  14. 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.

  15. Intracellular cytokine production and cognition in healthy older adults.

    Science.gov (United States)

    Simpson, Ellen E A; Hodkinson, Claire F; Maylor, Elizabeth A; McCormack, Jacqueline M; Rae, Gordon; Strain, Sean; Alexander, H Denis; Wallace, Julie M W

    2013-10-01

    Elevated concentrations of the pro-inflammatory cytokines IL-1β and IL-6 have been associated with impaired cognitive performance. There are, however, few studies that have examined the relationship between cytokine production and specific aspects of cognition in healthy older individuals. Two-colour flow cytometry was used to determine intracellular cytokine production by activated monocytes, and neuropsychological tests were performed using the Cambridge Neuropsychological Test Automated Battery (CANTAB) in 93 apparently healthy men and women aged 55-70 years. A series of hierarchical regression analyses was carried out to examine the contribution of IL-1β and IL-6 (% expression and production (antibody binding capacity (ABC))) to recognition, attention and working memory, after controlling for socio-demographic variables (age, sex and social class). IL-1β% expression and IL-6 production predicted aspects of working memory. Recognition memory was found to be sensitive to the affects of age and social class. The current study suggests that higher intracellular cytokine production by activated monocytes may be predictive of lower cognitive performance in working memory in healthy older individuals. These findings indicate that utilization of models for in vivo cytokine production upon immune challenge may be useful in studying specific aspects of memory affected during inflammatory responses, for example in individuals at risk for cognitive decline owing to age-related inflammatory disorders. PMID:23664267

  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. 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.

  18. 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.

  19. The effect of high dose digoxin on cytokines in healthy dogs

    Directory of Open Access Journals (Sweden)

    Haluk Dülger

    2002-01-01

    Full Text Available Background: Tumor necrosis factor (TNF-α and interleukin (IL-1β are pro-inflammatory cytokines, causing myocardial dysfunction and a negative inotropic effect. The drugs used to treat heart failure affect the production of cytokines. Digoxin, on which this study was focused, is one of the drugs for the treatment of heart failure.

  20. 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.

  1. 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.

  2. Vasculogenic Cytokines in Wound Healing

    OpenAIRE

    Wong, Victor W.; Crawford, Jeffrey D.

    2013-01-01

    Chronic wounds represent a growing healthcare burden that particularly afflicts aged, diabetic, vasculopathic, and obese patients. Studies have shown that nonhealing wounds are characterized by dysregulated cytokine networks that impair blood vessel formation. Two distinct forms of neovascularization have been described: vasculogenesis (driven by bone-marrow-derived circulating endothelial progenitor cells) and angiogenesis (local endothelial cell sprouting from existing vasculature). Researc...

  3. 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

  4. 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.

  5. Temporal Cytokine Profiles in Severely Burned Patients: A Comparison of Adults and Children

    OpenAIRE

    Finnerty, Celeste C.; Jeschke, Marc G.; Herndon, David N; Gamelli, Richard; Gibran, Nicole; Klein, Matthew; Silver, Geoff; Arnoldo, Brett; Remick, Daniel; Tompkins, Ronald G.

    2008-01-01

    A severe burn leads to hypermetabolism and catabolism resulting in compromised function and structural changes of essential organs. The release of cytokines has been implicated in this hypermetabolic response. The severity of the hypermetabolic response following burn injury increases with age, as does the mortality rate. Due to the relationship between the hypermetabolic and inflammatory responses, we sought to compare the plasma cytokine profiles following a severe burn in adults and in chi...

  6. 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

  7. The Predicted Value of Threatened Miscarriages Outcome by Plasma Levels of Th1/Th2 Cytokines and β-HCG%血清Th1/Th2细胞因子联合β-HCG预测先兆流产结局的价值

    Institute of Scientific and Technical Information of China (English)

    胡万芹; 杨丽华; 苏莹; 冷天艳

    2012-01-01

    Objective To explore the predicted value of threatened miscarriages outcome by plasma levels of Thl/Th2 cytokines and β -HCG. Methods We retrospectively analysed the plasma levels of IL2, IL10 and β -HCG in 60 women with threatened miscarriages in our hospital from 2009.1-2011.12, including 30 women with continual pregnancy and 30 women with unsuccessful pregnancy. The relationship between the indexes and the threatened miscarriages outcome was analysed. Results IL2/IL10 was significantly higher in unsuccessful pregnancy group than that in continual pregnancy group at the time that threatened miscarriages were diagnosed and the time that pregnancy outcome were clear (P 0.05). There was no significant difference in the level of P -HCG between the two groups when diagnosed (P>0.05). The level of β-HCG increased in continual pregnancy group and decreased in unsuccessful pregnancy group when the pregnancy outcome were clear (P <0.05). Conclusion There is no relationship between plasma IL2/IL10 and pregnancy weeks and embryo activity, increased IL2/IL10 means increased rate of unsuccessful pregnancy because of unbalanced maternal fetal immune function. It can be effectively predicted the threatened miscarriage outcome by combining plasma levels of Thl/Th2 cytokines and P -HCG, avoiding conservative management blindly.%目的 探讨血清Th1/Th2细胞因子联合β-HCG预测先兆流产结局的价值.方法 回顾分析2009年1月至2011年12月间昆明医科大学第二附属医院妇产科60例先兆流产孕妇血清IL2、IL10、β-HCG水平,继续妊娠者及妊娠失败者各30例,研究各指标与先兆流产结局的关系.结果 先兆流产诊断与妊娠结局明确当日,妊娠失败组IL2/IL10比值显著高于继续妊娠组(P<0.05),两组IL-2、IL-10和IL2/IL10水平在先兆流产诊断时与妊娠结局明确当日均无显著性变化(P>0.05);两组在先兆流产诊断时血β-HCG无差异(P>0.05),妊娠结局明确时妊娠失败组血HCG

  8. 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

  9. Avian cytokines in health and disease

    Directory of Open Access Journals (Sweden)

    Wigley P

    2003-01-01

    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.

  10. 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).

    Science.gov (United States)

    Rolland, Marine; Skov, Peter V; Larsen, Bodil K; Holm, Jørgen; Gómez-Requeni, Pedro; Dalsgaard, Johanne

    2016-08-01

    Strictly carnivorous fish with high requirements for dietary protein, such as rainbow trout (Oncorhynchus mykiss) are interesting models for studying the role of amino acids as key regulators of intermediary metabolism. Methionine is an essential amino acid for rainbow trout, and works as a signalling factor in different metabolic pathways. The study investigated the effect of increasing dietary methionine intake on the intermediary metabolism in the liver of juvenile rainbow trout. For this purpose, five diets were formulated with increasing methionine levels from 0.60 to 1.29% dry matter. 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 concentrations. The transcript levels of enzymes involved in lipid metabolism (fatty acid synthase, glucose 6 phosphate dehydrogenase and carnitine palmitoyl transferase 1 a), gluconeogenesis (fructose-1,6-biphosphatase) and amino acid catabolism (alanine amino transferase and glutamate dehydrogenase) were 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; Ptrout responded in a dose-dependent manner to increasing levels of dietary methionine. PMID:27105833

  11. Cytokine expression during syphilis infection in HIV-1-infected individuals

    DEFF Research Database (Denmark)

    Knudsen, Andreas; Benfield, Thomas; Kofoed, Kristian

    2009-01-01

    BACKGROUND: Little is known about cytokine responses to syphilis infection in HIV-1-infected individuals. METHODS: We retrospectively identified patients with HIV-1 and Treponema pallidum coinfection. Plasma samples from before, during, and after coinfection were analyzed for interleukin (IL)-2, IL...... syphilis.IL-10 and TNF-alpha levels correlated positively with plasma HIV RNA values at the time of diagnosis (r = 0.38, P = 0.023, and r = 0.64, P HIV-1 and early...... stage syphilis coinfection were associated with an increase in IL-10. IL-10 and TNF-alpha both decreased after treatment of syphilis. TNF-alpha and IL-10 correlated with low CD4 T cell counts and high plasma HIV RNA values....

  12. 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.

  13. 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.

  14. 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...... hypoglycaemia may be due to direct effects of similar molecules on glucose metabolism. These molecules appear to be phospholipids and we suggest that when fully characterized they might form the basis of antitoxic therapy for malaria....

  15. Clinical implication of perioperative inflammatory cytokine alteration.

    Science.gov (United States)

    Hsing, Chung-Hsi; Wang, Jhi-Joung

    2015-03-01

    Cytokines are key modulators of inflammatory responses, and play an important role in the defense and repair mechanisms following trauma. After traumatic injury, an immuno-inflammatory response is initiated immediately, and cytokines rapidly appear and function as a regulator of immunity. In pathologic conditions, imbalanced cytokines may provide systemic inflammatory responses or immunosuppression. Expression of perioperative cytokines vary by different intensities of surgical trauma and types of anesthesia and anesthetic agents. Inflammatory cytokines play important roles in postoperative organ dysfunction including central nervous system, cardiovascular, lung, liver, and kidney injury. Inhibition of cytokines could protect against traumatic injury in some circumstances, therefore cytokine inhibitors or antagonists might have the potential for reducing postoperative tissue/organ dysfunction. Cytokines are also involved in wound healing and post-traumatic pain. Application of cytokines for the improvement of surgical wound healing has been reported. Anesthesia-related immune response adjustment might reduce perioperative morbidity because it reduces proinflammatory cytokine expression; however, the overall effects of anesthetics on postoperative immune-inflammatory responses needs to be further investigated. PMID:25837846

  16. 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

  17. 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.

  18. 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.

  19. 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

    hormones are metabolized quickly by the enzyme dipeptidyl peptidase-IV (DPP-IV). It is well known that type-2 diabetic patients have an impaired incretin effect. Therefore, the aim of the present study was to investigate plasma DPP-IV activity in the fasting and the postprandial state in type-2 diabetic...... patients, DPP-IV activity was positively correlated to FPG and HbAlc and negatively to the duration of diabetes and age of the patients. No postprandial changes were seen in plasma DPP-IV activity in any of the groups. CONCLUSIONS: Plasma DPP-IVactivity increases in the fasting state and is positively...

  20. 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 ...

  1. 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.

  2. 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.

  3. 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...... in a double-blind study to infusion of NaCl 7.5% (HS), NaCl 0.9% (NS4), both 4 ml kg(-1), or NaCl 0.9% 32 ml kg(-1) (NS32) over 20 min. Blood was collected at baseline, 1, 4, and 24 h after surgery (n=34) for the determination of interleukin (IL)-1beta, IL-6, IL-8, IL-10, IL-12, IL-1ra, and tumour necrosis...... 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...

  4. Pharmacokinetics, safety and inducible cytokine responses during a phase 1 trial of the oral histone deacetylase inhibitor ITF2357 (givinostat).

    Science.gov (United States)

    Furlan, Antonio; Monzani, Valmen; Reznikov, Leonid L; Leoni, Flavio; Fossati, Gianluca; Modena, Daniela; Mascagni, Paolo; Dinarello, Charles A

    2011-01-01

    ITF2357 (givinostat) is a histone deacetylase inhibitor with antiinflammatory properties at low nanomolar concentrations. We report here a phase I safety and pharmacokinetics trial in healthy males administered 50, 100, 200, 400 or 600 mg orally. After 50 mg, mean maximal plasma concentrations reached 104 nmol/L 2 h after dosing, with a half-life of 6.9 h. After 100 mg, maximal concentration reached 199 nmol/L at 2.1 h with a half-life of 6.0 h. Repeat doses for 7 consecutive days of 50, 100 or 200 mg resulted in nearly the same kinetics. There were no serious adverse effects (AEs) and no organ toxicities. However, there was a dose-dependent but transient fall in platelets. After 7 daily doses of 50 or 100 mg, the mean decrease in platelets of 17 and 25% was not statistically significant and returned to baseline within 14 d. Blood removed from the subjects after oral dosing was cultured ex vivo with endotoxin, and the release of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-1Ra, interferon (IFN)-γ and IL-10 was determined. Maximal reduction in IL-1β, TNFα, IL-6 and IFNγ was observed 4 h after dosing but returned to baseline at 12 h. There was no significant reduction in IL-1Ra or IL-10. With daily dosing, the fall in cytokine production in blood cultures observed on day 7 was nearly the same as that of the first day. We conclude that dosing of 50 or 100 mg ITF2357 is safe in healthy humans and transiently but repeatedly reduces the production of proinflammatory cytokines without affecting production of antiinflammatory cytokines. PMID:21365126

  5. Mechanically loaded myotubes affect osteoclast formation

    NARCIS (Netherlands)

    P. Juffer; R.T. Jaspers; J. Klein-Nulend; A.D. Bakker

    2014-01-01

    In response to mechanical loading skeletal muscle produces numerous growth factors and cytokines that enter the circulation. We hypothesized that myotubes produce soluble factors that affect osteoclast formation and aimed to identify which osteoclastogenesis-modulating factors are differentially pro

  6. RX871024 reduces NO production but does not protect against pancreatic beta-cell death induced by proinflammatory cytokines

    DEFF Research Database (Denmark)

    Zaitseva, Irina I; Sharoyko, Vladimir; Størling, Joachim;

    2006-01-01

    cytokines and correlated with the decrease in p38 MAPK phosphorylation. Conversely, efaroxan did not affect cytokine-induced NO production. Our data indicate that a combination of pro-inflammatory cytokines IL-1beta, IFNgamma, and TNFalpha, conditions modelling those that take place in type 1 diabetes...... of the cytokines IL-1beta, IFNgamma, and TNFalpha. To address this issue, experiments involving different methods for detection of cell death, different concentrations of the cytokines, and a variety of conditions of preparation and culturing of ob/ob mouse islets and beta-cells have been carried out. Thoroughly...... performed experiments have not been able to demonstrate a protective effect of RX871024 and efaroxan on beta-cell death induced by the combination of cytokines. However, the inhibitory effect of RX871024 on NO production in ob/ob mouse islets and beta-cells was still observed in the presence of all three...

  7. 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)....

  8. Cytokines and mood in healthy young adults

    NARCIS (Netherlands)

    Jansen, J.; Fernstrand, A.M.; Van De Loo, A.J.A.E.; Garssen, J.; Verster, J.C.

    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

  9. 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

  10. 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.

  11. 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

  12. 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.

  13. Cytokine signalling in embryonic stem cells

    DEFF Research Database (Denmark)

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

    2006-01-01

    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......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...... signalling pathways have been documented. In addition, gp130 activation leads to both PI3K and Src activation. The canonical Wnt pathway is sufficient to maintain self-renewal of both human ES cells and mouse ES cells. It seems quite possible that the main pathway maintaining self-renewal in ES cells...

  14. 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.

  15. 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

  16. 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

  17. Soluble cytokine receptors in biological therapy.

    Science.gov (United States)

    Fernandez-Botran, Rafael; Crespo, Fabian A; Sun, Xichun

    2002-08-01

    Due to their fundamental involvement in the pathogenesis of many diseases, cytokines constitute key targets for biotherapeutic approaches. The discovery that soluble forms of cytokine receptors are involved in the endogenous regulation of cytokine activity has prompted substantial interest in their potential application as immunotherapeutic agents. As such, soluble cytokine receptors have many advantages, including specificity, low immunogenicity and high affinity. Potential disadvantages, such as low avidity and short in vivo half-lifes, have been addressed by the use of genetically-designed receptors, hybrid proteins or chemical modifications. The ability of many soluble cytokine receptors to inhibit the binding and biological activity of their ligands makes them very specific cytokine antagonists. Several pharmaceutical companies have generated a number of therapeutic agents based on soluble cytokine receptors and many of them are undergoing clinical trials. The most advanced in terms of clinical development is etanercept (Enbrel, Immunex), a fusion protein between soluble TNF receptor Type II and the Fc region of human IgG1. This TNF-alpha; antagonist was the first soluble cytokine receptor to receive approval for use in humans. In general, most agents based on soluble cytokine receptors have been safe, well-tolerated and have shown only minor side effects in the majority of patients. Soluble cytokine receptors constitute a new generation of therapeutic agents with tremendous potential for applications in a wide variety of human diseases. Two current areas of research are the identification of their most promising applications and characterisation of their long-term effects. PMID:12171504

  18. 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...... significance. However, serial quantitation of soluble tumour necrosis factor receptor I (sTNFRI) is more likely to reflect the degree of inflammatory activation induced by pretransplant conditioning....

  19. 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)

    Torres, Mariana Andrade; 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; de Andrade, André Furugen Cesar

    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 boar semen was cryopreserved without SP-SRF; however, it was not able to decrease tyrosine phosphorylation (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

  20. PPARα/γ激动剂对糖尿病伴冠心病患者血浆炎症因子的影响%Effects of PPAR α/γ dual agonists on plasma inflammatory cytokine in patients with diabetes complicated with coronary artery disease

    Institute of Scientific and Technical Information of China (English)

    韦金儒; 唐泉

    2012-01-01

    'y-agonist on plasma concentrations of inflammatory cytokine in patients with diabetes mellitus complicated with coronary artery disease (CAD). Methods Eighty CAD patients were divided into four groups- rosiglitazone group (n=20), bezafibrate group (n=20), combination of rosiglitazone and bezafibrate group(n=20) and control group(n= 20). After treatment, patients were followed-up for 12 weeks. Plasma sample was collected from each patient before and after the treatment, respectively. Then plasma concentrations of C-reactive protein(CRP) and monocyte chemoatactic protein-1 (MCP-1) were measured by enzyme-linked immunosorbent assay. At the same time, the changes of fasting plasma glucose (FPC), fasting insulin, insulin resistance index (IRI), hemoglobin Ale (HbAlc), lipid and body mass index were also investigated. Results At the end of 12 weeks, patients in rosiglitazone group,bezafibrate group and combined rosiglitazone and bezafibrate group showed significantly reduction in plasma concentrations of CRP, MCP-1, FPG, insulin, IRI, HbAlc, triglycerides, total cholesterol, low-density lipoprotein cholesterol, and increasion in concentration of high-density lipoprotein cholesterol (P<0.05), especially in combined rosiglitazone and bezafibrate group. Concentrations of MCP-1 secreted by monocyte which was induced by lipopolysaccharide in rosiglitazone group,bezafibrate group and combined rosiglitazone and bezafibrate group were siginificantly higher after 12 weeks treatment than thoae before treatment (P<0.05), and the decrease was most obviously in combined rosiglitazone and bezafibrate group. Decline in plasma concentrations of CRP appear to be correlated with the decrease of insulin (r=0.048,P<0.01) and insulin resistance index (r =0.496, P<0.001), but there was no correlation with other factors. Conclusions Combination of rosiglilazone and bezafibrale can increase insulin sensitivity, improve glucose metabolism and reduce the concentrations of CRP, MCP-1 in patients with diabetes

  1. Effects of Subacute Ruminal Acidosis on Plasma Cytokine and Hormone Contents in Dairy Goats%亚急性瘤胃酸中毒对奶山羊血浆细胞因子和激素含量的影响

    Institute of Scientific and Technical Information of China (English)

    胡红莲; 谢天宇; 杨淑青; 高民; 姚焰础

    2015-01-01

    本试验旨在研究以递增饲粮非纤维性碳水化合物与中性洗涤纤维比( NFC/NDF)方式诱导奶山羊发生亚急性瘤胃酸中毒( SARA)后,血浆细胞因子和激素含量的变化。选取9只体况良好,体重接近的泌乳期莎能奶山羊,随机分为3组(对照组、SARA组、恢复组, n=3),对照组饲喂基础饲粮,SARA组和恢复组先后饲喂NFC/NDF为1.40、1.79、2.31、3.23的4种试验饲粮诱导SARA发生,每种饲喂15 d,恢复组奶山羊诱导SARA后自由采食青干草30 d。对照组3只羊分别在饲养30、60(与SARA组同时)和90 d(与恢复组同时)屠宰。结果表明:1) SARA长期提高了血浆LPS浓度,恢复组与SARA组差异不显著( P>0.05)。2)与对照组相比,SARA组奶山羊血浆中促炎性细胞因子肿瘤坏死因子-α( TNF-α)、白细胞介素( IL)-1β和IL-6含量呈升高趋势(P>0.05),IL-2含量显著升高(P0.05),γ-干扰素(IFN-γ)含量显著降低(P0.05);SARA组奶山羊血浆中生长激素、胰岛素样生长因子-Ⅰ、胰岛素含量变化不显著(P>0.05),催乳素(PRL)和皮质醇(COR)含量均显著升高(P0.05),而COR含量则回归到对照组水平( P>0.05)。本研究结果显示,SARA可引起奶山羊血浆中长时间含有一定量的LPS,引发机体免疫和炎症反应,并引起内分泌激素的变化,这一系列变化导致奶山羊长期处于应激状态。%This experiment was conducted to investigate the effects of subacute ruminal acidosis ( SARA) in-duced by gradually increasing dietary non-fiber carbohydrate/neutral detergent fiber ratios ( NFC/NDF ) on plasma hormone and cytokine contents in dairy goats. Nine healthy lactating Saanen dairy goats with similar body weight were randomly allocated to three groups ( control group, SARA group and recovery group, n=3 ) . Dairy goats in control group were fed a basal diet;those in SARA group and recovery group were fed diets with different NFC/NDF (1.40, 1.79, 2.31 and 3.23, respectively, each for 15 days

  2. 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 

  3. 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

  4. Distinctive subcellular inhibition of cytokine-induced SRC by salubrinal and fluid flow.

    Science.gov (United States)

    Wan, Qiaoqiao; Xu, Wenxiao; Yan, Jing-long; Yokota, Hiroki; Na, Sungsoo

    2014-01-01

    A non-receptor protein kinase Src plays a crucial role in fundamental cell functions such as proliferation, migration, and differentiation. While inhibition of Src is reported to contribute to chondrocyte homeostasis, its regulation at a subcellular level by chemical inhibitors and mechanical stimulation has not been fully understood. In response to inflammatory cytokines and stress to the endoplasmic reticulum (ER) that increase proteolytic activities in chondrocytes, we addressed two questions: Do cytokines such as interleukin 1 beta (IL1β) and tumor necrosis factor alpha (TNFα) induce location-dependent Src activation? Can cytokine-induced Src activation be suppressed by chemically alleviating ER stress or by applying fluid flow? Using live cell imaging with two Src biosensors (i.e., cytosolic, and plasma membrane-bound biosensors) for a fluorescence resonance energy transfer (FRET) technique, we determined cytosolic Src activity as well as membrane-bound Src activity in C28/I2 human chondrocytes. In response to TNFα and IL1β, both cytosolic and plasma membrane-bound Src proteins were activated, but activation in the cytosol occurred earlier than that in the plasma membrane. Treatment with salubrinal or guanabenz, two chemical agents that attenuate ER stress, significantly decreased cytokine-induced Src activities in the cytosol, but not in the plasma membrane. In contrast, fluid flow reduced Src activities in the plasma membrane, but not in the cytosol. Collectively, the results demonstrate that Src activity is differentially regulated by salubrinal/guanabenz and fluid flow in the cytosol and plasma membrane. PMID:25157407

  5. Distinctive subcellular inhibition of cytokine-induced SRC by salubrinal and fluid flow.

    Directory of Open Access Journals (Sweden)

    Qiaoqiao Wan

    Full Text Available A non-receptor protein kinase Src plays a crucial role in fundamental cell functions such as proliferation, migration, and differentiation. While inhibition of Src is reported to contribute to chondrocyte homeostasis, its regulation at a subcellular level by chemical inhibitors and mechanical stimulation has not been fully understood. In response to inflammatory cytokines and stress to the endoplasmic reticulum (ER that increase proteolytic activities in chondrocytes, we addressed two questions: Do cytokines such as interleukin 1 beta (IL1β and tumor necrosis factor alpha (TNFα induce location-dependent Src activation? Can cytokine-induced Src activation be suppressed by chemically alleviating ER stress or by applying fluid flow? Using live cell imaging with two Src biosensors (i.e., cytosolic, and plasma membrane-bound biosensors for a fluorescence resonance energy transfer (FRET technique, we determined cytosolic Src activity as well as membrane-bound Src activity in C28/I2 human chondrocytes. In response to TNFα and IL1β, both cytosolic and plasma membrane-bound Src proteins were activated, but activation in the cytosol occurred earlier than that in the plasma membrane. Treatment with salubrinal or guanabenz, two chemical agents that attenuate ER stress, significantly decreased cytokine-induced Src activities in the cytosol, but not in the plasma membrane. In contrast, fluid flow reduced Src activities in the plasma membrane, but not in the cytosol. Collectively, the results demonstrate that Src activity is differentially regulated by salubrinal/guanabenz and fluid flow in the cytosol and plasma membrane.

  6. Selenium supplementation in patients undergoing hematopoietic stem cell transplantation: effects on pro-inflammatory cytokines levels

    OpenAIRE

    Daeian, Nesa; Radfar, Mania; Jahangard-Rafsanjani, Zahra; Hadjibabaie, Molouk; Ghavamzadeh, Ardeshir

    2014-01-01

    Background Pro-inflammatory cytokines including tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) play an important role in the development of hematopoietic stem cell transplantation (HSCT) complications. We explored the effect of Selenium as an antioxidant and anti-inflammatory agent on pro-inflammatory cytokines levels in HSCT candidates. Findings Plasma concentrations of TNF-α, IL-1β and IL-6 were measured in 74 patients from a double-blind, randomized, p...

  7. 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)

  8. 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.

  9. Direct association between pharyngeal viral secretion and host cytokine response in severe pandemic influenza

    Directory of Open Access Journals (Sweden)

    Castro Carmen

    2011-08-01

    Full Text Available Abstract Background Severe disease caused by 2009 pandemic influenza A/H1N1virus is characterized by the presence of hypercytokinemia. The origin of the exacerbated cytokine response is unclear. As observed previously, uncontrolled influenza virus replication could strongly influence cytokine production. The objective of the present study was to evaluate the relationship between host cytokine responses and viral levels in pandemic influenza critically ill patients. Methods Twenty three patients admitted to the ICU with primary viral pneumonia were included in this study. A quantitative PCR based method targeting the M1 influenza gene was developed to quantify pharyngeal viral load. In addition, by using a multiplex based assay, we systematically evaluated host cytokine responses to the viral infection at admission to the ICU. Correlation studies between cytokine levels and viral load were done by calculating the Spearman correlation coefficient. Results Fifteen patients needed of intubation and ventilation, while eight did not need of mechanical ventilation during ICU hospitalization. Viral load in pharyngeal swabs was 300 fold higher in the group of patients with the worst respiratory condition at admission to the ICU. Pharyngeal viral load directly correlated with plasma levels of the pro-inflammatory cytokines IL-6, IL-12p70, IFN-γ, the chemotactic factors MIP-1β, GM-CSF, the angiogenic mediator VEGF and also of the immuno-modulatory cytokine IL-1ra (p Conclusions Severe respiratory disease caused by the 2009 pandemic influenza virus is characterized by the existence of a direct association between viral replication and host cytokine response, revealing a potential pathogenic link with the severe disease caused by other influenza subtypes such as H5N1.

