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Sample records for significantly reduced cytokine

  1. Sucralfate significantly reduces ciprofloxacin concentrations in serum.

    OpenAIRE

    Garrelts, J C; Godley, P J; Peterie, J D; Gerlach, E H; Yakshe, C C

    1990-01-01

    The effect of sucralfate on the bioavailability of ciprofloxacin was evaluated in eight healthy subjects utilizing a randomized, crossover design. The area under the concentration-time curve from 0 to 12 h was reduced from 8.8 to 1.1 micrograms.h/ml by sucralfate (P less than 0.005). Similarly, the maximum concentration of ciprofloxacin in serum was reduced from 2.0 to 0.2 micrograms/ml (P less than 0.005). We conclude that concurrent ingestion of sucralfate significantly reduces the concentr...

  2. CLINICAL SIGNIFICANCE OF CYTOKINES SERUM LEVELS IN CHILDREN WITH CHICKEN POX

    Directory of Open Access Journals (Sweden)

    G. F. Zheleznikova

    2015-01-01

    Full Text Available The serum levels of cytokines IL-1β, IL-8, IL-6, IFNα, IFNγ, IL-4, IL-10 were tested in ELISA in 74 children with different courses of chicken pox. Moderate severity course of chicken pox was accompanied by significant increase of IL-1β, IL-8, IFNα, IFNγ, IL-10 levels, but severe course of infection was associated with cytokine response reduction. Manifestation of varicella-zoster virus encephalitis was accompanied by the rise of IL-1β, IL-6, IFNγ and IL-10 levels during the second week of disease. 

  3. Metoprolol Reduces Proinflammatory Cytokines and Atherosclerosis in ApoE−/− Mice

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    Marcus A. Ulleryd

    2014-01-01

    Full Text Available A few studies in animals and humans suggest that metoprolol (β1-selective adrenoceptor antagonist may have a direct antiatherosclerotic effect. However, the mechanism behind this protective effect has not been established. The aim of the present study was to evaluate the effect of metoprolol on development of atherosclerosis in ApoE−/− mice and investigate its effect on the release of proinflammatory cytokines. Male ApoE−/− mice were treated with metoprolol (2.5 mg/kg/h or saline for 11 weeks via osmotic minipumps. Atherosclerosis was assessed in thoracic aorta and aortic root. Total cholesterol levels and Th1/Th2 cytokines were analyzed in serum and macrophage content in lesions by immunohistochemistry. Metoprolol significantly reduced atherosclerotic plaque area in thoracic aorta (P<0.05 versus Control. Further, metoprolol reduced serum TNFα and the chemokine CXCL1 (P<0.01 versus Control for both as well as decreasing the macrophage content in the plaques (P<0.01 versus Control. Total cholesterol levels were not affected. In this study we found that a moderate dose of metoprolol significantly reduced atherosclerotic plaque area in thoracic aorta of ApoE−/− mice. Metoprolol also decreased serum levels of proinflammatory cytokines TNFα and CXCL1 and macrophage content in the plaques, showing that metoprolol has an anti-inflammatory effect.

  4. Metallothionein treatment reduces proinflammatory cytokines IL-6 and TNF-alpha and apoptotic cell death during experimental autoimmune encephalomyelitis (EAE)

    DEFF Research Database (Denmark)

    Penkowa, M; Hidalgo, J

    2001-01-01

    cytokines and apoptosis during EAE could contribute to the reported diminution of clinical symptoms and mortality in EAE-immunized rats receiving Zn-MT-II treatment. Our results demonstrate that MT-II reduces the CNS expression of proinflammatory cytokines and the number of apoptotic neurons during EAE......, which is characterized by significant inflammation and neuroglial damage. We have recently shown that the exogenous administration of the antioxidant protein zinc-metallothionein-II (Zn-MT-II) significantly decreased the clinical symptoms, mortality, and leukocyte infiltration of the CNS during EAE....... However, it is not known how EAE progression is regulated nor how cytokine production and cell death can be reduced. We herewith demonstrate that treatment with Zn-MT-II significantly decreased the CNS expression of IL-6 and TNF-alpha during EAE. Zn-MT-II treatment could also significantly reduce...

  5. Protective effects of myricitrin against osteoporosis via reducing reactive oxygen species and bone-resorbing cytokines

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Qiang; Gao, Bo; Wang, Long; Hu, Ya-Qian; Lu, Wei-Guang; Yang, Liu; Luo, Zhuo-Jing; Liu, Jian, E-mail: liujianhq@sina.com

    2014-11-01

    Oxidative stress is a crucial pathogenic factor in the development of osteoporosis. Myricitrin, isolated from Myrica cerifera, is a potent antioxidant. We hypothesized that myricitrin possessed protective effects against osteoporosis by partially reducing reactive oxygen species (ROS) and bone-resorbing cytokines in osteoblastic MC3T3-E1 cells and human bone marrow stromal cells (hBMSCs). We investigated myricitrin on osteogenic differentiation under oxidative stress. Hydrogen peroxide (H{sub 2}O{sub 2}) was used to establish an oxidative cell injury model. Our results revealed that myricitrin significantly improved some osteogenic markers in these cells. Myricitrin decreased lipid production and reduced peroxisome proliferator-activated receptor gamma-2 (PPARγ2) expression in hBMSCs. Moreover, myricitrin reduced the expression of receptor activator of nuclear factor kappa-B ligand (RANKL) and IL-6 and partially suppressed ROS production. In vivo, we established a murine ovariectomized (OVX) osteoporosis model. Our results demonstrated that myricitrin supplementation reduced serum malondialdehyde (MDA) activity and increased reduced glutathione (GSH) activity. Importantly, it ameliorated the micro-architecture of trabecular bones in the 4th lumbar vertebrae (L4) and distal femur. Taken together, these results indicated that the protective effects of myricitrin against osteoporosis are linked to a reduction in ROS and bone-resorbing cytokines, suggesting that myricitrin may be useful in bone metabolism diseases, particularly osteoporosis. - Highlights: • Myricitrin protects MC3T3-E1 cells and hBMSCs from oxidative stress. • It is accompanied by a decrease in oxidative stress and bone-resorbing cytokines. • Myricitrin decreases serum reactive oxygen species to some degree. • Myricitrin partly reverses ovariectomy effects in vivo. • Myricitrin may represent a beneficial anti-osteoporosis treatment method.

  6. Potent neutralizing anti-CD1d antibody reduces lung cytokine release in primate asthma model.

    Science.gov (United States)

    Nambiar, Jonathan; Clarke, Adam W; Shim, Doris; Mabon, David; Tian, Chen; Windloch, Karolina; Buhmann, Chris; Corazon, Beau; Lindgren, Matilda; Pollard, Matthew; Domagala, Teresa; Poulton, Lynn; Doyle, Anthony G

    2015-01-01

    CD1d is a receptor on antigen-presenting cells involved in triggering cell populations, particularly natural killer T (NKT) cells, to release high levels of cytokines. NKT cells are implicated in asthma pathology and blockade of the CD1d/NKT cell pathway may have therapeutic potential. We developed a potent anti-human CD1d antibody (NIB.2) that possesses high affinity for human and cynomolgus macaque CD1d (KD ∼100 pM) and strong neutralizing activity in human primary cell-based assays (IC50 typically <100 pM). By epitope mapping experiments, we showed that NIB.2 binds to CD1d in close proximity to the interface of CD1d and the Type 1 NKT cell receptor β-chain. Together with data showing that NIB.2 inhibited stimulation via CD1d loaded with different glycolipids, this supports a mechanism whereby NIB.2 inhibits NKT cell activation by inhibiting Type 1 NKT cell receptor β-chain interactions with CD1d, independent of the lipid antigen in the CD1d antigen-binding cleft. The strong in vitro potency of NIB.2 was reflected in vivo in an Ascaris suum cynomolgus macaque asthma model. Compared with vehicle control, NIB.2 treatment significantly reduced bronchoalveolar lavage (BAL) levels of Ascaris-induced cytokines IL-5, IL-8 and IL-1 receptor antagonist, and significantly reduced baseline levels of GM-CSF, IL-6, IL-15, IL-12/23p40, MIP-1α, MIP-1β, and VEGF. At a cellular population level NIB.2 also reduced numbers of BAL lymphocytes and macrophages, and blood eosinophils and basophils. We demonstrate that anti-CD1d antibody blockade of the CD1d/NKT pathway modulates inflammatory parameters in vivo in a primate inflammation model, with therapeutic potential for diseases where the local cytokine milieu is critical.

  7. Edaravone protects endotoxin-induced liver injury by inhibiting apoptosis and reducing proinflammatory cytokines.

    Science.gov (United States)

    Zong, L; Yu, Q H; Du, Y X; Deng, X M

    2014-02-01

    Studies have shown that edaravone may prevent liver injury. This study aimed to investigate the effects of edaravone on the liver injury induced by D-galactosamine (GalN) and lipopolysaccharide (LPS) in female BALB/c mice. Edaravone was injected into mice 30 min before and 4 h after GalN/LPS injection. The survival rate was determined within the first 24 h. Animals were killed 8 h after GalN/LPS injection, and liver injury was biochemically and histologically assessed. Hepatocyte apoptosis was measured by TUNEL staining; proinflammatory cytokines [tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6)] in the liver were assayed by ELISA; expression of caspase-8 and caspase-3 proteins was detected by Western blot assay; and caspase-3 activity was also determined. Results showed that GalN/LPS induced marked elevations in serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Edaravone significantly inhibited elevation of serum AST and ALT, accompanied by an improvement in histological findings. Edaravone lowered the levels of TNF-α and IL-6 and reduced the number of TUNEL-positive cells. In addition, 24 h after edaravone treatment, caspase-3 activity and mortality were reduced. Edaravone may effectively ameliorate GalN/LPS-induced liver injury in mice by reducing proinflammatory cytokines and inhibiting apoptosis.

  8. Edaravone protects endotoxin-induced liver injury by inhibiting apoptosis and reducing proinflammatory cytokines

    Energy Technology Data Exchange (ETDEWEB)

    Zong, L. [Second Military Medical University, Changhai Hospital, Department of Anesthesiology, Shanghai, China, Department of Anesthesiology, Changhai Hospital, Second Military Medical University, Shanghai (China); No. 82 Hospital of People' s Liberation Army, Department of Anesthesiology, Jiangsu, China, Department of Anesthesiology, No. 82 Hospital of People' s Liberation Army, Jiangsu (China); Yu, Q. H. [Second Military Medical University, Changhai Hospital, Department of Gastroenterology, Shanghai, China, Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai (China); Du, Y. X. [No. 82 Hospital of People' s Liberation Army, Department of Anesthesiology, Jiangsu, China, Department of Anesthesiology, No. 82 Hospital of People' s Liberation Army, Jiangsu (China); Deng, X. M. [Second Military Medical University, Changhai Hospital, Department of Anesthesiology, Shanghai, China, Department of Anesthesiology, Changhai Hospital, Second Military Medical University, Shanghai (China)

    2014-03-03

    Studies have shown that edaravone may prevent liver injury. This study aimed to investigate the effects of edaravone on the liver injury induced by D-galactosamine (GalN) and lipopolysaccharide (LPS) in female BALB/c mice. Edaravone was injected into mice 30 min before and 4 h after GalN/LPS injection. The survival rate was determined within the first 24 h. Animals were killed 8 h after GalN/LPS injection, and liver injury was biochemically and histologically assessed. Hepatocyte apoptosis was measured by TUNEL staining; proinflammatory cytokines [tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6)] in the liver were assayed by ELISA; expression of caspase-8 and caspase-3 proteins was detected by Western blot assay; and caspase-3 activity was also determined. Results showed that GalN/LPS induced marked elevations in serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Edaravone significantly inhibited elevation of serum AST and ALT, accompanied by an improvement in histological findings. Edaravone lowered the levels of TNF-α and IL-6 and reduced the number of TUNEL-positive cells. In addition, 24 h after edaravone treatment, caspase-3 activity and mortality were reduced. Edaravone may effectively ameliorate GalN/LPS-induced liver injury in mice by reducing proinflammatory cytokines and inhibiting apoptosis.

  9. Edaravone protects endotoxin-induced liver injury by inhibiting apoptosis and reducing proinflammatory cytokines

    Directory of Open Access Journals (Sweden)

    L. Zong

    2014-03-01

    Full Text Available Studies have shown that edaravone may prevent liver injury. This study aimed to investigate the effects of edaravone on the liver injury induced by D-galactosamine (GalN and lipopolysaccharide (LPS in female BALB/c mice. Edaravone was injected into mice 30 min before and 4 h after GalN/LPS injection. The survival rate was determined within the first 24 h. Animals were killed 8 h after GalN/LPS injection, and liver injury was biochemically and histologically assessed. Hepatocyte apoptosis was measured by TUNEL staining; proinflammatory cytokines [tumor necrosis factor-α (TNF-α and interleukin-6 (IL-6] in the liver were assayed by ELISA; expression of caspase-8 and caspase-3 proteins was detected by Western blot assay; and caspase-3 activity was also determined. Results showed that GalN/LPS induced marked elevations in serum aspartate aminotransferase (AST and alanine aminotransferase (ALT. Edaravone significantly inhibited elevation of serum AST and ALT, accompanied by an improvement in histological findings. Edaravone lowered the levels of TNF-α and IL-6 and reduced the number of TUNEL-positive cells. In addition, 24 h after edaravone treatment, caspase-3 activity and mortality were reduced. Edaravone may effectively ameliorate GalN/LPS-induced liver injury in mice by reducing proinflammatory cytokines and inhibiting apoptosis.

  10. Edaravone protects endotoxin-induced liver injury by inhibiting apoptosis and reducing proinflammatory cytokines

    International Nuclear Information System (INIS)

    Zong, L.; Yu, Q.H.; Du, Y.X.; Deng, X.M.

    2014-01-01

    Studies have shown that edaravone may prevent liver injury. This study aimed to investigate the effects of edaravone on the liver injury induced by D-galactosamine (GalN) and lipopolysaccharide (LPS) in female BALB/c mice. Edaravone was injected into mice 30 min before and 4 h after GalN/LPS injection. The survival rate was determined within the first 24 h. Animals were killed 8 h after GalN/LPS injection, and liver injury was biochemically and histologically assessed. Hepatocyte apoptosis was measured by TUNEL staining; proinflammatory cytokines [tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6)] in the liver were assayed by ELISA; expression of caspase-8 and caspase-3 proteins was detected by Western blot assay; and caspase-3 activity was also determined. Results showed that GalN/LPS induced marked elevations in serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Edaravone significantly inhibited elevation of serum AST and ALT, accompanied by an improvement in histological findings. Edaravone lowered the levels of TNF-α and IL-6 and reduced the number of TUNEL-positive cells. In addition, 24 h after edaravone treatment, caspase-3 activity and mortality were reduced. Edaravone may effectively ameliorate GalN/LPS-induced liver injury in mice by reducing proinflammatory cytokines and inhibiting apoptosis

  11. Quilting after mastectomy significantly reduces seroma formation

    African Journals Online (AJOL)

    reduce or prevent seroma formation among mastectomy patients ... of this prospective study is to evaluate the effect of surgical quilting ... Seroma was more common in smokers (p=0.003) and was not decreased by the .... explain its aetiology.

  12. Hypothermia Modulates Cytokine Responses After Neonatal Rat Hypoxic-Ischemic Injury and Reduces Brain Damage

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    Xiangpeng Yuan

    2014-11-01

    Full Text Available While hypothermia (HT is the standard-of-care for neonates with hypoxic ischemic injury (HII, the mechanisms underlying its neuroprotective effect are poorly understood. We examined ischemic core/penumbra and cytokine/chemokine evolution in a 10-day-old rat pup model of HII. Pups were treated for 24 hr after HII with HT (32℃; n = 18 or normothermia (NT, 35℃; n = 15. Outcomes included magnetic resonance imaging (MRI, neurobehavioral testing, and brain cytokine/chemokine profiling (0, 24, 48, and 72 hr post-HII. Lesion volumes (24 hr were reduced in HT pups (total 74%, p < .05; penumbra 68%, p < .05; core 85%, p = .19. Lesion volumes rebounded at 72 hr (48 hr post-HT with no significant differences between NT and HT pups. HT reduced interleukin-1β (IL-1β at all time points (p < .05; monocyte chemoattractant protein-1 (MCP-1 trended toward being decreased in HT pups (p = .09. The stem cell signaling molecule, stromal cell-derived factor-1 (SDF-1 was not altered by HT. Our data demonstrate that HT reduces total and penumbral lesion volumes (at 24 and 48 hr, potentially by decreasing IL-1β without affecting SDF-1. Disassociation between the increasing trend in HII volumes from 48 to 72 hr post-HII when IL-1β levels remained low suggests that after rewarming, mechanisms unrelated to IL-1β expression are likely to contribute to this delayed increase in injury. Additional studies should be considered to determine what these mechanisms might be and also to explore whether extending the duration or degree of HT might ameliorate this delayed increase in injury.

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

    International Nuclear Information System (INIS)

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

    2004-01-01

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

  14. Better cognitive control of emotional information is associated with reduced pro-inflammatory cytokine reactivity to emotional stress.

    Science.gov (United States)

    Shields, Grant S; Kuchenbecker, Shari Young; Pressman, Sarah D; Sumida, Ken D; Slavich, George M

    2016-01-01

    Stress is strongly associated with several mental and physical health problems that involve inflammation, including asthma, cardiovascular disease, certain types of cancer, and depression. It has been hypothesized that better cognitive control of emotional information may lead to reduced inflammatory reactivity to stress and thus better health, but to date no studies have examined whether differences in cognitive control predict pro-inflammatory cytokine responses to stress. To address this issue, we conducted a laboratory-based experimental study in which we randomly assigned healthy young-adult females to either an acute emotional stress (emotionally evocative video) or no-stress (control video) condition. Salivary levels of the key pro-inflammatory cytokines IL-1β, IL-6, and IL-8 were measured before and after the experimental manipulation, and following the last cytokine sample, we assessed participants' cognitive control of emotional information using an emotional Stroop task. We also assessed participants' cortisol levels before and after the manipulation to verify that documented effects were specific to cytokines and not simply due to increased nonwater salivary output. As hypothesized, the emotional stressor triggered significant increases in IL-1β, IL-6, and IL-8. Moreover, even in fully adjusted models, better cognitive control following the emotional (but not control) video predicted less pronounced cytokine responses to that stressor. In contrast, no effects were observed for cortisol. These data thus indicate that better cognitive control specifically following an emotional stressor is uniquely associated with less pronounced pro-inflammatory cytokine reactivity to such stress. These findings may therefore help explain why superior cognitive control portends better health over the lifespan.

  15. Th1-, Th2-, and Th17-associated cytokine expression in hypopharyngeal carcinoma and clinical significance.

    Science.gov (United States)

    Chen, Xuemei; Wang, Junfu; Wang, Rui; Su, Qinghong; Luan, Junwen; Huang, Haiyan; Zhou, Peng; Liu, Jinsheng; Xu, Xiaoqun

    2016-02-01

    Th0 cells differentiate into Th1 or Th2 depending on multiple transcription factors acting on specific time points to regulate gene expression. Th17 cells, a subset of IL-17-producing T cells distinct from Th1 or Th2 cells, have been described as key players in inflammation and autoimmune diseases as well as cancer development. In the present study, 53 patients with hypopharyngeal cancer were included. The expression levels of Th1-, Th2- and Th17-associated cytokines in hypopharyngeal cancer tissues and pericarcinoma tissues were detected. The relationship between Th1, Th2, or Th17 infiltration and metastasis was studied. Our results showed that the mRNA and protein expressions of Th1 cytokines were lower, while the expressions of Th2 and Th17 cytokines were higher in tumor tissues, and the intensity of expression was strengthened with clinical stage increasing. Cancer tissues had higher level expressions of Th2 and Th17 cytokines than that of pericarcinoma tissues. From the above data, we speculated that high expressions of Th2- and Th17-associated cytokines in hypopharyngeal carcinoma may contribute to cancer development and metastasis.

  16. Anticancer Drug 2-Methoxyestradiol Protects against Renal Ischemia/Reperfusion Injury by Reducing Inflammatory Cytokines Expression

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    Ying-Yin Chen

    2014-01-01

    Full Text Available Background. Ischemia/reperfusion (I/R injury is a major cause of acute renal failure and allograft dysfunction in kidney transplantation. ROS/inflammatory cytokines are involved in I/R injury. 2-Methoxyestradiol (2ME2, an endogenous metabolite of estradiol, inhibits inflammatory cytokine expression and is an antiangiogenic and antitumor agent. We investigated the inhibitory effect of 2ME2 on renal I/R injury and possible molecular actions. Methods. BALB/c mice were intraperitoneally injected with 2ME2 (10 or 20 mg/kg or vehicle 12 h before and immediately after renal I/R experiments. The kidney weight, renal function, tubular damages, and apoptotic response were examined 24 h after I/R injury. The expression of mRNA of interleukin-1β, tumor necrosis factor- (TNF α, caspase-3, hypoxia inducible factor- (HIF 1α, and proapoptotic Bcl-2/adenovirus E1B 19 kDa interacting protein 3 (BNIP3 in kidney tissue was determined using RT-PCR, while the expression of nuclear factor κB (NF-κB, BCL-2, and BCL-xL, activated caspase-9, and HIF-1α was determined using immunoblotting. In vitro, we determined the effect of 2ME2 on reactive oxygen species (ROS production and cell viability in antimycin-A-treated renal mesangial (RMC and tubular (NRK52E cells. Results. Serum creatinine and blood urea nitrogen were significantly higher in mice with renal I/R injury than in sham control and in I/R+2ME2-treated mice. Survival in I/R+2ME2-treated mice was higher than in I/R mice. Histological examination showed that 2ME2 attenuated tubular damage in I/R mice, which was associated with lower expression TNF-α, IL-1β, caspase-9, HIF-1α, and BNIP3 mRNA in kidney tissue. Western blotting showed that 2ME2 treatment substantially decreased the expression of activated caspase-9, NF-κB, and HIF-1α but increased the antiapoptotic proteins BCL-2 and BCL-xL in kidney of I/R injury. In vitro, 2MR2 decreased ROS production and increased cell viability in antimycin

  17. [Pulsatilla decoction inhibits vulvovaginal Candida albicans proliferation and reduces inflammatory cytokine levels in vulvovaginal candidiasis mice].

    Science.gov (United States)

    Xia, Dan; Zhang, Mengxiang; Shi, Gaoxiang; Xu, Zhiqing; Wu, Daqiang; Shao, Jing; Wang, Tianming; Wang, Changzhong

    2016-02-01

    To explore the possible regulatory effect of Pulsatilla decoction on Th17 cells and inflammatory cytokines of vulvovaginal candidiasis (VVC) mice. Seventy-two female Kunming mice were randomly assigned into six groups: a blank control group, a VVC model group, a fluconazole group and three Pulsatilla decoction groups (dose levels: 22.5, 15.0 and 7.5 g/kg, respectively). The VVC mouse models were established by vaginal inoculation with Candida albicans (C. albicans) in female mice in pseudoestrus state caused by estradiol injection. After 7-day treatment on VVC mice, the vaginal C. albicans burden was assessed using dilution spread plate method; the vaginal C. albicans morphology was observed by Gram staining method; the levels of interleukin 6 (IL-6), IL-17, IL-21 and tumor necrosis factor α (TNF-α) in sera were detected by ELISA. The content of the transcription factor retinoid related orphan receptor gamma t (RORγt) in vaginal tissues was detected by immunohistochemistry. The VVC mouse models were successfully developed. After treatment, the vaginal C. albicans burden of the fluconazole group and 22.5 g/kg Pulsatilla decoction group dropped significantly compared with that of the VVC model group. Gram staining showed that the VVC mice had lots of C. albicans hyphae in vaginal discharge, that 7.5 g/kg Pulsatilla decoction group remained the mycelia-phase C. albicans, and that 15.0 g/kg Pulsatilla decoction group had the majority of yeast-phase C. albicans and a few of mycelia-phase, while no hyphae and only very few of yeast-phase C. albicans were observed in 22.5 g/kg Pulsatilla decoction group and fluconazole group. After 7-day treatment, compared with the model group, the levels of IL-6, IL- 17, IL-21 and TNF-α in the sera of the fluconazole group, 15.0 and 22.5 g/kg Pulsatilla decoction groups were reduced significantly and the levels of RORγt in the vaginal tissues of the fluconazole group, 15.0 and 22.5 g/kg Pulsatilla decoction groups also decreased

  18. Reduced Pro-Inflammatory Cytokines after Eight Weeks of Low-Dose Naltrexone for Fibromyalgia

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    Luke Parkitny

    2017-04-01

    Full Text Available Fibromyalgia (FM is a complex, multi-symptom condition that predominantly affects women. The majority of those affected are unlikely to gain significant symptomatic control from the few treatments that are approved for FM. In this 10-week, single-blind, crossover trial we tested the immune effects of eight weeks of oral administration of low-dose naltrexone (LDN. We enrolled eight women with an average age of 46 years, symptom severity of 62 out of 100, and symptom duration of 14 years. We found that LDN was associated with reduced plasma concentrations of interleukin (IL-1β, IL-1Ra, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p40, IL-12p70, IL-15, IL-17A, IL-27, interferon (IFN-α, transforming growth factor (TGF-α, TGF-β, tumor necrosis factor (TNF-α, and granulocyte-colony stimulating factor (G-CSF. We also found a 15% reduction of FM-associated pain and an 18% reduction in overall symptoms. The findings of this pilot trial suggest that LDN treatment in fibromyalgia is associated with a reduction of several key pro-inflammatory cytokines and symptoms. The potential role of LDN as an atypical anti-inflammatory medication should be explored further.

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

    Science.gov (United States)

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

    2015-11-01

    We hypothesized that soy phytochemicals may have immunomodulatory properties that may affect prostate carcinogenesis and progression. A randomized, phase II trial was conducted in 32 patients with prostate cancer with asymptomatic biochemical recurrence but no measurable disease on standard staging studies. Patients were randomized to two slices of soy bread (34 mg isoflavones/slice) or soy bread containing almond powder daily as a source of β-glucosidase. Flow cytometry and bioplex assays were used to measure cytokines or immune cell phenotype in blood at baseline (day 0) and following intervention (day 56). Adequate blood samples were available at enrollment and day 56 and evaluated. Multiple plasma cytokines and chemokines were significantly decreased on day 56 versus baseline. Subgroup analysis indicated reduced TH1 (P = 0.028) and myeloid-derived suppressor cell (MDSC)-associated cytokines (P = 0.035). TH2 and TH17 cytokines were not significantly altered. Phenotypic analysis revealed no change in CD8(+) or CD4(+) T cells but showed increased CD56(+) natural killer (NK) cells (P = 0.038). The percentage of cells with a T regulatory cell phenotype (CD4(+)CD25(+)FoxP3(+)) was significantly decreased after 56 days of soy bread (P = 0.0136). Significantly decreased monocytic (CD33(+)HLADR(neg)CD14(+)) MDSC were observed in patients consuming soy bread (P = 0.0056). These data suggest that soy bread modulates systemic soluble and cellular biomarkers consistent with limiting inflammation and suppression of MDSCs. Additional studies to elucidate impact on the carcinogenic process or as a complement to immune-based therapy are required. ©2015 American Association for Cancer Research.

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

    Science.gov (United States)

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

    2017-09-01

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

  1. Reduced tissue osmolarity increases TRPV4 expression and pro-inflammatory cytokines in intervertebral disc cells

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    BA Walter

    2016-07-01

    Full Text Available The mechanical behaviour and cellular metabolism of intervertebral discs (IVDs and articular cartilage are strongly influenced by their proteoglycan content and associated osmotic properties. This osmotic environment is a biophysical signal that changes with disease and may contribute to the elevated matrix breakdown and altered biologic response to loading observed in IVD degeneration and osteoarthritis. This study tested the hypothesis that changes in osmo-sensation by the transient receptor potential vallinoid-4 (TRPV4 ion channel occur with disease and contribute to the inflammatory environment found during degeneration. Immunohistochemistry on bovine IVDs from an inflammatory organ culture model were used to investigate if TRPV4 is expressed in the IVD and how expression changes with degeneration. Western blot, live-cell calcium imaging, and qRT-PCR were used to investigate whether osmolarity changes or tumour necrosis factor α (TNFα regulate TRPV4 expression, and how altered TRPV4 expression influences calcium signalling and pro-inflammatory cytokine expression. TRPV4 expression correlated with TNFα expression, and was increased when cultured in reduced medium osmolarity and unaltered with TNFα-stimulation. Increased TRPV4 expression increased the calcium flux following TRPV4 activation and increased interleukin-1β (IL-1β and IL-6 gene expression in IVD cells. TRPV4 expression was qualitatively elevated in regions of aggrecan depletion in degenerated human IVDs. Collectively, results suggest that reduced tissue osmolarity, likely following proteoglycan degradation, can increase TRPV4 signalling and enhance pro-inflammatory cytokine production, suggesting changes in TRPV4 mediated osmo-sensation may contribute to the progressive matrix breakdown in disease.

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

    Science.gov (United States)

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

    2008-08-01

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

  3. Gold nanoparticles and diclofenac diethylammonium administered by iontophoresis reduce inflammatory cytokines expression in Achilles tendinitis

    Directory of Open Access Journals (Sweden)

    Dohnert MB

    2012-03-01

    Full Text Available Marcelo B Dohnert1,2, Mirelli Venâncio1, Jonathann C Possato1, Rodrigo C Zeferino1, Luciana H Dohnert2, Alexandra I Zugno1, Cláudio T De Souza1, Marcos MS Paula1, Thais F Luciano11Postgraduation Program in Health Sciences, Programa de Pós-graduação em Ciências da Saúde PPGCS, Universidade do Extremo Sul Catarinense, Criciúma, Santa Catarina, 2Department of Physiotherapy, Universidade Luterana do Brasil, Torres, Rio Grande do Sul, BrazilIntroduction: Tendinitis affects a substantial number of people in several occupations involving repetitive work or direct trauma. Iontophoresis is a therapeutic alternative used in the treatment of injury during the inflammatory phase. In recent years, gold nanoparticles (GNP have been studied due to their therapeutic anti-inflammatory capacity and as an alternative to the transport of several proteins. Purpose: This study evaluates the therapeutic effects of iontophoresis using GNPs and diclofenac diethylammonium on inflammatory parameters in rats challenged with traumatic tendinitis.Methods: Wistar rats were divided in three treatment groups (n = 15: (1 iontophoresis + diclofenac diethylammonium; (2 iontophoresis + GNP; and (3 iontophoresis + diclofenac diethylammonium + GNP. External control was formed by challenged tendons without treatment (n = 15. Iontophoresis was administered using 0.3 mA direct current on 1.5 cm² electrodes. Results: The levels of both inflammatory cytokines were significantly higher in untreated challenged rats, when compared with the control (5.398 ± 234 for interleukin 1 beta and 6.411 ± 432 for tumor necrosis factor alpha, which confirms the occurrence of an inflammatory stage in injury (P < 0.05. A significant decrease was observed in expression of cytokines interleukin 1 beta in the three treatment groups, in comparison with untreated challenged tendons, although, in the group treated with diclofenac and GNP, results were similar to the control (1.732 ± 239 (P < 0

  4. Kefir reduces insulin resistance and inflammatory cytokine expression in an animal model of metabolic syndrome.

    Science.gov (United States)

    Rosa, Damiana D; Grześkowiak, Łukasz M; Ferreira, Célia L L F; Fonseca, Ana Carolina M; Reis, Sandra A; Dias, Mariana M; Siqueira, Nathane P; Silva, Leticia L; Neves, Clóvis A; Oliveira, Leandro L; Machado, Alessandra B F; Peluzio, Maria do Carmo G

    2016-08-10

    There is growing evidence that kefir can be a promising tool in decreasing the risk of many diseases, including metabolic syndrome (MetS). The aim of the present study was to evaluate the effect of kefir supplementation in the diet of Spontaneously Hypertensive Rats (SHR) in which MetS was induced with monosodium glutamate (MSG), and to determine its effect on metabolic parameters, inflammatory and oxidation marker expression and glycemic index control. Thirty animals were used in this experiment. For the induction of MetS, twenty two-day-old male SHR received five consecutive intradermal injections of MSG. For the Negative Control, ten newborn male SHR received intradermal injections of saline solution (0.9% saline solution). After weaning, animals received standard diet and water ad libitum until reaching 3 months old, for the development of MetS. They were then divided into three groups (n = 10): negative control (NC, 1 mL saline solution per day), positive control (PC, 1 mL saline solution per day) and the Kefir group (1 mL kefir per day). Feeding was carried out by gavage for 10 weeks and the animals received standard food and water ad libitum. Obesity, insulin resistance, pro- and anti-inflammatory markers, and the histology of pancreatic and adipose tissues were among the main variables evaluated. Compared to the PC group, kefir supplementation reduced plasma triglycerides, liver lipids, liver triglycerides, insulin resistance, fasting glucose, fasting insulin, thoracic circumference, abdominal circumference, products of lipid oxidation, pro-inflammatory cytokine expression (IL-1β) and increased anti-inflammatory cytokine expression (IL-10). The present findings indicate that kefir has the potential to benefit the management of MetS.

  5. Motavizumab, A Neutralizing Anti-Respiratory Syncytial Virus (Rsv Monoclonal Antibody Significantly Modifies The Local And Systemic Cytokine Responses Induced By Rsv In The Mouse Model

    Directory of Open Access Journals (Sweden)

    Jafri Hasan S

    2007-10-01

    Full Text Available Abstract Motavizumab (MEDI-524 is a monoclonal antibody with enhanced neutralizing activity against RSV. In mice, motavizumab suppressed RSV replication which resulted in significant reduction of clinical parameters of disease severity. We evaluated the effect of motavizumab on the local and systemic immune response induced by RSV in the mouse model. Balb/c mice were intranasally inoculated with 106.5 PFU RSV A2 or medium. Motavizumab was given once intraperitoneally (1.25 mg/mouse as prophylaxis, 24 h before virus inoculation. Bronchoalveolar lavage (BAL and serum samples were obtained at days 1, 5 (acute and 28 (long-term post inoculation and analyzed with a multiplex assay (Beadlyte Upstate, NY for simultaneous quantitation of 18 cytokines: IL-1α, IL-1β, IL-2, IL-3, IL-4, IL-5, IL-6, KC (similar to human IL-8, IL-10, IL-12p40, IL-12p70, IL-13, IL-17, TNF-α, MCP-1, RANTES, IFN-γ and GM-CSF. Overall, cytokine concentrations were lower in serum than in BAL samples. By day 28, only KC was detected in BAL specimens at low concentrations in all groups. Administration of motavizumab significantly reduced (p

  6. 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...... 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...

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

    Science.gov (United States)

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

    2016-12-01

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

  8. Gold nanoparticles and diclofenac diethylammonium administered by iontophoresis reduce inflammatory cytokines expression in Achilles tendinitis.

    Science.gov (United States)

    Dohnert, Marcelo B; Venâncio, Mirelli; Possato, Jonathann C; Zeferino, Rodrigo C; Dohnert, Luciana H; Zugno, Alexandra I; De Souza, Cláudio T; Paula, Marcos M S; Luciano, Thais F

    2012-01-01

    Tendinitis affects a substantial number of people in several occupations involving repetitive work or direct trauma. Iontophoresis is a therapeutic alternative used in the treatment of injury during the inflammatory phase. In recent years, gold nanoparticles (GNP) have been studied due to their therapeutic anti-inflammatory capacity and as an alternative to the transport of several proteins. This study evaluates the therapeutic effects of iontophoresis using GNPs and diclofenac diethylammonium on inflammatory parameters in rats challenged with traumatic tendinitis. Wistar rats were divided in three treatment groups (n = 15): (1) iontophoresis + diclofenac diethylammonium; (2) iontophoresis + GNP; and (3) iontophoresis + diclofenac diethylammonium + GNP. External control was formed by challenged tendons without treatment (n = 15). Iontophoresis was administered using 0.3 mA direct current on 1.5 cm(2) electrodes. The levels of both inflammatory cytokines were significantly higher in untreated challenged rats, when compared with the control (5.398 ± 234 for interleukin 1 beta and 6.411 ± 432 for tumor necrosis factor alpha), which confirms the occurrence of an inflammatory stage in injury (P diclofenac and GNP, results were similar to the control (1.732 ± 239) (P diclofenac and GNPs presented decreased levels, compared with the control (3.221 ± 369) (P < 0.05). The results show the efficacy of drug administration using direct current to treat tendinitis in an animal model, and the potential anti-inflammatory, carrier, and enhancing effects of GNPs in iontophoresis.

  9. Reduced Fc∊RI-Mediated Release of Asthma-Promoting Cytokines and Chemokines from Human Basophils during Omalizumab Therapy

    Science.gov (United States)

    Oliver, Janet M.; Tarleton, Christy A.; Gilmartin, Laura; Archibeque, Tereassa; Qualls, Clifford R.; Diehl, Lorena; Wilson, Bridget S.; Schuyler, Mark

    2010-01-01

    Background Treating asthmatics with the humanized IgE-scavenging antibody, omalizumab (rhuMAb-E25, Xolair®), reduces airways inflammation and asthma symptoms. Previously, omalizumab was shown to cause a dramatic and reversible loss of cell surface high-affinity IgE receptors, Fc∊RI, from the peripheral blood basophils of asthmatics. The consequences of receptor loss for the Fc∊RI-mediated synthesis and release of cytokines implicated in allergic asthma have not been examined. Methods Fifteen asthmatic volunteers each received omalizumab for 12 weeks. Peripheral blood basophils were isolated before, during, 2 weeks after and 6 months after omalizumab. Basophils were assayed for the basal and anti-IgE-stimulated release of cytokines, chemokines and histamine. Pooled data were analyzed by repeated measures ANOVA and by paired t tests. Results Anti-IgE-stimulated human basophils synthesize and release Th2 cytokines (IL-4, IL-13) and chemokines (IL-8, RANTES). The anti-IgE-stimulated release of IL-4, IL-13 and IL-8 was reduced during omalizumab treatment and returned to pretreatment levels after omalizumab withdrawal. Omalizumab did not alter basophil histamine levels or basal and anti-IgE-stimulated histamine release. Conclusions Omalizumab may reduce asthma symptoms in part by suppressing the Fc∊RI-mediated production by basophils of Th2 cytokines and selected chemokines. Anti-IgE-stimulated basophil cytokine synthesis appears more sensitive than histamine release to the loss of Fc∊RI caused by omalizumab treatment. PMID:19844128

  10. Pro-inflammatory delipidizing cytokines reduce adiponectin secretion from human adipocytes without affecting adiponectin oligomerization

    NARCIS (Netherlands)

    Simons, Peter J.; van den Pangaart, Petra S.; Aerts, Johannes M. F. G.; Boon, Louis

    2007-01-01

    Adiponectin and, especially, its oligomeric complex composition have been suggested to be critical in determining insulin sensitivity. Pro-inflammatory cytokines play an important role in the development of insulin resistance in obesity and associated diseases. Therefore, we investigated the effect

  11. Inflammatory cytokine response and reduced heart rate variability in newborns with hypoxic-ischemic encephalopathy.

    Science.gov (United States)

    Al-Shargabi, T; Govindan, R B; Dave, R; Metzler, M; Wang, Y; du Plessis, A; Massaro, A N

    2017-06-01

    To determine whether systemic inflammation-modulating cytokine expression is related to heart rate variability (HRV) in newborns with hypoxic-ischemic encephalopathy (HIE). The data from 30 newborns with HIE were analyzed. Cytokine levels (IL-2, IL-4, IL-6, IL-8, IL-10, IL-13, IL-1β, TNF-α, IFN-λ) were measured either at 24 h of cooling (n=5), 72 h of cooling (n=4) or at both timepoints (n=21). The following HRV metrics were quantified in the time domain: alpha_S, alpha_L, root mean square (RMS) at short time scales (RMS_S), RMS at long time scales (RMS_L), while low-frequency power (LF) and high-frequency power (HF) were quantified in the frequency domain. The relationships between HRV metrics and cytokines were evaluated using mixed-models. IL-6, IL-8, IL-10, and IL-13 levels were inversely related to selected HRV metrics. Inflammation-modulating cytokines may be important mediators in the autonomic dysfunction observed in newborns with HIE.

  12. Forced expression of stabilized c-Fos in dendritic cells reduces cytokine production and immune responses in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Yoshida, Ryoko; Suzuki, Mayu; Sakaguchi, Ryota; Hasegawa, Eiichi; Kimura, Akihiro; Shichita, Takashi; Sekiya, Takashi [Department of Microbiology and Immunology, Keio University School of Medicine, 35 Shinanomachi, Shinjyuku-ku, Tokyo 160-8582 (Japan); Japan Science and Technology Agency, CREST, Chiyoda-ku 102-0075 (Japan); Shiraishi, Hiroshi [Division of Medical Biochemistry, Department of Biomolecular Sciences, Saga Medical School, Saga (Japan); Shimoda, Kouji [Department of Laboratory Animal Center, Keio University School of Medicine, Tokyo (Japan); Yoshimura, Akihiko, E-mail: yoshimura@a6.keio.jp [Department of Microbiology and Immunology, Keio University School of Medicine, 35 Shinanomachi, Shinjyuku-ku, Tokyo 160-8582 (Japan); Japan Science and Technology Agency, CREST, Chiyoda-ku 102-0075 (Japan)

    2012-06-29

    Highlights: Black-Right-Pointing-Pointer Dendritic cells expressing stabilized c-Fos produced less inflammatory cytokines. Black-Right-Pointing-Pointer Dendritic cells expressing stabilized c-Fos activated T cells less efficiently. Black-Right-Pointing-Pointer Transgenic mice expressing stabilized c-Fos were resistant to EAE model. -- Abstract: Intracellular cyclic adenosine monophosphate (cAMP) suppresses innate immunity by inhibiting proinflammatory cytokine production by monocytic cells. We have shown that the transcription factor c-Fos is responsible for cAMP-mediated suppression of inflammatory cytokine production, and that c-Fos protein is stabilized by IKK{beta}-mediated phosphorylation. We found that S308 is one of the major phosphorylation sites, and that the S308D mutation prolongs c-Fos halflife. To investigate the role of stabilized c-Fos protein in dendritic cells (DCs) in vivo, we generated CD11c-promoter-deriven c-FosS308D transgenic mice. As expected, bone marrow-derived DCs (BMDCs) from these Tg mice produced smaller amounts of inflammatory cytokines, including TNF-{alpha}, IL-12, and IL-23, but higher levels of IL-10, in response to LPS, than those from wild-type (Wt) mice. When T cells were co-cultured with BMDCs from Tg mice, production of Th1 and Th17 cytokines was reduced, although T cell proliferation was not affected. Tg mice demonstrated more resistance to experimental autoimmune encephalomyelitis (EAE) than did Wt mice. These data suggest that c-Fos in DCs plays a suppressive role in certain innate and adaptive immune responses.

  13. CLINICAL FEATURES AND SIGNIFICANCE OF CYTOKINE IL-4 IN CHILDREN WITH DENGUE AT A TERTIARY CARE CENTRE

    Directory of Open Access Journals (Sweden)

    Rakesh Manoharan

    2016-12-01

    Full Text Available BACKGROUND Dengue is a mosquito borne viral infection in tropical and subtropical regions caused by one of the four serotypes of dengue viruses (DENV1-DENV4. The consequences of DENV infection range from asymptomatic condition Dengue Fever (DF or severe forms such as Dengue Haemorrhagic Fever (DHF and Dengue Shock Syndrome (DSS. The host immune responses have been considered as the major factor responsible for dengue pathogenesis. Endothelial activation markers such as expression of adhesion molecules and receptors have been found to serve as biomarkers of severe dengue disease. In this study, the cytokine IL-4 is reviewed for its utility as potential biomarker of severe dengue disease. MATERIALS AND METHODS 120 children of paediatric age group from 1 month till 18 years of age with fever for more than 5 days with either dengue NS1 antigen or dengue IgM positive were included. 30 children who were admitted for noninfectious disease (e.g. surgery without fever, any systemic illness and preexisting illness (tuberculosis, asthma in SRMC and RI were taken as controls. Cases were classified as uncomplicated dengue (dengue without warning signs and complicated dengue (dengue with warning signs and severe dengue. Clinical features and IL-4 (ELISA kit were analysed and compared among the study population and statistical analysis done for the obtained data. RESULTS Analysis of clinical features among the study groups revealed children with complicated dengue had persistent vomiting (95%, abdominal pain (80%, decreased urine output (50%, bleeding manifestations (83.3%, hepatomegaly (70%, haemoconcentration with concurrent thrombocytopenia (93.3%, altered coagulation profile (28.3%, ICU stay (54.7%, leucocytosis (15%, leucopenia (66.6% and normal leucocytes (18.4%. Analysis of IL-4 levels revealed children with complicated dengue showed >6 fold elevation in IL-4 levels (p=0.003. Mean IL-4 levels in complicated dengue group was also statistically

  14. The significance of sensory appeal for reduced meat consumption.

    Science.gov (United States)

    Tucker, Corrina A

    2014-10-01

    Reducing meat (over-)consumption as a way to help address environmental deterioration will require a range of strategies, and any such strategies will benefit from understanding how individuals might respond to various meat consumption practices. To investigate how New Zealanders perceive such a range of practices, in this instance in vitro meat, eating nose-to-tail, entomophagy and reducing meat consumption, focus groups involving a total of 69 participants were held around the country. While it is the damaging environmental implications of intensive farming practices and the projected continuation of increasing global consumer demand for meat products that has propelled this research, when asked to consider variations on the conventional meat-centric diet common to many New Zealanders, it was the sensory appeal of the areas considered that was deemed most problematic. While an ecological rationale for considering these 'meat' alternatives was recognised and considered important by most, transforming this value into action looks far less promising given the recurrent sensory objections to consuming different protein-based foods or of reducing meat consumption. This article considers the responses of focus group participants in relation to each of the dietary practices outlined, and offers suggestions on ways to encourage a more environmentally viable diet. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Next-generation nozzle check valve significantly reduces operating costs

    Energy Technology Data Exchange (ETDEWEB)

    Roorda, O. [SMX International, Toronto, ON (Canada)

    2009-01-15

    Check valves perform an important function in preventing reverse flow and protecting plant and mechanical equipment. However, the variety of different types of valves and extreme differences in performance even within one type can change maintenance requirements and life cycle costs, amounting to millions of dollars over the typical 15-year design life of piping components. A next-generation non-slam nozzle check valve which prevents return flow has greatly reduced operating costs by protecting the mechanical equipment in a piping system. This article described the check valve varieties such as the swing check valve, a dual-plate check valve, and nozzle check valves. Advancements in optimized design of a non-slam nozzle check valve were also discussed, with particular reference to computer flow modelling such as computational fluid dynamics; computer stress modelling such as finite element analysis; and flow testing (using rapid prototype development and flow loop testing), both to improve dynamic performance and reduce hydraulic losses. The benefits of maximized dynamic performance and minimized pressure loss from the new designed valve were also outlined. It was concluded that this latest non-slam nozzle check valve design has potential applications in natural gas, liquefied natural gas, and oil pipelines, including subsea applications, as well as refineries, and petrochemical plants among others, and is suitable for horizontal and vertical installation. The result of this next-generation nozzle check valve design is not only superior performance, and effective protection of mechanical equipment but also minimized life cycle costs. 1 fig.

  16. PA positioning significantly reduces testicular dose during sacroiliac joint radiography

    Energy Technology Data Exchange (ETDEWEB)

    Mekis, Nejc [Faculty of Health Sciences, University of Ljubljana (Slovenia); Mc Entee, Mark F., E-mail: mark.mcentee@ucd.i [School of Medicine and Medical Science, University College Dublin 4 (Ireland); Stegnar, Peter [Jozef Stefan International Postgraduate School, Ljubljana (Slovenia)

    2010-11-15

    Radiation dose to the testes in the antero-posterior (AP) and postero-anterior (PA) projection of the sacroiliac joint (SIJ) was measured with and without a scrotal shield. Entrance surface dose, the dose received by the testicles and the dose area product (DAP) was used. DAP measurements revealed the dose received by the phantom in the PA position is 12.6% lower than the AP (p {<=} 0.009) with no statistically significant reduction in image quality (p {<=} 0.483). The dose received by the testes in the PA projection in SIJ imaging is 93.1% lower than the AP projection when not using protection (p {<=} 0.020) and 94.9% lower with protection (p {<=} 0.019). The dose received by the testicles was not changed by the use of a scrotal shield in the AP position (p {<=} 0.559); but was lowered by its use in the PA (p {<=} 0.058). Use of the PA projection in SIJ imaging significantly lowers, the dose received by the testes compared to the AP projection without significant loss of image quality.

  17. PA positioning significantly reduces testicular dose during sacroiliac joint radiography

    International Nuclear Information System (INIS)

    Mekis, Nejc; Mc Entee, Mark F.; Stegnar, Peter

    2010-01-01

    Radiation dose to the testes in the antero-posterior (AP) and postero-anterior (PA) projection of the sacroiliac joint (SIJ) was measured with and without a scrotal shield. Entrance surface dose, the dose received by the testicles and the dose area product (DAP) was used. DAP measurements revealed the dose received by the phantom in the PA position is 12.6% lower than the AP (p ≤ 0.009) with no statistically significant reduction in image quality (p ≤ 0.483). The dose received by the testes in the PA projection in SIJ imaging is 93.1% lower than the AP projection when not using protection (p ≤ 0.020) and 94.9% lower with protection (p ≤ 0.019). The dose received by the testicles was not changed by the use of a scrotal shield in the AP position (p ≤ 0.559); but was lowered by its use in the PA (p ≤ 0.058). Use of the PA projection in SIJ imaging significantly lowers, the dose received by the testes compared to the AP projection without significant loss of image quality.

  18. The oral histone deacetylase inhibitor ITF2357 reduces cytokines and protects islet ß cells in vivo and in vitro

    DEFF Research Database (Denmark)

    Lewis, Eli C; Blaabjerg, Lykke; Størling, Joachim

    2011-01-01

    of histone deacetylases (HDAC) are used commonly in humans but also possess antiinflammatory and cytokine-suppressing properties. Here we show that oral administration of the HDAC inhibitor ITF2357 to mice normalized streptozotocin (STZ)-induced hyperglycemia at the clinically relevant doses of 1.25-2.5 mg...... production and decreased apoptosis rates from 14.3% (vehicle) to 2.6% (ITF2357). Inducible nitric oxide synthase (iNOS) levels decreased in association with reduced islet-derived nitrite levels. In peritoneal macrophages and splenocytes, ITF2357 inhibited the production of nitrite, as well as that of TNFa...... and IFN¿ at an IC(50) of 25-50 nmol/L. In the insulin-producing INS cells challenged with the combination of IL-1ß plus IFN¿, apoptosis was reduced by 50% (P orally active HDAC inhibitor ITF2357 favors ß-cell survival during inflammatory conditions....

  19. Effects of Danggui Sini decoction on neuropathic pain: experimental studies and clinical pharmacological significance of inhibiting glial activation and proinflammatory cytokines in the spinal cord
.

    Science.gov (United States)

    Liu, Ming; Qiang, Qiu Hong; Ling, Qian; Yu, Chang Xi; Li, Xuejun; Liu, Suhuan; Yang, Shuyu

    2017-05-01

    Neuropathic pain responds poorly to drug treatments. Partial relief is achieved in only about half of the patients. Danggui Sini decoction (DSD), an aqueous extract of Angelica sinensis, Ramulus Cinnamomi, and Radix Puerariae, has been used extensively in China to treat inflammatory and ischemic diseases. The current study examined the putative effects of DSD on neuropathic pain. We used two commonly-used animal models: chronic constriction injury (CCI) and diabetic neuropathy for the study. And we examined effects of DSD on pain response, activation of microglia and astroglia in spinal dorsal horn, and expression of proinflammatory cytokines in the spinal cord. Consecutive intragastric administration of DSD (25 - 100 mg/kg) for 10 days inhibited the mechanical and thermal nociceptive response induced by CCI and diabetes without interfering with the normal pain response. Meanwhile, in both models, DSD inhibited the over-expression of specific markers for microglia (Iba-1) and astroglia (GFAP) activation in the spinal dorsal horn. DSD also reduced the elevated nuclear NF-κB level and inhibited the up-regulation of proinflammatory cytokines, such as IL-6, IL-1β, and TNF-α, in the spinal cord. DSD can alleviate CCI and diabetes-induced neuropathic pain, and its effectiveness might be due to the inhibition of neuroinflammation in the spinal dorsal horn. The anti-inflammation effect of DSD may be related to the suppression of spinal NF-κB activation and/or cytokines expression.
.

  20. Vinpocetine reduces diclofenac-induced acute kidney injury through inhibition of oxidative stress, apoptosis, cytokine production, and NF-κB activation in mice.

    Science.gov (United States)

    Fattori, Victor; Borghi, Sergio M; Guazelli, Carla F S; Giroldo, Andressa C; Crespigio, Jefferson; Bussmann, Allan J C; Coelho-Silva, Letícia; Ludwig, Natasha G; Mazzuco, Tânia L; Casagrande, Rubia; Verri, Waldiceu A

    2017-06-01

    Acute kidney injury (AKI) represents a complex clinical condition associated with significant morbidity and mortality. Approximately, 19-33% AKI episodes in hospitalized patients are related to drug-induced nephrotoxicity. Although, considered safe, non-steroidal anti-inflammatory drugs such as diclofenac have received special attention in the past years due to the potential risk of renal damage. Vinpocetine is a nootropic drug known to have anti-inflammatory properties. In this study, we investigated the effect and mechanisms of vinpocetine in a model of diclofenac-induced AKI. We observed that diclofenac increased proteinuria and blood urea, creatinine, and oxidative stress levels 24h after its administration. In renal tissue, diclofenac also increased oxidative stress and induced morphological changes consistent with renal damage. Moreover, diclofenac induced kidney cells apoptosis, up-regulated proinflammatory cytokines, and induced the activation of NF-κB in renal tissue. On the other hand, vinpocetine reduced diclofenac-induced blood urea and creatinine. In the kidneys, vinpocetine inhibited diclofenac-induced oxidative stress, morphological changes, apoptosis, cytokine production, and NF-κB activation. To our knowledge, this is the first study demonstrating that diclofenac-induced AKI increases NF-κB activation, and that vinpocetine reduces the nephrotoxic effects of diclofenac. Therefore, vinpocetine is a promising molecule for the treatment of diclofenac-induced AKI. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2015-01-01

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

  2. Progesterone promotes maternal-fetal tolerance by reducing human maternal T-cell polyfunctionality and inducing a specific cytokine profile.

    Science.gov (United States)

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

    2015-10-01

    Progesterone is a steroid hormone essential for the maintenance of human pregnancy, and its actions are thought to include promoting maternal immune tolerance of the semiallogenic fetus. We report that exposure of maternal T cells to progesterone at physiological doses induced a unique skewing of the cytokine production profile of CD4(+) and CD8(+) T cells, with reductions not only in potentially deleterious IFN-γ and TNF-α production but also in IL-10 and IL-5. Conversely, production of IL-4 was increased. Maternal T cells also became less polyfunctional, focussing cytokine production toward profiles including IL-4. This was accompanied by reduced T-cell proliferation. Using fetal and viral antigen-specific CD8(+) T-cell clones, we confirmed that this as a direct, nonantigen-specific effect. Yet human T cells lacked conventional nuclear progesterone receptors, implicating a membrane progesterone receptor. CD4(+) and CD8(+) T cells responded to progesterone in a dose-dependent manner, with subtle effects at concentrations comparable to those in maternal blood, but profound effects at concentrations similar to those at the maternal-fetal interface. This characterization of how progesterone modulates T-cell function is important in understanding the normal biology of pregnancy and informing the rational use of progesterone therapy in pregnancies at risk of fetal loss. © 2015 The Authors. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Changes in T-cell subpopulations and cytokine network during early period of ibrutinib therapy in chronic lymphocytic leukemia patients: the significant decrease in T regulatory cells number.

    Science.gov (United States)

    Podhorecka, Monika; Goracy, Aneta; Szymczyk, Agnieszka; Kowal, Malgorzata; Ibanez, Blanca; Jankowska-Lecka, Olga; Macheta, Arkadiusz; Nowaczynska, Aleksandra; Drab-Urbanek, Elzbieta; Chocholska, Sylwia; Jawniak, Dariusz; Hus, Marek

    2017-05-23

    B cell receptor (BCR) stimulation signal plays an important role in the pathogenesis of chronic lymphocytic leukemia (CLL), and kinase inhibitors directed toward the BCR pathway are now the promising anti-leukemic drugs. Ibrutinib, a Bruton tyrosine kinase inhibitor, demonstrates promising clinical activity in CLL. It is reported that ibrutinib, additionally to directly targeting leukemic cells, also inhibits the interactions of these cells with T cells, macrophages and accessory cells. Assessment of these mechanisms is important because of their non -direct anti-leukemic effects and to identify possible side effects connected with long-term drug administration.The aim of this study was to assess the in vivo effects of ibrutinib on T-cell subpopulations and cytokine network in CLL. The analysis was performed on a group of 19 patients during first month of ibrutinib therapy. The standard multicolor flow cytometry and cytometric bead array methods were used for assessment of T-cell subsets and cytokines/chemokines, respectively.The data obtained indicates that Ibrutinib treatment results in changes in T-cell subpopulations and cytokine network in CLL patients. Particularly, a significant reduction of T regulatory cells in peripheral blood was observed. By targeting these populations of T cells Ibrutinib can stimulate rejection of tumor cells by the immune system.

  4. A Newly Emergent Turkey Arthritis Reovirus Shows Dominant Enteric Tropism and Induces Significantly Elevated Innate Antiviral and T Helper-1 Cytokine Responses.

    Directory of Open Access Journals (Sweden)

    Tamer A Sharafeldin

    Full Text Available Newly emergent turkey arthritis reoviruses (TARV were isolated from tendons of lame 15-week-old tom turkeys that occasionally had ruptured leg tendons. Experimentally, these TARVs induced remarkable tenosynovitis in gastrocnemius tendons of turkey poults. The current study aimed to characterize the location and the extent of virus replication as well as the cytokine response induced by TARV during the first two weeks of infection. One-week-old male turkeys were inoculated orally with TARV (O'Neil strain. Copy numbers of viral genes were estimated in intestines, internal organs and tendons at ½, 1, 2, 3, 4, 7, 14 days Post inoculation (dpi. Cytokine profile was measured in intestines, spleen and leg tendons at 0, 4, 7 and 14 dpi. Viral copy number peaked in jejunum, cecum and bursa of Fabricius at 4 dpi. Copy numbers increased dramatically in leg tendons at 7 and 14 dpi while minimal copies were detected in internal organs and blood during the same period. Virus was detected in cloacal swabs at 1-2 dpi, and peaked at 14 dpi indicating enterotropism of the virus and its early shedding in feces. Elevation of IFN-α and IFN-β was observed in intestines at 7 dpi as well as a prominent T helper-1 response (IFN-γ at 7 and 14 dpi. IFN-γ and IL-6 were elevated in gastrocnemius tendons at 14 dpi. Elevation of antiviral cytokines in intestines occurred at 7dpi when a significant decline of viral replication in intestines was observed. T helper-1 response in intestines and leg tendons was the dominant T-helper response. These results suggest the possible correlation between viral replication and cytokine response in early infection of TARV in turkeys. Our findings provide novel insights which help elucidate viral pathogenesis in turkey tendons infected with TARV.

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

    International Nuclear Information System (INIS)

    Yu Tintin

    2006-01-01

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

  6. Clinical significance of determination of some serum cytokines (IL-8, IL-10, IL-18, M-CSF) levels in patients with periodontitis

    International Nuclear Information System (INIS)

    Wei Dong; Zhang Xiaolei; Yang Chunxiu; Chen Guanghua

    2008-01-01

    Objective: To explore the significance of changes of serum IL-8, IL-10, IL-18 and M-CSF levels in patients with periodontitis. Methods: Serum levels of IL-8, IL-10, M-CSF (with RIA) and IL-18 (with ELISA) were measured in 55 patients with periodontitis both before and after treatment as well as in 35 controls. Results: Before treatment, serum levels of IL-8, IL-10, IL-18 and M-CSF were significantly higher in the patients than those in the controls (P<0.01). After one month of treatment, the serum IL-8, IL-10, IL-18 and M-CSF levels decreased somewhat, but were still significantly higher than those in controls (P<0.05). Conclusion: There was disturbance of immunomodulation in patients with periodontitis as expressed by the changes of several cytokines levels in the eourse of the diseases. (authors)

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

    International Nuclear Information System (INIS)

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

    2001-01-01

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

  8. Stable Toll-Like Receptor 10 Knockdown in THP-1 Cells Reduces TLR-Ligand-Induced Proinflammatory Cytokine Expression

    Directory of Open Access Journals (Sweden)

    Hai Van Le

    2016-06-01

    Full Text Available Toll-like receptor 10 (TLR10 is the only orphan receptor whose natural ligand and function are unknown among the 10 human TLRs. In this study, to test whether TLR10 recognizes some known TLR ligands, we established a stable TLR10 knockdown human monocytic cell line THP-1 using TLR10 short hairpin RNA lentiviral particle and puromycin selection. Among 60 TLR10 knockdown clones that were derived from each single transduced cell, six clones were randomly selected, and then one of those clones, named E7, was chosen for the functional study. E7 exhibited approximately 50% inhibition of TLR10 mRNA and protein expression. Of all the TLRs, only the expression of TLR10 changed significantly in this cell line. Additionally, phorbol 12-myristate 13-acetate-induced macrophage differentiation of TLR10 knockdown cells was not affected in the knockdown cells. When exposed to TLR ligands, such as synthetic diacylated lipoprotein (FSL-1, lipopolysaccharide (LPS, and flagellin, significant induction of proinflammatory cytokine gene expression including Interleukin-8 (IL-8, Interleukin-1 beta (IL-1β, Tumor necrosis factor-alpha (TNF-α and Chemokine (C–C Motif Ligand 20 (CCL20 expression, was found in the control THP-1 cells, whereas the TLR10 knockdown cells exhibited a significant reduction in the expression of IL-8, IL-1β, and CCL20. TNF-α was the only cytokine for which the expression did not decrease in the TLR10 knockdown cells from that measured in the control cells. Analysis of putative binding sites for transcription factors using a binding-site-prediction program revealed that the TNF-α promoter does not have putative binding sites for AP-1 or c-Jun, comprising a major transcription factor along with NF-κB for TLR signaling. Our results suggest that TLR10 is involved in the recognition of FSL-1, LPS, and flagellin and TLR-ligand-induced expression of TNF-α does not depend on TLR10.

  9. Stable Toll-Like Receptor 10 Knockdown in THP-1 Cells Reduces TLR-Ligand-Induced Proinflammatory Cytokine Expression.

    Science.gov (United States)

    Le, Hai Van; Kim, Jae Young

    2016-06-01

    Toll-like receptor 10 (TLR10) is the only orphan receptor whose natural ligand and function are unknown among the 10 human TLRs. In this study, to test whether TLR10 recognizes some known TLR ligands, we established a stable TLR10 knockdown human monocytic cell line THP-1 using TLR10 short hairpin RNA lentiviral particle and puromycin selection. Among 60 TLR10 knockdown clones that were derived from each single transduced cell, six clones were randomly selected, and then one of those clones, named E7, was chosen for the functional study. E7 exhibited approximately 50% inhibition of TLR10 mRNA and protein expression. Of all the TLRs, only the expression of TLR10 changed significantly in this cell line. Additionally, phorbol 12-myristate 13-acetate-induced macrophage differentiation of TLR10 knockdown cells was not affected in the knockdown cells. When exposed to TLR ligands, such as synthetic diacylated lipoprotein (FSL-1), lipopolysaccharide (LPS), and flagellin, significant induction of proinflammatory cytokine gene expression including Interleukin-8 (IL-8), Interleukin-1 beta (IL-1β), Tumor necrosis factor-alpha (TNF-α) and Chemokine (C-C Motif) Ligand 20 (CCL20) expression, was found in the control THP-1 cells, whereas the TLR10 knockdown cells exhibited a significant reduction in the expression of IL-8, IL-1β, and CCL20. TNF-α was the only cytokine for which the expression did not decrease in the TLR10 knockdown cells from that measured in the control cells. Analysis of putative binding sites for transcription factors using a binding-site-prediction program revealed that the TNF-α promoter does not have putative binding sites for AP-1 or c-Jun, comprising a major transcription factor along with NF-κB for TLR signaling. Our results suggest that TLR10 is involved in the recognition of FSL-1, LPS, and flagellin and TLR-ligand-induced expression of TNF-α does not depend on TLR10.

  10. Local cytokine profile and cytological status in children with community-acquired pneumonia arising on the background of the reduced resistance of the organism

    Directory of Open Access Journals (Sweden)

    T. G. Malanicheva

    2017-01-01

    Full Text Available Research objective: to study the features of the cytokine profile and cytological status in children with community-acquired pneumonia, proceeding against a background of reduced resistance of the organism for improving treatment methods. 53 children aged 3 to 7 years were examined. The main group consisted of 30 children with community-acquired pneumonia, which ran against a background of reduced resistance of the body. The comparison group consisted of 23 children with community-acquired pneumonia who had good resistance. Local immunity was studied on the basis of  valuation of cytokine status parameters (tumor necrotic factor-α, interleukin-8, and interferon-γ and cellular composition with an estimate of destructive changes in neutrophils in induced sputum. It was revealed that in the main group of children there is a depression of the neutrophils’ release into the bronchial secretion and a marked increase in the number of neutrophils with maximum signs of destruction of the nucleus and cytoplasm against the background of cytokine status imbalance, manifested in an increase in the content of the tumor necrotic factor-α and a decrease in interleukin-8 and interferon- γ. Inclusion in the traditional therapy of community-acquired pneumonia in children who have a reduced resistance, anti-inflammatory drug fenspiride, eliminates the imbalance of proinflammatory cytokines and increases the release of functionally complete neutrophils in the bronchial secret.

  11. mRNA-binding protein TIA-1 reduces cytokine expression in human endometrial stromal cells and is down-regulated in ectopic endometrium.