  10. 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.

  11. 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. PMID:16188452

  12. 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.

  13. 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

  14. Cytokine production by cells in cerebrospinal fluid during experimental allergic encephalomyelitis in SJL/J mice

    DEFF Research Database (Denmark)

    Renno, T; Lin, J Y; Piccirillo, C;

    1994-01-01

    , normalized to actin, were almost undetectable in control tissues, and only slightly elevated in whole CNS tissue from animals with mild EAE. Both cytokine messages were strongly upregulated in CNS tissues derived from severely affected animals, consistent with previous observations correlating disease...... progression with infiltration by memory/effector CD4+ T cells, the major source of these cytokines. This cytokine upregulation was specific to the CNS, since other organs from the same animals did not express significant levels of IL-2 and IFN-gamma. CSF was obtained from the cisterna magna of unperfused mice...... and verified as such by absence of red blood cells (RBCs) and by immunoglobulin concentration orders of magnitude lower than in serum. Cytokine message was measured in RNA isolated from cells in CSF. Levels of IL-2 and IFN-gamma mRNA in CSF cells were significantly elevated in mild EAE and strongly upregulated...

  15. Respiratory Mechanics and Plasma Levels of Tumor Necrosis Factor Alpha and Interleukin 6 Are Affected by Gas Humidification during Mechanical Ventilation in Dogs

    OpenAIRE

    HERNÁNDEZ-JIMÉNEZ, CLAUDIA; García-Torrentera, Rogelio; Olmos-Zúñiga, J. Raúl; Jasso-Victoria, Rogelio; Miguel O Gaxiola-Gaxiola; 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 ...

  16. [The role of cytokines for the pathogenesis of psoriasis].

    Science.gov (United States)

    Kapp, A

    1993-04-01

    Psoriasis is an inflammatory skin disorder characterized by marked hyperproliferation of keratinocytes in association with vascular expansion, fibroblast activation, leucocyte infiltration, and alterations of eicosanoid metabolism and of cytokine production. However, it is unclear at present whether these changes are the cause or the effect of the significantly increased keratinocyte turnover. More than one mechanism is involved in triggering active psoriasis; genetic predisposition and environmental factors affecting the immune system have a particularly important role. Most of the therapeutic regimens used for the treatment of psoriasis are immunosuppressive. Therefore, it is tempting to speculate that a specific defect of the immune system is the major pathogenic principle in psoriasis. There are several lines of evidence suggesting that changes in cytokine production by keratinocytes and immunocompetent cells in the skin of the patients, particularly of interleukin-6 and TGF alpha, may play an important part in propagation of the inflammatory response in psoriasis. Further studies are required to find how far local T-cell activation is involved as a basic mechanism of initiation and maintenance of the psoriatic inflammatory response. Accordingly, parameters such as the evaluation of cytokine production in vitro and in vivo and the measurement of cellular activation products may be useful in the diagnosis and monitoring of psoriasis.

  17. 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.

  18. 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.

  19. 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.

  20. 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...

  1. Anti cytokine therapy in chronic inflammatory arthritis.

    Science.gov (United States)

    Thompson, Charlotte; Davies, Ruth; Choy, Ernest

    2016-10-01

    This is a review looking at anti cytokine therapy in Rheumatoid Arthritis (RA), Psoriatic Arthritis (PSA) and Ankylosing Spondylitis (AS). The review explores the similarities and differences in the clinical features, as well as treatments and cytokines involved in the development and propagation of the disease. Particular attention is paid to TNFα inhibitors IL-1ra, IL-6 and JAK kinase Inhibitors, anti IL23 and IL-12 and the new developments with anti-IL-17. PMID:27497159

  2. Side effects of cytokines approved for therapy.

    Science.gov (United States)

    Baldo, Brian A

    2014-11-01

    Cytokines, currently known to be more than 130 in number, are small MW (aldesleukin (rhIL-2), oprelvekin (rhIL-11), filgrastim and tbo-filgrastim (rhG-CSF), sargramostim (rhGM-CSF), metreleptin (rh-leptin) and the rh-erythropoietins, epoetin and darbepoietin alfa. Anakinra, a recombinant receptor antagonist for IL-1, is in the IL-1 family; recombinant interferons alfa-1, alfa-2, beta-1 and gamma-1 make up the interferon family; palifermin (rhKGF) and becaplermin (rhPDGF) are in the PDGF family; and rhBMP-2 and rhBMP-7 represent the TGFβ family. The main physicochemical features, FDA-approved indications, modes of action and side effects of these approved cytokines are presented. Underlying each adverse events profile is their pleiotropism, potency and capacity to release other cytokines producing cytokine 'cocktails'. Side effects, some serious, occur despite cytokines being endogenous proteins, and this therefore demands caution in attempts to introduce individual members into the clinic. This caution is reflected in the relatively small number of cytokines currently approved by regulatory agencies and by the fact that 14 of the FDA-approved preparations carry warnings, with 10 being black box warnings. PMID:25270293

  3. Fetuin-A induces cytokine expression and suppresses adiponectin production.

    Directory of Open Access Journals (Sweden)

    Anita M Hennige

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

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

    DEFF Research Database (Denmark)

    Rue, Nana; Vissing, John; Galbo, Henrik

    2014-01-01

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

  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. 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.

  7. 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...

  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. 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.

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

    Objective: To explore the role of endothelin and related cytokines (IL-5, IL-6, IL-8) in the development of bronchial asthma in pediatric patients. Methods: Plasma ET-1 (with RIA) and serum IL-5 (with ELISA), IL-6, IL-8 (with RIA) levels were measured in 42 pediatric patients with bronchial asthma and 30 controls. Results: The plasma ET-1 levels in the patients during acute attack (n=22) were significantly higher than those in patients during remission (n=20) as well as in controls (P0.05). Levels of ET-1 were positively correlated with those of IL-5 (during attack, r=0.560, P<0.01; during remission, r=0.435, P<0.01). Conclusion: ET and the cytokines IL-5, IL-6, IL-8 participated in the pathogenesis of bronchial asthma through different mechanisms and dynamic determination of which could reflect the progression of the disease. (authors)

  12. Cytokine Gene Polymorphisms in Egyptian Cases with Brain Tumors

    International Nuclear Information System (INIS)

    Background: Cytokines are proposed to play important roles in brain tumor biology as well as neuro degeneration or impaired neuronal function. Objectives: This work aimed to check the association of polymorphisms of cytokine genes in Egyptian cases with brain tumors. Methods: This work included 45 cases affected by brain tumors diagnosed as 24 benign and 21 malignant. Their median age was 45 years, and they were 20 males and 25 females. These cases were taken randomly from the Neurosurgery Department of Mansoura University Hospital, Egypt. Case genotypes were compared to 98 healthy unrelated controls from the same locality. DNA was amplified using PCR utilizing sequence specific primers (SSP) for detection of polymorphisms related to TNF-a-308 (G/A), IL-10-1082 (G/A), IL-6-174 (G/C) and IL-1Ra (VNTR) genes. Results: Cases affected with benign brain tumors showed a significant higher frequency of IL-10-1082 A/A [odds ratio (OR=8.0), p<0.001] and IL-6-174 C/C (OR=6.3, p=0.002) homozygous genotypes as compared to controls. Malignant cases, on the other hand, showed significantly higher frequency of IL-6-174 C/C (OR =4.8, p=0.002) homozygous genotype and TNF-a-308 A/A (OR=4.9, p<0.001) homozygous genotype when compared to controls. In the meantime, all cases showed no significant difference regarding the distribution of IL-1Ra VNTR genotype polymorphism compared to controls. Conclusions: Cytokine gene polymorphisms showed a pattern of association with brain tumors which may have potential impact on family counseling and disease management.

  13. Avian cytokines - the natural approach to therapeutics.

    Science.gov (United States)

    Lowenthal, J W; Lambrecht, B; van den Berg, T P; Andrew, M E; Strom, A D; Bean, A G

    2000-01-01

    While the effective use of antibiotics for the control of human disease has saved countless lives and has increased life expectancy over the past few decades, there are concerns arising from their usage in livestock. The use of antibiotic feed additives in food production animals has been linked to the emergence in the food chain of multiple drug-resistant bacteria that appear impervious to even the most powerful antimicrobial agents. Furthermore, the use of chemical antimicrobials has led to concerns involving environmental contamination and unwanted residues in food products. The imminent banning of antibiotic usage in livestock feed has intensified the search for environmentally-friendly alternative methods to control disease. Cytokines, as natural mediators and regulators of the immune response, offer exciting new alternatives to conventional chemical-based therapeutics. The utilisation of cytokines is becoming more feasible, particularly in poultry, with the recent cloning of a number of avian cytokine genes. Chickens offer an attractive small animal model system with which to study the effectiveness of cytokine therapy in the control of disease in intensive livestock. In this report we will review the status of avian cytokines and focus on our recent studies involving the therapeutic potential of chicken interferon gamma (ChIFN-gamma) as a vaccine adjuvant and a growth promoter. PMID:10717298

  14. 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.

  15. Interleukin-1 Family Cytokines in Liver Diseases

    Directory of Open Access Journals (Sweden)

    Hiroko Tsutsui

    2015-01-01

    Full Text Available The gene encoding IL-1 was sequenced more than 30 years ago, and many related cytokines, such as IL-18, IL-33, IL-36, IL-37, IL-38, IL-1 receptor antagonist (IL-1Ra, and IL-36Ra, have since been identified. IL-1 is a potent proinflammatory cytokine and is involved in various inflammatory diseases. Other IL-1 family ligands are critical for the development of diverse diseases, including inflammatory and allergic diseases. Only IL-1Ra possesses the leader peptide required for secretion from cells, and many ligands require posttranslational processing for activation. Some require inflammasome-mediated processing for activation and release, whereas others serve as alarmins and are released following cell membrane rupture, for example, by pyroptosis or necroptosis. Thus, each ligand has the proper molecular process to exert its own biological functions. In this review, we will give a brief introduction to the IL-1 family cytokines and discuss their pivotal roles in the development of various liver diseases in association with immune responses. For example, an excess of IL-33 causes liver fibrosis in mice via activation and expansion of group 2 innate lymphoid cells to produce type 2 cytokines, resulting in cell conversion into pro-fibrotic M2 macrophages. Finally, we will discuss the importance of IL-1 family cytokine-mediated molecular and cellular networks in the development of acute and chronic liver diseases.

  16. Induction of inflammatory cytokines by cartilage extracts.

    Science.gov (United States)

    Merly, Liza; Simjee, Shabana; Smith, Sylvia L

    2007-03-01

    Shark cartilage extracts were examined for induction of cytokines and chemokines in human peripheral blood leukocytes. Primary leukocyte cultures were exposed to a variety of aqueous and organic extracts prepared from several commercial brands of shark cartilage. From all commercial sources of shark cartilage tested the acid extracts induced higher levels of TNFalpha than other extracts. Different commercial brands of shark cartilage varied significantly in cytokine-inducing activity. TNFalpha induction was seen as early as 4 h and IFNgamma at detectable levels for up to four days. Shark cartilage extracts did not induce physiologically significant levels of IL-4. Results suggest that shark cartilage, preferentially, induces Th1 type inflammatory cytokines. When compared to bovine cartilage extract, collagen, and chondroitin sulfate, shark cartilage induced significantly higher levels of TNFalpha. Treatment with digestive proteases (trypsin and chymotrypsin) reduced the cytokine induction response by 80%, suggesting that the active component(s) in cartilage extracts is proteinaceous. The induction of Th1 type cytokine response in leukocytes is a significant finding since shark cartilage, taken as a dietary supplement for a variety of chronic degenerative diseases, would be contraindicated in cases where the underlying pathology of the chronic condition is caused by inflammation. PMID:17276897

  17. Surface plasma functionalization influences macrophage behavior on carbon nanowalls

    International Nuclear Information System (INIS)

    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: • N2 and O2 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. • O2 plasma treatment of CNW leads to a more activated macrophage phenotype

  18. 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.

  19. Combinatorial signals by inflammatory cytokines and chemokines mediate leukocyte interactions with extracellular matrix.

    Science.gov (United States)

    Vaday, G G; Franitza, S; Schor, H; Hecht, I; Brill, A; Cahalon, L; Hershkoviz, R; Lider, O

    2001-06-01

    On their extravasation from the vascular system into inflamed tissues, leukocytes must maneuver through a complex insoluble network of molecules termed the extracellular matrix (ECM). Leukocytes navigate toward their target sites by adhering to ECM glycoproteins and secreting degradative enzymes, while constantly orienting themselves in response to specific signals in their surroundings. Cytokines and chemokines are key biological mediators that provide such signals for cell navigation. Although the individual effects of various cytokines have been well characterized, it is becoming increasingly evident that the mixture of cytokines encountered in the ECM provides important combinatorial signals that influence cell behavior. Herein, we present an overview of previous and ongoing studies that have examined how leukocytes integrate signals from different combinations of cytokines that they encounter either simultaneously or sequentially within the ECM, to dynamically alter their navigational activities. For example, we describe our findings that tumor necrosis factor (TNF)-alpha acts as an adhesion-strengthening and stop signal for T cells migrating toward stromal cell-derived factor-1alpha, while transforming growth factor-beta down-regulates TNF-alpha-induced matrix metalloproteinase-9 secretion by monocytes. These findings indicate the importance of how one cytokine, such as TNF-alpha, can transmit diverse signals to different subsets of leukocytes, depending on its combination with other cytokines, its concentration, and its time and sequence of exposure. The combinatorial effects of multiple cytokines thus affect leukocytes in a step-by-step manner, whereby cells react to cytokine signals in their immediate vicinity by altering their adhesiveness, directional movement, and remodeling of the ECM. PMID:11404372

  20. 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...

  1. Plasma properties

    International Nuclear Information System (INIS)

    A cursory examination of the research activities of the Magneto-Fluid Dynamics Division for the calendar year 1988 shows the effects of the gradual transformation of the group. Although our principal activity, fusion plasma physics research, is unchanged, the work shows closer ties to problems relevant to present experiments than previously. Most notable is the concentrated effort on tokamak equilibrium and transport. We are exploring the implication of turbulence induced transport, resistive MHD effects, neoclassical transport, and possible interpretations of transport based on classical phenomena. In addition, one of our members has chosen to focus on problems of enhanced statistical methods for interpretation of experiments. All of this activity preceded the Tokamak Transport Initiative and reflects our active involvement and concern with the world-wide tokamak program. Since equilibrium and transport are by no means the only theoretical plasma physics problems affecting fusion devices we continue substantial efforts in wave propagation and heating, particle simulation of plasmas, stability theory, enhancement of numerical algorithms, and general plasma physics. We are attempting to develop effective numerical schemes for the Boltzmann equation, adaptive grid methods for MHD, and particle simulation of boundary and antenna effects. Many of these topics reflect our continuing concern to maintain a modest effort in the development of theoretical models and tools for problems of real significance to fusion, but not necessarily of immediate highest priority. We select problems which we expect to become extremely important in the future. Our space plasma physics activities, funded by agencies other than DOE, transfers knowledge learned in fusion plasma physics to another area and conversely stimulates work also relevant to fusion problems

  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. PMID:16050160

  3. 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.

  4. [Plant-Producers Of Recombinant Cytokines (Review)].

    Science.gov (United States)

    Burlakovskii, M S; Yemel'yanov, V V; Lutova, L A

    2016-01-01

    Cytokines are a family of signaling polypeptides involved in cell-cell interactions in the process of the immune response, as well as in the regulation of a number of normal physiological functions. Cytokines are used in medicine for the treatment of cancer, immune disorders, viral infections, and other socially significant diseases, but the extent of their use is limited by the high production cost of the active agent. The development of this area of pharmacology is associated with the success of genetic engineering, which allows the production of significant amounts of protein by transgenic organisms. The review discusses the latest advances in the production of various cytokines with the use of genetically modified plants. PMID:27266244

  5. 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.

  6. 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

  7. 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.

  8. Parasite-Specific IL-17-Type Cytokine Responses and Soluble IL-17 Receptor Levels in Alveolar Echinococcosis Patients

    Directory of Open Access Journals (Sweden)

    Christian J. Lechner

    2012-01-01

    Full Text Available Alveolar Echinococcosis (AE caused by the cestode Echinococcus multilocularis, is a severe helminth infection of man, where unrestricted parasite growth will ultimately result in organ failure and fatality. The tissue-infiltrative growth of the larval metacestode and the limited efficacy of available drugs complicate successful intervention in AE; patients often need life-long medication, and if possible, surgical resection of affected tissues and organs. Resistance to AE has been reported, but the determinants which confer protection are not known. ln this study, we analyzed in patients at distinct stages of Alveolar Echirococcosis, that is cured, stable and progressive AE, as well as in infection-free controls, the cellular production and plasma levels of pro-inflammatory cytokines lL-17A, lL-17B, lL-17F and their soluble receptors lL-17RA (slL-17RA and IL-17RB (sIL-17RB. Significantly elevated levels of IL-17B and slL-17RB were observed, whilst lL-17F and slL-17RA were reduced in patients with AE. Similarly, the cellular production of lL-17F and slL-L7RA in response to E. multilocularis antigens was low in AE patients, while levels of slL-17RB were highly enhanced. These observations suggest immune-modulating properties of E. multitocularis on lL-17 cytokine-mediated pro-inflammatory immune responses; this may facilitate the tissue infiltrative growth of the parasite and its persistence in the human host.

  9. 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.

  10. 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.

  11. 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.

  12. Cytokines and the hepatic acute phase response

    NARCIS (Netherlands)

    Moshage, H

    1997-01-01

    The acute phase response is an orchestrated response to tissue injury, infection or inflammation. A prominent feature of this response is the induction of acute phase proteins, which are involved in the restoration of homeostasis. Cytokines are important mediators of the acute phase response. Uncont

  13. 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...

  14. CYTOKINE PROFILING FOR CHEMICAL RESPIRATORY SENSITIZERS

    Science.gov (United States)

    CYTOKINE PROFILING FOR CHEMICAL RESPIRATORY SENSITIZERS. LM Plitnick1, SE Loveless2, GS Ladics2, MP Holsapple3, MJ Selgrade4, DM Sailstad4 & RJ Smialowicz4. 1UNC, Chapel Hill, NC; 2DuPont Co., Haskell Laboratory, Newark, DE; 3Dow Chemical, Midland, MI & 4USEPA, NHEERL, RTP, NC.

  15. Cytokines and Chemokines in Irritant Contact Dermatitis

    OpenAIRE

    Haur Yueh Lee; Marco Stieger; Nikhil Yawalkar; Masato Kakeda

    2013-01-01

    Irritant contact dermatitis is a result of activated innate immune response to various external stimuli and consists of complex interplay which involves skin barrier disruption, cellular changes, and release of proinflammatory mediators. In this review, we will focus on key cytokines and chemokines involved in the pathogenesis of irritant contact dermatitis and also contrast the differences between allergic contact dermatitis and irritant contact dermatitis.

  16. 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.

  17. Cytokines in atherosclerosis: an intricate balance

    NARCIS (Netherlands)

    M.C.S. Boshuizen

    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

  18. [Cytokines in the treatment of blood diseases].

    Science.gov (United States)

    Robak, T

    1995-01-01

    Cytokines are a class of signal peptides which represent a major communication network in living organism. Over the last decade, the discovery, cloning and purification of hematopoietic cytokines (interleukins, hematopoietic growth factors) has increased our understanding of the regulation, proliferation, differentiation and function of hematopoietic cells. More recently, the large scale production of the recombinant forms of these molecules has enabled to treat the patients with pharmacologic doses of cytokines. The therapeutic activity of interferon-alpha (IFN-alpha) has been demonstrated in patients with chronic myeloid leukaemia and other chronic myeloproliferative syndromes. IFN-gamma is useful in the prevention of infections in patients with chronic granulomatous disease. Erythropoietin (EPO) was the first hematopoietic growth factor available for clinical use, initially to treat anaemia in renal failure patients. The next cytokines introduced into the clinic were granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage CSF (GM-CSF). They are used successfully in haematological malignant disorders to stimulate granulopoiesis after chemotherapy or bone marrow transplantation and to help mobilise marrow stem cells for peripheral blood stem cell transplantation. Interleukin (IL)-1, -2, -3, -4, -6 and -11 have been tested in clinical trials. However, the value of these agents remains to be established. PMID:7544526

  19. Waves in unmagnetized plasma

    International Nuclear Information System (INIS)

    A review of linear and weakly non-linear theory of electron waves, ion waves and electromagnetic waves in plasmas is presented. The author restricts the discussion to an infinitely extended, homogeneous and isotropic plasma, not affected by external fields and described by Vlasov's and Maxwell's equations. (Auth.)

  20. Cytokines and Metabolic Patterns in Pediatric Patients with Critical Illness

    Directory of Open Access Journals (Sweden)

    George Briassoulis

    2010-01-01

    Full Text Available It is not known if cytokines, which are cell-derived mediators released during the host immune response to stress, affect metabolic response to stress during critical illness. The aim of this prospective study was to determine whether the metabolic response to stress is related to the inflammatory interleukin-6 (IL-6, 10 (IL-10, and other stress mediators' responses and to assess their relationships with different feeding patterns, nutritional markers, the severity of illness as assessed by the Multiple Organ System Failure (MOSF, the Pediatric Risk of Mortality Score (PRISM, systemic inflammatory response syndrome (SIRS, and mortality in critically ill children. Patients were classified as hypermetabolic, normometabolic, and hypometabolic when the measured resting energy expenditures (REE were >110%, 90–110% and, <90% of the predicted basal metabolic rate, respectively. The initial predominance of the hypometabolic pattern (48.6% declined within 1 week of acute stress (20%, and the hypermetabolic patterns dominated only after 2 weeks (60%. Only oxygen consumption (VO2 and carbon dioxide production (VCO2 (<.0001 but none of the cytokines and nutritional markers, were independently associated with a hypometabolic pattern. REE correlated with the IL-10 but not PRISM. In the presence of SIRS or sepsis, CRP, IL-6, IL-10, Prognostic Inflammatory and Nutritional Index (NI, and triglycerides—but not glucose, VO2, or VCO2 increased significantly. High IL-10 levels (=.0000 and low measured REE (=.0000 were independently associated with mortality (11.7%, which was higher in the hypometabolic compared to other metabolic patterns (<.005. Our results showed that only VO2 and VCO2, but not IL-6 or IL-10, were associated with a hypometabolic pattern which predominated the acute phase of stress, and was associated with increased mortality. Although in SIRS or sepsis, the cytokine response was reliably reflected by increases in NI and triglycerides, it was

  1. 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.

  2. T-lymphocyte cytokine profiles in compositae airborne dermatitis.

    Science.gov (United States)

    Stingeni, L; Agea, E; Lisi, P; Spinozzi, F

    1999-10-01

    Compositae airborne dermatitis is a well-recognized disorder characterized by erythematosquamous lesions and papules on light-exposed areas. The presence of positive patch test reactions and the absence of specific serum IgE suggest delayed-type hypersensitivity, the murine model of which is characterized by a Th1 cytokine production profile [high amounts of interferon (IFN)-gamma and interleukin (IL)-2; little or no IL-4 and IL-5]. The aim of this study was to evaluate the cytokine profile of T-cell lines and T-cell clones from peripheral blood in a 38-year-old non-atopic male woodcutter affected by seasonal airborne contact dermatitis. The patient showed positive patch test reactions to several Compositae extracts (Achillea millefolium, Chamomilla recutita, Tanacetum parthenium, T. vulgare) and sesquiterpene lactone mix. On prick testing with Compositae and other plants, serum-specific IgE levels and phototesting were negative or normal. Allergen-specific T-cell lines produced with Compositae extracts showed a good in vitro cell proliferation only to C. recutita extract. Serial cloning performed using the C. recutita-specific T-cell lines revealed an alphabeta+CD4+ phenotype with high amounts of IFN-gamma and IL-4 in T-cell clones. Thus, these cells expressed a preferential Th0 phenotype. These data suggest that in addition to IFN-gamma, other T-cell derived cytokines, such as IL-4, may play a part in the immunopathogenesis of contact dermatitis. PMID:10583117

  3. Plasma theory

    International Nuclear Information System (INIS)

    A series of lectures on plasma theory with the main headings: introduction; charged particles moving in em fields; the liquid model; transport phenomena in the plasma; wave propagation in plasmas; plasma instabilities. 57 figs. (qui)

  4. Exposure of human islets to cytokines can result in disproportionately elevated proinsulin release

    OpenAIRE

    Hostens, Katleen; Pavlovic, Dejan; Zambre, Yasmeeni; Ling, Zhidong; Van Schravendijk, Christiaan; Eizirik, Décio L.; Pipeleers, Daniel G.

    1999-01-01

    Infiltration of immunocytes into pancreatic islets precedes loss of β cells in type 1 diabetes. It is conceivable that local release of cytokines affects the function of β cells before their apoptosis. This study examines whether the elevated proinsulin levels that have been described in prediabetes can result from exposure of β cells to cytokines. Human β-cell preparations were cultured for 48 or 72 hours with or without IL-1β, TNF-α, or IFN-γ, alone or in combination. None of these conditio...

  5. 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.

  6. Influenza Vaccination Generates Cytokine-Induced Memory-like NK Cells: Impact of Human Cytomegalovirus Infection.

    Science.gov (United States)

    Goodier, Martin R; Rodriguez-Galan, Ana; Lusa, Chiara; Nielsen, Carolyn M; Darboe, Alansana; Moldoveanu, Ana L; White, Matthew J; Behrens, Ron; Riley, Eleanor M

    2016-07-01

    Human NK cells are activated by cytokines, immune complexes, and signals transduced via activating ligands on other host cells. After vaccination, or during secondary infection, adaptive immune responses can enhance both cytokine-driven and Ab-dependent NK cell responses. However, induction of NK cells for enhanced function after in vitro exposure to innate inflammatory cytokines has also been reported and may synergize with adaptive signals to potentiate NK cell activity during infection or vaccination. To test this hypothesis, we examined the effect of seasonal influenza vaccination on NK cell function and phenotype in 52 previously unvaccinated individuals. Enhanced, IL-2-dependent, NK cell IFN-γ responses to Influenza A/California/7/2009 virus were detected up to 4 wk postvaccination and higher in human CMV (HCMV)-seronegative (HCMV(-)) individuals than in HCMV-seropositive (HCMV(+)) individuals. By comparison, robust NK cell degranulation responses were observed both before and after vaccination, due to high titers of naturally occurring anti-influenza Abs in human plasma, and did not differ between HCMV(+) and HCMV(-) subjects. In addition to these IL-2-dependent and Ab-dependent responses, NK cell responses to innate cytokines were also enhanced after influenza vaccination; this was associated with proliferation of CD57(-) NK cells and was most evident in HCMV(+) subjects. Similar enhancement of cytokine responsiveness was observed when NK cells were cocultured in vitro with Influenza A/California/7/2009 virus, and this was at least partially dependent upon IFN-αβR2. In summary, our data indicate that attenuated or live viral vaccines promote cytokine-induced memory-like NK cells and that this process is influenced by HCMV infection. PMID:27233958

  7. 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.

  8. Influenza Vaccination Generates Cytokine-Induced Memory-like NK Cells: Impact of Human Cytomegalovirus Infection

    Science.gov (United States)

    Goodier, Martin R.; Rodriguez-Galan, Ana; Lusa, Chiara; Nielsen, Carolyn M.; Darboe, Alansana; Moldoveanu, Ana L.; White, Matthew J.; Behrens, Ron

    2016-01-01

    Human NK cells are activated by cytokines, immune complexes, and signals transduced via activating ligands on other host cells. After vaccination, or during secondary infection, adaptive immune responses can enhance both cytokine-driven and Ab-dependent NK cell responses. However, induction of NK cells for enhanced function after in vitro exposure to innate inflammatory cytokines has also been reported and may synergize with adaptive signals to potentiate NK cell activity during infection or vaccination. To test this hypothesis, we examined the effect of seasonal influenza vaccination on NK cell function and phenotype in 52 previously unvaccinated individuals. Enhanced, IL-2–dependent, NK cell IFN-γ responses to Influenza A/California/7/2009 virus were detected up to 4 wk postvaccination and higher in human CMV (HCMV)-seronegative (HCMV−) individuals than in HCMV-seropositive (HCMV+) individuals. By comparison, robust NK cell degranulation responses were observed both before and after vaccination, due to high titers of naturally occurring anti-influenza Abs in human plasma, and did not differ between HCMV+ and HCMV− subjects. In addition to these IL-2–dependent and Ab-dependent responses, NK cell responses to innate cytokines were also enhanced after influenza vaccination; this was associated with proliferation of CD57− NK cells and was most evident in HCMV+ subjects. Similar enhancement of cytokine responsiveness was observed when NK cells were cocultured in vitro with Influenza A/California/7/2009 virus, and this was at least partially dependent upon IFN-αβR2. In summary, our data indicate that attenuated or live viral vaccines promote cytokine-induced memory-like NK cells and that this process is influenced by HCMV infection. PMID:27233958

  9. 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.

  10. 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.

  11. 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. PMID:26661249

  12. 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.

  13. 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.

  14. Observation of the influence of atorvastatin on inflammatory cytokines in plasma of patients with acute hemorrhage of brain and the effect%阿托伐他汀对急性脑出血患者血浆炎性因子的影响及疗效观察

    Institute of Scientific and Technical Information of China (English)

    肖玉娟

    2015-01-01

    目的:探讨阿托伐他汀对急性脑出血患者血浆炎性因子的影响及临床疗效。方法:2013年2月-2014年7月收治急性脑出血患者60例,随机分成观察组和对照组各30例,对照组给予控制血压、血糖,降低颅内压,营养脑细胞的原则进行治疗。观察组在对照组的基础上加阿托伐他汀20 mg/次,1次/d,均连续治疗2周,观察 TNF-α和hs-CRP 治疗前后的变化。结果:观察组治疗前 TNF-α(44.1±14.2)μg/L,hs-CRP(11.0±3.1)mg/L,治疗后TNF-α(20.1±7.4)μg/L,hs-CRP(4.8±1.1)mg/L;对照组治疗前TNF-α(44.0±14.1)μg/L,hs-CRP(10.9±3.0)mg/L,治疗后TNF-α(32.6±14.8)μg/L,hs-CRP(7.8±2.1)mg/L;两组患者治疗前TNF-α和hs-CRP比较差异无统计学意义(P>0.05),治疗后与治疗前比较有统计学意义(P<0.05),两组治疗后比较有统计学意义(P<0.05);观察组总有效率96.7%,对照组总有效率84.3%,两组比较差异有统计学意义(P<0.05)。结论:阿托伐他汀可以明显降低炎性因子的影响,提高临床疗效,值得推广。%Objective:To explore the influence of atorvastatin on inflammatory cytokines in plasma of patients with acute hemorrhage of brain and the effect.Methods:60 patients with acute cerebral hemorrhage were selected from February 2013 to July 2014.They were randomly divided into the observation group and the control group with 30 cases in each group.The control group were given control of blood pressure and blood sugar,reducing intracranial pressure,brain cell nutrition therapy.The observation group were given atorvastatin 20 mg/time on the basis of the control group,1 time /day,continuously for 2 weeks.We observed the changes of TNF-α and hs-CRP before and after treatment.Results:In the observation group,before treatment,TNF-α was (44.1±14.2)μg/L,and hs-CRP was (11±3.1)mg/L;after treatment,TNF-α was (20.1±7.4)μg/L,and hs-CRP was (4.8±1.1) mg/L.In the control group

  15. 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...

  16. 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......Both (n-3) long-chain PUFA (LCPUFA) and linoleic acid [LA, 18:2(n-6)] improve cardiovascular disease (CVD) risk factors, but a high-LA intake may weaken the effect of (n-3) LCPUFA. In a controlled, double-blind, 2 x 2-factorial 8-wk intervention, we investigated whether fish oil combined......, C-reactive protein, interleukin-6, vascular cell adhesion molecule-1, P-selectin, oxidized LDL, cluster of differentiation antigen 40 ligand (CD40L), adiponectin, or fasting or postprandial BP or HR after adjustment for body weight changes. In conclusion, neither fish oil supplementation nor the LA...

  17. 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.

  18. Protective effects of cytokines on bone marrow suppression by radioimmurotherapy in animal model

    Energy Technology Data Exchange (ETDEWEB)

    Nakamura, Seiji [Ehime Univ., Shigenobu (Japan). School of Medicine

    1995-06-01

    In radioimmunotherapy, the dose limiting factor seems to be bone marrow suppression. Recombinant human granulocyte-colony stimulating factor (rhG-CSF), recombinant human erythropoietin (rhEPO), and recombinant human interleukin-6 (rhIL-6) are the hematopoietic growth factors which regulate the proliferation and differentiation of human bone marrow progenitor cell populations. We applied these cytokines to protect against bone marrow suppression induced by {sup 131}I-radioimmunotherapy in an animal model. Tumor (SCC-3: monocytic cell line)-bearing athymic mice were intraperitoneally injected with 13 MBq/35 {mu}g of {sup 131}I-labeled MoAb (YK-1: IgG1, Kappa). Three days after the injection, various cytokines were subcutaneously injected once a day for 15 days. In the control group, the peripheral blood cell counts decreased over the 20 days, but each cytokine shortened the period of cytopenia; rhG-CSF for granulocytes, rhEPO for erythrocytes, and rhIL-6 for platelets. The biodistribution of {sup 125}I-YK-1 was not changed by the various cytokines. Also, the growth of the tumor was not affected and the antitumor effect of {sup 131}I-YK-1 was not changed. Thus the application of cytokines for radioimmunotherapy was found to be effective in protecting against bone marrow suppression. (author).

  19. 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.

  20. 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.

  1. Changes in serum cytokines in response to musculoskeletal surgical trauma

    OpenAIRE

    Reikeras, Olav; Borgen, Pål; Reseland, Janne E; Lyngstadaas, Staale P

    2014-01-01

    Background Trauma induces local and subsequent systemic inflammatory reactions, and when the cytokine production is deregulated, a systemic inflammatory response syndrome with a potentially lethal outcome can occur. The understanding of the physiological mechanism of the cytokine network would be useful to better comprehend pathological conditions. Methods We analysed a panel of 30 cytokines in the serum of 20 patients operated with total hip replacement. Cytokine release was assessed postope...

  2. 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.

  3. 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

  4. 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

  5. Cytokine-producing T cell subsets in human leishmaniasis

    DEFF Research Database (Denmark)

    Kemp, Kåre

    2000-01-01

    Leishmania specific Th1/Th2 cells have been identified in humans as well as in mice. There is a correlation between the clinical outcome of the infection and the cytokine response profile. Generally, the production of Th2 cytokines leads to severe infection, whereas the production of Th1 cytokine...

  6. THE EFFECTS OF COMBINATORIAL EXPOSURE OF PRO-INFLAMMATORY AND ANTI-INFLAMMATORY CYTOKINES ON AIRWAY EPITHELIAL CELL RELEASE OF CHEMOTACTIC MEDIATORS

    Science.gov (United States)

    Asthma is a chronic inflammatory disorder of the airways affecting nearly 15 million individuals nationally. Within the inflamed asthmatic airway there exist complex interactions between many cells and the cytokines they release, in particular mast cells, eosinophils, T-lymphocy...

  7. Cytokines: muscle protein and amino acid metabolism

    DEFF Research Database (Denmark)

    van Hall, Gerrit

    2012-01-01

    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....... However, this does not seem applicable for inflammatory diseases or human models of sepsis, in which the enhanced imbalance between these two processes is observed within an enhanced, normal or reduced muscle protein turnover.......PURPOSE OF REVIEW: This review highlights the role of cytokines, in particular tumour necrosis factor alpha (TNF-α) and interleukin-6 (IL-6), in relation to the nature of human in-vivo muscle wasting in disease. RECENT FINDINGS: Infusion of human TNF-α and IL-6 in healthy individuals, acutely...

  8. Alteration of cytokine profile following hemorrhagic shock.

    Science.gov (United States)

    Lu, Sumin; Aguilar, Alex; Subramani, Kumar; Poulose, Ninu; Ayub, Ahmar; Raju, Raghavan

    2016-05-01

    Hemorrhage is one of the leading causes of death in patients with trauma. We recently demonstrated that resveratrol can improve cardiac function and prolong life following severe hemorrhagic injury (HI) in a rat model. The present work is focused on determining changes in NF-κB dependent gene expression in the heart and the systemic cytokine milieu following HI and the effect of resveratrol treatment. The results indicate an increase in phosphorylated NF-κB in the heart with a concomitant increase in the expression of NF-κB dependent genes following HI. There was also a significant increase of systemic cytokine levels, both pro and anti-inflammatory, following HI and resolution when treated with resveratrol. This study demonstrates the potential role NF-κB has in the physiological response to HI and the effectiveness of resveratrol in reducing immune activation. PMID:26851979

  9. Multiple cytokines are released when blood from patients with tuberculosis is stimulated with Mycobacterium tuberculosis antigens.

    Directory of Open Access Journals (Sweden)

    Kathryn L Kellar

    Full Text Available BACKGROUND: Mycobacterium tuberculosis (Mtb infection may cause overt disease or remain latent. Interferon gamma release assays (IGRAs detect Mtb infection, both latent infection and infection manifesting as overt disease, by measuring whole-blood interferon gamma (IFN-γ responses to Mtb antigens such as early secreted antigenic target-6 (ESAT-6, culture filtrate protein 10 (CFP-10, and TB7.7. Due to a lack of adequate diagnostic standards for confirming latent Mtb infection, IGRA sensitivity for detecting Mtb infection has been estimated using patients with culture-confirmed tuberculosis (CCTB for whom recovery of Mtb confirms the infection. In this study, cytokines in addition to IFN-γ were assessed for potential to provide robust measures of Mtb infection. METHODS: Cytokine responses to ESAT-6, CFP-10, TB7.7, or combinations of these Mtb antigens, for patients with CCTB were compared with responses for subjects at low risk for Mtb infection (controls. Three different multiplexed immunoassays were used to measure concentrations of 9 to 20 different cytokines. Responses were calculated by subtracting background cytokine concentrations from cytokine concentrations in plasma from blood stimulated with Mtb antigens. RESULTS: Two assays demonstrated that ESAT-6, CFP-10, ESAT-6+CFP-10, and ESAT-6+CFP-10+TB7.7 stimulated the release of significantly greater amounts of IFN-γ, IL-2, IL-8, MCP-1 and MIP-1β for CCTB patients than for controls. Responses to combination antigens were, or tended to be, greater than responses to individual antigens. A third assay, using whole blood stimulation with ESAT-6+CFP-10+TB7.7, revealed significantly greater IFN-γ, IL-2, IL-6, IL-8, IP-10, MCP-1, MIP-1β, and TNF-α responses among patients compared with controls. One CCTB patient with a falsely negative IFN-γ response had elevated responses with other cytokines. CONCLUSIONS: Multiple cytokines are released when whole blood from patients with CCTB is stimulated

  10. 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.

  11. The diverse applications of plasma

    Science.gov (United States)

    Sharma, Mukul; Dubey, Shivani; Darwhekar, Gajanan; Jain, Sudhir Kumar

    2015-07-01

    Plasma being the fourth state of matter has always been an attraction for Physicists and Chemists. With the advent of time, plasma energy has been recognized in having widening horizons in the field of Biomedical Sciences. Plasma medicine can be subdivided into three main fields; Non-thermal atmospheric-pressure direct plasma for medical therapy; Plasma-assisted modification of bio-relevant surfaces and Plasma-based bio-decontamination and sterilization. The basis of the research is that as it has free carrier molecules, it has the ability to target specific cells and regulate functions like wound healing. Plasma does not harm healthy human cells but can kill bacteria and possibly even cancer cells to help treat various diseases. Nosocomial infection control, prevention and containment of contagious diseases, disinfection of medical devices, surface treatment (heat and UV sensitive surfaces) are research of interest. Recent success in generating plasma at very low temperature ie. Cold plasma makes the therapy painless. It has the ability to activate cellular responses and important mechanisms in the body. They target specific molecules such as prothrombin for blood coagulation, cytokines for killing bacteria, and angiogenesis for tissue regeneration. Plasma has bactericidal, fungicidal and virucidal properties. Plasma technology has flourishing future in diverse fields like Textiles, Nanofabrication, Automotives, Waste management, Microbiology, Food Hygiene, Medical Science like Skin treatments, sterilisation of wounds, Hand disinfection, Dental treatments etc. Food hygiene using plasma can be achieved in disinfection of food containers, food surface disinfection, hygiene in food handling, preparation and packaging. Therefore Plasma is most promising field for budding Scientist for fluorishing research in Biological Sciences.

  12. The diverse applications of plasma

    International Nuclear Information System (INIS)

    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

  13. Cytokine Expression in Homozygous Sickle Cell Anaemia

    Directory of Open Access Journals (Sweden)

    Nnodim Johnkennedy

    2015-01-01

    Full Text Available Background: Sickle cell anaemia is an inherited disease in which the red blood cells become rigid and sticky, and change from being disc-shaped to being crescent-shaped. The change in shape is due to the presence of an abnormal form of haemoglobin. This results in severe pain and damage to some organs. Aim and Objective: The study was carried out to determine the levels of cytokine in sickle cell anemia. Material and Methods: Thirty confirmed sickle cell patients in steady state (HbSS-SS and thirty persons with normal haemoglobin (HbAA as well as sixteen sickle cell disease in crises (HbSS-cr between the ages of 15 to 30 years were selected in this study. Cytokines including interleukin 1 beta (IL- 1β, interleukin 2 (IL- 2, interleukin (IL-6, tumour necrosis factor alpha (TNF-α, and interferon gamma (IFN- λ were measured by commercially available ELISA kits. Results: The results obtained showed that the levels of TNF-α and IL-6 in sickle cell anaemia patients in crisis were significantly elevated when compared with sickle cell in steady state (P<0.05. Similarly, the levels of IL-1β, IL-6, and IFN- λ were significantly increased in sickle cell anaemia stable state when compared to HbAA subjects (P<0.05. Conclusion: This may probably implies that cytokine imbalance is implicated in the pathogenesis of sickle cell crisis. Also, cytokines could be used as an inflammatory marker as well as related marker in disease severity and hence therapeutic intervention.

  14. The Role of Cytokines in Sleep Regulation

    OpenAIRE

    Krueger, James M.

    2008-01-01

    Interleukin-1 beta (IL1) and tumor necrosis factor alpha (TNF) promote non-rapid eye movement sleep under physiological and inflammatory conditions. Additional cytokines are also likely involved but evidence is insufficient to conclude that they are sleep regulatory substances. Many of the symptoms induced by sleep loss, e.g. sleepiness, fatigue, poor cognition, enhanced sensitivity to pain, can be elicited by injection of exogenous IL1 or TNF. We propose that ATP, released during neurotransm...

  15. 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.

  16. Proteolytic inactivation of cytokines by Pseudomonas aeruginosa.

    OpenAIRE

    Parmely, M; Gale, A; Clabaugh, M.; Horvat, R; Zhou, W W

    1990-01-01

    Pseudomonas aeruginosa alkaline protease and elastase are thought to contribute to bacterial invasiveness, tissue damage, and immune suppression in animals and patients infected with the bacterium. This study examined the ability of the two proteases to inactivate a number of cytokines that mediate immune and inflammatory responses. Human recombinant gamma interferon (rIFN-gamma) and human recombinant tumor necrosis factor alpha were inactivated by both proteases. Murine rIFN-gamma was relati...

  17. Effect of Blood Component Coatings of Enosseal Implants on Proliferation and Synthetic Activity of Human Osteoblasts and Cytokine Production of Peripheral Blood Mononuclear Cells

    Science.gov (United States)

    Hulejova, Hana; Bartova, Jirina; Riedel, Tomas; Pesakova, Vlasta

    2016-01-01

    The study monitored in vitro early response of connective tissue cells and immunocompetent cells to enosseal implant materials coated by different blood components (serum, activated plasma, and plasma/platelets) to evaluate human osteoblast proliferation and synthetic activity and inflammatory response presented as a cytokine profile of peripheral blood mononuclear cells (PBMCs) under conditions imitating the situation upon implantation. The cells were cultivated on coated Ti-plasma-sprayed (Ti-PS), Ti-etched (Ti-Etch), Ti-hydroxyapatite (Ti-HA), and ZrO2 surfaces. The plasma/platelets coating supported osteoblast proliferation only on osteoconductive Ti-HA and Ti-Etch whereas activated plasma enhanced proliferation on all surfaces. Differentiation (BAP) and IL-8 production remained unchanged or decreased irrespective of the coating and surface; only the serum and plasma/platelets-coated ZrO2 exhibited higher BAP and IL-8 expression. RANKL production increased on serum and activated plasma coatings. PBMCs produced especially cytokines playing role in inflammatory phase of wound healing, that is, IL-6, GRO-α, GRO, ENA-78, IL-8, GM-CSF, EGF, and MCP-1. Cytokine profiles were comparable for all tested surfaces; only ENA-78, IL-8, GM-CSF, and MCP-1 expression depended on materials and coatings. The activated plasma coating led to uniformed surfaces and represented a favorable treatment especially for bioinert Ti-PS and ZrO2 whereas all coatings had no distinctive effect on bioactive Ti-HA and Ti-Etch.

  18. Carbohydrate plasma expanders for passive tumor targeting

    DEFF Research Database (Denmark)

    Hoffmann, Stefan; Caysa, Henrike; Kuntsche, Judith;

    2013-01-01

    inexpensive synthesis, constant availability, a good safety profile, biodegradability and the long clinical use as plasma expanders. Three polymers have been tested for cytotoxicity and cytokine activation in cell cultures and conjugated with a near-infrared fluorescent dye: hydroxyethyl starches (HES 200 k...

  19. 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.

  20. 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.

  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. 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.

  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. Intrinsically disordered cytoplasmic domains of two cytokine receptors mediate conserved interactions with membranes

    DEFF Research Database (Denmark)

    Haxholm, Gitte Wolfsberg; Nikolajsen, Louise Fletcher; Olsen, Johan Gotthardt;

    2015-01-01

    Class 1 cytokine receptors regulate essential biological processes through complex intracellular signaling networks. However, the structural platform for understanding their functions is currently incomplete as structure-function studies of the intracellular domains (ICDs) are critically lacking...... of the inner plasma membrane leaflet through conserved motifs resembling immuno T-cell receptor activation motifs(ITAMs). However, contrary to the observations made for ITAMs, lipid association of the prolactin and growth hormone receptor ICDs was shown to be unaccompanied by changes in transient secondary...... structure and independent of tyrosine phosphorylation. The data presented here provides a new structural platform for studying class 1 cytokine receptors and may implicate the membrane as an active component regulating intracellular signaling....

  5. 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.

  6. 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.

  7. 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. PMID:24170633

  8. Plasma properties

    International Nuclear Information System (INIS)

    This paper discusses the following topics: MHD plasma activity: equilibrium, stability and transport; statistical analysis; transport studies; edge physics studies; wave propagation analysis; basic plasma physics and fluid dynamics; space plasma; and numerical methods

  9. 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.

  10. 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.

  11. 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.

  12. Temporal Cytokine Profiles in Severely Burned Patients: A Comparison of Adults and Children

    Science.gov (United States)

    Finnerty, Celeste C; Jeschke, Marc G; Herndon, David N; Gamelli, Richard; Gibran, Nicole; Klein, Matthew; Silver, Geoff; Arnoldo, Brett; Remick, Daniel; Tompkins, Ronald G

    2008-01-01

    A severe burn leads to hypermetabolism and catabolism resulting in compromised function and structural changes of essential organs. The release of cytokines has been implicated in this hypermetabolic response. The severity of the hypermetabolic response following burn injury increases with age, as does the mortality rate. Due to the relationship between the hypermetabolic and inflammatory responses, we sought to compare the plasma cytokine profiles following a severe burn in adults and in children. We enrolled 25 adults and 24 children who survived a flame burn covering more than 20% of total body surface area (TBSA). The concentrations of 22 cytokines were measured using the Linco multiplex array system (St. Charles, MO, USA). Large perturbations in the expression of pro- and anti-inflammatory cytokines were seen following thermal injury. During the first week following burn injury, IFN-γ, IL-10, IL-17, IL-4, IL-6, and IL-8 were detected at significantly higher levels in adults compared with children, P < 0.05. Significant differences were measured during the second week post-burn for IL-1β (higher in children) and IL-5 (higher in adults), P < 0.05. IL-18 was more abundant in children compared with adults during the third week post-burn, P < 0.05. Between post-burn d 21 and d 66, IL-1α was detected at higher concentrations in pediatric compared with adult patients, P < 0.05. Only GM-CSF expression was significantly different at all time points; it was detected at lower levels in pediatric patients, P < 0.05. Eotaxin, G-CSF, IL-13, IL-15, IP-10, MCP-1, and MIP-1α were detected at significantly different concentrations in adult compared with pediatric patients at multiple time points, P < 0.05. There were no differences in IL-12, IL-2, IL-7, or TNF levels in adult compared with pediatric burn patients at any of these time points. Following severe flame burns, the cytokine profiles in pediatric patients differ compared with those in adult patients, which may

  13. 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

  14. 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.

  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. Understanding stress-induced immunosuppression: exploration of cytokine and chemokine gene profiles in chicken peripheral leukocytes.

    Science.gov (United States)

    Shini, S; Huff, G R; Shini, A; Kaiser, P

    2010-04-01

    that the delayed effects of chronic stress can suppress the immune response. Messenger RNA expression levels of transforming growth factor-beta4 (TGF-beta4) are also upregulated in cortisosterone-treated birds. It appears that the balance between T-helper (Th) 1 and Th2/T regulatory cytokine production is altered in conditions associated with significant changes in plasma corticosterone concentration. Experiments are underway to decipher the cytokine and chemokine responses to vaccination and bacterial challenge on the background of stress-induced immunosuppression. PMID:20308420

  17. Plasma Medicine

    Science.gov (United States)

    Laroussi, M.; Kong, M. G.; Morfill, G.; Stolz, W.

    2012-05-01

    Foreword R. Satava and R. J. Barker; Part I. Introduction to Non-equilibrium Plasma, Cell Biology, and Contamination: 1. Introduction M. Laroussi; 2. Fundamentals of non-equilibrium plasmas M. Kushner and M. Kong; 3. Non-equilibrium plasma sources M. Laroussi and M. Kong; 4. Basic cell biology L. Greene and G. Shama; 5. Contamination G. Shama and B. Ahlfeld; Part II. Plasma Biology and Plasma Medicine: 6. Common healthcare challenges G. Isbary and W. Stolz; 7. Plasma decontamination of surfaces M. Kong and M. Laroussi; 8. Plasma decontamination of gases and liquids A. Fridman; 9. Plasma-cell interaction: prokaryotes M. Laroussi and M. Kong; 10. Plasma-cell interaction: eukaryotes G. Isbary, G. Morfill and W. Stolz; 11. Plasma based wound healing G. Isbary, G. Morfill and W. Stolz; 12. Plasma ablation, surgery, and dental applications K. Stalder, J. Woloszko, S. Kalghatgi, G. McCombs, M. Darby and M. Laroussi; Index.

  18. 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.

  19. 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.

  20. Minocycline mitigates the gliogenic effects of proinflammatory cytokines on neural stem cells.

    Science.gov (United States)

    Vay, Sabine Ulrike; Blaschke, Stefan; Klein, Rebecca; Fink, Gereon Rudolf; Schroeter, Michael; Rueger, Maria Adele

    2016-02-01

    Mobilizing endogenous neural stem cells (NSCs) in the adult brain is designed to enhance the brain's regenerative capacity after cerebral lesions, e.g., as a result of stroke. Cerebral ischemia elicits neuroinflammatory processes affecting NSCs in multiple ways, the precise mechanisms of which currently remain elusive. An inhibitory effect of minocycline on microglia activation, a hallmark of postischemic neuroinflammation, has already been demonstrated in clinical trials, showing minocycline to be safe and potentially effective in ischemic stroke. Here we investigate the direct effects of minocycline and of proinflammatory cytokines on the differentiation potential of NSCs in vitro and in vivo. Primary fetal rat NSCs were treated with minocycline plus a combination of the proinflammatory cytokines tumor necrosis factor-α, interleukin 1β, and interleukin 6. The differentiation fate of NSCs was assessed immunocytochemically. To investigate the effects of minocycline and inflammation in vivo, minocycline or lipopolysaccharides were injected intraperitoneally into adult rats, with subsequent immunohistochemistry. Minocycline alone did not affect the differentiation potential of NSCs in vivo or in vitro. In contrast, proinflammatory cytokines accelerated the differentiation of NSCs, promoting an astrocytic fate while inhibiting neurogenesis in vitro and in vivo. It is interesting to note that minocycline counteracted this cytokine-induced rapid astrocytic differentiation and restored the neurogenic and oligodendrogliogenic potential of NSCs. Data suggest that minocycline antagonizes the rapid glial differentiation induced by proinflammatory cytokines following cerebral ischemia but without having a direct effect on the differentiation potential of NSCs. Thus, minocycline constitutes a promising drug for stroke research, counteracting the detrimental effects of postischemic neuroinflammation in multiple ways. PMID:26525774

  1. 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.