    Science.gov (United States)

    Karalok, Hakan Mete; Aydin, Ebru; Saglam, Ozlen; Torun, Aysenur; Guzeloglu-Kayisli, Ozlem; Lalioti, Maria D; Kristiansson, Helena; Duke, Cindy M P; Choe, Gina; Flannery, Clare; Kallen, Caleb B; Seli, Emre

    2014-12-01

    Cytokines and growth factors play important roles in endometrial function and the pathogenesis of endometriosis. mRNAs encoding cytokines and growth factors undergo rapid turnover; primarily mediated by adenosine- and uridine-rich elements (AREs) located in their 3'-untranslated regions. T-cell intracellular antigen (TIA-1), an mRNA-binding protein, binds to AREs in target transcripts, leading to decreased gene expression. The purpose of this article was to determine whether TIA-1 plays a role in the regulation of endometrial cytokine and growth factor expression during the normal menstrual cycle and whether TIA-1 expression is altered in women with endometriosis. Eutopic endometrial tissue obtained from women without endometriosis (n = 30) and eutopic and ectopic endometrial tissues from women with endometriosis (n = 17) were immunostained for TIA-1. Staining intensities were evaluated by histological scores (HSCOREs). The regulation of endometrial TIA-1 expression by immune factors and steroid hormones was studied by treating primary cultured human endometrial stromal cells (HESCs) with vehicle, lipopolysaccharide, TNF-α, IL-6, estradiol, or progesterone, followed by protein blot analyses. HESCs were engineered to over- or underexpress TIA-1 to test whether TIA-1 regulates IL-6 or TNF-α expression in these cells. We found that TIA-1 is expressed in endometrial stromal and glandular cells throughout the menstrual cycle and that this expression is significantly higher in the perimenstrual phase. In women with endometriosis, TIA-1 expression in eutopic and ectopic endometrium was reduced compared with TIA-1 expression in eutopic endometrium of unaffected control women. Lipopolysaccharide and TNF-α increased TIA-1 expression in HESCs in vitro, whereas IL-6 or steroid hormones had no effect. In HESCs, down-regulation of TIA-1 resulted in elevated IL-6 and TNF-α expression, whereas TIA-1 overexpression resulted in decreased IL-6 and TNF-α expression. Endometrial

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

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    Krüssel Jan-Steffen

    2010-11-01

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

  13. Significance of measurement of serum somatostatin (SS), growth hormone (GH), insulin-like growth factor-1 (IGF-1) and some related cytokines levels in patients with graves' disease

    International Nuclear Information System (INIS)

    Zhu Bao; Ma Yunbao; Zhang Xiaoyi

    2005-01-01

    Objective: To study the possible roles of the related hormones and cytokines in the pathogenesis of Graves' disease. Methods: Serum levels of SS, GH, IGF-1, IL-2, IL-4 and IL-6 were measured with RIA in 1) 36 patients with Graves' disease before any treatment 2) another 30 patients with Graves' disease after successful anti-thyroid drug therapy and 3) 35 controls. Results: In the untreated group, the serum levels of SS, GH, IGF-1, IL-4 and IL-6 were significantly higher but serum IL-2 levels were significantly lower than those in the controls (P<0.01). In the successfully treated group, the serum levels of SS, GH, IGF-1, IL-4 and IL-6 were significantly lower (P<0.05 or P<0.01), but serum IL-2 levels were significantly higher (P<0.01) than those in the untreated group. Conclusion: These parameters played significant roles in the pathogenesis of Graves' disease; however, the precise mechanism remained to be speculative and further studies required. (authors)

  14. Melatonin Treatment Reduces Oxidative Damage and Normalizes Plasma Pro-Inflammatory Cytokines in Patients Suffering from Charcot-Marie-Tooth Neuropathy: A Pilot Study in Three Children.

    Science.gov (United States)

    Chahbouni, Mariam; López, María Del Señor; Molina-Carballo, Antonio; de Haro, Tomás; Muñoz-Hoyos, Antonio; Fernández-Ortiz, Marisol; Guerra-Librero, Ana; Acuña-Castroviejo, Darío

    2017-10-14

    Charcot-Marie-Tooth neuropathy (CMT) is a motor and sensory neuropathy comprising a heterogeneous group of inherited diseases. The CMT1A phenotype is predominant in the 70% of CMT patients, with nerve conduction velocity reduction and hypertrophic demyelination. These patients have elevated oxidative stress and chronic inflammation. Currently, there is no effective cure for CMT; herein, we investigated whether melatonin treatment may reduce the inflammatory and oxidative damage in CMT1A patients. Three patients, aged 8-10 years, were treated with melatonin (60 mg at 21:00 h plus 10 mg at 09:00 h), and plasma levels of lipid peroxidation (LPO), nitrites (NOx), IL-1β, IL-2, IL-6, TNF-α, INF-γ, oxidized to reduced glutathione (GSSG/GSH) ratio, and the activities of superoxide dismutase (SOD), glutathione-S transferase (GST), glutathione peroxidase (GPx), and reductase (GRd), were determined in erythrocytes at 3 and 6 months of treatment. Healthy age- and sex-matched subjects were used as controls. The results showed increased activities of SOD, GST, GPx, and GRd in CMT1A patients, which were reduced at 3 and 6 months of treatment. The GSSG/GSH ratio significantly increased in the patients, returning to control values after melatonin treatment. The inflammatory process was confirmed by the elevation of all proinflammatory cytokines measured, which were also normalized by melatonin. LPO and NOx, which also were elevated in the patients, were normalized by melatonin. The results document beneficial effects of the use of melatonin in CMT1A patients to reduce the hyperoxidative and inflammatory condition, which may correlate with a reduction of the degenerative process.

  15. Combined exercise training reduces fatigue and modulates the cytokine profile of T-cells from multiple sclerosis patients in response to neuromediators.

    Science.gov (United States)

    Alvarenga-Filho, Helcio; Sacramento, Priscila M; Ferreira, Thais B; Hygino, Joana; Abreu, Jorge Eduardo Canto; Carvalho, Sonia Regina; Wing, Ana Cristina; Alvarenga, Regina Maria Papais; Bento, Cleonice A M

    2016-04-15

    Fatigue is a common and disabling symptom of multiple sclerosis (MS), a classical Th1- and Th17-mediated autoimmune disease. There is no effective pharmacological treatment for fatigue, but some reports point towards beneficial effects of physical activity on management of the fatigue in MS patients. As both MS and fatigue have been associated with dysregulated cytokine network production, the objective of the present study was to evaluate the impact of a physical activity program consisting of a 12-week series of combining Pilates and aerobic exercises on fatigue severity, determined by FSS, and cytokine production, quantified by ELISA, by T cells from MS patients (n=08) with low disability (EDSS≤2). The results showed decrease in FSSs in all patients at the end of physical activity intervention. Regarding the cytokines, a significant reduction of IL-22 release was observed in polyclonally-activated T cells form MS patients post-training follow-up. Interestingly, while the physical activity attenuated the ability of dopamine in up-regulating Th17-related cytokines, it enhanced the anti-inflammatory effects of serotonin, evidenced by high IL-10 production. In summary, all results suggest that programmed physical activity has beneficial effects on management of fatigue in MS patients, and it could be related, at least in part, to its ability in regulating neuroimmune parameters into T cell compartment. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Short-term heating reduces the anti-inflammatory effects of fresh raw garlic extracts on the LPS-induced production of NO and pro-inflammatory cytokines by downregulating allicin activity in RAW 264.7 macrophages.

    Science.gov (United States)

    Shin, Jung-Hye; Ryu, Ji Hyeon; Kang, Min Jung; Hwang, Cho Rong; Han, Jaehee; Kang, Dawon

    2013-08-01

    Garlic has a variety of biologic activities, including anti-inflammatory properties. Although garlic has several biologic activities, some people dislike eating fresh raw garlic because of its strong taste and smell. Therefore, garlic formulations involving heating procedures have been developed. In this study, we investigated whether short-term heating affects the anti-inflammatory properties of garlic. Fresh and heated raw garlic extracts (FRGE and HRGE) were prepared with incubation at 25 °C and 95 °C, respectively, for 2 h. Treatment with FRGE and HRGE significantly reduced the LPS-induced increase in the pro-inflammatory cytokine concentration (TNF-α, IL-1β, and IL-6) and NO through HO-1 upregulation in RAW 264.7 macrophages. The anti-inflammatory effect was greater in FRGE than in HRGE. The allicin concentration was higher in FRGE than in HRGE. Allicin treatment showed reduced production of pro-inflammatory cytokines and NO and increased HO-1 activity. The results show that the decrease in LPS-induced NO and pro-inflammatory cytokines in RAW 264.7 macrophages through HO-1 induction was greater for FRGE compared with HRGE. Additionally, the results indicate that allicin is responsible for the anti-inflammatory effect of FRGE. Our results suggest a potential therapeutic use of allicin in the treatment of chronic inflammatory disease. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Kluyveromyces marxianus and Saccharomyces boulardii Induce Distinct Levels of Dendritic Cell Cytokine Secretion and Significantly Different T Cell Responses In Vitro.

    Directory of Open Access Journals (Sweden)

    Ida M Smith

    Full Text Available Interactions between members of the intestinal microbiota and the mucosal immune system can significantly impact human health, and in this context, fungi and food-related yeasts are known to influence intestinal inflammation through direct interactions with specialized immune cells in vivo. The aim of the present study was to characterize the immune modulating properties of the food-related yeast Kluyveromyces marxianus in terms of adaptive immune responses indicating inflammation versus tolerance and to explore the mechanisms behind the observed responses. Benchmarking against a Saccharomyces boulardii strain with probiotic effects documented in clinical trials, we evaluated the ability of K. marxianus to modulate human dendritic cell (DC function in vitro. Further, we assessed yeast induced DC modulation of naive T cells toward effector responses dominated by secretion of IFNγ and IL-17 versus induction of a Treg response characterized by robust IL-10 secretion. In addition, we blocked relevant DC surface receptors and investigated the stimulating properties of β-glucan containing yeast cell wall extracts. K. marxianus and S. boulardii induced distinct levels of DC cytokine secretion, primarily driven by Dectin-1 recognition of β-glucan components in their cell walls. Upon co-incubation of yeast exposed DCs and naive T cells, S. boulardii induced a potent IFNγ response indicating TH1 mobilization. In contrast, K. marxianus induced a response dominated by Foxp3+ Treg cells, a characteristic that may benefit human health in conditions characterized by excessive inflammation and positions K. marxianus as a strong candidate for further development as a novel yeast probiotic.

  18. Kluyveromyces marxianus and Saccharomyces boulardii Induce Distinct Levels of Dendritic Cell Cytokine Secretion and Significantly Different T Cell Responses In Vitro.

    Science.gov (United States)

    Smith, Ida M; Baker, Adam; Christensen, Jeffrey E; Boekhout, Teun; Frøkiær, Hanne; Arneborg, Nils; Jespersen, Lene

    2016-01-01

    Interactions between members of the intestinal microbiota and the mucosal immune system can significantly impact human health, and in this context, fungi and food-related yeasts are known to influence intestinal inflammation through direct interactions with specialized immune cells in vivo. The aim of the present study was to characterize the immune modulating properties of the food-related yeast Kluyveromyces marxianus in terms of adaptive immune responses indicating inflammation versus tolerance and to explore the mechanisms behind the observed responses. Benchmarking against a Saccharomyces boulardii strain with probiotic effects documented in clinical trials, we evaluated the ability of K. marxianus to modulate human dendritic cell (DC) function in vitro. Further, we assessed yeast induced DC modulation of naive T cells toward effector responses dominated by secretion of IFNγ and IL-17 versus induction of a Treg response characterized by robust IL-10 secretion. In addition, we blocked relevant DC surface receptors and investigated the stimulating properties of β-glucan containing yeast cell wall extracts. K. marxianus and S. boulardii induced distinct levels of DC cytokine secretion, primarily driven by Dectin-1 recognition of β-glucan components in their cell walls. Upon co-incubation of yeast exposed DCs and naive T cells, S. boulardii induced a potent IFNγ response indicating TH1 mobilization. In contrast, K. marxianus induced a response dominated by Foxp3+ Treg cells, a characteristic that may benefit human health in conditions characterized by excessive inflammation and positions K. marxianus as a strong candidate for further development as a novel yeast probiotic.

  19. Sodium-Reduced Meat and Poultry Products Contain a Significant Amount of Potassium from Food Additives.

    Science.gov (United States)

    Parpia, Arti Sharma; Goldstein, Marc B; Arcand, JoAnne; Cho, France; L'Abbé, Mary R; Darling, Pauline B

    2018-05-01

    counterparts (mean difference [95% CI]: 486 [334-638]; Padditives appearing on the product label ingredient list, did not significantly differ between the two groups. Potassium additives are frequently added to sodium-reduced MPPs in amounts that significantly contribute to the potassium load for patients with impaired renal handling of potassium caused by chronic kidney disease and certain medications. Patients requiring potassium restriction should be counseled to be cautious regarding the potassium content of sodium-reduced MPPs and encouraged to make food choices accordingly. Copyright © 2018 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.

  20. A pilot weight reduction program over one year significantly reduced DNA strand breaks in obese subjects

    Directory of Open Access Journals (Sweden)

    Karl-Heinz Wagner

    2015-05-01

    Conclusion: A sustainable lifestyle change under supervision including physical activity and diet quality over a period of one year was not only responsible to reduce body weight and BMI but also led to significant reduction in all parameters of the comet assay. These results underline the importance of body weight reduction and highlight the positive changes in DNA stability.

  1. Indoline-3-propionate and 3-aminopropyl carbamates reduce lung injury and pro-inflammatory cytokines induced in mice by LPS.

    Science.gov (United States)

    Finkin-Groner, E; Moradov, D; Shifrin, H; Bejar, C; Nudelman, A; Weinstock, M

    2015-02-01

    In the search for safer and effective anti-inflammatory agents, we investigated the effect of methyl indoline-3-propionate and indoline-3-(3-aminopropyl) carbamates on LPS-induced lung injury and pro-inflammatory cytokines in mice. Their mechanism of action was determined in murine peritoneal macrophages. Lung injury was induced by intratracheal infusion of LPS and assessed by the change in lung weight and structure by light microscopy after staining by haematoxylin and eosin. In LPS-activated macrophages, MAPK proteins and IκBα were measured by Western blotting and the transcription factors, AP-1 and NF-κB by electromobility shift assay. Cytokines in the plasma and spleen of mice injected with LPS were measured by elisa-based assay. AN917 and AN680 (1-10 pM) decreased TNF-α protein in macrophages by inhibiting phosphorylation of p38 MAPK, IκBα degradation and activation of AP-1 and NF-κB without affecting cell viability. In vivo, these compounds (10 μmol · kg(-1)) markedly decreased lung injury induced by LPS and the elevation of TNF-α and IL-6 in lung, plasma and spleen. Activation of α-7nACh receptors contributed to the reduction of TNF-α by AN917, which inhibited AChE in the spleen by 35%. Indoline carbamates are potent inhibitors of pro-inflammatory mediators in murine macrophages and in mice injected with LPS, acting via the p38 MAPK, AP-1 and NF-κB cascades. Indirect α-7nACh receptor activation by AN917, through inhibition of AChE, contributes to its anti-inflammatory effect. Indoline carbamates may have therapeutic potential for lung injury and other diseases associated with chronic inflammation without causing immunosuppression. © 2014 The British Pharmacological Society.

  2. The significance of reduced respiratory chain enzyme activities: clinical, biochemical and radiological associations.

    Science.gov (United States)

    Mordekar, S R; Guthrie, P; Bonham, J R; Olpin, S E; Hargreaves, I; Baxter, P S

    2006-03-01

    Mitochondrial diseases are an important group of neurometabolic disorders in children with varied clinical presentations and diagnosis that can be difficult to confirm. To report the significance of reduced respiratory chain enzyme (RCE) activity in muscle biopsy samples from children. Retrospective odds ratio was used to compare clinical and biochemical features, DNA studies, neuroimaging, and muscle biopsies in 18 children with and 48 without reduced RCE activity. Children with reduced RCE activity were significantly more likely to have consanguineous parents, to present with acute encephalopathy and lactic acidaemia and/or within the first year of life; to have an axonal neuropathy, CSF lactate >4 mmol/l; and/or to have signal change in the basal ganglia. There were positive associations with a maternal family history of possible mitochondrial cytopathy; a presentation with failure to thrive and lactic acidaemia, ragged red fibres, reduced fibroblast fatty acid oxidation and with an abnormal allopurinol loading test. There was no association with ophthalmic abnormalities, deafness, epilepsy or myopathy. The association of these clinical, biochemical and radiological features with reduced RCE activity suggests a possible causative link.

  3. TNF-α-induced up-regulation of pro-inflammatory cytokines is reduced by phosphatidylcholine in intestinal epithelial cells

    Directory of Open Access Journals (Sweden)

    Griffiths Gareth

    2009-07-01

    Full Text Available Abstract Background Phosphatidylcholine (PC is a major lipid of the gastrointestinal mucus layer. We recently showed that mucus from patients suffering from ulcerative colitis has low levels of PC. Clinical studies reveal that the therapeutic addition of PC to the colonic mucus using slow release preparations is beneficial. The positive role of PC in this disease is still unclear; however, we have recently shown that PC has an intrinsic anti-inflammatory property. It could be demonstrated that the exogenous application of PC inhibits membrane-dependent actin assembly and TNF-α-induced nuclear NF-κB activation. We investigate here in more detail the hypothesis that the exogenous application of PC has anti-inflammatory properties. Methods PC species with different fatty acid side chains were applied to differentiated and non-differentiated Caco-2 cells treated with TNF-α to induce a pro-inflammatory response. We analysed TNF-α-induced NF-κB-activation via the transient expression of a NF-κB-luciferase reporter system. Pro-inflammatory gene transcription was detected with the help of a quantitative real time (RT-PCR analysis. We assessed the binding of TNF-α to its receptor by FACS and analysed lipid rafts by isolating detergent resistant membranes (DRMs. Results The exogenous addition of all PC species tested significantly inhibited TNF-α-induced pro-inflammatory signalling. The expression levels of IL-8, ICAM-1, IP-10, MCP-1, TNF-α and MMP-1 were significantly reduced after PC pre-treatment for at least two hours. The effect was comparable to the inhibition of NF-kB by the NF-kB inhibitor SN 50 and was not due to a reduced binding of TNF-α to its receptor or a decreased surface expression of TNF-α receptors. PC was also effective when applied to the apical side of polarised Caco-2 cultures if cells were stimulated from the basolateral side. PC treatment changed the compartmentation of the TNF-α-receptors 1 and 2 to DRMs. Conclusion PC

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

    Science.gov (United States)

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

    2011-10-01

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

  5. Insulin-Like growth factor-II (IGF-II) prevents proinflammatory cytokine-induced apoptosis and significantly improves islet survival after transplantation.

    Science.gov (United States)

    Hughes, Amy; Mohanasundaram, Daisy; Kireta, Svjetlana; Jessup, Claire F; Drogemuller, Chris J; Coates, P Toby H

    2013-03-15

    The early loss of functional islet mass (50-70%) due to apoptosis after clinical transplantation contributes to islet allograft failure. Insulin-like growth factor (IGF)-II is an antiapoptotic protein that is highly expressed in β-cells during development but rapidly decreases in postnatal life. We used an adenoviral (Ad) vector to overexpress IGF-II in isolated rat islets and investigated its antiapoptotic action against exogenous cytokines interleukin-1β- and interferon-γ-induced islet cell death in vitro. Using an immunocompromised marginal mass islet transplant model, the ability of Ad-IGF-II-transduced rat islets to restore euglycemia in nonobese diabetic/severe combined immunodeficient diabetic recipients was assessed. Ad-IGF-II transduction did not affect islet viability or function. Ad-IGF-II cytokine-treated islets exhibited decreased cell death (40% ± 2.8%) versus Ad-GFP and untransduced control islets (63.2% ± 2.5% and 53.6% ± 2.3%, respectively). Ad-IGF-II overexpression during cytokine treatment resulted in a marked reduction in terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive apoptotic cells (8.3% ± 1.4%) versus Ad-GFP control (41% ± 4.2%) and untransduced control islets (46.5% ± 6.2%). Western blot analysis confirmed that IGF-II inhibits apoptosis via activation of the phosphatidylinositol 3-kinase/Akt signaling pathway. Transplantation of IGF-II overexpressing islets under the kidney capsule of diabetic mice restored euglycemia in 77.8% of recipients compared with 18.2% and 47.5% of Ad-GFP and untransduced control islet recipients, respectively (Pislet transplant outcomes in vivo. Antiapoptotic gene transfer is a potentially powerful tool to improve islet survival after transplantation.

  6. Male circumcision significantly reduces prevalence and load of genital anaerobic bacteria.

    Science.gov (United States)

    Liu, Cindy M; Hungate, Bruce A; Tobian, Aaron A R; Serwadda, David; Ravel, Jacques; Lester, Richard; Kigozi, Godfrey; Aziz, Maliha; Galiwango, Ronald M; Nalugoda, Fred; Contente-Cuomo, Tania L; Wawer, Maria J; Keim, Paul; Gray, Ronald H; Price, Lance B

    2013-04-16

    Male circumcision reduces female-to-male HIV transmission. Hypothesized mechanisms for this protective effect include decreased HIV target cell recruitment and activation due to changes in the penis microbiome. We compared the coronal sulcus microbiota of men from a group of uncircumcised controls (n = 77) and from a circumcised intervention group (n = 79) at enrollment and year 1 follow-up in a randomized circumcision trial in Rakai, Uganda. We characterized microbiota using16S rRNA gene-based quantitative PCR (qPCR) and pyrosequencing, log response ratio (LRR), Bayesian classification, nonmetric multidimensional scaling (nMDS), and permutational multivariate analysis of variance (PerMANOVA). At baseline, men in both study arms had comparable coronal sulcus microbiota; however, by year 1, circumcision decreased the total bacterial load and reduced microbiota biodiversity. Specifically, the prevalence and absolute abundance of 12 anaerobic bacterial taxa decreased significantly in the circumcised men. While aerobic bacterial taxa also increased postcircumcision, these gains were minor. The reduction in anaerobes may partly account for the effects of circumcision on reduced HIV acquisition. The bacterial changes identified in this study may play an important role in the HIV risk reduction conferred by male circumcision. Decreasing the load of specific anaerobes could reduce HIV target cell recruitment to the foreskin. Understanding the mechanisms that underlie the benefits of male circumcision could help to identify new intervention strategies for decreasing HIV transmission, applicable to populations with high HIV prevalence where male circumcision is culturally less acceptable.

  7. A chimpanzee recognizes synthetic speech with significantly reduced acoustic cues to phonetic content.

    Science.gov (United States)

    Heimbauer, Lisa A; Beran, Michael J; Owren, Michael J

    2011-07-26

    A long-standing debate concerns whether humans are specialized for speech perception, which some researchers argue is demonstrated by the ability to understand synthetic speech with significantly reduced acoustic cues to phonetic content. We tested a chimpanzee (Pan troglodytes) that recognizes 128 spoken words, asking whether she could understand such speech. Three experiments presented 48 individual words, with the animal selecting a corresponding visuographic symbol from among four alternatives. Experiment 1 tested spectrally reduced, noise-vocoded (NV) synthesis, originally developed to simulate input received by human cochlear-implant users. Experiment 2 tested "impossibly unspeechlike" sine-wave (SW) synthesis, which reduces speech to just three moving tones. Although receiving only intermittent and noncontingent reward, the chimpanzee performed well above chance level, including when hearing synthetic versions for the first time. Recognition of SW words was least accurate but improved in experiment 3 when natural words in the same session were rewarded. The chimpanzee was more accurate with NV than SW versions, as were 32 human participants hearing these items. The chimpanzee's ability to spontaneously recognize acoustically reduced synthetic words suggests that experience rather than specialization is critical for speech-perception capabilities that some have suggested are uniquely human. Copyright © 2011 Elsevier Ltd. All rights reserved.

  8. Clinical significance of determination of levels of several cytokines (IL-1β, IL-2, IL-10 and TNF) in expressed prostatic fluid (EPS) from patients with various types of chronic prostatitis

    International Nuclear Information System (INIS)

    Gao Juxing; Zhang Jiyun

    2006-01-01

    Objective: To investigate the levels of several cytokines in EPS from patients with different types of chronic prostatitis. Methods: The EPS levels of IL-1β, IL-2, IL-10 and TNF were determined with RIA in 86 patients with various types of chronic prostatitis as well as in 30 controls. Results: The EPS levels of IL-1β, IL-2 and TNF in all the 86 patients with various types of chronic prostatitis were significantly higher than those in the controls (P 10/HP, lecithin body < + +) (n=31) were significantly higher than those in patients with CPPS IIIB (WRC < 10/HP, lecithin body normal, n=29)(P<0.05 or P<0.01 ), while the IL-10 levels were significantly lower (P<0.01). Conclusion: EPS levels of the cytokines IL-β, IL-2, TNF and IL-10 might be of value for diagnosis and classification of chronic prostatitis. (authors)

  9. Defibrillator charging before rhythm analysis significantly reduces hands-off time during resuscitation

    DEFF Research Database (Denmark)

    Hansen, L. K.; Folkestad, L.; Brabrand, M.

    2013-01-01

    BACKGROUND: Our objective was to reduce hands-off time during cardiopulmonary resuscitation as increased hands-off time leads to higher mortality. METHODS: The European Resuscitation Council (ERC) 2005 and ERC 2010 guidelines were compared with an alternative sequence (ALT). Pulseless ventricular...... physicians were included. All had prior experience in advanced life support. Chest compressions were shorter interrupted using ALT (mean, 6.7 vs 13.0 seconds). Analyzing data for ventricular tachycardia scenarios only, hands-off time was shorter using ALT (mean, 7.1 vs 18.2 seconds). In ERC 2010 vs ALT, 12...... physicians were included. Two physicians had not prior experience in advanced life support. Hands-off time was reduced using ALT (mean, 3.9 vs 5.6 seconds). Looking solely at ventricular tachycardia scenarios, hands-off time was shortened using ALT (mean, 4.5 vs 7.6 seconds). No significant reduction...

  10. "Curcumin-loaded Poly (d, l-lactide-co-glycolide) nanovesicles induce antinociceptive effects and reduce pronociceptive cytokine and BDNF release in spinal cord after acute administration in mice".

    Science.gov (United States)

    Pieretti, Stefano; Ranjan, Amalendu P; Di Giannuario, Amalia; Mukerjee, Anindita; Marzoli, Francesca; Di Giovannandrea, Rita; Vishwanatha, Jamboor K

    2017-10-01

    Given the poor bioavailability of curcumin, its antinociceptive effects are produced after chronic intravenous administration of high doses, while poly (d,l-lactide-co-glycolide)-loaded vesicles (PLGA) can improve drug delivery. This paper investigates the antinociceptive effects of curcumin-loaded PLGA nanovesicles (PLGA-CUR) administered via intravenous (i.v.) or intrathecal (i.t.) routes at low and high doses. The following models of pain were used: formalin test, zymosan-induced hyperalgesia and sciatic nerve ligation inducing neuropathic allodynia and hyperalgesia. PLGA-CUR administered intravenously was able to reduce the response to nociceptive stimuli in the formalin test and hyperalgesia induced by zymosan. Curcumin, instead, was inactive. Low-dose i.t. administration of PLGA-CUR significantly reduced allodynia produced by sciatic nerve ligation, whereas low doses of curcumin did not change the response to nociceptive stimuli. Long-lasting antinociceptive effects were observed when high doses of PLGA-CUR were administered intrathecally. At high doses, i.t. administration of curcumin only exerted rapid and transient antinociceptive effects. Measurement of cytokine and BDNF in the spinal cord of neuropathic mice demonstrate that the antinociceptive effects of PLGA-CUR depend on the reduction in cytokine release and BDNF in the spinal cord. The results demonstrate the effectiveness of PLGA-CUR and suggest that PLGA-CUR nanoformulation might be a new potential drug in the treatment of pain. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Reduced content of chloroatranol and atranol in oak moss absolute significantly reduces the elicitation potential of this fragrance material.

    Science.gov (United States)

    Andersen, Flemming; Andersen, Kirsten H; Bernois, Armand; Brault, Christophe; Bruze, Magnus; Eudes, Hervé; Gadras, Catherine; Signoret, Anne-Cécile J; Mose, Kristian F; Müller, Boris P; Toulemonde, Bernard; Andersen, Klaus Ejner

    2015-02-01

    Oak moss absolute, an extract from the lichen Evernia prunastri, is a valued perfume ingredient but contains extreme allergens. To compare the elicitation properties of two preparations of oak moss absolute: 'classic oak moss', the historically used preparation, and 'new oak moss', with reduced contents of the major allergens atranol and chloroatranol. The two preparations were compared in randomized double-blinded repeated open application tests and serial dilution patch tests in 30 oak moss-sensitive volunteers and 30 non-allergic control subjects. In both test models, new oak moss elicited significantly less allergic contact dermatitis in oak moss-sensitive subjects than classic oak moss. The control subjects did not react to either of the preparations. New oak moss is still a fragrance allergen, but elicits less allergic contact dermatitis in previously oak moss-sensitized individuals, suggesting that new oak moss is less allergenic to non-sensitized individuals. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. Dietary phytic acid modulates characteristics of the colonic luminal environment and reduces serum levels of proinflammatory cytokines in rats fed a high-fat diet.

    Science.gov (United States)

    Okazaki, Yukako; Katayama, Tetsuyuki

    2014-12-01

    Dietary phytic acid (PA; myo-inositol [MI] hexaphosphate) is known to inhibit colon carcinogenesis in rodents. Dietary fiber, which is a negative risk factor of colon cancer, improves characteristics of the colonic environment, such as the content of organic acids and microflora. We hypothesized that dietary PA would improve the colonic luminal environment in rats fed a high-fat diet. To test this hypothesis, rats were fed diets containing 30% beef tallow with 2.04% sodium PA, 0.4% MI, or 1.02% sodium PA + 0.2% MI for 3 weeks. Compared with the control diet, the sodium PA diet up-regulated cecal organic acids, including acetate, propionate, and n-butyrate; this effect was especially prominent for cecal butyrate. The sodium PA + MI diet also significantly increased cecal butyrate, although this effect was less pronounced when compared with the sodium PA diet. The cecal ratio of Lactobacillales, cecal and fecal mucins (an index of intestinal barrier function), and fecal β-glucosidase activity were higher in rats fed the sodium PA diet than in those fed the control diet. The sodium PA, MI, and sodium PA + MI diets decreased levels of serum tumor necrosis factor α, which is a proinflammatory cytokine. Another proinflammatory cytokine, serum interleukin-6, was also down-regulated by the sodium PA and sodium PA + MI diets. These data showed that PA may improve the composition of cecal organic acids, microflora, and mucins, and it may decrease the levels of serum proinflammatory cytokines in rats fed a high-fat, mineral-sufficient diet. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Kluyveromyces marxianus and Saccharomyces boulardii induce distinct levels of dendritic cell cytokine secretion and significantly different T cell responses In Vitro

    DEFF Research Database (Denmark)

    Smith, Ida Mosbech; Baker, Adam; Christensen, Jeffrey E

    2016-01-01

    induction of a Treg response characterized by robust IL-10 secretion. In addition, we blocked relevant DC surface receptors and investigated the stimulating properties of β-glucan containing yeast cell wall extracts. K. marxianus and S. boulardii induced distinct levels of DC cytokine secretion, primarily...... driven by Dectin-1 recognition of β-glucan components in their cell walls. Upon co-incubation of yeast exposed DCs and naive T cells, S. boulardii induced a potent IFNγ response indicating TH1 mobilization. In contrast, K. marxianus induced a response dominated by Foxp3+ Treg cells, a characteristic...... of the present study was to characterize the immune modulating properties of the food-related yeast Kluyveromyces marxianus in terms of adaptive immune responses indicating inflammation versus tolerance and to explore the mechanisms behind the observed responses. Benchmarking against a Saccharomyces boulardii...

  14. Four-phonon scattering significantly reduces intrinsic thermal conductivity of solids

    Science.gov (United States)

    Feng, Tianli; Lindsay, Lucas; Ruan, Xiulin

    2017-10-01

    For decades, the three-phonon scattering process has been considered to govern thermal transport in solids, while the role of higher-order four-phonon scattering has been persistently unclear and so ignored. However, recent quantitative calculations of three-phonon scattering have often shown a significant overestimation of thermal conductivity as compared to experimental values. In this Rapid Communication we show that four-phonon scattering is generally important in solids and can remedy such discrepancies. For silicon and diamond, the predicted thermal conductivity is reduced by 30% at 1000 K after including four-phonon scattering, bringing predictions in excellent agreement with measurements. For the projected ultrahigh-thermal conductivity material, zinc-blende BAs, a competitor of diamond as a heat sink material, four-phonon scattering is found to be strikingly strong as three-phonon processes have an extremely limited phase space for scattering. The four-phonon scattering reduces the predicted thermal conductivity from 2200 to 1400 W/m K at room temperature. The reduction at 1000 K is 60%. We also find that optical phonon scattering rates are largely affected, being important in applications such as phonon bottlenecks in equilibrating electronic excitations. Recognizing that four-phonon scattering is expensive to calculate, in the end we provide some guidelines on how to quickly assess the significance of four-phonon scattering, based on energy surface anharmonicity and the scattering phase space. Our work clears the decades-long fundamental question of the significance of higher-order scattering, and points out ways to improve thermoelectrics, thermal barrier coatings, nuclear materials, and radiative heat transfer.

  15. Incorporation of catalytic dehydrogenation into fischer-tropsch synthesis to significantly reduce carbon dioxide emissions

    Science.gov (United States)

    Huffman, Gerald P.

    2012-11-13

    A new method of producing liquid transportation fuels from coal and other hydrocarbons that significantly reduces carbon dioxide emissions by combining Fischer-Tropsch synthesis with catalytic dehydrogenation is claimed. Catalytic dehydrogenation (CDH) of the gaseous products (C1-C4) of Fischer-Tropsch synthesis (FTS) can produce large quantities of hydrogen while converting the carbon to multi-walled carbon nanotubes (MWCNT). Incorporation of CDH into a FTS-CDH plant converting coal to liquid fuels can eliminate all or most of the CO.sub.2 emissions from the water-gas shift (WGS) reaction that is currently used to elevate the H.sub.2 level of coal-derived syngas for FTS. Additionally, the FTS-CDH process saves large amounts of water used by the WGS reaction and produces a valuable by-product, MWCNT.

  16. Nano-CL-20/HMX Cocrystal Explosive for Significantly Reduced Mechanical Sensitivity

    Directory of Open Access Journals (Sweden)

    Chongwei An

    2017-01-01

    Full Text Available Spray drying method was used to prepare cocrystals of hexanitrohexaazaisowurtzitane (CL-20 and cyclotetramethylene tetranitramine (HMX. Raw materials and cocrystals were characterized using scanning electron microscopy, X-ray diffraction, differential scanning calorimetry, Raman spectroscopy, and Fourier transform infrared spectroscopy. Impact and friction sensitivity of cocrystals were tested and analyzed. Results show that, after preparation by spray drying method, microparticles were spherical in shape and 0.5–5 µm in size. Particles formed aggregates of numerous tiny plate-like cocrystals, whereas CL-20/HMX cocrystals had thicknesses of below 100 nm. Cocrystals were formed by C–H⋯O bonding between –NO2 (CL-20 and –CH2– (HMX. Nanococrystal explosives exhibited drop height of 47.3 cm, and friction demonstrated explosion probability of 64%. Compared with raw HMX, cocrystals displayed significantly reduced mechanical sensitivity.

  17. Implementation of standardized follow-up care significantly reduces peritonitis in children on chronic peritoneal dialysis.

    Science.gov (United States)

    Neu, Alicia M; Richardson, Troy; Lawlor, John; Stuart, Jayne; Newland, Jason; McAfee, Nancy; Warady, Bradley A

    2016-06-01

    The Standardizing Care to improve Outcomes in Pediatric End stage renal disease (SCOPE) Collaborative aims to reduce peritonitis rates in pediatric chronic peritoneal dialysis patients by increasing implementation of standardized care practices. To assess this, monthly care bundle compliance and annualized monthly peritonitis rates were evaluated from 24 SCOPE centers that were participating at collaborative launch and that provided peritonitis rates for the 13 months prior to launch. Changes in bundle compliance were assessed using either a logistic regression model or a generalized linear mixed model. Changes in average annualized peritonitis rates over time were illustrated using the latter model. In the first 36 months of the collaborative, 644 patients with 7977 follow-up encounters were included. The likelihood of compliance with follow-up care practices increased significantly (odds ratio 1.15, 95% confidence interval 1.10, 1.19). Mean monthly peritonitis rates significantly decreased from 0.63 episodes per patient year (95% confidence interval 0.43, 0.92) prelaunch to 0.42 (95% confidence interval 0.31, 0.57) at 36 months postlaunch. A sensitivity analysis confirmed that as mean follow-up compliance increased, peritonitis rates decreased, reaching statistical significance at 80% at which point the prelaunch rate was 42% higher than the rate in the months following achievement of 80% compliance. In its first 3 years, the SCOPE Collaborative has increased the implementation of standardized follow-up care and demonstrated a significant reduction in average monthly peritonitis rates. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  18. Intensity-modulated radiotherapy significantly reduces xerostomia compared with conventional radiotherapy

    International Nuclear Information System (INIS)

    Braam, Petra M.; Terhaard, Chris H.J. M.D.; Roesink, Judith M.; Raaijmakers, Cornelis P.J.

    2006-01-01

    Purpose: Xerostomia is a severe complication after radiotherapy for oropharyngeal cancer, as the salivary glands are in close proximity with the primary tumor. Intensity-modulated radiotherapy (IMRT) offers theoretical advantages for normal tissue sparing. A Phase II study was conducted to determine the value of IMRT for salivary output preservation compared with conventional radiotherapy (CRT). Methods and Materials: A total of 56 patients with oropharyngeal cancer were prospectively evaluated. Of these, 30 patients were treated with IMRT and 26 with CRT. Stimulated parotid salivary flow was measured before, 6 weeks, and 6 months after treatment. A complication was defined as a stimulated parotid flow rate <25% of the preradiotherapy flow rate. Results: The mean dose to the parotid glands was 48.1 Gy (SD 14 Gy) for CRT and 33.7 Gy (SD 10 Gy) for IMRT (p < 0.005). The mean parotid flow ratio 6 weeks and 6 months after treatment was respectively 41% and 64% for IMRT and respectively 11% and 18% for CRT. As a result, 6 weeks after treatment, the number of parotid flow complications was significantly lower after IMRT (55%) than after CRT (87%) (p = 0.002). The number of complications 6 months after treatment was 56% for IMRT and 81% for CRT (p = 0.04). Conclusions: IMRT significantly reduces the number of parotid flow complications for patients with oropharyngeal cancer

  19. Induction-heating MOCVD reactor with significantly improved heating efficiency and reduced harmful magnetic coupling

    KAUST Repository

    Li, Kuang-Hui; Alotaibi, Hamad S.; Sun, Haiding; Lin, Ronghui; Guo, Wenzhe; Torres-Castanedo, Carlos G.; Liu, Kaikai; Galan, Sergio V.; Li, Xiaohang

    2018-01-01

    In a conventional induction-heating III-nitride metalorganic chemical vapor deposition (MOCVD) reactor, the induction coil is outside the chamber. Therefore, the magnetic field does not couple with the susceptor well, leading to compromised heating efficiency and harmful coupling with the gas inlet and thus possible overheating. Hence, the gas inlet has to be at a minimum distance away from the susceptor. Because of the elongated flow path, premature reactions can be more severe, particularly between Al- and B-containing precursors and NH3. Here, we propose a structure that can significantly improve the heating efficiency and allow the gas inlet to be closer to the susceptor. Specifically, the induction coil is designed to surround the vertical cylinder of a T-shaped susceptor comprising the cylinder and a top horizontal plate holding the wafer substrate within the reactor. Therefore, the cylinder coupled most magnetic field to serve as the thermal source for the plate. Furthermore, the plate can block and thus significantly reduce the uncoupled magnetic field above the susceptor, thereby allowing the gas inlet to be closer. The results show approximately 140% and 2.6 times increase in the heating and susceptor coupling efficiencies, respectively, as well as a 90% reduction in the harmful magnetic flux on the gas inlet.

  20. Induction-heating MOCVD reactor with significantly improved heating efficiency and reduced harmful magnetic coupling

    KAUST Repository

    Li, Kuang-Hui

    2018-02-23

    In a conventional induction-heating III-nitride metalorganic chemical vapor deposition (MOCVD) reactor, the induction coil is outside the chamber. Therefore, the magnetic field does not couple with the susceptor well, leading to compromised heating efficiency and harmful coupling with the gas inlet and thus possible overheating. Hence, the gas inlet has to be at a minimum distance away from the susceptor. Because of the elongated flow path, premature reactions can be more severe, particularly between Al- and B-containing precursors and NH3. Here, we propose a structure that can significantly improve the heating efficiency and allow the gas inlet to be closer to the susceptor. Specifically, the induction coil is designed to surround the vertical cylinder of a T-shaped susceptor comprising the cylinder and a top horizontal plate holding the wafer substrate within the reactor. Therefore, the cylinder coupled most magnetic field to serve as the thermal source for the plate. Furthermore, the plate can block and thus significantly reduce the uncoupled magnetic field above the susceptor, thereby allowing the gas inlet to be closer. The results show approximately 140% and 2.6 times increase in the heating and susceptor coupling efficiencies, respectively, as well as a 90% reduction in the harmful magnetic flux on the gas inlet.

  1. Excreted/secreted Trichuris suis products reduce barrier function and suppress inflammatory cytokine production of intestinal epithelial cells

    DEFF Research Database (Denmark)

    Hiemstra, I. H.; Klaver, E. J.; Vrijland, K.

    2014-01-01

    The administration of helminths is considered a promising strategy for the treatment of autoimmune diseases due to their immunomodulatory properties. Currently, the application of the helminth Trichuris suis as a treatment for Crohn's disease is being studied in large multi-center clinical trials....... The intestinal epithelium forms an efficient barrier between the intestinal lumen containing the microbial flora and helminths, and dendritic cells (DCs) present in the lamina propria that determine the TH response. Here, we investigated how excreted/secreted (E/S) products of T. suis affect the barrier function...... of intestinal epithelial cells (IECs) in order to reach the DCs and modulate the immune response. We show that T. suis E/S products reduce the barrier function and the expression of the tight junction proteins EMP-1 and claudin-4 in IEC CMT93/69 monolayers in a glycan-dependent manner. This resulted...

  2. Using lytic bacteriophages to eliminate or significantly reduce contamination of food by foodborne bacterial pathogens.

    Science.gov (United States)

    Sulakvelidze, Alexander

    2013-10-01

    Bacteriophages (also called 'phages') are viruses that kill bacteria. They are arguably the oldest (3 billion years old, by some estimates) and most ubiquitous (total number estimated to be 10(30) -10(32) ) known organisms on Earth. Phages play a key role in maintaining microbial balance in every ecosystem where bacteria exist, and they are part of the normal microflora of all fresh, unprocessed foods. Interest in various practical applications of bacteriophages has been gaining momentum recently, with perhaps the most attention focused on using them to improve food safety. That approach, called 'phage biocontrol', typically includes three main types of applications: (i) using phages to treat domesticated livestock in order to reduce their intestinal colonization with, and shedding of, specific bacterial pathogens; (ii) treatments for decontaminating inanimate surfaces in food-processing facilities and other food establishments, so that foods processed on those surfaces are not cross-contaminated with the targeted pathogens; and (iii) post-harvest treatments involving direct applications of phages onto the harvested foods. This mini-review primarily focuses on the last type of intervention, which has been gaining the most momentum recently. Indeed, the results of recent studies dealing with improving food safety, and several recent regulatory approvals of various commercial phage preparations developed for post-harvest food safety applications, strongly support the idea that lytic phages may provide a safe, environmentally-friendly, and effective approach for significantly reducing contamination of various foods with foodborne bacterial pathogens. However, some important technical and nontechnical problems may need to be addressed before phage biocontrol protocols can become an integral part of routine food safety intervention strategies implemented by food industries in the USA. © 2013 Society of Chemical Industry.

  3. Pharmacological kynurenine 3-monooxygenase enzyme inhibition significantly reduces neuropathic pain in a rat model.

    Science.gov (United States)

    Rojewska, Ewelina; Piotrowska, Anna; Makuch, Wioletta; Przewlocka, Barbara; Mika, Joanna

    2016-03-01

    Recent studies have highlighted the involvement of the kynurenine pathway in the pathology of neurodegenerative diseases, but the role of this system in neuropathic pain requires further extensive research. Therefore, the aim of our study was to examine the role of kynurenine 3-monooxygenase (Kmo), an enzyme that is important in this pathway, in a rat model of neuropathy after chronic constriction injury (CCI) to the sciatic nerve. For the first time, we demonstrated that the injury-induced increase in the Kmo mRNA levels in the spinal cord and the dorsal root ganglia (DRG) was reduced by chronic administration of the microglial inhibitor minocycline and that this effect paralleled a decrease in the intensity of neuropathy. Further, minocycline administration alleviated the lipopolysaccharide (LPS)-induced upregulation of Kmo mRNA expression in microglial cell cultures. Moreover, we demonstrated that not only indirect inhibition of Kmo using minocycline but also direct inhibition using Kmo inhibitors (Ro61-6048 and JM6) decreased neuropathic pain intensity on the third and the seventh days after CCI. Chronic Ro61-6048 administration diminished the protein levels of IBA-1, IL-6, IL-1beta and NOS2 in the spinal cord and/or the DRG. Both Kmo inhibitors potentiated the analgesic properties of morphine. In summary, our data suggest that in neuropathic pain model, inhibiting Kmo function significantly reduces pain symptoms and enhances the effectiveness of morphine. The results of our studies show that the kynurenine pathway is an important mediator of neuropathic pain pathology and indicate that Kmo represents a novel pharmacological target for the treatment of neuropathy. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Intriguing model significantly reduces boarding of psychiatric patients, need for inpatient hospitalization.

    Science.gov (United States)

    2015-01-01

    As new approaches to the care of psychiatric emergencies emerge, one solution is gaining particular traction. Under the Alameda model, which has been put into practice in Alameda County, CA, patients who are brought to regional EDs with emergency psychiatric issues are quickly transferred to a designated emergency psychiatric facility as soon as they are medically stabilized. This alleviates boarding problems in area EDs while also quickly connecting patients with specialized care. With data in hand on the model's effectiveness, developers believe the approach could alleviate boarding problems in other communities as well. The model is funded by through a billing code established by California's Medicaid program for crisis stabilization services. Currently, only 22% of the patients brought to the emergency psychiatric facility ultimately need to be hospitalized; the other 78% are able to go home or to an alternative situation. In a 30-day study of the model, involving five community hospitals in Alameda County, CA, researchers found that ED boarding times were as much as 80% lower than comparable ED averages, and that patients were stabilized at least 75% of the time, significantly reducing the need for inpatient hospitalization.

  5. Significantly reduced hypoxemic events in morbidly obese patients undergoing gastrointestinal endoscopy: Predictors and practice effect

    Directory of Open Access Journals (Sweden)

    Basavana Gouda Goudra

    2014-01-01

    Full Text Available Background: Providing anesthesia for gastrointestinal (GI endoscopy procedures in morbidly obese patients is a challenge for a variety of reasons. The negative impact of obesity on the respiratory system combined with a need to share the upper airway and necessity to preserve the spontaneous ventilation, together add to difficulties. Materials and Methods: This retrospective cohort study included patients with a body mass index (BMI >40 kg/m 2 that underwent out-patient GI endoscopy between September 2010 and February 2011. Patient data was analyzed for procedure, airway management technique as well as hypoxemic and cardiovascular events. Results: A total of 119 patients met the inclusion criteria. Our innovative airway management technique resulted in a lower rate of intraoperative hypoxemic events compared with any published data available. Frequency of desaturation episodes showed statistically significant relation to previous history of obstructive sleep apnea (OSA. These desaturation episodes were found to be statistically independent of increasing BMI of patients. Conclusion: Pre-operative history of OSA irrespective of associated BMI values can be potentially used as a predictor of intra-procedural desaturation. With suitable modification of anesthesia technique, it is possible to reduce the incidence of adverse respiratory events in morbidly obese patients undergoing GI endoscopy procedures, thereby avoiding the need for endotracheal intubation.

  6. Significantly reduced hypoxemic events in morbidly obese patients undergoing gastrointestinal endoscopy: Predictors and practice effect.

    Science.gov (United States)

    Goudra, Basavana Gouda; Singh, Preet Mohinder; Penugonda, Lakshmi C; Speck, Rebecca M; Sinha, Ashish C

    2014-01-01

    Providing anesthesia for gastrointestinal (GI) endoscopy procedures in morbidly obese patients is a challenge for a variety of reasons. The negative impact of obesity on the respiratory system combined with a need to share the upper airway and necessity to preserve the spontaneous ventilation, together add to difficulties. This retrospective cohort study included patients with a body mass index (BMI) >40 kg/m(2) that underwent out-patient GI endoscopy between September 2010 and February 2011. Patient data was analyzed for procedure, airway management technique as well as hypoxemic and cardiovascular events. A total of 119 patients met the inclusion criteria. Our innovative airway management technique resulted in a lower rate of intraoperative hypoxemic events compared with any published data available. Frequency of desaturation episodes showed statistically significant relation to previous history of obstructive sleep apnea (OSA). These desaturation episodes were found to be statistically independent of increasing BMI of patients. Pre-operative history of OSA irrespective of associated BMI values can be potentially used as a predictor of intra-procedural desaturation. With suitable modification of anesthesia technique, it is possible to reduce the incidence of adverse respiratory events in morbidly obese patients undergoing GI endoscopy procedures, thereby avoiding the need for endotracheal intubation.

  7. Limonene reduces hyperalgesia induced by gp120 and cytokines by modulation of IL-1 β and protein expression in spinal cord of mice.

    Science.gov (United States)

    Piccinelli, Ana Claudia; Morato, Priscila Neder; Dos Santos Barbosa, Marcelo; Croda, Julio; Sampson, Jared; Kong, Xiangpeng; Konkiewitz, Elisabete Castelon; Ziff, Edward B; Amaya-Farfan, Jaime; Kassuya, Cândida Aparecida Leite

    2017-04-01

    We have investigated the antihyperalgesic effects of limonene in mice that received intrathecal injection of gp120. Male Swiss mice received gp120, IL-1β or TNF-α intrathecally or sterile saline as a control. A mechanical sensitivity test was performed at 2 and 3h after the injection. Spinal cord and blood samples were isolated for protein quantification. Intrathecal administration of gp120 increased mechanical sensitivity measured with an electronic Von Frey apparatus, at 2 and 3h after the injections. Limonene administered orally prior to gp120 administration significantly decreased this mechanical sensitivity at 3h after the gp120 injection. In addition, intrathecal injection of gp120 increased IL-1β and IL-10 in serum, and limonene prevented the ability of gp120 to increase these cytokines. Limonene also inhibited TNF-α and IL-1β-induced mechanical hyperalgesia. Western blot assay demonstrated limonene was capable of increasing SOD expression in the cytoplasm of cells from spinal cord at 4h after intrathecal IL-1β injection. These results demonstrate that gp120 causes mechanical hyperalgesia and a peripheral increase in IL-1β and IL-10, and that prior administration of limonene inhibits these changes. Also limonene modulates the activation of SOD expression in the spinal cord after spinal IL-1β application. The ability of limonene to inhibit the mechanical hyperalgesia induced by gp120, TNF-α and IL-1β emphasizes the anti-inflammatory action of limonene, specifically its ability to inhibit cytokine production and its consequences. Copyright © 2016. Published by Elsevier Inc.

  8. Regulation of human cytokines by Cordyceps militaris.

    Science.gov (United States)

    Sun, Yong; Shao, Yani; Zhang, Zhiguo; Wang, Lianfen; Mariga, Alfred M; Pang, Guangchang; Geng, Chaoyu; Ho, Chi-Tang; Hu, Qiuhui; Zhao, Liyan

    2014-12-01

    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. Copyright © 2014. Published by Elsevier B.V.

  9. 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.

  10. Environmental program with operational cases to reduce risk to the marine environment significantly

    International Nuclear Information System (INIS)

    Cline, J.T.; Forde, R.

    1991-01-01

    In this paper Amoco Norway Oil Company's environmental program is detailed, followed by example operational programs and achievements aimed to minimize environmental risks to the marine environment at Valhall platform. With a corporate goal to be a leader in protecting the environment, the appropriate strategies and policies that form the basis of the environmental management system are incorporated in the quality assurance programs. Also, included in the program are necessary organizational structures, responsibilities of environmental affairs and line organization personnel, compliance procedures and a waste task force obliged to implement operations improvements. An internal environmental audit system has been initiated, in addition to corporate level audits, which, when communicated to the line organization closes the environmental management loop through experience feed back. Environmental projects underway are significantly decreasing the extent and/or risk of pollution from offshore activities. The cradle to grave responsibility is assumed with waste separated offshore and onshore followed by disposal in audited sites. A $5 MM program is underway to control produced oily solids and reduce oil in produced water aiming to less than 20 ppm. When oil-based mud is used in deeper hole sections, drill solids disposed at sea average less than 60 g oil/kg dry cuttings using appropriate shaker screens, and a washing/centrifuge system to remove fines. Certain oily liquid wastes are being injected down hole whereas previously they were burned using a mud burner. Finally, a program is underway with a goal to eliminate sea discharge of oil on cuttings through injection disposal of oily wastes, drilling with alternative muds such as a cationic water base mud, and/or proper onshore disposal of oily wastes

  11. Simultaneous bilateral stereotactic procedure for deep brain stimulation implants: a significant step for reducing operation time.

    Science.gov (United States)

    Fonoff, Erich Talamoni; Azevedo, Angelo; Angelos, Jairo Silva Dos; Martinez, Raquel Chacon Ruiz; Navarro, Jessie; Reis, Paul Rodrigo; Sepulveda, Miguel Ernesto San Martin; Cury, Rubens Gisbert; Ghilardi, Maria Gabriela Dos Santos; Teixeira, Manoel Jacobsen; Lopez, William Omar Contreras

    2016-07-01

    OBJECT Currently, bilateral procedures involve 2 sequential implants in each of the hemispheres. The present report demonstrates the feasibility of simultaneous bilateral procedures during the implantation of deep brain stimulation (DBS) leads. METHODS Fifty-seven patients with movement disorders underwent bilateral DBS implantation in the same study period. The authors compared the time required for the surgical implantation of deep brain electrodes in 2 randomly assigned groups. One group of 28 patients underwent traditional sequential electrode implantation, and the other 29 patients underwent simultaneous bilateral implantation. Clinical outcomes of the patients with Parkinson's disease (PD) who had undergone DBS implantation of the subthalamic nucleus using either of the 2 techniques were compared. RESULTS Overall, a reduction of 38.51% in total operating time for the simultaneous bilateral group (136.4 ± 20.93 minutes) as compared with that for the traditional consecutive approach (220.3 ± 27.58 minutes) was observed. Regarding clinical outcomes in the PD patients who underwent subthalamic nucleus DBS implantation, comparing the preoperative off-medication condition with the off-medication/on-stimulation condition 1 year after the surgery in both procedure groups, there was a mean 47.8% ± 9.5% improvement in the Unified Parkinson's Disease Rating Scale Part III (UPDRS-III) score in the simultaneous group, while the sequential group experienced 47.5% ± 15.8% improvement (p = 0.96). Moreover, a marked reduction in the levodopa-equivalent dose from preoperatively to postoperatively was similar in these 2 groups. The simultaneous bilateral procedure presented major advantages over the traditional sequential approach, with a shorter total operating time. CONCLUSIONS A simultaneous stereotactic approach significantly reduces the operation time in bilateral DBS procedures, resulting in decreased microrecording time, contributing to the optimization of functional

  12. A High-Fat Diet Containing Lard Accelerates Prostate Cancer Progression and Reduces Survival Rate in Mice: Possible Contribution of Adipose Tissue-Derived Cytokines

    Directory of Open Access Journals (Sweden)

    Han Jin Cho

    2015-04-01

    Full Text Available To examine the effects of high-fat diet (HFD containing lard on prostate cancer development and progression and its underlying mechanisms, transgenic adenocarcinoma mouse prostate (TRAMP and TRAMP-C2 allograft models, as well as in vitro culture models, were employed. In TRAMP mice, HFD feeding increased the incidence of poorly differentiated carcinoma and decreased that of prostatic intraepithelial neoplasia in the dorsolateral lobes of the prostate, which was accompanied by increased expression of proteins associated with proliferation and angiogenesis. HFD feeding also led to increased metastasis and decreased survival rate in TRAMP mice. In the allograft model, HFD increased solid tumor growth, the expression of proteins related to proliferation/angiogenesis, the number of lipid vacuoles in tumor tissues, and levels of several cytokines in serum and adipose tissue. In vitro results revealed that adipose tissue-conditioned media from HFD-fed mice stimulated the proliferation and migration of prostate cancer cells and angiogenesis compared to those from control-diet-fed mice. These results indicate that the increase of adipose tissue-derived soluble factors by HFD feeding plays a role in the growth and metastasis of prostate cancer via endocrine and paracrine mechanisms. These results provide evidence that a HFD containing lard increases prostate cancer development and progression, thereby reducing the survival rate.

  13. Soil nitrate reducing processes drivers, mechanisms for spatial variation, and significance for nitrous oxide production

    OpenAIRE

    Giles, M.; Morley, N.; Baggs, E.M.; Daniell, T.J.

    2012-01-01

    The microbial processes of denitrification and dissimilatory nitrate reduction to ammonium\\ud (DNRA) are two important nitrate reducing mechanisms in soil, which are responsible for\\ud the loss of nitrate (NO−\\ud 3 ) and production of the potent greenhouse gas, nitrous oxide (N2O).\\ud A number of factors are known to control these processes, including O2 concentrations and\\ud moisture content, N, C, pH, and the size and community structure of nitrate reducing organisms\\ud responsible for the ...

  14. Pegasus project. DLC coating and low viscosity oil reduce energy losses significantly

    Energy Technology Data Exchange (ETDEWEB)

    Doerwald, Dave; Jacobs, Ruud [Hauzer Techno Coating (Netherlands). Tribological Coatings

    2012-03-15

    Pegasus, the flying horse from Greek mythology, is a suitable name for the research project initiated by a German automotive OEM with participation of Hauzer Techno Coating and several automotive suppliers. It will enable future automotive vehicles to reduce fuel consumption without losing power. The project described in this article focuses on the rear differential, because reducing friction here can contribute considerably to efficiency improvement of the whole vehicle. Surfaces, coating and oil viscosity have been investigated and interesting conclusions have been reached. (orig.)

  15. Mindfulness significantly reduces self-reported levels of anxiety and depression

    DEFF Research Database (Denmark)

    Würtzen, Hanne; Dalton, Susanne Oksbjerg; Elsass, Peter

    2013-01-01

    INTRODUCTION: As the incidence of and survival from breast cancer continue to raise, interventions to reduce anxiety and depression before, during and after treatment are needed. Previous studies have reported positive effects of a structured 8-week group mindfulness-based stress reduction program...

  16. Soil nitrate reducing processes – drivers, mechanisms for spatial variation, and significance for nitrous oxide production

    Science.gov (United States)

    Giles, Madeline; Morley, Nicholas; Baggs, Elizabeth M.; Daniell, Tim J.

    2012-01-01

    The microbial processes of denitrification and dissimilatory nitrate reduction to ammonium (DNRA) are two important nitrate reducing mechanisms in soil, which are responsible for the loss of nitrate (NO3−) and production of the potent greenhouse gas, nitrous oxide (N2O). A number of factors are known to control these processes, including O2 concentrations and moisture content, N, C, pH, and the size and community structure of nitrate reducing organisms responsible for the processes. There is an increasing understanding associated with many of these controls on flux through the nitrogen cycle in soil systems. However, there remains uncertainty about how the nitrate reducing communities are linked to environmental variables and the flux of products from these processes. The high spatial variability of environmental controls and microbial communities across small sub centimeter areas of soil may prove to be critical in determining why an understanding of the links between biotic and abiotic controls has proved elusive. This spatial effect is often overlooked as a driver of nitrate reducing processes. An increased knowledge of the effects of spatial heterogeneity in soil on nitrate reduction processes will be fundamental in understanding the drivers, location, and potential for N2O production from soils. PMID:23264770

  17. Soil nitrate reducing processes – drivers, mechanisms for spatial variation and significance for nitrous oxide production

    Directory of Open Access Journals (Sweden)

    Madeline Eleanore Giles

    2012-12-01

    Full Text Available The microbial processes of denitrification and dissimilatory nitrate reduction to ammonium (DNRA are two important nitrate reducing mechanisms in soil, which are responsible for the loss of nitrate (NO3-¬ and production of the potent greenhouse gas, nitrous oxide (N2O. A number of factors are known to control these processes, including O2 concentrations and moisture content, N, C, pH and the size and community structure of nitrate reducing organisms responsible for the processes. There is an increasing understanding associated with many of these controls on flux through the nitrogen cycle in soil systems. However, there remains uncertainty about how the nitrate reducing communities are linked to environmental variables and the flux of products from these processes. The high spatial variability of environmental controls and microbial communities across small sub cm areas of soil may prove to be critical in determining why an understanding of the links between biotic and abiotic controls has proved elusive. This spatial effect is often overlooked as a driver of nitrate reducing processes. An increased knowledge of the effects of spatial heterogeneity in soil on nitrate reduction processes will be fundamental in understanding the drivers, location and potential for N2O production from soils.

  18. Soil nitrate reducing processes - drivers, mechanisms for spatial variation, and significance for nitrous oxide production.

    Science.gov (United States)

    Giles, Madeline; Morley, Nicholas; Baggs, Elizabeth M; Daniell, Tim J

    2012-01-01

    The microbial processes of denitrification and dissimilatory nitrate reduction to ammonium (DNRA) are two important nitrate reducing mechanisms in soil, which are responsible for the loss of nitrate ([Formula: see text]) and production of the potent greenhouse gas, nitrous oxide (N(2)O). A number of factors are known to control these processes, including O(2) concentrations and moisture content, N, C, pH, and the size and community structure of nitrate reducing organisms responsible for the processes. There is an increasing understanding associated with many of these controls on flux through the nitrogen cycle in soil systems. However, there remains uncertainty about how the nitrate reducing communities are linked to environmental variables and the flux of products from these processes. The high spatial variability of environmental controls and microbial communities across small sub centimeter areas of soil may prove to be critical in determining why an understanding of the links between biotic and abiotic controls has proved elusive. This spatial effect is often overlooked as a driver of nitrate reducing processes. An increased knowledge of the effects of spatial heterogeneity in soil on nitrate reduction processes will be fundamental in understanding the drivers, location, and potential for N(2)O production from soils.

  19. Kluyveromyces marxianus and Saccharomyces boulardii Induce Distinct Levels of Dendritic Cell Cytokine Secretion and Significantly Different T Cell Responses In Vitro

    NARCIS (Netherlands)

    Smith, Ida M; Baker, Adam; Christensen, Jeffrey E; Boekhout, Teun; Frøkiær, Hanne; Arneborg, Nils; Jespersen, Lene

    2016-01-01

    Interactions between members of the intestinal microbiota and the mucosal immune system can significantly impact human health, and in this context, fungi and food-related yeasts are known to influence intestinal inflammation through direct interactions with specialized immune cells in vivo. The aim

  20. Reducing dysfunctional beliefs about sleep does not significantly improve insomnia in cognitive behavioral therapy.

    Science.gov (United States)

    Okajima, Isa; Nakajima, Shun; Ochi, Moeko; Inoue, Yuichi

    2014-01-01

    The present study examined to examine whether improvement of insomnia is mediated by a reduction in sleep-related dysfunctional beliefs through cognitive behavioral therapy for insomnia. In total, 64 patients with chronic insomnia received cognitive behavioral therapy for insomnia consisting of 6 biweekly individual treatment sessions of 50 minutes in length. Participants were asked to complete the Athens Insomnia Scale and the Dysfunctional Beliefs and Attitudes about Sleep scale both at the baseline and at the end of treatment. The results showed that although cognitive behavioral therapy for insomnia greatly reduced individuals' scores on both scales, the decrease in dysfunctional beliefs and attitudes about sleep with treatment did not seem to mediate improvement in insomnia. The findings suggest that sleep-related dysfunctional beliefs endorsed by patients with chronic insomnia may be attenuated by cognitive behavioral therapy for insomnia, but changes in such beliefs are not likely to play a crucial role in reducing the severity of insomnia.

  1. Gliovascular and cytokine interactions modulate brain endothelial barrier in vitro.

    Science.gov (United States)

    Chaitanya, Ganta V; Cromer, Walter E; Wells, Shannon R; Jennings, Merilyn H; Couraud, P Olivier; Romero, Ignacio A; Weksler, Babette; Erdreich-Epstein, Anat; Mathis, J Michael; Minagar, Alireza; Alexander, J Steven

    2011-11-23

    The glio-vascular unit (G-unit) plays a prominent role in maintaining homeostasis of the blood-brain barrier (BBB) and disturbances in cells forming this unit may seriously dysregulate BBB. The direct and indirect effects of cytokines on cellular components of the BBB are not yet unclear. The present study compares the effects of cytokines and cytokine-treated astrocytes on brain endothelial barrier. 3-dimensional transwell co-cultures of brain endothelium and related-barrier forming cells with astrocytes were used to investigate gliovascular barrier responses to cytokines during pathological stresses. Gliovascular barrier was measured using trans-endothelial electrical resistance (TEER), a sensitive index of in vitro barrier integrity. We found that neither TNF-α, IL-1β or IFN-γ directly reduced barrier in human or mouse brain endothelial cells or ECV-304 barrier (independent of cell viability/metabolism), but found that astrocyte exposure to cytokines in co-culture significantly reduced endothelial (and ECV-304) barrier. These results indicate that the barrier established by human and mouse brain endothelial cells (and other cells) may respond positively to cytokines alone, but that during pathological conditions, cytokines dysregulate the barrier forming cells indirectly through astrocyte activation involving reorganization of junctions, matrix, focal adhesion or release of barrier modulating factors (e.g. oxidants, MMPs). © 2011 Chaitanya et al; licensee BioMed Central Ltd.

  2. The Evolution of Polymer Composition during PHA Accumulation: The Significance of Reducing Equivalents

    Directory of Open Access Journals (Sweden)

    Liliana Montano-Herrera

    2017-03-01

    Full Text Available This paper presents a systematic investigation into monomer development during mixed culture Polyhydroxyalkanoates (PHA accumulation involving concurrent active biomass growth and polymer storage. A series of mixed culture PHA accumulation experiments, using several different substrate-feeding strategies, was carried out. The feedstock comprised volatile fatty acids, which were applied as single carbon sources, as mixtures, or in series, using a fed-batch feed-on-demand controlled bioprocess. A dynamic trend in active biomass growth as well as polymer composition was observed. The observations were consistent over replicate accumulations. Metabolic flux analysis (MFA was used to investigate metabolic activity through time. It was concluded that carbon flux, and consequently copolymer composition, could be linked with how reducing equivalents are generated.

  3. Significantly reduced c-axis thermal diffusivity of graphene-based papers

    Science.gov (United States)

    Han, Meng; Xie, Yangsu; Liu, Jing; Zhang, Jingchao; Wang, Xinwei

    2018-06-01

    Owing to their very high thermal conductivity as well as large surface-to-volume ratio, graphene-based films/papers have been proposed as promising candidates of lightweight thermal interface materials and lateral heat spreaders. In this work, we study the cross-plane (c-axis) thermal conductivity (k c ) and diffusivity (α c ) of two typical graphene-based papers, which are partially reduced graphene paper (PRGP) and graphene oxide paper (GOP), and compare their thermal properties with highly-reduced graphene paper and graphite. The determined α c of PRGP varies from (1.02 ± 0.09) × 10‑7 m2 s‑1 at 295 K to (2.31 ± 0.18) × 10‑7 m2 s‑1 at 12 K. This low α c is mainly attributed to the strong phonon scattering at the grain boundaries and defect centers due to the small grain sizes and high-level defects. For GOP, α c varies from (1.52 ± 0.05) × 10‑7 m2 s‑1 at 295 K to (2.28 ± 0.08) × 10‑7 m2 s‑1 at 12.5 K. The cross-plane thermal transport of GOP is attributed to the high density of functional groups between carbon layers which provide weak thermal transport tunnels across the layers in the absence of direct energy coupling among layers. This work sheds light on the understanding and optimizing of nanostructure of graphene-based paper-like materials for desired thermal performance.