  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. 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

  4. Integrated Review of the Association of Cytokines with Fibromyalgia and Fibromyalgia Core Symptoms

    OpenAIRE

    Menzies, Victoria; Lyon, Debra

    2009-01-01

    Fibromyalgia (FMS) is a chronic widespread pain and fatigue syndrome that affects 3 to 6 million adults in the United States. Core symptoms of fibromyalgia include pain, fatigue, and mood and sleep disturbances. To date, consensus has not been reached among researchers regarding the pathogenesis of FMS nor the specific role of cytokine activation on the neuroendocrine-immune response patterns in persons with FMS. The purpose of this article is to describe and synthesize the results of researc...

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

    OpenAIRE

    El-Bahr, Sabry M.; Wael M. EL-Deeb

    2013-01-01

    The aim of the present study was to evaluate the diagnostic value of Acute Phase Proteins (APP), lipid profiles and proinflammatory cytokines in healthy and bronchopneumonic water buffalo calves. Therefore, sixty water buffalo calves (9±1 month old, 175±15 kg) were divided into two equal groups, the first group represented healthy, control, calves whereas calves of the second group were affected with bronchopneumonia. Total leukocytic and differential counts were determined. Serum total pr...

  6. Systemic Cytokine and Interferon Responsiveness Patterns in HIV and HCV Mono and Co-Infections

    OpenAIRE

    Fernandez-Botran, Rafael; Joshi-Barve, Swati; Ghare, Smita; Barve, Shirish; Young, Mary; Plankey, Michael; Bordon, Jose

    2014-01-01

    The role of host response-related factors in the fast progression of liver disease in individuals co-infected with HIV and HCV viruses remains poorly understood. This study compared patterns of cytokines, caspase-1 activation, endotoxin exposure in plasma as well as interferon signaling in peripheral blood mononuclear cells from HIV/HCV co-infected (HIV+/HCV+), HCV mono-infected (HIV−/HCV+), HIV mono-infected (HIV+/HCV−) female patients and HIV- and HCV-uninfected women (HIV−/HCV−) who had en...

  7. 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.

  8. 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)

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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. Immunohistochemical staining of brain sections showed higher immunoreactivity of proinflammatory cytokines in certain brain regions of stressed rats compared with controls; lower immunoreactivity of myelin basic protein and fewer mature oligodendrocytes were seen in the prefrontal cortex, but no demyelination was detected. These results are interpreted and discussed in the context of recent findings from human and animal studies. Keywords: cytokines, depression, myelination, oligodendrocytes, stress 

  14. 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.

  15. Effects of ACL Reconstructive Surgery on Temporal Variations of Cytokine Levels in Synovial Fluid

    Directory of Open Access Journals (Sweden)

    Marco Bigoni

    2016-01-01

    Full Text Available Anterior cruciate ligament (ACL reconstruction restores knee stability but does not reduce the incidence of posttraumatic osteoarthritis induced by inflammatory cytokines. The aim of this research was to longitudinally measure IL-1β, IL-6, IL-8, IL-10, and TNF-α levels in patients subjected to ACL reconstruction using bone-patellar tendon-bone graft. Synovial fluid was collected within 24–72 hours of ACL rupture (acute, 1 month after injury immediately prior to surgery (presurgery, and 1 month thereafter (postsurgery. For comparison, a “control” group consisted of individuals presenting chronic ACL tears. Our results indicate that levels of IL-6, IL-8, and IL-10 vary significantly over time in reconstruction patients. In the acute phase, the levels of these cytokines in reconstruction patients were significantly greater than those in controls. In the presurgery phase, cytokine levels in reconstruction patients were reduced and comparable with those in controls. Finally, cytokine levels increased again with respect to control group in the postsurgery phase. The levels of IL-1β and TNF-α showed no temporal variation. Our data show that the history of an ACL injury, including trauma and reconstruction, has a significant impact on levels of IL-6, IL-8, and IL-10 in synovial fluid but does not affect levels of TNF-α and IL-1β.

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

    OpenAIRE

    Vuslat Yilmaz; Piraye Oflazer; Fikret Aysal; Hacer Durmus; Kostas Poulas; Yentur, Sibel P.; Yesim Gulsen-Parman; Socrates Tzartos; Alexander Marx; Erdem Tuzun; Feza Deymeer; Güher Saruhan-Direskeneli

    2015-01-01

    Neuromuscular transmission failure in myasthenia gravis (MG) is most commonly elicited by autoantibodies (ab) to the acetylcholine receptor or the muscle-specific kinase, constituting AChR-MG and MuSK-MG. It is controversial whether these MG subtypes arise through different T helper (Th) 1, Th2 or Th17 polarized immune reactions and how these reactions are blunted by immunosuppression. To address these questions, plasma levels of cytokines related to various Th subtypes were determined in pat...

  17. Revisiting the plasma sheath—dust in plasma sheath

    Science.gov (United States)

    Das, G. C.; Deka, R.; Bora, M. P.

    2016-04-01

    In this work, we have considered the formation of warm plasma sheath in the vicinity of a wall in a plasma with considerable presence of dust particles. As an example, we have used the parameters relevant in case of plasma sheath formed around surfaces of various solid bodies in space, though the results obtained in this work can be applied to any other physical situation such as laboratory plasma. In the ion-acoustic time scale, we neglect the dust dynamics. The dust particles affect the sheath dynamics by affecting the Poisson equation which determines the plasma potential in the sheath region. It is important to note that our calculations are valid only when the amount of dust particles is not sufficient so as to affect the plasma dynamics in the dust-acoustic time scale, but enough to affect the plasma sheath. We have assumed the current to a dust particle to be balanced throughout the analysis. This makes the grain potential dependent on plasma potential, which is then incorporated into the Poisson equation. The resultant numerical model becomes an initial value problem, which is described by a 1-D integro-differential equation, which is then solved self-consistently by incorporating the change in plasma potential caused by inclusion of the dust potential in the Poisson equation.

  18. The Association of Cytokines with Severe Dengue in Children

    OpenAIRE

    Mangione, Julia N.A.; Huy, Nguyen Tien; Lan, Nguyen Thi Phuong; Mbanefo, Evaristus Chibunna; Ha, Tran Thi Ngoc; Bao, Lam Quoc; Nga, Cao Thi Phi; Tuong, Vo Van; Dat, Tran Van; Thuy, Tran Thi; Tuan, Ha Manh; Huong, Vu Thi Que; Hirayama, Kenji

    2014-01-01

    Background: Dengue virus infection is a major public health problem. A hypothesis put forward for severe dengue is the cytokine storm, a sudden increase in cytokines that induces vascular permeability. Previous studies and our recent meta-analysis showed that IL-6, IL-8, IFNγ, TNFα, VEGF-A and VCAM-1 are associated with dengue shock syndrome. Therefore, in this study we aim to validate the association of these cytokines with severe dengue. Methods & Findings: In a hospital based-case control ...

  19. The Association of Cytokines with Severe Dengue in Children

    OpenAIRE

    Mangione, Julia N.A.; Huy, Nguyen Tien; Lan, Nguyen Thi Phuong; Mbanefo, Evaristus Chibunna; Ha, Tran Thi Ngoc; Bao, Lam Quoc; Nga, Cao Thi Phi; Tuong, Vo Van; Dat, Tran Van; Thuy, Tran Thi; Tuan, Ha Manh; Huong, Vu Thi Que; Hirayama, Kenji

    2014-01-01

    Background: Dengue virus infection is a major public health problem. A hypothesis put forward for severe dengue is the cytokine storm, a sudden increase in cytokines that induces vascular permeability. Previous studies and our recent meta-analysis showed that IL-6, IL-8, IFNγ, TNFα, VEGF-A and VCAM-1 are associated with dengue shock syndrome. Therefore, in this study we aim to validate the association of these cytokines with severe dengue. Methods & Findings: In a hospital based-case cont...

  20. Three-Dimensional Gradients of Cytokine Signaling between T Cells.

    Directory of Open Access Journals (Sweden)

    Kevin Thurley

    2015-04-01

    Full Text Available Immune responses are regulated by diffusible mediators, the cytokines, which act at sub-nanomolar concentrations. The spatial range of cytokine communication is a crucial, yet poorly understood, functional property. Both containment of cytokine action in narrow junctions between immune cells (immunological synapses and global signaling throughout entire lymph nodes have been proposed, but the conditions under which they might occur are not clear. Here we analyze spatially three-dimensional reaction-diffusion models for the dynamics of cytokine signaling at two successive scales: in immunological synapses and in dense multicellular environments. For realistic parameter values, we observe local spatial gradients, with the cytokine concentration around secreting cells decaying sharply across only a few cell diameters. Focusing on the well-characterized T-cell cytokine interleukin-2, we show how cytokine secretion and competitive uptake determine this signaling range. Uptake is shaped locally by the geometry of the immunological synapse. However, even for narrow synapses, which favor intrasynaptic cytokine consumption, escape fluxes into the extrasynaptic space are expected to be substantial (≥20% of secretion. Hence paracrine signaling will generally extend beyond the synapse but can be limited to cellular microenvironments through uptake by target cells or strong competitors, such as regulatory T cells. By contrast, long-range cytokine signaling requires a high density of cytokine producers or weak consumption (e.g., by sparsely distributed target cells. Thus in a physiological setting, cytokine gradients between cells, and not bulk-phase concentrations, are crucial for cell-to-cell communication, emphasizing the need for spatially resolved data on cytokine signaling.

  1. The human kidney as a regulator of body cytokine homeostasis

    OpenAIRE

    Bonanni, A.; A. Sofia; S. Saffioti; I. Mannucci; D. Verzola; P. Gramegna; L. Cappuccino; Garibotto, G.

    2011-01-01

    Evidence is accumulating that the human kidney is a major site for the removal of several cytokines and growth factors, which can accumulate in body pools in patients with acute and chronic kidney disease (CKD). In addition, progressive renal failure and the increase in circulating proinflammatory cytokines are associated with mortality, suggesting that altered cytokines handling by the kidney is associated with worse outcome. Also, the kidney itself may be damaged by signals arising by endot...

  2. Proinflammatory Cytokines in the Prefrontal Cortex of Teenage Suicide Victims

    OpenAIRE

    Pandey, Ghanshyam N.; Rizavi, Hooriyah S.; Ren, Xinguo; Fareed, Jawed; Hoppensteadt, Debra A.; Roberts, Rosalinda C.; ROBERT R CONLEY; Dwivedi, Yogesh

    2011-01-01

    Teenage suicide is a major public health concern, but its neurobiology is not well understood. Proinflammatory cytokines play an important role in stress and in the pathophysiology of depression—two major risk factors for suicide. Cytokines are increased in the serum of patients with depression and suicidal behavior; however, it is not clear if similar abnormality in cytokines occurs in brains of suicide victims. We therefore measured the gene and protein expression levels of proinflammatory ...

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

    OpenAIRE

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

    2015-01-01

    Preeclampsia is a pregnancy disease characterized by hypertension and proteinuria. Among several disorders, the imbalance of inflammatory cytokines and the alteration of vitamin D metabolism have been reported in preeclampsia. The effects of calcitriol upon inflammatory cytokines has been demonstrated. In healthy pregnant women there is a shift toward a Th2 cytokine profile, which is necessary for an adequate pregnancy outcome. As compared with normal pregnancy, high pro-inflammatory and low ...

  4. 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

    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...

  5. Increased miR-155 expression in peripheral blood mononuclear cells of primary immune thrombocytopenia patients was correlated with serum cytokine profiles.

    Science.gov (United States)

    Qian, Bao-Hua; Ye, Xin; Zhang, Lei; Sun, Yi; Zhang, Jian-Rong; Gu, Ming-Li; Qin, Qin; Chen, Jie; Deng, An-Mei

    2015-01-01

    We investigated the possible pathogenic role of a microRNA (miR-155) in primary immune thrombocytopenia (ITP). We used quantitative real-time PCR to determine the relative expression of miR-155 and SOCS1 (suppressor of cytokine signaling) mRNA in peripheral blood mononuclear cells (PBMCs) from 28 ITP patients and 28 healthy controls. Cytokine plasma levels were determined by ELISA. Possible associations between miR-155 levels and serum cytokine concentrations were assessed using Spearman or Pearson correlation analysis. Seven naive ITP patients were followed and the effects of medical treatment on miR-155 levels were assessed. Compared to healthy controls, ITP patients had increased miR-155 and decreased SOCS1 mRNA levels. ITP patients also had increased plasma IL-17A and decreased IL-4, IL-10 and TGF-β1 levels. miR-155 levels were negatively correlated with platelet counts, SOCS1 mRNA levels, and the plasma levels of IL-4, IL-10 and TGF-β1, but positively correlated with plasma IL-17A levels. Medical treatment for ITP decreased miR-155 levels. Thus, our results suggest that miR-155 might be involved in the pathogenesis of ITP by regulating cytokine profiles, which may be mediated by miR-155 targeting SOCS1. PMID:25413124

  6. 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

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

    Directory of Open Access Journals (Sweden)

    Vuslat Yilmaz

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

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

    Science.gov (United States)

    Yilmaz, Vuslat; Oflazer, Piraye; Aysal, Fikret; Durmus, Hacer; Poulas, Kostas; Yentur, Sibel P; Gulsen-Parman, Yesim; Tzartos, Socrates; Marx, Alexander; Tuzun, Erdem; Deymeer, Feza; Saruhan-Direskeneli, Güher

    2015-01-01

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

  9. CYTOKINE RESPONSE AND OTHER DIFFERENCES BETWEEN CRITICAL PHASES OF SEPSIS-ASSOCIATED SYSTEMIC INFLAMMATION

    Directory of Open Access Journals (Sweden)

    E. Yu. Gusev

    2014-01-01

    Full Text Available Acute sepsis (1-3 days after admission has been compared with tertiary peritonitis, as a clinical variant of prolonged sepsis (7 to 42 days after admission. A total of 153 patients were enrolled into the study, including 112 cases of multiple organ dysfunction syndrome (MODS, as assessed by SOFA score, of them thirty-one with septic shock; fatal outcomes, in 48 cases. Plasma concentrations of C-reactive protein, cytokines (IL-6, IL-8, IL-10, TNFα, cortisol, troponin I, myoglobin, D-dimer were detected by means of immunochemiluminesce assay (ImmuLite. Development of systemic inflammation (SI was evaluated by appropriate integral criteria. An association was established between SI development and critical complications in the both groups of patients. Meanwhile, hyperergic variants of SI development associated with high cytokine levels, proved to prevail in acute sepsis. On the contrary, hypoergic variants were more common in cases of tertiary peritonitis, being characterized by relatively low levels of cytokines, along with higher probability of other SI syndromes and risks of lethal outcomes. In summary, systemic inflammatory events in acute versus prolonged sepsis may proceed by different pathogenetic pathways.

  10. Acute and chronic cytokine responses to resistance exercise and training in people with multiple sclerosis.

    Science.gov (United States)

    Kjølhede, T; Dalgas, U; Gade, A B; Bjerre, M; Stenager, E; Petersen, T; Vissing, K

    2016-07-01

    Exercise is a well-established part of rehabilitation for people with multiple sclerosis (PwMS), and it has been hypothesized to stimulate an anti-inflammatory environment that might be disease modifying. Yet, investigations on exercise-induced immune responses are scarce and generally not paying attention to the medical treatments of the patient. At present, PwMS are routinely enrolled in immunosuppressive medication, but exercise-induced immunomodulatory effects have not been investigated under these circumstances. The objective of this study was to investigate the acute and chronic cytokines responses to resistance exercise training in medicated PwMS. Thirty-five people with relapsing-remitting multiple sclerosis (MS) treated with interferon (IFN)-β, were randomized to a 24-week progressive resistance training (PRT) or control group. Plasma interleukin (IL)-1β, IL-4, IL-10, IL-17F, IL-23, tumor necrosis factor-α and IFN-γ were measured before and after 24 weeks of PRT. The acute effect was evaluated following standardized single-bout resistance exercise in the untrained and the trained state. No changes were observed in resting cytokine levels after PRT. However, an indication of reduced IL-17F secretion following resistance exercise was observed in the trained compared with the untrained state. This study suggests little acute and chronic effect of PRT on cytokine levels in IFN-treated PwMS. PMID:26105554

  11. Aspects on the cytokine load in trauma with special reference to blood components and local versus systemic cytokine activity

    OpenAIRE

    Kristiansson, Marianne

    1997-01-01

    ASPECTS ON THE CYTOKINE LOAD IN TRAUMA with special reference to BLOOD COMPONENTS and LOCAL VERSUS SYSTEMIC CYTOKINE ACTIVITY by Marianne Kristiansson, M.D. Dissertation from the Department of Anaesthesiology and Intensive Care, Huddinge University Hospital Karolinska Institute, Stockholm and Department of Clinical Immunology, Umeå University Hospital, Umeå, Sweden Cytokines and their inhibitors are thought to be involved in many of the pathophysiologi...

  12. 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

  13. Urinary cytokines in Schistosoma haematobium-infected schoolchildren from Tana Delta District of Kenya

    DEFF Research Database (Denmark)

    Njaanake, Kariuki H.; Simonsen, Paul Erik; Vennervald, Birgitte J;

    2014-01-01

    , for the first time, reports on the relationship between selected cytokines in urine and infection with S. haematobium in children from an area highly affected by this parasite. METHODS: Children aged 5-12 years from two primary schools in Tana Delta District of Kenya were examined for S. haematobium...

  14. High Levels of Proinflammatory Cytokines, but Not Markers of Tissue Injury, in Unaffected Intestinal Areas from Patients with IBD

    Directory of Open Access Journals (Sweden)

    Alberto J. León

    2009-01-01

    Full Text Available Intestinal alterations in IBD are triggered and maintained by an overexpression of proinflammatory cytokines. Additionally, increased immune activation has been found in the adjacent intestinal areas without displaying any apparent histological alterations, however, the regulatory environment is not well established. Biopsy specimens from patients with ulcerative colitis (UC and Crohn's disease (CD, from both affected and unaffected areas, and also from a group of colonic biopsies from healthy controls, were included in our study. Cytokines and markers of mucosal damage were analyzed by real-time PCR, and some of the results confirmed by western-blot and ELISA. Levels of IFNγ, TNFα, IL-6, IL-15, IL-18, and IL-23 were increased (above healthy controls in both affected and unaffected areas from IBD. IL-1β, IL-6, IL-12, and IL-27 were higher in affected areas compared to unaffected ones in UC but not CD. In general, a correlation was observed between mRNA levels of these cytokines and both iNOS and Granzyme B. SOCS-2 and SOCS-3 were also increased in the affected areas. In conclusion, the unaffected areas from IBD show increased levels of a restricted set of cytokines that may exert immune activating roles in these areas without being able to trigger tissue damage.

  15. [Gene therapy with cytokines against cervical cancer].

    Science.gov (United States)

    Bermúdez-Morales, Victor Hugo; Peralta-Zaragoza, Oscar; Madrid-Marina, Vicente

    2005-01-01

    Gene therapy is an excellent alternative for treatment of many diseases. Capacity to manipulate the DNA has allowed direct the gene therapy to correct the function of an altered gene, to increase the expression of a gene and to favour the activation of the immune response. This way, it can intend the use of the DNA like medication able to control, to correct or to cure many diseases. Gene therapy against cancer has an enormous potential, and actually the use of the DNA has increased to control diverse cancer in animal models, with very encouraging results that have allowed its applications in experimental protocols in human. This work concentrates a review of the foundations of the gene therapy and its application on cervical cancer, from the point of view of the alterations of the immune system focused on the tumour micro-environment, and the use of the cytokines as immunomodulators. PMID:16983992

  16. 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.

  17. 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

  18. 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

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

    Science.gov (United States)

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

    2016-01-01

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

  20. Relationship between plasma analytes and SPARE-AD defined brain atrophy patterns in ADNI.

    Directory of Open Access Journals (Sweden)

    Jon B Toledo

    Full Text Available Different inflammatory and metabolic pathways have been associated with Alzheimeŕs disease (AD. However, only recently multi-analyte panels to study a large number of molecules in well characterized cohorts have been made available. These panels could help identify molecules that point to the affected pathways. We studied the relationship between a panel of plasma biomarkers (Human DiscoveryMAP and presence of AD-like brain atrophy patterns defined by a previously published index (SPARE-AD at baseline in subjects of the ADNI cohort. 818 subjects had MRI-derived SPARE-AD scores, of these subjects 69% had plasma biomarkers and 51% had CSF tau and Aβ measurements. Significant analyte-SPARE-AD and analytes correlations were studied in adjusted models. Plasma cortisol and chromogranin A showed a significant association that did not remain significant in the CSF signature adjusted model. Plasma macrophage inhibitory protein-1α and insulin-like growth factor binding protein 2 showed a significant association with brain atrophy in the adjusted model. Cortisol levels showed an inverse association with tests measuring processing speed. Our results indicate that stress and insulin responses and cytokines associated with recruitment of inflammatory cells in MCI-AD are associated with its characteristic AD-like brain atrophy pattern and correlate with clinical changes or CSF biomarkers.

  1. Novel cytokines and cytokine-producing T cells in allergic disorders.

    Science.gov (United States)

    Wisniewski, Julia A; Borish, Larry

    2011-01-01

    Allergic diseases reflect various pathways of T lymphocyte inflammation and largely comprise T helper (Th) 2-associated processes. Recent investigations have identified pathways involved in promoting Th2 responses. Additionally, novel T-cell subtypes, each with its own distinct cytokine profile, contribute to the heterogeneous presentations of allergic diseases. This article focuses on recent developments including novel effector (nuocytes, Th9, and Th22) and regulatory T-cell (Treg) families of lymphocytes as well as cytokines that are central in driving Th2 differentiation (interleukin [IL]-4, IL-9, IL-25, thymic stromal lymphopoietin [TSLP], and IL-33). Recent literature and investigations were reviewed. Unregulated IL-25, TSLP, and IL-33 activity results in activation of Th2 cells, mast cells, dendritic cells, eosinophils, and basophils, leading to inflammatory processes that define allergic disease. As such, these cytokines are central mediators capable of instigating the inflammatory processes responsible for allergen-mediated diseases. The previous paradigm of Th1/Th2 imbalance driving allergic disease is expanded by identification of novel T helper families (nuocytes, Th9, Th17, and Th22) with their signature cytokines, which provide alterative avenues for investigation of neutrophil-predominant asthma and other heterogeneous presentations of allergic diseases. IL-25, TSLP, and IL-33 are attractive targets for therapeutics designed to ameliorate Th2-mediated diseases such as allergic rhinitis and asthma. Moreover, the ability to delineate novel regulatory and effector T-cell lineages among CD4(+) T cells challenges the Th1/Th2 paradigm of allergic disease and invites further avenues of investigation into the role of these cells in allergic disease. PMID:21439160

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-09-01

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

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

    International Nuclear Information System (INIS)

    The hypothalamic paraventricular nucleus (PVN) and rostral ventrolateral medulla (RVLM) play a critical role in the generation and maintenance of sympathetic nerve activity. The renin–angiotensin system (RAS) in the brain is involved in the pathogenesis of hypertension. This study was designed to determine whether inhibition of the angiotensin-converting enzyme (ACE) in the PVN modulates cytokines and attenuates oxidative stress (ROS) in the RVLM, and decreases the blood pressure and sympathetic activity in renovascular hypertensive rats. Renovascular hypertension was induced in male Sprague–Dawley rats by the two-kidney one-clip (2K1C) method. Renovascular hypertensive rats received bilateral PVN infusion with ACE inhibitor lisinopril (LSP, 10 μg/h) or vehicle via osmotic minipump for 4 weeks. Mean arterial pressure (MAP), renal sympathetic nerve activity (RSNA), and plasma proinflammatory cytokines (PICs) were significantly increased in renovascular hypertensive rats. The renovascular hypertensive rats also had higher levels of ACE in the PVN, and lower level of interleukin-10 (IL-10) in the RVLM. In addition, the levels of PICs, the chemokine MCP-1, the subunit of NAD(P)H oxidase (gp91phox) and ROS in the RVLM were increased in hypertensive rats. PVN treatment with LSP attenuated those changes occurring in renovascular hypertensive rats. Our findings suggest that the beneficial effects of ACE inhibition in the PVN in renovascular hypertension are partly due to modulation cytokines and attenuation oxidative stress in the RVLM. - Highlights: • Chronic ACE inhibition in PVN on renovascular hypertension was investigated. • 2K1C resulted in sympathoexcitation, increased plasma PICs and hypertension. • 2K1C rats had higher levels of cytokines and reactive oxygen species (ROS) in RVLM. • Chronic inhibiting PVN ACE attenuates cytokines and ROS in RVLM in hypertension

  4. Cytokine gene polymorphisms associated with symptomatic parvovirus B19 infection

    OpenAIRE

    Kerr, J R; McCoy, M; Burke, B; Mattey, D L; Pravica, V.; Hutchinson, I V

    2003-01-01

    Background: The immune system has been implicated in the pathogenesis of certain clinical manifestations of parvovirus B19 infection, including rash and arthralgia. Cytokines feature in the pathogenesis of parvovirus B19 infection, so inherited variability in cytokine responses to B19 infection might have a bearing on the symptomatology of parvovirus B19 infection.

  5. Cytokine expression & TGF-beta signaling in cervical cancer

    NARCIS (Netherlands)

    Kloth, Judith Nathalie

    2009-01-01

    Immune surveillance is of utmost importance in preventing cervical carcinogenesis. Cytokines play a central role in directing and fine tuning the immune response. In cancer, cytokines can either be involved in stimulating the anti-tumor immune response or in tumor growth and progression. The studies

  6. Inflammatory cytokines and risk of coronary heart disease

    DEFF Research Database (Denmark)

    Kaptoge, Stephen; Seshasai, Sreenivasa Rao Kondapally; Gao, Pei;

    2014-01-01

    Because low-grade inflammation may play a role in the pathogenesis of coronary heart disease (CHD), and pro-inflammatory cytokines govern inflammatory cascades, this study aimed to assess the associations of several pro-inflammatory cytokines and CHD risk in a new prospective study, including meta...