  4. Bovine leukemia virus reduces anti-viral cytokine activities and NK cytotoxicity by inducing TGF-β secretion from regulatory T cells.

    Science.gov (United States)

    Ohira, Kosuke; Nakahara, Ayako; Konnai, Satoru; Okagawa, Tomohiro; Nishimori, Asami; Maekawa, Naoya; Ikebuchi, Ryoyo; Kohara, Junko; Murata, Shiro; Ohashi, Kazuhiko

    2016-03-01

    CD4(+)CD25(high)Foxp3(+) T cells suppress excess immune responses that lead to autoimmune and/or inflammatory diseases, and maintain host immune homeostasis. However, CD4(+)CD25(high)Foxp3(+) T cells reportedly contribute to disease progression by over suppressing immune responses in some chronic infections. In this study, kinetic and functional analyses of CD4(+)CD25(high)Foxp3(+) T cells were performed in cattle with bovine leukemia virus (BLV) infections, which have reported immunosuppressive characteristics. In initial experiments, production of the Th1 cytokines IFN-γ and TNF-α was reduced in BLV-infected cattle compared with uninfected cattle, and numbers of IFN-γ or TNF-α producing CD4(+) T cells decreased with disease progression. In contrast, IFN-γ production by NK cells was inversely correlated with BLV proviral loads in infected cattle. Additionally, during persistent lymphocytosis disease stages, NK cytotoxicity was depressed as indicated by low expression of the cytolytic protein perforin. Concomitantly, total CD4(+)CD25(high)Foxp3(+) T cell numbers and percentages of TGF-β(+) cells were increased, suggesting that TGF-β plays a role in the functional declines of CD4(+) T cells and NK cells. In further experiments, recombinant bovine TGF-β suppressed IFN-γ and TNF-α production by CD4(+) T cells and NK cytotoxicity in cultured cells. These data suggest that TGF-β from CD4(+)CD25(high)Foxp3(+) T cells is immunosuppressive and contributes to disease progression and the development of opportunistic infections during BLV infection.

  5. Technological significances to reduce the material problems. Feasibility of heat flux reduction

    International Nuclear Information System (INIS)

    Yamazaki, Seiichiro; Shimada, Michiya.

    1994-01-01

    For a divertor plate in a fusion power reactor, a high temperature coolant must be used for heat removal to keep thermal efficiency high. It makes the temperature and thermal stress of wall materials higher than the design limits. Issues of the coolant itself, e.g. burnout of high temperature water, will also become a serious problem. Sputtering erosion of the surface material will be a great concern of its lifetime. Therefore, it is necessary to reduce the heat and particle loads to the divertor plate technologically. The feasibility of some technological methods of heat reduction, such as separatrix sweeping, is discussed. As one of the most promising ideas, the methods of radiative cooling of the divertor plasma are summarized based on the recent results of large tokamaks. The feasibility of remote radiative cooling and gas divertor is discussed. The ideas are considered in recent design studies of tokamak power reactors and experimental reactors. By way of example, conceptual designs of divertor plate for the steady state tokamak power reactor are described. (author)

  6. Cytokine production and visualized effects in the feto-maternal unit. Quantitative and topographic data on cytokines during intrauterine disease.

    Science.gov (United States)

    Stallmach, T; Hebisch, G; Joller-Jemelka, H I; Orban, P; Schwaller, J; Engelmann, M

    1995-09-01

    A large array of cytokines show high activity in amniotic fluid. Attempts have been made to quantify the concentrations or to track rising levels for diagnostic purposes when examining disturbances of the feto-maternal unit. However, the kinetics of cytokine production in the amniotic fluid are not well understood, and there is lack of knowledge about concomitant levels in fetal and maternal blood. The presence of cytokines in fetal and placental cells was demonstrated by immunohistochemistry using mAb. Cytokines were quantified by enzymimmunoassay in amniotic fluid and fetal and maternal blood. This was done with regard to two disease states that quite frequently complicate the course of pregnancy, namely chorioamnionitis and intrauterine growth retardation. The cytokines examined were G-CSF, GM-CSF, TNF-alpha, IL-1, IL-6, and IL-8. In chorioamnionitis, all cytokines, except GM-CSF, were elevated about 100 times in the amniotic fluid. An accompanying increase in maternal and fetal blood was only found for IL-6 and G-CSF; IL-8 was elevated in fetal blood only. Intrauterine growth retardation was characterized by elevated levels of TNF-alpha in the amniotic fluid, whereas G-CSF, GM-CSF, and IL-1 beta were significantly reduced. Immunohistochemistry showed that under normal conditions the cytokines are to be found in a characteristic distribution in certain cell types in the fetus, the placenta, and the placental bed. With rising concentrations, more cells seemed to be recruited for cytokine production, especially macrophages and decidual cells. In chorioamnionitis, fetal extramedullary granulopoiesis was augmented, and in intrauterine growth retardation, erythropoiesis as well as granulopoiesis were depressed. Not only inflammatory disease but also intrauterine growth retardation is characterized by a changing cytokine pattern. Alterations in fetal hematopoiesis observed at postmortem examination of perinatal deaths can be correlated to changes in cytokine

  7. Thrombolysis significantly reduces transient myocardial ischaemia following first acute myocardial infarction

    DEFF Research Database (Denmark)

    Mickley, H; Pless, P; Nielsen, J R

    1992-01-01

    In order to investigate whether thrombolysis affects residual myocardial ischaemia, we prospectively performed a predischarge maximal exercise test and early out-of-hospital ambulatory ST segment monitoring in 123 consecutive men surviving a first acute myocardial infarction (AMI). Seventy......-four patients fulfilled our criteria for thrombolysis, but only the last 35 patients included received thrombolytic therapy. As thrombolysis was not available in our Department at the start of the study, the first 39 patients included were conservatively treated (controls). No significant differences...... in baseline clinical characteristics were found between the two groups. In-hospital atrial fibrillation and digoxin therapy was more prevalent in controls (P less than 0.05). During exercise, thrombolysed patients reached a higher maximal work capacity compared with controls: 160 +/- 41 vs 139 +/- 34 W (P...

  8. Selenium Supplementation Significantly Reduces Thyroid Autoantibody Levels in Patients with Chronic Autoimmune Thyroiditis

    DEFF Research Database (Denmark)

    Wichman, Johanna Eva Märta; Winther, Kristian Hillert; Bonnema, Steen Joop

    2016-01-01

    BACKGROUND: Selenium supplementation may decrease circulating thyroid autoantibodies in patients with chronic autoimmune thyroiditis (AIT), but the available trials are heterogenous. This study expands and critically reappraises the knowledge on this topic. METHODS: A literature search identified...... 3366 records. Controlled trials in adults (≥18 years of age) with AIT, comparing selenium with or without levothyroxine (LT4), versus placebo and/or LT4, were eligible. Assessed outcomes were serum thyroid peroxidase (TPOAb) and thyroglobulin (TgAb) autoantibody levels, and immunomodulatory effects...... and LT4-untreated. Heterogeneity was estimated using I(2), and quality of evidence was assessed per outcome, using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) guidelines. RESULTS: In LT4-treated populations, the selenium group had significantly lower TPOAb levels after...

  9. A case of gastric endocrine cell carcinoma which was significantly reduced in size by radiotherapy

    International Nuclear Information System (INIS)

    Azakami, Kiyoshi; Nishida, Kouji; Tanikawa, Ken

    2016-01-01

    In 2010, the World Health Organization classified gastric neuroendocrine tumors (NETs) into three types: NET grade (G) 1, NET G2 and neuroendocrine carcinoma (NEC). NECs are associated with a very poor prognosis. The patient was an 84-year-old female who was initially diagnosed by gastrointestinal endoscope with type 3 advanced gastric cancer with stenosis of the gastric cardia. Her overall status and performance status did not allow for operations or intensive chemotherapy. Palliative radiotherapy was performed and resulted in a significant reduction in the size of the tumor as well as the improvement of the obstructive symptoms. She died 9 months after radiotherapy. An autopsy provided a definitive diagnosis of gastric endocrine cell carcinoma, and the effectiveness of radiotherapy was pathologically-confirmed. Palliative radiotherapy may be a useful treatment option for providing symptom relief, especially for old patients with unresectable advanced gastric neuroendocrine carcinoma. (author)

  10. Ad libitum Mediterranean and Low Fat Diets both Significantly Reduce Hepatic Steatosis: a Randomized Controlled Trial.

    Science.gov (United States)

    Properzi, Catherine; O'Sullivan, Therese A; Sherriff, Jill L; Ching, Helena L; Jeffrey, Garry P; Buckley, Rachel F; Tibballs, Jonathan; MacQuillan, Gerry C; Garas, George; Adams, Leon A

    2018-05-05

    Although diet induced weight loss is first-line treatment for patients with non-alcoholic fatty liver disease (NAFLD), long-term maintenance is difficult. The optimal diet for either improvement in NAFLD or associated cardio-metabolic risk factors regardless of weight loss, is unknown. We examined the effect of two ad libitum isocaloric diets [Mediterranean (MD) or Low Fat (LF)] on hepatic steatosis and cardio-metabolic risk factors. Subjects with NAFLD were randomized to a 12-week blinded dietary intervention (MD vs LF). Hepatic steatosis was determined via magnetic resonance spectroscopy (MRS). From a total of 56 subjects enrolled, 49 subjects completed the intervention and 48 were included for analysis. During the intervention, subjects on the MD had significantly higher total and monounsaturated fat but lower carbohydrate and sodium intakes compared to LF subjects (pfat reduction between the groups (p=0.32), with mean (SD) relative reductions of 25.0% (±25.3%) in LF and 32.4% (±25.5%) in MD. Liver enzymes also improved significantly in both groups. Weight loss was minimal and not different between groups [-1.6 (±2.1)kg in LF vs -2.1 (±2.5)kg in MD, (p=0.52)]. Within-group improvements in the Framingham risk score, total cholesterol, serum triglyceride, and HbA1c were observed in the MD (all pvs. 64%, p=0.048). Ad libitum low fat and Mediterranean diets both improve hepatic steatosis to a similar degree. This article is protected by copyright. All rights reserved. © 2018 by the American Association for the Study of Liver Diseases.

  11. Social networking strategies that aim to reduce obesity have achieved significant although modest results.

    Science.gov (United States)

    Ashrafian, Hutan; Toma, Tania; Harling, Leanne; Kerr, Karen; Athanasiou, Thanos; Darzi, Ara

    2014-09-01

    The global epidemic of obesity continues to escalate. Obesity accounts for an increasing proportion of the international socioeconomic burden of noncommunicable disease. Online social networking services provide an effective medium through which information may be exchanged between obese and overweight patients and their health care providers, potentially contributing to superior weight-loss outcomes. We performed a systematic review and meta-analysis to assess the role of these services in modifying body mass index (BMI). Our analysis of twelve studies found that interventions using social networking services produced a modest but significant 0.64 percent reduction in BMI from baseline for the 941 people who participated in the studies' interventions. We recommend that social networking services that target obesity should be the subject of further clinical trials. Additionally, we recommend that policy makers adopt reforms that promote the use of anti-obesity social networking services, facilitate multistakeholder partnerships in such services, and create a supportive environment to confront obesity and its associated noncommunicable diseases. Project HOPE—The People-to-People Health Foundation, Inc.

  12. Targeting Heparin to Collagen within Extracellular Matrix Significantly Reduces Thrombogenicity and Improves Endothelialization of Decellularized Tissues.

    Science.gov (United States)

    Jiang, Bin; Suen, Rachel; Wertheim, Jason A; Ameer, Guillermo A

    2016-12-12

    Thrombosis within small-diameter vascular grafts limits the development of bioartificial, engineered vascular conduits, especially those derived from extracellular matrix (ECM). Here we describe an easy-to-implement strategy to chemically modify vascular ECM by covalently linking a collagen binding peptide (CBP) to heparin to form a heparin derivative (CBP-heparin) that selectively binds a subset of collagens. Modification of ECM with CBP-heparin leads to increased deposition of functional heparin (by ∼7.2-fold measured by glycosaminoglycan composition) and a corresponding reduction in platelet binding (>70%) and whole blood clotting (>80%) onto the ECM. Furthermore, addition of CBP-heparin to the ECM stabilizes long-term endothelial cell attachment to the lumen of ECM-derived vascular conduits, potentially through recruitment of heparin-binding growth factors that ultimately improve the durability of endothelialization in vitro. Overall, our findings provide a simple yet effective method to increase deposition of functional heparin on the surface of ECM-based vascular grafts and thereby minimize thrombogenicity of decellularized tissue, overcoming a significant challenge in tissue engineering of bioartificial vessels and vascularized organs.

  13. Thyroid function appears to be significantly reduced in Space-borne MDS mice

    Science.gov (United States)

    Saverio Ambesi-Impiombato, Francesco; Curcio, Francesco; Fontanini, Elisabetta; Perrella, Giuseppina; Spelat, Renza; Zambito, Anna Maria; Damaskopoulou, Eleni; Peverini, Manola; Albi, Elisabetta

    It is known that prolonged space flights induced changes in human cardiovascular, muscu-loskeletal and nervous systems whose function is regulated by the thyroid gland but, until now, no data were reported about thyroid damage during space missions. We have demonstrated in vitro that, during space missions (Italian Soyuz Mission "ENEIDE" in 2005, Shuttle STS-120 "ESPERIA" in 2007), thyroid in vitro cultured cells did not respond to thyroid stimulating hor-mone (TSH) treatment; they appeared healthy and alive, despite their being in a pro-apopotic state characterised by a variation of sphingomyelin metabolism and consequent increase in ce-ramide content. The insensitivity to TSH was largely due to a rearrangement of specific cell membrane microdomains, acting as platforms for TSH-receptor (TEXUS-44 mission in 2008). To study if these effects were present also in vivo, as part of the Mouse Drawer System (MDS) Tissue Sharing Program, we performed experiments in mice maintained onboard the Interna-tional Space Station during the long-duration (90 days) exploration mission STS-129. After return to earth, the thyroids isolated from the 3 animals were in part immediately frozen to study the morphological modification in space and in part immediately used to study the effect of TSH treatment. For this purpose small fragments of tissue were treated with 10-7 or 10-8 M TSH for 1 hour by using untreated fragments as controls. Then the fragments were fixed with absolute ethanol for 10 min at room temperature and centrifuged for 20 min. at 3000 x g. The supernatants were used for cAMP analysis whereas the pellet were used for protein amount determination and for immunoblotting analysis of TSH-receptor, sphingomyelinase and sphingomyelin-synthase. The results showed a modification of the thyroid structure and also the values of cAMP production after treatment with 10-7 M TSH for 1 hour were significantly lower than those obtained in Earth's gravity. The treatment with TSH

  14. Conjugated primary bile salts reduce permeability of endotoxin through bacteria-stimulated intestinal epithelial cells and synergize with lecithin in suppression of inflammatory cytokine production

    DEFF Research Database (Denmark)

    Parlesak, Alexandr; Schaeckeler, Simone; Moser, Lydia

    2007-01-01

    : The effect of CPBS (0.5 mM and 1.5 mM), phosphatidylcholine(0.38 mM), and human bile (0.5% vol/vol) on the barrier function was assessed by the measurement of transepithelial electrical resistance, by endotoxin permeability through the intestinal epithelial cell layer, and by basolateral cytokine enzyme...

  15. The immunological response and post-treatment survival of DC-vaccinated melanoma patients are associated with increased Th1/Th17 and reduced Th3 cytokine responses.

    Science.gov (United States)

    Durán-Aniotz, Claudia; Segal, Gabriela; Salazar, Lorena; Pereda, Cristián; Falcón, Cristián; Tempio, Fabián; Aguilera, Raquel; González, Rodrigo; Pérez, Claudio; Tittarelli, Andrés; Catalán, Diego; Nervi, Bruno; Larrondo, Milton; Salazar-Onfray, Flavio; López, Mercedes N

    2013-04-01

    Immunization with autologous dendritic cells (DCs) loaded with a heat shock-conditioned allogeneic melanoma cell lysate caused lysate-specific delayed type hypersensitivity (DTH) reactions in a number of patients. These responses correlated with a threefold prolonged long-term survival of DTH(+) with respect to DTH(-) unresponsive patients. Herein, we investigated whether the immunological reactions associated with prolonged survival were related to dissimilar cellular and cytokine responses in blood. Healthy donors and melanoma patient's lymphocytes obtained from blood before and after vaccinations and from DTH biopsies were analyzed for T cell population distribution and cytokine release. Peripheral blood lymphocytes from melanoma patients have an increased proportion of Th3 (CD4(+) TGF-β(+)) regulatory T lymphocytes compared with healthy donors. Notably, DTH(+) patients showed a threefold reduction of Th3 cells compared with DTH(-) patients after DCs vaccine treatment. Furthermore, DCs vaccination resulted in a threefold augment of the proportion of IFN-γ releasing Th1 cells and in a twofold increase of the IL-17-producing Th17 population in DTH(+) with respect to DTH(-) patients. Increased Th1 and Th17 cell populations in both blood and DTH-derived tissues suggest that these profiles may be related to a more effective anti-melanoma response. Our results indicate that increased proinflammatory cytokine profiles are related to detectable immunological responses in vivo (DTH) and to prolonged patient survival. Our study contributes to the understanding of immunological responses produced by DCs vaccines and to the identification of follow-up markers for patient outcome that may allow a closer individual monitoring of patients.

  16. 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.

  17. Interaction between FOXO1A-209 Genotype and Tea Drinking is Significantly Associated with Reduced Mortality at Advanced Ages

    DEFF Research Database (Denmark)

    Zeng, Yi; Chen, Huashuai; Ni, Ting

    2016-01-01

    Based on the genotypic/phenotypic data from Chinese Longitudinal Healthy Longevity Survey (CLHLS) and Cox proportional hazard model, the present study demonstrates that interactions between carrying FOXO1A-209 genotypes and tea drinking are significantly associated with lower risk of mortality...... at advanced ages. Such significant association is replicated in two independent Han Chinese CLHLS cohorts (p =0.028-0.048 in the discovery and replication cohorts, and p =0.003-0.016 in the combined dataset). We found the associations between tea drinking and reduced mortality are much stronger among carriers...... of the FOXO1A-209 genotype compared to non-carriers, and drinking tea is associated with a reversal of the negative effects of carrying FOXO1A-209 minor alleles, that is, from a substantially increased mortality risk to substantially reduced mortality risk at advanced ages. The impacts are considerably...

  18. Mangifera indica L. extract (Vimang) and mangiferin reduce the airway inflammation and Th2 cytokines in murine model of allergic asthma.

    Science.gov (United States)

    Rivera, Dagmar García; Hernández, Ivones; Merino, Nelson; Luque, Yilian; Álvarez, Alina; Martín, Yanet; Amador, Aylin; Nuevas, Lauro; Delgado, René

    2011-10-01

    The aim was to study the effects of Mangifera indica extract and its major component mangiferin on lung inflammation response and Th2 cytokine production using a murine experimental model of allergic asthma. BALB/c mice were intraperitoneally sensitized with 10 µg of ovoalbumin (OVA) adsorbed on aluminium hydroxide on days 0, 7 and 14. Seven days after the last injection, the mice were challenged with 2% aerosolized OVA inhalation for 30 min beginning on day 21 and continuing until day 24. To evaluate the protective effect, mice were orally treated with M. indica extract (50, 100 or 250 mg/kg) or mangiferin (50 mg/kg) from days 0 to 24. Anti-OVA immunoglobulin E, interleukin (IL)-4 and IL-5 were determined by ELISA and lungs were analysed by histology. M. indica extract and mangiferin produced a marked reduction of airway inflammation around vessels and bronchi, inhibition of IL-4 and IL-5 cytokines in bronchoalveolar lavage fluid and lymphocyte culture supernatant, IgE levels and lymphocyte proliferation. This is the first pre-clinical report of the anti-inflammatory properties of M. indica extract and mangiferin in experimental asthma and it could be an important part of pre-clinical requirement necessary for its use to complement the treatment of this complex disease. © 2011 The Authors. JPP © 2011 Royal Pharmaceutical Society.

  19. A Recombinant Multi-Stage Vaccine against Paratuberculosis Significantly Reduces Bacterial Level in Tissues without Interference in Diagnostics

    DEFF Research Database (Denmark)

    Jungersen, Gregers; Thakur, Aneesh; Aagaard, C.

    , PPDj-specific IFN-γ responses or positive PPDa or PPDb skin tests developed in vaccinees. Antibodies and cell-mediated immune responses were developed against FET11 antigens, however. At necropsy 8 or 12 months of age, relative Map burden was determined in a number of gut tissues by quantitative IS900...... PCR and revealed significantly reduced levels of Map and reduced histopathology. Diagnostic tests for antibody responses and cell-mediated immune responses, used as surrogates of infection, corroborated the observed vaccine efficacy: Five of seven non‐vaccinated calves seroconverted in ID Screen......-γ assay responses from 40 to 52 weeks compared to non-vaccinated calves. These results indicate the FET11 vaccine can be used to accelerate eradication of paratuberculosis while surveillance or test-and-manage control programs for tuberculosis and Johne’s disease remain in place. Funded by EMIDA ERA...

  20. Lime and Phosphate Amendment Can Significantly Reduce Uptake of Cd and Pb by Field-Grown Rice

    Directory of Open Access Journals (Sweden)

    Rongbo Xiao

    2017-03-01

    Full Text Available Agricultural soils are suffering from increasing heavy metal pollution, among which, paddy soil polluted by heavy metals is frequently reported and has elicited great public concern. In this study, we carried out field experiments on paddy soil around a Pb-Zn mine to study amelioration effects of four soil amendments on uptake of Cd and Pb by rice, and to make recommendations for paddy soil heavy metal remediation, particularly for combined pollution of Cd and Pb. The results showed that all the four treatments can significantly reduce the Cd and Pb content in the late rice grain compared with the early rice, among which, the combination amendment of lime and phosphate had the best remediation effects where rice grain Cd content was reduced by 85% and 61%, respectively, for the late rice and the early rice, and by 30% in the late rice grain for Pb. The high reduction effects under the Ca + P treatment might be attributed to increase of soil pH from 5.5 to 6.7. We also found that influence of the Ca + P treatment on rice production was insignificant, while the available Cd and Pb content in soil was reduced by 16.5% and 11.7%, respectively.

  1. Reduced bone mineral density is not associated with significantly reduced bone quality in men and women practicing long-term calorie restriction with adequate nutrition.

    Science.gov (United States)

    Villareal, Dennis T; Kotyk, John J; Armamento-Villareal, Reina C; Kenguva, Venkata; Seaman, Pamela; Shahar, Allon; Wald, Michael J; Kleerekoper, Michael; Fontana, Luigi

    2011-02-01

    Calorie restriction (CR) reduces bone quantity but not bone quality in rodents. Nothing is known regarding the long-term effects of CR with adequate intake of vitamin and minerals on bone quantity and quality in middle-aged lean individuals. In this study, we evaluated body composition, bone mineral density (BMD), and serum markers of bone turnover and inflammation in 32 volunteers who had been eating a CR diet (approximately 35% less calories than controls) for an average of 6.8 ± 5.2 years (mean age 52.7 ± 10.3 years) and 32 age- and sex-matched sedentary controls eating Western diets (WD). In a subgroup of 10 CR and 10 WD volunteers, we also measured trabecular bone (TB) microarchitecture of the distal radius using high-resolution magnetic resonance imaging. We found that the CR volunteers had significantly lower body mass index than the WD volunteers (18.9 ± 1.2 vs. 26.5 ± 2.2 kg m(-2) ; P = 0.0001). BMD of the lumbar spine (0.870 ± 0.11 vs. 1.138 ± 0.12 g cm(-2) , P = 0.0001) and hip (0.806 ± 0.12 vs. 1.047 ± 0.12 g cm(-2) , P = 0.0001) was also lower in the CR than in the WD group. Serum C-terminal telopeptide and bone-specific alkaline phosphatase concentration were similar between groups, while serum C-reactive protein (0.19 ± 0.26 vs. 1.46 ± 1.56 mg L(-1) , P = 0.0001) was lower in the CR group. Trabecular bone microarchitecture parameters such as the erosion index (0.916 ± 0.087 vs. 0.877 ± 0.088; P = 0.739) and surface-to-curve ratio (10.3 ± 1.4 vs. 12.1 ± 2.1, P = 0.440) were not significantly different between groups. These findings suggest that markedly reduced BMD is not associated with significantly reduced bone quality in middle-aged men and women practicing long-term calorie restriction with adequate nutrition.

  2. Smoking cessation programmes in radon affected areas: can they make a significant contribution to reducing radon-induced lung cancers?

    International Nuclear Information System (INIS)

    Denman, A.R.; Groves-Kirkby, C.J.; Timson, K.; Shield, G.; Rogers, S.; Phillips, P.S.

    2008-01-01

    Domestic radon levels in parts of the UK are sufficiently high to increase the risk of lung cancer in the occupants. Public health campaigns in Northamptonshire, a designated radon affected area with 6.3% of homes having average radon levels over the UK action level of 200 Bq m -3 , have encouraged householders to test for radon and then to carry out remediation in their homes, but have been only partially successful. Only 40% of Northamptonshire houses have been tested, and only 15% of householders finding raised levels proceed to remediate. Of those who did remediate, only 9% smoked, compared to a countywide average of 28.8%. This is unfortunate, since radon and smoking combine to place the individual at higher risk by a factor of around 4, and suggests that current strategies to reduce domestic radon exposure are not reaching those most at risk. During 2004-5, the NHS Stop Smoking Services in Northamptonshire assisted 2,808 smokers to quit to the 4-week stage, with some 30% of 4-week quitters remaining quitters at 1 year. We consider whether smoking cessation campaigns make significant contributions to radon risk reduction on their own, by assessing individual occupants' risk of developing lung cancer from knowledge of their age, gender, and smoking habits, together with he radon level in their house. The results demonstrate that smoking cessation programmes have significant added value in radon affected areas, and contribute a greater health benefit than reducing radon levels in the smokers' homes, whilst they remain smokers. Additionally, results are presented from a questionnaire-based survey of quitters, addressing their reasons for seeking help in quitting smoking, and whether knowledge of radon risks influenced this decision. The impact of these findings on future public health campaigns to reduce the impact of radon and smoking are discussed. (author)

  3. Lipid Replacement Therapy Drink Containing a Glycophospholipid Formulation Rapidly and Significantly Reduces Fatigue While Improving Energy and Mental Clarity

    Directory of Open Access Journals (Sweden)

    Robert Settineri

    2011-08-01

    Full Text Available Background: Fatigue is the most common complaint of patients seeking general medical care and is often treated with stimulants. It is also important in various physical activities of relatively healthy men and women, such as sports performance. Recent clinical trials using patients with chronic fatigue have shown the benefit of Lipid Replacement Therapy in restoring mitochondrial electron transport function and reducing moderate to severe chronic fatigue. Methods: Lipid Replacement Therapy was administered for the first time as an all-natural functional food drink (60 ml containing polyunsaturated glycophospholipids but devoid of stimulants or herbs to reduce fatigue. This preliminary study used the Piper Fatigue Survey instrument as well as a supplemental questionnaire to assess the effects of the glycophospholipid drink on fatigue and the acceptability of the test drink in adult men and women. A volunteer group of 29 subjects of mean age 56.2±4.5 years with various fatigue levels were randomly recruited in a clinical health fair setting to participate in an afternoon open label trial on the effects of the test drink. Results: Using the Piper Fatigue instrument overall fatigue among participants was reduced within the 3-hour seminar by a mean of 39.6% (p<0.0001. All of the subcategories of fatigue showed significant reductions. Some subjects responded within 15 minutes, and the majority responded within one hour with increased energy and activity and perceived improvements in cognitive function, mental clarity and focus. The test drink was determined to be quite acceptable in terms of taste and appearance. There were no adverse events from the energy drink during the study.Functional Foods in Health and Disease 2011; 8:245-254Conclusions: The Lipid Replacement Therapy functional food drink appeared to be a safe, acceptable and potentially useful new method to reduce fatigue, sustain energy and improve perceptions of mental function.

  4. Central and peripheral administration of antisense oligonucleotide targeting amyloid-β protein precursor improves learning and memory and reduces neuroinflammatory cytokines in Tg2576 (AβPPswe) mice.

    Science.gov (United States)

    Farr, Susan A; Erickson, Michelle A; Niehoff, Michael L; Banks, William A; Morley, John E

    2014-01-01

    Alzheimer's disease (AD) is a progressive neurodegenerative disease. Currently, there are no therapies to stop or reverse the symptoms of AD. We have developed an antisense oligonucleotide (OL-1) against the amyloid-β protein precursor (AβPP) that can decrease AβPP expression and amyloid-β protein (Aβ) production. This antisense rapidly crosses the blood-brain barrier, reverses learning and memory impairments, reduces oxidative stress, and restores brain-to-blood efflux of Aβ in SAMP8 mice. Here, we examined the effects of this AβPP antisense in the Tg2576 mouse model of AD. We administered the OL-1 antisense into the lateral ventricle 3 times at 2week intervals. Seventy-two hours after the third injection, we tested learning and memory in T-maze foot shock avoidance. In the second study, we injected the mice with OL-1 antisense 3 times at 2-week intervals via the tail vein. Seventy-two hours later, we tested learning and memory T-maze, novel object recognition, and elevated plus maze. At the end of behavioral testing, brain tissue was collected. OL-1 antisense administered centrally improved acquisition and retention of T-maze foot shock avoidance. OL-1 antisense administered via tail vein improved learning and memory in both T-maze foot shock avoidance and novel object-place recognition. In the elevated plus maze, the mice which received OL-1 antisense spent less time in the open arms and had fewer entries into the open arms indicating reduced disinhibitation. Biochemical analyses reveal significant reduction of AβPP signal and a reduction of measures of neuroinflammation. The current findings support the therapeutic potential of OL-1 AβPP antisense.

  5. Significant Association between Sulfate-Reducing Bacteria and Uranium-Reducing Microbial Communities as Revealed by a Combined Massively Parallel Sequencing-Indicator Species Approach▿ †

    Science.gov (United States)

    Cardenas, Erick; Wu, Wei-Min; Leigh, Mary Beth; Carley, Jack; Carroll, Sue; Gentry, Terry; Luo, Jian; Watson, David; Gu, Baohua; Ginder-Vogel, Matthew; Kitanidis, Peter K.; Jardine, Philip M.; Zhou, Jizhong; Criddle, Craig S.; Marsh, Terence L.; Tiedje, James M.

    2010-01-01

    Massively parallel sequencing has provided a more affordable and high-throughput method to study microbial communities, although it has mostly been used in an exploratory fashion. We combined pyrosequencing with a strict indicator species statistical analysis to test if bacteria specifically responded to ethanol injection that successfully promoted dissimilatory uranium(VI) reduction in the subsurface of a uranium contamination plume at the Oak Ridge Field Research Center in Tennessee. Remediation was achieved with a hydraulic flow control consisting of an inner loop, where ethanol was injected, and an outer loop for flow-field protection. This strategy reduced uranium concentrations in groundwater to levels below 0.126 μM and created geochemical gradients in electron donors from the inner-loop injection well toward the outer loop and downgradient flow path. Our analysis with 15 sediment samples from the entire test area found significant indicator species that showed a high degree of adaptation to the three different hydrochemical-created conditions. Castellaniella and Rhodanobacter characterized areas with low pH, heavy metals, and low bioactivity, while sulfate-, Fe(III)-, and U(VI)-reducing bacteria (Desulfovibrio, Anaeromyxobacter, and Desulfosporosinus) were indicators of areas where U(VI) reduction occurred. The abundance of these bacteria, as well as the Fe(III) and U(VI) reducer Geobacter, correlated with the hydraulic connectivity to the substrate injection site, suggesting that the selected populations were a direct response to electron donor addition by the groundwater flow path. A false-discovery-rate approach was implemented to discard false-positive results by chance, given the large amount of data compared. PMID:20729318

  6. Significant association between sulfate-reducing bacteria and uranium-reducing microbial communities as revealed by a combined massively parallel sequencing-indicator species approach.

    Science.gov (United States)

    Cardenas, Erick; Wu, Wei-Min; Leigh, Mary Beth; Carley, Jack; Carroll, Sue; Gentry, Terry; Luo, Jian; Watson, David; Gu, Baohua; Ginder-Vogel, Matthew; Kitanidis, Peter K; Jardine, Philip M; Zhou, Jizhong; Criddle, Craig S; Marsh, Terence L; Tiedje, James M

    2010-10-01

    Massively parallel sequencing has provided a more affordable and high-throughput method to study microbial communities, although it has mostly been used in an exploratory fashion. We combined pyrosequencing with a strict indicator species statistical analysis to test if bacteria specifically responded to ethanol injection that successfully promoted dissimilatory uranium(VI) reduction in the subsurface of a uranium contamination plume at the Oak Ridge Field Research Center in Tennessee. Remediation was achieved with a hydraulic flow control consisting of an inner loop, where ethanol was injected, and an outer loop for flow-field protection. This strategy reduced uranium concentrations in groundwater to levels below 0.126 μM and created geochemical gradients in electron donors from the inner-loop injection well toward the outer loop and downgradient flow path. Our analysis with 15 sediment samples from the entire test area found significant indicator species that showed a high degree of adaptation to the three different hydrochemical-created conditions. Castellaniella and Rhodanobacter characterized areas with low pH, heavy metals, and low bioactivity, while sulfate-, Fe(III)-, and U(VI)-reducing bacteria (Desulfovibrio, Anaeromyxobacter, and Desulfosporosinus) were indicators of areas where U(VI) reduction occurred. The abundance of these bacteria, as well as the Fe(III) and U(VI) reducer Geobacter, correlated with the hydraulic connectivity to the substrate injection site, suggesting that the selected populations were a direct response to electron donor addition by the groundwater flow path. A false-discovery-rate approach was implemented to discard false-positive results by chance, given the large amount of data compared.

  7. Reducing Eating Disorder Onset in a Very High Risk Sample with Significant Comorbid Depression: A Randomized Controlled Trial

    Science.gov (United States)

    Taylor, C. Barr; Kass, Andrea E.; Trockel, Mickey; Cunning, Darby; Weisman, Hannah; Bailey, Jakki; Sinton, Meghan; Aspen, Vandana; Schecthman, Kenneth; Jacobi, Corinna; Wilfley, Denise E.

    2015-01-01

    Objective Eating disorders (EDs) are serious problems among college-age women and may be preventable. An indicated on-line eating disorder (ED) intervention, designed to reduce ED and comorbid pathology, was evaluated. Method 206 women (M age = 20 ± 1.8 years; 51% White/Caucasian, 11% African American, 10% Hispanic, 21% Asian/Asian American, 7% other) at very high risk for ED onset (i.e., with high weight/shape concerns plus a history of being teased, current or lifetime depression, and/or non-clinical levels of compensatory behaviors) were randomized to a 10-week, Internet-based, cognitive-behavioral intervention or wait-list control. Assessments included the Eating Disorder Examination (EDE to assess ED onset), EDE-Questionnaire, Structured Clinical Interview for DSM Disorders, and Beck Depression Inventory-II. Results ED attitudes and behaviors improved more in the intervention than control group (p = 0.02, d = 0.31); although ED onset rate was 27% lower, this difference was not significant (p = 0.28, NNT = 15). In the subgroup with highest shape concerns, ED onset rate was significantly lower in the intervention than control group (20% versus 42%, p = 0.025, NNT = 5). For the 27 individuals with depression at baseline, depressive symptomatology improved more in the intervention than control group (p = 0.016, d = 0.96); although ED onset rate was lower in the intervention than control group, this difference was not significant (25% versus 57%, NNT = 4). Conclusions An inexpensive, easily disseminated intervention might reduce ED onset among those at highest risk. Low adoption rates need to be addressed in future research. PMID:26795936

  8. Reducing eating disorder onset in a very high risk sample with significant comorbid depression: A randomized controlled trial.

    Science.gov (United States)

    Taylor, C Barr; Kass, Andrea E; Trockel, Mickey; Cunning, Darby; Weisman, Hannah; Bailey, Jakki; Sinton, Meghan; Aspen, Vandana; Schecthman, Kenneth; Jacobi, Corinna; Wilfley, Denise E

    2016-05-01

    Eating disorders (EDs) are serious problems among college-age women and may be preventable. An indicated online eating disorder (ED) intervention, designed to reduce ED and comorbid pathology, was evaluated. 206 women (M age = 20 ± 1.8 years; 51% White/Caucasian, 11% African American, 10% Hispanic, 21% Asian/Asian American, 7% other) at very high risk for ED onset (i.e., with high weight/shape concerns plus a history of being teased, current or lifetime depression, and/or nonclinical levels of compensatory behaviors) were randomized to a 10-week, Internet-based, cognitive-behavioral intervention or waitlist control. Assessments included the Eating Disorder Examination (EDE, to assess ED onset), EDE-Questionnaire, Structured Clinical Interview for DSM Disorders, and Beck Depression Inventory-II. ED attitudes and behaviors improved more in the intervention than control group (p = .02, d = 0.31); although ED onset rate was 27% lower, this difference was not significant (p = .28, NNT = 15). In the subgroup with highest shape concerns, ED onset rate was significantly lower in the intervention than control group (20% vs. 42%, p = .025, NNT = 5). For the 27 individuals with depression at baseline, depressive symptomatology improved more in the intervention than control group (p = .016, d = 0.96); although ED onset rate was lower in the intervention than control group, this difference was not significant (25% vs. 57%, NNT = 4). An inexpensive, easily disseminated intervention might reduce ED onset among those at highest risk. Low adoption rates need to be addressed in future research. (c) 2016 APA, all rights reserved).

  9. Morinda citrifolia (Noni Fruit Juice Reduces Inflammatory Cytokines Expression and Contributes to the Maintenance of Intestinal Mucosal Integrity in DSS Experimental Colitis

    Directory of Open Access Journals (Sweden)

    Beatriz Coutinho de Sousa

    2017-01-01

    Full Text Available Morinda citrifolia L. (noni has been shown to treat different disorders. However, data concerning its role in the treatment of intestinal inflammation still require clarification. In the current study, we investigated the effects of noni fruit juice (NFJ in the treatment of C57BL/6 mice, which were continuously exposed to dextran sulfate sodium (DSS for 9 consecutive days. NFJ consumption had no impact on the reduction of the clinical signs of the disease or on weight loss. Nonetheless, when a dilution of 1 : 10 was used, the intestinal architecture of the mice was preserved, accompanied by a reduction in the inflammatory infiltrate. Regardless of the concentration of NFJ, a decrease in both the activity of myeloperoxidase and the key inflammatory cytokines, TNF-α and IFN-γ, was also observed in the intestine. Furthermore, when NFJ was diluted 1 : 10 and 1 : 100, a reduction in the production of nitric oxide and IL-17 was detected in gut homogenates. Overall, the treatment with NFJ was effective in different aspects associated with disease progression and worsening. These results may point to noni fruit as an important source of anti-inflammatory molecules with a great potential to inhibit the progression of inflammatory diseases, such as inflammatory bowel disease.

  10. Potent corticosteroid cream (mometasone furoate) significantly reduces acute radiation dermatitis: results from a double-blind, randomized study

    International Nuclear Information System (INIS)

    Bostroem, Aasa; Lindman, Henrik; Swartling, Carl; Berne, Berit; Bergh, Jonas

    2001-01-01

    Purpose: Radiation-induced dermatitis is a very common side effect of radiation therapy, and may necessitate interruption of the therapy. There is a substantial lack of evidence-based treatments for this condition. The aim of this study was to investigate the effect of mometasone furoate cream (MMF) on radiation dermatitis in a prospective, double-blind, randomized study. Material and methods: The study comprised 49 patients with node-negative breast cancer. They were operated on with sector resection and scheduled for postoperative radiotherapy using photons with identical radiation qualities and dosage to the breast parenchyma. The patients were randomized to receive either MMF or emollient cream. The cream was applied on the irradiated skin twice a week from the start of radiotherapy until the 12th fraction (24 Gy) and thereafter once daily until 3 weeks after completion of radiation. Both groups additionally received non-blinded emollient cream daily. The intensity of the acute radiation dermatitis was evaluated on a weekly basis regarding erythema and pigmentation, using a reflectance spectrophotometer together with visual scoring of the skin reactions. Results: MMF in combination with emollient cream treatment significantly decreased acute radiation dermatitis (P=0.0033) compared with emollient cream alone. There was no significant difference in pigmentation between the two groups. Conclusions: Adding MMF, a potent topical corticosteroid, to an emollient cream is statistically significantly more effective than emollient cream alone in reducing acute radiation dermatitis

  11. Reduced frontal and occipital lobe asymmetry on the CT-scans of schizophrenic patients. Its specificity and clinical significance

    International Nuclear Information System (INIS)

    Falkai, P.; Schneider, T.; Greve, B.; Klieser, E.; Bogerts, B.

    1995-01-01

    Frontal and occipital lobe widths were determined in the computed tomographic (CT) scans of 135 schizophrenic patients, 158 neuro psychiatrically healthy and 102 psychiatric control subjects, including patients with affective psychosis, neurosis and schizoaffective psychosis. Most healthy right-handed subjects demonstrate a relative enlargement of the right frontal as well as left occipital lobe compared to the opposite hemisphere. These normal frontal and occipital lobe asymmetries were selectively reduced in schizophrenics (f.: 5%, p < .0005; o.: 3%, p < .05), irrespective of the pathophysiological subgroup. Schizophrenic neuroleptic non-responders revealed a significant reduction of frontal lobe asymmetry (3%, p < .05), while no correlation between BPRS-sub scores and disturbed cerebral laterality could be detected. In sum the present study demonstrates the disturbed cerebral lateralisation in schizophrenic patients supporting the hypothesis of interrupted early brain development in schizophrenia. (author)

  12. Walking with a four wheeled walker (rollator) significantly reduces EMG lower-limb muscle activity in healthy subjects.

    Science.gov (United States)

    Suica, Zorica; Romkes, Jacqueline; Tal, Amir; Maguire, Clare

    2016-01-01

    To investigate the immediate effect of four-wheeled- walker(rollator)walking on lower-limb muscle activity and trunk-sway in healthy subjects. In this cross-sectional design electromyographic (EMG) data was collected in six lower-limb muscle groups and trunk-sway was measured as peak-to-peak angular displacement of the centre-of-mass (level L2/3) in the sagittal and frontal-planes using the SwayStar balance system. 19 subjects walked at self-selected speed firstly without a rollator then in randomised order 1. with rollator 2. with rollator with increased weight-bearing. Rollator-walking caused statistically significant reductions in EMG activity in lower-limb muscle groups and effect-sizes were medium to large. Increased weight-bearing increased the effect. Trunk-sway in the sagittal and frontal-planes showed no statistically significant difference between conditions. Rollator-walking reduces lower-limb muscle activity but trunk-sway remains unchanged as stability is likely gained through forces generated by the upper-limbs. Short-term stability is gained but the long-term effect is unclear and requires investigation. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Modest hypoxia significantly reduces triglyceride content and lipid droplet size in 3T3-L1 adipocytes

    Energy Technology Data Exchange (ETDEWEB)

    Hashimoto, Takeshi, E-mail: thashimo@fc.ritsumei.ac.jp [Faculty of Sport and Health Science, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga 525-8577 (Japan); Yokokawa, Takumi; Endo, Yuriko [Faculty of Sport and Health Science, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga 525-8577 (Japan); Iwanaka, Nobumasa [Ritsumeikan Global Innovation Research Organization, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga 525-8577 (Japan); Higashida, Kazuhiko [Faculty of Sport and Health Science, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga 525-8577 (Japan); Faculty of Sport Science, Waseda University, 2-579-15 Mikajima, Tokorozawa, Saitama 359-1192 (Japan); Taguchi, Sadayoshi [Faculty of Sport and Health Science, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga 525-8577 (Japan)

    2013-10-11

    Highlights: •Long-term hypoxia decreased the size of LDs and lipid storage in 3T3-L1 adipocytes. •Long-term hypoxia increased basal lipolysis in 3T3-L1 adipocytes. •Hypoxia decreased lipid-associated proteins in 3T3-L1 adipocytes. •Hypoxia decreased basal glucose uptake and lipogenic proteins in 3T3-L1 adipocytes. •Hypoxia-mediated lipogenesis may be an attractive therapeutic target against obesity. -- Abstract: Background: A previous study has demonstrated that endurance training under hypoxia results in a greater reduction in body fat mass compared to exercise under normoxia. However, the cellular and molecular mechanisms that underlie this hypoxia-mediated reduction in fat mass remain uncertain. Here, we examine the effects of modest hypoxia on adipocyte function. Methods: Differentiated 3T3-L1 adipocytes were incubated at 5% O{sub 2} for 1 week (long-term hypoxia, HL) or one day (short-term hypoxia, HS) and compared with a normoxia control (NC). Results: HL, but not HS, resulted in a significant reduction in lipid droplet size and triglyceride content (by 50%) compared to NC (p < 0.01). As estimated by glycerol release, isoproterenol-induced lipolysis was significantly lowered by hypoxia, whereas the release of free fatty acids under the basal condition was prominently enhanced with HL compared to NC or HS (p < 0.01). Lipolysis-associated proteins, such as perilipin 1 and hormone-sensitive lipase, were unchanged, whereas adipose triglyceride lipase and its activator protein CGI-58 were decreased with HL in comparison to NC. Interestingly, such lipogenic proteins as fatty acid synthase, lipin-1, and peroxisome proliferator-activated receptor gamma were decreased. Furthermore, the uptake of glucose, the major precursor of 3-glycerol phosphate for triglyceride synthesis, was significantly reduced in HL compared to NC or HS (p < 0.01). Conclusion: We conclude that hypoxia has a direct impact on reducing the triglyceride content and lipid droplet size via

  14. Modest hypoxia significantly reduces triglyceride content and lipid droplet size in 3T3-L1 adipocytes

    International Nuclear Information System (INIS)

    Hashimoto, Takeshi; Yokokawa, Takumi; Endo, Yuriko; Iwanaka, Nobumasa; Higashida, Kazuhiko; Taguchi, Sadayoshi

    2013-01-01

    Highlights: •Long-term hypoxia decreased the size of LDs and lipid storage in 3T3-L1 adipocytes. •Long-term hypoxia increased basal lipolysis in 3T3-L1 adipocytes. •Hypoxia decreased lipid-associated proteins in 3T3-L1 adipocytes. •Hypoxia decreased basal glucose uptake and lipogenic proteins in 3T3-L1 adipocytes. •Hypoxia-mediated lipogenesis may be an attractive therapeutic target against obesity. -- Abstract: Background: A previous study has demonstrated that endurance training under hypoxia results in a greater reduction in body fat mass compared to exercise under normoxia. However, the cellular and molecular mechanisms that underlie this hypoxia-mediated reduction in fat mass remain uncertain. Here, we examine the effects of modest hypoxia on adipocyte function. Methods: Differentiated 3T3-L1 adipocytes were incubated at 5% O 2 for 1 week (long-term hypoxia, HL) or one day (short-term hypoxia, HS) and compared with a normoxia control (NC). Results: HL, but not HS, resulted in a significant reduction in lipid droplet size and triglyceride content (by 50%) compared to NC (p < 0.01). As estimated by glycerol release, isoproterenol-induced lipolysis was significantly lowered by hypoxia, whereas the release of free fatty acids under the basal condition was prominently enhanced with HL compared to NC or HS (p < 0.01). Lipolysis-associated proteins, such as perilipin 1 and hormone-sensitive lipase, were unchanged, whereas adipose triglyceride lipase and its activator protein CGI-58 were decreased with HL in comparison to NC. Interestingly, such lipogenic proteins as fatty acid synthase, lipin-1, and peroxisome proliferator-activated receptor gamma were decreased. Furthermore, the uptake of glucose, the major precursor of 3-glycerol phosphate for triglyceride synthesis, was significantly reduced in HL compared to NC or HS (p < 0.01). Conclusion: We conclude that hypoxia has a direct impact on reducing the triglyceride content and lipid droplet size via

  15. A pilot study: Horticulture-related activities significantly reduce stress levels and salivary cortisol concentration of maladjusted elementary school children.

    Science.gov (United States)

    Lee, Min Jung; Oh, Wook; Jang, Ja Soon; Lee, Ju Young

    2018-04-01

    The effects of three horticulture-related activities (HRAs), including floral arranging, planting, and flower pressing were compared to see if they influenced changes on a stress scale and on salivary cortisol concentrations (SCC) in maladjusted elementary school children. Twenty maladjusted elementary school children were randomly assigned either to an experimental or control group. The control group carried out individual favorite indoor activities under the supervision of a teacher. Simultaneously, the ten children in the experimental group participated in a HRA program consisting of flower arrangement (FA), planting (P), and flower pressing (PF) activities, in which the other ten children in the control group did not take part. During nine sessions, the activities were completed as follows: FA-FA-FA, P-P-P, and PF-PF-PF; each session lasted 40 min and took place once a week. For the quantitative analysis of salivary cortisol, saliva was collected from the experimental group one week before the HRAs and immediately after the activities for 9 consecutive weeks at the same time each session. In the experimental group, stress scores of interpersonal relationship, school life, personal problems, and home life decreased after the HRAs by 1.3, 1.8, 4.2, and 1.3 points, respectively. In particular, the stress score of school life was significantly reduced (P < 0.01). In addition, from the investigation of the SCCs for the children before and after repeating HRAs three times, it was found that flower arrangement, planting, and flower pressing activities reduced the SCCs by ≥37% compared to the SCCs prior to taking part in the HRAs. These results indicate that HRAs are associated with a reduction in the stress levels of maladjusted elementary school children. Copyright © 2018. Published by Elsevier Ltd.

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

    Directory of Open Access Journals (Sweden)

    Areej M. Assaf

    2017-12-01

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

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

    Science.gov (United States)

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

    2017-12-01

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

  18. Cerebral Embolic Protection During Transcatheter Aortic Valve Replacement Significantly Reduces Death and Stroke Compared With Unprotected Procedures.

    Science.gov (United States)

    Seeger, Julia; Gonska, Birgid; Otto, Markus; Rottbauer, Wolfgang; Wöhrle, Jochen

    2017-11-27

    The aim of this study was to evaluate the impact of cerebral embolic protection on stroke-free survival in patients undergoing transcatheter aortic valve replacement (TAVR). Imaging data on cerebral embolic protection devices have demonstrated a significant reduction in number and volume of cerebral lesions. A total of 802 consecutive patients were enrolled. The Sentinel cerebral embolic protection device (Claret Medical Inc., Santa Rosa, California) was used in 34.9% (n = 280) of consecutive patients. In 65.1% (n = 522) of patients TAVR was performed in the identical setting except without cerebral embolic protection. Neurological follow-up was done within 7 days post-procedure. The primary endpoint was a composite of all-cause mortality or all-stroke according to Valve Academic Research Consortium-2 criteria within 7 days. Propensity score matching was performed to account for possible confounders. Both filters of the device were successfully positioned in 280 of 305 (91.8%) consecutive patients. With use of cerebral embolic protection rate of disabling and nondisabling stroke was significantly reduced from 4.6% to 1.4% (p = 0.03; odds ratio: 0.29, 95% confidence interval: 0.10 to 0.93) in the propensity-matched population (n = 560). The primary endpoint occurred significantly less frequently, with 2.1% (n = 6 of 280) in the protected group compared with 6.8% (n = 19 of 280) in the control group (p = 0.01; odds ratio: 0.30; 95% confidence interval: 0.12 to 0.77). In multivariable analysis Society of Thoracic Surgeons score for mortality (p = 0.02) and TAVR without protection (p = 0.02) were independent predictors for the primary endpoint. In patients undergoing TAVR use of a cerebral embolic protection device demonstrated a significant higher rate of stroke-free survival compared with unprotected TAVR. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  19. Dermal application of nitric oxide releasing acidified nitrite-containing liniments significantly reduces blood pressure in humans.

    Science.gov (United States)

    Opländer, Christian; Volkmar, Christine M; Paunel-Görgülü, Adnana; Fritsch, Thomas; van Faassen, Ernst E; Mürtz, Manfred; Grieb, Gerrit; Bozkurt, Ahmet; Hemmrich, Karsten; Windolf, Joachim; Suschek, Christoph V

    2012-02-15

    Vascular ischemic diseases, hypertension, and other systemic hemodynamic and vascular disorders may be the result of impaired bioavailability of nitric oxide (NO). NO but also its active derivates like nitrite or nitroso compounds are important effector and signal molecules with vasodilating properties. Our previous findings point to a therapeutical potential of cutaneous administration of NO in the treatment of systemic hemodynamic disorders. Unfortunately, no reliable data are available on the mechanisms, kinetics and biological responses of dermal application of nitric oxide in humans in vivo. The aim of the study was to close this gap and to explore the therapeutical potential of dermal nitric oxide application. We characterized with human skin in vitro and in vivo the capacity of NO, applied in a NO-releasing acidified form of nitrite-containing liniments, to penetrate the epidermis and to influence local as well as systemic hemodynamic parameters. We found that dermal application of NO led to a very rapid and significant transepidermal translocation of NO into the underlying tissue. Depending on the size of treated skin area, this translocation manifests itself through a significant systemic increase of the NO derivates nitrite and nitroso compounds, respectively. In parallel, this translocation was accompanied by an increased systemic vasodilatation and blood flow as well as reduced blood pressure. We here give evidence that in humans dermal application of NO has a therapeutic potential for systemic hemodynamic disorders that might arise from local or systemic insufficient availability of NO or its bio-active NO derivates, respectively. Copyright © 2012 Elsevier Inc. All rights reserved.

  20. Significant change of local atomic configurations at surface of reduced activation Eurofer steels induced by hydrogenation treatments

    Energy Technology Data Exchange (ETDEWEB)

    Greculeasa, S.G.; Palade, P.; Schinteie, G. [National Institute for Materials Physics, P.O. Box MG-7, 77125, Bucharest-Magurele (Romania); Kuncser, A.; Stanciu, A. [National Institute for Materials Physics, P.O. Box MG-7, 77125, Bucharest-Magurele (Romania); University of Bucharest, Faculty of Physics, 77125, Bucharest-Magurele (Romania); Lungu, G.A. [National Institute for Materials Physics, P.O. Box MG-7, 77125, Bucharest-Magurele (Romania); Porosnicu, C.; Lungu, C.P. [National Institute for Laser, Plasma and Radiation Physics, 77125, Bucharest-Magurele (Romania); Kuncser, V., E-mail: kuncser@infim.ro [National Institute for Materials Physics, P.O. Box MG-7, 77125, Bucharest-Magurele (Romania)

    2017-04-30

    Highlights: • Engineering of Eurofer slab properties by hydrogenation treatments. • Hydrogenation modifies significantly the local atomic configurations at the surface. • Hydrogenation increases the expulsion of the Cr atoms toward the very surface. • Approaching binomial atomic distribution by hydrogenation in the next surface 100 nm. - Abstract: Reduced-activation steels such as Eurofer alloys are candidates for supporting plasma facing components in tokamak-like nuclear fusion reactors. In order to investigate the impact of hydrogen/deuterium insertion in their crystalline lattice, annealing treatments in hydrogen atmosphere have been applied on Eurofer slabs. The resulting samples have been analyzed with respect to local structure and atomic configuration both before and after successive annealing treatments, by X-ray diffractometry (XRD), scanning electron microscopy and energy dispersive spectroscopy (SEM-EDS), X-ray photoelectron spectroscopy (XPS) and conversion electron Mössbauer spectroscopy (CEMS). The corroborated data point out for a bcc type structure of the non-hydrogenated alloy, with an average alloy composition approaching Fe{sub 0.9}Cr{sub 0.1} along a depth of about 100 nm. EDS elemental maps do not indicate surface inhomogeneities in concentration whereas the Mössbauer spectra prove significant deviations from a homogeneous alloying. The hydrogenation increases the expulsion of the Cr atoms toward the surface layer and decreases their oxidation, with considerable influence on the surface properties of the steel. The hydrogenation treatment is therefore proposed as a potential alternative for a convenient engineering of the surface of different Fe-Cr based alloys.

  1. Optical trapping of nanoparticles with significantly reduced laser powers by using counter-propagating beams (Presentation Recording)

    Science.gov (United States)

    Zhao, Chenglong; LeBrun, Thomas W.

    2015-08-01

    Gold nanoparticles (GNP) have wide applications ranging from nanoscale heating to cancer therapy and biological sensing. Optical trapping of GNPs as small as 18 nm has been successfully achieved with laser power as high as 855 mW, but such high powers can damage trapped particles (particularly biological systems) as well heat the fluid, thereby destabilizing the trap. In this article, we show that counter propagating beams (CPB) can successfully trap GNP with laser powers reduced by a factor of 50 compared to that with a single beam. The trapping position of a GNP inside a counter-propagating trap can be easily modulated by either changing the relative power or position of the two beams. Furthermore, we find that under our conditions while a single-beam most stably traps a single particle, the counter-propagating beam can more easily trap multiple particles. This (CPB) trap is compatible with the feedback control system we recently demonstrated to increase the trapping lifetimes of nanoparticles by more than an order of magnitude. Thus, we believe that the future development of advanced trapping techniques combining counter-propagating traps together with control systems should significantly extend the capabilities of optical manipulation of nanoparticles for prototyping and testing 3D nanodevices and bio-sensing.

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

    Science.gov (United States)

    Sordillo, Peter P; Helson, Lawrence

    2015-01-01

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

  3. Cytokines as endogenous pyrogens.

    Science.gov (United States)

    Dinarello, C A

    1999-03-01

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

  4. New scanning technique using Adaptive Statistical lterative Reconstruction (ASIR) significantly reduced the radiation dose of cardiac CT

    International Nuclear Information System (INIS)

    Tumur, Odgerel; Soon, Kean; Brown, Fraser; Mykytowycz, Marcus

    2013-01-01

    The aims of our study were to evaluate the effect of application of Adaptive Statistical Iterative Reconstruction (ASIR) algorithm on the radiation dose of coronary computed tomography angiography (CCTA) and its effects on image quality of CCTA and to evaluate the effects of various patient and CT scanning factors on the radiation dose of CCTA. This was a retrospective study that included 347 consecutive patients who underwent CCTA at a tertiary university teaching hospital between 1 July 2009 and 20 September 2011. Analysis was performed comparing patient demographics, scan characteristics, radiation dose and image quality in two groups of patients in whom conventional Filtered Back Projection (FBP) or ASIR was used for image reconstruction. There were 238 patients in the FBP group and 109 patients in the ASIR group. There was no difference between the groups in the use of prospective gating, scan length or tube voltage. In ASIR group, significantly lower tube current was used compared with FBP group, 550mA (450–600) vs. 650mA (500–711.25) (median (interquartile range)), respectively, P<0.001. There was 27% effective radiation dose reduction in the ASIR group compared with FBP group, 4.29mSv (2.84–6.02) vs. 5.84mSv (3.88–8.39) (median (interquartile range)), respectively, P<0.001. Although ASIR was associated with increased image noise compared with FBP (39.93±10.22 vs. 37.63±18.79 (mean ±standard deviation), respectively, P<001), it did not affect the signal intensity, signal-to-noise ratio, contrast-to-noise ratio or the diagnostic quality of CCTA. Application of ASIR reduces the radiation dose of CCTA without affecting the image quality.

  5. New scanning technique using Adaptive Statistical Iterative Reconstruction (ASIR) significantly reduced the radiation dose of cardiac CT.

    Science.gov (United States)

    Tumur, Odgerel; Soon, Kean; Brown, Fraser; Mykytowycz, Marcus

    2013-06-01

    The aims of our study were to evaluate the effect of application of Adaptive Statistical Iterative Reconstruction (ASIR) algorithm on the radiation dose of coronary computed tomography angiography (CCTA) and its effects on image quality of CCTA and to evaluate the effects of various patient and CT scanning factors on the radiation dose of CCTA. This was a retrospective study that included 347 consecutive patients who underwent CCTA at a tertiary university teaching hospital between 1 July 2009 and 20 September 2011. Analysis was performed comparing patient demographics, scan characteristics, radiation dose and image quality in two groups of patients in whom conventional Filtered Back Projection (FBP) or ASIR was used for image reconstruction. There were 238 patients in the FBP group and 109 patients in the ASIR group. There was no difference between the groups in the use of prospective gating, scan length or tube voltage. In ASIR group, significantly lower tube current was used compared with FBP group, 550 mA (450-600) vs. 650 mA (500-711.25) (median (interquartile range)), respectively, P ASIR group compared with FBP group, 4.29 mSv (2.84-6.02) vs. 5.84 mSv (3.88-8.39) (median (interquartile range)), respectively, P ASIR was associated with increased image noise compared with FBP (39.93 ± 10.22 vs. 37.63 ± 18.79 (mean ± standard deviation), respectively, P ASIR reduces the radiation dose of CCTA without affecting the image quality. © 2013 The Authors. Journal of Medical Imaging and Radiation Oncology © 2013 The Royal Australian and New Zealand College of Radiologists.

  6. Secukinumab Significantly Reduces Psoriasis-Related Work Impairment and Indirect Costs Compared With Ustekinumab and Etanercept in the United Kingdom.

    Science.gov (United States)

    Warren, R B; Halliday, A; Graham, C N; Gilloteau, I; Miles, L; McBride, D

    2018-05-30

    Psoriasis causes work productivity impairment that increases with disease severity. Whether differential treatment efficacy translates into differential indirect cost savings is unknown. To assess work hours lost and indirect costs associated with secukinumab versus ustekinumab and etanercept in the United Kingdom (UK). This was a post hoc analysis of work impairment data collected in the CLEAR study (secukinumab vs. ustekinumab) and applied to the FIXTURE study (secukinumab vs. etanercept). Weighted weekly and annual average indirect costs per patient per treatment were calculated from (1) overall work impairment derived from Work Productivity and Activity Impairment data collected in CLEAR at 16 and 52 weeks by Psoriasis Area and Severity Index (PASI) response level; (2) weekly/annual work productivity loss by PASI response level; (3) weekly and annual indirect costs by PASI response level, based on hours of work productivity loss; and (4) weighted average indirect costs for each treatment. In the primary analysis, work impairment data for employed patients in CLEAR at Week 16 were used to compare secukinumab and ustekinumab. Secondary analyses were conducted at different timepoints and with patient cohorts, including FIXTURE. In CLEAR, 452 patients (67%) were employed at baseline. At Week 16, percentages of weekly work impairment/mean hours lost decreased with higher PASI: PASI hours; PASI 50-74: 13.3%/4.45 hours; PASI 75-89: 6.4%/2.14 hours; PASI ≥90: 4.9%/1.65 hours. Weighted mean weekly/annual work hours lost were significantly lower for secukinumab than ustekinumab (1.96/102.51 vs. 2.40/125.12; P=0.0006). Results were consistent for secukinumab versus etanercept (2.29/119.67 vs. 3.59/187.17; Ρreduced work impairment and associated indirect costs of psoriasis compared with ustekinumab and etanercept at Week 16 through 52 in the UK. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  7. Inflammatory cytokines and immune system modulation by aerobic ...

    African Journals Online (AJOL)

    Keywords: Immune function, inflammatory cytokines, aerobic exercise, resistance exercise, aging. ... Physical exercise is effective in reducing (or ameliorate) the ..... moderate resistance training program increases muscle .... Nutrition Metabo-.

  8. Cytokines and Liver Diseases

    Directory of Open Access Journals (Sweden)

    Herbert Tilg

    2001-01-01

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

  9. Oxidation of naturally reduced uranium in aquifer sediments by dissolved oxygen and its potential significance to uranium plume persistence

    Science.gov (United States)

    Davis, J. A.; Smith, R. L.; Bohlke, J. K.; Jemison, N.; Xiang, H.; Repert, D. A.; Yuan, X.; Williams, K. H.

    2015-12-01

    The occurrence of naturally reduced zones is common in alluvial aquifers in the western U.S.A. due to the burial of woody debris in flood plains. Such reduced zones are usually heterogeneously dispersed in these aquifers and characterized by high concentrations of organic carbon, reduced mineral phases, and reduced forms of metals, including uranium(IV). The persistence of high concentrations of dissolved uranium(VI) at uranium-contaminated aquifers on the Colorado Plateau has been attributed to slow oxidation of insoluble uranium(IV) mineral phases found in association with these reducing zones, although there is little understanding of the relative importance of various potential oxidants. Four field experiments were conducted within an alluvial aquifer adjacent to the Colorado River near Rifle, CO, wherein groundwater associated with the naturally reduced zones was pumped into a gas-impermeable tank, mixed with a conservative tracer (Br-), bubbled with a gas phase composed of 97% O2 and 3% CO2, and then returned to the subsurface in the same well from which it was withdrawn. Within minutes of re-injection of the oxygenated groundwater, dissolved uranium(VI) concentrations increased from less than 1 μM to greater than 2.5 μM, demonstrating that oxygen can be an important oxidant for uranium in such field systems if supplied to the naturally reduced zones. Dissolved Fe(II) concentrations decreased to the detection limit, but increases in sulfate could not be detected due to high background concentrations. Changes in nitrogen species concentrations were variable. The results contrast with other laboratory and field results in which oxygen was introduced to systems containing high concentrations of mackinawite (FeS), rather than the more crystalline iron sulfides found in aged, naturally reduced zones. The flux of oxygen to the naturally reduced zones in the alluvial aquifers occurs mainly through interactions between groundwater and gas phases at the water table

  10. A Single Bout of Fasting (24 h) Reduces Basal Cytokine Expression and Minimally Impacts the Sterile Inflammatory Response in the White Adipose Tissue of Normal Weight F344 Rats.

    Science.gov (United States)

    Speaker, Kristin J; Paton, Madeline M; Cox, Stewart S; Fleshner, Monika

    2016-01-01

    Sterile inflammation occurs when inflammatory proteins are increased in blood and tissues by nonpathogenic states and is a double-edged sword depending on its cause (stress, injury, or disease), duration (transient versus chronic), and inflammatory milieu. Short-term fasting can exert a host of health benefits through unknown mechanisms. The following experiment tested if a 24 h fast would modulate basal and stress-evoked sterile inflammation in plasma and adipose. Adult male F344 rats were either randomized to ad libitum access to food or fasted for 24 h prior to 0 (control), 10, or 100, 1.5 mA-5 s intermittent, inescapable tail shocks (IS). Glucose, nonesterified free fatty acids (NEFAs), insulin, leptin, and corticosterone were measured in plasma and tumor necrosis factor- (TNF-) α , interleukin- (IL-) 1 β , IL-6, and IL-10 in plasma, and subcutaneous, intraperitoneal, and visceral compartments of white adipose tissue (WAT). In control rats, a 24 h fast reduced all measured basal cytokines in plasma and visceral WAT, IL-1 β and IL-6 in subcutaneous WAT, and IL-6 in intraperitoneal WAT. In stressed rats (IS), fasting reduced visceral WAT TNF- α , subcutaneous WAT IL-1 β , and plasma insulin and leptin. Short-term fasting may thus prove to be a useful dietary strategy for reducing peripheral inflammatory states associated with visceral obesity and chronic stress.

  11. A Single Bout of Fasting (24 h Reduces Basal Cytokine Expression and Minimally Impacts the Sterile Inflammatory Response in the White Adipose Tissue of Normal Weight F344 Rats

    Directory of Open Access Journals (Sweden)

    Kristin J. Speaker

    2016-01-01

    Full Text Available Sterile inflammation occurs when inflammatory proteins are increased in blood and tissues by nonpathogenic states and is a double-edged sword depending on its cause (stress, injury, or disease, duration (transient versus chronic, and inflammatory milieu. Short-term fasting can exert a host of health benefits through unknown mechanisms. The following experiment tested if a 24 h fast would modulate basal and stress-evoked sterile inflammation in plasma and adipose. Adult male F344 rats were either randomized to ad libitum access to food or fasted for 24 h prior to 0 (control, 10, or 100, 1.5 mA-5 s intermittent, inescapable tail shocks (IS. Glucose, nonesterified free fatty acids (NEFAs, insulin, leptin, and corticosterone were measured in plasma and tumor necrosis factor- (TNF- α, interleukin- (IL- 1β, IL-6, and IL-10 in plasma, and subcutaneous, intraperitoneal, and visceral compartments of white adipose tissue (WAT. In control rats, a 24 h fast reduced all measured basal cytokines in plasma and visceral WAT, IL-1β and IL-6 in subcutaneous WAT, and IL-6 in intraperitoneal WAT. In stressed rats (IS, fasting reduced visceral WAT TNF-α, subcutaneous WAT IL-1β, and plasma insulin and leptin. Short-term fasting may thus prove to be a useful dietary strategy for reducing peripheral inflammatory states associated with visceral obesity and chronic stress.

  12. [Study on the correlation of the effect of entecavir on Th1/Th2 cytokines level in the treatment of chronic hepatitis].

    Science.gov (United States)

    Li, L; Jing, Y B; Liu, J; Wang, C L; Liu, B

    2017-08-20

    Objective: To explore the expression level of peripheral blood Th1/Th2 type cytokines of chronic hepatitis b (CHB) patients in the entecavir (ETV) antiviral treatment, analyze the relationship between various cytokines, and the correlation among of cytokines and HBV DNA loads. Methods: Luminex Liquid Chip Technology was applied to detect the peripheral blood Th1/Th2 type cytokines expression level of CHB patients; At the same time, liver function was detected by Fully Automatic Biochemical Analyzer; HBV DNA loads were detected by PCR Method; Hepatitis b virology markers were detected by Chemiluminescence Method. F-test and Pearson correlation analysis were used for statistical analysis. Results: Before ETV antiviral treatment, peripheral blood Th1 cytokines IFN gamma expression level in patients with CHB increased significantly ( P = 0.010) compared with the healthy control group while TNF alpha expression level having no statistically significant difference ( P = 0.095); Th2 type cytokines IL-4, IL-6, IL-10 levels decreased obviously ( P = 0.039, P = 0.014, P = 0.026) compared with those in the control group. After 48 weeks of treatment, Th1 cytokines IFN gamma and TNF alpha expression levels were reduced significantly (19.2±5.03 pg/ml vs 24.69±6.51 pg/ml, and 6.09±4.99 pg/ml vs 9.50±7.34 pg/ml, P Th1/Th2 type cytokines. And there was no correlation between the various cytokines and HBV DNA loads in patients with CHB. Conclusion: ETV can not only inhibit HBV DNA replication, reducing HBV DNA loads, but also contribute to regulate Th1/Th2 type cytokines expression level in patients with CHB, but there was no correlation between the levels of various cytokines, various cytokines and HBV DNA loads.

  13. Vaccination of pigs two weeks before infection significantly reduces transmission of foot-and-mouth disease virus

    NARCIS (Netherlands)

    Eble, P.L.; Bouma, A.; Bruin, de M.G.M.; Hemert-Kluitenberg, van F.; Oirschot, van J.T.; Dekker, A.

    2004-01-01

    The objective of this study was to investigate whether and at what time interval could vaccination reduce transmission of foot-and-Mouth disease virus (FMDV) among pigs. Reduction of virus transmission by vaccination was determined experimentally. Transmission of FMDV was studied in three groups of

  14. 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...

  15. 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....

  16. Interleukin-6 blockade raises LDL via reduced catabolism rather than via increased synthesis: a cytokine-specific mechanism for cholesterol changes in rheumatoid arthritis.

    Science.gov (United States)

    Robertson, Jamie; Porter, Duncan; Sattar, Naveed; Packard, Chris J; Caslake, Muriel; McInnes, Iain; McCarey, David

    2017-11-01

    Patients with rheumatoid arthritis (RA) have reduced serum low-density lipoprotein cholesterol (LDL-c), which increases following therapeutic IL-6 blockade. We aimed to define the metabolic pathways underlying these lipid changes. In the KALIBRA study, lipoprotein kinetic studies were performed on 11 patients with severe active RA at baseline and following three intravenous infusions of the IL-6R blocker tocilizumab. The primary outcome measure was the fractional catabolic rate (FCR) of LDL. Serum total cholesterol (4.8 vs 5.7 mmol/L, p=0.003), LDL-c (2.9 vs 3.4 mmol/L, p=0.014) and high-density lipoprotein cholesterol (1.23 vs 1.52 mmol/L, p=0.006) increased following tocilizumab therapy. The LDL FCR fell from a state of hypercatabolism to a value approximating that of the normal population (0.53 vs 0.27 pools/day, p=0.006). Changes in FCR correlated tightly with changes in serum LDL-c and C-reactive protein but not Clinical Disease Activity Index. Patients with RA have low serum LDL-c due to hypercatabolism of LDL particles. IL-6 blockade normalises this catabolism in a manner associating with the acute phase response (and thus hepatic IL-6 signalling) but not with RA disease activity as measured clinically. We demonstrate that IL-6 is one of the key drivers of inflammation-driven dyslipidaemia. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  17. ClusterSignificance: A bioconductor package facilitating statistical analysis of class cluster separations in dimensionality reduced data

    DEFF Research Database (Denmark)

    Serviss, Jason T.; Gådin, Jesper R.; Eriksson, Per

    2017-01-01

    , e.g. genes in a specific pathway, alone can separate samples into these established classes. Despite this, the evaluation of class separations is often subjective and performed via visualization. Here we present the ClusterSignificance package; a set of tools designed to assess the statistical...... significance of class separations downstream of dimensionality reduction algorithms. In addition, we demonstrate the design and utility of the ClusterSignificance package and utilize it to determine the importance of long non-coding RNA expression in the identity of multiple hematological malignancies....

  18. Pigment Epithelium-Derived Factor Reduces Apoptosis and Pro-Inflammatory Cytokine Gene Expression in a Murine Model of Focal Retinal Degeneration

    Directory of Open Access Journals (Sweden)

    Yujuan Wang

    2013-10-01

    Full Text Available AMD (age-related macular degeneration is a neurodegenerative disease causing irreversible central blindness in the elderly. Apoptosis and inflammation play important roles in AMD pathogenesis. PEDF (pigment epithelium-derived factor is a potent neurotrophic and anti-inflammatory glycoprotein that protects the retinal neurons and photoreceptors against cell death caused by pathological insults. We studied the effects of PEDF on focal retinal lesions in DKO rd8 (Ccl2 −/− /Cx3cr1 −/− on C57BL/6N [Crb1rd8 ] mice, a model for progressive, focal rd (retinal degeneration. First, we found a significant decrease in PEDF transcript expression in DKO rd8 mouse retina and RPE (retinal pigment epithelium than WT (wild-type, C57BL/6N. Next, cultured DKO rd8 RPE cells secreted lower levels of PEDF protein in the media than WT. Then the right eyes of DKO rd8 mice were injected intravitreously with recombinant human PEDF protein (1 μg, followed by a subconjunctival injection of PEDF (3 μg 4 weeks later. The untreated left eyes served as controls. The effect of PEDF was assessed by fundoscopy, ocular histopathology and A2E {[2,6-dimethyl-8-(2,6,6-trimethyl-1-cyclohexen-1-yl-1E,3E,5E,7E-octatetra-enyl]-1-(2-hydroxyethyl-4-[4-methyl-6(2,6,6-trimethyl-1-cyclohexen-1-yl 1E,3E,5E,7E-hexatrienyl]-pyridinium} levels, as well as apoptotic and inflammatory molecules. The PEDF-treated eyes showed slower progression or attenuation of the focal retinal lesions, fewer and/or smaller photoreceptor and RPE degeneration, and significantly lower A2E, relative to the untreated eyes. In addition, lower expression of apoptotic and inflammatory molecules were detected in the PEDF-treated than untreated eyes. Our results establish that PEDF potently stabilizes photoreceptor degeneration via suppression of both apoptotic and inflammatory pathways. The multiple beneficial effects of PEDF represent a novel approach for potential AMD treatment.

  19. Pigment epithelium-derived factor reduces apoptosis and pro-inflammatory cytokine gene expression in a murine model of focal retinal degeneration.

    Science.gov (United States)

    Wang, Yujuan; Subramanian, Preeti; Shen, Defen; Tuo, Jingsheng; Becerra, S Patricia; Chan, Chi-Chao

    2013-11-26

    AMD (age-related macular degeneration) is a neurodegenerative disease causing irreversible central blindness in the elderly. Apoptosis and inflammation play important roles in AMD pathogenesis. PEDF (pigment epithelium-derived factor) is a potent neurotrophic and anti-inflammatory glycoprotein that protects the retinal neurons and photoreceptors against cell death caused by pathological insults. We studied the effects of PEDF on focal retinal lesions in DKO rd8 (Ccl2(-/-)/Cx3cr1(-/-) on C57BL/6N [Crb1(rd8)]) mice, a model for progressive, focal rd (retinal degeneration). First, we found a significant decrease in PEDF transcript expression in DKO rd8 mouse retina and RPE (retinal pigment epithelium) than WT (wild-type, C57BL/6N). Next, cultured DKO rd8 RPE cells secreted lower levels of PEDF protein in the media than WT. Then the right eyes of DKO rd8 mice were injected intravitreously with recombinant human PEDF protein (1 μg), followed by a subconjunctival injection of PEDF (3 μg) 4 weeks later. The untreated left eyes served as controls. The effect of PEDF was assessed by fundoscopy, ocular histopathology and A2E {[2,6-dimethyl-8-(2,6,6-trimethyl-1-cyclohexen-1-yl)-1E,3E,5E,7E-octatetra-enyl]-1-(2-hydroxyethyl)-4-[4-methyl-6(2,6,6-trimethyl-1-cyclohexen-1-yl) 1E,3E,5E,7E-hexatrienyl]-pyridinium} levels, as well as apoptotic and inflammatory molecules. The PEDF-treated eyes showed slower progression or attenuation of the focal retinal lesions, fewer and/or smaller photoreceptor and RPE degeneration, and significantly lower A2E, relative to the untreated eyes. In addition, lower expression of apoptotic and inflammatory molecules were detected in the PEDF-treated than untreated eyes. Our results establish that PEDF potently stabilizes photoreceptor degeneration via suppression of both apoptotic and inflammatory pathways. The multiple beneficial effects of PEDF represent a novel approach for potential AMD treatment.

  20. Hypothyroidism and depression: Are cytokines the link?

    Directory of Open Access Journals (Sweden)

    Parimal S Tayde

    2017-01-01

    Full Text Available Context: Primary hypothyroidism has been thought of as an inflammatory condition characterized by raised levels of cytokines such as C-reactive protein (CRP, interleukin-6 (IL-6, and tumor necrosis factor-alpha (TNF-α. Depression is also well known to occur in hypothyroidism. Depression is also characterized by elevated inflammatory cytokines. We planned to study whether cytokines play an important part in linking these two conditions. Objectives: (1 To know the prevalence of depression in overt hypothyroidism due to autoimmune thyroid disease. (2 To correlate the levels of inflammatory markers with the occurrence of depression. (3 To study the effect of levothyroxine on inflammatory markers and depression. Materials and Methods: In this longitudinal, case–controlled study, 33 patients with autoimmune hypothyroidism (thyroid-stimulating hormone >10 uIU/ml were included with 33 age-, sex-, and body max index-matched healthy controls. Individuals were tested for Serum TNF-α, IL-6, high-sensitivity-CRP (hs-CRP. They were assessed for depression using Montgomery Asberg Depression Rating Scale (MADRS and World Health Organization Quality of Life (QOL Scale. Patients received L Thyroxine titrated to achieve euthyroidism and were reassessed for inflammatory markers and cognitive dysfunction. Results: Nineteen patients (57% had mild to moderate depression (MADRS >11. After 6 months of treatment, eight patients (42% had remission of depression with significant improvement in QOL scores (P < 0.05. TNF-α, IL-6, and hs-CRP were significantly elevated in patients compared with controls and reduced with therapy but did not reach baseline as controls. The change in inflammatory markers correlated with improvement in QOL scores in social and environmental domains (P < 0.01. Conclusions: Primary autoimmune hypothyroidism is an inflammatory state characterized by elevated cytokines which decline with LT4 therapy. It is associated with depression and poor

  1. Human osteoarthritic cartilage shows reduced in vivo expression of IL-4, a chondroprotective cytokine that differentially modulates IL-1β-stimulated production of chemokines and matrix-degrading enzymes in vitro.

    Directory of Open Access Journals (Sweden)

    Elisa Assirelli

    Full Text Available BACKGROUND: In osteoarthritis (OA, an inflammatory environment is responsible for the imbalance between the anabolic and catabolic activity of chondrocytes and, thus, for articular cartilage derangement. This study was aimed at providing further insight into the impairment of the anabolic cytokine IL-4 and its receptors in human OA cartilage, as well as the potential ability of IL-4 to antagonize the catabolic phenotype induced by IL-1β. METHODOLOGY/PRINCIPAL FINDINGS: The in vivo expression of IL-4 and IL-4 receptor subunits (IL-4R, IL-2Rγ, IL-13Rα1 was investigated on full thickness OA or normal knee cartilage. IL-4 expression was found to be significantly lower in OA, both in terms of the percentage of positive cells and the amount of signal per cell. IL-4 receptor type I and II were mostly expressed in mid-deep cartilage layers. No significant difference for each IL-4 receptor subunit was noted. IL-4 anti-inflammatory and anti-catabolic activity was assessed in vitro in the presence of IL-1β and/or IL-4 for 24 hours using differentiated high density primary OA chondrocyte also exhibiting the three IL-4 R subunits found in vivo. Chemokines, extracellular matrix degrading enzymes and their inhibitors were evaluated at mRNA (real time PCR and protein (ELISA or western blot levels. IL-4 did not affect IL-1β-induced mRNA expression of GRO-α/CXCL1, IL-8/CXCL8, ADAMTS-5, TIMP-1 or TIMP-3. Conversely, IL-4 significantly inhibited RANTES/CCL5, MIP-1α/CCL3, MIP-1β/CCL4, MMP-13 and ADAMTS-4. These results were confirmed at protein level for RANTES/CCL5 and MMP-13. CONCLUSIONS/SIGNIFICANCE: Our results indicate for the first time that OA cartilage has a significantly lower expression of IL-4. Furthermore, we found differences in the spectrum of biological effects of IL-4. The findings that IL-4 has the ability to hamper the IL-1β-induced release of both MMP-13 and CCL5/RANTES, both markers of OA chondrocytes, strongly indicates IL-4 as a

  2. A novel multi-stage subunit vaccine against paratuberculosis induces significant immunity and reduces bacterial burden in tissues (P4304)

    DEFF Research Database (Denmark)

    Thakur, Aneesh; Aagaard, Claus; Riber, Ulla

    2013-01-01

    Effective control of paratuberculosis is hindered by lack of a vaccine preventing infection, transmission and without diagnostic interference with tuberculosis. We have developed a novel multi-stage recombinant subunit vaccine in which a fusion of four early expressed MAP antigens is combined...... characterized by a significant containment of bacterial burden in gut tissues compared to non-vaccinated animals. There was no cross-reaction with bovine tuberculosis in vaccinated animals. This novel multi-stage vaccine has the potential to become a marker vaccine for paratuberculosis....

  3. Reduced expression of circRNA hsa_circ_0003159 in gastric cancer and its clinical significance.

    Science.gov (United States)

    Tian, Mengqian; Chen, Ruoyu; Li, Tianwen; Xiao, Bingxiu

    2018-03-01

    Circular RNAs (circRNAs) play a crucial role in the occurrence of several diseases including cancers. However, little is known about circRNAs' diagnostic values for gastric cancer, one of the worldwide most common diseases of mortality. The hsa_circ_0003159 levels in 108 paired gastric cancer tissues and adjacent non-tumorous tissues from surgical patients with gastric cancer were first detected by real-time quantitative reverse transcription-polymerase chain reaction. Then, the relationships between hsa_circ_0003159 expression levels in gastric cancer tissues and the clinicopathological factors of patients with gastric cancer were analyzed. Finally, its diagnostic value was evaluated through the receiver operating characteristic curve. Compared with paired adjacent non-tumorous tissues, hsa_circ_0003159 expression was significantly down-regulated in gastric cancer tissues. What is more, we found that hsa_circ_0003159 expression levels were significantly negatively associated with gender, distal metastasis, and tumor-node-metastasis stage. All of the results suggest that hsa_circ_0003159 may be a potential cancer marker of patients with gastric cancer. © 2017 Wiley Periodicals, Inc.

  4. β-Hydroxy-β-methylbutyrate (HMB) supplementation and resistance exercise significantly reduce abdominal adiposity in healthy elderly men.

    Science.gov (United States)

    Stout, Jeffrey R; Fukuda, David H; Kendall, Kristina L; Smith-Ryan, Abbie E; Moon, Jordan R; Hoffman, Jay R

    2015-04-01

    The effects of 12-weeks of HMB ingestion and resistance training (RT) on abdominal adiposity were examined in 48 men (66-78 yrs). All participants were randomly assigned to 1 of 4 groups: no-training placebo (NT-PL), HMB only (NT-HMB), RT with PL (RT-PL), or HMB with RT (RT-HMB). DXA was used to estimate abdominal fat mass (AFM) by placing the region of interest over the L1-L4 region of the spine. Outcomes were assessed by ANCOVA, with Bonferroni-corrected pairwise comparisons. Baseline AFM values were used as the covariate. The ANCOVA indicated a significant difference (p = 0.013) between group means for the adjusted posttest AFM values (mean (kg) ± SE: NT-PL = 2.59 ± 0.06; NT-HMB = 2.59 ± 0.61; RT-PL = 2.59 ± 0.62; RT-HMB = 2.34 ± 0.61). The pairwise comparisons indicated that AFM following the intervention period in the RT-HMB group was significantly less than NT-PL (p = 0.013), NT-HMB (p = 0.011), and RT-PL (p = 0.010). These data suggested that HMB in combination with 12 weeks of RT decreased AFM in elderly men. Copyright © 2015. Published by Elsevier Inc.

  5. Wind Erosion Caused by Land Use Changes Significantly Reduces Ecosystem Carbon Storage and Carbon Sequestration Potentials in Grassland

    Science.gov (United States)

    Li, P.; Chi, Y. G.; Wang, J.; Liu, L.

    2017-12-01

    Wind erosion exerts a fundamental influence on the biotic and abiotic processes associated with ecosystem carbon (C) cycle. However, how wind erosion under different land use scenarios will affect ecosystem C balance and its capacity for future C sequestration are poorly quantified. Here, we established an experiment in a temperate steppe in Inner Mongolia, and simulated different intensity of land uses: control, 50% of aboveground vegetation removal (50R), 100% vegetation removal (100R) and tillage (TI). We monitored lateral and vertical carbon flux components and soil characteristics from 2013 to 2016. Our study reveals three key findings relating to the driving factors, the magnitude and consequence of wind erosion on ecosystem C balance: (1) Frequency of heavy wind exerts a fundamental control over the severity of soil erosion, and its interaction with precipitation and vegetation characteristics explained 69% variation in erosion intensity. (2) With increases in land use intensity, the lateral C flux induced by wind erosion increased rapidly, equivalent to 33%, 86%, 111% and 183% of the net ecosystem exchange of the control site under control, 50R, 100R and TI sites, respectively. (3) After three years' treatment, erosion induced decrease in fine fractions led to 31%, 43%, 85% of permanent loss of C sequestration potential in the surface 5cm soil for 50R, 100R and TI sites. Overall, our study demonstrates that lateral C flux associated with wind erosion is too large to be ignored. The loss of C-enriched fine particles not only reduces current ecosystem C content, but also results in irreversible loss of future soil C sequestration potential. The dynamic soil characteristics need be considered when projecting future ecosystem C balance in aeolian landscape. We also propose that to maintain the sustainability of grassland ecosystems, land managers should focus on implementing appropriate land use rather than rely on subsequent managements on degraded soils.

  6. Postoperative Stiffness Requiring Manipulation Under Anesthesia Is Significantly Reduced After Simultaneous Versus Staged Bilateral Total Knee Arthroplasty.

    Science.gov (United States)

    Meehan, John P; Monazzam, Shafagh; Miles, Troy; Danielsen, Beate; White, Richard H

    2017-12-20

    adjust for relevant risk factors, the 90-day odds ratio (OR) of undergoing manipulation after simultaneous bilateral TKA was significantly lower than that for unilateral TKA (OR = 0.70; 95% confidence interval [CI], 0.57 to 0.86) and staged bilateral TKA (OR = 0.71; 95% CI, 0.57 to 0.90). Similarly, at 180 days, the odds of undergoing manipulation were significantly lower after simultaneous bilateral TKA than after both unilateral TKA (OR = 0.71; 95% CI, 0.59 to 0.84) and staged bilateral TKA (OR = 0.76; 95% CI, 0.63 to 0.93). The frequency of manipulation was significantly associated with younger age, fewer comorbidities, black race, and the absence of obesity. Although the ORs were small (close to 1), simultaneous bilateral TKA had a significantly decreased rate of stiffness requiring manipulation under anesthesia at 90 days and 180 days after knee replacement compared with that after staged bilateral TKA and unilateral TKA. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

  7. Significance of surface functionalization of Gold Nanorods for reduced effect on IgG stability and minimization of cytotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Alex, Sruthi Ann; Rajiv, Sundaramoorthy [Centre for Nanobiotechnology, VIT University, Vellore (India); Chakravarty, Sujay [UGC-DAE CSR, Kalpakkam, Node, Kokilamedu (India); Chandrasekaran, N. [Centre for Nanobiotechnology, VIT University, Vellore (India); Mukherjee, Amitava, E-mail: amit.mookerjea@gmail.com [Centre for Nanobiotechnology, VIT University, Vellore (India)

    2017-02-01

    side effect of AuNRs by modifying capping. • Polymer-coated AuNRs safe for in vitro assays, but hamper protein functioning. • PEG-AuNRs reduced toxicity to lymphocyte cells and lesser effect on IgG. • Highlights importance of neutral PEGylated particles for theranostic applications.

  8. Significance of surface functionalization of Gold Nanorods for reduced effect on IgG stability and minimization of cytotoxicity

    International Nuclear Information System (INIS)

    Alex, Sruthi Ann; Rajiv, Sundaramoorthy; Chakravarty, Sujay; Chandrasekaran, N.; Mukherjee, Amitava

    2017-01-01

    side effect of AuNRs by modifying capping. • Polymer-coated AuNRs safe for in vitro assays, but hamper protein functioning. • PEG-AuNRs reduced toxicity to lymphocyte cells and lesser effect on IgG. • Highlights importance of neutral PEGylated particles for theranostic applications.

  9. [Intra-Articular Application of Tranexamic Acid Significantly Reduces Blood Loss and Transfusion Requirement in Primary Total Knee Arthroplasty].

    Science.gov (United States)

    Lošťák, J; Gallo, J; Špička, J; Langová, K

    2016-01-01

    PURPOSE OF THE STUDY The aim of this prospective study was to investigate the effect of topical application of tranexamic acid (TXA, Exacyl) on the amount of post-operative blood loss, and blood transfusion requirement in patients undergoing primary total knee arthroplasty (TKA). Attention was paid to early complications potentially associated with TXA administration, such as haematoma, wound exudate, or knee swelling. In addition, the economic benefit of TXA treatment was also taken into account. MATERIAL AND METHODS The study included 238 patients (85 men and 153 women) who underwent primary total knee arthroplasty (TKA) at our department between January 2013 and November 2015. A group of 119 patients (41 men and 78 women) received intraarticular TXA injections according to the treatment protocol (TXA group). A control group matched in basic characteristics to the TXA group also consisted of 119 patients. The average age in the TXA group was 69.8 years, and the most frequent indication for TKA surgery was primary knee osteoarthritis (81.5%). In each patient, post-operative volume of blood lost from drains and total blood loss including hidden blood loss were recorded, as well as post-operative haemoglobin and haematocrit levels. On discharge of each patient from hospital, the size and site of a haematoma; wound exudate, if present after post-operative day 4; joint swelling; range of motion and early revision surgery, if performed, were evaluated. Requirements of analgesic drugs after surgery were also recorded. RESULTS In the TXA group, blood losses from drains were significantly lower than in the control group (456.7 ± 270.8 vs 640.5 ±448.2; p = 0.004). The median value for blood losses from drains was lower by 22% and the average value for total blood loss, including hidden losses, was also lower than in the control group (762.4 ± 345.2 ml vs 995.5 ± 457.3 ml). The difference in the total amount of blood loss between the two groups was significant (p = 0

  10. Weight loss significantly reduces serum lipocalin-2 levels in overweight and obese women with polycystic ovary syndrome.

    Science.gov (United States)

    Koiou, Ekaterini; Tziomalos, Konstantinos; Katsikis, Ilias; Kandaraki, Eleni A; Kalaitzakis, Emmanuil; Delkos, Dimitrios; Vosnakis, Christos; Panidis, Dimitrios

    2012-01-01

    Serum lipocalin-2 levels are elevated in obese patients. We assessed serum lipocalin-2 levels in polycystic ovary syndrome (PCOS) and the effects of weight loss or metformin on these levels. Forty-seven overweight/obese patients with PCOS [body mass index (BMI) >27 kg/m(2)] were instructed to follow a low-calorie diet, to exercise and were given orlistat or sibutramine for 6 months. Twenty-five normal weight patients with PCOS (BMI weight and 25 overweight/obese healthy female volunteers comprised the control groups. Serum lipocalin-2 levels did not differ between overweight/obese patients with PCOS and overweight/obese controls (p = 0.258), or between normal weight patients with PCOS and normal weight controls (p = 0.878). Lipocalin-2 levels were higher in overweight/obese patients with PCOS than in normal weight patients with PCOS (p weight loss resulted in a fall in lipocalin-2 levels (p weight patients with PCOS, treatment with metformin did not affect lipocalin-2 levels (p = 0.484). In conclusion, PCOS per se is not associated with elevated lipocalin-2 levels. Weight loss induces a significant reduction in lipocalin-2 levels in overweight/obese patients with PCOS.

  11. Cytokine profile of rats fed a diet containing shrimp

    Directory of Open Access Journals (Sweden)

    Elizabeth Lage Borges

    2013-02-01

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

  12. Alpha-mangostin inhibits both dengue virus production and cytokine/chemokine expression.

    Science.gov (United States)

    Tarasuk, Mayuri; Songprakhon, Pucharee; Chimma, Pattamawan; Sratongno, Panudda; Na-Bangchang, Kesara; Yenchitsomanus, Pa-Thai

    2017-08-15

    Since severe dengue virus (DENV) infection in humans associates with both high viral load and massive cytokine production - referred to as "cytokine storm", an ideal drug for treatment of DENV infection should efficiently inhibit both virus production and cytokine expression. In searching for such an ideal drug, we discovered that α-mangostin (α-MG), a major bioactive compound purified from the pericarp of the mangosteen fruit (Garcinia mangostana Linn), which has been used in traditional medicine for several conditions including trauma, diarrhea, wound infection, pain, fever, and convulsion, inhibits both DENV production in cultured hepatocellular carcinoma HepG2 and Huh-7 cells, and cytokine/chemokine expression in HepG2 cells. α-MG could also efficiently inhibit all four serotypes of DENV. Treatment of DENV-infected cells with α-MG (20μM) significantly reduced the infection rates of four DENV serotypes by 47-55%. α-MG completely inhibited production of DENV-1 and DENV-3, and markedly reduced production of DENV-2 and DENV-4 by 100 folds. Furthermore, it could markedly reduce cytokine (IL-6 and TNF-α) and chemokine (RANTES, MIP-1β, and IP-10) transcription. These actions of α-MG are more potent than those of antiviral agent (ribavirin) and anti-inflammatory drug (dexamethasone). Thus, α-MG is potential to be further developed as therapeutic agent for DENV infection. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Cytokines in human milk.

    Science.gov (United States)

    Garofalo, Roberto

    2010-02-01

    Epidemiologic studies conducted in the past 30 years to investigate the protective functions of human milk strongly support the notion that breastfeeding prevents infantile infections, particularly those affecting the gastrointestinal and respiratory tracts. However, more recent clinical and experimental observations also suggest that human milk not only provides passive protection, but also can directly modulate the immunological development of the recipient infant. The study of this remarkable defense system in human milk has been difficult because of its biochemical complexity, the small concentration of certain bioactive components, the compartmentalization of some of these agents, the dynamic quantitative and qualitative changes of milk during lactation, and the lack of specific reagents to quantify these agents. However, a host of bioactive substances, including hormones, growth factors, and immunological factors such as cytokines, have been identified in human milk. Cytokines are pluripotent polypeptides that act in autocrine/paracrine fashions by binding to specific cellular receptors. They operate in networks and orchestrate the development and functions of immune system. Several different cytokines and chemokines have been discovered in human milk in the past years, and the list is growing very rapidly. This article will review the current knowledge about the increasingly complex network of chemoattractants, activators, and anti-inflammatory cytokines present in human milk and their potential role in compensating for the developmental delay of the neonate immune system. Copyright 2010. Published by Mosby, Inc.

  14. Recombinant Cytokines from Plants

    Czech Academy of Sciences Publication Activity Database

    Sirko, A.; Vaněk, Tomáš; Gora-Sochacka, A.; Redkiewicz, P.

    2011-01-01

    Roč. 12, č. 6 (2011), s. 3536-3552 ISSN 1661-6596 Institutional research plan: CEZ:AV0Z50380511 Keywords : cytokines * pharmaceutical proteins * plant-based production systems Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.598, year: 2011

  15. Cytokine loops driving senescence

    Czech Academy of Sciences Publication Activity Database

    Bartek, Jiří; Hodný, Zdeněk; Lukáš, Jan

    2008-01-01

    Roč. 10, č. 8 (2008), s. 887-889 ISSN 1465-7392 Institutional research plan: CEZ:AV0Z50520514 Keywords : cellular senescence * cytokines * autocrine feedback loop Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 17.774, year: 2008

  16. Human Tubal-Derived Mesenchymal Stromal Cells Associated with Low Level Laser Therapy Significantly Reduces Cigarette Smoke-Induced COPD in C57BL/6 mice.

    Directory of Open Access Journals (Sweden)

    Jean Pierre Schatzmann Peron

    Full Text Available Cigarette smoke-induced chronic obstructive pulmonary disease is a very debilitating disease, with a very high prevalence worldwide, which results in a expressive economic and social burden. Therefore, new therapeutic approaches to treat these patients are of unquestionable relevance. The use of mesenchymal stromal cells (MSCs is an innovative and yet accessible approach for pulmonary acute and chronic diseases, mainly due to its important immunoregulatory, anti-fibrogenic, anti-apoptotic and pro-angiogenic. Besides, the use of adjuvant therapies, whose aim is to boost or synergize with their function should be tested. Low level laser (LLL therapy is a relatively new and promising approach, with very low cost, no invasiveness and no side effects. Here, we aimed to study the effectiveness of human tube derived MSCs (htMSCs cell therapy associated with a 30mW/3J-660 nm LLL irradiation in experimental cigarette smoke-induced chronic obstructive pulmonary disease. Thus, C57BL/6 mice were exposed to cigarette smoke for 75 days (twice a day and all experiments were performed on day 76. Experimental groups receive htMSCS either intraperitoneally or intranasally and/or LLL irradiation either alone or in association. We show that co-therapy greatly reduces lung inflammation, lowering the cellular infiltrate and pro-inflammatory cytokine secretion (IL-1β, IL-6, TNF-α and KC, which were followed by decreased mucus production, collagen accumulation and tissue damage. These findings seemed to be secondary to the reduction of both NF-κB and NF-AT activation in lung tissues with a concomitant increase in IL-10. In summary, our data suggests that the concomitant use of MSCs + LLLT may be a promising therapeutic approach for lung inflammatory diseases as COPD.

  17. From meatless Mondays to meatless Sundays: motivations for meat reduction among vegetarians and semi-vegetarians who mildly or significantly reduce their meat intake.

    Science.gov (United States)

    De Backer, Charlotte J S; Hudders, Liselot

    2014-01-01

    This study explores vegetarians' and semi-vegetarians' motives for reducing their meat intake. Participants are categorized as vegetarians (remove all meat from their diet); semi-vegetarians (significantly reduce meat intake: at least three days a week); or light semi-vegetarians (mildly reduce meat intake: once or twice a week). Most differences appear between vegetarians and both groups of semi-vegetarians. Animal-rights and ecological concerns, together with taste preferences, predict vegetarianism, while an increase in health motives increases the odds of being semi-vegetarian. Even within each group, subgroups with different motives appear, and it is recommended that future researchers pay more attention to these differences.

  18. Calcium Contributes to the Cytotoxic Interaction Between Diclofenac and Cytokines.

    Science.gov (United States)

    Maiuri, Ashley R; Breier, Anna B; Turkus, Jonathan D; Ganey, Patricia E; Roth, Robert A

    2016-02-01

    Diclofenac (DCLF) is a widely used non-steroidal anti-inflammatory drug that is associated with idiosyncratic, drug-induced liver injury (IDILI) in humans. The mechanisms of DCLF-induced liver injury are unknown; however, patients with certain inflammatory diseases have an increased risk of developing IDILI, which raises the possibility that immune mediators play a role in the pathogenesis. DCLF synergizes with the cytokines tumor necrosis factor-alpha (TNF) and interferon-gamma (IFN) to cause hepatocellular apoptosis in vitro by a mechanism that involves activation of the endoplasmic reticulum (ER) stress response pathway and of the mitogen-activated protein kinases, c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK). DCLF also causes an increase in intracellular calcium (Ca(++)) in hepatocytes, but the role of this in the cytotoxic synergy between DCLF and cytokines is unknown. We tested the hypothesis that Ca(++) contributes to DCLF/cytokine-induced cytotoxic synergy. Treatment of HepG2 cells with DCLF led to an increase in intracellular Ca(++) at 6 and 12 h, and this response was augmented in the presence of TNF and IFN at 12 h. The intracellular Ca(++) chelator BAPTA/AM reduced cytotoxicity and caspase-3 activation caused by DCLF/cytokine cotreatment. BAPTA/AM also significantly reduced DCLF-induced activation of the ER stress sensor, protein kinase RNA-like ER kinase (PERK), as well as activation of JNK and ERK. Treatment of cells with an inositol trisphosphate receptor antagonist almost completely eliminated DCLF/cytokine-induced cytotoxicity and decreased DCLF-induced activation of PERK, JNK, and ERK. These findings indicate that Ca(++) contributes to DCLF/cytokine-induced cytotoxic synergy by promoting activation of the ER stress-response pathway and JNK and ERK. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  19. Cytokine ratios in chronic periodontitis and type 2 diabetes mellitus.

    Science.gov (United States)

    Acharya, Anirudh B; Thakur, Srinath; Muddapur, M V; Kulkarni, Raghavendra D

    Chronic periodontitis may influence systemic cytokines in type 2 diabetes. This study aimed to evaluate the cytokine ratios in type 2 diabetes with, and without chronic periodontitis. Gingival status, periodontal, glycemic parameters and serum cytokines were evaluated in participants grouped as healthy, chronic periodontitis, and type 2 diabetes with, and without chronic periodontitis. Cytokine ratios showed significant differences in type 2 diabetes and chronic periodontitis, were highest in participants having both type 2 diabetes and chronic periodontitis, with a statistically significant cut-off point and area under curve by receiver operating characteristic. Copyright © 2016 Diabetes India. Published by Elsevier Ltd. All rights reserved.

  20. Cytokines: muscle protein and amino acid metabolism

    DEFF Research Database (Denmark)

    van Hall, Gerrit

    2012-01-01

    raises TNF-α and IL-6 to moderate levels, has only identified IL-6 as a potent cytokine, decreasing systemic amino acid levels and muscle protein metabolism. The marked decrease in circulatory and muscle amino acid concentrations was observed with a concomitant reduction in both the rates of muscle...... of IL-6 on the regulation of muscle protein metabolism but indirectly via IL-6 reducing amino acid availability. SUMMARY: Recent studies suggest that the best described cytokines TNF-α and IL-6 are unlikely to be the major direct mediators of muscle protein loss in inflammatory diseases. However...

  1. The bio-complex "reaction pattern in vertebrate cells" reduces cytokine-induced cellular adhesion molecule mRNA expression in human endothelial cells by attenuation of NF-kappaB translocation.

    Science.gov (United States)

    Rönnau, Cindy; Liebermann, Herbert E H; Helbig, Franz; Staudt, Alexander; Felix, Stephan B; Ewert, Ralf; Landsberger, Martin

    2009-02-28

    The bio-complex "reaction pattern in vertebrate cells" (RiV) is mainly represented by characteristic exosome-like particles--probably as reaction products of cells to specific stress. The transcription factor NF-kappaB plays a central role in inflammation. We tested the hypothesis that RiV particle preparations (RiV-PP) reduce cellular adhesion molecule (CAM) expression (ICAM-1, VCAM-1, E-selectin) by the attenuation of NF-kappaB translocation in human umbilical vein endothelial cells (HUVEC). After 4 hours, pre-incubation of HUVEC with RiV-PP before stimulation with TNF-alpha significantly reduced ICAM-1 (65.5+/-10.3%) and VCAM-1 (71.1+/-12.3%) mRNA expression compared to TNF-alpha-treated cells (100%, n=7). ICAM-1 surface expression was significantly albeit marginally reduced in RiV/TNF-alpha- treated cells (92.0+/-5.6%, n=4). No significant effect was observed on VCAM-1 surface expression. In RiV/TNF-alpha-treated cells (n=4), NF-kappaB subunits p50 (85.7+/-4.1%) and p65 (85.0+/-1.8%) nuclear translocation was significantly reduced. RiV-PP may exert an anti-inflammatory effect in HUVEC by reducing CAM mRNA expression via attenuation of p50 and p65 translocation.

  2. Detection of autoantibodies to cytokines

    DEFF Research Database (Denmark)

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

    2000-01-01

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

  3. Cytokine production by oral and peripheral blood neutrophils in adult periodontitis.

    Science.gov (United States)

    Galbraith, G M; Hagan, C; Steed, R B; Sanders, J J; Javed, T

    1997-09-01

    Proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin 1 beta (IL-1 beta) also possess bone-resorptive properties, and are generally considered to play a role in the pathogenesis of periodontal disease. In the present study, TNF-alpha and IL-1 beta production by oral and peripheral blood polymorphonuclear leukocytes (PMN) was examined in 40 patients with adult periodontitis and 40 orally healthy matched controls. Oral PMN released considerable amounts of both cytokines in unstimulated culture, and there was no difference between patients and controls when the cytokine levels were corrected for cell number. However, when the effect of disease activity was examined, cytokine release by oral PMN was found to be greatest in patients with advanced periodontitis. Within the healthy control group, IL-1 beta production by oral PMN was significantly higher in males (Mann-Whitney test, P = 0.0008). Examination of IL-1 beta production by peripheral blood PMN exposed to recombinant human granulocyte-macrophage colony stimulating factor revealed no difference between the patient and control groups. In contrast, IL-1 beta production by peripheral blood PMN was significantly reduced in patients with advanced disease (Mann-Whitney test, P = 0.02), and peripheral PMN IL-1 beta synthesis was greater in female controls (Mann-Whitney test, P = 0.054). No effect of race on cytokine production could be discerned in patients or controls. These results indicate that several factors influence cytokine production in oral health and disease, and that a dichotomy in cytokine gene expression exists between oral and peripheral blood PMN in adult periodontitis.

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

    Science.gov (United States)

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

    2011-01-01

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

  5. Fasting metabolism modulates the interleukin-12/interleukin-10 cytokine axis.

    Directory of Open Access Journals (Sweden)

    Johannes J Kovarik

    Full Text Available A crucial role of cell metabolism in immune cell differentiation and function has been recently established. Growing evidence indicates that metabolic processes impact both, innate and adaptive immunity. Since a down-stream integrator of metabolic alterations, mammalian target of rapamycin (mTOR, is responsible for controlling the balance between pro-inflammatory interleukin (IL-12 and anti-inflammatory IL-10, we investigated the effect of upstream interference using metabolic modulators on the production of pro- and anti-inflammatory cytokines. Cytokine release and protein expression in human and murine myeloid cells was assessed after toll-like receptor (TLR-activation and glucose-deprivation or co-treatment with 5'-adenosine monophosphate (AMP-activated protein kinase (AMPK activators. Additionally, the impact of metabolic interference was analysed in an in-vivo mouse model. Glucose-deprivation by 2-deoxy-D-glucose (2-DG increased the production of IL-12p40 and IL-23p19 in monocytes, but dose-dependently inhibited the release of anti-inflammatory IL-10. Similar effects have been observed using pharmacological AMPK activation. Consistently, an inhibition of the tuberous sclerosis complex-mTOR pathway was observed. In line with our in vitro observations, glycolysis inhibition with 2-DG showed significantly reduced bacterial burden in a Th2-prone Listeria monocytogenes mouse infection model. In conclusion, we showed that fasting metabolism modulates the IL-12/IL-10 cytokine balance, establishing novel targets for metabolism-based immune-modulation.

  6. Fasting metabolism modulates the interleukin-12/interleukin-10 cytokine axis

    Science.gov (United States)

    Kernbauer, Elisabeth; Hölzl, Markus A.; Hofer, Johannes; Gualdoni, Guido A.; Schmetterer, Klaus G.; Miftari, Fitore; Sobanov, Yury; Meshcheryakova, Anastasia; Mechtcheriakova, Diana; Witzeneder, Nadine; Greiner, Georg; Ohradanova-Repic, Anna; Waidhofer-Söllner, Petra; Säemann, Marcus D.; Decker, Thomas

    2017-01-01

    A crucial role of cell metabolism in immune cell differentiation and function has been recently established. Growing evidence indicates that metabolic processes impact both, innate and adaptive immunity. Since a down-stream integrator of metabolic alterations, mammalian target of rapamycin (mTOR), is responsible for controlling the balance between pro-inflammatory interleukin (IL)-12 and anti-inflammatory IL-10, we investigated the effect of upstream interference using metabolic modulators on the production of pro- and anti-inflammatory cytokines. Cytokine release and protein expression in human and murine myeloid cells was assessed after toll-like receptor (TLR)-activation and glucose-deprivation or co-treatment with 5′-adenosine monophosphate (AMP)-activated protein kinase (AMPK) activators. Additionally, the impact of metabolic interference was analysed in an in-vivo mouse model. Glucose-deprivation by 2-deoxy-D-glucose (2-DG) increased the production of IL-12p40 and IL-23p19 in monocytes, but dose-dependently inhibited the release of anti-inflammatory IL-10. Similar effects have been observed using pharmacological AMPK activation. Consistently, an inhibition of the tuberous sclerosis complex-mTOR pathway was observed. In line with our in vitro observations, glycolysis inhibition with 2-DG showed significantly reduced bacterial burden in a Th2-prone Listeria monocytogenes mouse infection model. In conclusion, we showed that fasting metabolism modulates the IL-12/IL-10 cytokine balance, establishing novel targets for metabolism-based immune-modulation. PMID:28742108

  7. Censored correlated cytokine concentrations

    DEFF Research Database (Denmark)

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

    2013-01-01

    ) can be used to describe the relative concentration between two cytokines, and the GMR ratio (GMRR) can be used to compare two groups. The problem is how to estimate GMRRs from censored distributions.We evaluated methods, including simple deletion and substitution, in simulated and real data. One...... stacking method that uses clustered variance-covariance estimation allowing homogeneous (Stackc) or inhomogeneous (Stackh) variances. We compare it with direct estimation of the bivariate Tobit likelihood function (Bitobit) and multiple imputation. We assess sensitivity to inhomogeneity and non...

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

    Science.gov (United States)

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

    2013-10-01

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

  9. Study of cytokines microenvironment during autoimmune diseases ...

    African Journals Online (AJOL)

    22, IL-23, TNF-α and TGF-β) were determined. We used the immunoenzymatic technology to assess the titer of cytokines. We found that there was no significant variation of TNF-α level in normal controls and autoimmune diseases ...

  10. Cytokine regulation of immune tolerance

    OpenAIRE

    Wu, Jie; Xie, Aini; Chen, Wenhao

    2014-01-01

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

  11. Class I Cytokine Receptors

    DEFF Research Database (Denmark)

    Steinocher, Helena

    , the minimal determinants for specificity between membrane spanning helices were investigated with small artificial low complexity peptides, prior found to activate the EPOR in cells. The placement of single methyl group in the so called transmembrane aptamers (traptamers) determined the stabilizing effect...... characteristics of membrane spanning helices, was designed and hGHR TMD and hEPOR TMD produced in sufficient amounts for spectroscopic investigations. The isolated hGHR TMD was revealed to associate in dimeric complexes in detergent micelles and first presumptions about the dimer interface could be made. Further...... the traptamers on the hEPOR TMD dimeric complex in detergent micelles. To gain a better understanding of hGHR regulation a point mutation in the hGHR intracellular domain (ICD), which has recently been linked to lung cancer, was characterized. The mutation was found to decrease binding of suppressor of cytokine...

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

    Science.gov (United States)

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

    2017-10-01

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

  13. Diclofenac enhances proinflammatory cytokine-induced phagocytosis of cultured microglia via nitric oxide production

    International Nuclear Information System (INIS)

    Kakita, Hiroki; Aoyama, Mineyoshi; Nagaya, Yoshiaki; Asai, Hayato; Hussein, Mohamed Hamed; Suzuki, Mieko; Kato, Shin; Saitoh, Shinji; Asai, Kiyofumi

    2013-01-01

    Influenza-associated encephalopathy (IAE) is a central nervous system complication with a high mortality rate, which is increased significantly by the non-steroidal anti-inflammatory drug diclofenac sodium (DCF). In the present study, we investigated the effects of DCF on brain immune cells (i.e. microglia) stimulated with three proinflammatory cytokines, namely tumor necrosis factor-α, interleukin-1β, and interferon-γ. Similar to previous findings in astrocytes, all three cytokines induced the expression of inducible NO synthase (iNOS), as well as NO production, in microglia. The addition of DCF to the culture system augmented iNOS expression and NO production. Immunocytochemical analysis and the phagocytosis assay revealed that cytokine treatment induced morphological changes to and phagocytosis by the microglia. The addition of DCF to the culture system enhanced microglial activation, as well as the phagocytic activity of cytokine-stimulated microglia. Inhibitors of nuclear factor (NF)-κB inhibited iNOS gene expression in cytokine-stimulated microglia with or without DCF, suggesting that the NF-κB pathway is one of the main signaling pathways involved. The iNOS inhibitor N G -monomethyl-L-arginine (L-NMMA) reduced both cytokine-induced phagocytosis and phagocytosis induced by the combination of cytokines plus DCF. Furthermore, the NO donor sodium nitroprusside induced phagocytosis, indicating that NO production is a key regulator of microglial phagocytosis. In conclusion, DCF acts synergistically with proinflammatory cytokines to increase the production of NO in microglia, leading to phagocytic activity of the activated microglia. These findings, together with previous observations regarding astrocytes, may explain the significant increase in mortality of IAE patients treated with DCF. - Highlights: ► Influenza-associated encephalopathy (IAE) is associated with a high mortality rate. ► Hyperimmunization in the brain is believed to be responsible for IAE

  14. Diclofenac enhances proinflammatory cytokine-induced phagocytosis of cultured microglia via nitric oxide production

    Energy Technology Data Exchange (ETDEWEB)

    Kakita, Hiroki [Department of Molecular Neurobiology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan); Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan); Aoyama, Mineyoshi, E-mail: ao.mine@med.nagoya-cu.ac.jp [Department of Molecular Neurobiology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan); Nagaya, Yoshiaki; Asai, Hayato [Department of Molecular Neurobiology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan); Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan); Hussein, Mohamed Hamed [Neonatal Intensive Care Unit, Pediatric Hospital, Cairo University, Cairo 11559 (Egypt); Maternal and Child Health Department, VACSERA, 51 Wizaret El-Zeraa-Agouza, Giza 22311 (Egypt); Suzuki, Mieko [Department of Molecular Neurobiology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan); Kato, Shin [Department of Molecular Neurobiology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan); Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan); Saitoh, Shinji [Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan); Asai, Kiyofumi [Department of Molecular Neurobiology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan)

    2013-04-15

    Influenza-associated encephalopathy (IAE) is a central nervous system complication with a high mortality rate, which is increased significantly by the non-steroidal anti-inflammatory drug diclofenac sodium (DCF). In the present study, we investigated the effects of DCF on brain immune cells (i.e. microglia) stimulated with three proinflammatory cytokines, namely tumor necrosis factor-α, interleukin-1β, and interferon-γ. Similar to previous findings in astrocytes, all three cytokines induced the expression of inducible NO synthase (iNOS), as well as NO production, in microglia. The addition of DCF to the culture system augmented iNOS expression and NO production. Immunocytochemical analysis and the phagocytosis assay revealed that cytokine treatment induced morphological changes to and phagocytosis by the microglia. The addition of DCF to the culture system enhanced microglial activation, as well as the phagocytic activity of cytokine-stimulated microglia. Inhibitors of nuclear factor (NF)-κB inhibited iNOS gene expression in cytokine-stimulated microglia with or without DCF, suggesting that the NF-κB pathway is one of the main signaling pathways involved. The iNOS inhibitor N{sup G}-monomethyl-L-arginine (L-NMMA) reduced both cytokine-induced phagocytosis and phagocytosis induced by the combination of cytokines plus DCF. Furthermore, the NO donor sodium nitroprusside induced phagocytosis, indicating that NO production is a key regulator of microglial phagocytosis. In conclusion, DCF acts synergistically with proinflammatory cytokines to increase the production of NO in microglia, leading to phagocytic activity of the activated microglia. These findings, together with previous observations regarding astrocytes, may explain the significant increase in mortality of IAE patients treated with DCF. - Highlights: ► Influenza-associated encephalopathy (IAE) is associated with a high mortality rate. ► Hyperimmunization in the brain is believed to be responsible for

  15. Withaferin A Associated Differential Regulation of Inflammatory Cytokines

    Directory of Open Access Journals (Sweden)

    Seema Dubey

    2018-02-01

    Full Text Available A role of inflammation-associated cytokines/chemokines has been implicated in a wide variety of human diseases. Here, we investigated the regulation of inflammatory cytokines released by monocyte-derived THP-1 cells following treatment with the dietary agent withaferin A (WFA. Membrane-based cytokine array profiling of the culture supernatant from adenosine triphosphate-stimulated WFA-treated THP-1 cells showed differential regulation of multiple cytokines/chemokines. A selected group of cytokines/chemokines [interleukin-1 beta (IL-1β, CCL2/MCP-1, granulocyte-macrophage colony stimulating factor, PDGF-AA, PTX3, cystatin-3, relaxin-2, TNFRSF8/CD30, and ACRP30] was validated at the transcription level using qPCR. In silico analysis for transcriptional binding factors revealed the presence of nuclear factor-kappa B (NF-κB in a group of downregulated cytokine gene promoters. WFA treatment of THP-1 cells blocks the nuclear translocation of NF-kB and corresponds with the reduced levels of cytokine secretion. To further understand the differential expression of cytokines/chemokines, we showed that WFA alters the nigericin-induced co-localization of NLRP3 and ASC proteins, thereby inhibiting caspase-1 activation, which is responsible for the cleavage and maturation of pro-inflammatory cytokines IL-1β and IL-18. These data suggest that dietary agent WFA concurrently targets NF-κB and the inflammasome complex, leading to inhibition of IL-1β and IL-18, respectively, in addition to differential expression of multiple cytokines/chemokines. Taken together, these results provide a rationale for using WFA to further explore the anti-inflammatory mechanism of cytokines/chemokines associated with inflammatory diseases.

  16. Prenatal prochloraz treatment significantly increases pregnancy length and reduces offspring weight but does not affect social-olfactory memory in rats

    DEFF Research Database (Denmark)

    Dmytriyeva, Oksana; Klementiev, Boris; Berezin, Vladimir

    2013-01-01

    Metabolites of the commonly used imidazole fungicide prochloraz are androgen receptor antagonists. They have been shown to block androgen-driven development and compromise reproductive function. We tested the effect of prochloraz on cognitive behavior following exposure to this fungicide during...... the perinatal period. Pregnant Wistar rats were administered a 200mg/kg dose of prochloraz on gestational day (GD) 7, GD11, and GD15. The social recognition test (SRT) was performed on 7-week-old male rat offspring. We found an increase in pregnancy length and a significantly reduced pup weight on PND15 and PND...

  17. 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...

  18. Cytokines and uveitis, a review

    NARCIS (Netherlands)

    de Vos, A. F.; Hoekzema, R.; Kijlstra, A.

    1992-01-01

    Although the exact pathogenic mechanisms underlying uveitis are unknown, cytokines appear to be involved in this inflammatory disorder. This review describes the studies in which the uveitogenic properties of several cytokines, including tumor necrosis factor (TNF), interleukin 1 (IL-1), IL-6, IL-8

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

    Science.gov (United States)

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

    2016-03-29

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

  20. Cytokine Gene Polymorphisms across Tuberculosis Clinical Spectrum in Pakistani Patients

    Science.gov (United States)

    Ansari, Ambreen; Talat, Najeeha; Jamil, Bushra; Hasan, Zahra; Razzaki, Tashmeem; Dawood, Ghaffar; Hussain, Rabia

    2009-01-01

    Background Pakistan ranks 7th globally in terms of tuberculosis (TB) disease burden (incidence 181/100000 pop./yr; prevalence of 329/pop./yr). Reports from different populations show variable associations of TB susceptibility and severity with cytokine gene polymorphisms. Tuberculosis clinical severity is multi-factorial and cytokines play a pivotal role in the modulation of disease severity. We have recently reported that the ratio of two key cytokines (IFNγ and IL10) show significant correlation with the severity spectrum of tuberculosis. The objective of the current study was to analyze the frequency of cytokine gene polymorphisms linked to high and low responder phenotypes (IFNγ +874 T hi→A lo and IL10 −1082 G lo→A hi) in tuberculosis patients. Methods and Findings Study groups were stratified according to disease site as well as disease severity: Pulmonary N = 111 (Minimal, PMN = 19; Moderate, PMD = 63; Advance, PAD = 29); Extra-pulmonary N = 67 (Disseminated DTB = 20, Localized LTB = 47) and compared with healthy controls (TBNA = 188). Genotype analyses were carried out using amplification refractory mutation system-PCR (ARMS-PCR) and stimulated whole blood (WB) culture assay was used for assessing cytokine profiles. Our results suggest that the IFNγ +874 TT genotype and T allele was overrepresented in PMN (p = 0.01) and PMD (p = 0.02). IFNγ +874 TT in combination with IL10 GG lo genotypes showed the highest association (χ2 = 6.66, OR = 6.06, 95% CI = 1.31–28.07, p = 0.01). IFNγ AA lo on the other hand in combination with IL10 GG lo increased the risk of PAD (OR = 5.26; p = 0.005) and DTB (OR = 3.59; p = 0.045). Conclusion These findings are consistent with the role of IL10 in reducing collateral tissue damage and the protective role of IFNγ in limiting disease in the lung. PMID:19274101

  1. Cytokine modulation by glucocorticoids: mechanisms and actions in cellular studies.

    Science.gov (United States)

    Brattsand, R; Linden, M

    1996-01-01

    Glucocorticoids inhibit the expression and action of most cytokines. This is part of the in vivo feed-back system between inflammation-derived cytokines and CNS-adrenal produced corticosteroids with the probable physiological relevance to balance parts of the host defence and anti-inflammatory systems of the body. Glucocorticoids modulate cytokine expression by a combination of genomic mechanisms. The activated glucocorticoid-receptor complex can (i) bind to and inactivate key proinflammatory transcription factors (e.g. AP-1, NF kappa B). This takes place at the promotor responsive elements of these factors, but has also been reported without the presence of DNA; (ii) via glucocorticoid responsive elements (GRE), upregulate the expression of cytokine inhibitory proteins, e.g. I kappa B, which inactivates the transcription factor NF kappa B and thereby the secondary expression of a series of cytokines; (iii) reduce the half-life time and utility of cytokine mRNAs. In studies with triggered human blood mononuclear cells in culture, glucocorticoids strongly diminish the production of the 'initial phase' cytokines IL-1 beta and TNF-alpha and the 'immunomodulatory' cytokines IL-2, IL-3, IL-4, IL-5, IL-10, IL-12 and IFN-gamma, as well as of IL-6, IL-8 and the growth factor GM-CSF. While steroid treatment broadly attenuates cytokine production, it cannot modulate it selectively, e.g. just the TH0, the TH1 or the TH2 pathways. The production of the 'anti-inflammatory' IL-10 is also inhibited. The exceptions of steroid down-regulatory activity on cytokine expression seem to affect 'repair phase' cytokines like TGF-beta and PDGF. These are even reported to be upregulated, which may explain the rather weak steroid dampening action on healing and fibrotic processes. Some growth factors, e.g. G-CSF and M-CSF, are only weakly affected. In addition to diminishing the production of a cytokine, steroids can also often inhibit its subsequent actions. Because cytokines work in

  2. The effectiveness of the anti-CD11d treatment is reduced in rat models of spinal cord injury that produce significant levels of intraspinal hemorrhage.

    Science.gov (United States)

    Geremia, N M; Hryciw, T; Bao, F; Streijger, F; Okon, E; Lee, J H T; Weaver, L C; Dekaban, G A; Kwon, B K; Brown, A

    2017-09-01

    We have previously reported that administration of a CD11d monoclonal antibody (mAb) improves recovery in a clip-compression model of SCI. In this model the CD11d mAb reduces the infiltration of activated leukocytes into the injured spinal cord (as indicated by reduced intraspinal MPO). However not all anti-inflammatory strategies have reported beneficial results, suggesting that success of the CD11d mAb treatment may depend on the type or severity of the injury. We therefore tested the CD11d mAb treatment in a rat hemi-contusion model of cervical SCI. In contrast to its effects in the clip-compression model, the CD11d mAb treatment did not improve forelimb function nor did it significantly reduce MPO levels in the hemi-contused cord. To determine if the disparate results using the CD11d mAb were due to the biomechanical nature of the cord injury (compression SCI versus contusion SCI) or to the spinal level of the injury (12th thoracic level versus cervical) we further evaluated the CD11d mAb treatment after a T12 contusion SCI. In contrast to the T12 clip compression SCI, the CD11d mAb treatment did not improve locomotor recovery or significantly reduce MPO levels after T12 contusion SCI. Lesion analyses revealed increased levels of hemorrhage after contusion SCI compared to clip-compression SCI. SCI that is accompanied by increased intraspinal hemorrhage would be predicted to be refractory to the CD11d mAb therapy as this approach targets leukocyte diapedesis through the intact vasculature. These results suggest that the disparate results of the anti-CD11d treatment in contusion and clip-compression models of SCI are due to the different pathophysiological mechanisms that dominate these two types of spinal cord injuries. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

  3. Proinflammatory cytokines in open versus laparoscopic cholecystectomy

    International Nuclear Information System (INIS)

    Abu-Eshy, Saeed A.; Al-Rofaidi, Abdallah A.; Al-Faki, Ahmed S.; Ghalib, Hashim W.; Moosa, Riyadh A.; Sadik, Ali A.; Salati, Mohammad I.

    2002-01-01

    Laparoscopic cholecystectomy, a minimal access surgery, is fast replacing open cholecystectomy and is being associated with less trauma. The objective of this study was to compare the proinflammatory cytokine levels in both laparoscopic cholecystectomy and open cholecystectomy. This study was carried out at Aseer Central Hospital, Aseer region, Abha Private Hospital and the College of Medicine and Medical Sciences, King Khalid University, Abha, Kingdom of Saudi Arabia, during the time period October 1998 through to November 2000. Sixty-one patients were included in the study, 27 of them had laparoscopic cholecystectomy and 34 had open cholecystectomy. Cytokines [Interleukin-6 Interleukin-1b, Tumor necrosis factor -a and Interleukin- 8] were measured in blood samples collected from the patients before, at and 24 hours post surgery, using commercially available kits. Interleukin-6 levels were significantly increased at 24 hours post surgery in the open cholecystectomy group of patients compared to the laparoscopic cholecystectomy group (P<0.04). No differences were found in the other cytokines levels (Interleukin-1b, tumor necrosis factor -a and Interleukin-8) between the open cholecystectomy and laparoscopic cholecystectomy groups. Laparoscopic cholecystectomy, a minimal access surgery, is associated with lower levels of the proinflammatory interleukin-6 cytokine compared to open cholecystectomy. (author)

  4. Cytokine induction of sol–gel-derived TiO2 and SiO2 coatings on metallic substrates after implantation to rat femur

    Science.gov (United States)

    Urbanski, Wiktor; Marycz, Krzysztof; Krzak, Justyna; Pezowicz, Celina; Dragan, Szymon Feliks

    2017-01-01

    Material surface is a key determinant of host response on implanted biomaterial. Therefore, modification of the implant surface may optimize implant–tissue reactions. Inflammatory reaction is inevitable after biomaterial implantation, but prolonged inflammation may lead to adverse reactions and subsequent implant failure. Proinflammatory activities of cytokines like interleukin (IL)-1, IL-6, and tumor necrosis factor-alpha (TNF-α) are attractive indicators of these processes and ultimately characterize biocompatibility. The objective of the study was to evaluate local cytokine production after implantation of stainless steel 316L (SS) and titanium alloy (Ti6Al4V) biomaterials coated with titanium dioxide (TiO2) and silica (SiO2) coatings prepared by sol–gel method. Biomaterials were implanted into rat femur and after 12 weeks, bones were harvested. Bone–implant tissue interface was evaluated; immunohistochemical staining was performed to identify IL-6, TNF-α, and Caspase-1. Histomorphometry (AxioVision Rel. 4.6.3 software) of tissue samples was performed in order to quantify the cytokine levels. Both the oxide coatings on SS and Ti6Al4V significantly reduced cytokine production. However, the lowest cytokine levels were observed in TiO2 groups. Cytokine content in uncoated groups was lower in Ti6Al4V than in SS, although coating of either metal reduced cytokine production to similar levels. Sol–gel TiO2 or SiO2 coatings reduced significantly the production of proinflammatory cytokines by local tissues, irrespective of the material used as a substrate, that is, either Ti6Al4V or SS. This suggests lower inflammatory response, which directly points out improvement of materials’ biocompatibility. PMID:28280331

  5. Glatiramer Acetate administration does not reduce damage after cerebral ischemia in mice.

    Science.gov (United States)

    Poittevin, Marine; Deroide, Nicolas; Azibani, Feriel; Delcayre, Claude; Giannesini, Claire; Levy, Bernard I; Pocard, Marc; Kubis, Nathalie

    2013-01-15

    Inflammation plays a key role in ischemic stroke pathophysiology: microglial/macrophage cells and type-1 helper cells (Th1) seem deleterious, while type-2 helper cells (Th2) and regulatory T cells (Treg) seem protective. CD4 Th0 differentiation is modulated by microglial cytokine secretion. Glatiramer Acetate (GA) is an immunomodulatory drug that has been approved for the treatment of human multiple sclerosis by means of a number of mechanisms: reduced microglial activation and pro-inflammatory cytokine production, Th0 differentiation shifting from Th2 to Th2 and Treg with anti-inflammatory cytokine production and increased neurogenesis. We induced permanent (pMCAo) or transient middle cerebral artery occlusion (tMCAo) and GA (2 mg) or vehicle was injected subcutaneously immediately after cerebral ischemia. Mice were sacrificed at D3 to measure neurological deficit, infarct volume, microglial cell density and qPCR of TNFα and IL-1β (pro-inflammatory microglial cytokines), IFNγ (Th2 cytokine), IL-4 (Th2 cytokine), TGFβ and IL-10 (Treg cytokines), and at D7 to evaluate neurological deficit, infarct volume and neurogenesis assessment. We showed that in GA-treated pMCAo mice, infarct volume, microglial cell density and cytokine secretion were not significantly modified at D3, while neurogenesis was enhanced at D7 without significant infarct volume reduction. In GA-treated tMCAo mice, microglial pro-inflammatory cytokines IL-1β and TNFα were significantly decreased without modification of microglial/macrophage cell density, cytokine secretion, neurological deficit or infarct volume at D3, or modification of neurological deficit, neurogenesis or infarct volume at D7. In conclusion, Glatiramer Acetate administered after cerebral ischemia does not reduce infarct volume or improve neurological deficit in mice despite a significant increase in neurogenesis in pMCAo and a microglial pro-inflammatory cytokine reduction in tMCAo. Copyright © 2012 Elsevier B.V. All rights

  6. Autoimmunity and Cytokine Imbalance in Inherited Epidermolysis Bullosa

    Directory of Open Access Journals (Sweden)

    Susanna Esposito

    2016-09-01

    Full Text Available In order to evaluate the serum anti-skin autoantibodies and cytokine concentrations in patients with different epidermolysis bullosa (EB types and severity, 42 EB patients and 38 controls were enrolled. Serum anti-skin antibodies were significantly higher in the patients than in the controls (p = 0.008, p < 0.001, p < 0.001, p < 0.001 and p < 0.001 for desmoglein 1 (DSG1 desmoglein 3 (DSG3, bullous pemphigoid 180 (BP180, BP230 and type VII collagen (COL7, respectively. The same trend was observed for interleukin (IL-1β, IL-2, IL-6, IL-10, tumor necrosis factor-β, and interferon-γ (p < 0.001, p < 0.001, p < 0.001, p = 0.008, p < 0.001 and p = 0.002, respectively. Increases in anti-skin antibodies and cytokine concentrations were higher in patients with recessive dystrophic EB than in those with different types of EB, in generalized cases than in localized ones, and in patients with higher Birmingham Epidermolysis Bullosa Severity (BEBS scores than in those with a lower score. The BEBS score was directly correlated with BP180, BP230, COL7 (p = 0.015, p = 0.008 and p < 0.001, respectively and IL-6 (p = 0.03, whereas IL-6 appeared significantly associated with DSG1, DSG3, BP180, BP230 and COL7 (p = 0.015, p = 0.023, p = 0.023, p = 0.015 and p = 0.005, respectively. This study showed that autoimmunity and inflammatory responses are frequently activated in EB, mainly in severe forms, suggesting the use of immunosuppressive drugs or biologicals that are active against pro-inflammatory cytokines to reduce clinical signs and symptoms of disease.