  7. Autophagy modulates the Mycobacterium tuberculosis-induced cytokine response

    NARCIS (Netherlands)

    Kleinnijenhuis, J.; Oosting, M.; Plantinga, T.S.; Meer, J.W.M. van der; Joosten, L.A.B.; Crevel, R. van; Netea, M.G.

    2011-01-01

    Both autophagy and pro-inflammatory cytokines are involved in the host defence against mycobacteria, but little is known regarding the effect of autophagy on Mycobacterium tuberculosis (MTB)-induced cytokine production. In the present study, we assessed the effect of autophagy on production of monoc

  8. Cytokines: abnormalities in major depression and implications for pharmacological treatment.

    LENUS (Irish Health Repository)

    O'Brien, Sinead M

    2012-02-03

    The role of cytokines in depression was first considered when the cytokine interferon resulted in "sickness behaviour", the symptoms of which are similar to those of major depression. The latter is associated with an increase in pro-inflammatory cytokines such as interleukin-1 (IL-1), interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF-alpha). These cytokines are potent modulators of corticotropin-releasing hormone (CRH) which produces heightened hypothalamic-pituitary-adrenal axis (HPA) activity characterized by increases in ACTH and cortisol, both of which are reported elevated in major depression. Antidepressant treatment has immunomodulatory effects with increases in the production of IL-10, which is an anti-inflammatory cytokine. This review based on a Medline search from 1980-2003, focuses on the evidence available of cytokine changes in acute stress, chronic stress and major depression. It examines the effects of antidepressant treatment on immune parameters in both animal models and clinical trials. We suggest that future antidepressants may target the immune system by either blocking the actions of pro-inflammatory cytokines or increasing the production of anti-inflammatory cytokines.

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

    Science.gov (United States)

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

    2015-08-01

    Preeclampsia is a pregnancy disease characterized by hypertension and proteinuria. Among several disorders, the imbalance of inflammatory cytokines and the alteration of vitamin D metabolism have been reported in preeclampsia. The effects of calcitriol upon inflammatory cytokines has been demonstrated. In healthy pregnant women there is a shift toward a Th2 cytokine profile, which is necessary for an adequate pregnancy outcome. As compared with normal pregnancy, high pro-inflammatory and low anti-inflammatory cytokine levels have been observed in preeclamptic women. Preeclampsia has been associated with low calcitriol levels and vitamin D deficiency is correlated with a higher risk of the development of this disease. It has been demonstrated that placenta is a source as well as the target of calcitriol and cytokines and placental dysfunction has been associated with preeclampsia. Therefore, the present manuscript includes a review about serum calcitriol levels in non-pregnant, pregnant, and preeclamptic women as well as a review on the fetoplacental vitamin D metabolism in healthy and preeclamptic pregnancies. In addition, circulating and fetoplacental inflammatory cytokines in healthy and preeclamptic pregnancies are reviewed. Finally, the effects of calcitriol upon placental pro-inflammatory cytokines are also explored. In conclusion, maternal and placental calcitriol levels are low in preeclampsia which may explain, at least in part, high pro-inflammatory cytokine levels in this disease. PMID:26247971

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

    Directory of Open Access Journals (Sweden)

    David Barrera

    2015-08-01

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

  11. Role of inflammatory cytokines in peripheral nerve injury

    Institute of Scientific and Technical Information of China (English)

    Federica Fregnan; Luisa Muratori; Anabel Rodriguez Sim(o)es; Maria Giuseppina Giacobini-Robecchi; Stefania Raimondo

    2012-01-01

    Inflammatory events occurring in the distal part of an injured peripheral nerve have,nowadays,a great resonance.Investigating the timing of action of the several cytokines in the important stages of Wallerian degeneration helps to understand the regenerative process and design pharmacologic intervention that promotes and expedites recovery.The complex and synergistic action of inflammatory cytokines finally promotes axonal regeneration.Cytokines can be divided into pro-and anti-inflammatory cytokines that upregutate and downregulate,respectively,the production of inflammatory mediators.While pro-inflammatory cytokines are expressed in the first phase of Wallerian degeneration and promote the recruitment of macrophages,anti-inflammatory cytokines are expressed after this recruitment and downregulate the production of all cytokines,thus determining the end of the process.In this review,we describe the major inflammatory cytokines involved in Wallerian degeneration and the early phases of nerve regeneration.In particular,we focus on interleukin-1,interleukin-2,interleukin-6,tumor necrosis factor-β,interleukin-10 and transforming growth factor-β.

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

    International Nuclear Information System (INIS)

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

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

    DEFF Research Database (Denmark)

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

    2000-01-01

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

  14. 384-Well Multiplexed Luminex Cytokine Assays for Lead Optimization.

    Science.gov (United States)

    Tang, Huaping; Panemangalore, Reshma; Yarde, Melissa; Zhang, Litao; Cvijic, Mary Ellen

    2016-07-01

    Cytokines serve as a major mechanism of communication between immune cells and are the functional molecules at the end of immune pathways. Abnormalities in cytokines are involved in a wide variety of diseases, including chronic inflammation, autoimmune diseases, and cancer. Cytokines are not only direct targets of therapeutics but also important biomarkers for assessing drug efficacy and safety. Traditionally, enzyme-linked immunosorbent assays (ELISA) were most popular for identifying and quantifying cytokines. However, ELISA is expensive, labor intensive, and low throughput. Here, we report the development of a miniaturized Luminex (Austin, TX) assay platform to establish a panel of high-throughput, multiplexed assays for measuring cytokines in human whole blood. The miniaturized 384-well Luminex assay uses animal studies and patient samples for translational research. PMID:27095819

  15. The role of cytokines in immunological tolerance: potential for therapy.

    Science.gov (United States)

    Harber, M; Sundstedt, A; Wraith, D

    2000-11-27

    Current immunosuppression protocols, although often effective, are nonspecific and therefore hazardous. Consequently, immunological tolerance that is antigen specific and does not globally depress the patient's immune system has become one of the Holy Grails of immunology. Since the discovery that cytokines have immunomodulatory effects, extensive research has investigated the potential of these molecules to induce and maintain specific immunological tolerance in the context of transplantation, allergy and autoimmunity. In this article, we review the possible mechanisms by which cytokines can modulate the immune response and the animal models that frequently confound the theory that a single cytokine, or group of cytokines, can induce tolerance in a predictable manner. Finally, we discuss the role of cytokines at a paracrine level, particularly in the context of inducing and maintaining antigen-specific, regulatory T cells with the clinical potential to suppress specific immune responses.

  16. Role of IL-38 and Its Related Cytokines in Inflammation

    Directory of Open Access Journals (Sweden)

    Xianli Yuan

    2015-01-01

    Full Text Available Interleukin- (IL- 38 is a recently discovered cytokine and is the tenth member of the IL-1 cytokine family. IL-38 shares structural features with IL-1 receptor antagonist (IL-1Ra and IL-36Ra. IL-36R is the specific receptor of IL-38, a partial receptor antagonist of IL-36. IL-38 inhibits the production of T-cell cytokines IL-17 and IL-22. IL-38 also inhibits the production of IL-8 induced by IL-36γ, thus inhibiting inflammatory responses. IL-38-related cytokines, including IL-1Ra and IL-36Ra, are involved in the regulation of inflammation and immune responses. The study of IL-38 and IL-38-related cytokines might provide new insights for developing anti-inflammatory treatments in the near future.

  17. Affective Urbanism

    DEFF Research Database (Denmark)

    Samson, Kristine

    . Under these circumstances affective aesthetics operate strategically within the urban field of interests, capital flows and desires of the social. This ‘affective urbanism’ (Anderson & Holden 2008) is linked to a society influenced by new kinds of information flows, where culture is mediated and enacted...... and cultural festivals, both practices indicate that design is implemented as means of creating affective spaces in the city. Both cases show how immaterial production of affects and emotions in the city can be seen in relation to economic potential and urban development. Finally, I will discuss whether urban......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...

  18. Allergen-Specific Cytokine Polarization Protects Shetland Ponies against Culicoides obsoletus-Induced Insect Bite Hypersensitivity.

    Directory of Open Access Journals (Sweden)

    Chantal Meulenbroeks

    Full Text Available The immunological mechanisms explaining development of an allergy in some individuals and not in others remain incompletely understood. Insect bite hypersensitivity (IBH is a common, seasonal, IgE-mediated, pruritic skin disorder that affects considerable proportions of horses of different breeds, which is caused by bites of the insect Culicoides obsoletus (C. obsoletus. We investigated the allergen-specific immune status of individual horses that had either been diagnosed to be healthy or to suffer of IBH. Following intradermal allergen injection, skin biopsies were taken of IBH-affected and healthy ponies and cytokine expression was determined by RT-PCR. In addition, allergen-specific antibody titers were measured and cytokine expression of in vitro stimulated, allergen-specific CD4 T-cells was determined. 24 hrs after allergen injection, a significant increase in mRNA expression of the type-2 cytokine IL-4 was observed in the skin of IBH-affected Shetland ponies. In the skin of healthy ponies, however, an increase in IFNγ mRNA expression was found. Analysis of allergen-specific antibody titers revealed that all animals produced allergen-specific antibodies, and allergen-specific stimulation of CD4 T-cells revealed a significant higher percentage of IFNγ-expressing CD4 T-cells in healthy ponies compared to IBH-affected ponies. These data indicate that horses not affected by IBH, in contrast to the so far established dogma, are not immunologically ignorant but have a Th1-skewed allergen-specific immune response that appears to protect against IBH-associated symptoms. To our knowledge this is the first demonstration of a natural situation, in which an allergen-specific immune skewing is protective in an allergic disorder.

  19. Pro- and anti-inflammatory cytokine gene single-nucleotide polymorphisms in inflammatory bowel disease.

    Science.gov (United States)

    López-Hernández, R; Valdés, M; Campillo, J A; Martínez-García, P; Salama, H; Bolarin, J M; Martínez, H; Moya-Quiles, M R; Minguela, A; Sánchez-Torres, A; Botella, C; Salgado, G; Miras, M; Carballo, F; Muro, M

    2015-02-01

    Anti-inflammatory cytokines have an important role in disease, tumour and transplant processes. Alterations in the regulation of several cytokines have been implicated in a variety of inflammatory disorders, including IBD (inflammatory bowel disease) [Crohn's disease (CD) and ulcerative colitis (UC)]. Cytokine polymorphisms are also known to affect the level of gene expression. Thus, the aim of this study was to determine the relationship between cytokine polymorphisms and the IBD pathologies in a Spanish population. Polymorphisms analysis was performed using PCR-SSOP using a microbeads luminex assay. The following polymorphisms were determined: TNFα [-238G/A (rs361525) and -308G/A (rs1800629)], IFNγ [+874A/T (rs62559044)], TGFβ [+869C/T (rs1982073) and +915G/C (rs1800471)], IL10 [-1082A/A (rs1800896), -592A/C (rs1800872), -819C/T (rs1800871)], IL6 [-174C/G (rs1800795)], IL12p40 [3'UTR -1188A/C (rs3212227)], IL1α [-889C/T (rs1800587)], IL1β [-511C/T (rs1143634) and +3962C/T (rs1143633)], IL1R [Pst-1 1970C/T] and IL1RA [Mspa-1 11100C/T]. No statistical differences in TNFα, IFNγ, TGFβ, IL10, IL6, IL1α, IL1β, IL1R and IL1Ra genotypes and allele distributions between the IBD groups and healthy controls were found. However, we observed significant differences in the 3'UTR -1188A/C polymorphism of IL12p40. So -1188A allele was increased in patients with UC and the -1188C allele (high IL12p40 production) was increased in patients with CD with respect to controls. These data are in concordance with the fact that CD has been shown to be associated with a Th1 T-cell-mediated inflammation model and high IL12/IFNγ production at histological affected sites. These data suggest that cytokine polymorphisms in TNFα, IFNγ, TGFβ, IL10, IL6 and IL1α, IL1β, IL1R and IL1Ra cytokine gene do not seem to be relevant in IBD susceptibility and IL12p40 3'UTR -1188A/C polymorphism seems to be associated with a differential IBD development. PMID:25359546

  20. H pylori seropositivity and cytokine gene polymorphisms

    Institute of Scientific and Technical Information of China (English)

    Yasuaki Saijo; Eiji Yoshioka; Tomonori Fukui; Mariko Kawaharada; Fumihiro Sata; Hirokazu Sato; Reiko Kishi

    2007-01-01

    AIM: To investigate whether the pro- and antiinflammatory cytokine gene polymorphisms, IL1B-511C/T,IL1B-31C/T, IL6-634C/G, TNF-1031T/C, TNF-857C/T, and IL10-1082A/G, interact with smoking and drinking habits to influence infection with H pylori.METHODS: The subjects were 410 Japanese transit company employees. C-reactive protein and conventional cardiovascular risk factors were evaluated. Serum anti-H pylori antibodies were measured. The genotypes of IL1B-511C/T, IL1B-31C/T, IL6-634C/G, TNF-1031T/C,TNF-857C/T, and IL10-1082A/G polymorphisms were determined by allelic discrimination using fluorogenic probes and a 5'nuclease assay.RESULTS: In gender- and age-adjusted logistic analyses,the subjects with TNF-857T/T had a significantly lower odds ratio (OR) for H pylori seropositivity (reference -857C/C; OR = 0.15, 95% CI: 0.03-0.59, P = 0.007).After stratification according to smoking and drinking status, among never-smokers, the subjects with IL1B-511C/T had a significantly lower OR (reference -511C/C;OR = 0.30, 95% CI: 0.10-0.90, P = 0.032). Among drinkers in the 1-5 times/wk category, the subjects with IL1B-511T/T had a significantly lower OR (reference C/C; OR = 0.38, 95% CI: 0.16-0.95, P = 0.039), and the subjects with IL1B-31C/T and T/T had a significantly higher OR (reference C/C; C/T: OR = 2.59, 95% CI, P =0.042: 1.04-6.47; C/C: OR = 3.17, 95% CI: 1.23-8.14,P = 0.017). Among current smokers, the subjects with IL6-634C/G had a significantly higher OR (reference C/C;OR = 2.28, 95% CI: 1.13-4.58, P = 0.021). However,the interactions terms between the aforementioned genotypes and lifestyles were not statistically significant.CONCLUSION: Contrary to previous findings, the results herein suggest that the TNF-857T/T genotype may be protective against chronic infection with H pylori. Drinking and smoking habits may influence the effect of cytokine gene polymorphisms. Further studies are required to clarify the effects of the pro- and anti-inflammatory cytokine

  1. Genetic diversity in cytokines associated with immune variation and resistance to multiple pathogens in a natural rodent population.

    Directory of Open Access Journals (Sweden)

    Andrew K Turner

    2011-10-01

    Full Text Available Pathogens are believed to drive genetic diversity at host loci involved in immunity to infectious disease. To date, studies exploring the genetic basis of pathogen resistance in the wild have focussed almost exclusively on genes of the Major Histocompatibility Complex (MHC; the role of genetic variation elsewhere in the genome as a basis for variation in pathogen resistance has rarely been explored in natural populations. Cytokines are signalling molecules with a role in many immunological and physiological processes. Here we use a natural population of field voles (Microtus agrestis to examine how genetic diversity at a suite of cytokine and other immune loci impacts the immune response phenotype and resistance to several endemic pathogen species. By using linear models to first control for a range of non-genetic factors, we demonstrate strong effects of genetic variation at cytokine loci both on host immunological parameters and on resistance to multiple pathogens. These effects were primarily localized to three cytokine genes (Interleukin 1 beta (Il1b, Il2, and Il12b, rather than to other cytokines tested, or to membrane-bound, non-cytokine immune loci. The observed genetic effects were as great as for other intrinsic factors such as sex and body weight. Our results demonstrate that genetic diversity at cytokine loci is a novel and important source of individual variation in immune function and pathogen resistance in natural populations. The products of these loci are therefore likely to affect interactions between pathogens and help determine survival and reproductive success in natural populations. Our study also highlights the utility of wild rodents as a model of ecological immunology, to better understand the causes and consequences of variation in immune function in natural populations including humans.

  2. Plasma Science Committee (PLSC)

    International Nuclear Information System (INIS)

    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. This report discusses ion of the PLSC work

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

    Directory of Open Access Journals (Sweden)

    Eduardo Anitua

    Full Text Available 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.

  4. Affective Maps

    DEFF Research Database (Denmark)

    Salovaara-Moring, Inka

    . In particular, mapping environmental damage, endangered species, and human made disasters has become one of the focal point of affective knowledge production. These ‘more-than-humangeographies’ practices include notions of species, space and territory, and movement towards a new political ecology. This type...... 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...

  5. Role of Pro-Inflammatory Cytokines and Biochemical Markers in the Pathogenesis of Type 1 Diabetes: Correlation with Age and Glycemic Condition in Diabetic Human Subjects

    Science.gov (United States)

    Zubair, Swaleha; Ajmal, Mohd; Siddiqui, Sheelu Shafiq; Moin, Shagufta; Owais, Mohammad

    2016-01-01

    Background Type 1 diabetes mellitus is a chronic inflammatory disease involving insulin producing β-cells destroyed by the conjoined action of auto reactive T-cells, inflammatory cytokines and monocytic cells. The aim of this study was to elucidate the status of pro-inflammatory cytokines and biochemical markers and possible correlation of these factors towards outcome of the disease. Methods The study was carried out on 29 T1D subjects and 20 healthy subjects. Plasma levels of oxidative stress markers, enzymatic and non-enzymatic antioxidants were estimated employing biochemical assays. The levels of pro-inflammatory cytokines such as by IL-1β & IL-17 in the serum were determined by ELISA, while the expression of TNF-α, IL-23 & IFN-γ was ascertained by qRT-PCR. Results The onset of T1D disease was accompanied with elevation in levels of Plasma malondialdehyde, protein carbonyl content and nitric oxide while plasma vitamin C, reduced glutathione and erythrocyte sulfhydryl groups were found to be significantly decreased in T1D patients as compared to healthy control subjects. Activity of antioxidant enzymes, superoxide dismutase, catalase, glutathione reductase and glutathione-s-transferase showed a significant suppression in the erythrocytes of T1D patients as compared to healthy subjects. Nevertheless, the levels of pro-inflammatory cytokines IL-1β and IL-17A were significantly augmented (***p≤.001) on one hand, while expression of T cell based cytokines IFN-γ, TNF-α and IL-23 was also up-regulated (*p≤.05) as compared to healthy human subjects. Conclusion The level of pro-inflammatory cytokines and specific biochemical markers in the serum of the patient can be exploited as potential markers for type 1 diabetes pathogenesis. The study suggests that level of inflammatory markers is up-regulated in T1D patients in an age dependent manner. PMID:27575603

  6. Plasma antennas

    CERN Document Server

    Anderson, Theodore

    2011-01-01

    The plasma antenna is an emerging technology that partially or fully utilizes ionized gas as the conducting medium instead of metal to create an antenna. The key advantages of plasma antennas are that they are highly reconfigurable and can be turned on and off. The disadvantage is that the plasma antennas require energy to be ionized. This unique resource provides you with a solid understanding of the efficient design and prototype development of plasma antennas, helping you to meet the challenge of reducing the power required to ionize the gas at various plasma densities. You also find thorou

  7. Biofilm-forming Pseudomonas aeruginosa bacteria undergo lipopolysaccharide structural modifications and induce enhanced inflammatory cytokine response in human monocytes.

    Science.gov (United States)

    Ciornei, Cristina D; Novikov, Alexey; Beloin, Christophe; Fitting, Catherine; Caroff, Martine; Ghigo, Jean-Marc; Cavaillon, Jean-Marc; Adib-Conquy, Minou

    2010-10-01

    To determine whether growth of bacteria in biofilms triggers a specific immune response, we compared cytokine induction in human monocytes and mouse macrophages by planktonic and biofilm bacteria. We compared Pseudomonas aeruginosa and Staphylococcus aureus, two bacteria often colonizing the airways of cystic fibrosis patients. Planktonic and biofilm S. aureus induced equivalent amounts of cytokine in human monocytes. In contrast, biofilm-forming P. aeruginosa induced a higher production of tumor necrosis factor and interleukin-6 than their planktonic counterpart, both for clinical isolates and laboratory strains. This increased cytokine production was partly dependent on phagocytosis. In contrast, no difference in cytokine induction was observed with mouse macrophages. We investigated the structures of the lipopolysaccharides (LPSs) of these Gram-negative bacteria in biofilm and planktonic cultures of P. aeruginosa. Switch between the two life-styles was shown to cause several reversible LPS structure modifications affecting the lipid A and polysaccharide moieties of both clinical isolates and laboratory strains. In addition, LPS isolated from biofilm-grown bacteria induced slightly more inflammatory cytokines than that extracted from its planktonic counterpart. Our results, therefore, show that P. aeruginosa biofilm LPS undergoes structural modifications that only partially contribute to an increased inflammatory response from human monocytes. PMID:19710099

  8. Cognitive impairment effects of early life stress in adolescents can be predicted with early biomarkers: Impacts of sex, experience, and cytokines.

    Science.gov (United States)

    Grassi-Oliveira, Rodrigo; Honeycutt, Jennifer A; Holland, Freedom H; Ganguly, Prabarna; Brenhouse, Heather C

    2016-09-01

    Childhood adversity increases vulnerability to psychiatric disorders that emerge in adolescence, in a sex-dependent manner. Early adversity modeled in rodents with maternal separation (MS) affects cognition and medial prefrontal cortex (mPFC) circuitry. Humans and animals exposed to early life adversity also display heightened circulating inflammatory cytokines, however the predictive relationship of these early measures with later behavioral deficits is unknown. Here, male and female rats were exposed to MS or control rearing during the postnatal period (P2-21). Blood samples were taken at distinct developmental time points for analysis of the pro-inflammatory cytokine IL-1β and the anti-inflammatory cytokines IL-4, and IL-10, followed by win-shift cognitive testing and analysis of mPFC parvalbumin (PVB) immunofluorescent interneurons in adolescence. Regression analyses were conducted to explore the relationship between early cytokines and adolescent behavioral measures. We observed sex- and age-dependent effects of MS on circulating cytokines. MS also yielded adolescent decreases in mPFC PVB and cognitive deficits, which were predicted by early cytokine expression in a sex- and experience-dependent manner. Taken together, the present data reveals that circulating cytokines and PVB levels are predictive of adolescent cognitive deficits, and therefore provide compelling evidence for a putative role of early biomarkers in mediating MS-induced behavioral dysfunction. Importantly, predictive relationships often depended on sex and on MS history, suggesting that early life experiences may yield individualistic mechanisms of vulnerability compared to the general population. PMID:27235636

  9. Cognitive impairment effects of early life stress in adolescents can be predicted with early biomarkers: Impacts of sex, experience, and cytokines.

    Science.gov (United States)

    Grassi-Oliveira, Rodrigo; Honeycutt, Jennifer A; Holland, Freedom H; Ganguly, Prabarna; Brenhouse, Heather C

    2016-09-01

    Childhood adversity increases vulnerability to psychiatric disorders that emerge in adolescence, in a sex-dependent manner. Early adversity modeled in rodents with maternal separation (MS) affects cognition and medial prefrontal cortex (mPFC) circuitry. Humans and animals exposed to early life adversity also display heightened circulating inflammatory cytokines, however the predictive relationship of these early measures with later behavioral deficits is unknown. Here, male and female rats were exposed to MS or control rearing during the postnatal period (P2-21). Blood samples were taken at distinct developmental time points for analysis of the pro-inflammatory cytokine IL-1β and the anti-inflammatory cytokines IL-4, and IL-10, followed by win-shift cognitive testing and analysis of mPFC parvalbumin (PVB) immunofluorescent interneurons in adolescence. Regression analyses were conducted to explore the relationship between early cytokines and adolescent behavioral measures. We observed sex- and age-dependent effects of MS on circulating cytokines. MS also yielded adolescent decreases in mPFC PVB and cognitive deficits, which were predicted by early cytokine expression in a sex- and experience-dependent manner. Taken together, the present data reveals that circulating cytokines and PVB levels are predictive of adolescent cognitive deficits, and therefore provide compelling evidence for a putative role of early biomarkers in mediating MS-induced behavioral dysfunction. Importantly, predictive relationships often depended on sex and on MS history, suggesting that early life experiences may yield individualistic mechanisms of vulnerability compared to the general population.

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

    DEFF Research Database (Denmark)

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

    2011-01-01

    Apolipoprotein CIII (ApoCIII) is mainly synthesized in the liver and is important for triglyceride metabolism. The plasma concentration of ApoCIII is elevated in patients with type 1 diabetes (T1D), and in vitro ApoCIII causes apoptosis in pancreatic ß-cells in the absence of inflammatory stress...... µg/ml) did not cause apoptosis. In the presence of the islet-cytotoxic cytokines IL-1ß + interferon-¿, ApoCIII reduced cytokine-mediated islet cell death and impairment of ß-cell function. ApoCIII had no effects on mitogen-activated protein kinases (c-Jun N-terminal kinase, p38, and ERK) and had...... of the survival serine-threonine kinase Akt. Inhibition of the Akt signaling pathway by the phosphatidylinositol 3 kinase inhibitor LY294002 counteracted the antiapoptotic effect of ApoCIII on cytokine-induced apoptosis. We conclude that ApoCIII in the presence of T1D-relevant proinflammatory cytokines reduces...

  11. Divergent T-Cell Cytokine Patterns in Inflammatory Arthritis

    Science.gov (United States)

    Simon, A. K.; Seipelt, E.; Sieper, J.

    1994-08-01

    A major immunoregulatory mechanism in inflammatory infections and allergic diseases is the control of the balance of cytokines secreted by Th1/Th2 subsets of T helper (Th) cells. This might also be true in autoimmune diseases; a Th2 pattern that prevents an effective immune response in infections with intracellular bacteria may favor immunosuppression in autoimmune diseases. The pattern of cytokine expression was compared in the synovial tissue from patients with a typical autoimmune disease, rheumatoid arthritis, and with a disorder with similar synovial pathology but driven by persisting exogenous antigen, reactive arthritis. We screened 12 rheumatoid and 9 reactive arthritis synovial tissues by PCR and in situ hybridization for their expression of T-cell cytokines. The cytokine pattern differs significantly between the two diseases; rheumatoid arthritis samples express a Th1-like pattern whereas in reactive arthritis interferon γ expression is accompanied by that of interleukin 4. Studying the expression of cytokines by in situ hybridization confirmed the results found by PCR; they also show an extremely low frequency of cytokine-transcribing cells. In a double-staining experiment, it was demonstrated that interleukin 4 is made by CD4 cells. These experiments favor the possibility of therapeutic intervention in inflammatory rheumatic diseases by means of inhibitory cytokines.