  7. Hypoxis hemerocallidea Significantly Reduced Hyperglycaemia and Hyperglycaemic-Induced Oxidative Stress in the Liver and Kidney Tissues of Streptozotocin-Induced Diabetic Male Wistar Rats

    Directory of Open Access Journals (Sweden)

    Oluwafemi O. Oguntibeju

    2016-01-01

    Full Text Available Background. Hypoxis hemerocallidea is a native plant that grows in the Southern African regions and is well known for its beneficial medicinal effects in the treatment of diabetes, cancer, and high blood pressure. Aim. This study evaluated the effects of Hypoxis hemerocallidea on oxidative stress biomarkers, hepatic injury, and other selected biomarkers in the liver and kidneys of healthy nondiabetic and streptozotocin- (STZ- induced diabetic male Wistar rats. Materials and Methods. Rats were injected intraperitoneally with 50 mg/kg of STZ to induce diabetes. The plant extract-Hypoxis hemerocallidea (200 mg/kg or 800 mg/kg aqueous solution was administered (daily orally for 6 weeks. Antioxidant activities were analysed using a Multiskan Spectrum plate reader while other serum biomarkers were measured using the RANDOX chemistry analyser. Results. Both dosages (200 mg/kg and 800 mg/kg of Hypoxis hemerocallidea significantly reduced the blood glucose levels in STZ-induced diabetic groups. Activities of liver enzymes were increased in the diabetic control and in the diabetic group treated with 800 mg/kg, whereas the 200 mg/kg dosage ameliorated hepatic injury. In the hepatic tissue, the oxygen radical absorbance capacity (ORAC, ferric reducing antioxidant power (FRAP, catalase, and total glutathione were reduced in the diabetic control group. However treatment with both doses improved the antioxidant status. The FRAP and the catalase activities in the kidney were elevated in the STZ-induced diabetic group treated with 800 mg/kg of the extract possibly due to compensatory responses. Conclusion. Hypoxis hemerocallidea demonstrated antihyperglycemic and antioxidant effects especially in the liver tissue.

  8. Prenatal prochloraz treatment significantly increases pregnancy length and reduces offspring weight but does not affect social-olfactory memory in rats.

    Science.gov (United States)

    Dmytriyeva, Oksana; Klementiev, Boris; Berezin, Vladimir; Bock, Elisabeth

    2013-07-01

    Metabolites of the commonly used imidazole fungicide prochloraz are androgen receptor antagonists. They have been shown to block androgen-driven development and compromise reproductive function. We tested the effect of prochloraz on cognitive behavior following exposure to this fungicide during the perinatal period. Pregnant Wistar rats were administered a 200 mg/kg dose of prochloraz on gestational day (GD) 7, GD11, and GD15. The social recognition test (SRT) was performed on 7-week-old male rat offspring. We found an increase in pregnancy length and a significantly reduced pup weight on PND15 and PND40 but no effect of prenatal prochloraz exposure on social investigation or acquisition of social-olfactory memory. Copyright © 2012 Elsevier GmbH. All rights reserved.

  9. Mimetics of Suppressor of cytokine signalling 3: novel potential therapeutics in triple breast cancer.

    Science.gov (United States)

    La Manna, Sara; Lee, Eunmi; Ouzounova, Maria; Di Natale, Concetta; Novellino, Ettore; Merlino, Antonello; Korkaya, Hasan; Marasco, Daniela

    2018-05-11

    Suppressor of cytokine signaling (SOCS) family of proteins plays critical role in the regulation of immune responses controlling JAK/STAT mediated inflammatory cytokines. Among the members, SOCS1 and SOCS3 contain a kinase inhibitory region (KIR) and SOCS3 binds to JAK/STAT/gp130 complex by inhibiting the downstream signaling and suppressing inflammatory cytokines. Loss or reduced levels of SOCS3 have been linked to cancer-associated inflammation and suppressive immunity leading to enhanced tumour growth and metastasis. In line with these reports, we previously demonstrated that proteolytic degradation of SOCS3 in triple negative breast cancer (TNBC) subtype drives the expression of inflammatory cytokines. Therefore, we postulated that SOCS3 mimetics might suppress the inflammatory cytokine production in TNBC subtype and inhibit tumor growth and metastasis. Here we designed and characterized five linear peptides derived from the N-terminal region of SOCS3 encompassing regions that interface with the JAK2/gp130 complex by using the Circular Dichroism and Surface Plasmon Resonance spectroscopies. The KIRESS peptide resulted the sequence containing the most part of the hot-spots required for binding to JAK2 and was further investigated in vivo in mouse xenografts of MDA-MB-231-luci tumours as models of human TNBC subtype. Expectedly, this peptide showed a significant inhibition of primary tumour growth and pulmonary metastasis. Our studies suggest that SOCS3 peptidomimetics may possess a therapeutic potential in aggressive cancers, such as TNBC subtype, with activated inflammatory cytokines. This article is protected by copyright. All rights reserved. © 2018 UICC.

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Mersedeh Tohidnezhad

    2017-01-01

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

  12. Cytokine and Antioxidant Regulation in the Intestine of the Gray Mouse Lemur (Microcebus murinus During Torpor

    Directory of Open Access Journals (Sweden)

    Shannon N. Tessier

    2015-04-01

    Full Text Available During food shortages, the gray mouse lemur (Microcebus murinus of Madagascar experiences daily torpor thereby reducing energy expenditures. The present study aimed to understand the impacts of torpor on the immune system and antioxidant response in the gut of these animals. This interaction may be of critical importance given the trade-off between the energetically costly immune response and the need to defend against pathogen entry during hypometabolism. The protein levels of cytokines and antioxidants were measured in the small intestine (duodenum, jejunum, and ileum and large intestine of aroused and torpid lemurs. While there was a significant decrease of some pro-inflammatory cytokines (IL-6 and TNF-α in the duodenum and jejunum during torpor as compared to aroused animals, there was no change in anti-inflammatory cytokines. We observed decreased levels of cytokines (IL-12p70 and M-CSF, and several chemokines (MCP-1 and MIP-2 but an increase in MIP-1α in the jejunum of the torpid animals. In addition, we evaluated antioxidant response by examining the protein levels of antioxidant enzymes and total antioxidant capacity provided by metabolites such as glutathione (and others. Our results indicated that levels of antioxidant enzymes did not change between torpor and aroused states, although antioxidant capacity was significantly higher in the ileum during torpor. These data suggest a suppression of the immune response, likely as an energy conservation measure, and a limited role of antioxidant defenses in supporting torpor in lemur intestine.

  13. Intermittent fasting during Ramadan attenuates proinflammatory cytokines and immune cells in healthy subjects.

    Science.gov (United States)

    Faris, Mo'ez Al-Islam E; Kacimi, Safia; Al-Kurd, Ref'at A; Fararjeh, Mohammad A; Bustanji, Yasser K; Mohammad, Mohammad K; Salem, Mohammad L

    2012-12-01

    Intermittent fasting and caloric restriction have been shown to extend life expectancy and reduce inflammation and cancer promotion in animal models. It was hypothesized that intermittent prolonged fasting practiced during the month of Ramadan (RIF) could positively affect the inflammatory state. To investigate this hypothesis, a cross-sectional study was designed to investigate the impact of RIF on selected inflammatory cytokines and immune biomarkers in healthy subjects. Fifty (21 men and 29 women) healthy volunteers who practiced Ramadan fasting were recruited for the investigation of circulating proinflammatory cytokines (interleukin [IL]-1β, IL-6, and tumor necrosis factor α), immune cells (total leukocytes, monocytes, granulocytes, and lymphocytes), and anthropometric and dietary assessments. The investigations were conducted 1 week before Ramadan fasting, at the end of the third week of Ramadan, and 1 month after the cessation of Ramadan month. The proinflammatory cytokines IL-1β, IL-6, and tumor necrosis factor α; systolic and diastolic blood pressures; body weight; and body fat percentage were significantly lower (P fasting. Immune cells significantly decreased during Ramadan but still remained within the reference ranges. These results indicate that RIF attenuates inflammatory status of the body by suppressing proinflammatory cytokine expression and decreasing body fat and circulating levels of leukocytes. Copyright © 2012 Elsevier Inc. All rights reserved.

  14. Cytokines, cytokine antagonists, and soluble adhesion molecules in pediatric OMS and other neuroinflammatory disorders.

    Science.gov (United States)

    Pranzatelli, Michael R; Tate, Elizabeth D; McGee, Nathan R; Colliver, Jerry A

    2013-03-15

    To test for hypothesized disease- and treatment-induced changes in cytokines and adhesion molecules in children with opsoclonus-myoclonus syndrome (OMS). Multiplex bead assay technology was used for simultaneous measurement of 34 soluble cytokines in cerebrospinal fluid (CSF) and serum. Soluble intercellular adhesion molecule-1 (sICAM-1) and vascular cell adhesion molecule-1 (sVCAM-1) were measured by ELISA. In total, there were 388 children (239 OMS, 114 controls, and 35 other inflammatory neurological disorders (OIND)). In untreated OMS, mean CSF IL-6 was elevated 2.3-fold, but 67-fold in OIND, without significant differences in other CSF cytokines. Mean serum concentrations of sIL-2Ra (+50%) and CXCL1 (+70%) (pOMS than controls (p=0.005), as was serum CCL11 and IL-13 in treated OMS. Mean CSF CCL4 and IL-1Ra were selectively higher in IVIg-treated OMS (p≤0.0001). CSF sICAM-1 was elevated only in OIND (3.3-fold); serum sICAM-1 was higher in untreated OMS (+21%); and sVCAM-1 was not affected. No correlations with OMS severity or duration were identified. Novel cytokine, cytokine antagonist, and soluble adhesion molecule abnormalities due to OMS or treatment were found. However, the normality of much of the data strengthens previous findings implicating B cell mechanisms. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. Glycophospholipid Formulation with NADH and CoQ10 Significantly Reduces Intractable Fatigue in Western Blot-Positive ‘Chronic Lyme Disease’ Patients: Preliminary Report

    Directory of Open Access Journals (Sweden)

    Garth L. Nicolson

    2012-03-01

    Full Text Available Background: An open label 8-week preliminary study was conducted in a small number of patients to determine if a combination oral supplement containing a mixture of phosphoglycolipids, coenzyme Q10 and microencapsulated NADH and other nutrients could affect fatigue levels in long-term, Western blot-positive, multi-symptom ‘chronic Lyme disease’ patients (also called ‘post-treatment Lyme disease’ or ‘post Lyme syndrome’ with intractable fatigue. Methods: The subjects in this study were 6 males (mean age = 45.1 ± 12.4 years and 10 females (mean age = 54.6 ± 7.4 years with ‘chronic Lyme disease’ (determined by multiple symptoms and positive Western blot analysis that had been symptomatic with chronic fatigue for an average of 12.7 ± 6.6 years. They had been seen by multiple physicians (13.3 ± 7.6 and had used many other remedies, supplements and drugs (14.4 ± 7.4 without fatigue relief. Fatigue was monitored at 0, 7, 30 and 60 days using a validated instrument, the Piper Fatigue Scale.Results: Patients in this preliminary study responded to the combination test supplement, showing a 26% reduction in overall fatigue by the end of the 8-week trial (p< 0.0003. Analysis of subcategories of fatigue indicated that there were significant improvements in the ability to complete tasks and activities as well as significant improvements in mood and cognitive abilities. Regression analysis of the data indicated that reductions in fatigue were consistent and occurred with a high degree of confidence (R2= 0.998. Functional Foods in Health and Disease 2012, 2(3:35-47 Conclusions: The combination supplement was a safe and effective method to significantly reduce intractable fatigue in long-term patients with Western blot-positive ‘chronic Lyme disease.’

  16. Long-term use of amiodarone before heart transplantation significantly reduces early post-transplant atrial fibrillation and is not associated with increased mortality after heart transplantation

    Directory of Open Access Journals (Sweden)

    Rivinius R

    2016-02-01

    group (P=0.0123. There was no statistically significant difference between patients with and without long-term use of amiodarone prior to HTX in 1-year (P=0.8596, 2-year (P=0.8620, 5-year (P=0.2737, or overall follow-up mortality after HTX (P=0.1049. Moreover, Kaplan–Meier survival analysis showed no statistically significant difference in overall survival (P=0.1786.Conclusion: Long-term use of amiodarone in patients before HTX significantly reduces early post-transplant AF and is not associated with increased mortality after HTX. Keywords: amiodarone, atrial fibrillation, heart failure, heart transplantation, mortality

  17. A proper choice of route significantly reduces air pollution exposure--a study on bicycle and bus trips in urban streets.

    Science.gov (United States)

    Hertel, Ole; Hvidberg, Martin; Ketzel, Matthias; Storm, Lars; Stausgaard, Lizzi

    2008-01-15

    A proper selection of route through the urban area may significantly reduce the air pollution exposure. This is the main conclusion from the presented study. Air pollution exposure is determined for two selected cohorts along the route going from home to working place, and back from working place to home. Exposure is determined with a street pollution model for three scenarios: bicycling along the shortest possible route, bicycling along the low exposure route along less trafficked streets, and finally taking the shortest trip using public transport. Furthermore, calculations are performed for the cases the trip takes place inside as well as outside the traffic rush hours. The results show that the accumulated air pollution exposure for the low exposure route is between 10% and 30% lower for the primary pollutants (NO(x) and CO). However, the difference is insignificant and in some cases even negative for the secondary pollutants (NO(2) and PM(10)/PM(2.5)). Considering only the contribution from traffic in the travelled streets, the accumulated air pollution exposure is between 54% and 67% lower for the low exposure route. The bus is generally following highly trafficked streets, and the accumulated exposure along the bus route is therefore between 79% and 115% higher than the high exposure bicycle route (the short bicycle route). Travelling outside the rush hour time periods reduces the accumulated exposure between 10% and 30% for the primary pollutants, and between 5% and 20% for the secondary pollutants. The study indicates that a web based route planner for selecting the low exposure route through the city might be a good service for the public. In addition the public may be advised to travel outside rush hour time periods.

  18. Interleukin-24 as a target cytokine of environmental aryl hydrocarbon receptor agonist exposure in the lung

    Energy Technology Data Exchange (ETDEWEB)

    Luo, Yueh-Hsia; Kuo, Yu-Chun; Tsai, Ming-Hsien; Ho, Chia-Chi; Tsai, Hui-Ti; Hsu, Chin-Yu; Chen, Yu-Cheng; Lin, Pinpin, E-mail: pplin@nhri.org.tw

    2017-06-01

    Exposure to environmental aryl hydrocarbon receptor (AhR) agonists, such as halogenated aromatic hydrocarbons and polycyclic aromatic hydrocarbons (PAHs), has great impacts on the development of various lung diseases. As emerging molecular targets for AhR agonists, cytokines may contribute to the inflammatory or immunotoxic effects of environmental AhR agonists. However, general cytokine expression may not specifically indicate environmental AhR agonist exposure. By comparing cytokine and chemokine expression profiles in human lung adenocarcinoma cell line CL5 treated with AhR agonists and the non-AhR agonist polychlorinated biphenyl (PCB) 39, we identified a target cytokine of environmental AhR agonist exposure of in the lungs. Thirteen cytokine and chemokine genes were altered in the AhR agonists-treated cells, but none were altered in the PCB39-treated cells. Interleukin (IL)-24 was the most highly induced gene among AhR-modulated cytokines. Cotreatment with AhR antagonist completely prevented IL-24 induction by AhR agonists in the CL5 cells. Knockdown AhR expression with short-hairpin RNA (shRNA) significantly reduced benzo[a]pyrene (BaP)-induced IL-24 mRNA levels. We further confirmed that gene transcription, but not mRNA stability, was involved in IL-24 upregulation by BaP. Particulate matter (PM) in the ambient air contains some PAHs and is reported to activate AhR. Oropharyngeal aspiration of PM significantly increased IL-24 levels in lung epithelia and in bronchoalveolar lavage fluid of mice 4 weeks after treatment. Thus, our data suggests that IL-24 is a pulmonary exposure target cytokine of environmental AhR agonists. - Graphical abstract: (A) Cytokine and chemokine gene expressions were examined in CL5 cells treated with AhR and non-AhR agonists. Thirteen cytokines and chemokines genes were altered in the AhR agonist-treated cells, but not in the non-AhR agonist-treated cells. IL-24 was the most highly induced gene among the AhR-modulated cytokines. (B

  19. A Rosa canina - Urtica dioica - Harpagophytum procumbens/zeyheri Combination Significantly Reduces Gonarthritis Symptoms in a Randomized, Placebo-Controlled Double-Blind Study.

    Science.gov (United States)

    Moré, Margret; Gruenwald, Joerg; Pohl, Ute; Uebelhack, Ralf

    2017-12-01

    The special formulation MA212 (Rosaxan) is composed of rosehip ( Rosa canina L.) puree/juice concentrate, nettle ( Urtica dioica L.) leaf extract, and devil's claw ( Harpagophytum procumbens DC. ex Meisn. or Harpagophytum zeyheri Decne.) root extract and also supplies vitamin D. It is a food for special medical purposes ([EU] No 609/2013) for the dietary management of pain in patients with gonarthritis.This 12-week randomized, placebo-controlled double-blind parallel-design study aimed to investigate the efficacy and safety of MA212 versus placebo in patients with gonarthritis.A 3D-HPLC-fingerprint (3-dimensional high pressure liquid chromatography fingerprint) of MA212 demonstrated the presence of its herbal ingredients. Ninety-two randomized patients consumed 40 mL of MA212 (n = 46) or placebo (n = 44) daily. The Western Ontario and McMaster Universities Arthritis Index (WOMAC), quality-of-life scores at 0, 6, and 12 weeks, and analgesic consumption were documented. Statistically, the initial WOMAC subscores/scores did not differ between groups. During the study, their means significantly improved in both groups. The mean pre-post change of the WOMAC pain score (primary endpoint) was 29.87 in the MA212 group and 10.23 in the placebo group. The group difference demonstrated a significant superiority in favor of MA212 (p U  < 0.001; p t  < 0.001). Group comparisons of all WOMAC subscores/scores at 6 and 12 weeks reached same significances. Compared to placebo, both physical and mental quality of life significantly improved with MA212. There was a trend towards reduced analgesics consumption with MA212, compared to placebo. In the final efficacy evaluation, physicians (p Chi  < 0.001) and patients (p Chi  < 0.001) rated MA212 superior to placebo. MA212 was well tolerated.This study demonstrates excellent efficacy for MA212 in gonarthritis patients. Georg Thieme Verlag KG Stuttgart · New York.

  20. Myocardial fatty acid imaging with 123I-BMIPP in patients with chronic right ventricular pressure overload. Clinical significance of reduced uptake in interventricular septum

    International Nuclear Information System (INIS)

    Hori, Yoshiro; Ishida, Yoshio; Fukuchi, Kazuki; Hayashida, Kouhei; Takamiya, Makoto

    2002-01-01

    Regionally reduced 123 I-beta-methyliodophenyl pentadecanoic acid (123I-BMIPP) uptake in the interventricular septum (SEP) is observed in some patients with chronic right ventricular (RV) pressure overload. We studied the significance of this finding by comparing it with mean pulmonary arterial pressure (mPAP). 123 I-BMIPP SPECT imaging was carried out in 21 patients with pulmonary hypertension (PH; 51+-14 years; 11 men and 10 women; 7 with primary pulmonary hypertension, 11 with pulmonary thromboembolism, and 3 with atrial septal defect). mPAP ranged from 25 to 81 mmHg (49±16 mmHg). Using a midventricular horizontal long-axis plane, regional BMIPP distributions in the RV free wall and SEP were estimated by referring to those in the LV free wall. Count ratios of the RV free wall and SEP to the LV free wall (RV/LV, SEP/LV) were determined by ROI analysis. RV/LV showed a linear correlation with mPAP (r=0.42). However, SEP/LV was inversely correlated with mPAP (r=-0.49). When SEP/RV was compared among three regions of SEP in each patient, basal SEP/RV was most sensitively decreased in response to increased mPAP (r=-0.70). These results suggest that the assessment of septal tracer uptake in 123 I-BMIPP SPECT imaging is useful for evaluating the severity of RV pressure overload in patients with PH. (author)

  1. [Changes of the immune cells, cytokines and growth hormone in teenager drug addicts].

    Science.gov (United States)

    Kuang, Ying-min; Zhu, Yue-chun; Kuang, Ying; Sun, Yuan; Hua, Chen; He, Wen-yi

    2007-09-01

    To investigate the effect of heroin on the immune function, growth and development in the teenager heroin addicts by measuring their T-lymphocyte subsets, Th1/Th2 cytokines and serum growth hormone. Tlymphocyte subsets of peripheral blood from the teenager heroin addicts were measured by direct microvolume whole blood immunofluorescent staining technique by flow cytometer (FCM). Thl / Th2 cytokines were measured by BD cytometric bead array and serum growth hormone was assayed using the chemiluminescence method in the 20 teenager heroin addicts and 23 healthy teenagers. The levels of CD3(+), CD3(+) + CD4(+), CD3(+) + CD4(+)/CD3(+)+ CD8(+), Th1 cytokines(IL-2, TNF-alpha and IFN-gamma) and Th2 cytokines(IL-4 and IL-10) reduced significantly in the teenager heroin addicts compared with the healthy control group (P teenager heroin addicts was remarkably higher than that in control group (Pteenager heroin addicts. Besides, it can increase the level of serum growth hormone of the teenager heroin addicts.

  2. A New Application for Albumin Dialysis in Extracorporeal Organ Support: Characterization of a Putative Interaction Between Human Albumin and Proinflammatory Cytokines IL-6 and TNFα.

    Science.gov (United States)

    Pfensig, Claudia; Dominik, Adrian; Borufka, Luise; Hinz, Michael; Stange, Jan; Eggert, Martin

    2016-04-01

    Albumin dialysis in extracorporeal organ support is often performed in the treatment of liver failure as it facilitates the removal of toxic components from the blood. Here, we describe a possible effect of albumin dialysis on proinflammatory cytokine levels in vitro. Initially, albumin samples were incubated with different amounts of cytokines and analyzed by enzyme-linked immunosorbent assay (ELISA). Analysis of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNFα) levels indicated that increased concentrations of albumin reduce the measureable amount of the respective cytokines. This led to the hypothesis that the used proinflammatory cytokines may interact with albumin. Size exclusion chromatography of albumin spiked with cytokines was carried out using high-performance liquid chromatography analysis. The corresponding fractions were evaluated by immunoblotting. We detected albumin and cytokines in the same fractions indicating an interaction of the small-sized cytokines IL-6 and TNFα with the larger-sized albumin. Finally, a two-compartment albumin dialysis in vitro model was used to analyze the effect of albumin on proinflammatory cytokines in the recirculation circuit during 6-h treatment. These in vitro albumin dialysis experiments indicated a significant decrease of IL-6, but not of TNFα, when albumin was added to the dialysate solution. Taken together, we were able to show a putative in vitro interaction of human albumin with the proinflammatory cytokine IL-6, but with less evidence for TNFα, and demonstrated an additional application for albumin dialysis in liver support therapy where IL-6 removal might be indicated. Copyright © 2015 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

  3. Cytokine-mediated inflammation mediates painful neuropathy from metabolic syndrome.

    Directory of Open Access Journals (Sweden)

    Can Zhang

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

  4. 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.

  5. 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.

  6. PARP-1 depletion in combination with carbon ion exposure significantly reduces MMPs activity and overall increases TIMPs expression in cultured HeLa cells

    International Nuclear Information System (INIS)

    Ghorai, Atanu; Sarma, Asitikantha; Chowdhury, Priyanka; Ghosh, Utpal

    2016-01-01

    Hadron therapy is an innovative technique where cancer cells are precisely killed leaving surrounding healthy cells least affected by high linear energy transfer (LET) radiation like carbon ion beam. Anti-metastatic effect of carbon ion exposure attracts investigators into the field of hadron biology, although details remain poor. Poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors are well-known radiosensitizer and several PARP-1 inhibitors are in clinical trial. Our previous studies showed that PARP-1 depletion makes the cells more radiosensitive towards carbon ion than gamma. The purpose of the present study was to investigate combining effects of PARP-1 inhibition with carbon ion exposure to control metastatic properties in HeLa cells. Activities of matrix metalloproteinases-2, 9 (MMP-2, MMP-9) were measured using the gelatin zymography after 85 MeV carbon ion exposure or gamma irradiation (0- 4 Gy) to compare metastatic potential between PARP-1 knock down (HsiI) and control cells (H-vector - HeLa transfected with vector without shRNA construct). Expression of MMP-2, MMP-9, tissue inhibitor of MMPs such as TIMP-1, TIMP-2 and TIMP-3 were checked by immunofluorescence and western blot. Cell death by trypan blue, apoptosis and autophagy induction were studied after carbon ion exposure in each cell-type. The data was analyzed using one way ANOVA and 2-tailed paired-samples T-test. PARP-1 silencing significantly reduced MMP-2 and MMP-9 activities and carbon ion exposure further diminished their activities to less than 3 % of control H-vector. On the contrary, gamma radiation enhanced both MMP-2 and MMP-9 activities in H-vector but not in HsiI cells. The expression of MMP-2 and MMP-9 in H-vector and HsiI showed different pattern after carbon ion exposure. All three TIMPs were increased in HsiI, whereas only TIMP-1 was up-regulated in H-vector after irradiation. Notably, the expressions of all TIMPs were significantly higher in HsiI than H-vector at 4 Gy. Apoptosis was

  7. Symmetric dimeric bisbenzimidazoles DBP(n reduce methylation of RARB and PTEN while significantly increase methylation of rRNA genes in MCF-7 cancer cells.

    Directory of Open Access Journals (Sweden)

    Svetlana V Kostyuk

    Full Text Available Hypermethylation is observed in the promoter regions of suppressor genes in the tumor cancer cells. Reactivation of these genes by demethylation of their promoters is a prospective strategy of the anticancer therapy. Previous experiments have shown that symmetric dimeric bisbenzimidazoles DBP(n are able to block DNA methyltransferase activities. It was also found that DBP(n produces a moderate effect on the activation of total gene expression in HeLa-TI population containing epigenetically repressed avian sarcoma genome.It is shown that DBP(n are able to penetrate the cellular membranes and accumulate in breast carcinoma cell MCF-7, mainly in the mitochondria and in the nucleus, excluding the nucleolus. The DBP(n are non-toxic to the cells and have a weak overall demethylation effect on genomic DNA. DBP(n demethylate the promoter regions of the tumor suppressor genes PTEN and RARB. DBP(n promotes expression of the genes RARB, PTEN, CDKN2A, RUNX3, Apaf-1 and APC "silent" in the MCF-7 because of the hypermethylation of their promoter regions. Simultaneously with the demethylation of the DNA in the nucleus a significant increase in the methylation level of rRNA genes in the nucleolus was detected. Increased rDNA methylation correlated with a reduction of the rRNA amount in the cells by 20-30%. It is assumed that during DNA methyltransferase activity inhibition by the DBP(n in the nucleus, the enzyme is sequestered in the nucleolus and provides additional methylation of the rDNA that are not shielded by DBP(n.It is concluded that DBP (n are able to accumulate in the nucleus (excluding the nucleolus area and in the mitochondria of cancer cells, reducing mitochondrial potential. The DBP (n induce the demethylation of a cancer cell's genome, including the demethylation of the promoters of tumor suppressor genes. DBP (n significantly increase the methylation of ribosomal RNA genes in the nucleoli. Therefore the further study of these compounds is needed

  8. Holstein-Friesian calves selected for divergence in residual feed intake during growth exhibited significant but reduced residual feed intake divergence in their first lactation.

    Science.gov (United States)

    Macdonald, K A; Pryce, J E; Spelman, R J; Davis, S R; Wales, W J; Waghorn, G C; Williams, Y J; Marett, L C; Hayes, B J

    2014-03-01

    Residual feed intake (RFI), as a measure of feed conversion during growth, was estimated for around 2,000 growing Holstein-Friesian heifer calves aged 6 to 9 mo in New Zealand and Australia, and individuals from the most and least efficient deciles (low and high RFI phenotypes) were retained. These animals (78 New Zealand cows, 105 Australian cows) were reevaluated during their first lactation to determine if divergence for RFI observed during growth was maintained during lactation. Mean daily body weight (BW) gain during assessment as calves had been 0.86 and 1.15 kg for the respective countries, and the divergence in RFI between most and least efficient deciles for growth was 21% (1.39 and 1.42 kg of dry matter, for New Zealand and Australia, respectively). At the commencement of evaluation during lactation, the cows were aged 26 to 29 mo. All were fed alfalfa and grass cubes; it was the sole diet in New Zealand, whereas 6 kg of crushed wheat/d was also fed in Australia. Measurements of RFI during lactation occurred for 34 to 37 d with measurements of milk production (daily), milk composition (2 to 3 times per week), BW and BW change (1 to 3 times per week), as well as body condition score (BCS). Daily milk production averaged 13.8 kg for New Zealand cows and 20.0 kg in Australia. No statistically significant differences were observed between calf RFI decile groups for dry matter intake, milk production, BW change, or BCS; however a significant difference was noted between groups for lactating RFI. Residual feed intake was about 3% lower for lactating cows identified as most efficient as growing calves, and no negative effects on production were observed. These results support the hypothesis that calves divergent for RFI during growth are also divergent for RFI when lactating. The causes for this reduced divergence need to be investigated to ensure that genetic selection programs based on low RFI (better efficiency) are robust. Copyright © 2014 American Dairy

  9. Fisetin Inhibits Hyperglycemia-Induced Proinflammatory Cytokine Production by Epigenetic Mechanisms

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    Hye Joo Kim

    2012-01-01

    Full Text Available Diabetes is characterized by a proinflammatory state, and several inflammatory processes have been associated with both type 1 and type 2 diabetes and the resulting complications. High glucose levels induce the release of proinflammatory cytokines. Fisetin, a flavonoid dietary ingredient found in the smoke tree (Cotinus coggygria, and is also widely distributed in fruits and vegetables. Fisetin is known to exert anti-inflammatory effects via inhibition of the NF-κB signaling pathway. In this study, we analyzed the effects of fisetin on proinflammatory cytokine secretion and epigenetic regulation, in human monocytes cultured under hyperglycemic conditions. Human monocytic (THP-1 cells were cultured under control (14.5 mmol/L mannitol, normoglycemic (NG, 5.5 mmol/L glucose, or hyperglycemic (HG, 20 mmol/L glucose conditions, in the absence or presence of fisetin. Fisetin was added (3–10 μM for 48 h. While the HG condition significantly induced histone acetylation, NF-κB activation, and proinflammatory cytokine (IL-6 and TNF-α release from THP-1 cells, fisetin suppressed NF-κB activity and cytokine release. Fisetin treatment also significantly reduced CBP/p300 gene expression, as well as the levels of acetylation and HAT activity of the CBP/p300 protein, which is a known NF-κB coactivator. These results suggest that fisetin inhibits HG-induced cytokine production in monocytes, through epigenetic changes involving NF-κB. We therefore propose that fisetin supplementation be considered for diabetes prevention.

  10. Cytokine-like factor-1, a novel soluble protein, shares homology with members of the cytokine type I receptor family.

    Science.gov (United States)

    Elson, G C; Graber, P; Losberger, C; Herren, S; Gretener, D; Menoud, L N; Wells, T N; Kosco-Vilbois, M H; Gauchat, J F

    1998-08-01

    In this report we describe the identification, cloning, and expression pattern of human cytokine-like factor 1 (hCLF-1) and the identification and cloning of its murine homologue. They were identified from expressed sequence tags using amino acid sequences from conserved regions of the cytokine type I receptor family. Human CLF-1 and murine CLF-1 shared 96% amino acid identity and significant homology with many cytokine type I receptors. CLF-1 is a secreted protein, suggesting that it is either a soluble subunit within a cytokine receptor complex, like the soluble form of the IL-6R alpha-chain, or a subunit of a multimeric cytokine, e.g., IL-12 p40. The highest levels of hCLF-1 mRNA were observed in lymph node, spleen, thymus, appendix, placenta, stomach, bone marrow, and fetal lung, with constitutive expression of CLF-1 mRNA detected in a human kidney fibroblastic cell line. In fibroblast primary cell cultures, CLF-1 mRNA was up-regulated by TNF-alpha, IL-6, and IFN-gamma. Western blot analysis of recombinant forms of hCLF-1 showed that the protein has the tendency to form covalently linked di- and tetramers. These results suggest that CLF-1 is a novel soluble cytokine receptor subunit or part of a novel cytokine complex, possibly playing a regulatory role in the immune system and during fetal development.

  11. Early human pregnancy serum cytokine levels predict autoimmunity in offspring.

    Science.gov (United States)

    Lindehammer, Sabina Resic; Björck, Sara; Lynch, Kristian; Brundin, Charlotte; Marsal, Karel; Agardh, Daniel; Fex, Malin

    2011-09-01

    It is generally believed that pregnancy is mediated by a Th2 response, which includes cytokines that promote placental growth and are involved in inducing tolerance to the foetus. If the balance between Th1/and Th2-mediated cytokines is disrupted, systemic and local changes could predispose the foetus to future disease. Therefore, a shift in the Th1/Th2 balance during pregnancy, possibly caused by underlying environmental factors, could be associated with post-partum autoimmune disease in the offspring. Based on this presumption, we used celiac disease as a model to investigate whether autoimmunity is triggered in the foetus during early pregnancy, observed as changes in the mother's cytokine profile. Ten cytokines were measured by electro-chemi-luminescent multiplex ELISA in serum samples obtained from mothers during early pregnancy. Cases included women with children who had developed verified celiac disease before the age of 5, who were compared with other women as matched controls. We observed that 7 out of 10 cytokine levels were significantly increased in our case mothers when compared to controls. Five of these belonged to what is generally known as a Th1-mediated response (TNFα, IFNγ, IL-2, IL-1β and IL-12) and two were Th2 cytokines (IL-13 and IL-10). However, the IL-10 cytokine is known to have features from both arms of the immune system. These results were confirmed in a logistic regression model where five out of the initial seven cytokines remained. This study suggests that increase in Th1 serum cytokines may be associated with celiac disease in offspring.

  12. Leucocytes, cytokines and satellite cells

    DEFF Research Database (Denmark)

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

    2012-01-01

    uncertain. The COX enzymes regulate satellite cell activity, as demonstrated in animal models; however the roles of the COX enzymes in human skeletal muscle need further investigation. We suggest using the term 'muscle damage' with care. Comparisons between studies and individuals must consider changes......-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...

  13. 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....

  14. Differentiated THP-1 Cells Exposed to Pathogenic and Nonpathogenic Borrelia Species Demonstrate Minimal Differences in Production of Four Inflammatory Cytokines.

    Science.gov (United States)

    Stokes, John V; Moraru, Gail M; McIntosh, Chelsea; Kummari, Evangel; Rausch, Keiko; Varela-Stokes, Andrea S

    2016-11-01

    Tick-borne borreliae include Lyme disease and relapsing fever agents, and they are transmitted primarily by ixodid (hard) and argasid (soft) tick vectors, respectively. Tick-host interactions during feeding are complex, with host immune responses influenced by biological differences in tick feeding and individual differences within and between host species. One of the first encounters for spirochetes entering vertebrate host skin is with local antigen-presenting cells, regardless of whether the tick-associated Borrelia sp. is pathogenic. In this study, we performed a basic comparison of cytokine responses in THP-1-derived macrophages after exposure to selected borreliae, including a nonpathogen. By using THP-1 cells, differentiated to macrophages, we eliminated variations in host response and reduced the system to an in vitro model to evaluate the extent to which the Borrelia spp. influence cytokine production. Differentiated THP-1 cells were exposed to four Borrelia spp., Borrelia hermsii (DAH), Borrelia burgdorferi (B31), B. burgdorferi (NC-2), or Borrelia lonestari (LS-1), or lipopolysaccharides (LPS) (activated) or media (no treatment) controls. Intracellular and secreted interferon (IFN)-γ, interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α were measured using flow cytometric and Luminex-based assays, respectively, at 6, 24, and 48 h postexposure time points. Using a general linear model ANOVA for each cytokine, treatment (all Borrelia spp. and LPS compared to no treatment) had a significant effect on secreted TNF-α only. Time point had a significant effect on intracellular IFN-γ, TNF-α and IL-6. However, we did not see significant differences in selected cytokines among Borrelia spp. Thus, in this model, we were unable to distinguish pathogenic from nonpathogenic borreliae using the limited array of selected cytokines. While unique immune profiles may be detectable in an in vitro model and may reveal predictors for pathogenicity in borreliae

  15. Cytokine Status, Thyroid Autoantibodies and Their Dynamic Changes During the Treatment of Graves' Disease

    Directory of Open Access Journals (Sweden)

    V V Lazanovich

    2008-09-01

    Full Text Available It has been found during the research that the changes of Th1 and Th2 marker cytokine content in Graves Disease are dynamic and are directly correlated not only with the severity of autoimmune thyrotoxicosis, but also with the method of treatment used and duration of Thiamazole therapy. The beginning of autoimmune thyrotoxicosis shows the largest amounts of both pro-inflammatory (IL-1a, IL-8, IFN-γ and anti-inflammatory (IL-10 cytokines which are significantly reduced during Thiamazole therapy, with the exception of the cases of severe disease course. Thyroid resection does not result in immunologic remission either, which is confirmed by persisting high serum levels of IL-1a, IL-8, IFN-γ, IL-10 and TSH antibodies in the severe GBD group. Among the unfavorable prognostic factors for recurrent disease are high serum levels of TSH antibodies, IL-1a and IFN-γ during pre-surgery period.

  16. SALMON SOFT ROE DNA ON BLOOD CELLS SECRETION OF CYTOKINES IN HEALTHY DONORS

    Directory of Open Access Journals (Sweden)

    L. N. Fedjanina

    2005-01-01

    Full Text Available Abstract. Salmon soft roe DNA influence on healthy donors blood cells secretion of early hemopoietic factors (IL-3, GM-CSF, TNFα as well as biologically active substance influence on cytokine balance of Тh1 and Тh2 responses (IFNγ, IL-10 in vitro was studied. It is established, that DNA has modulatory effect on secretion of all investigated cytokines - IL-3, GM-CSF, TNFα, INFγ and IL-10 by blood cells of healthy donors, increases their initially low concentration, reduces initially high and does not have essential influence at an average level of their secretion. Under action of DNA IFNγ level (stimulation index=3,3 increases more significantly than IL-10 level (stimulation index =1,9. Thus, salmon soft roe DNA possesses immunomodulatory properties.

  17. Curcumin protects against radiation-induced acute and chronic cutaneous toxicity in mice and decreases mRNA expression of inflammatory and fibrogenic cytokines

    International Nuclear Information System (INIS)

    Okunieff, Paul; Xu Jianhua; Hu Dongping; Liu Weimin; Zhang Lurong; Morrow, Gary; Pentland, Alice; Ryan, Julie L.; Ding, Ivan M.D.

    2006-01-01

    Purpose: To determine whether curcumin ameliorates acute and chronic radiation skin toxicity and to examine the expression of inflammatory cytokines (interleukin [IL]-1, IL-6, IL-18, IL-1Ra, tumor necrosis factor [TNF]-α, and lymphotoxin-β) or fibrogenic cytokines (transforming growth factor [TGF]-β) during the same acute and chronic phases. Methods and Materials: Curcumin was given intragastrically or intraperitoneally to C3H/HeN mice either: 5 days before radiation; 5 days after radiation; or both 5 days before and 5 days after radiation. The cutaneous damage was assessed at 15-21 days (acute) and 90 days (chronic) after a single 50 Gy radiation dose was given to the hind leg. Skin and muscle tissues were collected for measurement of cytokine mRNA. Results: Curcumin, administered before or after radiation, markedly reduced acute and chronic skin toxicity in mice (p < 0.05). Additionally, curcumin significantly decreased mRNA expression of early responding cytokines (IL-1 IL-6, IL-18, TNF-α, and lymphotoxin-β) and the fibrogenic cytokine, TGF-β, in cutaneous tissues at 21 days postradiation. Conclusion: Curcumin has a protective effect on radiation-induced cutaneous damage in mice, which is characterized by a downregulation of both inflammatory and fibrogenic cytokines in irradiated skin and muscle, particularly in the early phase after radiation. These results may provide the molecular basis for the application of curcumin in clinical radiation therapy

  18. Leukocyte-depletion of blood components does not significantly reduce the risk of infectious complications. Results of a double-blinded, randomized study

    DEFF Research Database (Denmark)

    Titlestad, I. L.; Ebbesen, L. S.; Ainsworth, A. P.

    2001-01-01

    Allogeneic blood transfusions are claimed to be an independent risk factor for postoperative infections in open colorectal surgery due to immunomodulation. Leukocyte-depletion of erythrocyte suspensions has been shown in some open randomized studies to reduce the rate of postoperative infection t...

  19. 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.

  20. Picroside II Attenuates Airway Inflammation by Downregulating the Transcription Factor GATA3 and Th2-Related Cytokines in a Mouse Model of HDM-Induced Allergic Asthma.

    Directory of Open Access Journals (Sweden)

    Jin Choi

    Full Text Available Picroside II isolated from Pseudolysimachion rotundum var. subintegrum has been used as traditional medicine to treat inflammatory diseases. In this study, we assessed whether picroside II has inhibitory effects on airway inflammation in a mouse model of house dust mite (HDM-induced asthma. In the HDM-induced asthmatic model, picroside II significantly reduced inflammatory cell counts in the bronchoalveolar lavage fluid (BALF, the levels of total immunoglobulin (Ig E and HDM-specific IgE and IgG1 in serum, airway inflammation, and mucus hypersecretion in the lung tissues. ELISA analysis showed that picroside II down-regulated the levels of Th2-related cytokines (including IL-4, IL-5, and IL-13 and asthma-related mediators, but it up-regulated Th1-related cytokine, IFNγ in BALF. Picroside II also inhibited the expression of Th2 type cytokine genes and the transcription factor GATA3 in the lung tissues of HDM-induced mice. Finally, we demonstrated that picroside II significantly decreased the expression of GATA3 and Th2 cytokines in developing Th2 cells, consistent with in vivo results. Taken together, these results indicate that picroside II has protective effects on allergic asthma by reducing GATA3 expression and Th2 cytokine bias.

  1. Oxidative stress and proinflammatory cytokines contribute to demyelination and axonal damage in a cerebellar culture model of neuroinflammation.

    Science.gov (United States)

    di Penta, Alessandra; Moreno, Beatriz; Reix, Stephanie; Fernandez-Diez, Begoña; Villanueva, Maite; Errea, Oihana; Escala, Nagore; Vandenbroeck, Koen; Comella, Joan X; Villoslada, Pablo

    2013-01-01

    Demyelination and axonal damage are critical processes in the pathogenesis of multiple sclerosis (MS). Oxidative stress and pro-inflammatory cytokines elicited by inflammation mediates tissue damage. To monitor the demyelination and axonal injury associated with microglia activation we employed a model using cerebellar organotypic cultures stimulated with lipopolysaccharide (LPS). Microglia activated by LPS released pro-inflammatory cytokines (IL-1β, IL-6 and TNFα), and increased the expression of inducible nitric oxide synthase (iNOS) and production of reactive oxygen species (ROS). This activation was associated with demyelination and axonal damage in cerebellar cultures. Axonal damage, as revealed by the presence of non-phosphorylated neurofilaments, mitochondrial accumulation in axonal spheroids, and axonal transection, was associated with stronger iNOS expression and concomitant increases in ROS. Moreover, we analyzed the contribution of pro-inflammatory cytokines and oxidative stress in demyelination and axonal degeneration using the iNOS inhibitor ethyl pyruvate, a free-scavenger and xanthine oxidase inhibitor allopurinol, as well as via blockage of pro-inflammatory cytokines using a Fc-TNFR1 construct. We found that blocking microglia activation with ethyl pyruvate or allopurinol significantly decreased axonal damage, and to a lesser extent, demyelination. Blocking TNFα significantly decreased demyelination but did not prevented axonal damage. Moreover, the most common therapy for MS, interferon-beta, was used as an example of an immunomodulator compound that can be tested in this model. In vitro, interferon-beta treatment decreased oxidative stress (iNOS and ROS levels) and the release of pro-inflammatory cytokines after LPS stimulation, reducing axonal damage. The model of neuroinflammation using cerebellar culture stimulated with endotoxin mimicked myelin and axonal damage mediated by the combination of oxidative stress and pro-inflammatory cytokines

  2. Oxidative Stress and Proinflammatory Cytokines Contribute to Demyelination and Axonal Damage in a Cerebellar Culture Model of Neuroinflammation

    Science.gov (United States)

    di Penta, Alessandra; Moreno, Beatriz; Reix, Stephanie; Fernandez-Diez, Begoña; Villanueva, Maite; Errea, Oihana; Escala, Nagore; Vandenbroeck, Koen; Comella, Joan X.; Villoslada, Pablo

    2013-01-01

    Background Demyelination and axonal damage are critical processes in the pathogenesis of multiple sclerosis (MS). Oxidative stress and pro-inflammatory cytokines elicited by inflammation mediates tissue damage. Methods/Principal Findings To monitor the demyelination and axonal injury associated with microglia activation we employed a model using cerebellar organotypic cultures stimulated with lipopolysaccharide (LPS). Microglia activated by LPS released pro-inflammatory cytokines (IL-1β, IL-6 and TNFα), and increased the expression of inducible nitric oxide synthase (iNOS) and production of reactive oxygen species (ROS). This activation was associated with demyelination and axonal damage in cerebellar cultures. Axonal damage, as revealed by the presence of non-phosphorylated neurofilaments, mitochondrial accumulation in axonal spheroids, and axonal transection, was associated with stronger iNOS expression and concomitant increases in ROS. Moreover, we analyzed the contribution of pro-inflammatory cytokines and oxidative stress in demyelination and axonal degeneration using the iNOS inhibitor ethyl pyruvate, a free-scavenger and xanthine oxidase inhibitor allopurinol, as well as via blockage of pro-inflammatory cytokines using a Fc-TNFR1 construct. We found that blocking microglia activation with ethyl pyruvate or allopurinol significantly decreased axonal damage, and to a lesser extent, demyelination. Blocking TNFα significantly decreased demyelination but did not prevented axonal damage. Moreover, the most common therapy for MS, interferon-beta, was used as an example of an immunomodulator compound that can be tested in this model. In vitro, interferon-beta treatment decreased oxidative stress (iNOS and ROS levels) and the release of pro-inflammatory cytokines after LPS stimulation, reducing axonal damage. Conclusion The model of neuroinflammation using cerebellar culture stimulated with endotoxin mimicked myelin and axonal damage mediated by the combination of

  3. NNZ-2566 treatment inhibits neuroinflammation and pro-inflammatory cytokine expression induced by experimental penetrating ballistic-like brain injury in rats

    Directory of Open Access Journals (Sweden)

    Tortella Frank C

    2009-08-01

    Full Text Available Abstract Background Inflammatory cytokines play a crucial role in the pathophysiology of traumatic brain injury (TBI, exerting either deleterious effects on the progression of tissue damage or beneficial roles during recovery and repair. NNZ-2566, a synthetic analogue of the neuroprotective tripeptide Glypromate®, has been shown to be neuroprotective in animal models of brain injury. The goal of this study was to determine the effects of NNZ-2566 on inflammatory cytokine expression and neuroinflammation induced by penetrating ballistic-like brain injury (PBBI in rats. Methods NNZ-2566 or vehicle (saline was administered intravenously as a bolus injection (10 mg/kg at 30 min post-injury, immediately followed by a continuous infusion of NNZ-2566 (3 mg/kg/h, or equal volume of vehicle, for various durations. Inflammatory cytokine gene expression from the brain tissue of rats exposed to PBBI was evaluated using microarray, quantitative real time PCR (QRT-PCR, and enzyme-linked immunosorbent assay (ELISA array. Histopathology of the injured brains was examined using hematoxylin and eosin (H&E and immunocytochemistry of inflammatory cytokine IL-1β. Results NNZ-2566 treatment significantly reduced injury-mediated up-regulation of IL-1β, TNF-α, E-selectin and IL-6 mRNA during the acute injury phase. ELISA cytokine array showed that NZ-2566 treatment significantly reduced levels of the pro-inflammatory cytokines IL-1β, TNF-α and IFN-γ in the injured brain, but did not affect anti-inflammatory cytokine IL-6 levels. Conclusion Collectively, these results suggest that the neuroprotective effects of NNZ-2566 may, in part, be functionally attributed to the compound's ability to modulate expression of multiple neuroinflammatory mediators in the injured brain.

  4. Dosha phenotype specific Ayurveda intervention ameliorates asthma symptoms through cytokine modulations: Results of whole system clinical trial.

    Science.gov (United States)

    Joshi, Kalpana S; Nesari, Tanuja M; Dedge, Amrish P; Dhumal, Vikram R; Shengule, Sushant A; Gadgil, Maithili S; Salvi, Sundeep; Valiathan, Marthanda Varma Sankaran

    2017-02-02

    .0001) was observed in asthmatic patients who underwent Ayurvedic treatment. Circulating levels of IgE (p<0.03) and eosinophil numbers (p=0.001) reduced significantly in the asthmatics after Ayurvedic treatment. This was associated with significant reduction in levels of circulating cytokines. Levels of Th2, Th1 and inflammatory cytokines in the peripheral blood were higher than healthy control participants at baseline (p values <0.0001) and reduced significantly after ayurvedic intervention. This proof of concept study highlights the potential benefits and possible mechanism of Ayurvedic interventions in patients with mild-to-moderate asthma. The interventions significantly reduced IgE and eosinophil count, also improved lung function and reduced levels of circulating Th2 cytokines. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  5. Gallic Acid Decreases Inflammatory Cytokine Secretion Through Histone Acetyltransferase/Histone Deacetylase Regulation in High Glucose-Induced Human Monocytes.

    Science.gov (United States)

    Lee, Wooje; Lee, Sang Yeol; Son, Young-Jin; Yun, Jung-Mi

    2015-07-01

    Hyperglycemia contributes to diabetes and several diabetes-related complications. Gallic acid is a polyhydroxy phenolic compound found in various natural products. In this study, we investigated the effects and mechanism of gallic acid on proinflammatory cytokine secretion in high glucose-induced human monocytes (THP-1 cells). THP-1 cells were cultured under normoglycemic or hyperglycemic conditions, in the absence or presence of gallic acid. Hyperglycemic conditions significantly induced histone acetylation, nuclear factor-κB (NF-κB) activation, and proinflammatory cytokine release from THP-1 cells, whereas gallic acid suppressed NF-κB activity and cytokine release. It also significantly reduced CREB-binding protein/p300 (CBP/p300, a NF-κB coactivator) gene expression, acetylation levels, and CBP/p300 histone acetyltransferase (HAT) activity. In addition, histone deacetylase 2 (HDAC2) expression was significantly induced. These results suggest that gallic acid inhibits hyperglycemic-induced cytokine production in monocytes through epigenetic changes involving NF-κB. Therefore, gallic acid may have potential for the treatment and prevention of diabetes and its complications.

  6. 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

  7. Performance evaluation of FlowCytomix assays to quantify cytokines in patients with rheumatoid arthritis

    Science.gov (United States)

    Wang, Xuefeng; Dong, Liyang; Liang, Yong; Ni, Hongchang; Tang, Jun; Xu, Chengcheng; Zhou, Yuepeng; Su, Yuting; Wang, Jun; Chen, Deyu; Mao, Chaoming

    2015-01-01

    Objectives: To compare the cytokine profile in RA patients and healthy control by using two methods-FlowCytomix assay and traditional ELISA. Methods: Cytokine levels were evaluated by FlowCytomix assay and ELISA in serum and supernatants of peripheral blood mononuclear cells (PBMC) cultures with and without stimulation by phytohaemagglutinin (PHA). Results: The levels of IL-6, IL-1β, and TNF-α were significantly higher in sera of RA patients than those of healthy controls. The levels of IL-22, IL-6, IL-1β, TNF-α, and IL-10 were higher in unstimulated PBMC culture supernatant of RA patients than those of healthy controls. PHA stimulation significantly increased the production of proinflammatory cytokines from PBMC with RA patients. Compared with detectable cytokine levels in sera, cytokine concentration in the supernatant of PBMCs was remarkably higher. FlowCytomix and ELISA showed significant correlation in detecting cytokines. However, the FlowCytomix assay detected more cytokines than ELISA. Conclusion: The supernatant of PBMCs provide a fine condition for the study of cytokine production because of the lack of interference factors in sera. The FlowCytomix assay is more sensitive than ELISA in detecting cytokines from RA patients. Multiple cytokine signatures using FlowCytomix assay may represent a more realistic approach in the future of personalized medicine in RA. PMID:26629129

  8. Reduced memory skills and increased hair cortisol levels in recent Ecstasy/MDMA users: significant but independent neurocognitive and neurohormonal deficits.

    Science.gov (United States)

    Downey, Luke A; Sands, Helen; Jones, Lewis; Clow, Angela; Evans, Phil; Stalder, Tobias; Parrott, Andrew C

    2015-05-01

    The goals of this study were to measure the neurocognitive performance of recent users of recreational Ecstasy and investigate whether it was associated with the stress hormone cortisol. The 101 participants included 27 recent light users of Ecstasy (one to four times in the last 3 months), 23 recent heavier Ecstasy users (five or more times) and 51 non-users. Rivermead paragraph recall provided an objective measure for immediate and delayed recall. The prospective and retrospective memory questionnaire provided a subjective index of memory deficits. Cortisol levels were taken from near-scalp 3-month hair samples. Cortisol was significantly raised in recent heavy Ecstasy users compared with controls, whereas hair cortisol in light Ecstasy users was not raised. Both Ecstasy groups were significantly impaired on the Rivermead delayed word recall, and both groups reported significantly more retrospective and prospective memory problems. Stepwise regression confirmed that lifetime Ecstasy predicted the extent of these memory deficits. Recreational Ecstasy is associated with increased levels of the bio-energetic stress hormone cortisol and significant memory impairments. No significant relationship between cortisol and the cognitive deficits was observed. Ecstasy users did display evidence of a metacognitive deficit, with the strength of the correlations between objective and subjective memory performances being significantly lower in the Ecstasy users. Copyright © 2015 John Wiley & Sons, Ltd.

  9. Metaldyne: Plant-Wide Assessment at Royal Oak Finds Opportunities to Improve Manufacturing Efficiency, Reduce Energy Use, and Achieve Significant Cost Savings

    Energy Technology Data Exchange (ETDEWEB)

    2005-05-01

    This case study prepared for the U.S. Department of Energy's Industrial Technologies Program describes a plant-wide energy assessment conducted at the Metaldyne, Inc., forging plant in Royal Oak, Michigan. The assessment focused on reducing the plant's operating costs, inventory, and energy use. If the company were to implement all the recommendations that came out of the assessment, its total annual energy savings for electricity would be about 11.5 million kWh and annual cost savings would be $12.6 million.

  10. Cytokine Correlations in Youth with Tic Disorders

    OpenAIRE

    Parker-Athill, E. Carla; Ehrhart, Jared; Tan, Jun; Murphy, Tanya K.

    2015-01-01

    Background: Studies have noted immunological disruptions in patients with tic disorders, including increased serum cytokine levels. This study aimed to determine whether or not cytokine levels could be correlated with tic symptom severity in patients with a diagnosed tic disorder.

  11. 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

  12. Cytokine Response to Exercise and Its Modulation

    OpenAIRE

    Katsuhiko Suzuki

    2018-01-01

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

  13. The co registration of initial PET on the CT-radiotherapy reduces significantly the variabilities of anatomo-clinical target volume in the child hodgkin disease

    International Nuclear Information System (INIS)

    Metwally, H.; Blouet, A.; David, I.; Rives, M.; Izar, F.; Courbon, F.; Filleron, T.; Laprie, A.; Plat, G.; Vial, J.

    2009-01-01

    It exists a great interobserver variability for the anatomo-clinical target volume (C.T.V.) definition in children suffering of Hodgkin disease. In this study, the co-registration of the PET with F.D.G. on the planning computed tomography has significantly lead to a greater coherence in the clinical target volume definition. (N.C.)

  14. The effects of dietary phenolic compounds on cytokine and antioxidant production by A549 cells.

    Science.gov (United States)

    Gauliard, Benoit; Grieve, Douglas; Wilson, Rhoda; Crozier, Alan; Jenkins, Carol; Mullen, William D; Lean, Michael

    2008-06-01

    Levels of inflammatory cytokines are raised in chronic obstructive pulmonary disease (COPD). A diet rich in antioxidant vitamins may protect against the development of COPD. This study examined the effects of phenolic compounds and food sources on cytokine and antioxidant production by A549 cells. The effects of the following phenolic compounds on basal and interleukin (IL)-1-stimulated release of IL-8, IL-6, and reduced glutathione (GSH) were examined: resveratrol; Bouvrage, a commercially available raspberry juice (Ella Drinks Ltd., Alloa, Clacksmannanshire, UK); and quercetin 3'-sulfate. Purification of the raspberry juice by high-performance liquid chromatography gave three fractions: Fraction 1 contained phenolic acid and vitamin C, Fraction 2 contained flavonoids and ellagic acid, and Fraction 3 contained anthocyanins and ellagitannins. IL-8 production was increased in the presence of IL-1 (165 vs. 6,011 pg/mL, P or =50 micromol/mL significantly inhibited IL-8 and IL-6 production. Similar findings were made with raspberry juice at concentrations > or =25 microL/mL, and Fractions 1 and 3 were best able to inhibit IL-8 production. Quercetin 3'-sulfate, at 25 micromol/mL, inhibited IL-8 and IL-6 production. The changes observed in IL-8 were paralleled by changes in tumor necrosis factor-alpha. Thus, phenolic compounds can significantly alter cytokine and antioxidant production.

  15. Cytokines cause functional and structural damage to isolated islets of Langerhans

    DEFF Research Database (Denmark)

    Mandrup-Poulsen, T; Bendtzen, K; Bendixen, G

    1985-01-01

    Cytokines are soluble, antigen non-specific, non-immunoglobulin mediators produced and secreted by blood mononuclear cells interacting in the cellular immune-response. To test the possibility that cytokines participate in the autoimmune destruction of the pancreatic beta-cells leading to insulin-......-release, and contents of insulin and glucagon in islets incubated with cytokine-rich supernatants were markedly reduced. This impairment of islet function was due to a cytotoxic effect of cytokine-rich supernatants as judged by disintegration of normal light-microscopic morphology....

  16. Markers of liver function and inflammatory cytokines modulation by ...

    African Journals Online (AJOL)

    Conclusion: Aerobic exercise training modulates inflammatory cytokine levels and markers of liver function in patients with nonalcoholic ... and is associated with over nutrition and under activity, ... of these subjects with leptin reduced liver fat and liver enzyme ... tissue, muscle-released interleukin-6 inhibition of tumor.

  17. Soluble CD36 and risk markers of insulin resistance and atherosclerosis are elevated in polycystic ovary syndrome and significantly reduced during pioglitazone treatment

    DEFF Research Database (Denmark)

    Glintborg, Dorte; Højlund, Kurt; Andersen, Marianne

    2007-01-01

    Objective: We investigated the relation between soluble CD36 (sCD36), risk markers of atherosclerosis and body composition, and glucose and lipid metabolism in polycystic ovary syndrome (PCOS) Research Design and Methods: Thirty PCOS patients were randomized to pioglitazone, 30 mg/day or placebo...... units), oxLDL (44.9 (26.9 - 75.1) vs. 36.1 (23.4 - 55.5) U/l), and hsCRP (0.26 (0.03 - 2.41) vs. 0.12 (0.02 - 0.81) mg/dl) were significantly increased in PCOS patients vs. controls (geometric mean (+/- 2SD)). In PCOS, positive correlations were found between central fat mass and sCD36 (r=0.43), hs......CRP (r=0.43), and IL-6 (r=0.42), all pPCOS patients and controls (n=44). sCD36 and oxLDL were significant...

  18. Does Liposomal Bupivacaine (Exparel) Significantly Reduce Postoperative Pain/Numbness in Symptomatic Teeth with a Diagnosis of Necrosis? A Prospective, Randomized, Double-blind Trial.

    Science.gov (United States)

    Glenn, Brandon; Drum, Melissa; Reader, Al; Fowler, Sara; Nusstein, John; Beck, Mike

    2016-09-01

    Medical studies have shown some potential for infiltrations of liposomal bupivacaine (Exparel; Pacira Pharmaceuticals, San Diego, CA), a slow-release bupivacaine solution, to extend postoperative benefits of numbness/pain relief for up to several days. Because the Food and Drug Administration has approved Exparel only for infiltrations, we wanted to evaluate if it would be effective as an infiltration to control postoperative pain. The purpose of this study was to compare an infiltration of bupivacaine with liposomal bupivacaine for postoperative numbness and pain in symptomatic patients diagnosed with pulpal necrosis experiencing moderate to severe preoperative pain. One hundred patients randomly received a 4.0-mL buccal infiltration of either bupivacaine or liposomal bupivacaine after endodontic debridement. For postoperative pain, patients were given ibuprofen/acetaminophen, and they could receive narcotic pain medication as an escape. Patients recorded their level of numbness, pain, and medication use the night of the appointment and over the next 5 days. Success was defined as no or mild postoperative pain and no narcotic use. The success rate was 29% for the liposomal group and 22% for the bupivacaine group, with no significant difference (P = .4684) between the groups. Liposomal bupivacaine had some effect on soft tissue numbness, pain, and use of non-narcotic medications, but it was not clinically significant. There was no significant difference in the need for escape medication. For symptomatic patients diagnosed with pulpal necrosis experiencing moderate to severe preoperative pain, a 4.0-mL infiltration of liposomal bupivacaine did not result in a statistically significant increase in postoperative success compared with an infiltration of 4.0 mL bupivacaine. Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  19. Anti-inflammatory homoeopathic drug dilutions restrain lipopolysaccharide-induced release of pro-inflammatory cytokines: In vitro and in vivo evidence

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    Umesh B Mahajan

    2017-01-01

    Full Text Available Context: The lipopolysaccharide (LPS-induced cytokine release and oxidative stress are validated experimental parameters used to test anti-inflammatory activity. We investigated the effects of homoeopathic mother tinctures, 6 CH, 30 CH and 200 CH dilutions of Arnica montana, Thuja occidentalis and Bryonia alba against LPS (1 μg/ml-induced cytokine release from RAW-264.7 cells and human whole-blood culture. Materials and Methods: For in vivo evaluations, mice were orally treated with 0.1 ml drug dilutions twice a day for 5 days followed by an intraperitoneal injection of 0.5 mg/kg LPS. After 24 h, the mice were sacrificed and serum levels of pro-inflammatory cytokines and nitric oxide were determined. The extent of oxidative stress was determined in the liver homogenates as contents of reduced glutathione, malondialdehyde, superoxide dismutase and catalase. Results: The tested drug dilutions significantly reduced in vitro LPS-induced release of tumour necrosis factor-α, interleukin-1 (IL-1 and IL-6 from the RAW-264.7 cells and human whole blood culture. Similar suppression of cytokines was evident in mice serum samples. These drugs also protected mice from the LPS-induced oxidative stress in liver tissue. Conclusions: Our findings substantiate the protective effects of Arnica, Thuja and Bryonia homoeopathic dilutions against LPS-induced cytokine elevations and oxidative stress. This study authenticates the claims of anti-inflammatory efficacy of these homoeopathic drugs.

  20. Reduced estimated glomerular filtration rate (eGFR 73 m2 ) at first transurethral resection of bladder tumour is a significant predictor of subsequent recurrence and progression.

    Science.gov (United States)

    Blute, Michael L; Kucherov, Victor; Rushmer, Timothy J; Damodaran, Shivashankar; Shi, Fangfang; Abel, E Jason; Jarrard, David F; Richards, Kyle A; Messing, Edward M; Downs, Tracy M

    2017-09-01

    To evaluate if moderate chronic kidney disease [CKD; estimated glomerular filtration rate (eGFR) 73 m 2 ] is associated with high rates of non-muscle-invasive bladder cancer (NMIBC) recurrence or progression. A multi-institutional database identified patients with serum creatinine values prior to first transurethral resection of bladder tumour (TURBT). The CKD-epidemiology collaboration formula calculated patient eGFR. Cox proportional hazards models evaluated associations with recurrence-free (RFS) and progression-free survival (PFS). In all, 727 patients were identified with a median (interquartile range [IQR]) patient age of 69.8 (60.1-77.6) years. Data for eGFR were available for 632 patients. During a median (IQR) follow-up of 3.7 (1.5-6.5) years, 400 (55%) patients had recurrence and 145 (19.9%) patients had progression of tumour stage or grade. Moderate or severe CKD was identified in 183 patients according to eGFR. Multivariable analysis identified an eGFR of 73 m 2 (hazard ratio [HR] 1.5, 95% confidence interval [CI]: 1.2-1.9; P = 0.002) as a predictor of tumour recurrence. The 5-year RFS rate was 46% for patients with an eGFR of ≥60 mL/min/1.73 m 2 and 27% for patients with an eGFR of 73 m 2 (P 73 m 2 (HR 3.7, 95% CI: 1.75-7.94; P = 0.001) was associated with progression to muscle-invasive disease. The 5-year PFS rate was 83% for patients with an eGFR of ≥60 mL/min/1.73 m 2 and 71% for patients with an eGFR of 73 m 2 (P = 0.01). Moderate CKD at first TURBT is associated with reduced RFS and PFS. Patients with reduced renal function should be considered for increased surveillance. © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.

  1. The Role of Cytokines and Chemokines in Filovirus Infection

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    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.

  2. The Role of Cytokines and Chemokines in Filovirus Infection.

    Science.gov (United States)

    Bixler, Sandra L; Goff, Arthur J

    2015-10-23

    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.

  3. The role of cytokine deficiencies and cytokine autoantibodies in clinical dermatology

    DEFF Research Database (Denmark)

    Liszewski, Walter; Gniadecki, Robert

    2016-01-01

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

  4. INDUCTION OF CYTOKINE PRODUCTION IN CHEETAH (ACINONYX JUBATUS) PERIPHERAL BLOOD MONONUCLEAR CELLS AND VALIDATION OF FELINE-SPECIFIC CYTOKINE ASSAYS FOR ANALYSIS OF CHEETAH SERUM.

    Science.gov (United States)

    Franklin, Ashley D; Crosier, Adrienne E; Vansandt, Lindsey M; Mattson, Elliot; Xiao, Zhengguo

    2015-06-01

    Peripheral blood mononuclear cells (PBMCs) were isolated from the whole blood of cheetahs (Acinonyx jubatus ; n=3) and stimulated with lipopolysaccharides (LPS) to induce the production of proinflammatory cytokines TNF-α, IL-1β, and IL-6 for establishment of cross-reactivity between these cheetah cytokines and feline-specific cytokine antibodies provided in commercially available Feline DuoSet® ELISA kits (R&D Systems, Inc., Minneapolis, Minnesota 55413, USA). This study found that feline-specific cytokine antibodies bind specifically to cheetah proinflammatory cytokines TNF-α, IL-1β, and IL-6 from cell culture supernatants. The assays also revealed that cheetah PBMCs produce a measurable, cell concentration-dependent increase in proinflammatory cytokine production after LPS stimulation. To enable the use of these kits, which are designed for cell culture supernatants for analyzing cytokine concentrations in cheetah serum, percent recovery and parallelism of feline cytokine standards in cheetah serum were also evaluated. Cytokine concentrations in cheetah serum were approximated based on the use of domestic cat standards in the absence of cheetah standard material. In all cases (for cytokines TNF-α, IL-1β, and IL-6), percent recovery increased as the serum sample dilution increased, though percent recovery varied between cytokines at a given dilution factor. A 1:2 dilution of serum resulted in approximately 45, 82, and 7% recovery of TNF-α, IL-1β, and IL-6 standards, respectively. Adequate parallelism was observed across a large range of cytokine concentrations for TNF-α and IL-1β; however, a significant departure from parallelism was observed between the IL-6 standard and the serum samples (P=0.004). Therefore, based on our results, the Feline DuoSet ELISA (R&D Systems, Inc.) kits are valid assays for the measurement of TNF-α and IL-1β in cheetah serum but should not be used for accurate measurement of IL-6.

  5. Intra-articular laser treatment plus Platelet Rich Plasma (PRP) significantly reduces pain in many patients who had failed prior PRP treatment

    Science.gov (United States)

    Prodromos, Chadwick C.; Finkle, Susan; Dawes, Alexander; Dizon, Angelo

    2018-02-01

    INTRODUCTION: In our practice Platelet Rich Plasma (PRP) injections effectively reduce pain in most but not all arthritic patients. However, for patients who fail PRP treatment, no good alternative currently exists except total joint replacement surgery. Low level laser therapy (LLLT) on the surface of the skin has not been helpful for arthritis patients in our experience. However, we hypothesized that intra-articular laser treatment would be an effective augmentation to PRP injection and would increase its efficacy in patients who had failed prior PRP injection alone. METHODS: We offered Intra-articular Low Level Laser Therapy (IAL) treatment in conjunction with repeat PRP injection to patients who had received no benefit from PRP injection alone at our center. They were the treatment group. They were not charged for PRP or IAL. They also served as a historical control group since they had all had failed PRP treatment alone. 28 patients (30 joints) accepted treatment after informed consent. 22 knees, 4 hips, 2 shoulder glenohumeral joints and 1 first carpo-metacarpal (1st CMC) joint were treated RESULTS: All patients were followed up at 1 month and no adverse events were seen from the treatment. At 6 months post treatment 46% of patients had good outcomes, and at 1 year 17% still showed improvement after treatment. 11 patients failed treatment and went on to joint replacement. DISCUSSION: A single treatment of IAL with PRP salvaged 46% of patients who had failed PRP treatment alone, allowing avoidance of surgery and good pain control.

  6. Glucagon-like peptide-1 acutely affects renal blood flow and urinary flow rate in spontaneously hypertensive rats despite significantly reduced renal expression of GLP-1 receptors.

    Science.gov (United States)

    Ronn, Jonas; Jensen, Elisa P; Wewer Albrechtsen, Nicolai J; Holst, Jens Juul; Sorensen, Charlotte M

    2017-12-01

    Glucagon-like peptide-1 (GLP-1) is an incretin hormone increasing postprandial insulin release. GLP-1 also induces diuresis and natriuresis in humans and rodents. The GLP-1 receptor is extensively expressed in the renal vascular tree in normotensive rats where acute GLP-1 treatment leads to increased mean arterial pressure (MAP) and increased renal blood flow (RBF). In hypertensive animal models, GLP-1 has been reported both to increase and decrease MAP. The aim of this study was to examine expression of renal GLP-1 receptors in spontaneously hypertensive rats (SHR) and to assess the effect of acute intrarenal infusion of GLP-1. We hypothesized that GLP-1 would increase diuresis and natriuresis and reduce MAP in SHR. Immunohistochemical staining and in situ hybridization for the GLP-1 receptor were used to localize GLP-1 receptors in the kidney. Sevoflurane-anesthetized normotensive Sprague-Dawley rats and SHR received a 20 min intrarenal infusion of GLP-1 and changes in MAP, RBF, heart rate, dieresis, and natriuresis were measured. The vasodilatory effect of GLP-1 was assessed in isolated interlobar arteries from normo- and hypertensive rats. We found no expression of GLP-1 receptors in the kidney from SHR. However, acute intrarenal infusion of GLP-1 increased MAP, RBF, dieresis, and natriuresis without affecting heart rate in both rat strains. These results suggest that the acute renal effects of GLP-1 in SHR are caused either by extrarenal GLP-1 receptors activating other mechanisms (e.g., insulin) to induce the renal changes observed or possibly by an alternative renal GLP-1 receptor. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

  7. Peak medial (but not lateral) hamstring activity is significantly lower during stance phase of running. An EMG investigation using a reduced gravity treadmill.

    Science.gov (United States)

    Hansen, Clint; Einarson, Einar; Thomson, Athol; Whiteley, Rodney

    2017-09-01

    The hamstrings are seen to work during late swing phase (presumably to decelerate the extending shank) then during stance phase (presumably stabilizing the knee and contributing to horizontal force production during propulsion) of running. A better understanding of this hamstring activation during running may contribute to injury prevention and performance enhancement (targeting the specific role via specific contraction mode). Twenty active adult males underwent surface EMG recordings of their medial and lateral hamstrings while running on a reduced gravity treadmill. Participants underwent 36 different conditions for combinations of 50%-100% altering bodyweight (10% increments) & 6-16km/h (2km/h increments, i.e.: 36 conditions) for a minimum of 6 strides of each leg (maximum 32). EMG was normalized to the peak value seen for each individual during any stride in any trial to describe relative activation levels during gait. Increasing running speed effected greater increases in EMG for all muscles than did altering bodyweight. Peak EMG for the lateral hamstrings during running trials was similar for both swing and stance phase whereas the medial hamstrings showed an approximate 20% reduction during stance compared to swing phase. It is suggested that the lateral hamstrings work equally hard during swing and stance phase however the medial hamstrings are loaded slightly less every stance phase. Likely this helps explain the higher incidence of lateral hamstring injury. Hamstring injury prevention and rehabilitation programs incorporating running should consider running speed as more potent stimulus for increasing hamstring muscle activation than impact loading. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. The changing face of cytokines in the brain: perspectives from EAE

    DEFF Research Database (Denmark)

    Wheeler, R D; Owens, T

    2005-01-01

    There has been a significant increase in the number of cytokines known to exist, over the past few years. This has led to a re-examination of the established roles of cytokines, as the functions of newly identified members are characterized. In this review, we describe how the recent discovery...... effector cell, and may even have a regulatory function. The impact of this on current understanding of cytokine networks underlying CNS inflammation in EAE is discussed....

  9. Nitric oxide synthase modulates CFA-induced thermal hyperalgesia through cytokine regulation in mice.

    Science.gov (United States)

    Chen, Yong; Boettger, Michael K; Reif, Andreas; Schmitt, Angelika; Uçeyler, Nurcan; Sommer, Claudia

    2010-03-02

    Although it has been largely demonstrated that nitric oxide synthase (NOS), a key enzyme for nitric oxide (NO) production, modulates inflammatory pain, the molecular mechanisms underlying these effects remain to be clarified. Here we asked whether cytokines, which have well-described roles in inflammatory pain, are downstream targets of NO in inflammatory pain and which of the isoforms of NOS are involved in this process. Intraperitoneal (i.p.) pretreatment with 7-nitroindazole sodium salt (7-NINA, a selective neuronal NOS inhibitor), aminoguanidine hydrochloride (AG, a selective inducible NOS inhibitor), L-N(G)-nitroarginine methyl ester (L-NAME, a non-selective NOS inhibitor), but not L-N(5)-(1-iminoethyl)-ornithine (L-NIO, a selective endothelial NOS inhibitor), significantly attenuated thermal hyperalgesia induced by intraplantar (i.pl.) injection of complete Freund's adjuvant (CFA). Real-time reverse transcription-polymerase chain reaction (RT-PCR) revealed a significant increase of nNOS, iNOS, and eNOS gene expression, as well as tumor necrosis factor-alpha (TNF), interleukin-1 beta (IL-1beta), and interleukin-10 (IL-10) gene expression in plantar skin, following CFA. Pretreatment with the NOS inhibitors prevented the CFA-induced increase of the pro-inflammatory cytokines TNF and IL-1beta. The increase of the anti-inflammatory cytokine IL-10 was augmented in mice pretreated with 7-NINA or L-NAME, but reduced in mice receiving AG or L-NIO. NNOS-, iNOS- or eNOS-knockout (KO) mice had lower gene expression of TNF, IL-1beta, and IL-10 following CFA, overall corroborating the inhibitor data. These findings lead us to propose that inhibition of NOS modulates inflammatory thermal hyperalgesia by regulating cytokine expression.

  10. Nitric oxide synthase modulates CFA-induced thermal hyperalgesia through cytokine regulation in mice

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    Üçeyler Nurcan

    2010-03-01

    Full Text Available Abstract Background Although it has been largely demonstrated that nitric oxide synthase (NOS, a key enzyme for nitric oxide (NO production, modulates inflammatory pain, the molecular mechanisms underlying these effects remain to be clarified. Here we asked whether cytokines, which have well-described roles in inflammatory pain, are downstream targets of NO in inflammatory pain and which of the isoforms of NOS are involved in this process. Results Intraperitoneal (i.p. pretreatment with 7-nitroindazole sodium salt (7-NINA, a selective neuronal NOS inhibitor, aminoguanidine hydrochloride (AG, a selective inducible NOS inhibitor, L-N(G-nitroarginine methyl ester (L-NAME, a non-selective NOS inhibitor, but not L-N(5-(1-iminoethyl-ornithine (L-NIO, a selective endothelial NOS inhibitor, significantly attenuated thermal hyperalgesia induced by intraplantar (i.pl. injection of complete Freund's adjuvant (CFA. Real-time reverse transcription-polymerase chain reaction (RT-PCR revealed a significant increase of nNOS, iNOS, and eNOS gene expression, as well as tumor necrosis factor-alpha (TNF, interleukin-1 beta (IL-1β, and interleukin-10 (IL-10 gene expression in plantar skin, following CFA. Pretreatment with the NOS inhibitors prevented the CFA-induced increase of the pro-inflammatory cytokines TNF and IL-1β. The increase of the anti-inflammatory cytokine IL-10 was augmented in mice pretreated with 7-NINA or L-NAME, but reduced in mice receiving AG or L-NIO. NNOS-, iNOS- or eNOS-knockout (KO mice had lower gene expression of TNF, IL-1β, and IL-10 following CFA, overall corroborating the inhibitor data. Conclusion These findings lead us to propose that inhibition of NOS modulates inflammatory thermal hyperalgesia by regulating cytokine expression.

  11. Inhibitory Effects of Soyeum Pharmacopuncture (SPP on LPS-induced Inflammation Related Cytokine Expressions of RAW 264.7 cells

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    Yoon Mi-Young

    2007-12-01

    Full Text Available Aim : This study was done to investigate whether SPP has inhibitory effects on the activation of RAW 264.7 cells. Method : In tumor necrosis factor-a (TNF-a/ interleukin-1b (IL-1b and IL-6, the mRNA expression of molecular indicators related to inflammatory changes of the Reumatoid Arthritis (RA were examined using quantitative real-time PCR. Results : The treatment of SPP significantly suppressed the expression of proinflammatory cytokines and chemokines such as TNF-a, IL-1b, IL-6 compared with the control. The expression of NOS-II was considerably reduced, which was accompanied by a reduction in the production of nitric oxide (NO. It also reduced the expression of TNF-αin serum of Balb/c mice compared with control group. Conclusion : SPP is an effective herbal material for suppressing the inflammation related cytokines of RAW 264.7 cells.

  12. Proinflammatory cytokine levels in patients with conversion disorder.

    Science.gov (United States)

    Tiyekli, Utkan; Calıyurt, Okan; Tiyekli, Nimet Dilek

    2013-06-01

    It was aimed to evaluate the relationship between proinflammatory cytokine levels and conversion disorder both commonly known as stress regulated. Baseline proinflammatory cytokine levels-[Tumour necrosis factor alpha (TNF-α), Interleukin-1 beta (IL-1β), Interleukin-6 (IL-6)]-were evaluated with enzyme-linked immunosorbent assay in 35 conversion disorder patients and 30 healthy controls. Possible changes in proinflammatory cytokine levels were evaluated again, after their acute phase in conversion disorder patients. Statistically significant decreased serum TNF-α levels were obtained in acute phase of conversion disorder. Those levels increased after acute conversion phase. There were no statistically significant difference observed between groups in serum IL-1β and (IL-6) levels. Stress associated with conversion disorder may suppress immune function in acute conversion phase and may have diagnostic and therapeutic value.

  13. Antibody-cytokine fusion proteins for improving efficacy and safety of cancer therapy.

    Science.gov (United States)

    Valedkarimi, Zahra; Nasiri, Hadi; Aghebati-Maleki, Leili; Majidi, Jafar

    2017-11-01

    Cytokines are key players in the regulation of immune responses both in physiological and pathological states. A number of cytokines have been evaluated in clinical trials and shown promising results in the treatment of different malignancies. Despite this, the clinical application of these molecules may be plagued by undesirable side effects The development of recombinant antibody-cytokine fusion proteins, which offer a means for target delivery of cytokines toward the tumor site, has significantly improved the therapeutic index of these immunomodulatory molecules. Selective tumor localization is provided by the monoclonal antibody component of the fusion protein that binds to the molecules present on the surface of tumor cells or accumulated preferentially in the diseased site. In this manner, the cytokine element is specifically located at the tumor site and can stimulate immune cells with appropriate cytokine receptors. Over the recent years, several antibody-cytokine fusion proteins have been developed with the capacity to target a wide variety of cancers whose application, in some cases, has led to complete rejection of the tumor. These findings support the notion that antibody-cytokine fusion proteins represent huge potential for cancer therapy. This review presents an overview of the advances made in the field of targeted cytokine delivery, which is made possible by genetically engineering antibody-cytokine fusion proteins. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  14. The chemical digestion of Ti6Al7Nb scaffolds produced by Selective Laser Melting reduces significantly ability of Pseudomonas aeruginosa to form biofilm.

    Science.gov (United States)

    Junka, Adam F; Szymczyk, Patrycja; Secewicz, Anna; Pawlak, Andrzej; Smutnicka, Danuta; Ziółkowski, Grzegorz; Bartoszewicz, Marzenna; Chlebus, Edward

    2016-01-01

    In our previous work we reported the impact of hydrofluoric and nitric acid used for chemical polishing of Ti-6Al-7Nb scaffolds on decrease of the number of Staphylococcus aureus biofilm forming cells. Herein, we tested impact of the aforementioned substances on biofilm of Gram-negative microorganism, Pseudomonas aeruginosa, dangerous pathogen responsible for plethora of implant-related infections. The Ti-6Al-7Nb scaffolds were manufactured using Selective Laser Melting method. Scaffolds were subjected to chemical polishing using a mixture of nitric acid and fluoride or left intact (control group). Pseudomonal biofilm was allowed to form on scaffolds for 24 hours and was removed by mechanical vortex shaking. The number of pseudomonal cells was estimated by means of quantitative culture and Scanning Electron Microscopy. The presence of nitric acid and fluoride on scaffold surfaces was assessed by means of IR and rentgen spetorscopy. Quantitative data were analysed using the Mann-Whitney test (P ≤ 0.05). Our results indicate that application of chemical polishing correlates with significant drop of biofilm-forming pseudomonal cells on the manufactured Ti-6Al-7Nb scaffolds ( p = 0.0133, Mann-Whitney test) compared to the number of biofilm-forming cells on non-polished scaffolds. As X-ray photoelectron spectroscopy revealed the presence of fluoride and nitrogen on the surface of scaffold, we speculate that drop of biofilm forming cells may be caused by biofilm-supressing activity of these two elements.

  15. CYTOKINES GENETIC POLYMORPHISM: THE PAST AND THE FUTURE

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    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.

  16. Cucurbita ficifolia (Cucurbitaceae) modulates inflammatory cytokines and IFN-γ in obese mice.

    Science.gov (United States)

    Fortis-Barrera, Á; García-Macedo, R; Almanza-Perez, J C; Blancas-Flores, G; Zamilpa-Alvarez, A; Flores-Sáenz, J L; Cruz, M; Román-Ramos, R; Alarcón-Aguilar, F J

    2017-02-01

    This study investigated the effect of aqueous extract of Cucurbita ficifolia Bouché on systemic chronic inflammation in an obesity model induced by monosodium glutamate (MSG) via modulating the expression of adipokines (TNF-α, IL-6, resistin, and adiponectin) and immune-regulatory cytokines (IFN-γ and IL-10). Cucurbita ficifolia extract was administered daily by gavage to lean and MSG-obese mice for 30 days. At the end of treatment, cytokine mRNA expression in adipose tissue was determined by real-time polymerase chain reaction (PCR), and the protein levels of these cytokines were also quantified by enzyme-linked immunosorbent assay (ELISA). Cucurbita ficifolia extract decreased body mass and inflammation in MSG-obese mice by reducing the expression of TNF-α and IL-6; these decreases were parallel to significant reductions in protein levels. The extract also increased protein levels of IL-10 in lean mice and IFN-γ in both lean and MSG-obese mice. In conclusion, C. ficifolia extract modulates systemic chronic inflammation in MSG-obese mice and could have a beneficial effect on the adaptive immune system in obesity.

  17. Intestinal alkaline phosphatase administration in newborns decreases systemic inflammatory cytokine expression in a neonatal necrotizing enterocolitis rat model.

    Science.gov (United States)

    Rentea, Rebecca M; Liedel, Jennifer L; Fredrich, Katherine; Welak, Scott R; Pritchard, Kirkwood A; Oldham, Keith T; Simpson, Pippa M; Gourlay, David M

    2012-10-01

    Supplementation of intestinal alkaline phosphatase (IAP), an endogenous protein expressed in the intestines, decreases the severity of necrotizing enterocolitis (NEC)-associated intestinal injury and permeability. We hypothesized that IAP administration is protective in a dose-dependent manner of the inflammatory response in a neonatal rat model. Pre- and full-term newborn Sprague-Dawley rat pups were sacrificed on day of life 3. Control pups were vaginally delivered and dam fed. Preterm pups were delivered via cesarean section and exposed to intermittent hypoxia and formula feeds containing lipopolysaccharide (NEC) with and without IAP. Three different standardized doses were administered to a group of pups treated with 40, 4, and 0.4U/kg of bovine IAP (NEC+IAP40, IAP4, or IAP0.4U). Reverse transcription-real-time polymerase chain reaction (RT-PCR) for inducible nitric oxide synthase (iNOS) and tumor necrosis factor (TNF)-α on liver and lung tissues and serum cytokine analysis for interleukin (IL)-1β, IL-6, IL-10, and TNF-α were performed. Data were analyzed by Kruskal-Wallis and Mann-Whitney tests, expressed as mean±standard error of the mean and P≤0.05 considered significant. Levels of cytokines IL-1β, IL-6, and TNF-α increased significantly in NEC versus control, returning to control levels with increasing doses of supplemental enteral IAP. Hepatic and pulmonary TNF-α and iNOS messenger ribonucleic acid expressions increased in NEC, and the remaining elevated despite IAP supplementation. Proinflammatory cytokine expression is increased systemically with intestinal NEC injury. Administration of IAP significantly reduces systemic proinflammatory cytokine expression in a dose-dependent manner. Early supplemental enteral IAP may reduce NEC-related injury and be useful for reducing effects caused by a proinflammatory cascade. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. Elevated levels of numerous cytokines in drainage fluid after primary total hip arthroplasty.

    Science.gov (United States)

    van der Heide, Huub J L; van der Kraan, Peter M; Rijnberg, Willard J; Buma, Pieter; Schreurs, B Willem

    2010-12-01

    As cytokines are involved in wound healing and other inflammatory processes, it could be valuable to measure their levels at the operative site. This study was conducted to investigate whether different cytokines are measurable in drainage fluid and, when measurable, whether we can find a difference in cytokine levels between one and six hours postoperatively. Samples from the drainage system in 30 consecutive patients undergoing primary total hip replacement were collected at one and six hours after closure of the wound. Levels of several cytokines were measured in the drainage fluids. A significant elevation of almost all cytokines was observed between the sample after one hour and six hours postoperatively. We found a strong correlation between the different pro-inflammatory cytokines. The IL-6 to IL-10 ratio were also raised, showing a pro-inflammatory predominance. Levels were much higher than those previously shown in serum.

  19. Dendritic Cell Stimulation by IFN-β Alters T Cell Function via Modulation of Cytokine Secretion in Diabetes Type 1

    Directory of Open Access Journals (Sweden)

    Abediankenari Saeid

    2009-10-01

    Full Text Available During antigen capture and processing, mature dendritic cells (DC express large amounts of peptide-MHC complexes and accessory molecules on their surface. We investigated the role of IFN-β in induction HLA-G expression on the monocyte derived DC and cytokine profile in diabetes type 1. We accomplished secretary pattern and total cytokine production of the Th1 cytokine (IL-2, γIFN and Th2 cytokines (IL-4, IL-10 before and after mixed leukocyte reaction (MLR of 30 diabetic patients and 30 normal subjects.   In this study a significant increase of IL-10 and γIFN reduction after IFN-β Therapy in culture in presence of HLA-G bearing DC as compared to control were seen. It is seen that dendritic cell causes IL-10 production of T cell in vitro that reduce T cell activation from diabetes patients and normal subjects resulted to the production and expression of HLA-G on these cells from both groups. Using mixed leukocyte reaction, it was found that IFN-β-treated dendritic cell mediated the inhibition of autologous T cell activation via IL-10 production and level of HLA-G on dendritic cell may be correlated to disease activity in diabetes patients and it could also serve as a useful marker for disease progress and treatment.

  20. The SaeR/S gene regulatory system induces a pro-inflammatory cytokine response during Staphylococcus aureus infection.

    Directory of Open Access Journals (Sweden)

    Robert L Watkins

    Full Text Available Community-associated methicillin-resistant Staphylococcus aureus accounts for a large portion of the increased staphylococcal disease incidence and can cause illness ranging from mild skin infections to rapidly fatal sepsis syndromes. Currently, we have limited understanding of S. aureus-derived mechanisms contributing to bacterial pathogenesis and host inflammation during staphylococcal disease. Herein, we characterize an influential role for the saeR/S two-component gene regulatory system in mediating cytokine induction using mouse models of S. aureus pathogenesis. Invasive S. aureus infection induced the production of localized and systemic pro-inflammatory cytokines, including tumor necrosis factor alpha (TNF-α, interferon gamma (IFN-γ, interleukin (IL-6 and IL-2. In contrast, mice infected with an isogenic saeR/S deletion mutant demonstrated significantly reduced pro-inflammatory cytokine levels. Additionally, secreted factors influenced by saeR/S elicited pro-inflammatory cytokines in human blood ex vivo. Our study further demonstrated robust saeR/S-mediated IFN-γ production during both invasive and subcutaneous skin infections. Results also indicated a critical role for saeR/S in promoting bacterial survival and enhancing host mortality during S. aureus peritonitis. Taken together, this study provides insight into specific mechanisms used by S. aureus during staphylococcal disease and characterizes a relationship between a bacterial global regulator of virulence and the production of pro-inflammatory mediators.

  1. 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

  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. 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....

  4. Th-17 regulatory cytokines IL-21, IL-23, and IL-6 enhance neutrophil production of IL-17 cytokines during asthma.

    Science.gov (United States)

    Halwani, Rabih; Sultana, Asma; Vazquez-Tello, Alejandro; Jamhawi, Amer; Al-Masri, Abeer A; Al-Muhsen, Saleh

    2017-11-01

    In a subset of severe asthma patients, chronic airway inflammation is associated with infiltration of neutrophils, Th-17 cells and elevated expression of Th-17-derived cytokines (e.g., interleukin [IL]-17, IL-21, IL-22). Peripheral neutrophils from allergic asthmatics are known to express higher IL-17 cytokine levels than those from healthy subjects, but the regulatory mechanisms involved are not well understood. We hypothesize that Th-17 regulatory cytokines could modulate IL-17 expression in neutrophils. Peripheral blood neutrophils isolated from asthmatics were stimulated with IL-21, IL-23, and IL-6 cytokines and their ability to produce IL-17A and IL-17F was determined relative to healthy controls. Signal transducer and activator of transcription 3 (STAT3) phosphorylation levels were measured in stimulated neutrophil using flow cytometry. The requirement for STAT3 phosphorylation was determined by blocking its activation using a specific chemical inhibitor. Stimulating asthmatic neutrophils with IL-21, 23, and 6 enhanced the production of IL-17A and IL-17F at significantly higher levels comparatively to healthy controls. Stimulating neutrophils with IL-21, IL-23, and IL-6 cytokines enhanced STAT3 phosphorylation, in all cases. Interestingly, inhibiting STAT3 phosphorylation using a specific chemical inhibitor dramatically blocked the ability of neutrophils to produce IL-17, demonstrating that STAT3 activation is the major factor mediating IL-17 gene expression. These findings suggest that neutrophil infiltration in lungs of severe asthmatics may represent an important source of pro-inflammatory IL-17A and -F cytokines, a production enhanced by Th-17 regulatory cytokines, and thus providing a feedback mechanism that sustains inflammation. Our results suggest that STAT3 pathway could be a potential target for regulating neutrophilic inflammation during severe asthma.

  5. Th1/Th2 cytokine expression in diabetic retinopathy.

    Science.gov (United States)

    Cao, Y L; Zhang, F Q; Hao, F Q

    2016-07-15

    Diabetic retinopathy (DR), an important complication of diabetes mellitus (DM), is not well understood. T helper cell balance (Th1/Th2) is involved in various autoimmune diseases; however, its role in DR is not understood. This study explores changes in Th1 and Th2 cytokine expression during DR. Blood samples were collected from 25 healthy volunteers (normal control group), 35 patients with type 2 DM (T2DM group) without DR, and 30 cases of T2DM patients with DR (DR group). Real-time PCR was used to measure mRNA expression of IL-2 and TNF-α, secreted from Th1 cells, and of IL-4 and IL-10, secreted from Th2 cells. We used ELISA to detect cytokine expression in serum to analyze the correlation between Th1 and Th2 cytokines. IL-2 and TNF-αmRNA and protein expression levels in the T2DM and DR groups were significantly higher than in the normal control group (P 0.05). IL-2 and TNF-αwere negatively correlated with IL-4 and IL-10 in the DR group, respectively. We found that Th1 cytokine secretion was higher and Th2 cytokines secretion was lower during DR, leading to a Th1/ Th2 imbalance, suggesting that Th1/Th2 imbalance is a side effect for DR occurrence and development.

  6. Cytokine changes in tears and relationship to contact lens discomfort.

    Science.gov (United States)

    Willcox, Mark D P; Zhao, Zhenjun; Naduvilath, Thomas; Lazon de la Jara, Percy

    2015-01-01

    To determine the reproducibility of a multiplex bead assay for measuring cytokines in tears and correlations between ocular discomfort with or without contact lens wear and the concentration of cytokines in tears. Ninety participants (divided into two groups) were enrolled in this prospective study. They were asked to rate their ocular comfort and collect their tears in the morning and just before sleep for 10 days with or without contact lenses. The participants collected their tears using a glass microcapillary tube for both stages. Galyfilcon A lenses were worn on a daily disposable basis during the contact lens stage, and comfort scores and tears were collected before lens insertion and prior to lens removal at the end of the day. Tears were analyzed for cytokine concentrations using a 27-plex multibead assay. Correlations were sought between cytokine concentrations and comfort. There was a significant (p-0.5 Log pg/ml, p-0.2 Log pg/ml, ptears was correlated to ocular comfort, but this was not changed by contact lens wear. Ocular comfort during the day is magnified by contact lens wear. However, the increase in the change in comfort during lens wear was not associated with changes in 15 cytokines in the tear film.

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

    Science.gov (United States)

    Prieto, G Aleph; Cotman, Carl W

    2017-04-01

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

  8. Consumption of Bifidobacterium animalis subsp. lactis BB-12 in yogurt reduced expression of TLR-2 on peripheral blood-derived monocytes and pro-inflammatory cytokine secretion in young adults.

    Science.gov (United States)

    Meng, Huicui; Ba, Zhaoyong; Lee, Yujin; Peng, Jiayu; Lin, Junli; Fleming, Jennifer A; Furumoto, Emily J; Roberts, Robert F; Kris-Etherton, Penny M; Rogers, Connie J

    2017-03-01

    Probiotic bacteria modulate immune parameters and inflammatory outcomes. Emerging evidence demonstrates that the matrix used to deliver probiotics may influence the efficacy of probiotic interventions in vivo. The aims of the current study were to evaluate (1) the effect of one species, Bifidobacterium animalis subsp. lactis BB-12 at a dose of log10 ± 0.5 CFUs/day on immune responses in a randomized, partially blinded, 4-period crossover, free-living study, and (2) whether the immune response to BB-12 differed depending on the delivery matrix. Healthy adults (n = 30) aged 18-40 years were recruited and received four treatments in a random order: (A) yogurt smoothie alone; smoothie with BB-12 added (B) before or (C) after yogurt fermentation, or (D) BB-12 given in capsule form. At baseline and after each 4-week treatment, peripheral blood mononuclear cells (PBMCs) were isolated, and functional and phenotypic marker expression was assessed. BB-12 interacted with peripheral myeloid cells via Toll-like receptor 2 (TLR-2). The percentage of CD14 + HLA-DR + cells in peripheral blood was increased in male participants by all yogurt-containing treatments compared to baseline (p = 0.0356). Participants who consumed yogurt smoothie with BB-12 added post-fermentation had significantly lower expression of TLR-2 on CD14 + HLA-DR + cells (p = 0.0186) and reduction in TNF-α secretion from BB-12- (p = 0.0490) or LPS-stimulated (p = 0.0387) PBMCs compared to baseline. These findings not only demonstrate a potential anti-inflammatory effect of BB-12 in healthy adults, but also indicate that the delivery matrix influences the immunomodulatory properties of BB-12.

  9. Brain acetylcholinesterase activity controls systemic cytokine levels through the cholinergic anti-inflammatory pathway

    Science.gov (United States)

    Pavlov, Valentin A.; Parrish, William R.; Rosas-Ballina, Mauricio; Ochani, Mahendar; Puerta, Margot; Ochani, Kanta; Chavan, Sangeeta; Al-Abed, Yousef; Tracey, Kevin J.

    2015-01-01

    The excessive release of cytokines by the immune system contributes importantly to the pathogenesis of inflammatory diseases. Recent advances in understanding the biology of cytokine toxicity led to the discovery of the “cholinergic anti-inflammatory pathway,” defined as neural signals transmitted via the vagus nerve that inhibit cytokine release through a mechanism that requires the alpha7 subunit-containing nicotinic acetylcholine receptor (α7nAChR). Vagus nerve regulation of peripheral functions is controlled by brain nuclei and neural networks, but despite considerable importance, little is known about the molecular basis for central regulation of the vagus nerve-based cholinergic anti-inflammatory pathway. Here we report that brain acetylcholinesterase activity controls systemic and organ specific TNF production during endotoxemia. Peripheral administration of the acetylcholinesterase inhibitor galantamine significantly reduced serum TNF levels through vagus nerve signaling, and protected against lethality during murine endotoxemia. Administration of a centrally-acting muscarinic receptor antagonist abolished the suppression of TNF by galantamine, indicating that suppressing acetylcholinesterase activity, coupled with central muscarinic receptors, controls peripheral cytokine responses. Administration of galantamine to α7nAChR knockout mice failed to suppress TNF levels, indicating that the α7nAChR-mediated cholinergic anti-inflammatory pathway is required for the anti-inflammatory effect of galantamine. These findings show that inhibition of brain acetylcholinesterase suppresses systemic inflammation through a central muscarinic receptor-mediated and vagal- and α7nAChR-dependent mechanism. Our data also indicate that a clinically used centrally-acting acetylcholinesterase inhibitor can be utilized to suppress abnormal inflammation to therapeutic advantage. PMID:18639629

  10. The Clinical Detection Significance of Serum Cytokines,C-reactive Protein and White Cell of Chil-dren with Severe Pneumonia%重症肺炎患儿血清细胞因子、C反应蛋白及白细胞的临床检测意义

    Institute of Scientific and Technical Information of China (English)

    余小平; 蒋鹏; 夏翠英

    2016-01-01

    重症肺炎患儿治疗的有效率,也有助于预后评估。%Objective To analyze the clinical detection significance of serum cytokines,C reactive pro-tein (CRP) and white cell(WBC) of children with severe pneumonia.Methods Total of 86 children with pneumonia in the First People′s Hospital of Liangshan Yi Autonomous Prefecture Chang′an Branch from Mar.2014 to Mar.2015 were included in the study,according to the severity of pneumonia they were divided into a severe pneumonia group and an ordinary pneumonia group,43 patients each.Clinical symptoms were observed and serum cytokines[tumor necrosis factor-α(TNF-α),soluble intercellular adhesion molecule-1 (sICAM-1),interleukin(IL)-6,IL-8],CRP and WBC level changes were compared.Results The propor-tions of children with symptoms of fever or chills,difficult breathing,irritability,etc.of the severe pneumonia group were higher than the ordinary pneumonia group, the differences were statistically significant ( P <0.01).In acute stage,the level of TNF-α,sICAM-1,IL-6,IL-8,CRP and WBC of the severe pneumonia group were higher the ordinary pneumonia group [ ( 52.7 ±5.4 ) ng/L vs ( 36.0 ±5.5 ) ng/L, ( 41.6 ± 4.20) pg/L vs (25.7 ±3.6) pg/L,(45.4 ±4.3) ng/L vs (23.6 ±2.5) ng/L,(40.4 ±5.5) ng/L vs (28.6 ±3.5) ng/L,(32.6 ±4.2) mg/L vs (12.2 ±1.6) mg/L,(12.0 ±1.3) ×109/L vs (9.1 ± 1.4) ×109/L],the differences were statistically significant(P <0.01).In the recovery stage,the TNF-α, sICAM-1,IL-6,IL-8,CRP and WBC levels of both groups were lower than the acute stage;and the severe pneumonia group were significantly higher than the ordinary pneumonia group[(27.4 ±3.2) ng/L vs (12.4 ± 1.4) ng/L,(22.6 ±3.3) pg/L vs ( 9.0 ±1.1) pg/L,(25.6 ±1.2) ng/L vs (10.7 ±1.6) ng/L, (20.8 ±3.4) ng/L vs (11.2 ±1.5) ng/L,(10.4 ±1.0) mg/L vs (5.3 ±0.6) mg/L,(8.4 ±1.2) × 109/L vs (7.3 ±1.0) ×109/L],the differences were statistically significant(P<0.01).Conclusion The detection of TNF-α,sICAM-1,IL -6,IL-8,CRP and

  11. Serum cytokine levels in Kleine-Levin syndrome

    DEFF Research Database (Denmark)

    Kornum, Birgitte Rahbek; Rico, Thomas; Lin, Ling

    2015-01-01

    in USA, France, and Taiwan in a clinical setting. Processing of the samples was performed at the Stanford Center for Sleep Sciences and Medicine. RESULTS: We did not observe any changes in serum cytokine levels during KLS episodes compared to between episodes. In a small cohort of asymptomatic KLS...... patients and age- and gender matched healthy controls (n = 8/group) whose blood samples were all collected and processed at the same day; asymptomatic KLS patients had significantly higher levels of serum sVCAM1 cytokine compared to healthy controls. CONCLUSION: These data suggest that KLS episodes...... unknown. The objective of this study was to determine serum cytokine levels in patients with KLS during and between episodes. PATIENTS/METHODS: Fifty-two typical KLS patients were included in the study of whom 17 patients donated blood samples both during and between episodes. Blood samples were collected...

  12. Nuclear energy significantly reduces carbon dioxide emissions

    International Nuclear Information System (INIS)

    Koprda, V.

    2006-01-01

    This article is devoted to nuclear energy, to its acceptability, compatibility and sustainability. Nuclear energy is non-dispensable part of energy sources with vast innovation potential. The safety of nuclear energy, radioactive waste deposition, and prevention of risk from misuse of nuclear material have to be very seriously adjudged and solved. Nuclear energy is one of the ways how to decrease the contamination of atmosphere with carbon dioxide and it solves partially also the problem of global increase of temperature and climate changes. Given are the main factors responsible for the renaissance of nuclear energy. (author)

  13. Altered Circulating Inflammatory Cytokines Are Associated with Anovulatory Polycystic Ovary Syndrome (PCOS) Women Resistant to Clomiphene Citrate Treatment.

    Science.gov (United States)

    Wang, LianLian; Qi, HongBo; Baker, Philip N; Zhen, QianNa; Zeng, Qing; Shi, Rui; Tong, Chao; Ge, Qian

    2017-03-01

    BACKGROUND Polycystic ovary syndrome (PCOS) is a common gynecological disease characterized by chronic oligoanovulation, clinical/biochemical hyperandrogenism, polycystic ovaries, and insulin resistance. Accumulating evidence has shown that PCOS-related ovarian dysfunction is the main cause of anovulatory infertility. Clomiphene citrate (CC) is the first-line therapy for PCOS patients; however, approximately 15-40% PCOS patients are resistant to CC treatment. It has been demonstrated that PCOS is a chronic pro-inflammatory state, as some pro-inflammatory cytokines were elevated in the peripheral circulation of PCOS patients, but whether altered inflammatory cytokines expression in PCOS patients is associated with blunted response to CC remains unknown. MATERIAL AND METHODS We recruited 44 CC-resistant PCOS patients, along with 55 age and body mass index (BMI)-matched CC-sensitive PCOS patients. Ovulation was induced by administrating 50-100 mg/day CC on days 5 to 9 of each menstrual cycle. The cytokine profiles were detected by cytokine antibody microarrays and further validated by ELISAs. RESULTS CC-resistant patients had higher levels of high-sensitivity C-reactive protein (hsCRP) than the CC-sensitive individuals. A growth factor, angiopoietin-2, was significantly reduced [1.64 (0.93-1.95) vs. 1.08 (0.85-1.34), p<0.05], while a chemokine CXCL-16 was significantly increased (9.10±2.35 vs. 10.41±2.82, p<0.05) in CC-resistant patients compared to the CC-sensitive subjects. CXCL-16 was positively correlated with hsCRP (r=0.33, p<0.01). Logistic regression analysis showed that angiopoietin-2 and CXCL-16 are associated with CC resistance. CONCLUSIONS Circulating cytokines are disturbed in CC-resistant PCOS patients. Altered angiopoietin-2 and CXCL-16 levels might compromise the responsiveness of the ovary to CC through up-regulating angiogenesis and inflammation.

  14. The Role of Cytokines in the Pathophysiology of Suicidal Behavior

    Science.gov (United States)

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

    2016-01-01

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

  15. Cytokines, Type 2 DM and the Metabolic Syndrome | Ogbera ...

    African Journals Online (AJOL)

    comparable in the DM subjects with and without the Mets and also comparable in obese DM and non obese DM subjects. Of the Mets defining criteria, waist circumference (WC) and Triglyceride (TG) were found to be significantly associated with only two of the studied cytokines. The correlation coefficient and p values of ...

  16. Does lipoic acid consumption affect the cytokine profile in multiple sclerosis patients: a double-blind, placebo-controlled, randomized clinical trial.

    Science.gov (United States)

    Khalili, Mohammad; Azimi, Amirreza; Izadi, Vajihe; Eghtesadi, Shahryar; Mirshafiey, Abbas; Sahraian, Mohamad Ali; Motevalian, Abbas; Norouzi, Abbas; Sanoobar, Meisam; Eskandari, Ghazaleh; Farhoudi, Mehdi; Amani, Firouz

    2014-01-01

    A limited amount of data exists regarding the effect of lipoic acid (LA), an oral antioxidant supplement, on cytokine profiles among multiple sclerosis (MS) patients. We aimed to assess the effect of daily consumption of LA on the cytokine profiles in MS patients. In this double-blind, placebo-controlled, randomized clinical trial, 52 relapsing-remitting MS patients with an age range of 18-50 years were recruited into 2 groups: LA consumption (1,200 mg/day) or placebo. Patients followed their prescribed supplements for 12 weeks. Fasting blood samples for cytokine profile measurement were collected at baseline and after the intervention. Anthropometric parameters were measured based on the standard guidelines. INF-γ, ICAM-1, TGF-β and IL-4 were significantly reduced in the LA group compared to the placebo group [(INF-γ: 0.82 ± 0.2 vs. 0.2 ± 0.2 pg/ml, p consumption of 1,200 mg LA per day beneficially affects several inflammatory cytokines including INF-γ, ICAM-1 TGF-β and IL-4. Further investigations are needed to verify the beneficial role of LA on other cytokine profiles among MS patients.

  17. CYTOKINE DISBALANCE AT HERPESVIRUS MYOCARDITIS

    Directory of Open Access Journals (Sweden)

    Peremot S. D

    2016-12-01

    Full Text Available Viral myocarditis is a heterogeneous group of diseases not only by etiologic factors, which belong to different families of Vira kingdom, but is also characterized by a unique mechanism of inflammatory process and cytokine levels specific for each of them. According to numerous researches in сardio-immunology, at herpesvirus infection of the cardiovascular system occur both systemic and localized violations of the immune response. Unfortunately, the accessible literature did not provide the data analysis of complex cardio-immunological research that would take into account the features of herpesvirus myocarditis clinical course. This grounds relevance of immunodiagnosis directed on the exposure of dysimmunities by study of indices of general and local immunity with the estimation of the immune status in patients depending on the stage of exasperation or relapse of chronic herpetic infection in the complex of diagnostic tests. The purpose of our research was to determine features of the state of the immune system with the complex analysis of cytokine profile data, immune and interferon statuses in subacute and chronic forms of herpesvirus myocarditis. Materials and methods. 87 myocarditis patients who were receiving inpatient treatment in medical establishments of Kharkiv were examined. The average age was (M ± m 36 ± 3,46 years old. The diagnosis of myocarditis was established according to the order № 436 by the Ministry of Healthcare of Ukraine from 03.07.2006 of clinical findings protocol. In accordance with the term of myocarditis clinical course, the patients were divided in two sub-groups: 44 patients with subacute (from 2 to 6 months, and 43 patients with chronic (over 6 months clinical course of viral myocarditis. The control group correlated with patients of basic group by age and gender and consisted of 40 practically healthy persons without implications of cardial pathology. Definition of cytokine concentration: IL-2, IL-4, IL-6

  18. Cytokine-Modulating Strategies and Newer Cytokine Targets for Arthritis Therapy

    Directory of Open Access Journals (Sweden)

    Shivaprasad H. Venkatesha

    2014-12-01

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

  19. Cytokine induction of sol–gel-derived TiO2 and SiO2 coatings on metallic substrates after implantation to rat femur

    Directory of Open Access Journals (Sweden)

    Urbanski W

    2017-02-01

    Full Text Available Wiktor Urbanski,1 Krzysztof Marycz,2 Justyna Krzak,3 Celina Pezowicz,4 Szymon Feliks Dragan1 1Department of Orthopaedic Surgery and Traumatology, Wroclaw University Hospital, 2Electron Microscope Laboratory, Wroclaw University of Environmental and Life Sciences, 3Institute of Materials Science and Applied Mechanics, 4Division of Biomedical Engineering and Experimental Mechanics, Wroclaw University of Technology, Wroclaw, Poland Abstract: Material surface is a key determinant of host response on implanted biomaterial. Therefore, modification of the implant surface may optimize implant–tissue reactions. Inflammatory reaction is inevitable after biomaterial implantation, but prolonged inflammation may lead to adverse reactions and subsequent implant failure. Proinflammatory activities of cytokines like interleukin (IL-1, IL-6, and tumor necrosis factor-alpha (TNF-α are attractive indicators of these processes and ultimately characterize biocompatibility. The objective of the study was to evaluate local cytokine production after implantation of stainless steel 316L (SS and titanium alloy (Ti6Al4V biomaterials coated with titanium dioxide (TiO2 and silica (SiO2 coatings prepared by sol–gel method. Biomaterials were implanted into rat femur and after 12 weeks, bones were harvested. Bone–implant tissue interface was evaluated; immunohistochemical staining was performed to identify IL-6, TNF-α, and Caspase-1. Histomorphometry (AxioVision Rel. 4.6.3 software of tissue samples was performed in order to quantify the cytokine levels. Both the oxide coatings on SS and Ti6Al4V significantly reduced cytokine production. However, the lowest cytokine levels were observed in TiO2 groups. Cytokine content in uncoated groups was lower in Ti6Al4V than in SS, although coating of either metal reduced cytokine production to similar levels. Sol–gel TiO2 or SiO2 coatings reduced significantly the production of proinflammatory cytokines by local tissues

  20. Cord Blood Cells Responses to IL2, IL7 and IL15 Cytokines for mTOR Expression

    Directory of Open Access Journals (Sweden)

    Anahita Mohammadian

    2017-04-01

    Full Text Available Purpose: Mammalian target of rapamycin (mTORis important in hematopoiesis and affect cell growth,differentiation and survival. Although previous studies were identified the effect of cytokines on the mononuclear cells development however the cytokines effect on mTOR in cord blood mononuclear cells was unclear. The aim of this study was to evaluate mTOR expression in cord blood mononuclear and cord blood stem cells (CD34+ cells in culture conditions for lymphoid cell development. Methods: Isolation of The mononuclear cells (MNCs from umbilical cord blood were done with use of Ficollpaque density gradient. We evaluated cultured cord blood mononuclear and CD34+ cells in presece of IL2, IL7 and IL15 at distinct time points during 21 days by using flow cytometry. In this study, we presented the role of IL2, IL7 and IL15 on the expression of mTOR in cord blood cells. Results: mTOR expression were increased in peresence of IL2, IL7 and IL15 in day 14 and afterword reduced. However in persence of IL2 and IL15 expression of mTOR significantly reduced. mTOR expression in CD34+ cells decreased significantly from day7 to day 21 in culture. Conclusion: cytokines play important role in mTOR expression during hematopoiesis and development of cord blood mononuclear cells.

  1. Cytokine Response to Exercise and Its Modulation

    Directory of Open Access Journals (Sweden)

    Katsuhiko Suzuki

    2018-01-01

    Full Text Available Strenuous exercise induces such inflammatory responses as leukocytosis (neutrophilia and symptoms as delayed-onset muscle soreness and swelling. However, the association between inflammatory mediator cytokines and oxidative stress is not fully delineated. Herein, in addition to basic background information on cytokines, research findings on exertional effects on cytokine release and the underlying mechanisms and triggers are introduced. Then, the associations among cytokine responses, oxidative stress, and tissue damage are described not only in overloaded skeletal muscle, but also in other internal organs. Furthermore, we introduce preventive countermeasures against the exhaustive exercise-induced pathogenesis together with the possibility of antioxidant interventions.

  2. 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.

  3. Pro-Inflammatory Cytokine Levels in HIV Infected and Uninfected Pregnant Women with and without Preeclampsia.

    Science.gov (United States)

    Maharaj, Niren Ray; Phulukdaree, Alisa; Nagiah, Savania; Ramkaran, Prithiksha; Tiloke, Charlette; Chuturgoon, Anil Amichund

    2017-01-01

    Preeclampsia and HIV/AIDS are inflammatory conditions that contribute significantly to adverse maternal and foetal outcomes. The immune reconstitution effects of HAART on inflammatory mediators has not been adequately studied in pregnancy and may impact on the inflammatory cytokine network in women with co-morbid preeclampsia. Our study evaluated changes in pro-inflammatory cytokines IL-2, TNF-α, IFN-γ and IL-6 in HIV infected preeclamptic women on HAART. A prospective experimental study was conducted at Prince Mshiyeni Memorial Hospital between July 2013 and September 2014. One hundred and ninety three pregnant women were recruited into 4 groups: uninfected normotensive (50; 26%), infected normotensive (45; 23%), uninfected preeclamptic (53; 28%) and infected preeclamptic women (45; 23%). Serum levels of cytokines TNF-α, IFN- γ, IL-2 and IL-6 were determined using commercially available kits and a Cytometric Bead Array (CBA). Comparative data was recorded and analysed descriptively. In the control groups (normotensive), significantly lower values were found in IL-2 (p = 0.010), TNF-α (p = 0.045), and IL-6 (p = 0.005); and a non-significant decrease was observed in IFN-γ (p = 0.345) in HIV infected women on HAART compared to uninfected controls. In the experimental group (preeclamptic) women, significantly reduced levels were observed in IL-2 and TNF-α (p = 0.001; p = 0.000) and non-significant decreases were observed in IFN-γ and IL-6 (p = 0.023; p = 0.086) in HIV infected women on HAART compared with uninfected preeclamptic women. Non-significant differences were observed between uninfected preeclamptic and normotensive women. In uncomplicated/normotensive pregnancies, HIV/HAART is associated with significant decreases in IL-2, TNF-α and IL-6, and in preeclamptic women significant decreases in IL-2 and TNF-α were observed. These findings suggest that HIV/HAART impacts on pro-inflammatory cytokines in women with co-morbid preeclampsia. This provides a

  4. Pro-Inflammatory Cytokine Levels in HIV Infected and Uninfected Pregnant Women with and without Preeclampsia.

    Directory of Open Access Journals (Sweden)

    Niren Ray Maharaj

    Full Text Available Preeclampsia and HIV/AIDS are inflammatory conditions that contribute significantly to adverse maternal and foetal outcomes. The immune reconstitution effects of HAART on inflammatory mediators has not been adequately studied in pregnancy and may impact on the inflammatory cytokine network in women with co-morbid preeclampsia. Our study evaluated changes in pro-inflammatory cytokines IL-2, TNF-α, IFN-γ and IL-6 in HIV infected preeclamptic women on HAART.A prospective experimental study was conducted at Prince Mshiyeni Memorial Hospital between July 2013 and September 2014. One hundred and ninety three pregnant women were recruited into 4 groups: uninfected normotensive (50; 26%, infected normotensive (45; 23%, uninfected preeclamptic (53; 28% and infected preeclamptic women (45; 23%. Serum levels of cytokines TNF-α, IFN- γ, IL-2 and IL-6 were determined using commercially available kits and a Cytometric Bead Array (CBA. Comparative data was recorded and analysed descriptively.In the control groups (normotensive, significantly lower values were found in IL-2 (p = 0.010, TNF-α (p = 0.045, and IL-6 (p = 0.005; and a non-significant decrease was observed in IFN-γ (p = 0.345 in HIV infected women on HAART compared to uninfected controls. In the experimental group (preeclamptic women, significantly reduced levels were observed in IL-2 and TNF-α (p = 0.001; p = 0.000 and non-significant decreases were observed in IFN-γ and IL-6 (p = 0.023; p = 0.086 in HIV infected women on HAART compared with uninfected preeclamptic women. Non-significant differences were observed between uninfected preeclamptic and normotensive women.In uncomplicated/normotensive pregnancies, HIV/HAART is associated with significant decreases in IL-2, TNF-α and IL-6, and in preeclamptic women significant decreases in IL-2 and TNF-α were observed. These findings suggest that HIV/HAART impacts on pro-inflammatory cytokines in women with co-morbid preeclampsia. This provides

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

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    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.

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

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    E. S. Zhugrova

    2008-01-01

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

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

    Science.gov (United States)

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

    2017-02-01

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

  8. Cisplatin ototoxicity involves cytokines and STAT6 signaling network

    Institute of Scientific and Technical Information of China (English)

    Hyung-Jin Kim; Jeong-Dug Sul; Channy Park; Sang-Young Chung; Sung-Kyun Moon; David J Lim; Hong-Seob So; Raekil Park; Gi-Su Oh; Jeong-Han Lee; Ah-Ra Lyu; Hye-Min Ji; Sang-Heon Lee; Jeho Song; Sung-Joo Park; Yong-Ouk You

    2011-01-01

    We herein investigated the role of the STAT signaling cascade in the production of pro-inflammatory cytokines and cisplatin ototoxicity. A significant hearing impairment caused by cisplatin injection was observed in Balb/c (wild type,WT) and STAT4-/-,but not in STAT6-/- mice. Moreover,the expression levels of the protein and mRNA of proinflammatory cytokines,including TNF-α,IL-1β,and IL-6,were markedly increased in the serum and cochlea of WT and STAT4+,but not STAT6-/- mice. Organotypic culture revealed that the shape of stereocilia bundles and arrays of sensory hair cell layers in the organ of Corti from STAT6-/- mice were intact after treatment with cisplatin,whereas those from WT and STAT4-/- mice were highly distorted and disarrayed after the treatment. Cisplatin induced the phosphorylation of STAT6 in HEI-OC1 auditory cells,and the knockdown of STAT6 by STAT6-specific siRNA significantly protected HEI-OC1 auditory cells from cisplatin-induced cell death and inhibited pro-inflammatory cytokine production. We further demonstrated that IL-4 and IL-13 induced by cisplatin modulated the phosphorylation of STAT6 by binding with IL-4 receptor alpha and IL-13Rα1. These findings suggest that STAT6 signaling plays a pivotal role in cisplatin-mediated pro-inflammatory cytokine production and ototoxicity.

  9. Prognosis Relevance of Serum Cytokines in Pancreatic Cancer

    Science.gov (United States)

    Alejandre, Maria José; Palomino-Morales, Rogelio J.; Prados, Jose; Aránega, Antonia; Delgado, Juan R.; Irigoyen, Antonio; Martínez-Galán, Joaquina; Ortuño, Francisco M.

    2015-01-01

    The overall survival of patients with pancreatic ductal adenocarcinoma is extremely low. Although gemcitabine is the standard used chemotherapy for this disease, clinical outcomes do not reflect significant improvements, not even when combined with adjuvant treatments. There is an urgent need for prognosis markers to be found. The aim of this study was to analyze the potential value of serum cytokines to find a profile that can predict the clinical outcome in patients with pancreatic cancer and to establish a practical prognosis index that significantly predicts patients' outcomes. We have conducted an extensive analysis of serum prognosis biomarkers using an antibody array comprising 507 human cytokines. Overall survival was estimated using the Kaplan-Meier method. Univariate and multivariate Cox's proportional hazard models were used to analyze prognosis factors. To determine the extent that survival could be predicted based on this index, we used the leave-one-out cross-validation model. The multivariate model showed a better performance and it could represent a novel panel of serum cytokines that correlates to poor prognosis in pancreatic cancer. B7-1/CD80, EG-VEGF/PK1, IL-29, NRG1-beta1/HRG1-beta1, and PD-ECGF expressions portend a poor prognosis for patients with pancreatic cancer and these cytokines could represent novel therapeutic targets for this disease. PMID:26346854

  10. Prognosis Relevance of Serum Cytokines in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Carolina Torres

    2015-01-01

    Full Text Available The overall survival of patients with pancreatic ductal adenocarcinoma is extremely low. Although gemcitabine is the standard used chemotherapy for this disease, clinical outcomes do not reflect significant improvements, not even when combined with adjuvant treatments. There is an urgent need for prognosis markers to be found. The aim of this study was to analyze the potential value of serum cytokines to find a profile that can predict the clinical outcome in patients with pancreatic cancer and to establish a practical prognosis index that significantly predicts patients’ outcomes. We have conducted an extensive analysis of serum prognosis biomarkers using an antibody array comprising 507 human cytokines. Overall survival was estimated using the Kaplan-Meier method. Univariate and multivariate Cox’s proportional hazard models were used to analyze prognosis factors. To determine the extent that survival could be predicted based on this index, we used the leave-one-out cross-validation model. The multivariate model showed a better performance and it could represent a novel panel of serum cytokines that correlates to poor prognosis in pancreatic cancer. B7-1/CD80, EG-VEGF/PK1, IL-29, NRG1-beta1/HRG1-beta1, and PD-ECGF expressions portend a poor prognosis for patients with pancreatic cancer and these cytokines could represent novel therapeutic targets for this disease.

  11. Cytokine profile of cervical cancer cells

    NARCIS (Netherlands)

    Hazelbag, S; Fleuren, GJ; Baelde, JJ; Schuuring, E; Kenter, GG; Gorter, A

    2001-01-01

    Objective. In patients with cervical carcinoma, the presence of cytokines produced by T(H)2 cells, and the presence of an eosinophilic inflammatory infiltrate, has been associated with a less effective immune response and tumor progression. In the present study, we have investigated the cytokine

  12. Cytokine profile of cervical cancer cells

    NARCIS (Netherlands)

    Hazelbag, S; Fleuren, GJ; Baelde, JJ; Schuuring, E; Kenter, GG; Gorter, A

    Objective. In patients with cervical carcinoma, the presence of cytokines produced by T(H)2 cells, and the presence of an eosinophilic inflammatory infiltrate, has been associated with a less effective immune response and tumor progression. In the present study, we have investigated the cytokine

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

    Science.gov (United States)

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

    2016-03-15

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

  14. Glycine regulates the production of pro-inflammatory cytokines in lean and monosodium glutamate-obese mice.

    Science.gov (United States)

    Alarcon-Aguilar, F J; Almanza-Perez, Julio; Blancas, Gerardo; Angeles, Selene; Garcia-Macedo, Rebeca; Roman, Ruben; Cruz, Miguel

    2008-12-03

    Fat tissue plays an important role in the regulation of inflammatory processes. Increased visceral fat has been associated with a higher production of cytokines that triggers a low-grade inflammatory response, which eventually may contribute to the development of insulin resistance. In the present study, we investigated whether glycine, an amino acid that represses the expression in vitro of pro-inflammatory cytokines in Kupffer and 3T3-L1 cells, can affect in vivo cytokine production in lean and monosodium glutamate-induced obese mice (MSG/Ob mice). Our data demonstrate that glycine treatment in lean mice suppressed TNF-alpha transcriptional expression in fat tissue, and serum protein levels of IL-6 were suppressed, while adiponectin levels were increased. In MSG/Ob mice, glycine suppressed TNF-alpha and IL-6 gene expression in fat tissue and significantly reduced protein levels of IL-6, resistin and leptin. To determine the role of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) in the modulation of this inflammatory response evoked by glycine, we examined its expression levels in fat tissue. Glycine clearly increased PPAR-gamma expression in lean mice but not in MSG/Ob mice. Finally, to identify alterations in glucose metabolism by glycine, we also examined insulin levels and other biochemical parameters during an oral glucose tolerance test. Glycine significantly reduced glucose tolerance and raised insulin levels in lean but not in obese mice. In conclusion, our findings suggest that glycine suppresses the pro-inflammatory cytokines production and increases adiponectin secretion in vivo through the activation of PPAR-gamma. Glycine might prevent insulin resistance and associated inflammatory diseases.

  15. Diverse manifestations of tumorigenicity and immunogenicity displayed by the poorly immunogenic B16-BL6 melanoma transduced with cytokine genes.

    Science.gov (United States)

    Arca, M J; Krauss, J C; Strome, S E; Cameron, M J; Chang, A E

    1996-05-01

    We evaluated the in vivo response to the poorly immunogenic B16-BL6 (BL6) murine melanoma genetically altered to secrete interleukin-2 (IL-2), IL-4, interferon gamma (IFN gamma) and granulocyte/macrophage-colony-stimulating factor (GM-CSF). Three parameters were evaluated: (1) tumorigenicity, (2) vaccination of naive animals, and (3) assessment of antitumor reactivity of T cells derived from tumor-draining lymph nodes (TDLN). Secretion of IL-2 abrogated the tumorigenicity of BL6, while IFN gamma and IL-4 partially reduced tumorigenicity, and GM-CSF had no effect. Protective immunity to wild-type tumor challenge could not be achieved by vaccination with irradiated cytokine-secreting tumors, although IL-2 and IL-4 secretion appeared to retard the growth of the challenge inoculum significantly. An alternative method to evaluate the immunogenicity of the cytokine-secreting tumors was to measure the ability of T cells obtained from TDLN to mediate regression of wild-type tumor in adoptive immunotherapy. Neither IL-2 nor IFN gamma secretion resulted in the induction of immune T cells. By contrast, GM-CSF and IL-4 secretion were found to induce immune T cells in the TDLN with GM-CSF being superior to IL-4. The combined secretion of GM-CSF and IL-4 did not lead to enhanced induction of immune T cells. GM-CSF secretion was found to upregulate B7-1 expression in TDLN, consistent with an increase in the population of antigen-presenting cells. These studies demonstrated that reduced tumorigenicity by cytokine secretion did not correlate with increased immunogenicity. With the cytokines examined, there was limited capability of developing protective immunity against the BL6 tumor. Nevertheless, GM-CSF and IL-4 secretion significantly enhanced T cell immune reactivity to the poorly immunogenic BL6 tumor.

  16. Cytokine signalling in embryonic stem cells

    DEFF Research Database (Denmark)

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

    2006-01-01

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

  17. Splenocyte proliferation, NK cell activation and cytokines production by extract of Scrophularia variegata; an in vitro study on mice spleen cells

    Directory of Open Access Journals (Sweden)

    A. Azadmehr

    2016-10-01

    Full Text Available Background and objectives:Scrophularia variegata M. Beib. (Scrophulariaceae is a medicinal plant, used for various inflammatory diseases in Iranian Traditional Medicine. In the present study, we evaluated the immune modulation and antioxidant effects of the hydroalcoholic extract of S.  variegata. Methods: The splenocytes were harvested from the spleen of Balb/c mice and were cultured. The splenocyte proliferation, NK cell activity, cytokines production and antioxidant effects were evaluated by MTT assay, enzyme- linked immunosorbent assay (ELISA and DPPH assay, respectively. Results: The S. variegata extract significantly increased splenocyte proliferation. The results indicated that the extract increased NK cell cytotoxicity of Yac-1 tumor cells and at the concentration of 50-200 µg/mL significantly increased IFN-γ and IL-2 cytokines, although the level of IL-4 cytokine was significantly reduced. The antioxidant activity was observed in the extract with IC50 302.34±0.11 μg/mL.Conclusion: The increasing in the splenocyte proliferation, anti-tumor NK cell cytotoxicity and cytokine secretion were indicated as potent immunomodulatory effects. These results suggest that S. variegata could be considered in the treatment of immunopathological disorders such as allergy and cancer; however, future studies are necessary.

  18. Regulatory T cell levels and cytokine production in active non-infectious uveitis: in-vitro effects of pharmacological treatment.

    Science.gov (United States)

    Molins, B; Mesquida, M; Lee, R W J; Llorenç, V; Pelegrín, L; Adán, A

    2015-03-01

    The aim of this study was to quantify the proportion of regulatory T cells (Treg ) and cytokine expression by peripheral blood mononuclear cells (PBMCs) in patients with active non-infectious uveitis, and to evaluate the effect of in-vitro treatment with infliximab, dexamethasone and cyclosporin A on Treg levels and cytokine production in PBMCs from uveitis patients and healthy subjects. We included a group of 21 patients with active non-infectious uveitis and 18 age-matched healthy subjects. The proportion of forkhead box protein 3 (FoxP3)(+) Treg cells and intracellular tumour necrosis factor (TNF)-α expression in CD4(+) T cells was determined by flow cytometry. PBMCs were also either rested or activated with anti-CD3/anti-CD28 and cultured in the presence or absence of dexamethasone, cyclosporin A and infliximab. Supernatants of cultured PBMCs were collected and TNF-α, interleukin (IL)-10, IL-17 and interferon (IFN)-γ levels were measured by enzyme-linked immunosorbent assay (ELISA). No significant differences were observed in nTreg levels between uveitis patients and healthy subjects. However, PBMCs from uveitis patients produced significantly higher amounts of TNF-α and lower amounts of IL-10. Dexamethasone treatment in vitro significantly reduced FoxP3(+) Treg levels in PBMCs from both healthy subjects and uveitis patients, and all tested drugs significantly reduced TNF-α production in PBMCs. Dexamethasone and cyclosporin A significantly reduced IL-17 and IFN-γ production in PBMCs and dexamethasone up-regulated IL-10 production in activated PBMCs from healthy subjects. Our results suggest that PBMCs from patients with uveitis express more TNF-α and less IL-10 than healthy subjects, and this is independent of FoxP3(+) Treg levels. Treatment with infliximab, dexamethasone and cyclosporin A in vitro modulates cytokine production, but does not increase the proportion of FoxP3(+) Treg cells. © 2014 British Society for Immunology.

  19. Effect of polybrominated diphenyl ether congeners on placental cytokine production.

    Science.gov (United States)

    Arita, Yuko; Yeh, Corinne; Thoma, Theodosia; Getahun, Darios; Menon, Ramkumar; Peltier, Morgan R

    2018-02-01

    Polybrominated diphenyl ethers (PBDEs) are pollutants that may increase the risk of preterm birth. In previous studies, we found that a mixture of PBDEs altered the expression of biomarkers for preterm birth by the placenta. However, there are 209 different PBDE congeners with different tissue distributions. How these different congeners may alter the production of immunomodulators by the placenta that help to maintain the survival of the fetal allograft is unclear. Therefore, we compared the effects 5 common congeners on basal and bacteria-stimulated cytokine production by the placenta. Placental explant cultures were incubated with 20 μM of PBDE congeners 47, 99, 100, 153, 209 or vehicle in the presence and absence of Escherichia coli for 20 h. Conditioned medium was harvested and concentrations of IL-1β, TNF-α, IL-6, sgp130, HO-1, IL-10, BDNF, and 8-IsoP quantified. For unstimulated cultures, all congeners, except for PBDE-47, reduced the production of IL-1β and IL-6 production was enhanced by PBDE-153. BDNF concentrations tended to be reduced by most PBDE congeners and IL-10 production was enhanced by PBDE-99, -153, and -209. 8-IsoP production was enhanced by PBDE-153, but not the other congeners. For bacteria-stimulated cultures, PBDE-47 increased IL-1β production and PBDE-47, -153, and -209 tended to reduce TNF-α production. IL-6 production was enhanced by all PBDEs except 153. IL-10 production was enhanced by all congeners except for PBDE-47. All congeners significantly enhanced BDNF and 8-IsoP. These results suggest that PBDEs can alter the expression of placental biomarkers in a congener and infection-dependent manner. Copyright © 2018 Elsevier B.V. All rights reserved.