  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. Aberrant expression of Treg-associated cytokine IL-35 along with IL-10 and TGF-β in acute myeloid leukemia.

    Science.gov (United States)

    Wu, Hao; Li, Peng; Shao, Na; Ma, Jingjing; Ji, Min; Sun, Xiulian; Ma, Daoxin; Ji, Chunyan

    2012-05-01

    Acute myeloid leukemia (AML) is the most common hematological malignancy in adults, characterized by distorted proliferation and the development of myeloid cells and their precursors in the blood and bone marrow. Interleukin 35 (IL-35), a novel inhibitory cytokine secreted by regulatory T (Treg) cells is a novel potential target used for the therapeutic manipulation of Treg activity in order to treat cancer and autoimmune diseases. To investigate the role and imbalance of Treg-related cytokines in the pathogenesis of AML, we measured the plasma concentration of three Treg-associated cytokines [IL-35, IL-10 and transforming growth factor-β (TGF-β)] and evaluated their clinical relevance. The concentration of IL-35, IL-10 and TGF-β in plasma specimens from 55 patients with AML [27 newly diagnosed (ND) patients and 28 in complete remission (CR)] and 24 controls was analyzed using the enzyme-linked immunosorbent assay method. Significantly higher levels of plasma IL-35 and IL-10 were observed in AML ND patients compared with healthy controls or AML CR patients. IL-10 concentrations were positively correlated with TGF-β, whereas no correlations were found between the other cytokines. IL-10 levels were positively correlated with white blood cell (WBC) and neutrophil (NEU) count but there were no correlations between IL-35 and TGF-β with WBC and NEU count. In conclusion, we demonstrated for the first time that AML ND patients have increased plasma concentrations of IL-35, suggesting that this cytokine is involved in the pathophysiological process of the disease, and that further research is required to address this issue.

  14. Study on the therapeutic effect of cytokine on acute radiation syndrome induced by 60Co γ ray exposure

    International Nuclear Information System (INIS)

    Objective: To examine the therapeutic effect of combined administration of rhIL-11 and rhG-CSF on acute radiation syndrome induced by 60Coγ ray exposure in beagles. Methods: Sixteen beagles were randomly divided into the control (n=5), symptomatic treatment group (n=5) and cytokine treatment group (n=6). All the beagles in the three groups were exposed to the whole-body irradiation of 60Co γ ray at a dose of 4.5 Gy. The animals in the second group accepted active symptomatic treatment. The animals in the cytokine treatment group were sub-cutaneously administered rhIL -11 and rhG -CSF besides active symptomatic treatment. Hemogram of peripheral blood, pristine apoptosis and necrosis ratio of nucleated cells, the content of IL-2 and IFN-γ in plasma and formation of bone marrow were used to evaluate the therapeutic effect. Results: In the cytokine treatment group, the animal' survival rate 45 days after exposure was increased and hemogram of peripheral blood was improved significantly. The rate of pristine apoptosis and necrosis of nucleated cell declined obviously. Early, the content of both IL-2 and IFN-γ in plasma was up significantly, then the content of IL-2 rapidly descended, but that of IFN-γ was relatively stable. Conclusion: The combined administration of rhIL-11 and rhG-CSF significantly improved the recovery of hematopoietic and immunological function. (authors)

  15. Role of cytokine p40 family in multiple sclerosis

    OpenAIRE

    Brahmachari, S.; Pahan, K.

    2008-01-01

    Over the last couple of decades of neuro-immunological research, the p40 family of cytokines has emerged out as one of the most intriguing areas of interest because of multi-faceted roles of these cytokine in immune-modulation and inflammation. The IL-12, the most widely studied cytokine of this family, is well-characterized for its Th1-favoring activity, and therefore plays a key role in the pathophysiology of Th1-mediated autoimmune diseases like multiple sclerosis (MS). On the other hand, ...

  16. Effect of Blood Component Coatings of Enosseal Implants on Proliferation and Synthetic Activity of Human Osteoblasts and Cytokine Production of Peripheral Blood Mononuclear Cells

    Science.gov (United States)

    Hulejova, Hana; Bartova, Jirina; Riedel, Tomas; Pesakova, Vlasta

    2016-01-01

    The study monitored in vitro early response of connective tissue cells and immunocompetent cells to enosseal implant materials coated by different blood components (serum, activated plasma, and plasma/platelets) to evaluate human osteoblast proliferation and synthetic activity and inflammatory response presented as a cytokine profile of peripheral blood mononuclear cells (PBMCs) under conditions imitating the situation upon implantation. The cells were cultivated on coated Ti-plasma-sprayed (Ti-PS), Ti-etched (Ti-Etch), Ti-hydroxyapatite (Ti-HA), and ZrO2 surfaces. The plasma/platelets coating supported osteoblast proliferation only on osteoconductive Ti-HA and Ti-Etch whereas activated plasma enhanced proliferation on all surfaces. Differentiation (BAP) and IL-8 production remained unchanged or decreased irrespective of the coating and surface; only the serum and plasma/platelets-coated ZrO2 exhibited higher BAP and IL-8 expression. RANKL production increased on serum and activated plasma coatings. PBMCs produced especially cytokines playing role in inflammatory phase of wound healing, that is, IL-6, GRO-α, GRO, ENA-78, IL-8, GM-CSF, EGF, and MCP-1. Cytokine profiles were comparable for all tested surfaces; only ENA-78, IL-8, GM-CSF, and MCP-1 expression depended on materials and coatings. The activated plasma coating led to uniformed surfaces and represented a favorable treatment especially for bioinert Ti-PS and ZrO2 whereas all coatings had no distinctive effect on bioactive Ti-HA and Ti-Etch. PMID:27651560

  17. Effects of glutamine supplementation on splenocyte cytokine mRNA expression in rats with septic peritonitis

    Institute of Scientific and Technical Information of China (English)

    Sung-Ling Yeh; Yu-Ni Lai; Huey-Fang Shang; Ming-Tsan Lin; Wan-Chun Chiu; Wei-Jao Chen

    2005-01-01

    AIM: To investigate the effects of glutamine (GLN)-enriched diets before and GLN-containing total parenteral nutrition (TPN) after sepsis or both on the secretion of cytokines and their mRNA expression levels in splenocytes of rats with septic peritonitis.METHODS: Rats were assigned to a control group and 4experimental groups. The control group and experimental groups 1 and 2 were fed a semipurified diet, while experimental groups 3 and 4 had part of the casein replaced by GLN which provided 25% of the total nitrogen.After rats were fed with these diets for 10 d, sepsis was induced by cecal ligation and puncture (CLP), whereas the control group underwent a sham operation, at the same time, an internal jugular vein was cannulated. All rats were maintained on TPN for 3 d. The control group and experimental groups 1 and 3 were infused with conventional TPN, while the TPN in experimental groups 2 and 4 was supplemented with GLN, providing 25% of the total nitrogen in the TPN solution. All rats were kiued 3 d after sham operation or CLP to examine their splenocyte subpopulation distribution and cytokine expression levels.RESULTS: Most cytokines could not be detected in plasma except for IL-10. No difference in plasma IL-10 was observed among the 5 groups. The IL-2, IL-4, IL-10, and TNF-α mRNA expression levels in splenocytes were significantly higher in experimental groups 2 and 4 than in the control group and group 1. The mRNA expression of IFN-γ was significantly higher in the GLN-supplemented groups than in the control group and experimental group 1. The proportion of CD45Ra+ was increased, while those of CD3+ and CD4+ were decreased in experimental group 1 after CLP was performed. There were no differences in spleen CD3+ lymphocyte distributions between the control and GLN-supplemented groups.CONCLUSION:GLN supplementation can maintain Tlymphocyte populations in the spleen and significantly enhance the mRNA expression levels of Th1 and Th2cytokines and TNF-α in

  18. IL-35 is a novel responsive anti-inflammatory cytokine--a new system of categorizing anti-inflammatory cytokines.

    Science.gov (United States)

    Li, Xinyuan; Mai, Jietang; Virtue, Anthony; Yin, Ying; Gong, Ren; Sha, Xiaojin; Gutchigian, Stefanie; Frisch, Andrew; Hodge, Imani; Jiang, Xiaohua; Wang, Hong; Yang, Xiao-Feng

    2012-01-01

    It remains unknown whether newly identified anti-inflammatory/immunosuppressive cytokine interleukin-35 (IL-35) is different from other anti-inflammatory cytokines such as IL-10 and transforming growth factor (TGF)-β in terms of inhibition of inflammation initiation and suppression of full-blown inflammation. Using experimental database mining and statistical analysis methods we developed, we examined the tissue expression profiles and regulatory mechanisms of IL-35 in comparison to other anti-inflammatory cytokines. Our results suggest that in contrast to TGF-β, IL-35 is not constitutively expressed in human tissues but it is inducible in response to inflammatory stimuli. We also provide structural evidence that AU-rich element (ARE) binding proteins and microRNAs target IL-35 subunit transcripts, by which IL-35 may achieve non-constitutive expression status. Furthermore, we propose a new system to categorize anti-inflammatory cytokines into two groups: (1) the house-keeping cytokines, such as TGF-β, inhibit the initiation of inflammation whereas (2) the responsive cytokines including IL-35 suppress inflammation in full-blown stage. Our in-depth analyses of molecular events that regulate the production of IL-35 as well as the new categorization system of anti-inflammatory cytokines are important for the design of new strategies of immune therapies.

  19. IL-1 beta-induced chemokine and Fas expression are inhibited by suppressor of cytokine signalling-3 in insulin-producing cells

    DEFF Research Database (Denmark)

    Jacobsen, M.L.B.; Ronn, S.G.; Bruun, C.;

    2009-01-01

    of genes encoding the Fas receptor and several chemokines. We have previously shown that suppressor of cytokine signalling (SOCS)-3 inhibits IL-1 beta- and IFN-gamma-induced nitric oxide production in a beta cell line. The aim of this study was to investigate whether SOCS-3 can influence cytokine......Chemokines recruit activated immune cells to sites of inflammation and are important mediators of insulitis. Activation of the pro-apoptotic receptor Fas leads to apoptosis-mediated death of the Fas-expressing cell. The pro-inflammatory cytokines IL-1 beta and IFN-gamma regulate the transcription......-induced Fas and chemokine expression in beta cells. Using a beta cell line with inducible Socs3 expression or primary neonatal rat islet cells transduced with a Socs3-encoding adenovirus, we employed real-time RT-PCR analysis to investigate whether SOCS-3 affects cytokine-induced chemokine and Fas m...

  20. IL-1beta-induced chemokine and Fas expression are inhibited by suppressor of cytokine signalling-3 in insulin-producing cells

    DEFF Research Database (Denmark)

    Jacobsen, M L B; Rønn, S G; Bruun, C;

    2008-01-01

    the transcription of genes encoding the Fas receptor and several chemokines. We have previously shown that suppressor of cytokine signalling (SOCS)-3 inhibits IL-1beta- and IFN-gamma-induced nitric oxide production in a beta cell line. The aim of this study was to investigate whether SOCS-3 can influence cytokine......AIMS/HYPOTHESIS: Chemokines recruit activated immune cells to sites of inflammation and are important mediators of insulitis. Activation of the pro-apoptotic receptor Fas leads to apoptosis-mediated death of the Fas-expressing cell. The pro-inflammatory cytokines IL-1beta and IFN-gamma regulate......-induced Fas and chemokine expression in beta cells. METHODS: Using a beta cell line with inducible Socs3 expression or primary neonatal rat islet cells transduced with a Socs3-encoding adenovirus, we employed real-time RT-PCR analysis to investigate whether SOCS-3 affects cytokine-induced chemokine and Fas m...

  1. Increased Blood Levels of Growth Factors, Proinflammatory Cytokines, and Th17 Cytokines in Patients with Newly Diagnosed Type 1 Diabetes.

    Directory of Open Access Journals (Sweden)

    Kristi Alnek

    Full Text Available The production of several cytokines could be dysregulated in type 1 diabetes (T1D. In particular, the activation of T helper (Th type 1 (Th1 cells has been proposed to underlie the autoimmune pathogenesis of the disease, although roles for inflammatory processes and the Th17 pathway have also been shown. Nevertheless, despite evidence for the role of cytokines before and at the onset of T1D, the corresponding findings are inconsistent across studies. Moreover, conflicting data exist regarding the blood cytokine levels in T1D patients. The current study was performed to investigate genetic and autoantibody markers in association with the peripheral blood cytokine profiles by xMap multiplex technology in newly diagnosed young T1D patients and age-matched healthy controls. The onset of young-age T1D was characterized by the upregulation of growth factors, including granulocyte macrophage-colony stimulating factor (GM-CSF and interleukin (IL-7, the proinflammatory cytokine IL-1β (but not IL-6 or tumor necrosis factor [TNF]-α, Th17 cytokines, and the regulatory cytokines IL-10 and IL-27. Ketoacidosis and autoantibodies (anti-IA-2 and -ZnT8, but not human leukocyte antigen (HLA genotype, influenced the blood cytokine levels. These findings broaden the current understanding of the dysregulation of systemic levels of several key cytokines at the young-age onset of T1D and provide a further basis for the development of novel immunoregulatory treatments in this disease.

  2. Increased Blood Levels of Growth Factors, Proinflammatory Cytokines, and Th17 Cytokines in Patients with Newly Diagnosed Type 1 Diabetes

    Science.gov (United States)

    Heilman, Kaire; Peet, Aleksandr; Varik, Karin; Uibo, Raivo

    2015-01-01

    The production of several cytokines could be dysregulated in type 1 diabetes (T1D). In particular, the activation of T helper (Th) type 1 (Th1) cells has been proposed to underlie the autoimmune pathogenesis of the disease, although roles for inflammatory processes and the Th17 pathway have also been shown. Nevertheless, despite evidence for the role of cytokines before and at the onset of T1D, the corresponding findings are inconsistent across studies. Moreover, conflicting data exist regarding the blood cytokine levels in T1D patients. The current study was performed to investigate genetic and autoantibody markers in association with the peripheral blood cytokine profiles by xMap multiplex technology in newly diagnosed young T1D patients and age-matched healthy controls. The onset of young-age T1D was characterized by the upregulation of growth factors, including granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin (IL)-7, the proinflammatory cytokine IL-1β (but not IL-6 or tumor necrosis factor [TNF]-α), Th17 cytokines, and the regulatory cytokines IL-10 and IL-27. Ketoacidosis and autoantibodies (anti-IA-2 and -ZnT8), but not human leukocyte antigen (HLA) genotype, influenced the blood cytokine levels. These findings broaden the current understanding of the dysregulation of systemic levels of several key cytokines at the young-age onset of T1D and provide a further basis for the development of novel immunoregulatory treatments in this disease. PMID:26636339

  3. Different particle determinants induce apoptosis and cytokine release in primary alveolar macrophage cultures

    Directory of Open Access Journals (Sweden)

    Schwarze Per E

    2006-06-01

    Full Text Available Abstract Background Particles are known to induce both cytokine release (MIP-2, TNF-α, a reduction in cell viability and an increased apoptosis in alveolar macrophages. To examine whether these responses are triggered by the same particle determinants, alveolar macrophages were exposed in vitro to mineral particles of different physical-chemical properties. Results The crystalline particles of the different stone types mylonite, gabbro, basalt, feldspar, quartz, hornfels and fine grain syenite porphyr (porphyr, with a relatively equal size distribution (≤ 10 μm, but different chemical/mineral composition, all induced low and relatively similar levels of apoptosis. In contrast, mylonite and gabbro induced a marked MIP-2 response compared to the other particles. For particles of smaller size, quartz (≤ 2 μm seemed to induce a somewhat stronger apoptotic response than even smaller quartz (≤ 0.5 μm and larger quartz (≤ 10 μm in relation to surface area, and was more potent than hornfels and porphyr (≤ 2 μm. The reduction in cell viability induced by quartz of the different sizes was roughly similar when adjusted to surface area. With respect to cytokines, the release was more marked after exposure to quartz ≤ 0.5 μm than to quartz ≤ 2 μm and ≤ 10 μm. Furthermore, hornfels (≤ 2 μm was more potent than the corresponding hornfels (≤ 10 μm and quartz (≤ 2 μm to induce cytokine responses. Pre-treatment of hornfels and quartz particles ≤ 2 μm with aluminium lactate, to diminish the surface reactivity, did significantly reduce the MIP-2 response to hornfels. In contrast, the apoptotic responses to the particles were not affected. Conclusion These results indicate that different determinants of mineral/stone particles are critical for inducing cytokine responses, reduction in cell viability and apoptosis in alveolar macrophages. The data suggest that the particle surface reactivity was critical for cytokine responses

  4. Interactions between Cytokines, Congenital Anomalies of Kidney and Urinary Tract and Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Ana Cristina Simões e Silva

    2013-01-01

    Full Text Available Fetal hydronephrosis is the most common anomaly detected on antenatal ultrasound, affecting 1–5% of pregnancies. Postnatal investigation has the major aim in detecting infants with severe urinary tract obstruction and clinically significant urinary tract anomalies among the heterogeneous universe of patients. Congenital uropathies are frequent causes of pediatric chronic kidney disease (CKD. Imaging techniques clearly contribute to this purpose; however, sometimes, these exams are invasive, very expensive, and not sufficient to precisely define the best approach as well as the prognosis. Recently, biomarkers have become a focus of clinical research as potentially useful diagnostic tools in pediatric urological diseases. In this regard, recent studies suggest a role for cytokines and chemokines in the pathophysiology of CAKUT and for the progression to CKD. Some authors proposed that the evaluation of these inflammatory mediators might help the management of postnatal uropathies and the detection of patients with high risk to developed chronic kidney disease. Therefore, the aim of this paper is to revise general aspects of cytokines and the link between cytokines, CAKUT, and CKD by including experimental and clinical evidence.

  5. Inflammatory Cytokines: Potential Biomarkers of Immunologic Dysfunction in Autism Spectrum Disorders

    Directory of Open Access Journals (Sweden)

    Ningan Xu

    2015-01-01

    Full Text Available Autism is a disorder of neurobiological origin characterized by problems in communication and social skills and repetitive behavior. After more than six decades of research, the etiology of autism remains unknown, and no biomarkers have been proven to be characteristic of autism. A number of studies have shown that the cytokine levels in the blood, brain, and cerebrospinal fluid (CSF of autistic subjects differ from that of healthy individuals; for example, a series of studies suggests that interleukin-6 (IL-6, tumor necrosis factor-α (TNF-α, and interferon-γ (IFN-γ are significantly elevated in different tissues in autistic subjects. However, the expression of some cytokines, such as IL-1, IL-2, transforming growth factor-β (TGF-β, and granulocyte-macrophage colony-stimulating factor (GM-CSF, is controversial, and different studies have found various results in different tissues. In this review, we focused on several types of proinflammatory and anti-inflammatory cytokines that might affect different cell signal pathways and play a role in the pathophysiological mechanism of autistic spectrum disorders.

  6. Type-1-cytokines synergize with oncogene inhibition to induce tumor growth arrest

    Science.gov (United States)

    Acquavella, Nicolas; Clever, David; Yu, Zhiya; Roelke-Parker, Melody; Palmer, Douglas C.; Xi, Liqiang; Pflicke, Holger; Ji, Yun; Gros, Alena; Hanada, Ken-ichi; Goldlust, Ian S.; Mehta, Gautam U.; Klebanoff, Christopher A.; Crompton, Joseph G.; Sukumar, Madhusudhanan; Morrow, James J.; Franco, Zulmarie; Gattinoni, Luca; Liu, Hui; Wang, Ena; Marincola, Francesco; Stroncek, David F.; Lee, Chyi-Chia R.; Raffeld, Mark; Bosenberg, Marcus W.; Roychoudhuri, Rahul; Restifo, Nicholas P.

    2014-01-01

    Both targeted inhibition of oncogenic driver mutations and immune-based therapies show efficacy in treatment of patients with metastatic cancer but responses can be either short-lived or incompletely effective. Oncogene inhibition can augment the efficacy of immune-based therapy but mechanisms by which these two interventions might cooperate are incompletely resolved. Using a novel transplantable BRAFV600E-mutant murine melanoma model (SB-3123), we explore potential mechanisms of synergy between the selective BRAFV600E inhibitor vemurafenib and adoptive cell transfer (ACT)-based immunotherapy. We found that vemurafenib cooperated with ACT to delay melanoma progression without significantly affecting tumor infiltration or effector function of endogenous or adoptively transferred CD8+ T cells as previously observed. Instead, we found that the T-cell cytokines IFNγ and TNFα synergized with vemurafenib to induce cell-cycle arrest of tumor cells in vitro. This combinatorial effect was recapitulated in human melanoma-derived cell lines and was restricted to cancers bearing a BRAFV600E-mutation. Molecular profiling of treated SB-3123 indicated that the provision of vemurafenib promoted the sensitization of SB-3123 to the anti-proliferative effects of T-cell effector cytokines. The unexpected finding that immune cytokines synergize with oncogene inhibitors to induce growth arrest have major implications for understanding cancer biology at the intersection of oncogenic and immune signaling and provides a basis for design of combinatorial therapeutic approaches for patients with metastatic cancer. PMID:25358764

  7. High efficiency cell-specific targeting of cytokine activity

    Science.gov (United States)

    Garcin, Geneviève; Paul, Franciane; Staufenbiel, Markus; Bordat, Yann; van der Heyden, José; Wilmes, Stephan; Cartron, Guillaume; Apparailly, Florence; de Koker, Stefaan; Piehler, Jacob; Tavernier, Jan; Uzé, Gilles

    2014-01-01

    Systemic toxicity currently prevents exploiting the huge potential of many cytokines for medical applications. Here we present a novel strategy to engineer immunocytokines with very high targeting efficacies. The method lies in the use of mutants of toxic cytokines that markedly reduce their receptor-binding affinities, and that are thus rendered essentially inactive. Upon fusion to nanobodies specifically binding to marker proteins, activity of these cytokines is selectively restored for cell populations expressing this marker. This ‘activity-by-targeting’ concept was validated for type I interferons and leptin. In the case of interferon, activity can be directed to target cells in vitro and to selected cell populations in mice, with up to 1,000-fold increased specific activity. This targeting strategy holds promise to revitalize the clinical potential of many cytokines.

  8. Influence of phthalates on cytokine production in monocytes and macrophages

    DEFF Research Database (Denmark)

    Hansen, Juliana Frohnert; Bendtzen, Klaus; Boas, Malene;

    2015-01-01

    BACKGROUND: 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......://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...

  9. Affect Regulation

    DEFF Research Database (Denmark)

    Pedersen, Signe Holm; Poulsen, Stig Bernt; Lunn, Susanne

    2014-01-01

    Gergely and colleagues’ state that their Social Biofeedback Theory of Parental Affect Mirroring” can be seen as a kind of operationalization of the classical psychoanalytic concepts of holding, containing and mirroring. This article examines to what extent the social biofeedback theory of parenta...

  10. Morphine reduces local cytokine expression and neutrophil infiltration after incision

    Directory of Open Access Journals (Sweden)

    Li Xiangqi

    2007-10-01

    Full Text Available Abstract Background Inflammation and nociceptive sensitization are hallmarks of tissue surrounding surgical incisions. Recent studies demonstrate that several cytokines may participate in the enhancement of nociception near these wounds. Since opioids like morphine interact with neutrophils and other immunocytes, it is possible that morphine exerts some of its antinociceptive action after surgical incision by altering the vigor of the inflammatory response. On the other hand, keratinocytes also express opioid receptors and have the capacity to produce cytokines after injury. Our studies were directed towards determining if opioids alter cytokine production near incisions and to identify cell populations responsible for producing these cytokines. Results A murine incisional model was used to measure the effects of acute morphine administration (0.1–10 mg/kg on nociceptive thresholds, neutrophil infiltration and cytokine production in hind paw skin 30 minutes and 2 hours after incision. Incised hind paws displayed profound allodynia which was reduced by morphine (0.1–10 mg/kg in the 2 hours following incision. Skin samples harvested from these mice showed enhanced levels of 5 cytokines: IL-1β, IL-6, tumor necrosis factor alpha (TNFα, granulocyte colony stimulating factor (G-CSF and keratinocyte-derived cytokine (KC. Morphine reduced these incision-stimulated levels. Separate analyses measuring myeloperoxidase (MPO and using immunohistochemistry demonstrated that morphine dose-dependently reduced the infiltration of neutrophils into the peri-incisional tissue. The dose of morphine required for reduction of cytokine accumulation, however, was below that required for inhibition of peri-incisional neutrophil infiltration. Additional immunohistochemical studies revealed wound edge keratinocytes as being an important source of cytokines in the acute phase after incision. Conclusion Acute morphine administration of doses as low as 0.1 mg/kg reduces

  11. Influence of plasma impulse on graphite surface

    International Nuclear Information System (INIS)

    Graphite is candidate material for a defence barrier of fusion reactor so the knowledge of its futures is necessary in constructing of different fusion devices. Most part of researches were made with use of continuous plasma flow. This report presents the measurements of impulse plasma affect on the graphite surface. Plasma was generated on coaxial plasma accelerator CPA. Hydrogen and nitrogen were taken as plasma-forming gases. Graphite examples were tested in different regimes of CPA. Main characters of radiation process were measured. There were found the creation of graphite erosion out of the surface. Also there were found the injection of plasma forming gas into depth of graphite. 2 refs

  12. Theory of plasma electrodynamics

    International Nuclear Information System (INIS)

    The subject of this report is the physics of the electromagnetic behaviour of unmagnetized plasmas. After basic kinetic concepts, the dispersion relation of the plasma modes are developed, with emphasis on the comparison between the analytical expressions and the exact numerical solutions, especially on Landau dampings. Then, collisional dampings are presented. The mode couplings which drive parametric instabilities are then treated. Finally, the non-linear mechanisms, the pump depletion, designed as weak non-linearity, and the strong non-linearities which affect the longitudinal modes are discussed

  13. Plasma physics

    CERN Document Server

    Drummond, James E

    2013-01-01

    A historic snapshot of the field of plasma physics, this fifty-year-old volume offers an edited collection of papers by pioneering experts in the field. In addition to assisting students in their understanding of the foundations of classical plasma physics, it provides a source of historic context for modern physicists. Highly successful upon its initial publication, this book was the standard text on plasma physics throughout the 1960s and 70s.Hailed by Science magazine as a ""well executed venture,"" the three-part treatment ranges from basic plasma theory to magnetohydrodynamics and microwa

  14. Plasma undulator

    International Nuclear Information System (INIS)

    Two types of the undulator which is developed as a generator of the highly brilliant light for the synchrotron radiation sources and the free electron lasers, are newly proposed using the array of slender plasmas columns. One is the magnetic field type, in which the undulator force on the relativistic electron beam is generated with the electric current flowing through the plasma columns. The other is the electric field type, in which the undulator force is generated with the periodic variation of the density between the slender plasma columns. The production methods and stabilization ones of plasma columns are discussed. (author)

  15. Inflammatory cytokines in degeneration, regeneration and maintenance of sciatic nerve

    OpenAIRE

    Yokoyama, Shigeru

    2011-01-01

    Inflammatory cytokines play important roles in a variety of pathophysiological changes associated with traumatic injury and demyelinating disorders in the peripheral nervous system. After sciatic nerve injury, proinflammatory cytokines such as interleukin 1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNFα) are produced by and act on neurons, Schwann cells, and infiltrating inflammatory cells at the lesion site. Underlying these processes is receptor-mediated activation of intr...