  20. Effect of Yanhuning in combined with azithromycin on the inflammatory cytokines and immunological function in children with mycoplasma pneumonia

    Institute of Scientific and Technical Information of China (English)

    Guo Hui; Ge Liang

    2017-01-01

    Objective: To explore the effect of Yanhuning in combined with azithromycin on the inflammatory cytokines and immunological function in children with mycoplasma pneumonia. Methods: A total of 130 children with mycoplasma pneumonia were included in the study and randomized into the treatment group (n=65) and the control group (n=65). The patients in the control group were given azithromycin. On the above basis, the patients in the treatment group were given Yanhuning. The patients in the two groups were continuously treated for 7 d. The levels of serum inflammatory cytokines and immunological function indicators before and after treatment in the two groups were detected and compared. Results: When compared with before treatment, the serum IL-2 level after treatment in the two groups was significantly elevated, while IL-4, IL-10, IL-13, IL-6, TNF-α, and IFN-γ levels were significantly reduced; moreover, the improvement in the treatment group was significantly superior to that in the control group. When compared with before treatment, CD3+, CD4+, and CD4+/CD8+ after treatment in the two groups were significantly elevated, and those in the treatment group were significantly higher than those in the control group, while CD8+ was significantly reduced, but the comparison between the two groups was not statistically significant. When compared with before treatment, RBC-C3bR after treatment in the two groups was significantly elevated, while RBC-ICR was significantly reduced; moreover, the improvement in the treatment group was significantly superior to that in the control group. Conclusions: Yanhuning in combined with azithromycin in the treatment of mycoplasma pneumonia in children can significantly enhance the immunological function, and reduce the inflammatory reaction, with an effect significantly superior to that by single application of azithromycin.

  1. 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.

  2. GCN2-Dependent Metabolic Stress Is Essential for Endotoxemic Cytokine Induction and Pathology

    Science.gov (United States)

    Liu, Haiyun; Huang, Lei; Bradley, Jillian; Liu, Kebin; Bardhan, Kankana; Ron, David; Mellor, Andrew L.; Munn, David H.

    2014-01-01

    Activated inflammatory macrophages can express indoleamine 2,3-dioxygenase (IDO) and thus actively deplete their own tryptophan supply; however, it is not clear how amino acid depletion influences macrophage behavior in inflammatory environments. In this report, we demonstrate that the stress response kinase GCN2 promotes macrophage inflammation and mortality in a mouse model of septicemia. In vitro, enzymatic amino acid consumption enhanced sensitivity of macrophages to the Toll-like receptor 4 (TLR4) ligand lipopolysaccharide (LPS) with significantly increased interleukin 6 (IL-6) production. Tryptophan withdrawal induced the stress response proteins ATF4 and CHOP/GADD153; however, LPS stimulation rapidly enhanced expression of both proteins. Moreover, LPS-driven cytokine production under amino acid-deficient conditions was dependent on GCN2, as GCN2 knockout (GCN2KO) macrophages had a significant reduction of cytokine gene expression after LPS stimulation. To test the in vivo relevance of these findings, monocytic-lineage-specific GCN2KO mice were challenged with a lethal dose of LPS intraperitoneally (i.p.). The GCN2KO mice showed reduced inflammatory responses, with decreased IL-6 and IL-12 expression correlating with significant reduction in animal mortality. Thus, the data show that amino acid depletion stress signals (via GCN2) synergize with proinflammatory signals to potently increase innate immune responsiveness. PMID:24248597

  3. Cytokine Release and Focal Adhesion Proteins in Normal Thyroid Cells Cultured on the Random Positioning Machine

    Directory of Open Access Journals (Sweden)

    Elisabeth Warnke

    2017-08-01

    Full Text Available Background/Aims: Spaceflight impacts on the function of the thyroid gland in vivo. In vitro normal and malignant thyrocytes assemble in part to multicellular spheroids (MCS after exposure to the random positioning machine (RPM, while a number of cells remain adherent (AD. We aim to elucidate possible differences between AD and MCS cells compared to 1g-controls of normal human thyroid cells. Methods: Cells of the human follicular epithelial thyroid cell line Nthy-ori 3-1 were incubated for up to 72 h on the RPM. Afterwards, they were investigated by phase-contrast microscopy, quantitative real-time PCR and by determination of cytokines released in their supernatants. Results: A significant up-regulation of IL6, IL8 and CCL2 gene expression was found after a 4h RPM-exposure, when the whole population was still growing adherently. MCS and AD cells were detected after 24 h on the RPM. At this time, a significantly reduced gene expression in MCS compared to 1g-controls was visible for IL6, IL8, FN1, ITGB1, LAMA1, CCL2, and TLN1. After a 72 h RPM-exposure, IL-6, IL-8, and TIMP-1 secretion rates were increased significantly. Conclusion: Normal thyrocytes form MCS within 24 h. Cytokines seem to be involved in the initiation of MCS formation via focal adhesion proteins.

  4. Serum Profiles of Cytokines in Behcet’s Disease

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    Alireza Sadeghi

    2017-05-01

    Full Text Available Introduction: Behcet’s disease (BD is a chronic systemic autoinflammatory vasculitis which is handled by the variety of proteins like cytokines. Therefore, cytokines are considered as one of the prototypic factors during inflammatory responses of BD. Consequently, the present study was designed for evaluation of cytokine profiles in Iranian BD cases, including those with and without uveitis. Materials and Method: All cases were divided into three groups based on ophthalmologic exam results: BD with uveitis, BD without uveitis, and recovered uveitis BD. Cases with a history of BD recovery were placed in the group of recovered uveitis. The patients with infectious uveitis as well as other collagen vascular diseases and patients who have used biologics to treat ocular immune-mediated diseases were excluded. Finally, after venous blood sampling, levels of cytokines were quantified and statistical approaches were performed for measurements. Results: Enrolled cases were divided to 26 patients with active uveitis, 25 patients with recovered uveitis and 24 patients without uveitis and interestingly, just IL-2 was the only cytokine that showed statistical difference in patients with BD uveitis in comparison with other groups (pvalue = 0.02. The pair wise comparison showed a significant difference between the patients with and without uveitis groups (pvalue = 0.004 as well as patients with uveitis and recovered uveitis groups (pvalue = 0.002. Discussion: Significant elevation of IL-2 in patients with uveitis (in comparison with recovered or without uveitis cases demonstrates that it may be one of the main proteins that enroll in the pathophysiology of BD uveitis and may be considered as a new target for refractory disease therapies. Studies with larger samples can help to obtain more accurate conclusions.

  5. Cytokine profiles in localized scleroderma and relationship to clinical features.

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    Kurzinski, Katherine; Torok, Kathryn S

    2011-08-01

    Localized scleroderma (LS) is a disfiguring autoimmune disease of the skin and underlying tissue that mainly affects the pediatric population. Inflammation of the tissue leads to fibrosis and atrophy, causing physical and psychological disability that can continue throughout childhood into adulthood. Available therapies for LS have had variable effects and are associated with morbidity themselves. A better understanding of the pathophysiology of LS, especially during the active inflammatory phase, would lead to more directed and efficacious therapies. As in systemic sclerosis (SSc), the other form of scleroderma, T-helper (Th) cells and their associated cytokines have been suggested to contribute significantly to the pathophysiology of LS supported by the presence of cytokines from these lineages in the sera and tissue of LS patients. It is postulated that the imbalance between Th1/Th2/Th17 cell subsets drives inflammation in the early stages of disease (Th1 and Th17 predominant) and fibrosis in the later stages of scleroderma (Th2 predominant). We review the available experimental data regarding cytokines in LS and compare them to available clinical disease severity and activity features. This provides the platform to launch further investigations into the role of select cytokines in the pathogenesis of LS and to provide directed therapeutic options in the future. Published by Elsevier Ltd.

  6. Inflammatory Cytokines and Sleep Disturbance in Patients with Temporomandibular Disorders.

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    Park, Ji Woon; Chung, Jin Woo

    2016-01-01

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

  7. EVALUATION OF CYTOKINE GENE POLYMORPHISM IN B CELL LYMPHOID MALIGNANCIES

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    E. L. Nazarova

    2014-01-01

    Full Text Available Previous studies with some solid tumors has shown that polymorphisms of certain cytokine genes may be used as predictors of clinical outcome in the patients. It seemed important to evaluate potential correlations between production of certain pro- and anti-inflammatory cytokines and co-receptor molecules, and promoter polymorphism of the cytokine genes involved into regulation of cell proliferation, differentiation, apoptosis, lipid metabolism and blood clotting in the patients with hematological malignancies. The article contains our results concerning associations between of IL-1β, -2, -4, -10, -17, TNFα, and allelic polymorphisms of their genes in 62 patients with B cell lymphoid malignancies in an ethnically homogenous group (self-identified as Russians. We have shown that the GА and AA genotypes of the G-308A polymorphism in TNFα gene are significantly associated with increased production of this cytokine, being more common in aggressive non-Hodgkin lymphomas, more rare in multiple myeloma and in indolent non-Hodgkin lymphomas.

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

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

    2012-03-01

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

  9. Effects of WR1065 on 6-hydroxydopamine-induced motor imbalance: Possible involvement of oxidative stress and inflammatory cytokines.

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    Kheradmand, Afshin; Nayebi, Alireza M; Jorjani, Masoumeh; Khalifeh, Solmaz; Haddadi, Rasool

    2016-08-03

    Over production of reactive oxygen species (ROS) is postulated to be the main contributor in degeneration of nigrostriatal dopaminergic neurons. In this study we investigated the effects of WR1065, a free radical scavenger, on motor imbalance, oxidative stress parameters and inflammatory cytokines in CSF and brain of hemi-parkinsonian rats. Lesion of dopaminergic neurons was done by unilateral infusion of 6-hydroxydopamine into the central region of the substentia nigra pars compacta (SNc) to induce hemi-parkinsonism and motor imbalance in rats. WR1065 (20, 40 and 80μg/2μl/rat) was administered three days before 6-OHDA administration. After three weeks behavioral study was performed and then brain and CSF samples were collected to assess tumor necrosis factor (TNFα), interlukin (IL-1β), reduced glutathione (GSH), and malondialdehyde (MDA). WR1065 pre-treatment in rats before receiving 6-OHDA, improved significantly motor impairment and caused reduction of MDA and inflammatory cytokines TNFα and IL-1β levels, while GSH level significantly increased when compared with lesioned rats. Our study indicated that WR1065 could improve 6-OHDA-induced motor imbalance. Furthermore, it decreased lipid peroxidation and inflammatory cytokines and restored the level of GSH up to normal range. We suggest that WR1065 can be proposed as a potential neuroprotective agent in motor impairments of PD. However to prove this hypothesis more clinical trial studies should be done. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  10. Effects of corticosteroid on the expressions of neuropeptide and cytokine mRNA and on tenocyte viability in lateral epicondylitis

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    Han Soo

    2012-10-01

    Full Text Available Abstract Background The purpose of this study was to determine the reaction mechanism of corticosteroid by analyzing the expression patterns of neuropeptides (substance P (SP, calcitonin gene related peptide (CGRP and of cytokines (interleukin (IL-1α, tumor growth factor (TGF-β after corticosteroid treatment in lateral epicondylitis. In addition, we also investigated whether corticosteroid influenced tenocyte viability. Methods The corticosteroid triamcinolone acetonide (TAA was applied to cultured tenocytes of lateral epicondylitis, and the changes in the mRNA expressions of neuropeptides and cytokines and tenocyte viabilities were analyzed at seven time points. Quantitative real-time polymerase chain reaction and an MTT assay were used. Results The expression of SP mRNA was maximally inhibited by TAA at 24 hours but recovered at 72 hours, and the expressions of CGRP mRNA and IL-1α mRNA were inhibited at 24 and 3 hours, respectively. The expression of TGF-β mRNA was not significant. Tenocyte viability was significantly reduced by TAA at 24 hours. Conclusions We postulate that the reaction mechanism predominantly responsible for symptomatic relief after a corticosteroid injection involves the inhibitions of neuropeptides and cytokines, such as, CGRP and IL-1α. However the tenocyte viability was compromised by a corticosteroid.

  11. Th17 cytokines differentiate obesity from obesity-associated type 2 diabetes and promote TNFα production.

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    Ip, Blanche; Cilfone, Nicholas A; Belkina, Anna C; DeFuria, Jason; Jagannathan-Bogdan, Madhumita; Zhu, Min; Kuchibhatla, Ramya; McDonnell, Marie E; Xiao, Qiang; Kepler, Thomas B; Apovian, Caroline M; Lauffenburger, Douglas A; Nikolajczyk, Barbara S

    2016-01-01

    T cell inflammation plays pivotal roles in obesity-associated type 2 diabetes (T2DM). The identification of dominant sources of T cell inflammation in humans remains a significant gap in understanding disease pathogenesis. It was hypothesized that cytokine profiles from circulating T cells identify T cell subsets and T cell cytokines that define T2DM-associated inflammation. Multiplex analyses were used to quantify T cell-associated cytokines in αCD3/αCD28-stimulated PBMCs, or B cell-depleted PBMCs, from subjects with T2DM or BMI-matched controls. Cytokine measurements were subjected to multivariate (principal component and partial least squares) analyses. Flow cytometry detected intracellular TNFα in multiple immune cell subsets in the presence/absence of antibodies that neutralize T cell cytokines. T cell cytokines were generally higher in T2DM samples, but Th17 cytokines are specifically important for classifying individuals correctly as T2DM. Multivariate analyses indicated that B cells support Th17 inflammation in T2DM but not control samples, while monocytes supported Th17 inflammation regardless of T2DM status. Partial least squares regression analysis indicated that both Th17 and Th1 cytokines impact %HbA1c. Among various T cell subsets, Th17 cells are major contributors to inflammation and hyperglycemia and are uniquely supported by B cells in obesity-associated T2DM. © 2015 The Obesity Society.

  12. Pre-Treatment Deep Curettage Can Significantly Reduce Tumour Thickness in Thick Basal Cell Carcinoma While Maintaining a Favourable Cosmetic Outcome When Used in Combination with Topical Photodynamic Therapy

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    Christensen, E.; Mork, C.; Foss, O. A.

    2011-01-01

    Topical photodynamic therapy (PDT) has limitations in the treatment of thick skin tumours. The aim of the study was to evaluate the effect of pre-PDT deep curettage on tumour thickness in thick (≥2 mm) basal cell carcinoma (BCC). Additionally, 3-month treatment outcome and change of tumour thickness from diagnosis to treatment were investigated. At diagnosis, mean tumour thickness was 2.3 mm (range 2.0-4.0). Pre- and post-curettage biopsies were taken from each tumour prior to PDT. Of 32 verified BCCs, tumour thickness was reduced by 50% after deep curettage (ρ≤0.001) . Mean tumour thickness was also reduced from diagnosis to treatment. At 3-month followup, complete tumour response was found in 93% and the cosmetic outcome was rated excellent or good in 100% of cases. In conclusion, deep curettage significantly reduces BCC thickness and may with topical PDT provide a favourable clinical and cosmetic short-term outcome.

  13. Evaluating the effects of protective ventilation on organ-specific cytokine production in porcine experimental postoperative sepsis.

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    Sperber, Jesper; Lipcsey, Miklós; Larsson, Anders; Larsson, Anders; Sjölin, Jan; Castegren, Markus

    2015-05-10

    Protective ventilation with lower tidal volume (VT) and higher positive end-expiratory pressure (PEEP) reduces the negative additive effects of mechanical ventilation during systemic inflammatory response syndrome. We hypothesised that protective ventilation during surgery would affect the organ-specific immune response in an experimental animal model of endotoxin-induced sepsis-like syndrome. 30 pigs were laparotomised for 2 hours (h), after which a continuous endotoxin infusion was started at 0.25 micrograms × kg(-1) × h(-1) for 5 h. Catheters were placed in the carotid artery, hepatic vein, portal vein and jugular bulb. Animals were randomised to two protective ventilation groups (n = 10 each): one group was ventilated with VT 6 mL × kg(-1) during the whole experiment while the other group was ventilated during the surgical phase with VT of 10 mL × kg(-1). In both groups PEEP was 5 cmH2O during surgery and increased to 10 cmH2O at the start of endotoxin infusion. A control group (n = 10) was ventilated with VT of 10 mL × kg(-1) and PEEP 5 cm H20 throughout the experiment. In four sample locations we a) simultaneously compared cytokine levels, b) studied the effect of protective ventilation initiated before and during endotoxemia and c) evaluated protective ventilation on organ-specific cytokine levels. TNF-alpha levels were highest in the hepatic vein, IL-6 levels highest in the artery and jugular bulb and IL-10 levels lowest in the artery. Protective ventilation initiated before and during endotoxemia did not differ in organ-specific cytokine levels. Protective ventilation led to lower levels of TNF-alpha in the hepatic vein compared with the control group, whereas no significant differences were seen in the artery, portal vein or jugular bulb. Variation between organs in cytokine output was observed during experimental sepsis. We see no implication from cytokine levels for initiating protective ventilation before endotoxemia. However, during endotoxemia

  14. Cytokines: applications in domestic food animals.

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    Blecha, F

    1991-01-01

    Cytokines such as human, bovine, and porcine interferons and human and bovine interleukin-1 and interleukin-2 have been used in vivo in cattle and pigs. Colony-stimulating factors and tumor necrosis factor alpha have been evaluated in vitro in food animals. Studies to evaluate cytokines in domestic food animals have shown that specific and nonspecific immunomodulation is possible in immunosuppressed or pathogen-exposed animals. Cytokine prophylaxis or therapy in food animals may have the greatest potential for control of respiratory disease and mastitis.

  15. Administration of probiotics influences F4 (K88)-positive enterotoxigenic Escherichia coli attachment and intestinal cytokine expression in weaned pigs.

    Science.gov (United States)

    Daudelin, Jean-François; Lessard, Martin; Beaudoin, Frédéric; Nadeau, Eric; Bissonnette, Nathalie; Boutin, Yvan; Brousseau, Jean-Philippe; Lauzon, Karoline; Fairbrother, John Morris

    2011-05-23

    This study evaluated the effect of the probiotics Pediococcus acidilactici and Saccharomyces cerevisiae boulardii on the intestinal colonization of O149 enterotoxigenic Escherichia coli harbouring the F4 (K88) fimbriae (ETEC F4) and on the expression of ileal cytokines in weaned pigs. At birth, different litters of pigs were randomly assigned to one of the following treatments: 1) control without antibiotics or probiotics (CTRL); 2) reference group in which chlortetracycline and tiamulin were added to weanling feed (ATB); 3) P. acidilactici; 4) S. cerevisiae boulardii; or 5) P. acidilactici + S. cerevisiae boulardii. Probiotics were administered daily (1 × 10(9) CFU per pig) during the lactation period and after weaning (day 21). At 28 days of age, all pigs were orally challenged with an ETEC F4 strain, and a necropsy was performed 24 h later. Intestinal segments were collected to evaluate bacterial colonization in the small intestine and ileal cytokine expressions. Attachment of ETEC F4 to the intestinal mucosa was significantly reduced in pigs treated with P. acidilactici or S. cerevisiae boulardii in comparison with the ATB group (P = 0.01 and P = 0.03, respectively). In addition, proinflammatory cytokines, such as IL-6, were upregulated in ETEC F4 challenged pigs treated with P. acidilactici alone or in combination with S. cerevisiae boulardii compared with the CTRL group. In conclusion, the administration of P. acidilactici or S. cerevisiae boulardii was effective in reducing ETEC F4 attachment to the ileal mucosa, whereas the presence of P. acidilactici was required to modulate the expression of intestinal inflammatory cytokines in pigs challenged with ETEC F4.

  16. Administration of probiotics influences F4 (K88-positive enterotoxigenic Escherichia coli attachment and intestinal cytokine expression in weaned pigs

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    Daudelin Jean-François

    2011-05-01

    Full Text Available Abstract This study evaluated the effect of the probiotics Pediococcus acidilactici and Saccharomyces cerevisiae boulardii on the intestinal colonization of O149 enterotoxigenic Escherichia coli harbouring the F4 (K88 fimbriae (ETEC F4 and on the expression of ileal cytokines in weaned pigs. At birth, different litters of pigs were randomly assigned to one of the following treatments: 1 control without antibiotics or probiotics (CTRL; 2 reference group in which chlortetracycline and tiamulin were added to weanling feed (ATB; 3 P. acidilactici; 4 S. cerevisiae boulardii; or 5 P. acidilactici + S. cerevisiae boulardii. Probiotics were administered daily (1 × 109 CFU per pig during the lactation period and after weaning (day 21. At 28 days of age, all pigs were orally challenged with an ETEC F4 strain, and a necropsy was performed 24 h later. Intestinal segments were collected to evaluate bacterial colonization in the small intestine and ileal cytokine expressions. Attachment of ETEC F4 to the intestinal mucosa was significantly reduced in pigs treated with P. acidilactici or S. cerevisiae boulardii in comparison with the ATB group (P = 0.01 and P = 0.03, respectively. In addition, proinflammatory cytokines, such as IL-6, were upregulated in ETEC F4 challenged pigs treated with P. acidilactici alone or in combination with S. cerevisiae boulardii compared with the CTRL group. In conclusion, the administration of P. acidilactici or S. cerevisiae boulardii was effective in reducing ETEC F4 attachment to the ileal mucosa, whereas the presence of P. acidilactici was required to modulate the expression of intestinal inflammatory cytokines in pigs challenged with ETEC F4.

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

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    Mitsuaki Kimura

    2017-07-01

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

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

    Science.gov (United States)

    Harm, Stephan; Gabor, Franz; Hartmann, Jens

    2015-01-01

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

  19. Serum cytokine profile in the subclinical form of visceral leishmaniasis

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    Gama M.E.A.

    2004-01-01

    Full Text Available The factors determining the development or not of visceral leishmaniasis (VL have not been completely identified, but a Leishmania-specific cellular immune response seems to play a fundamental role in the final control of infection. Few studies are available regarding the production of cytokines in the subclinical form of VL, with only the production of IFN-g and TNF-a known. The aim of the present study was to identify immunological markers for the oligosymptomatic or subclinical form of VL. A prospective cohort study was conducted on 784 children aged 0 to 5 years from an endemic area in the State of Maranhão, Brazil, between January 1998 and December 2001. During 30 consecutive months of follow-up, 33 children developed the oligosymptomatic form of the disease and 12 the acute form. During the clinical manifestations, serum cytokine levels were determined in 27 oligosymptomatic children and in nine patients with the acute form using a quantitative sandwich enzyme immunoassay. In the subclinical form of VL, variable levels of IL-2 were detected in 52.3% of the children, IL-12 in 85.2%, IFN-g in 48.1%, IL-10 in 88.9%, and TNF-a in 100.0%, with the last two cytokines showing significantly lower levels than in the acute form. IL-4 was not detected in oligosymptomatic individuals. Multiple discriminant analysis used to determine the profile or combination of cytokines predominating in the subclinical form revealed both a Leishmania resistance (Th1 and susceptibility (Th2 profile. The detection of both Th1 and Th2 cytokine profiles explains the self-limited evolution accompanied by the discrete alterations observed for the subclinical form of VL.

  20. Interactions between cytokines and nitric oxide.

    Science.gov (United States)

    Liew, F Y

    1995-01-01

    There is now an impressive range of evidence supporting the important role of cytokines in sleep regulation (see Krueger et al., 1995; De Simoni et al., 1995). It has also been reported that inhibition of nitric oxide (NO) synthesis suppresses sleep in rabbits (Kapás et al., 1994). This is not surprising, since NO is closely involved in neurotransmission (Garthwaite, 1991; Schuman and Madison, 1994) and cytokines are the major inducers of NO synthesis (Hibbs et al., 1990). Further, it is now clear that NO plays an important role in modulating immune responses, possibly through the differential regulation of cytokine synthesis (Taylor-Robinson et al., 1994). In this article, I will provide evidence for the interactions between cytokines and nitric oxide, and discuss their implications in the regulation of immune responses. I shall illustrate these mainly with results from my coworkers and I, from our laboratory rather than attempting an exhaustive review of the subject.

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

    Science.gov (United States)

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

    2014-12-15

    The mechanism of cytokine secretion from T lymphocytes plays an important role in the immune response of dogs and parasitic skin infestations. Assessment of the cytokine profile of naturally S. scabiei var. canis infested dogs could augment understanding of the pathobiology of canine sarcoptic mange. Therefore, the present study examined the cytokines in peripheral blood mononuclear cells of dogs suffering from sarcoptic mange. Thirteen dogs naturally infected with sarcoptic mange participated in the study. The dogs were found positive for S. scabiei var. canis mites in skin scraping examinations and revealed at least three clinical inclusion criteria. Another five clinically healthy dogs were kept as healthy controls. Peripheral blood mononuclear cells were isolated from heparinized blood samples and used for extraction of mRNA. Further, cDNA was synthesized by using 1 mg of mRNA by reverse transcription using oligonucleotide primers. Relative levels of cytokine expression were compared with normalized glyceraldehyde-3-phosphate dehydrogenase (GAPDH) transcripts. The levels of interleukin-4, interleukin-5 and transforming growth factor beta (TGF-β) mRNA expression in dogs with sarcoptic mange were significantly higher (P ≤ 0.01), whereas the level of tumor necrosis factor alpha (TNF-α) was significantly lower (P ≤ 0.01) in comparison with the healthy dogs. No remarkable difference was seen for interleukin-2 mRNA expression between these animals. An overproduction IL-4 and IL-5 might be involved in immuno-pathogenesis of canine sarcoptic mange. S. scabiei var. canis mites possibly induce an overproduction of TGF-β and reduced expression of TNF-α and thus could be conferring the immune suppression of infested dogs. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Effect of Docosahexaenoic Acid (DHA) Supplementation on Inflammatory Cytokine Levels in Infants at High Genetic Risk for Type 1 Diabetes

    Science.gov (United States)

    Chase, H. Peter; Boulware, David; Rodriguez, Henry; Donaldson, David; Chritton, Sonia; Rafkin-Mervis, Lisa; Krischer, Jeffrey; Skyler, Jay S.; Clare-Salzler, Michael

    2014-01-01

    OBJECTIVE Type 1 diabetes (T1D) results from the inflammatory destruction of pancreatic β-cells. In the present study, we investigated the effect of docosahexaenoic acid (DHA) supplementation on stimulated inflammatory cytokine production in white blood cells (WBC) from infants with a high genetic risk for T1D. RESEARCH DESIGN AND METHODS This was a multicenter, two-arm, randomized, double blind pilot trial of DHA supplementation, beginning either in the last trimester of pregnancy (41 infants) or in the first five months after birth (57 infants). Levels of DHA in infant and maternal red blood cell (RBC) membranes and in breast milk were analyzed by gas chromatography/mass spectrometry. Inflammatory cytokines were assayed from whole blood culture supernatants using the Luminex Multiplex assay after stimulation with high dose lipopolysaccharide (LPS), 1μg/mL. RESULTS The levels of RBC DHA were increased by 61–100% in treated compared to control infants at ages 6 to 36 months. There were no statistically significant reductions in production of the inflammatory cytokines, IL-1β, TNFα or IL-12p40 at any of the 6 time points measured. The inflammatory marker, hsCRP, was significantly lower in breast-fed DHA-treated infants compared to all formula-fed infants at age 12 months. Three infants (two received DHA) were removed from the study as a result of developing ≥ two persistently positive biochemical islet autoantibodies. CONCLUSIONS This pilot trial showed that supplementation of infant diets with DHA is safe and fulfilled the pre-study goal of increasing infant RBC DHA levels by at least 20%. Inflammatory cytokine production was not consistently reduced. PMID:25039804

  3. Effect of docosahexaenoic acid supplementation on inflammatory cytokine levels in infants at high genetic risk for type 1 diabetes.

    Science.gov (United States)

    Chase, H Peter; Boulware, David; Rodriguez, Henry; Donaldson, David; Chritton, Sonia; Rafkin-Mervis, Lisa; Krischer, Jeffrey; Skyler, Jay S; Clare-Salzler, Michael

    2015-06-01

    Type 1 diabetes (T1D) results from the inflammatory destruction of pancreatic β-cells. In this study, we investigated the effect of docosahexaenoic acid (DHA) supplementation on stimulated inflammatory cytokine production in white blood cells (WBC) from infants with a high genetic risk for T1D. This was a multicenter, two-arm, randomized, double-blind pilot trial of DHA supplementation, beginning either in the last trimester of pregnancy (41 infants) or in the first 5 months after birth (57 infants). Levels of DHA in infant and maternal red blood cell (RBC) membranes and in breast milk were analyzed by gas chromatography/mass spectrometry. Inflammatory cytokines were assayed from whole blood culture supernatants using the Luminex multiplex assay after stimulation with high dose lipopolysaccharide (LPS), 1 µg/mL. The levels of RBC DHA were increased by 61-100% in treated compared to control infants at ages 6-36 months. There were no statistically significant reductions in production of the inflammatory cytokines, IL-1β, TNFα, or IL-12p40 at any of the six timepoints measured. The inflammatory marker, high-sensitivity C-reactive protein (hsCRP), was significantly lower in breast-fed DHA-treated infants compared to all formula-fed infants at the age of 12 months. Three infants (two received DHA) were removed from the study as a result of developing ≥two persistently positive biochemical islet autoantibodies. This pilot trial showed that supplementation of infant diets with DHA is safe and fulfilled the pre-study goal of increasing infant RBC DHA levels by at least 20%. Inflammatory cytokine production was not consistently reduced. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. Beneficial effects of cytokine induced hyperlipidemia.

    Science.gov (United States)

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

    1998-01-01

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

  5. Cytokine Profiles of Severe Influenza Virus-Related Complications in Children

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    Andrew Fiore-Gartland

    2017-11-01

    Full Text Available RationaleEffective immunomodulatory therapies for children with life-threatening “cytokine storm” triggered by acute influenza infection are lacking. Understanding the immune profiles of children progressing to severe lung injury and/or septic shock could provide insight into pathogenesis.ObjectivesTo compare the endotracheal and serum cytokine profiles of children with influenza-related critical illness and to identify their associations with severe influenza-associated complications.MethodsChildren with influenza-related critical illness were enrolled across 32 hospitals in development (N = 171 and validation (N = 73 cohorts (December 2008 through May 2016. Concentrations of 42 cytokines were measured in serum and endotracheal samples and clustered into modules of covarying cytokines. Relative concentrations of cytokines and cytokine modules were tested for associations with acute lung injury (ALI, shock requiring vasopressors, and death/ECMO.Measurements and main resultsModules of covarying cytokines were more significantly associated with disease severity than individual cytokines. In the development cohort, increased levels of a serum module containing IL6, IL8, IL10, IP10, GCSF, MCP1, and MIP1α [shock odds ratio (OR = 3.37, family-wise error rate (FWER p < 10−4], and decreased levels of a module containing EGF, FGF2, SCD40L, and PAI-1 (shock OR = 0.43, FWER p = 0.002, were both associated with ALI, shock, and death-ECMO independent of age and bacterial coinfection. Both of these associations were confirmed in the validation cohort. Endotracheal and serum cytokine associations differed markedly and were differentially associated with clinical outcomes.ConclusionWe identified strong positive and negative associations of cytokine modules with the most severe influenza-related complications in children, providing new insights into the pathogenesis of influenza-related critical illness in children. Effective

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

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    Ron L H Har

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

  7. Impact of anesthesia, analgesia, and euthanasia technique on the inflammatory cytokine profile in a rodent model of severe burn injury.

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    Al-Mousawi, Ahmed M; Kulp, Gabriela A; Branski, Ludwik K; Kraft, Robert; Mecott, Gabriel A; Williams, Felicia N; Herndon, David N; Jeschke, Marc G

    2010-09-01

    Anesthetics used in burn and trauma animal models may be influencing results by modulating inflammatory and acute-phase responses. Accordingly, we determined the effects of various anesthetics, analgesia, and euthanasia techniques in a rodent burn model. Isoflurane (ISO), ketamine-xylazine (KX), or pentobarbital (PEN) with or without buprenorphine were administered before scald-burn in 72 rats that were euthanized without anesthesia by decapitation after 24 h and compared with unburned shams. In a second experiment, 120 rats underwent the same scald-burn injury using KX, and 24 h later were euthanized under anesthesia or carbon dioxide (CO2). In addition, we compared euthanasia by exsanguination with that of decapitation. Serum cytokine levels were determined by an enzyme-linked immunosorbent assay. In the first experiment, ISO was associated with elevation of cytokine-induced neutrophil chemoattractant 2 (CINC-2) and monocyte chemotactic protein 1 (MCP-1), and KX and PEN was associated with elevation of CINC-1,CINC-2, IL-6, and MCP-1. Pentobarbital also decreased IL-1". IL-6 increased significantly when ISO or PEN were combined with buprenorphine. In the second experiment, euthanasia performed by exsanguination under ISO was associated with reduced levels of IL-1", CINC-1, CINC-2, and MCP-1, whereas KX reduced CINC-2 and increased IL-6 levels. Meanwhile, PEN reduced levels of IL-1" and MCP-1, and CO2 reduced CINC-2 and MCP-1. In addition,decapitation after KX, PEN, or CO2 decreased IL-1" and MCP-1, although we found no significant difference between ISO and controls. Euthanasia by exsanguination compared with decapitation using the same agent also led to modulation of several cytokines. Differential expression of inflammatory markers with the use of anesthetics and analgesics should be considered when designing animal studies and interpreting results because these seem to have a significant modulating impact. Our findings indicate that brief anesthesia with ISO

  8. MnSOD and catalase transgenes demonstrate that protection of islets from oxidative stress does not alter cytokine toxicity.

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    Chen, Hainan; Li, Xiaoyan; Epstein, Paul N

    2005-05-01

    Reactive oxygen species (ROS) and nitric oxide (NO) are proposed mediators of cytokine-induced beta-cell destruction in type 1 diabetes. We produced transgenic mice with increased beta-cell expression of manganese superoxide dismutase (MnSOD) and catalase. Expression of these antioxidants increased beta-cell ROS scavenging and improved beta-cell survival after treatment with different sources of ROS. MnSOD or catalase conferred protection against streptozotocin (STZ)-induced beta-cell injury. Coexpression of MnSOD and catalase provided synergistic protection against peroxynitrite and STZ. To determine the potential effect of these antioxidants on cytokine-induced toxicity, we exposed isolated islets to a cytokine mixture, including interleukin-1beta and interferon-gamma. Cytokine toxicity was measured as reduced metabolic activity after 6 days and reduced insulin secretion after 1 day. Cytokines increased ROS production, and both antioxidants were effective in reducing cytokine-induced ROS. However, MnSOD and/or catalase provided no protection against cytokine-induced injury. To understand this, the nuclear factor-kappaB (NF-kappaB) signaling cascade was investigated. Antioxidants reduced NF-kappaB activation by ROS, but none of the antioxidants altered activation by cytokines, as measured by inhibitor of kappaB phosphorylation, NF-kappaB translocation, inducible NO synthase activation, and NO production. Our data agree with previous reports that antioxidants benefit beta-cell survival against ROS damage, but they are not consistent with reports that antioxidants reduce cytokine toxicity. ROS appear to have no role in cytokine toxicity in primary beta-cells.

  9. Role of cytokines in development of pre-eclampsia associated with periodontal disease - Cohort Study.

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    Kumar, Ashok; Begum, Nargis; Prasad, Sudha; Lamba, Arundeep K; Verma, Mahesh; Agarwal, Sarita; Sharma, Shashi

    2014-04-01

    The present study was designed to find any association of cytokines in women with periodontal disease and development of pre-eclampsia in North Indian population. A total of 504 consecutively registered primigravida with a single live pregnancy were recruited at 14-18 weeks of gestation from antenatal clinic of Maulana Azad Medical College & associated Lok Nayak Hospital and Maulana Azad Institute of Dental Sciences, New Delhi. One periodontist performed oral health examination of all patients at inclusion into study. Blood samples were collected to measure the level of cytokines IL-4, IL-10, TNF-α and IFN-γ. The profile of blood levels of cytokines from women with periodontal disease was observed. The log serum levels of TNF-α & IL-4 at 16-18 weeks of gestation were significantly higher in women with periodontal disease (4.13 ± 2.06; 0.47 ± 1.56 pg/ml respectively) than in women with healthy gums (2.16 ± 1.51; 0.02 ± 1.84 pg/ml respectively, p Periodontal disease is associated with log serum TNF-α levels at cut-off ≥14.43 pg/ml at sensitivity 71.2% and specificity 62% (OR = 4.04; 95%CI = 2.77-5.87). Woman with periodontal disease who later developed pre-eclampsia had lower levels of TNF-α (3.72 ± 1.33 pg/ml) than those with periodontal disease who did not develop pre-eclampsia (4.20 ± 2.15 pg/ml, p ≥ 0.05). Reduced TNF-α level secretion in the early second trimester in women with periodontal disease appears to be associated with the development of pre-eclampsia. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

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

    2017-09-18

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

  11. Antioxidants inhibit SAA formation and pro-inflammatory cytokine release in a human cell model of alkaptonuria.

    Science.gov (United States)

    Spreafico, Adriano; Millucci, Lia; Ghezzi, Lorenzo; Geminiani, Michela; Braconi, Daniela; Amato, Loredana; Chellini, Federico; Frediani, Bruno; Moretti, Elena; Collodel, Giulia; Bernardini, Giulia; Santucci, Annalisa

    2013-09-01

    Alkaptonuria (AKU) is an ultra-rare autosomal recessive disease that currently lacks an appropriate therapy. Recently we provided experimental evidence that AKU is a secondary serum amyloid A (SAA)-based amyloidosis. The aim of the present work was to evaluate the use of antioxidants to inhibit SAA amyloid and pro-inflammatory cytokine release in AKU. We adopted a human chondrocytic cell AKU model to evaluate the anti-amyloid capacity of a set of antioxidants that had previously been shown to counteract ochronosis in a serum AKU model. Amyloid presence was evaluated by Congo red staining. Homogentisic acid-induced SAA production and pro-inflammatory cytokine release (overexpressed in AKU patients) were evaluated by ELISA and multiplex systems, respectively. Lipid peroxidation was evaluated by means of a fluorescence-based assay. Our AKU model allowed us to prove the efficacy of ascorbic acid combined with N-acetylcysteine, taurine, phytic acid and lipoic acid in significantly inhibiting SAA production, pro-inflammatory cytokine release and membrane lipid peroxidation. All the tested antioxidant compounds were able to reduce the production of amyloid and may be the basis for establishing new therapies for AKU amyloidosis.

  12. Influence of DC-CIK in advanced colorectal cancer patients on T lymphocyte subsets and cytokines

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    Rong Wang

    2016-07-01

    Full Text Available Objective: To explore the effects of dendritic cells (DC-cytokine induced killer cells (CIK treatment on T lymphocyte subsets and cytokines in patients with advanced colorectal cancer. Methods: A total of 84 cases patients with advanced colorectal cancer were divided into two groups according to random number table method, each 42 cases, both two groups were given FOLFOX scheme chemotherapy, on the basis, the observation group were given supplementary DC-CIK treatment, compared the T lymphocy te subgroup: CD3+, CD4+, CD8+, CD4+/CD8+, Th1 cytokines, interleukin-2 (IL-2 and interferon gamma-γ (FN-γ, Th2 cytokines: interleukin 6 (IL-6, interleukin 4 (IL-4 of the two groups before and after treatment. Results: Compared with before treatment, the CD3+, CD4+, CD8+, CD4+/CD8+, Th1 cytokines IL-2 and IFN-γ in observation group were significantly higher than after treatment , the CD3+, CD4+, CD8+, CD4+/CD8+, Th1 cytokines IL-2 and IFN-γ in control group were significantly lower than after treatment, and the differences were all statistically significant; The CD3+, CD4+, CD8+, CD4+/CD8+, Th1 cytokines IL-2 and IFN-γ in observation group after treatment were significantly higher than those in control group after treatment with statistical difference; CD8+, Th2 cytokines IL-4, IL-6 in two groups had no statistical significance before and after treatment. Conclusion: Chemotherapy can cause the immune function restrained in patients with advanced colorectal cancer, and DC-CIK supplementary therapy can significantly improve the immune function, enhance the anti tumor immune responses.

  13. Cervical cerclage placement decreases local levels of proinflammatory cytokines in patients with cervical insufficiency.

    Science.gov (United States)

    Monsanto, Stephany P; Daher, Silvia; Ono, Erika; Pendeloski, Karen Priscilla Tezotto; Trainá, Évelyn; Mattar, Rosiane; Tayade, Chandrakant

    2017-10-01

    . Compared with normal women, patients with cervical insufficiency have elevated levels of proinflammatory cytokines in cervicovaginal fluid but not in serum, suggesting a dysregulation of the local immune environment. Cerclage intervention led to a significant decline in these proinflammatory cytokines, suggesting that cerclage may help reduce local inflammation in cervical insufficiency. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Changes of serum cytokines levels after drug therapy in epileptic patients

    International Nuclear Information System (INIS)

    Xie Jianping; Li Suping; Xiong Gang

    2004-01-01

    Objective: To explore the role of the cytokines interleukin-2 (IL-2), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in the neuroimmune modulation of epilepsy through measurement of the changes of the serum levels of the these cytokines after drug therapy in epileptic patients. Methods: Serum IL-2, IL-6, TNF-α levels were measured with RIA in 43 patients with epilepsy both before and after drug therapy for 3-6 months as well as 32 controls. Results: Before treatment, serum levels of these cytokines in the patients were significantly higher than those in the controls (p<0.001). After treatment, 18 of the 43 patients were regarded as treatment very successful, with attack numbers decreased more than 75%. Some of this group of patient had their serum cytokines levels significantly dropped down, but the mean level for the group as a whole did not change much. In the rest 25 patients with less successful result, changes were not significant with the levels increased in a few cases. Among the cytokines, levels of IL-2 were significantly positively correlated to those of IL-6 and TNF-α (r=0.47, p<0.01, r=0.55, p<0.01). Conclusion: Increased levels of the cytokines in the epileptic patients suggest an activated immune state. However, the changes of levels after therapy are not predictable and do not necessarily drop down significantly even with very successful treatment

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

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    Hsu, Peter; Nanan, Ralph

    2014-10-01

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

  16. Virulent Type A Francisella tularensis actively suppresses cytokine responses in human monocytes

    Science.gov (United States)

    Gillette, Devyn D.; Curry, Heather M.; Cremer, Thomas; Ravneberg, David; Fatehchand, Kavin; Shah, Prexy A.; Wewers, Mark D.; Schlesinger, Larry S.; Butchar, Jonathan P.; Tridandapani, Susheela; Gavrilin, Mikhail A.

    2014-01-01

    Background: Human monocyte inflammatory responses differ between virulent and attenuated Francisella infection. Results: A mixed infection model showed that the virulent F. tularensis Schu S4 can attenuate inflammatory cytokine responses to the less virulent F. novicida in human monocytes. Conclusion: F. tularensis dampens inflammatory response by an active process. Significance: This suppression may contribute to enhanced pathogenicity of F. tularensis. Francisella tularensis is a Gram-negative facultative bacterium that can cause the disease tularemia, even upon exposure to low numbers of bacteria. One critical characteristic of Francisella is its ability to dampen or subvert the host immune response. Previous work has shown that monocytes infected with highly virulent F. tularensis subsp. tularensis strain Schu S4 responded with a general pattern of quantitatively reduced pro-inflammatory signaling pathway genes and cytokine production in comparison to those infected with the less virulent related F. novicida. However, it has been unclear whether the virulent Schu S4 was merely evading or actively suppressing monocyte responses. By using mixed infection assays with F. tularensis and F. novicida, we show that F. tularensis actively suppresses monocyte pro-inflammatory responses. Additional experiments show that this suppression occurs in a dose-dependent manner and is dependent upon the viability of F. tularensis. Importantly, F. tularensis was able to suppress pro-inflammatory responses to earlier infections with F. novicida. These results lend support that F. tularensis actively dampens human monocyte responses and this likely contributes to its enhanced pathogenicity. PMID:24783062

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

    Science.gov (United States)

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

    2015-01-01

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

  18. 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.

  19. Integration of the thiol redox status with cytokine response to physical training in professional basketball players.

    Science.gov (United States)

    Zembron-Lacny, A; Slowinska-Lisowska, M; Ziemba, A

    2010-01-01

    The present study was designed to evaluate the plasma markers of reactive oxygen species (ROS) activity and cytokines, and their relationship with thiol redox status of basketball players during training. Sixteen professional players of the Polish Basketball Extraleague participated in the study. The study was performed during the preparatory period and the play-off round. Markers of ROS activity (lipid peroxidation TBARS, protein carbonylation PC) and reduced glutathione (GSH) demonstrated regularity over time, i.e. TBARS, PC and GSH were elevated at the beginning and decreased at the end of training periods. Oxidized glutathione (GSSG) was not affected by exercise training. Thiol redox status (GSH(total)-2GSSG/GSSG) correlated with TBARS and PC in both training periods. The level of interleukin-6 (IL-6) was increased and positively correlated with thiol redox (r=0.423) in the preparatory period, whereas tumor necrosis factor alpha (TNFalpha) was increased and inversely correlated with thiol redox (r= 0.509) in the play-off round. The present study showed significant shifts in markers of ROS activity, thiol redox status and inflammatory mediators (IL-6, TNFalpha) following professional sport training as well as correlation between changes in thiol redox and cytokine response.

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

    Science.gov (United States)

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

    2015-08-01

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

  1. Short communication: Inhibitory effects of dietary aflatoxin B1 on cytokines expression and T-cell subsets in the cecal tonsil of broiler chickens

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    Chunyu Liu

    2016-08-01

    Full Text Available Aflatoxin B1 (AFB1 is the most toxic form among the mycotoxins. Cytokines are important mediators of the immune system. T-cell subsets play a crucial role in cell-mediated immunity. The aim of present study was to evaluate the effects of dietary AFB1 on the cytokines expression and T-cell subsets in the cecal tonsil of broiler chickens throughout a 21-day experimental period. One hundred and fifty six one-day-old broiler chickens were randomly divided into control group (0 mg AFB1/kg feed and AFB1 group (0.6 mg pure AFB1/kg feed. At 7, 14 and 21 days of age, the levels of seven cytokines (IL-2, IL-4, IL-6, IL-10, IL-17, IFN-γ and TNF-α mRNA expression as well as the proportions of T-cell subsets (CD3+, CD3+CD4+, CD3+CD8+ by qRT-PCR and flow cytometry methods were assessed in the cecal tonsils. The levels of the seven cytokines mRNA expression and the percentages of T-cell subsets significantly decreased at 14 and 21 days of age in the AFB1 group compared with the control group. However, the CD4+/CD8+ ratio was not significantly changed. These results demonstrate that 0.6 mg/kg AFB1 dietary exposure reduced the levels of cytokines mRNA expression and the percentages of T-cell subsets in the cecal tonsils of broiler chickens, suggesting that the cell-mediated immunity of cecal tonsils might be impaired in broilers.

  2. Short communication: Inhibitory effects of dietary aflatoxin B1 on cytokines expression and T-cell subsets in the cecal tonsil of broiler chickens

    Energy Technology Data Exchange (ETDEWEB)

    Liu, C.; Jiang, M.; Fang, J.; Peng, X.; Cui, H.

    2016-11-01

    Afatoxin B1 (AFB1) is the most toxic form among the mycotoxins. Cytokines are important mediators of the immune system. T-cell subsets play a crucial role in cell-mediated immunity. The aim of present study was to evaluate the effects of dietary AFB1 on the cytokines expression and T-cell subsets in the cecal tonsil of broiler chickens throughout a 21-day experimental period. One hundred and fifty six one-day-old broiler chickens were randomly divided into control group (0 mg AFB1/kg feed) and AFB1 group (0.6 mg pure AFB1/kg feed). At 7, 14 and 21 days of age, the levels of seven cytokines (IL-2, IL-4, IL-6, IL-10, IL-17, IFN-γ and TNF-α) mRNA expression as well as the proportions of T-cell subsets (CD3+, CD3+CD4+, CD3+CD8+) by qRT-PCR and flow cytometry methods were assessed in the cecal tonsils. The levels of the seven cytokines mRNA expression and the percentages of T-cell subsets significantly decreased at 14 and 21 days of age in the AFB1 group compared with the control group. However, the CD4+/CD8+ ratio was not significantly changed. These results demonstrate that 0.6 mg/kg AFB1 dietary exposure reduced the levels of cytokines mRNA expression and the percentages of T-cell subsets in the cecal tonsils of broiler chickens, suggesting that the cell-mediated immunity of cecal tonsils might be impaired in broilers. (Author)

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

    Science.gov (United States)

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

    2014-10-01

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

  4. [Effect of sucralfate on cytokines in rat with paraquat poisoning].

    Science.gov (United States)

    Zhu, Junbo; Yu, Yongtao; Li, Hongbo; Zheng, Fenshuang; Lin, Ruyun; Yang, Chun'ai

    2018-03-01

    To explore the effect of sucralfate on cytokines in rats with paraquat (PQ) poisoning. Seventy-two healthy male Sprague-Dawley (SD) rats were randomly divided into PQ model group, sodium bicarbonate intervention group (SB group) and sucralfate suspension gel group (LTL group), with 24 rats in each group. The rat model of PQ poisoning was reproduced by one-time intragastric administration of PQ solution 25 mg/kg. The rats in SB group and LTL group were intragastricly administrated with 5 mL×kg -1 ×d -1 of 100 g/L sodium bicarbonate or 200 g/L sucralfate at 2 hours after exposing to PQ, and the rats in PQ model group were given the same amount of sterile saline. The abdominal aortic blood of rats was collected at 1, 3, 6, and 10 days after PQ poisoning, and the levels of serum tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10) and transforming growth factor-β1 (TGF-β1) were determined by enzyme-linked immunosorbent assay (ELISA). The left lung tissue was harvested, and lung wet/dry weight (W/D) ratio was assessed. With prolonged exposure, lung W/D ratios in all the groups were increased gradually, reached the peak at 10 days, but in the SB group and LTL group, the amplitude of increase was obviously reduced, the ratios were significantly decreased at 6 days and 10 days as compared with those in PQ model group (SB group vs. PQ model group: 4.99±0.79 vs. 6.98±0.86 at 6 days, 5.61±0.36 vs. 7.36±0.95 at 10 days; LTL group vs. PQ model group: 4.61±0.24 vs. 6.98±0.86 at 6 days, 4.24±0.20 vs. 7.36±0.95 at 10 days, all P 0.05). After PQ poisoning, the levels of TNF-α, IL-10 and TGF-β1 were elevated, and reached the peak at 3 days and then decreased gradually. Compared with the PQ model group, serum TNF-α, IL-10 and TGF-β1 levels in SB group and LTL group were decreased significantly [SB group vs. PQ model group: 3-day TNF-α (ng/L) was 147.6±12.3 vs. 168.2±11.3, 3-day IL-10 (ng/L) was 65.4±3.2 vs. 115.1±9.2, 3-day TGF-β1 (ng/L) was 356.3±50.3 vs

  5. INTEGRAL EVALUATION OF THE CYTOKINE SYSTEM IN VIRAL MYOCARDITIS

    Directory of Open Access Journals (Sweden)

    Peremot S. D.

    2017-10-01

    -10, INF-γ, TNF-α in serum was measured by enzyme-linked immunosorbent assay using commercial enzyme immunoassay kits for Thermo Scientific ™ (IL-2R IL-4, IL-6, IL-10, TNF alpha, IFN gamma ELISA Kit, Human, USA and Stat Fax 303 Plus spectrophotometer. Statistical processing of all received data was carried out on a personal computer using the program Statistica, version 6.1 (StatSoft Inc., USA [1]. Results & discussion. Analysis of levels of pro- and anti-inflammatory cytokines in patients indicates an imbalance in their system, which is characterized primarily by a significant increase in the level of IL-6 prophylaxis to (134.09 ± 22.72 pg / ml (control level 11.83 ± 1, 64 pg / ml and a relatively moderate increase in IL-2 and TNF-α levels in subacute myocarditis. Such an increase in the level of IL-6, in our opinion, is due to the dualism of the action of this interleukin, the proinflammatory nature of its action at the final stage of inflammation changes to anti-inflammatory. As a consequence, in combination with IL-10, it limits the secretion of TNF-α. That is why its level remains high and with chronic herpesviral myocarditis and exceeds the level of the control group more than 8 times. In addition, in the chronic form of the course of herpesviral myocarditis, an increase in the levels of anti-inflammatory IL4 and IL-10 cytokines is observed in 2.9 and 3.1 times, respectively. And the level of IL-10 increased not only in comparison with the level of the control group, but also exceeded by 1.5 times the corresponding index for subacute myocarditis. In order to optimize the analysis of cytokine imbalance, an integral assessment of the levels of inflammatory mediators from opposing groups was carried out. Calculation of the integral indicator (II of the cytokine balance was performed by determining the values of cytokine indices as the ratios of the levels of proinflammatory and anti-inflammatory sera in the examined patients to the reference values of the

  6. Treatment with a belly-board device significantly reduces the volume of small bowel irradiated and results in low acute toxicity in adjuvant radiotherapy for gynecologic cancer: results of a prospective study

    International Nuclear Information System (INIS)

    Martin, Joseph; Fitzpatrick, Kathryn; Horan, Gail; McCloy, Roisin; Buckney, Steve; O'Neill, Louise; Faul, Clare

    2005-01-01

    Background and purpose: To determine whether treatment prone on a belly-board significantly reduces the volume of small bowel irradiated in women receiving adjuvant radiotherapy for gynecologic cancer, and to prospectively study acute small bowel toxicity using an accepted recording instrument. Material and methods: Thirty-two gynecologic patients underwent simulation with CT scanning supine and prone. Small bowel was delineated on every CT slice, and treatment was prone on the belly-board using 3-5 fields-typically Anterior, Right and Left Lateral, plus or minus Lateral Boosts. Median prescribed dose was 50.4 Gy and all treatments were delivered in 1.8 Gy fractions. Concomitant Cisplatin was administered in 13 patients with cervical carcinoma. Comparison of small bowel dose-volumes was made between supine and prone, with each subject acting as their own matched pair. Acute small bowel toxicity was prospectively measured using the Common Toxicity Criteria: Version 2.0. Results: Treatment prone on the belly-board significantly reduced the volume of small bowel receiving ≥100; ≥95; ≥90; and ≥80% of the prescribed dose, but not ≥50%. This was found whether volume was defined in cubic centimeters or % of total small bowel volume. Of 29 evaluable subjects, 2 (7%) experienced 1 episode each of grade 3 diarrhoea. All other toxicity events were grade 2 or less and comprised diarrhoea (59%), abdominal pain or cramping (48%), nausea (38%), anorexia (17%), vomiting (10%). There were no Grade 4 events and no treatment days were lost due to toxicity. Conclusions: Treatment prone on a belly-board device results in significant small bowel sparing, during adjuvant radiotherapy for gynecologic cancer. The absence of Grade 4 events or Treatment Days Lost compares favorably with the published literature

  7. Caprine arthritis encephalitis virus dysregulates the expression of cytokines in macrophages.

    Science.gov (United States)

    Lechner, F; Machado, J; Bertoni, G; Seow, H F; Dobbelaere, D A; Peterhans, E

    1997-01-01

    Caprine arthritis encephalitis virus (CAEV) is a lentivirus of goats that leads to chronic mononuclear infiltration of various tissues, in particular, the radiocarpal joints. Cells of the monocyte/macrophage lineage are the major host cells of CAEV in vivo. We have shown that infection of cultured goat macrophages with CAEV results in an alteration of cytokine expression in vitro. Constitutive expression of interleukin 8 (IL-8) and monocyte chemoattractant protein 1 (MCP-1) was increased in infected macrophages, whereas transforming growth factor beta1 (TGF-beta1) mRNA was down-regulated. When macrophages were infected with a CAEV clone lacking the trans-acting nuclear regulatory gene tat, IL-8 and MCP-1 were also increased. No significant differences from cells infected with the wild-type clone were observed, suggesting that Tat is not required for the increased expression of IL-8 and MCP-1 in infected macrophages. Furthermore, infection with CAEV led to an altered pattern of cytokine expression in response to lipopolysaccharide (LPS), heat-killed Listeria monocytogenes plus gamma interferon, or fixed cells of Staphylococcus aureus Cowan I. In infected macrophages, tumor necrosis factor alpha, IL-1beta, IL-6, and IL-12 p40 mRNA expression was reduced in response to all stimuli tested whereas changes in expression of granulocyte-macrophage colony-stimulating factor depended on the stimulating agent. Electrophoretic mobility shift assays demonstrated that, in contrast to effects of human immunodeficiency virus infection of macrophages, CAEV infection had no effect on the level of constitutive nuclear factor-kappaB (NF-kappaB) activity or on the level of LPS-stimulated NF-kappaB activity, suggesting that NF-kappaB is not involved in altered regulation of cytokine expression in CAEV-infected cells. In contrast, activator protein 1 (AP-1) binding activity was decreased in infected macrophages. These data show that CAEV infection may result in a dysregulation of

  8. Cytokine Signatures Discriminate Highly Frequent Acute Hepatitis a Virus and Hepatitis E Virus Coinfections from Monoinfections in Mexican Pediatric Patients.

    Science.gov (United States)

    Realpe-Quintero, Mauricio; Copado-Villagrana, Edgar Daniel; Trujillo-Ochoa, Jorge Luis; Alvarez, Angel Hilario; Panduro, Arturo; Fierro, Nora Alma

    2017-07-01

    The frequency of hepatitis A virus and hepatitis E virus infections and their cytokine profiles were analyzed in Mexican pediatric patients with acute hepatitis. A high frequency of coinfections was found. Significant overexpression of interleukin (IL)-4, IL-12, IL-13 and interferon-gamma during hepatitis A virus monoinfections and limited secretion of cytokines in hepatitis E virus infections were observed.

  9. IL-10 dependent suppression of type 1, type 2 and type 17 cytokines in active pulmonary tuberculosis.

    Directory of Open Access Journals (Sweden)

    Nathella Pavan Kumar

    Full Text Available Although Type 1 cytokine responses are considered protective in pulmonary tuberculosis (PTB, their role as well as those of Type 2, 17 and immunoregulatory cytokines in tuberculous lymphadenitis (TBL and latent tuberculosis (LTB have not been well studied.To identify cytokine responses associated with pulmonary tuberculosis (TB, TB lymphadenitits and latent TB, we examined mycobacterial antigen-specific immune responses of PTB, TBL and LTB individuals. More specifically, we examined ESAT-6 and CFP-10 induced Type 1, Type 2 and Type 17 cytokine production and their regulation using multiplex ELISA.PTB individuals exhibited a significantly lower baseline as well as antigen-specific production of Type 1 (IFNγ, TNFα and IL-2; Type 2 (IL-4 and Type 17 (IL-17A and IL-17F cytokines in comparison to both TBL and LTB individuals. TBL individuals exhibited significantly lower antigen-specific IFNγ responses alone in comparison to LTB individuals. Although, IL-10 levels were not significantly higher, neutralization of IL-10 during antigen stimulation resulted in significantly enhanced production of IFNγ, IL-4 and IL-17A in PTB individuals, indicating that IL-10 mediates (at least partially the suppression of cytokine responses in PTB.Pulmonary TB is characterized by an IL-10 dependent antigen-specific suppression of Type 1, Type 2 and Type 17 cytokines, reflecting an important association of these cytokines in the pathogenesis of active TB.

  10. Suppressor of cytokine signaling (SOCS)5 ameliorates influenza infection via inhibition of EGFR signaling.

    Science.gov (United States)

    Kedzierski, Lukasz; Tate, Michelle D; Hsu, Alan C; Kolesnik, Tatiana B; Linossi, Edmond M; Dagley, Laura; Dong, Zhaoguang; Freeman, Sarah; Infusini, Giuseppe; Starkey, Malcolm R; Bird, Nicola L; Chatfield, Simon M; Babon, Jeffrey J; Huntington, Nicholas; Belz, Gabrielle; Webb, Andrew; Wark, Peter Ab; Nicola, Nicos A; Xu, Jianqing; Kedzierska, Katherine; Hansbro, Philip M; Nicholson, Sandra E

    2017-02-14

    Influenza virus infections have a significant impact on global human health. Individuals with suppressed immunity, or suffering from chronic inflammatory conditions such as COPD, are particularly susceptible to influenza. Here we show that suppressor of cytokine signaling (SOCS) five has a pivotal role in restricting influenza A virus in the airway epithelium, through the regulation of epidermal growth factor receptor (EGFR). Socs5 -deficient mice exhibit heightened disease severity, with increased viral titres and weight loss. Socs5 levels were differentially regulated in response to distinct influenza viruses (H1N1, H3N2, H5N1 and H11N9) and were reduced in primary epithelial cells from COPD patients, again correlating with increased susceptibility to influenza. Importantly, restoration of SOCS5 levels restricted influenza virus infection, suggesting that manipulating SOCS5 expression and/or SOCS5 targets might be a novel therapeutic approach to influenza.

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

    Science.gov (United States)

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

    2017-07-01

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

  12. Genetic and cytokine changes associated with symptomatic stages of CLL.

    Science.gov (United States)

    Agarwal, Amit; Cooke, Lawrence; Riley, Christopher; Qi, Wenqing; Mount, David; Mahadevan, Daruka

    2014-09-01

    The pathogenesis and drug resistance of symptomatic CLL patients involves genetic changes associated with the CLL clone as well as changes within the microenvironment. To further understand these processes, we compared early stage CLL to symptomatic late stage using gene expression and serum cytokine profiling to gain insight of the genetic and microenvironment changes associated with the most severe form of the disease. Patients were classified into low stage (Rai stage 0/I/II) and high stage (Rai stage III/IV). Gene expression profiles were obtained on pretreatment samples using the HG-U133A 2.0 Affymetrix platform. A comparison of low versus high stage CLL revealed a set of 21 genes differentially expressed genes. 15 genes were up regulated in the high stage compared to low stage while 6 genes were down regulated. Analysis of GO molecular function revealed 9 of 21 genes were involved in transcription factor activity. Serum cytokine profiles showed six cytokines to be significantly different in high stage patients. Two chemokines, SDF-1/CXCL12 and uPAR known to be involved in stem cell mobilization and homing were increased in serum of high stage patients. This study has identified therapeutic targets for symptomatic CLL patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Expression of cytokines in aqueous humor from fungal keratitis patients.

    Science.gov (United States)

    Zhang, Yingnan; Liang, Qingfeng; Liu, Yang; Pan, Zhiqiang; Baudouin, Christophe; Labbé, Antoine; Lu, Qingxian

    2018-04-19

    Although a series of reports on corneal fungal infection have been published, studies on pathogenic mechanisms and inflammation-associated cytokines remain limited. In this study, aqueous humor samples from fungal keratitis patients were collected to examine cytokine patterns and cellular profile for the pathogenesis of fungal keratitis. The aqueous humor samples were collected from ten patients with advanced stage fungal keratitis. Eight aqueous humor samples from patients with keratoconus or corneal dystrophy were taken as control. Approximately 100 μl to 300 μl of aqueous humor in each case were obtained for examination. The aqueous humor samples were centrifuged and the cells were stained and examined under optical microscope. Bacterial and fungal cultures were performed on the aqueous humor and corneal buttons of all patients. Cytokines related to inflammation including IL-1β, IL-6, IL-8, IL-10, TNF-α, and IFN-γ were examined using multiplex bead-based Luminex liquid protein array systems. Fungus infection was confirmed in these ten patients by smear stains and/or fungal cultures. Bacterial and fungal cultures revealed negative results in all aqueous humor specimens. Polymorphonuclear leukocytes were the predominant infiltrating cells in the aqueous humor of fungal keratitis. At the advanced stages of fungal keratitis, the levels of IL-1β, IL-6, IL-8, and IFN-γ in the aqueous humor were significantly increased when compared with control (phumor was associated with fungal keratitis.

  14. Serum cytokine levels in patients with hepatocellular carcinoma.

    Science.gov (United States)

    Capone, Francesca; Costantini, Susan; Guerriero, Eliana; Calemma, Rosa; Napolitano, Maria; Scala, Stefania; Izzo, Francesco; Castello, Giuseppe

    2010-06-01

    The role played by the microenvironment in cancer induction, promotion and progression is crucial. Emerging evidence suggests that cytokines, chemokines and growth factors are major players in carcinogenesis. Therefore, a detailed understanding of factors and mechanisms associated with the processes leading from inflammation to cancer could improve the therapeutic strategies against this disease. We have used hepatocarcinoma as our model in this study. We evaluated the serum levels of 50 different cytokines, chemokines and growth factors in patients affected by HCC with chronic HCV-related hepatitis and liver cirrhosis using multiplex biometric ELISA-based immunoassay. Our data showed that some pro-inflammatory molecules were significantly up-regulated in these patients, and highlighted the complexity of the cytokine network in this disease. This work suggests the need to monitor these proteins in order to define a profile that could characterize patients with HCC or to help identify useful markers. This could lead to better definition of the disease state, and to an increased understanding of the relationships between chronic inflammation and cancer.

  15. The Staphyloccous aureus Eap protein activates expression of proinflammatory cytokines.

    Science.gov (United States)

    Scriba, Thomas J; Sierro, Sophie; Brown, Eric L; Phillips, Rodney E; Sewell, Andrew K; Massey, Ruth C

    2008-05-01

    The extracellular adhesion protein (Eap) secreted by the major human pathogen Staphylococcus aureus is known to have several effects on human immunity. We have recently added to knowledge of these roles by demonstrating that Eap enhances interactions between major histocompatibility complex molecules and human leukocytes. Several studies have indicated that Eap can induce cytokine production by human peripheral blood mononuclear cells (PBMCs). To date, there has been no rigorous attempt to identify the breadth of cytokines produced by Eap stimulation or to identify the cell subsets that respond. Here, we demonstrate that Eap induces the secretion of the proinflammatory cytokines interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) by CD14(+) leukocytes (monocytes and macrophages) within direct ex vivo PBMC populations (note that granulocytes are also CD14(+) but are largely depleted from PBMC preparations). Anti-intercellular adhesion molecule 1 (CD54) antibodies inhibited this induction and implicated a role for this known Eap binding protein in cellular activation. IL-6 and TNF-alpha secretion by murine cells exposed to Eap was also observed. The activation of CD14(+) cells by Eap suggests that it could play a significant role in both septic shock and fever, two of the major pathological features of S. aureus infections.

  16. Histone deacetylase 3 supports endochondral bone formation by controlling cytokine signaling and matrix remodeling

    Science.gov (United States)

    Carpio, Lomeli R.; Bradley, Elizabeth W.; McGee-Lawrence, Meghan E.; Weivoda, Megan M.; Poston, Daniel D.; Dudakovic, Amel; Xu, Ming; Tchkonia, Tamar; Kirkland, James L.; van Wijnen, Andre J.; Oursler, Merry Jo; Westendorf, Jennifer J.