  16. Role of cytokines in myocardial ischemia and reperfusion

    Directory of Open Access Journals (Sweden)

    H. S. Sharma

    1997-01-01

    Full Text Available Mediators of myocardial inflammation, predominantly cytokines, have for many years been implicated in the healing processes after infarction. In recent years, however, more attention has been paid to the possibility that the inflammation may result in deleterious complications for myocardial infarction. The proinflammatory cytokines may mediate myocardial dysfunction associated with myocardial infarction, severe congestive heart failure, and sepsis. A growing body of literature suggests that inflammatory mediators could play a crucial role in ischemia–reperfusion injury. Furthermore, ischemia–reperfusion not only results in the local transcriptional and translational upregulation of cytokines but also leads to tissue infiltration by inflammatory cells. These inflammatory cells are a ready source of a variety of cytokines which could be lethal for the cardiomyocytes. At the cellular level it has been shown that hypoxia causes a series of well documented changes in cardiomyocytes that includes loss of contractility, changes in lipid metabolism and subsequent irreversible cell membrane damage leading to cell death. For instance, hypoxic cardiomyocytes produce interleukin-6 (IL-6 which could contribute to the myocardial dysfunction observed in ischemia reperfusion injury. Ischemia followed by reperfusion induces a number of other multi-potent cytokines, such as IL-1, IL-8, tumor necrosis factor-α (TNF-α, transforming growth factor-β1 (TGF-β1 as well as an angiogenic cytokine/ growth factor, vascular endothelial growth factor (VEGF, in the heart. Intrestingly, these multipotent cytokines (e.g. TNF-α may induce an adaptive cytoprotective response in the reperfused myocardium. In this review, we have included a number of cytokines that may contribute to ventricular dysfunction and/or to the cytoprotective and adaptive changes in the reperfused heart.

  17. Aspergillus fumigatus Conidial Melanin Modulates Host Cytokine Response

    OpenAIRE

    Chai, Louis; Netea, Mihai; SUGUI, JANYCE; Vonk, Alieke; van de Sande, Wendy; Warris, Adilia; Kwon-Chung, Kyung; Jan Kullberg, Bart

    2009-01-01

    textabstractMelanin biopigments have been linked to fungal virulence. Aspergillus fumigatus conidia are melanised and are weakly immunogenic. We show that melanin pigments on the surface of resting Aspergillus fumigatus conidia may serve to mask pathogen-associated molecular patterns (PAMPs)-induced cytokine response. The albino conidia induced significantly more proinflammatory cytokines in human peripheral blood mononuclear cells (PBMC), as compared to melanised wild-type conidia. Blocking ...

  18. Assessment by Flow Cytometry of Cytokine Production in Malnourished Children

    OpenAIRE

    Rodríguez, Leonor; González, Cristina; Flores, Luis; Jiménez-Zamudio, Luis; Graniel, Jaime; Ortiz, Rocío

    2005-01-01

    Malnutrition in children is associated with an increased risk of infection and death. Multiple abnormalities in the immune response, including cytokine production, in protein energy-malnourished children have been described and could account for the increased severity and frequency of infections. In this study, we used flow cytometry to investigate the effects of malnutrition on the production of cytokines (interleukin-2 [IL-2], gamma interferon [IFN-γ], IL-4, and IL-10) in CD4+ and CD8+ cell...

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

    Directory of Open Access Journals (Sweden)

    Sung S Choi

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

  20. Cytokine signatures of human whole blood for monitoring immunosuppression

    OpenAIRE

    He, Yi; Luo, Yuwei; Lao, Xiaobin; Tan, Liping; Sun, Erwei

    2014-01-01

    How to evaluate status of the immune system is extremely critical for clinical immunosuppressive treatment. In this study, we tested the secretion of cytokines in undiluted whole blood samples stimulated with Phorbol 12-myristate 13-acetate (PMA) and ionomycin (IONO), and compared the effects of dexamethasone (DEX), cyclosporine A (CsA) or mycophenolic acid (MPA), either alone or in combination, on cytokine profiles. The results showed that both DEX and CsA dose-dependently inhibited the prod...

  1. Cytokines in the systemic inflammatory response syndrome: a review

    OpenAIRE

    Jaffer, U; Wade, R G; Gourlay, T

    2010-01-01

    Introduction Patients subject to major surgery, suffering sepsis, major trauma, or following cardiopulmonary bypass exhibit a systemic inflammatory response. This inflammatory response involves a complex array of inflammatory polypeptide molecules known as cytokines. It is well accepted that the loss of local control of the release of these cytokines leads to systemic inflammation and potentially deleterious consequences including the Systemic Inflammatory Response Syndrome, Multi-Organ Dysfu...

  2. Vitamin D and Serum Cytokines in a Randomized Clinical Trial

    OpenAIRE

    Eleanor Yusupov; Melissa Li-Ng; Simcha Pollack; James K. Yeh; Mageda Mikhail; Aloia, John F

    2010-01-01

    Background. The role of vitamin D in the body's ability to fight influenza and URI's may be dependent on regulation of specific cytokines that participate in the host inflammatory response. The aim of this study was to test the hypothesis that vitamin D can influence intracellular signaling to regulate the production of cytokines. Subjects and Methods. This study was a 3-month prospective placebo-controlled trial of vitamin D3 supplementation in ambulatory adults [Li-Ng et al., 2009]....

  3. Atomic and molecular processes in fusion plasmas

    Energy Technology Data Exchange (ETDEWEB)

    Janev, R.K. [International Atomic Energy Agency, Vienna (Austria)

    1997-01-01

    The role of atomic and molecular processes in achieving and maintaining the conditions for thermonuclear burn in a magnetically confined fusion plasma is described. Emphasis is given to the energy balance and power and particle exhaust issues. The most important atomic and molecular processes which affect the radiation losses and impurity transport in the core plasma, the neutral particle transport in the plasma edge and the radiative cooling of divertor plasmas are discussed in greater detail. (author)

  4. Short-chain fatty acids act as antiinflammatory mediators by regulating prostaglandin E_2 and cytokines

    Institute of Scientific and Technical Information of China (English)

    Mary Ann Cox; James Jackson; Michaela Stanton; Alberto Rojas-Triana; Loretta Bober; Maureen Laverty; Xiaoxin Yang; Feng Zhu; Jianjun Liu; Suke Wang; Frederick Monsma; Galya Vassileva; Maureen Maguire; Eric Gustafson; Marvin Bayne; Chuan-Chu Chou; Daniel Lundell; Chung-Her Jenh

    2009-01-01

    AIM: To investigate the effect of short-chain fatty acids(SCFAs) on production of prostaglandin E_2 (PGE_2),cytokines and chemokines in human monocytes.METHODS: Human neutrophils and monocytes were isolated from human whole blood by using 1-Step Polymorph and RosetteSep Human Monocyte Enrichment Cocktail, respectively. Human GPR41 and GPR43 mRNA expression was examined by quantitative realtimepolymerase chain reaction. The calcium flux assay was used to examine the biological activities of SCFAs in human neutrophils and monocytes. The effect of SCFAs on human monocytes and peripheral blood mononuclear cells (PBMC) was studied by measuring PGE_2, cytokines and chemokines in the supernatant.The effect of SCFAs in vivo was examined by intraplantar injection into rat paws.RESULTS: Human GPR43 is highly expressed in human neutrophils and monocytes. SCFAs induce robust calcium flux in human neutrophils, but not in human monocytes. In this study, we show that SCFAs can induce human monocyte release of PGE_2 and that this effect can be enhanced in the presence of lipopolysaccharide(LPS). In addition, we demonstrate that PGE_2 production induced by SCFA was inhibited by pertussis toxin, suggesting the involvement of a receptor-mediated mechanism. Furthermore, SCFAs can specifically inhibit constitutive monocyte chemotactic protein-1(MCP-1) production and LPS-induced interleukin-10(IL-10) production in human monocytes without affecting the secretion of other cytokines and chemokines examined. Similar activities were observed in human PBMC for the release of PGE_2, MCP-1 and IL-10 after SCFA treatment. In addition, SCFAs inhibit LPS-induced production of tumor necrosis factor-α and interferon-γ in human PBMC. Finally, we show that SCFAs and LPS can induce PGE_2 production in vivo by intraplantar injectioninto rat paws ( P < 0.01).CONCLUSION: SCFAs can have distinct antiinflammatory activities due to their regulation of PGE_2, cytokine and chemokine release from human immune

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

    Directory of Open Access Journals (Sweden)

    Sabry M. El-Bahr

    2013-01-01

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

  6. Controlled meal frequency without caloric restriction alters peripheral blood mononuclear cell cytokine production

    Directory of Open Access Journals (Sweden)

    Longo Dan L

    2011-03-01

    Full Text Available Abstract Background Intermittent fasting (IF improves healthy lifespan in animals by a mechanism involving reduced oxidative damage and increased resistance to stress. However, no studies have evaluated the impact of controlled meal frequency on immune responses in human subjects. Objective A study was conducted to establish the effects of controlled diets with different meal frequencies, but similar daily energy intakes, on cytokine production in healthy male and female subjects. Design In a crossover study design with an intervening washout period, healthy normal weight middle-age male and female subjects (n = 15 were maintained for 2 months on controlled on-site one meal per day (OMD or three meals per day (TMD isocaloric diets. Serum samples and peripheral blood mononuclear cells (PBMCs culture supernatants from subjects were analyzed for the presence of inflammatory markers using a multiplex assay. Results There were no significant differences in the inflammatory markers in the serum of subjects on the OMD or TMD diets. There was an increase in the capacity of PBMCs to produce cytokines in subjects during the first month on the OMD or TMD diets. Lower levels of TNF-α, IL-17, MCP-1 and MIP-1β were produced by PBMCs from subjects on the OMD versus TMD diet. Conclusions PBMCs of subjects on controlled diets exhibit hypersensitivities to cellular stimulation suggesting that stress associated with altered eating behavior might affect cytokine production by immune cells upon stimulation. Moreover, stimulated PBMCs derived from healthy individuals on a reduced meal frequency diet respond with a reduced capability to produce cytokines.

  7. Intricacies for Posttranslational Tumor-Targeted Cytokine Gene Therapy

    Directory of Open Access Journals (Sweden)

    Jeffry Cutrera

    2013-01-01

    Full Text Available The safest and most effective cytokine therapies require the favorable accumulation of the cytokine in the tumor environment. While direct treatment into the neoplasm is ideal, systemic tumor-targeted therapies will be more feasible. Electroporation-mediated transfection of cytokine plasmid DNA including a tumor-targeting peptide-encoding sequence is one method for obtaining a tumor-targeted cytokine produced by the tumor-bearing patient’s tissues. Here, the impact on efficacy of the location of targeting peptide, choice of targeting peptide, tumor histotype, and cytokine utilization are studied in multiple syngeneic murine tumor models. Within the same tumor model, the location of the targeting peptide could either improve or reduce the antitumor effect of interleukin (IL12 gene treatments, yet in other tumor models the tumor-targeted IL12 plasmid DNAs were equally effective regardless of the peptide location. Similarly, the same targeting peptide that enhances IL12 therapies in one model fails to improve the effect of either IL15 or PF4 for inhibiting tumor growth in the same model. These interesting and sometimes contrasting results highlight both the efficacy and personalization of tumor-targeted cytokine gene therapies while exposing important aspects of these same therapies which must be considered before progressing into approved treatment options.

  8. Cytokine and Immuno-Gene Therapy for Solid Tumors

    Institute of Scientific and Technical Information of China (English)

    Chuan-Yuan Li; Qian Huang; Hsiang-Fu Kung

    2005-01-01

    Despite recent progress in our understanding of cancer biology and in many areas of cancer treatment, the success rate for cancer therapy remains dismal. Immunotherapy for cancer has long been an exciting field for many cancer researchers due to the possibility to mobilize the body's own immune system to eradicate cancer not only locally but also systemically. Since its initial discovery, cytokine-based immunotherapy has been vigorously and extensively investigated for cancer treatment due to the perception of it as a relatively easily purifiable, injectable form of cancer treatment agent. However, so far most cytokine-based therapy trials have fallen short of expectations. One of main obstacles is the difficulty to achieve therapeutically relevant dosage in patients without generating excessive normal tissue toxicity. The emergence of novel gene therapy approach to deliver therapeutic cytokine to tumors locally generated great excitement since it has the potential of generating sustained high local concentration of immunostimulatory cytokine without raising the systemic levels of the cytokines, which is responsible for most of the observed toxicity. In this review, we will attempt to provide an overview of the field and discuss some of the problems associated with cytokine-based immuno-gene therapy and potential solutions.Cellular & Molecular Immunology. 2005;2(2):81-91.

  9. Cytokine and Immuno-Gene Therapy for Solid Tumors

    Institute of Scientific and Technical Information of China (English)

    Chuan-YuanLi; QianHuang; Hsiang-FuKung

    2005-01-01

    Despite recent progress in our understanding of cancer biology and in many areas of cancer treatment, the success rate for cancer therapy remains dismal. Immunotherapy for cancer has long been an exciting field for many cancer researchers due to the possibility to mobilize the body's own immune system to eradicate cancer not only locally but also systemically. Since its initial discovery, cytokine-based immunotherapy has been vigorously and extensively investigated for cancer treatment due to the perception of it as a relatively easily purifiable, injectable form of cancer treatment agent. However, so far most cytokine-based therapy trials have fallen short ofexpectations. One of main obstacles is the difficulty to achieve therapeutically relevant dosage in patients without generating excessive normal tissue toxicity. The emergence of novel gene therapy approach to deliver therapeutic cytokine to tumors locally generated great excitement since it has the potential of generating sustained high local concentration of immunostimulatory cytokine without raising the systemic levels of the cytokines, which is responsible for most of the observed toxicity. In this review, we will attempt to provide an overview of the field and discuss some of the problems associated with cytokine-based immuno-gene therapy and potential solutions. Cellular & Molecular Immunology. 2005;2(2):81-91.

  10. A genetically encoded bioluminescent indicator for illuminating proinflammatory cytokines.

    Science.gov (United States)

    Kim, Sung Bae; Ozawa, Takeaki; Umezawa, Yoshio

    2016-01-01

    We introduce a method to evaluate the activities of cytokines based on the nuclear transport of NF-κB. A pair of bioluminescent indicators was made for conferring cytokine sensitivity to cervical carcinoma-derived HeLa cells. The principle is based on reconstitution of split fragments of Renilla reniformis luciferase (RLuc) by protein splicing with a DnaE intein from Synechocystis sp. PCC6803. The bioluminescence intensity of thus reconstituted RLuc in the HeLa cells was used as a measure of the activities for cytokines. With the present method, we evaluated the activities of various cytokines based on the nuclear transport of NF-κB in human cervical carcinoma-derived HeLa cells carrying the indicators. The present approach to evaluating the activities of cytokines may provide a potential clinical value in monitoring drug activity and directing treatment for various diseases related with NF-κB. The method highlights the experimental procedure from our original publications, Anal. Biochem. 2006, 359, 147-149 and Proc. Natl. Acad. Sci. U. S. A. 2004, 101, 11542. The summary of the method is: •Cytokine activities are determined within 2 h after stimulation.•Temporarily inactivated split-luciferase fragments are reconstituted by protein splicing.•Nucleartrafficking of NF-κB was illuminated for gauging the ligand-driven activity. PMID:27489781

  11. INVESTIGATION OF CYTOKINE PROFILE IN PATIENTS WITH REACTIVE ARTHRITIS

    Directory of Open Access Journals (Sweden)

    T. V. Gaponova

    2008-01-01

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

  12. Effect of NaCl and Helicobacter pylori vacuolating cytotoxin on cytokine expression and viability

    Institute of Scientific and Technical Information of China (English)

    Juan Sun; Kazuo Aoki; Jin-Xu Zheng; Bing-Zhong Su; Xiao-Hui Ouyang; Junichi Misumi

    2006-01-01

    AIM: To determine whether Helicobacter pylori (H pylori) vacuolating cytotoxin (VacA) regulates release of proinflammatory cytokines (IL-1β, IL-8, TNF-α, and IL-6)or alters gastric epithelial cell viability and to determine whether NaCl affects these VacA-induced changes.METHODS: Vacuolating activity was determined by measuring the uptake of neutral red into vacuoles of VacA-treated human gastric epithelial (AGS) cells. AGS cell viability was assessed by direct cell counting. Specific enzyme-linked immunosorbent assays (ELISA) and reverse transcriptase-polymerase chain reaction(RT-PCR)were performed to examine the effects of Hpylori VacA and NaCl on cell pro-inflammatory cytokine production in AGS cells. Immunohistochemical staining of gastric tissue from Mongolian gerbils was used to confirm VacA-induced pro-inflammatory cytokine production and the effects of NaCl on this VacA-induced response.RESULTS: Addition of VacA alone reduced AGS cell viability (P< 0.05), and this reduction was enhanced by high doses of NaCl (P< 0.05). VacA alone induced expression of TNF-α, IL-8 and IL-1β, while NaCl alone induced expression of TNF-α and IL-1β. Changes in mRNA levels in the presence of both VacA and NaCl were more complicated. For the case of TNF-a, expression was dosedependent on NaCl. IL-6 mRNA was not detected. However, low levels of IL-6 were detected by ELISA. Positive immunohistochemical staining of IL- 1, IL-6, and TNF-αwas found in gastric tissue of H pylori-infected gerbils fed with either a normal diet or a high salt diet. However,the staining of these three cytokines was stronger in H pylori-infected animals fed with a 5g/kg NaCl diet.CONCLUSION: VacA decreases the viability of AGS cells, and this effect can be enhanced by NaCl. NaCl also affects the production of pro-inflammatory cytokines induced by Vac A, suggesting that NaCl plays an important role in Hpylori-induced gastric epithelial cell cytotoxicity.

  13. Proinflammatory and anti-inflammatory cytokines in adolescents from Southeast Bulgarian cities with different levels of air pollution.

    Science.gov (United States)

    Dobreva, Zlatka Georgieva; Kostadinova, Gergana Stoianova; Popov, Borislav Nikolov; Petkov, Georgi Stefanov; Stanilova, Spaska Angelova

    2015-12-01

    Epidemiological studies demonstrated that the exposure of different air pollutants including particulate matter (PM) has been related to adverse effect on immune system. Current study was designed to investigate cytokines in blood plasma of adolescent persons continuously exposed to different degrees of ambient air pollutions. Tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), IL-12p40, and IL-10 were chosen as cytokines of proinflammatory and anti-inflammatory immune response. The peripheral venous blood was taken from adolescents living in the cities of Stara Zagora region, Southeast Bulgaria, that is, in Stara Zagora, Kazanlak, and Chirpan. The quantity of cytokines in plasma samples was determined by enzyme-linked immunosorbent assay. Results demonstrated that youths living in Stara Zagora showed significantly smaller quantity of TNF-α, compared with adolescents from Kazanlak and Chirpan. Moreover, adolescents living in Stara Zagora showed significantly higher quantity of IL-10 than students from Kazanlak and Chirpan. Analysis of the data of air quality gives reason to assert that PM10 and PM2.5 have been the main atmospheric pollutants around the monitoring points. The complex air quality assessment based on these criteria determined that the highest air pollution was in the city of Stara Zagora, followed by Chirpan and the relatively unpolluted town was Kazanlak. We concluded that air pollutants, mostly PM2.5, can modulate cytokine production and can change the balance between proinflammatory TNF-α and anti-inflammatory IL-10 production. Increased levels of IL-10 combined with decreased level of TNF-α in adolescents living in Stara Zagora can serve as a biomarker for suppression of T helper 1 (Th1) cell-mediated immunity and exacerbation of Th2 humoral immune response and could be a prerequisite for the development of allergic and autoimmune diseases. PMID:23771874

  14. Cytokines Expression Profile and Kinetics of Peste des petits ruminants Virus Antigen and Antibody in Infected and Vaccinated Goats

    Institute of Scientific and Technical Information of China (English)

    Arun Patel; Kaushal Kishor Rajak; Vinayagamurthy Balamurugan; Arnab Sen; Shashi Bhusan Sudhakar; Veerakyathappa Bhanuprakash; Raj Kumar Singh; Awadh Bihari Pandey

    2012-01-01

    The present study deals with the co-ordination of cytokine(IL-4 and IFN-γ) expression and kinetics of peste des petits ruminants(PPR) virus antigen and antibody in PPRV infected and vaccinated goats.The infected animals exhibited mixed cytokine(both TH1 and TH2) responses in the initial phase of the disease.The infected and dead goats had increased IFN-γ response before their death; while IL-4 remained at the base level.The cytokine expression in recovered animals was almost similar to that of vaccinated ones,where a unique biphasic response of IL-4 expression was observed with an up-regulation of IFN-γ on 7th days post vaccination(dpv).Analysis of PPR virus antigen and antibody kinetics in different components of blood from infected and vaccinated animals revealed that the PPR virus antigen load was highest in plasma followed by serum and blood of the infected animals,whereas vaccinated animals showed only marginal positivity on 9th dpv.The antibody titer was high in serum followed by plasma and blood in both vaccinated and infected animals.Therefore,it is inferred that the presence of antigen and antibody were significant with the expression of cytokine,and that a decreased response of IL-4 was noticed during intermediate phase of the disease i.e.,7 to 12th days post infection(dpi).This indicates the ability to mount a functional TH2 response after 14th dpi could be a critical determinant in deciding the survival of the PPR infected animal.

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

    Directory of Open Access Journals (Sweden)

    Bozza Patricia T

    2008-06-01

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

  16. Identification of enhanced cytokine generation following sepsis. Dream of magic bullet for mortality prediction and therapeutic evaluation

    Directory of Open Access Journals (Sweden)

    H Hamishehkar

    2010-09-01

    Full Text Available "n  "nBackground and the purpose of the study: sepsis is one of the most widespread and lethal disease in Intensive Care Units (ICU. Based on pathophisyology of sepsis, it seems that routine laboratory tests combined with analysis of pro-inflammatory cytokines plasma levels, help clinicians to have more information about disease progress and its correct management. "nMethods:This was a prospective observational study to determine the predictive role of Tumor Necrosis Factor alpha (TNF-α, Interleukin (IL-1β and IL-6 as three main pro-inflammatory cytokines and Acute Physiology and Chronic Health Evaluation (APACHE II and Sequential Organ Failure Assessment (SOFA as two scoring systems in mortality of critically ill patients with severe sepsis. Fifty and five patients with criteria of severe sepsis were included in this study. An exclusion criterion was post Cardiopulmonary Resuscitation (CPR status. Cytokines (TNF-α, IL-1β and IL-6 were assayed in the first, third and seventh days in blood of patients. Results and major conclusion:Among three measured cytokines, sequential levels of TNF-α and IL-6 showed significant differences between survivors and nonsurvivors. IL-6 had a good correlation with outcome and scoring systems during the period of this study. The areas under the receiver operating characteristic (AUROC curve indicated that APACHE II (0.858, 0.848, 0.861 and IL-6 (0.797, 0.799, 0.899 had discriminative power in prediction of mortality during sequental measured days. Multiple logestic regression analysis identified that evaluation of APACHE II and TNF-α in the first day and APACHE II and IL-6 in the third and seventh days of severe septic patients are independent outcome predictors. Results of this study suggest that IL-6 and APACHE II are useful cytokine and scoring systems respectively in prediction of mortality and clinical evaluation of severe septic patients.

  17. Aluminium fluoride and magnesium, activators of heterotrimeric GTP-binding proteins, affect high-affinity binding of the fungal toxin fusicoccin to the fusicoccin-binding protein in oat root plasma membranes.

    NARCIS (Netherlands)

    de Boer, A.H.; Van der Molen, G.W.; Prins, H.B.A.; Korthout, H.A.A.J.; van der Hoeven, P.C.J.

    1994-01-01

    The fusicoccin-binding protein was solubilised from purified oat root plasma membranes. The solubilised protein retained full binding activity, provided that protease inhibitors were included. Sodium fluoride reduced the high-affinity [H-3]fusicoccin binding to almost zero in a concentration-depende

  18. Repeated topical treatment, in contrast to single oral doses, with Vitamin A-containing preparations does not affect plasma concentrations of retinol, retinyl esters or retinoic acids in female subjects of child-bearing age

    NARCIS (Netherlands)

    Nohynek, G.J.; Meuling, W.J.A.; Vaes, W.H.J.; Lawrence, R.S.; Shapiro, S.; Schulte, S.; Steiling, W.; Bausch, J.; Gerber, E.; Sasa, H.; Nau, H.

    2006-01-01

    Background: Vitamin A is widely used in cosmetic preparations. Given that oral Vitamin A and its metabolites present a potential reproductive risk, the present study investigated the effect of topical Vitamin A on human endogenous plasma levels of Vitamin A and its metabolites. Methods: Two groups o

  19. Circulating Cytokines and Cytokine Receptors in Infliximab Treatment Failure Due to TNF-α Independent Crohn Disease

    DEFF Research Database (Denmark)

    Steenholdt, Casper; Coskun, Mehmet; Buhl, Sine;

    2016-01-01

    The inflammatory response at infliximab (IFX) treatment failure due to tumor necrosis factor (TNF)-α-independent Crohn disease activity is unknown.This is an exploratory, hypothesis-generating study based on samples collected in a clinical trial among patients failing conventional IFX dosages......-IFX antibodies. Circulating cytokines and cytokine receptors were assessed by enzyme-linked immunosorbent assay: granulocyte-macrophage colony-stimulating factor, interferon-γ, interleukin (IL)-1α, IL-1β, IL-1Ra, IL-6, IL-10, IL-12p70, soluble TNF receptor (sTNF-R) 1, sTNF-R2, IL-17A, and monocyte chemotactic...... to predominantly TNF-α-independent signaling pathways in their disease. Cytokine and cytokine receptor levels were comparable between patients with nonimmune PK failure and PD failure at time of manifestation of IFX failure, but with higher IL-6 and sTNF-R2 levels among IFX treatment failures as compared...

  20. ATP Is Required and Advances Cytokine-Induced Gap Junction Formation in Microglia In Vitro

    Directory of Open Access Journals (Sweden)

    Pablo J. Sáez

    2013-01-01

    Full Text Available Microglia are the immune cells in the central nervous system. After injury microglia release bioactive molecules, including cytokines and ATP, which modify the functional state of hemichannels (HCs and gap junction channels (GJCs, affecting the intercellular communication via extracellular and intracellular compartments, respectively. Here, we studied the role of extracellular ATP and several cytokines as modulators of the functional state of microglial HCs and GJCs using dye uptake and dye coupling techniques, respectively. In microglia and the microglia cell line EOC20, ATP advanced the TNF-α/IFN-γ-induced dye coupling, probably through the induction of IL-1β release. Moreover, TNF-α/IFN-γ, but not TNF-α plus ATP, increased dye uptake in EOC20 cells. Blockade of Cx43 and Panx1 HCs prevented dye coupling induced by TNF-α/IFN-γ, but not TNF-α plus ATP. In addition, IL-6 prevented the induction of dye coupling and HC activity induced by TNF-α/IFN-γ in EOC20 cells. Our data support the notion that extracellular ATP affects the cellular communication between microglia through autocrine and paracrine mechanisms, which might affect the timing of immune response under neuroinflammatory conditions.

  1. Affective Networks

    Directory of Open Access Journals (Sweden)

    Jodi Dean

    2010-02-01

    Full Text Available This article sets out the idea of affective networks as a constitutive feature of communicative capitalism. It explores the circulation of intensities in contemporary information and communication networks, arguing that this circulation should be theorized in terms of the psychoanalytic notion of the drive. The article includes critical engagements with theorists such as Guy Debord, Jacques Lacan, Tiziana Terranova, and Slavoj Zizek.

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

    Science.gov (United States)

    Ip, Margaret; Chu, Yi Jun; Yung, Irene M. H.; Cheung, Catherine S. K.; Zheng, Lin; Lam, Judy S. Y.; Wong, Ka Tak; Sin, Winnie W. Y.; Choi, Kin Wing; Lee, Nelson

    2016-01-01

    Background We aimed to study the pathogenic roles of High-Mobility Group Box 1 (HMGB1) / Receptor-for-Advanced-Glycation-End-products (RAGE) signaling and pro-inflammatory cytokines in patients with active pulmonary tuberculosis (PTB). Methods A prospective study was conducted among non-HIV adults newly-diagnosed with active PTB at two acute-care hospitals (n = 80); age-and-sex matched asymptomatic individuals (tested for latent TB) were used for comparison (n = 45). Plasma concentrations of 8 cytokines/chemokines, HMGB1, soluble-RAGE, and transmembrane-RAGE expressed on monocytes/dendritic cells, were measured. Gene expression (mRNA) of HMGB1, RAGE, and inflammasome-NALP3 was quantified. Patients’ PBMCs were stimulated with recombinant-HMGB1 and MTB-antigen (lipoarabinomannan) for cytokine induction ex vivo. Results In active PTB, plasma IL-8/CXCL8 [median(IQR), 6.0(3.6–15.1) vs 3.6(3.6–3.6) pg/ml, PCXCL8 (adjusted OR 1.12, 95%CI 1.02–1.23 per unit increase, P = 0.021) and HMGB1 (adjusted OR 1.42 per unit increase, 95%CI 1.08–1.87, P = 0.012) concentrations were independent predictors for respiratory failure, as well as for ICU admission/death. Gene expression of HMGB1, RAGE, and inflammasome-NALP3 were upregulated (1.2−2.8 fold). Transmembrane-RAGE was increased, whereas the decoy soluble-RAGE was significantly depleted. RAGE and HMGB1 gene expressions positively correlated with cytokine levels (IL-8/CXCL8, IL-6, sTNFR1) and clinico-/radiographical severity (e.g. extent of consolidation rs +0.240, P = 0.034). Ex vivo, recombinant-HMGB1 potentiated cytokine release (e.g. TNF-α) when combined with lipoarabinomannan. Conclusion In patients with active PTB, HMGB1/RAGE signaling and pro-inflammatory cytokines may play important roles in pathogenesis and disease manifestations. Our clinico-immunological data can provide basis for the development of new strategies for disease monitoring, management and control. PMID:27434276

  3. Plasma properties

    International Nuclear Information System (INIS)

    The Magneto-Fluid Dynamics Division continues to study a broad range of problems originating in plasma physics. Its principal focus is fusion plasma physics, and most particularly topics of particular significance for the world magnetic fusion program. During the calendar year 1990 we explored a wide range of topics including RF-induced transport as a plasma control mechanism, edge plasma modelling, further statistical analysis of L and H mode tokamak plasmas, antenna design, simulation of the edge of a tokamak plasma and the L-H transition, interpretation of the CCT experimental results at UCLA, turbulent transport, studies in chaos, the validity of moment approximations to kinetic equations and improved neoclassical modelling. In more basic studies we examined the statistical mechanisms of Coulomb systems and applied plasma ballooning mode theory to conventional fluids in order to obtain novel fluid dynamics stability results. In space plasma physics we examined the problem of reconnection, the effect of Alfven waves in space environments, and correct formulation of boundary conditions of the Earth for waves in the ionosphere

  4. Extracellular matrix assessment of infected chronic venous leg ulcers: role of metalloproteinases and inflammatory cytokines.

    Science.gov (United States)

    Serra, Raffaele; Grande, Raffaele; Buffone, Gianluca; Molinari, Vincenzo; Perri, Paolo; Perri, Aldina; Amato, Bruno; Colosimo, Manuela; de Franciscis, Stefano

    2016-02-01

    Chronic venous ulcer (CVU) represents a dreaded complication of chronic venous disease (CVD). The onset of infection may further delay the already precarious healing process in such lesions. Some evidences have shown that matrix metalloproteinases (MMPs) are involved and play a central role in both CVUs and infectious diseases. Two groups of patients were enrolled to evaluate the expression of MMPs in infected ulcers and the levels of inflammatory cytokines as well as their prevalence. Group I comprised 63 patients (36 females and 27 males with a median age of 68·7 years) with infected CVUs, and group II (control group) comprised 66 patients (38 females and 28 males with a median age of 61·2 years) with non-infected venous ulcers. MMP evaluation and dosage of inflammatory cytokines in plasma and wound fluid was performed by means of enzyme-linked immunosorbent assay test; protein extraction and immunoblot analysis were performed on biopsied wounds. The first three most common agents involved in CVUs were Staphylococcus aureus (38·09%), Corynebacterium striatum (19·05%) and Pseudomonas aeruginosa (12·7%). In this study, we documented overall higher levels of MMP-1 and MMP-8 in patients with infected ulcers compared to those with uninfected ulcers that showed higher levels of MMP-2 and MMP-9. We also documented higher levels of interleukin (IL)-1, IL-6, IL-8, vascular endothelial growth factor and tumour necrosis factor-alpha in patients with infected ulcers with respect to those with uninfected ulcers, documenting a possible association between infection, MMP activation, cytokine secretions and symptoms. The present results could represent the basis for further studies on drug use that mimic the action of tissue inhibitors of metalloproteinases in order to make infected CVU more manageable.

  5. PLASMA DEVICE

    Science.gov (United States)

    Baker, W.R.

    1961-08-22

    A device is described for establishing and maintaining a high-energy, rotational plasma for use as a fast discharge capacitor. A disc-shaped, current- conducting plasma is formed in an axinl magnetic field and a crossed electric field, thereby creating rotational kinetic enengy in the plasma. Such energy stored in the rotation of the plasma disc is substantial and is convertible tc electrical energy by generator action in an output line electrically coupled to the plasma volume. Means are then provided for discharging the electrical energy into an external circuit coupled to the output line to produce a very large pulse having an extremely rapid rise time in the waveform thereof. (AE C)

  6. 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)

    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 with formaldehyde solution, embedded with paraffin and stained by SP immunohistochemistry. Intercellular adhesion molecule-1 (ICAM-1) expression was measured through the determination of the light density with computer imaging technology. Results Compared with that of the patients with simple VSD, the light density of ICAM-1 and plasma level of ET-1 increased in patients with PH; but plasma level of NO decreased (P<0.05). Positive correlation was observed between ICAM-1 and ET-1/NO (P<0.05). Conclusion Endothelia cells activation and imbalance of ET-1/NO might play an important role in the development of PH.

  7. Defining an appropriate leucoreduction strategy by serial assessment of cytokine levels in platelet concentrates prepared by different methods

    Science.gov (United States)

    Kaur, Daljit; Sharma, Ratti Ram; Marwaha, Neelam

    2015-01-01

    Background and Objectives: Different methods of platelet concentrate preparations leave behind certain number of residual leukocytes, accounting for most of the febrile nonhemolytic transfusion reactions, especially in multitransfused patients. Various inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6 are generated during storage and have been implicated for these adverse effects. We have studied the levels of these cytokines and their correlation with leucocyte contents in platelet concentrates prepared by three different methods. Study Design and Methods: Five pools of platelet rich plasma platelet concentrates (PRP-PC) and buffy-coat platelet concentrates (BC-PC) each were prepared and divided into two halves. One half of the pool was leucofiltered (LF), whereas the other half was stored as such. Ten apheresis units were also included in the study. All the platelet concentrates were assessed for leucocyte load and cytokine content (IL-1β, IL-6, and TNF-α) on different days of storage (0, 3, and 5) using Nageotte chamber and commercially available immunoassays respectively. Results: There was a statistically significant rise in cytokine levels (IL-1β, IL-6, and TNF-α) in nonleucofiltered (NLF) random donor platelet concentrates (RDPs) (PRP-PC and BC-PC) during storage (day 3 and 5) whereas LF RDP concentrates (PRP-PC and BC-PC) and apheresis platelet concentrates (AP-PC) did not show any significant rise in cytokine levels (on day 3 and 5) over the baseline values at day 0. Conclusion: This data suggests that although AP-PCs are superior to PRP-PC (NLF) and BC-PC (NLF) in terms of in vitro quality control parameters and cytokine generation during storage, BC-PC mode of platelet preparation followed by leucofiltration is the best method to store platelets and minimise the cytokine accumulation. This strategy is best suited for transfusion in multitransfused hematooncologic patients, who cannot afford single

  8. Defining an appropriate leucoreduction strategy by serial assessment of cytokine levels in platelet concentrates prepared by different methods

    Directory of Open Access Journals (Sweden)

    Daljit Kaur

    2015-01-01

    Full Text Available Background and Objectives: Different methods of platelet concentrate preparations leave behind certain number of residual leukocytes, accounting for most of the febrile nonhemolytic transfusion reactions, especially in multitransfused patients. Various inflammatory cytokines, such as tumor necrosis factor-α (TNF-α, interleukin-1β (IL-1β, and IL-6 are generated during storage and have been implicated for these adverse effects. We have studied the levels of these cytokines and their correlation with leucocyte contents in platelet concentrates prepared by three different methods. Study Design and Methods: Five pools of platelet rich plasma platelet concentrates (PRP-PC and buffy-coat platelet concentrates (BC-PC each were prepared and divided into two halves. One half of the pool was leucofiltered (LF, whereas the other half was stored as such. Ten apheresis units were also included in the study. All the platelet concentrates were assessed for leucocyte load and cytokine content (IL-1β, IL-6, and TNF-α on different days of storage (0, 3, and 5 using Nageotte chamber and commercially available immunoassays respectively. Results: There was a statistically significant rise in cytokine levels (IL-1β, IL-6, and TNF-α in nonleucofiltered (NLF random donor platelet concentrates (RDPs (PRP-PC and BC-PC during storage (day 3 and 5 whereas LF RDP concentrates (PRP-PC and BC-PC and apheresis platelet concentrates (AP-PC did not show any significant rise in cytokine levels (on day 3 and 5 over the baseline values at day 0. Conclusion: This data suggests that although AP-PCs are superior to PRP-PC (NLF and BC-PC (NLF in terms of in vitro quality control parameters and cytokine generation during storage, BC-PC mode of platelet preparation followed by leucofiltration is the best method to store platelets and minimise the cytokine accumulation. This strategy is best suited for transfusion in multitransfused hematooncologic patients, who cannot afford

  9. Proinflammatory Cytokine IL-6 and JAK-STAT Signaling Pathway in Myeloproliferative Neoplasms

    Directory of Open Access Journals (Sweden)

    Vladan P. Čokić

    2015-01-01

    Full Text Available The recent JAK1/2 inhibitor trial in myeloproliferative neoplasms (MPNs showed that reducing inflammation can be more beneficial than targeting gene mutants. We evaluated the proinflammatory IL-6 cytokine and JAK-STAT signaling pathway related genes in circulating CD34+ cells of MPNs. Regarding laboratory data, leukocytosis has been observed in polycythemia vera (PV and JAK2V617F mutation positive versus negative primary myelofibrosis (PMF patients. Moreover, thrombocytosis was reduced by JAK2V617F allele burden in essential thrombocythemia (ET and PMF. 261 significantly changed genes have been detected in PV, 82 in ET, and 94 genes in PMF. The following JAK-STAT signaling pathway related genes had augmented expression in CD34+ cells of MPNs: CCND3 and IL23A regardless of JAK2V617F allele burden; CSF3R, IL6ST, and STAT1/2 in ET and PV with JAK2V617F mutation; and AKT2, IFNGR2, PIM1, PTPN11, and STAT3 only in PV. STAT5A gene expression was generally reduced in MPNs. IL-6 cytokine levels were increased in plasma, as well as IL-6 protein levels in bone marrow stroma of MPNs, dependent on JAK2V617F mutation presence in ET and PMF patients. Therefore, the JAK2V617F mutant allele burden participated in inflammation biomarkers induction and related signaling pathways activation in MPNs.

  10. CYTOKINES GENETIC POLYMORPHISM: THE PAST AND THE FUTURE

    Directory of Open Access Journals (Sweden)

    L. V. Puzyryova

    2016-01-01

    Full Text Available The molecular genetics opens the new horizons in modern medicine, especially now when many diseases are given huge value in a type of their prevalence among various groups of population. Extremely high interleukin genes polymorphism degrees are studied well especially genetic polymorphism of tumor necrosis factor. Patients with HIV infection in the territory of Russia cause now the highest degree of mortality that is the most actual and socially significant problem of healthcare. This problems studying attracts many researchers. Works in respect of genetic immunity to a virus and influence of cytokines production on the disease forecast are especially interesting. One of the HIV replication influencing factors are cytokines, some of which, including the tumor necrosis factor and interleukin-6 can promote replication of HIV, raising an expression of virus regulatory genes. During disease progress in parallel of anti-inflammatory cytokines level increase (causing in this case rather ineffective antibodies level increase there is an T-helpers suppression stimulating a strong cellular component. Cytokine network functioning during HIV infection depends on many reasons which the individual variation in cytokine production caused by a number of genetic features, as well as an existence of opportunistic infection. Cytokines polymorphism determination in HIV infected patients is necessary in clinical practice for disease progression forecast to adverse fast transition to AIDS that it is important to consider in a choice of tactics of the supporting therapy of HIV-positive patients. Considering insufficient efficiency of modern methods of treatment, restoration and modulation of cytokines balance will increase anti-virus activity of immune system, influencing the factors blocking replication of a HIV.

  11. Norovirus in symptomatic and asymptomatic individuals: cytokines and viral shedding.

    Science.gov (United States)

    Newman, K L; Moe, C L; Kirby, A E; Flanders, W D; Parkos, C A; Leon, J S

    2016-06-01

    Noroviruses (NoV) are the most common cause of epidemic gastroenteritis world-wide. NoV infections are often asymptomatic, although individuals still shed large amounts of NoV in their stool. Understanding the differences between asymptomatic and symptomatic individuals would help in elucidating mechanisms of NoV pathogenesis. Our goal was to compare the serum cytokine responses and faecal viral RNA titres of asymptomatic and symptomatic NoV-infected individuals. We tested serum samples from infected subjects (n = 26; 19 symptomatic, seven asymptomatic) from two human challenge studies of GI.1 NoV for 16 cytokines. Samples from prechallenge and days 1-4 post-challenge were tested for these cytokines. Cytokine levels were compared to stool NoV RNA titres quantified previously by reverse transcription-polymerase chain reaction (RT-qPCR). While both symptomatic and asymptomatic groups had similar patterns of cytokine responses, the symptomatic group generally exhibited a greater elevation of T helper type 1 (Th1) and Th2 cytokines and IL-8 post-challenge compared to the asymptomatic group (all P viral RNA titre was associated positively with daily IL-6 concentration and negatively with daily IL-12p40 concentration (all P viral RNA titre, duration of viral shedding or cumulative shedding. Symptomatic individuals, compared to asymptomatic, have greater immune system activation, as measured by serum cytokines, but they do not have greater viral burden, as measured by titre and shedding, suggesting that symptoms may be immune-mediated in NoV infection. PMID:26822517

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

    Science.gov (United States)

    Martínez-Varea, Alicia; Pellicer, Begoña; Serra, Vicente; Hervás-Marín, David; Martínez-Romero, Alicia; Bellver, José; Perales-Marín, Alfredo; Pellicer, Antonio

    2015-01-01

    This prospective longitudinal study aimed at comparing maternal immune response among naturally conceived (NC; n = 25), in vitro fertilization (IVF; n = 25), and egg donation (ED; n = 25) pregnancies. The main outcome measures were, firstly, to follow up plasma levels of interleukin (IL) 1 beta, IL2, IL4, IL5, IL6, IL8, IL10, IL17, interferon gamma, tumor necrosis factor-alpha (TNFα), transforming growth factor-beta (TGFβ), regulated upon activation normal T-cell expressed and secreted (RANTES), stromal cell-derived factor 1 alpha (SDF1α), and decidual granulocyte-macrophage colony-stimulating factor (GM-CSF) during the three trimesters of pregnancy during the three trimesters of pregnancy; secondly, to evaluate if the cytokine and chemokine pattern of ED pregnant women differs from that of those with autologous oocytes and, thirdly, to assess if women with preeclampsia show different cytokine and chemokine profile throughout pregnancy versus women with uneventful pregnancies. Pregnant women in the three study groups displayed similar cytokine and chemokine pattern throughout pregnancy. The levels of all quantified cytokines and chemokines, except RANTES, TNFα, IL8, TGFβ, and SDF1α, rose in the second trimester compared with the first, and these higher values remained in the third trimester. ED pregnancies showed lower SDF1α levels in the third trimester compared with NC and IVF pregnancies. Patients who developed preeclampsia displayed higher SDF1α plasma levels in the third trimester. PMID:26346343

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

    Directory of Open Access Journals (Sweden)

    Alicia Martínez-Varea

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Charles E Bane

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

  15. Acute and chronic cytokine responses to resistance exercise and training in people with multiple sclerosis

    DEFF Research Database (Denmark)

    Kjølhede, Tue; Dalgas, Ulrik; Brolin Gade, Anne;

    2015-01-01

    necrosis factor-α and IFN-γ were measured before and after 24 weeks of PRT. The acute effect was evaluated following standardized single-bout resistance exercise in the untrained and the trained state. No changes were observed in resting cytokine levels after PRT. However, an indication of reduced IL-17F......Exercise is a well-established part of rehabilitation for people with multiple sclerosis (PwMS), and it has been hypothesized to stimulate an anti-inflammatory environment that might be disease modifying. Yet, investigations on exercise-induced immune responses are scarce and generally not paying...... responses to resistance exercise training in medicated PwMS. Thirty-five people with relapsing-remitting multiple sclerosis (MS) treated with interferon (IFN)-β, were randomized to a 24-week progressive resistance training (PRT) or control group. Plasma interleukin (IL)-1β, IL-4, IL-10, IL-17F, IL-23, tumor...

  16. Kinetics of pro-inflammatory cytokines, interleukin-10, and virus neutralising antibodies during acute ephemeral fever virus infections in Brahman cattle.

    Science.gov (United States)

    Barigye, R; Melville, L F; Davis, S; Walsh, S; Hunt, N; Hunt, R; Elliot, N

    2015-12-15

    While fever and inflammation are hallmark features of bovine ephemeral fever (BEF), the cytokine networks that underlie the acute phase of the disease have not been empirically defined in cattle. This study characterised the plasma kinetics of proinflammatory cytokines (IL-1β, IL-6, TNF-α) and IL-10 during acute BEF and elucidated on the relationship between the onset of the virus neutralizing antibody response and resolution of viraemia in natural BEF virus (BEFV) infections in cattle. Plasma from three BEFV-infected and three uninfected cattle was tested for the study cytokines by a cELISA, viraemia monitored by qRT-PCR, and virus neutralizing antibody titres determined using a standard protocol. Unlike the negative controls, plasma concentrations of IL-1β, TNF-α, IL-6, and IL-10 were consistently increased in the three virus-infected animals. Two of the infected heifers were recumbent and pyrexic on the first day of monitoring and increased cytokine production was already in progress by the time viraemia was detected in all the three infected animals. In all the virus-infected heifers, IL-1β was the most strongly expressed cytokine, IL-6 and IL-10 manifested intermediate plasma concentrations while TNF-α was the least expressed and demonstrated bi-phasic peaks three and five days after the onset of pyrexia. In two of the BEFV-infected heifers, viraemia resolved on the day of seroconversion while in the other infected animal, viral RNA was detectable up to three days after seroconversion. The present data document variable increase in plasma IL-1β, IL-6, TNF-α, and IL-10 during natural BEFV infections and the fact that upregulation of all but TNF-α precedes seroconversion. In addition to virus neutralising antibodies, it is likely that cytokine-mediated cellular mechanisms may be required for resolution of viraemia in BEF. Considering the anti-inflammatory properties of IL-10, its upregulation may potentially antagonise the fever response in BEFV

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-12-01

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

  18. Mechanism of inflammatory cytokines in osteoarthritis pain%炎症细胞因子在骨性关节炎疼痛中的作用机制

    Institute of Scientific and Technical Information of China (English)

    姚志华; 裘敏蕾; 樊天佑

    2014-01-01

    In order to provide theoretical basis for the clinical treatment of osteoarthritis, the mechanism of inflammatory cytokines in osteoarthritis pain was investigated. A computer-based search of PubMed and China National Knowledge Infrastructure ( CNKI ) database was performed for the related articles with the keywords of“inflammatory cytokines, interleukin, tumor necrosis factor, chemokines, osteoarthritis pain, neuropathic pain and biochemical mechanisms”in English or in Chinese. The literatures related to the mechanism of inlfammatory cytokines in osteoarthritis pain were selected. A total of 84 literatures were primarily selected and 42 articles were reviewed according to the inclusion criteria. Osteoarthritis pain is one of the main factors affecting the life quality of the patients, and a variety of abnormal cells of the peripheral and central nervous systems were involved. Inlfammatory cytokines played an important role in the pathogenesis of osteoarthritis. The relationship between osteoarthritis pain and common inlfammatory cytokines were reviewed in the review, so as to explore the important role of inlfammatory cytokines in osteoarthritis pain and provide theoretical basis for the clinical treatment of osteoarthritis.

  19. Association of cytokine gene polymorphisms in CWP and its severity in Turkish coal workers

    Energy Technology Data Exchange (ETDEWEB)

    Ates, I.; Suzen, H.S.; Yucesoy, B.; Tekin, I.O.; Karakaya, A. [Ankara University, Ankara (Turkey)

    2008-10-15

    Cytokines appear to play a key role in some inflammatory reactions affecting the interactions among pro- and anti-inflammatory mechanisms that result in several diseases such as coal workers' pneumoconiosis (CWP). In this study, to determine the cytokine gene profiles of Turkish coal miners, we performed genotyping analysis to investigate the polymorphisms of CWP-related pro-inflammatory (TNFA, IL1A, IL1B, and IL6) and anti-inflammatory cytokines (IL-1RN and TGFB1). Genotyping was carried out by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. TNFA (-238) gene polymorphism principally affected CWP development and severity (OR=3.47: 95% CI, 1.12-10.77 and OR=4.30: 95% CI, 1.25-14.74, respectively) and also risk of CWP (OR=3.79: 95% CI, 1.37-10.46). The TNFA (-308) variant was associated with a risk for the CWP severity (OR = 2.84: 95% CI, 1.08-7.39). A protective effect of IL6 was found on the development (OR = 0.48: 95% CI, 0.21-0.93) and severity of CWP (OR = 0.37: 95% CI, 0.15-0.91). We suggest that TNFA (-238) variant may be a risk factor in both development and the severity, of CWP while TNFA (-308) variant seems to be important only in disease severity On the other hand, IL6 variant may have a protective effect on the development and disease severity.

  20. Systemic cytokine and interferon responsiveness Patterns in HIV and HCV mono and co-infections.

    Science.gov (United States)

    Fernandez-Botran, Rafael; Joshi-Barve, Swati; Ghare, Smita; Barve, Shirish; Young, Mary; Plankey, Michael; Bordon, Jose

    2014-11-01

    The role of host response-related factors in the fast progression of liver disease in individuals co-infected with HIV and HCV viruses remains poorly understood. This study compared patterns of cytokines, caspase-1 activation, endotoxin exposure in plasma as well as interferon signaling in peripheral blood mononuclear cells from HIV/HCV co-infected (HIV(+)/HCV(+)), HCV mono-infected (HIV(-)/HCV(+)), HIV mono-infected (HIV(+)/HCV(-)) female patients and HIV- and HCV-uninfected women (HIV(-)/HCV(-)) who had enrolled in the Women's Interagency HIV Study (WIHS). HIV(+)/HCV(+) women had higher plasma levels of pro-inflammatory cytokines as well as caspase-1 compared with other groups. Both HIV(+)/HCV(+) and HIV(+)/HCV(-) women had significantly higher sCD14 levels compared with other groups. Peripheral blood mononuclear cells from HCV mono-infected patients had reduced levels of phosphorylation of STAT1 compared with other groups as well as lower basal levels of expression of the IFN-stimulated genes, OAS1, ISG15, and USP18 (UBP43). Basal expression of USP18, a functional antagonist of ISG15, as well as USP18/ISG15 ratios were increased in the HIV(+)/HCV(+) group compared with HIV(-)/HCV(+) and HIV(+)/HCV(-) groups. A more pronounced systemic inflammatory profile as well as increased expression ratios of USP18 to ISG15 may contribute to the more rapid progression of liver disease in HIV(+)/HCV(+) individuals. PMID:24955730