    2017-01-01

    Histone deacetylase (HDAC) inhibitors are efficacious epigenetic-based therapies for some cancers and neurological disorders; however, each of these drugs inhibits multiple HDACs and has detrimental effects on the skeleton. To better understand how HDAC inhibitors affect endochondral bone formation, we conditionally deleted one of their targets, Hdac3, pre- and postnatally in type II collagen α1 (Col2α1)–expressing chondrocytes. Embryonic deletion was lethal, but postnatal deletion of Hdac3 delayed secondary ossification center formation, altered maturation of growth plate chondrocytes, and increased osteoclast activity in the primary spongiosa. HDAC3-deficient chondrocytes exhibited increased expression of cytokine and matrix-degrading genes (Il-6, Mmp3, Mmp13, and Saa3) and a reduced abundance of genes related to extracellular matrix production, bone development, and ossification (Acan, Col2a1, Ihh, and Col10a1). Histone acetylation increased at and near genes that had increased expression. The acetylation and activation of nuclear factor κB (NF-κB) were also increased in HDAC3-deficient chondrocytes. Increased cytokine signaling promoted autocrine activation of Janus kinase (JAK)–signal transducer and activator of transcription (STAT) and NF-κB pathways to suppress chondrocyte maturation, as well as paracrine activation of osteoclasts and bone resorption. Blockade of interleukin-6 (IL-6)–JAK–STAT signaling, NF-κB signaling, and bromodomain extraterminal proteins, which recognize acetylated lysines and promote transcriptional elongation, significantly reduced Il-6 and Mmp13 expression in HDAC3-deficient chondrocytes and secondary activation in osteoclasts. The JAK inhibitor ruxolitinib also reduced osteoclast activity in Hdac3 conditional knockout mice. Thus, HDAC3 controls the temporal and spatial expression of tissue-remodeling genes and inflammatory responses in chondrocytes to ensure proper endochondral ossification during development. PMID

  17. Cytokine profile and lymphocyte subsets in type 2 diabetes

    Directory of Open Access Journals (Sweden)

    C.O. Francisco

    2016-01-01

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

  18. Aqueous proinflammatory cytokines in acute primary angle-closure eyes

    Directory of Open Access Journals (Sweden)

    Yao-Ming Liu

    2017-05-01

    Full Text Available AIM: To evaluate changes of proinflammatory cytokines in aqueous humor of patients with acute primary angle-closure (APAC and age-related cataracts. METHODS: Twenty eyes of 20 APAC patients and 15 eyes of 15 age-related cataract patients were included in this cross-sectional study. Aqueous humor samples were collected prospectively. The levels of 20 proinflammatory cytokines were evaluated in the aqueous humor of the APAC and cataract patients using the multiplex bead immunoassay technique. Clinical data were collected for correlation analysis. RESULTS: Seven of the 20 proinflammatory cytokines included in the magnetic bead panel were detectable in both APAC eyes and cataract eyes: interleukin (IL-10, IL-12, IL-15, IL-21, IL-6, chemokine (C-C motif ligand 20, and tumor necrosis factor alpha (TNF-α. IL-27 was only detectable in APAC eyes. Compared with the cataract eyes, the APAC eyes had significantly elevated concentrations of IL-12 (P=0.036, IL-15 (P=0.001, IL-6 (P=0.012, and IL-27 (only detectable in APAC eyes. Age was positively correlated with IL-12 (P=0.022 and IL-6 (P=0.037, and time elapsed between APAC onset and aqueous humor samples collection was positively correlated with IL-15 (P=0.037, IL-27 (P=0.040, and TNF-α (P=0.042. CONCLUSION: Several proinflammatory cytokines including IL-12,IL-15, IL-6 and IL-27, were elevated in the APAC eyes and may be implicated in its pathologic mechanism.

  19. Peripheral blood cytokine and chemokine profiles in juvenile localized scleroderma

    Science.gov (United States)

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

    2015-01-01

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

  20. Differential Serum Cytokine Levels and Risk of Lung Cancer between African and European Americans

    Science.gov (United States)

    Pine, Sharon R.; Mechanic, Leah E.; Enewold, Lindsey; Bowman, Elise D.; Ryan, Bríd M.; Cote, Michele L.; Wenzlaff, Angela S.; Loffredo, Christopher A.; Olivo-Marston, Susan; Chaturvedi, Anil; Caporaso, Neil E.; Schwartz, Ann G.; Harris, Curtis C.

    2015-01-01

    Background African Americans have a higher risk of developing lung cancer than European Americans. Previous studies suggested that certain circulating cytokines were associated with lung cancer. We hypothesized that variations in serum cytokine levels exist between African Americans and European Americans, and increased circulating cytokine levels contribute to lung cancer differently in the two races. Methods Differences in ten serum cytokine levels, interleukin (IL)-1β, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, granulocyte macrophage colony-stimulating factor (GMCSF), interferon (IFN)-γ and tumor necrosis factor (TNF)-α between 170 African-American and 296 European-American controls from the National Cancer Institute-Maryland (NCI-MD) case-control study were assessed. Associations of the serum cytokine levels with lung cancer were analyzed. Statistically significant results were replicated in the prospective Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial and the Wayne State University (WSU) Karmanos Cancer Institute case-control study. Results Six cytokines: IL-4, IL-5, IL-8, IL-10, IFNγ, and TNFα, were significantly higher among European-American as compared to African-American controls. Elevated IL-6 and IL-8 levels were associated with lung cancer among both races in all three studies. Elevated IL-1β, IL-10 and TNFα levels were associated with lung cancer only among African Americans. The association between elevated TNFα levels and lung cancer among European Americans was significant after adjustment for additional factors. Conclusions Serum cytokine levels vary by race and might contribute to lung cancer differently between African Americans and European Americans. Impact Future work examining risk prediction models of lung cancer can measure circulating cytokines to accurately characterize risk within racial groups. PMID:26711330

  1. Salivary cytokine levels in early gingival inflammation

    DEFF Research Database (Denmark)

    Belstrøm, Daniel; Damgaard, Christian; Könönen, Eija

    2017-01-01

    Salivary protein levels have been studied in periodontitis. However, there is lack of information on salivary cytokine levels in early gingival inflammation. The aim of this study was to determine salivary levels of vascular endothelial growth factor (VEGF), interleukin (IL)-8, monocyte chemoattr......Salivary protein levels have been studied in periodontitis. However, there is lack of information on salivary cytokine levels in early gingival inflammation. The aim of this study was to determine salivary levels of vascular endothelial growth factor (VEGF), interleukin (IL)-8, monocyte...

  2. Proinflammatory Cytokines as Regulators of Vaginal Microbiota.

    Science.gov (United States)

    Kremleva, E A; Sgibnev, A V

    2016-11-01

    It was shown that IL-1β, IL-8, and IL-6 in concentrations similar to those in the vagina of healthy women stimulated the growth of normal microflora (Lactobacillus spp.) and suppressed the growth and biofilm production by S. aureus and E. coli. On the contrary, these cytokines in higher concentrations typical of vaginal dysbiosis suppressed normal microflora and stimulated the growth of opportunistic microorganisms. TGF-β1 in both doses produced a stimulating effects on study vaginal microsymbionts. It is hypothesized that pro-inflammatory cytokines serve as the molecules of interspecies communication coordinating the interactions of all components of the vaginal symbiotic system.

  3. Design and methods of the Echo WISELY (Will Inappropriate Scenarios for Echocardiography Lessen SignificantlY) study: An investigator-blinded randomized controlled trial of education and feedback intervention to reduce inappropriate echocardiograms.

    Science.gov (United States)

    Bhatia, R Sacha; Ivers, Noah; Yin, Cindy X; Myers, Dorothy; Nesbitt, Gillian; Edwards, Jeremy; Yared, Kibar; Wadhera, Rishi; Wu, Justina C; Wong, Brian; Hansen, Mark; Weinerman, Adina; Shadowitz, Steven; Johri, Amer; Farkouh, Michael; Thavendiranathan, Paaladinesh; Udell, Jacob A; Rambihar, Sherryn; Chow, Chi-Ming; Hall, Judith; Thorpe, Kevin E; Rakowski, Harry; Weiner, Rory B

    2015-08-01

    Appropriate use criteria (AUC) for transthoracic echocardiography (TTE) were developed to address concerns regarding inappropriate use of TTE. A previous pilot study suggests that an educational and feedback intervention can reduce inappropriate TTEs ordered by physicians in training. It is unknown if this type of intervention will be effective when targeted at attending level physicians in a variety of clinical settings. The aim of this international, multicenter study is to evaluate the hypothesis that an AUC-based educational and feedback intervention will reduce the proportion of inappropriate echocardiograms ordered by attending physicians in the ambulatory environment. In an ongoing multicentered, investigator-blinded, randomized controlled trial across Canada and the United States, cardiologists and primary care physicians practicing in the ambulatory setting will be enrolled. The intervention arm will receive (1) a lecture outlining the AUC and most recent available evidence highlighting appropriate use of TTE, (2) access to the American Society of Echocardiography mobile phone app, and (3) individualized feedback reports e-mailed monthly summarizing TTE ordering behavior including information on inappropriate TTEs and brief explanations of the inappropriate designation. The control group will receive no education on TTE appropriate use and order TTEs as usual practice. The Echo WISELY (Will Inappropriate Scenarios for Echocardiography Lessen Significantly in an education RCT) study is the first multicenter randomized trial of an AUC-based educational intervention. The study will examine whether an education and feedback intervention will reduce the rate of outpatient inappropriate TTEs ordered by attending level cardiologists and primary care physicians (www.clinicaltrials.gov identifier NCT02038101). Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Violacein Treatment Modulates Acute and Chronic Inflammation through the Suppression of Cytokine Production and Induction of Regulatory T Cells.

    Directory of Open Access Journals (Sweden)

    Liana Verinaud

    Full Text Available Inflammation is a necessary process to control infection. However, exacerbated inflammation, acute or chronic, promotes deleterious effects in the organism. Violacein (viola, a quorum sensing metabolite from the Gram-negative bacterium Chromobacterium violaceum, has been shown to protect mice from malaria and to have beneficial effects on tumors. However, it is not known whether this drug possesses anti-inflammatory activity. In this study, we investigated whether viola administration is able to reduce acute and chronic autoimmune inflammation. For that purpose, C57BL/6 mice were intraperitoneally injected with 1 μg of LPS and were treated with viola (3.5mg/kg via i.p. at the same time-point. Three hours later, the levels of inflammatory cytokines in the sera and phenotypical characterization of leukocytes were determined. Mice treated with viola presented a significant reduction in the production of inflammatory cytokines compared with untreated mice. Interestingly, although viola is a compound derived from bacteria, it did not induce inflammation upon administration to naïve mice. To test whether viola would protect mice from an autoimmune inflammation, Experimental Autoimmune Encephalomyelitis (EAE-inflicted mice were given viola i.p. at disease onset, at the 10th day from immunization. Viola-treated mice developed mild EAE disease in contrast with placebo-treated mice. The frequencies of dendritic cells and macrophages were unaltered in EAE mice treated with viola. However, the sole administration of viola augmented the levels of splenic regulatory T cells (CD4+Foxp3+. We also found that adoptive transfer of viola-elicited regulatory T cells significantly reduced EAE. Our study shows, for the first time, that violacein is able to modulate acute and chronic inflammation. Amelioration relied in suppression of cytokine production (in acute inflammation and stimulation of regulatory T cells (in chronic inflammation. New studies must be

  5. Systemic and Local Cytokine Profile following Spinal Cord Injury in Rats: A Multiplex Analysis

    Directory of Open Access Journals (Sweden)

    Yana O. Mukhamedshina

    2017-10-01

    Full Text Available Our study of the changes in cytokine profile in blood serum and in the spinal cord after traumatic spinal cord injury (SCI has shown that an inflammatory reaction and immunological response are not limited to the CNS, but widespread. This fact was confirmed by changes detected in a cytokine profile in blood serum samples [MIP-1α, interleukin 1 (IL-1 α, IL-2, IL-5, IL-1β, MCP-1, RANTES]. There were also changes in the levels of MIP-1α, IL-1α, IL-2, IL-5, IL-18, GM-colony-stimulating factor, IL-17α, IFN-γ, IL-10, IL-13, MCP-1, and GRO KC CINC-1 in samples of the rat injured spinal cord. The results underscore the complex cytokine network imbalance exhibited after SCI and show significant changes in the concentrations of 14 cytokines/chemokines with different inflammatory and immunological activities.

  6. The effect of garlic tablet on pro-inflammatory cytokines in postmenopausal osteoporotic women: a randomized controlled clinical trial.

    Science.gov (United States)

    Mozaffari-Khosravi, Hassan; Hesabgar, Hamideh-al-Sadat; Owlia, Mohammad-Bagher; Hadinedoushan, Hossein; Barzegar, Kazem; Fllahzadeh, Mohammad Hossein

    2012-12-01

    Menopause is one of the important causes of osteoporosis which results from estrogen deficiency. In addition, some clinical and experimental evidence indicates that there is an association between increasing pro-inflammatory cytokine activity and postmenopausal bone loss. The purpose of this study was to determine the effect of garlic tablet on pro-inflammatory cytokines in postmenopausal osteoporotic women. The present study was a double-blind randomized controlled clinical trial in Yazd conducted during November 2009 until July 2010. The sample included 44 postmenopausal osteoporotic women who were randomly assigned into two groups: the garlic group (GG) and the placebo group (PG). Participants in GG took two garlic tablets daily for 1 month and the participants in PG took placebo tablets in the same manner. Serum interlukin-1, interlukin-6, and tumor necrosis factor alpha (TNF-α) were measured using the ELISA method before and after the intervention. Also, 24-hour dietary recall was recorded for estimation of daily intake of some nutrients. Data were analyzed using SPSS software. There was no statistically significant difference between interlukin-1 and interlukin-6 in the two groups before and after the intervention. The mean of TNF-α did not show any statistically significant difference between the two groups before and after the intervention, but it was significantly reduced by about 47% (from 31.14±50.53 to 19.33±22.19 ng/ml, P-value = 0.05) in GG after the intervention, However, no significant difference was seen in PG. The present study produced some evidence for an immunomodulatory effect of garlic, as well as the modulation of cytokine production.

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

    Science.gov (United States)

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

    2018-05-15

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

  8. Early induction of cytokines/cytokine receptors and Cox2, and activation of NF-κB in 4-nitroquinoline 1-oxide-induced murine oral cancer model

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Yu-Ching [Department of Medical Research, China Medical University Hospital, Taichung 404, Taiwan (China); Department of Veterinary Medicine, National Chung Hsing University, Taichung 402, Taiwan (China); Ho, Heng-Chien; Lee, Miau-Rong [Department of Biochemistry, China Medical University, Taichung 404, Taiwan (China); Lai, Kuang-Chi [Department of Surgery, China Medical University Beigang Hospital, Yunlin 651, Taiwan (China); School of Medicine, China Medical University, Taichung 404, Taiwan (China); Yeh, Chung-Min; Lin, Yueh-Min [Department of Pathology, Changhua Christian Hospital, Changhua 500, Taiwan (China); Ho, Tin-Yun [School of Chinese Medicine, China Medical University, Taichung 404, Taiwan (China); Hsiang, Chien-Yun, E-mail: cyhsiang@mail.cmu.edu.tw [Department of Microbiology, China Medical University, Taichung 404, Taiwan (China); Chung, Jing-Gung, E-mail: jgchung@mail.cmu.edu.tw [Department of Biological Science and Technology, China Medical University, Taichung 404, Taiwan (China); Department of Biotechnology, Asia University, Taichung 413, Taiwan (China)

    2012-07-15

    The purpose of this study was to identify the genes induced early in murine oral carcinogenesis. Murine tongue tumors induced by the carcinogen, 4-nitroquinoline 1-oxide (4-NQO), and paired non-tumor tissues were subjected to microarray analysis. Hierarchical clustering of upregulated genes in the tumor tissues revealed an association of induced genes with inflammation. Cytokines/cytokine receptors induced early were subsequently identified, clearly indicating their involvement in oral carcinogenesis. Hierarchical clustering also showed that cytokine-mediated inflammation was possibly linked with Mapk6. Cox2 exhibited the greatest extent (9–18 fold) of induction in the microarray data, and its early induction was observed in a 2 h painting experiment by RT-PCR. MetaCore analysis showed that overexpressed Cox2 may interact with p53 and transcriptionally inhibit expression of several downstream genes. A painting experiment in transgenic mice also demonstrated that NF-κB activates early independently of Cox2 induction. MetaCore analysis revealed the most striking metabolic alterations in tumor tissues, especially in lipid metabolism resulting from the reduction of Pparα and Rxrg. Reduced expression of Mapk12 was noted, and MetaCore analysis established its relationship with decreased efficiency of Pparα phosphorylation. In conclusion, in addition to cytokines/cytokine receptors, the early induction of Cox2 and NF-κB activation is involved in murine oral carcinogenesis.

  9. Early induction of cytokines/cytokine receptors and Cox2, and activation of NF-κB in 4-nitroquinoline 1-oxide-induced murine oral cancer model

    International Nuclear Information System (INIS)

    Liu, Yu-Ching; Ho, Heng-Chien; Lee, Miau-Rong; Lai, Kuang-Chi; Yeh, Chung-Min; Lin, Yueh-Min; Ho, Tin-Yun; Hsiang, Chien-Yun; Chung, Jing-Gung

    2012-01-01

    The purpose of this study was to identify the genes induced early in murine oral carcinogenesis. Murine tongue tumors induced by the carcinogen, 4-nitroquinoline 1-oxide (4-NQO), and paired non-tumor tissues were subjected to microarray analysis. Hierarchical clustering of upregulated genes in the tumor tissues revealed an association of induced genes with inflammation. Cytokines/cytokine receptors induced early were subsequently identified, clearly indicating their involvement in oral carcinogenesis. Hierarchical clustering also showed that cytokine-mediated inflammation was possibly linked with Mapk6. Cox2 exhibited the greatest extent (9–18 fold) of induction in the microarray data, and its early induction was observed in a 2 h painting experiment by RT-PCR. MetaCore analysis showed that overexpressed Cox2 may interact with p53 and transcriptionally inhibit expression of several downstream genes. A painting experiment in transgenic mice also demonstrated that NF-κB activates early independently of Cox2 induction. MetaCore analysis revealed the most striking metabolic alterations in tumor tissues, especially in lipid metabolism resulting from the reduction of Pparα and Rxrg. Reduced expression of Mapk12 was noted, and MetaCore analysis established its relationship with decreased efficiency of Pparα phosphorylation. In conclusion, in addition to cytokines/cytokine receptors, the early induction of Cox2 and NF-κB activation is involved in murine oral carcinogenesis.

  10. Malassezia Yeast and Cytokine Gene Polymorphism in Atopic Dermatitis.

    Science.gov (United States)

    Jain, Charu; Das, Shukla; Ramachandran, V G; Saha, Rumpa; Bhattacharya, S N; Dar, Sajad

    2017-03-01

    Atopic Dermatitis (AD) is a recurrent chronic condition associated with microorganism and their interaction with the susceptible host. Malassezia yeast is a known commensal which is thought to provoke the recurrent episodes of symptoms in atopic dermatitis patients. Malassezia immunomodulatory properties along with defective skin barrier in such host, results in disease manifestation. Here, we studied Single Nucleotide Polymorphism (SNP) in IL10 and IFN γ genes of the host and its relation with susceptibility to Malassezia infection. To isolate Malassezia yeast from AD patients and compare the genetic susceptibility of the host by correlating the cytokine gene polymorphism with the control subjects. Study was conducted from January 2012 to January 2013. It was a prospective observational study done in Department of Microbiology and Department of Dermatology and Venereology in University College of Medical Sciences and GTB Hospital, Delhi. Sample size comprised of 38 cases each of AD. Skin scrapings were used for fungal culture on Sabouraud Dextrose Agar (SDA) and Modified Dixon Agar (MDA) and isolated were identified as per conventional phenotypic methods. Genomic DNA was extracted from blood samples collected from all study subjects. Cytokine genotyping was carried out by Amplification Refractory Mutations System- Polymerase Chain Reaction (ARMS-PCR) with sequence specific primers. Three SNPs (IL10-1082A/G; IL10-819/592C/T; IFN-γ+874A/T) in two cytokine genes were assessed in all the patients and healthy controls. Chi-Square Test or Fisher's-Exact Test and Bonferroni's correction. In AD group, Malassezia yeasts were cultured in 24 out of 38 samples and thus the identification rate was 63.1 percent as compared to healthy group, 52.6 percent (20/38). Significant difference in allele, or genotype distribution were observed in IL10-819/592C/T and IFN-γ+874A/T gene polymorphism in AD group. Higher isolation rate in cases as compared to control group highlights the

  11. Two novel functions of hyaluronidase from Streptococcus agalactiae are enhanced intracellular survival and inhibition of proinflammatory cytokine expression.

    Science.gov (United States)

    Wang, Zhaofei; Guo, Changming; Xu, Yannan; Liu, Guangjin; Lu, Chengping; Liu, Yongjie

    2014-06-01

    Streptococcus agalactiae is the causative agent of septicemia and meningitis in fish. Previous studies have shown that hyaluronidase (Hyl) is an important virulence factor in many Gram-positive bacteria. To investigate the role of S. agalactiae Hyl during interaction with macrophages, we inactivated the gene encoding extracellular hyaluronidase, hylB, in a clinical Hyl(+) isolate. The isogenic hylb mutant (Δhylb) displayed reduced survival in macrophages compared to the wild type and stimulated a significantly higher release of proinflammatory cytokines, such as interleukin-1β (IL-1β), IL-6, and tumor necrosis factor alpha (TNF-α), than the wild type in macrophages as well as in mice. Furthermore, only Hyl(+) strains could grow utilizing hyaluronic acid (HA) as the sole carbon source, suggesting that Hyl permits the organism to utilize host HA as an energy source. Fifty percent lethal dose (LD50) determinations in zebrafish demonstrated that the hylb mutant was highly attenuated relative to the wild-type strain. Experimental infection of BALB/c mice revealed that bacterial loads in the blood, spleen, and brain at 16 h postinfection were significantly reduced in the ΔhylB mutant compared to those in wild-type-infected mice. In conclusion, hyaluronidase has a strong influence on the intracellular survival of S. agalactiae and proinflammatory cytokine expression, suggesting that it plays a key role in S. agalactiae pathogenicity.

  12. Inhibition of Pro-inflammatory Mediators and Cytokines by Chlorella Vulgaris Extracts.

    Science.gov (United States)

    Sibi, G; Rabina, Santa

    2016-01-01

    The aim of this study was to determine the in vitro anti-inflammatory activities of solvent fractions from Chlorella vulgaris by inhibiting the production of pro-inflammatory mediators and cytokines. Methanolic extracts (80%) of C. vulgaris were prepared and partitioned with solvents of increasing polarity viz., n-hexane, chloroform, ethanol, and water. Various concentrations of the fractions were tested for cytotoxicity in RAW 264.7 cells using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, and the concentrations inducing cell growth inhibition by about 50% (IC50) were chosen for further studies. Lipopolysaccharide (LPS) stimulated RAW 264.7 cells were treated with varying concentrations of C. vulgaris fractions and examined for its effects on nitric oxide (NO) production by Griess assay. The release of prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), and interleukin 6 (IL-6) were quantified using enzyme-linked immunosorbent assay using Celecoxib and polymyxin B as positive controls. MTT assay revealed all the solvent fractions that inhibited cell growth in a dose-dependent manner. Of all the extracts, 80% methanolic extract exhibited the strongest anti-inflammatory activity by inhibiting NO production (P < 0.01), PGE2 (P < 0.05), TNF-α, and IL-6 (P < 0.001) release in LPS induced RAW 264.7 cells. Both hexane and chloroform fractions recorded a significant (P < 0.05) and dose-dependent inhibition of LPS induced inflammatory mediators and cytokines in vitro. The anti-inflammatory effect of ethanol and aqueous extracts was not significant in the study. The significant inhibition of inflammatory mediators and cytokines by fractions from C. vulgaris suggests that this microalga would be a potential source of developing anti-inflammatory agents and a good alternate for conventional steroidal and nonsteroidal anti-inflammatory drugs. C. vulgaris extracts have potential anti-inflammatory activitySolvent extraction using methanol

  13. Current status and challenges of cytokine pharmacology

    Czech Academy of Sciences Publication Activity Database

    Zídek, Zdeněk; Anzenbacher, P.; Kmoníčková, Eva

    2009-01-01

    Roč. 157, č. 3 (2009), s. 342-361 ISSN 0007-1188 R&D Projects: GA ČR GA305/08/0535; GA MŠk 1M0508 Institutional research plan: CEZ:AV0Z50390512 Keywords : cytokines * immunotherapy * immunopharmacology Subject RIV: FR - Pharmacology ; Medidal Chemistry Impact factor: 5.204, year: 2009

  14. 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...

  15. Cytokines in Sjögren's syndrome

    NARCIS (Netherlands)

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

    2009-01-01

    Cytokines play a central role in the regulation of immunity and are often found to be deregulated in autoimmune diseases. Sjögren'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

  16. Cytokine gene expression of peripheral blood lymphocytes ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-03-20

    Mar 20, 2009 ... Key words: Lipopolysaccharide, lymphocytes, TLRs, cytokines. INTRODUCTION. Lipopolysaccharide (LPS), a predominant glycolipid in the outer membranes of Gam-negative bacteria, stimulates monocyte, macrophages, and neutrophils and increase expression of cell adhesion molecules (Trent et al., ...

  17. Cytokines in atherosclerosis: an intricate balance

    NARCIS (Netherlands)

    Boshuizen, M.C.S.

    2016-01-01

    Atherosclerosis is the underlying pathology in the majority of clinical manifestations of cardiovascular diseases, which are nowadays the main global cause of mortality. Atherosclerosis is a lipid-driven chronic inflammatory disease of the arterial wall. This inflammatory response, with cytokines as

  18. Cytokines as biomarkers of nanoparticle immunotoxicity.

    Science.gov (United States)

    Elsabahy, Mahmoud; Wooley, Karen L

    2013-06-21

    Nanoscale objects, whether of biologic origin or synthetically created, are being developed into devices for a variety of bionanotechnology diagnostic and pharmaceutical applications. However, the potential immunotoxicity of these nanomaterials and mechanisms by which they may induce adverse reactions have not received sufficient attention. Nanomaterials, depending on their characteristics and compositions, can interact with the immune system in several ways and either enhance or suppress immune system function. Cytokines perform pleiotropic functions to mediate and regulate the immune response and are generally recognized as biomarkers of immunotoxicity. While the specificity and validity of certain cytokines as markers of adverse immune response has been established for chemicals, small and macromolecular drugs, research on their applicability for predicting and monitoring the immunotoxicity of engineered nanomaterials is still ongoing. The goal of this review is to provide guidelines as to important cytokines that can be utilized for evaluating the immunotoxicity of nanomaterials and to highlight the role of those cytokines in mediating adverse reactions, which is of particular importance for the clinical development of nanopharmaceuticals and other nanotechnology-based products. Importantly, the rational design of nanomaterials of low immunotoxicity will be discussed, focusing on synthetic nanodevices, with emphasis on both the nanoparticle-forming materials and the embedded cargoes.

  19. Cytokine Gene Expression in Response to SnSAG1 in Horses with Equine Protozoal Myeloencephalitis

    Science.gov (United States)

    Spencer, Jennifer A.; Deinnocentes, Patricia; Moyana, Edith M.; Guarino, Anthony J.; Ellison, Siobhan E.; Bird, R. Curtis; Blagburn, Byron L.

    2005-01-01

    Equine protozoal myeloencephalitis (EPM) is a neurologic syndrome seen in horses from the Americas and is mainly caused by Sarcocystis neurona. Recently, a 29-kDa surface antigen from S. neurona merozoites was identified as being highly immunodominant on a Western blot. This antigen has been sequenced and cloned, and the expressed protein has been named SnSAG1. In a previous study, cell-mediated immune responses to SnSAG1 were shown to be statistically significantly reduced in horses with EPM in comparison to EPM-negative control horses. It therefore appears as though the parasite is able to induce immunosuppression towards parasite-derived antigens as parasite-specific responses are decreased. Isolated peripheral blood lymphocytes from 21 EPM (cerebrospinal fluid [CSF] Western blot)-negative horses with no clinical signs and 21 horses with clinical signs of EPM (CSF Western blot positive) were cocultured with SnSAG1 for 48 and 72 h, and the effect on cytokine production was investigated by means of reverse transcriptase PCR. Cytokines assayed include gamma interferon (IFN-γ), tumor necrosis factor alpha, interleukin (IL)-2, IL-4, and IL-6. β-Actin was used as the housekeeping gene. A Wilcoxon signed-rank test of the findings indicated that there was a statistically significant decrease in IFN-γ production after 48 h in culture for samples from horses with clinical disease. There was also a statistically significant increase in IL-4 production after 72 h in culture for samples from horses with EPM. These results further support the notion that this parasite is able to subvert the immune system in horses with clinical disease. PMID:15879026

  20. Curcumin mitigates lithium-induced thyroid dysfunction by modulating antioxidant status, apoptosis and inflammatory cytokines

    Directory of Open Access Journals (Sweden)

    Sanaa M. Abd El-Twab

    2016-08-01

    Full Text Available Lithium is an integral drug used in the management of acute mania, unipolar and bipolar depression and prophylaxis of bipolar disorders. It has also been shown to reduce suicidal risk and short term mortality. Few experimental studies have demonstrated the thyroid toxicity caused by lithium as well as the possible protective effect of curcumin. Twenty four male albino rats were divided into three groups; group I (control group, group II received lithium carbonate daily for 6 weeks and group III received the same dose of lithium carbonate as group II concomitantly with curcumin for 6 weeks. The specimens were prepared for histopathological, immunohistochemical and biochemical examination. Lithium-induced thyroid dysfunction evidenced by the histopathological and immunohistochemical changes represented by detached cells and vacuolated cytoplasm of some follicular cells and highly significant increase in positive immunostained of thyroglobulin and caspase-3 respectively. Moreover, a significant decrease in serum free triiodothyonine (FT3, free thyroxine (FT4 concomitant with significantly increased thyroid stimulating hormone (TSH and pro-inflammatory cytokines, and thyroid lipid peroxidation (MDA and nitric oxide (NO levels. Curcumin counteracted lithium-induced oxidative stress and inflammation as assessed by restoration of the antioxidant defenses and diminishing of pro-inflammatory cytokines and improvements in the degenerative changes of the thyroid gland. In conclusion, the present study provides evidence that curcumin exerts thyroprotective effects against lithium carbonate mediated by its antioxidant, anti-inflammatory and anti-apoptotic effect as indicated by caspase-3. This report also confers that the use of this drug should be justified for long treatment under direct medical supervision.

  1. Longer period of oral administration of aspartame on cytokine response in Wistar albino rats.

    Science.gov (United States)

    Choudhary, Arbind Kumar; Sheela Devi, Rathinasamy

    2015-03-01

    Aspartame is a non-nutritive sweetener particularly used in 'diet' and 'low calorie' products and also in a variety of foods, drugs and hygiene products. Aspartame is metabolized by gut esterases and peptidases to three common chemicals: the amino acids, aspartic acid and phenylalanine, and small amounts of methanol. The aim of the present study was to assess potential changes in molecular mediators of aspartame as a chemical stressor in rats. The effects of long-term administration of aspartame (40 mg/kg body weight/day) were tested in Wistar Albino rats. The treatment effects were assessed in different conditions, including control groups. After 90 days of treatment, circulating concentrations of different parameters were assessed: corticosterone, lipid peroxidation, antioxidant activity, nitric oxide, reduced glutathione and cytokines (interleukin 2, interleukin 4, tumor necrosis factor-α and interferon-γ). The results show that there was a significant increase in plasma corticosterone, serum lipid peroxidation and nitric oxide level along with a decrease in enzymatic and non-enzymatic antioxidant as well as significant decrease in interleukin 2, tumor necrosis factor-α and interferon-γ. There was also a significant increase in interleukin 4 irrespective of whether the animals were immunized or not. The findings clearly point out that aspartame acts as a chemical stressor because of increased corticosterone level and increased lipid peroxidation and nitric oxide level induce generation of free radicals in serum which may be the reason for variation of cytokine level and finally results in alteration of immune function. Aspartame metabolite methanol or formaldehyde may be the causative factors behind the changes observed. Copyright © 2014 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

  2. Neuropathic pain and cytokines: current perspectives

    Directory of Open Access Journals (Sweden)

    Clark AK

    2013-11-01

    Full Text Available Anna K Clark, Elizabeth A Old, Marzia Malcangio Wolfson Centre for Age Related Diseases, King's College London, London, UK Abstract: Neuropathic pain represents a major problem in clinical medicine because it causes debilitating suffering and is largely resistant to currently available analgesics. A characteristic of neuropathic pain is abnormal response to somatic sensory stimulation. Thus, patients suffering peripheral neuropathies may experience pain caused by stimuli which are normally nonpainful, such as simple touching of the skin or by changes in temperature, as well as exaggerated responses to noxious stimuli. Convincing evidence suggests that this hypersensitivity is the result of pain remaining centralized. In particular, at the first pain synapse in the dorsal horn of the spinal cord, the gain of neurons is increased and neurons begin to be activated by innocuous inputs. In recent years, it has become appreciated that a remote damage in the peripheral nervous system results in neuronal plasticity and changes in microglial and astrocyte activity, as well as infiltration of macrophages and T cells, which all contribute to central sensitization. Specifically, the release of pronociceptive factors such as cytokines and chemokines from neurons and non-neuronal cells can sensitize neurons of the first pain synapse. In this article we review the current evidence for the role of cytokines in mediating spinal neuron–non-neuronal cell communication in neuropathic pain mechanisms following peripheral nerve injury. Specific and selective control of cytokine-mediated neuronal–glia interactions results in attenuation of the hypersensitivity to both noxious and innocuous stimuli observed in neuropathic pain models, and may represent an avenue for future therapeutic intervention. Keywords: anti-inflammatory cytokines, proinflammatory cytokines, microglia, astrocytes, first pain synapse

  3. Left-colon water exchange preserves the benefits of whole colon water exchange at reduced cecal intubation time conferring significant advantage in diagnostic colonoscopy - a prospective, randomized controlled trial.

    Science.gov (United States)

    Wang, Xiangping; Luo, Hui; Xiang, Yi; Leung, Felix W; Wang, Limei; Zhang, Linhui; Liu, Zhiguo; Wu, Kaichun; Fan, Daiming; Pan, Yanglin; Guo, Xuegang

    2015-07-01

    Whole-colon water exchange (WWE) reduces insertion pain, increases cecal intubation success and adenoma detection rate, but requires longer insertion time, compared to air insufflation (AI) colonoscopy. We hypothesized that water exchange limited to the left colon (LWE) can speed up insertion with equivalent results. This prospective, randomized controlled study (NCT01735266) allocated patients (18-80 years) to WWE, LWE or AI group (1:1:1). The primary outcome was cecal intubation time. Three hundred subjects were randomized to the WWE (n = 100), LWE (n = 100) or AI group (n = 100). Ninety-four to ninety-five per cent of patients underwent diagnostic colonoscopy. Baseline characteristics were balanced. The median insertion time was shorter in LWE group (4.8 min (95%CI: 3.2-6.2)) than those in WWE (7.5 min (95%CI: 6.0-10.3)) and AI (6.4 min (95%CI: 4.2-9.8)) (both p rates in unsedated patients of the two water exchange methods (WWE 99%, LWE 99%) were significantly higher than that (89.8%) in AI group (p = 0.01). The final success rates were comparable among the three groups after sedation was given. Maximum pain scores and number of patients needing abdominal compression between WWE and LWE groups were comparable, both lower than those in AI group (p higher in WWE group. By preserving the benefits of WWE and reducing insertion time, LWE is appropriate for diagnostic colonoscopy, especially in settings with tight scheduling of patients. The higher PDR in the right colon in WWE group deserves to be further investigated.

  4. Cytokines and depression in cancer patients and caregivers

    Directory of Open Access Journals (Sweden)

    Li M

    2017-11-01

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

  5. Cytokine Gene Polymorphisms in Egyptian Cases with Brain Tumors

    International Nuclear Information System (INIS)

    Badr El-Din, N.K.; Abdel-Hady, E.K.; Salem, F.K.; Settin, A.; ALI, N.

    2009-01-01

    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.

  6. Polybrominated diphenyl ethers enhance the production of proinflammatory cytokines by the placenta.

    Science.gov (United States)

    Peltier, M R; Klimova, N G; Arita, Y; Gurzenda, E M; Murthy, A; Chawala, K; Lerner, V; Richardson, J; Hanna, N

    2012-09-01

    Polybrominated diphenyl ether(s) (PBDE) are ubiquitous environmental contaminants that bind and cross the placenta but their effects on pregnancy outcome are unclear. It is possible that environmental contaminants increase the risk of inflammation-mediated pregnancy complications such as preterm birth by promoting a proinflammatory environment at the maternal-fetal interface. We hypothesized that PBDE would reduce IL-10 production and enhance the production of proinflammatory cytokines associated with preterm labor/birth by placental explants. Second-trimester placental explants were cultured in either vehicle (control) or 2 μM PBDE mixture of congers 47, 99 and 100 for 72 h. Cultures were then stimulated with 10(6) CFU/ml heat-killed Escherichia coli for a final 24 h incubation and conditioned medium was harvested for quantification of cytokines and PGE(2). COX-2 content and viability of the treated tissues were then quantified by tissue ELISA and MTT reduction activity, respectively. PBDE pre-treatment reduced E. coli-stimulated IL-10 production and significantly increased E. coli-stimulated IL-1β secretion. PBDE exposure also increased basal and bacteria-stimulated COX-2 expression. Basal, but not bacteria-stimulated PGE(2), was also enhanced by PBDE exposure. No effect of PBDE on viability of the explants cultures was detected. In summary, pre-exposure of placental explants to congers 47, 99, and 100 enhanced the placental proinflammatory response to infection. This may increase the risk of infection-mediated preterm birth by lowering the threshold for bacteria to stimulate a proinflammatory response(s). Copyright © 2012 Elsevier Ltd. All rights reserved.

  7. Effects of nonpathogenic bacteria on cytokine secretion by human intestinal mucosa.

    Science.gov (United States)

    Borruel, Natalia; Casellas, Francesc; Antolín, María; Llopis, Marta; Carol, Monica; Espíin, Eloy; Naval, Javier; Guarner, Francisco; Malagelada, Juan R

    2003-04-01

    The human intestine harbors a complex microbial ecosystem, and the mucosa is the interface between the immune system and the luminal environment. The aim of this study was to elucidate whether host-bacteria interactions influence mucosal cytokine production. Macroscopically normal colonic specimens were obtained at surgery from eight patients with neoplasm, and inflamed ileal specimens were obtained from two patients with Crohn's disease. Mucosal explants were cultured for 24 h with either nonpathogenic Escherichia coli ECOR-26, Lactobacillus casei DN-114 001, L. casei DN-114 056, L. casei ATCC-334, or Lactobacillus bulgaricus LB-10. Each study included blank wells with no bacteria. Tissue and bacteria viability were confirmed by LDH release and culture. Concentration of tumor necrosis factor (TNF)alpha, transforming growth factor beta1, interleukin (IL)-8, and IL-10 was measured in supernatants. In parallel experiments, neutralizing anti-TNFalpha antibody was added to the culture. Co-culture of mucosa with bacteria did not modify LDH release. Co-culture with L. casei strains significantly reduced TNFalpha release, whereas E. coli increased it. These effects were observed both in normal and inflamed mucosa. In combination studies, L. casei DN-114 001 prevented TNFalpha stimulation by E. coli. L. casei DN-114 001 also reduced IL-8 release via a TNFalpha-independent pathway. L. casei DN-114 056 or E. coli increased IL-10 release in the presence of neutralizing anti-TNFalpha. Nonpathogenic bacteria interact with human intestinal mucosa and can induce changes in cytokine production that are strain specific.

  8. Aloe vera downregulates LPS-induced inflammatory cytokine production and expression of NLRP3 inflammasome in human macrophages.

    Science.gov (United States)

    Budai, Marietta M; Varga, Aliz; Milesz, Sándor; Tőzsér, József; Benkő, Szilvia

    2013-12-01

    Aloe vera has been used in traditional herbal medicine as an immunomodulatory agent inducing anti-inflammatory effects. However, its role on the IL-1β inflammatory cytokine production has not been studied. IL-1β production is strictly regulated both at transcriptional and posttranslational levels through the activity of Nlrp3 inflammasome. In this study we aimed to determine the effect of Aloe vera on the molecular mechanisms of Nlrp3 inflammasome-mediated IL-1β production in LPS-activated human THP-1 cells and monocyte-derived macrophages. Our results show that Aloe vera significantly reduced IL-8, TNFα, IL-6 and IL-1β cytokine production in a dose dependent manner. The inhibitory effect was substantially more pronounced in the primary cells. We found that Aloe vera inhibited the expression of pro-IL-1β, Nlrp3, caspase-1 as well as that of the P2X7 receptor in the LPS-induced primary macrophages. Furthermore, LPS-induced activation of signaling pathways like NF-κB, p38, JNK and ERK were inhibited by Aloe vera in these cells. Altogether, we show for the first time that Aloe vera-mediated strong reduction of IL-1β appears to be the consequence of the reduced expression of both pro-IL-1β as well as Nlrp3 inflammasome components via suppressing specific signal transduction pathways. Furthermore, we show that the expression of the ATP sensor P2X7 receptor is also downregulated by Aloe vera that could also contribute to the attenuated IL-1β cytokine secretion. These results may provide a new therapeutic approach to regulate inflammasome-mediated responses. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. ELECTROACUPUNCTURE AT THE WANGU ACUPOINT SUPPRESSES EXPRESSION OF INFLAMMATORY CYTOKINES IN THE HIPPOCAMPUS OF RATS WITH VASCULAR DEMENTIA.

    Science.gov (United States)

    Fang, Yanan; Sui, Rubo

    2016-01-01

    Vascular dementia (VD) is the most frequent psychiatric complication of stroke, and is often difficult to treat. Incidence rate of vascular cognition impairment is still 70% after stroke in one year (Sui R et al.2011). Stroke patients with VD suffer from a higher mortality rate and have worse functional outcomes and quality of life. However, despite the extensive literatures on this topic, there is no agreement on the causal mechanisms and effective therapy for VD. The objective of this study is to examine if electroacupuncture at the Wangu acupoint (GB 12), whose position is similar to the cerebellar fastigial nucleus, could reduce inflammatory cytokines in the hippocampus of rats with vascular dementia (VD). The 54 healthy, male, Sprague-Dawley (SD) rats, 9 months old, and of clean grade (300-450) g, were randomly divided into three groups: sham surgery group, VD group and electro-acupuncture group. The ethology scores of VD rats were evaluated and the mRNA expressions of inflammatory cytokines (TNF-α, IL-6 and IL-1β) in the hippocampus were assessed and the hippocampal tissues were observed by hematoxylin-eosin staining. Compared with the VD group, in the electroacupuncture group, the rats' learning ability improved significantly and the mRNA expression of TNF-α, IL-6 and IL-1β decreased. Simultaneously, the damage extent of nerve cells in the hippocampal tissues decreased, with their morphology recovered to nearly normal. Electro-acupuncture at the Wangu acupoint can decrease the levels of inflammatory cytokines in the hippocampus, reduce the damage extent of nerve cells in the hippocampus, and thus provide a new neuroprotective method in VD.

  10. The role of substrate morphology for the cytokine release profile of immature human primary macrophages

    Energy Technology Data Exchange (ETDEWEB)

    Bartneck, Matthias [Department of Medicine III, Medical Faculty, RWTH Aachen, Pauwelsstr. 30, 52074 Aachen (Germany); Heffels, Karl-Heinz [Department and Chair of Functional Materials in Medicine and Dentistry, University of Würzburg, Pleicherwall 2, 97070 Würzburg (Germany); Bovi, Manfred [Electron Microscopic Facility, Medical Faculty, RWTH Aachen (Germany); Groll, Jürgen [Department and Chair of Functional Materials in Medicine and Dentistry, University of Würzburg, Pleicherwall 2, 97070 Würzburg (Germany); Zwadlo-Klarwasser, Gabriele [Interdisciplinary Center for Clinical Research and Dept. of Dermatology, Medical Faculty, RWTH Aachen, Pauwelsstr. 30, 52056 Aachen (Germany)

    2013-12-01

    There is increasing evidence that the physicochemical nature of any given material is a dominant factor for the release of cytokines by innate immune cells, specifically of macrophages, and thus majorly influences their interaction with other cell types. Recently, we could show that the 3D structure of star shaped polytheylene oxide–polypropylene oxide co-polymers (sP(EO-stat-PO))-hydrogel coated substrates has a stronger influence on the release pattern of cytokines after 7 days of culture than surface chemistry. Here, we focused on the analysis of cytokine release over time and a more detailed analysis of cell morphology by scanning electron microscopy (SEM). Therefore, we compared different strategies for SEM sample preparation and found that using osmium tetroxide combined with aqua bidest led to best preparation results. For cytokine release we show significant changes from day 3 to day 7 of cell culture. After 3 days, the sP(EO-stat-PO)-coated substrates led to an induction of pro-angiogenic CCL3 and CCL4, and of low amounts of the anti-inflammatory IL10, which declined at day 7. In contrast, pleiotropic IL6 and the pro-inflammatory TNFα and IL1β were expressed stronger at day 7 than at day 3. - Highlights: • Strategies for the preparation of macrophages on hydrogel materials (Fig. 1) • Cytokine release of immature macrophages on the substrates (Fig. 2 and Table 1) • Changes in cytokine release during macrophage maturation (Table 2)

  11. The role of substrate morphology for the cytokine release profile of immature human primary macrophages

    International Nuclear Information System (INIS)

    Bartneck, Matthias; Heffels, Karl-Heinz; Bovi, Manfred; Groll, Jürgen; Zwadlo-Klarwasser, Gabriele

    2013-01-01

    There is increasing evidence that the physicochemical nature of any given material is a dominant factor for the release of cytokines by innate immune cells, specifically of macrophages, and thus majorly influences their interaction with other cell types. Recently, we could show that the 3D structure of star shaped polytheylene oxide–polypropylene oxide co-polymers (sP(EO-stat-PO))-hydrogel coated substrates has a stronger influence on the release pattern of cytokines after 7 days of culture than surface chemistry. Here, we focused on the analysis of cytokine release over time and a more detailed analysis of cell morphology by scanning electron microscopy (SEM). Therefore, we compared different strategies for SEM sample preparation and found that using osmium tetroxide combined with aqua bidest led to best preparation results. For cytokine release we show significant changes from day 3 to day 7 of cell culture. After 3 days, the sP(EO-stat-PO)-coated substrates led to an induction of pro-angiogenic CCL3 and CCL4, and of low amounts of the anti-inflammatory IL10, which declined at day 7. In contrast, pleiotropic IL6 and the pro-inflammatory TNFα and IL1β were expressed stronger at day 7 than at day 3. - Highlights: • Strategies for the preparation of macrophages on hydrogel materials (Fig. 1) • Cytokine release of immature macrophages on the substrates (Fig. 2 and Table 1) • Changes in cytokine release during macrophage maturation (Table 2)

  12. 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.

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

    Science.gov (United States)

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

    2017-11-01

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

  14. Role of Cytokines as a Double-edged Sword in Sepsis

    Science.gov (United States)

    CHAUDHRY, HINA; ZHOU, JUHUA; ZHONG, YIN; ALI, MIR MUSTAFA; MCGUIRE, FRANKLIN; NAGARKATTI, PRAKASH S.; NAGARKATTI, MITZI

    2014-01-01

    Background Sepsis is a deadly immunological disorder and its pathophysiology is still poorly understood. We aimed to determine if specific pro-inflammatory and anti-inflammatory cytokines can be used as diagnostic and therapeutic targets for sepsis. Materials and Methods Recent publications in the MEDLINE database were searched for articles regarding the clinical significance of inflammatory cytokines in sepsis. Results In response to pathogen infection, pro-inflammatory cytokines [interleukin-6 (IL-6), IL-8, IL-18 and tumor necrosis factor-α (TNF-α)] and anti-inflammatory cytokine (IL-10) increased in patients with sepsis. Importantly, a decrease in IL-6 was associated with a better prognosis and overproduction of IL-10 was found to be the main predictor of severity and fatal outcome. Conclusion Both pro-inflammatory and anti-inflammatory cytokines constitute a double-edged sword in sepsis; on one hand they are critical to eliminate the infection while on the other, excessive production can cause tissue and organ damage. Increase in cytokines such as IL-6, Il-8, IL-10, IL-18 and TNF-α may have implications in diagnosis and treatment of sepsis. PMID:24292568

  15. Cytokines and Growth Factors Expressed by Human Cutaneous Melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Elias, Elias G., E-mail: george.elias@medstar.net; Hasskamp, Joanne H.; Sharma, Bhuvnesh K. [Maryland Melanoma Center, Weinberg Cancer Institute, Franklin Square Hospital Center, Baltimore, MD (United States)

    2010-05-07

    Cytokines and growth factors have biologic effects that could stimulate tumor growth, invasion and angiogenesis. The incidence of 24 factors was investigated in 25 cultured human melanoma cell lines and in 62 fixed tissues at different stages of the disease. Over 80% of the human melanoma cell lines expressed TGF-β, IL-8, IL-6, VEGF, PDGF-AA and OPN. Significantly higher TGF-β, IGF-1 and IL-15 were determined in primary lesions compared to distant metastases by immunohistochemistry. Illustrating the complexity of the milieu of the tumor microenvironment, some of these factors may have to be considered in targeted therapy.

  16. Cytokines and Growth Factors Expressed by Human Cutaneous Melanoma

    Directory of Open Access Journals (Sweden)

    Elias G. Elias

    2010-05-01

    Full Text Available Cytokines and growth factors have biologic effects that could stimulate tumor growth, invasion and angiogenesis. The incidence of 24 factors was investigated in 25 cultured human melanoma cell lines and in 62 fixed tissues at different stages of the disease. Over 80% of the human melanoma cell lines expressed TGF-β, IL-8, IL-6, VEGF, PDGF-AA and OPN. Significantly higher TGF-β, IGF-1 and IL-15 were determined in primary lesions compared to distant metastases by immunohistochemistry. Illustrating the complexity of the milieu of the tumor microenvironment, some of these factors may have to be considered in targeted therapy.

  17. Involvement of reactive oxygen species in brominated diphenyl ether-47-induced inflammatory cytokine release from human extravillous trophoblasts in vitro

    International Nuclear Information System (INIS)

    Park, Hae-Ryung; Kamau, Patricia W.; Loch-Caruso, Rita

    2014-01-01

    Polybrominated diphenyl ethers (PBDEs) are widely used flame retardant compounds. Brominated diphenyl ether (BDE)-47 is one of the most prevalent PBDE congeners found in human breast milk, serum and placenta. Despite the presence of PBDEs in human placenta, effects of PBDEs on placental cell function are poorly understood. The present study investigated BDE-47-induced reactive oxygen species (ROS) formation and its role in BDE-47-stimulated proinflammatory cytokine release in a first trimester human extravillous trophoblast cell line, HTR-8/SVneo. Exposure of HTR-8/SVneo cells for 4 h to 20 μM BDE-47 increased ROS generation 1.7 fold as measured by the dichlorofluorescein (DCF) assay. Likewise, superoxide anion production increased approximately 5 fold at 10 and 15 μM and 9 fold at 20 μM BDE-47 with a 1-h exposure, as measured by cytochrome c reduction. BDE-47 (10, 15 and 20 μM) decreased the mitochondrial membrane potential by 47–64.5% at 4, 8 and 24 h as assessed with the fluorescent probe Rh123. Treatment with 15 and 20 μM BDE-47 stimulated cellular release and mRNA expression of IL-6 and IL-8 after 12 and 24-h exposures: the greatest increases were a 35-fold increased mRNA expression at 12 h and a 12-fold increased protein concentration at 24 h for IL-6. Antioxidant treatments (deferoxamine mesylate, (±)α-tocopherol, or tempol) suppressed BDE-47-stimulated IL-6 release by 54.1%, 56.3% and 37.7%, respectively, implicating a role for ROS in the regulation of inflammatory pathways in HTR-8/SVneo cells. Solvent (DMSO) controls exhibited statistically significantly decreased responses compared with non-treated controls for IL-6 release and IL-8 mRNA expression, but these responses were not consistent across experiments and times. Nonetheless, it is possible that DMSO (used to dissolve BDE-47) may have attenuated the stimulatory actions of BDE-47 on cytokine responses. Because abnormal activation of proinflammatory responses can disrupt trophoblast functions

  18. Involvement of reactive oxygen species in brominated diphenyl ether-47-induced inflammatory cytokine release from human extravillous trophoblasts in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Park, Hae-Ryung, E-mail: heaven@umich.edu; Kamau, Patricia W.; Loch-Caruso, Rita

    2014-01-15

    Polybrominated diphenyl ethers (PBDEs) are widely used flame retardant compounds. Brominated diphenyl ether (BDE)-47 is one of the most prevalent PBDE congeners found in human breast milk, serum and placenta. Despite the presence of PBDEs in human placenta, effects of PBDEs on placental cell function are poorly understood. The present study investigated BDE-47-induced reactive oxygen species (ROS) formation and its role in BDE-47-stimulated proinflammatory cytokine release in a first trimester human extravillous trophoblast cell line, HTR-8/SVneo. Exposure of HTR-8/SVneo cells for 4 h to 20 μM BDE-47 increased ROS generation 1.7 fold as measured by the dichlorofluorescein (DCF) assay. Likewise, superoxide anion production increased approximately 5 fold at 10 and 15 μM and 9 fold at 20 μM BDE-47 with a 1-h exposure, as measured by cytochrome c reduction. BDE-47 (10, 15 and 20 μM) decreased the mitochondrial membrane potential by 47–64.5% at 4, 8 and 24 h as assessed with the fluorescent probe Rh123. Treatment with 15 and 20 μM BDE-47 stimulated cellular release and mRNA expression of IL-6 and IL-8 after 12 and 24-h exposures: the greatest increases were a 35-fold increased mRNA expression at 12 h and a 12-fold increased protein concentration at 24 h for IL-6. Antioxidant treatments (deferoxamine mesylate, (±)α-tocopherol, or tempol) suppressed BDE-47-stimulated IL-6 release by 54.1%, 56.3% and 37.7%, respectively, implicating a role for ROS in the regulation of inflammatory pathways in HTR-8/SVneo cells. Solvent (DMSO) controls exhibited statistically significantly decreased responses compared with non-treated controls for IL-6 release and IL-8 mRNA expression, but these responses were not consistent across experiments and times. Nonetheless, it is possible that DMSO (used to dissolve BDE-47) may have attenuated the stimulatory actions of BDE-47 on cytokine responses. Because abnormal activation of proinflammatory responses can disrupt trophoblast functions

  19. Principal component analysis identifies patterns of cytokine expression in non-small cell lung cancer patients undergoing definitive radiation therapy.

    Directory of Open Access Journals (Sweden)

    Susannah G Ellsworth

    Full Text Available Radiation treatment (RT stimulates the release of many immunohumoral factors, complicating the identification of clinically significant cytokine expression patterns. This study used principal component analysis (PCA to analyze cytokines in non-small cell lung cancer (NSCLC patients undergoing RT and explore differences in changes after hypofractionated stereotactic body radiation therapy (SBRT and conventionally fractionated RT (CFRT without or with chemotherapy.The dataset included 141 NSCLC patients treated on prospective clinical protocols; PCA was based on the 128 patients who had complete CK values at baseline and during treatment. Patients underwent SBRT (n = 16, CFRT (n = 18, or CFRT (n = 107 with concurrent chemotherapy (ChRT. Levels of 30 cytokines were measured from prospectively collected platelet-poor plasma samples at baseline, during RT, and after RT. PCA was used to study variations in cytokine levels in patients at each time point.Median patient age was 66, and 22.7% of patients were female. PCA showed that sCD40l, fractalkine/C3, IP10, VEGF, IL-1a, IL-10, and GMCSF were responsible for most variability in baseline cytokine levels. During treatment, sCD40l, IP10, MIP-1b, fractalkine, IFN-r, and VEGF accounted for most changes in cytokine levels. In SBRT patients, the most important players were sCD40l, IP10, and MIP-1b, whereas fractalkine exhibited greater variability in CFRT alone patients. ChRT patients exhibited variability in IFN-γ and VEGF in addition to IP10, MIP-1b, and sCD40l.PCA can identify potentially significant patterns of cytokine expression after fractionated RT. Our PCA showed that inflammatory cytokines dominate post-treatment cytokine profiles, and the changes differ after SBRT versus CFRT, with vs without chemotherapy. Further studies are planned to validate these findings and determine the clinical significance of the cytokine profiles identified by PCA.

  20. Policaptil Gel Retard significantly reduces body mass index and hyperinsulinism and may decrease the risk of type 2 diabetes mellitus (T2DM) in obese children and adolescents with family history of obesity and T2DM.

    Science.gov (United States)

    Stagi, Stefano; Lapi, Elisabetta; Seminara, Salvatore; Pelosi, Paola; Del Greco, Paolo; Capirchio, Laura; Strano, Massimo; Giglio, Sabrina; Chiarelli, Francesco; de Martino, Maurizio

    2015-02-15

    Treatments for childhood obesity are critically needed because of the risk of developing co-morbidities, although the interventions are frequently time-consuming, frustrating, difficult, and expensive. We conducted a longitudinal, randomised, clinical study, based on a per protocol analysis, on 133 obese children and adolescents (n = 69 males and 64 females; median age, 11.3 years) with family history of obesity and type 2 diabetes mellitus (T2DM). The patients were divided into three arms: Arm A (n = 53 patients), Arm B (n = 45 patients), and Arm C (n = 35 patients) patients were treated with a low-glycaemic-index (LGI) diet and Policaptil Gel Retard, only a LGI diet, or only an energy-restricted diet (ERD), respectively. The homeostasis model assessment of insulin resistance (HOMA-IR) and the Matsuda, insulinogenic and disposition indexes were calculated at T0 and after 1 year (T1). At T1, the BMI-SD scores were significantly reduced from 2.32 to 1.80 (p 1) in Arm A and from 2.23 to 1.99 (p 13.2% to 5.6%; p 1) and B (p 1) and B (p obese children and adolescents with family history of obesity and T2DM.

  1. Cytokine Correlations in Youth with Tic Disorders

    Science.gov (United States)

    Parker-Athill, E. Carla; Ehrhart, Jared; Tan, Jun

    2015-01-01

    Abstract Background: Studies have noted immunological disruptions in patients with tic disorders, including increased serum cytokine levels. This study aimed to determine whether or not cytokine levels could be correlated with tic symptom severity in patients with a diagnosed tic disorder. Methods: Twenty-one patients, ages 4–17 years (average 10.63±2.34 years, 13 males), with a clinical diagnosis of Tourette's syndrome (TS) or chronic tic disorder (CTD), were selected based on having clinic visits that coincided with a tic symptom exacerbation and a remission. Ratings of tic severity were assessed using the Yale Global Tic Severity Scale (YGTSS) and serum cytokine levels (interleukin [IL]-2, IL-4, IL-5, IL-10, IL-12p70, IL-13, interferon [IFN]-γ, tumor necrosis factor [TNF]-α, and granulocyte macrophage-colony stimulating factor [GM-CSF]) were measured using Luminex xMAP technology. Results: During tic symptom exacerbation, patients had higher median serum TNF-α levels (z=−1.962, p=0.05), particularly those on antipsychotics (U=9.00, p=0.033). Increased IL-13 was also associated with antipsychotic use during exacerbation (U=4.00, p=0.043) despite being negatively correlated to tic severity scores (ρ=−0.599, p=018), whereas increased IL-5 was associated with antibiotic use (U=6.5, p=0.035). During tic symptom remission, increased serum IL-4 levels were associated with antipsychotic (U=6.00, p=0.047) and antibiotic (U=1.00, p=0.016) use, whereas increased IL-12p70 (U=4.00, p=0.037) was associated with antibiotic use. Conclusions: These findings suggest a role for cytokine dysregulation in the pathogenesis of tic disorders. It also points toward the mechanistic involvement and potential diagnostic utility of cytokine monitoring, particularly TNF-α levels. Larger, systematic studies are necessary to further delineate the role of cytokines and medication influences on immunological profiling in tic disorders. PMID:25658821

  2. Cytokine correlations in youth with tic disorders.

    Science.gov (United States)

    Parker-Athill, E Carla; Ehrhart, Jared; Tan, Jun; Murphy, Tanya K

    2015-02-01

    Studies have noted immunological disruptions in patients with tic disorders, including increased serum cytokine levels. This study aimed to determine whether or not cytokine levels could be correlated with tic symptom severity in patients with a diagnosed tic disorder. Twenty-one patients, ages 4-17 years (average 10.63±2.34 years, 13 males), with a clinical diagnosis of Tourette's syndrome (TS) or chronic tic disorder (CTD), were selected based on having clinic visits that coincided with a tic symptom exacerbation and a remission. Ratings of tic severity were assessed using the Yale Global Tic Severity Scale (YGTSS) and serum cytokine levels (interleukin [IL]-2, IL-4, IL-5, IL-10, IL-12p70, IL-13, interferon [IFN]-γ, tumor necrosis factor [TNF]-α, and granulocyte macrophage-colony stimulating factor [GM-CSF]) were measured using Luminex xMAP technology. During tic symptom exacerbation, patients had higher median serum TNF-α levels (z=-1.962, p=0.05), particularly those on antipsychotics (U=9.00, p=0.033). Increased IL-13 was also associated with antipsychotic use during exacerbation (U=4.00, p=0.043) despite being negatively correlated to tic severity scores (ρ=-0.599, p=018), whereas increased IL-5 was associated with antibiotic use (U=6.5, p=0.035). During tic symptom remission, increased serum IL-4 levels were associated with antipsychotic (U=6.00, p=0.047) and antibiotic (U=1.00, p=0.016) use, whereas increased IL-12p70 (U=4.00, p=0.037) was associated with antibiotic use. These findings suggest a role for cytokine dysregulation in the pathogenesis of tic disorders. It also points toward the mechanistic involvement and potential diagnostic utility of cytokine monitoring, particularly TNF-α levels. Larger, systematic studies are necessary to further delineate the role of cytokines and medication influences on immunological profiling in tic disorders.

  3. Drug targets in the cytokine universe for autoimmune disease.

    Science.gov (United States)

    Liu, Xuebin; Fang, Lei; Guo, Taylor B; Mei, Hongkang; Zhang, Jingwu Z

    2013-03-01

    In autoimmune disease, a network of diverse cytokines is produced in association with disease susceptibility to constitute the 'cytokine milieu' that drives chronic inflammation. It remains elusive how cytokines interact in such a complex network to sustain inflammation in autoimmune disease. This has presented huge challenges for successful drug discovery because it has been difficult to predict how individual cytokine-targeted therapy would work. Here, we combine the principles of Chinese Taoism philosophy and modern bioinformatics tools to dissect multiple layers of arbitrary cytokine interactions into discernible interfaces and connectivity maps to predict movements in the cytokine network. The key principles presented here have important implications in our understanding of cytokine interactions and development of effective cytokine-targeted therapies for autoimmune disorders. Copyright © 2012 Elsevier Ltd. All rights reserved.

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    uncharacterized. Moreover, the data obtained regarding the origin of cytokine secretions, the levels of secretion associated with tumor development, and the possible clinical relevance of cytokines remain controversial. Therefore, we profiled 27 cytokines in 78 breast tumor interstitial fluid (TIF) samples, 43...... normal interstitial fluid (NIF) samples, and 25 matched serum samples obtained from BC patients with Luminex xMAP multiplex technology. Eleven cytokines exhibited significantly higher levels in the TIF samples compared with the NIF samples: interleukin (IL)-7, IL-10, fibroblast growth factor-2, IL-13......, IL-7, IL-10, and PDGFβ also exhibited a correlation between the TIF samples and matched sera. In a survival analysis, high levels of IL-5, a hallmark TH2 cytokine, in the TIF samples were associated with a worse prognosis. These findings have important implications for BC immunotherapy research....

  5. Pre-existing adenovirus immunity modifies a complex mixed Th1 and Th2 cytokine response to an Ad5/HIV-1 vaccine candidate in humans.

    Directory of Open Access Journals (Sweden)

    Samuel O Pine

    2011-04-01

    Full Text Available The results of the recent Step Study highlight a need to clarify the effects of pre-existing natural immunity to a vaccine vector on vaccine-induced T-cell responses. To investigate this interaction, we examined the relationship between pre-existing Ad5 immunity and T-cell cytokine response profiles in healthy, HIV-uninfected recipients of MRKAd5 HIV-1 gag vaccine (HVTN 050, ClinicalTrials.gov #NCT00849732. Participants were grouped by baseline Ad5 neutralizing antibody titer as either Ad5-seronegative (titer ≤18; n = 36 or Ad5-seropositive (titer >200; n = 34. Samples from vaccine recipients were analyzed for immune responses to either HIV-1 Gag peptide pools or Ad5 empty vector using an ex vivo assay that measures thirty cytokines in the absence of long-term culture. The overall profiles of cytokine responses to Gag and Ad5 had similar combinations of induced Th1- and Th2-type cytokines, including IFN-γ, IL-2, TNF-α, IP-10, IL-13, and IL-10, although the Ad5-specific responses were uniformly higher than the Gag-specific responses (p<0.0001 for 9 out of 11 significantly expressed analytes. At the peak response time point, PBMC from Ad5-seronegative vaccinees secreted significantly more IP-10 in response to Gag (p = 0.008, and significantly more IP-10 (p = 0.0009, IL-2 (p = 0.006 and IL-10 (p = 0.05 in response to Ad5 empty vector than PBMC from Ad5-seropositive vaccinees. Additionally, similar responses to the Ad5 vector prior to vaccination were observed in almost all subjects, regardless of Ad5 neutralizing antibody status, and the levels of secreted IFN-γ, IL-10, IL-1Ra and GM-CSF were blunted following vaccination. The cytokine response profile of Gag-specific T cells mirrored the Ad5-specific response present in all subjects before vaccination, and included a number of Th1- and Th2-associated cytokines not routinely assessed in current vaccine trials, such as IP-10, IL-10, IL-13, and GM-CSF. Together, these

  6. Measurement of inflammatory cytokines and thrombomodulin in chronic subdural hematoma.

    Science.gov (United States)

    Kitazono, Masatoshi; Yokota, Hiroyuki; Satoh, Hidetaka; Onda, Hidetaka; Matsumoto, Gaku; Fuse, Akira; Teramoto, Akira

    2012-01-01

    Inflammation and the coagulation system may influence the genesis of chronic subdural hematoma (CSDH). The appearance of CSDH on computed tomography (CT) varies with the stage of the hematoma. This study investigated the pathogenesis and the recurrence of CSDH by comparing cytokine levels with the CT features of CSDH in 26 patients with 34 CSDHs who underwent single burr-hole surgery at our hospital between October 2004 and November 2006. The hematoma components removed during the procedure were examined, and the hematoma serum levels of cytokines measured such as thrombomodulin (TM), interleukin-6 (IL-6), tumor necrosis factor-α (TNFα), and interleukin-10 (IL-10). Using CT, mixed density hematomas were distinguished from other homogeneous hematomas, and found that the TM level was significantly higher in mixed density hematomas than in homogeneous hematomas (p = 0.043). Mixed density hematomas were classified into three subtypes (laminar, separated, and trabecular hematomas). The TM level was significantly higher in laminar and separated hematomas than in other hematomas (p = 0.01). The levels of IL-6, TNFα, and IL-10 were extremely high, but showed no significant differences in relation to the CT features. Mixed density hematomas had high recurrence rate, as reported previously, and TM level was high in mixed density hematomas such as laminar and separated mixed density hematomas. The present findings suggest that the types of CSDH associated with high TM levels tend to have higher recurrence rate.

  7. St. John's wort attenuates irinotecan-induced diarrhea via down-regulation of intestinal pro-inflammatory cytokines and inhibition of intestinal epithelial apoptosis

    International Nuclear Information System (INIS)

    Hu Zeping; Yang Xiaoxia; Chan Suiyung; Xu Anlong; Duan Wei; Zhu Yizhun; Sheu, F.-S.; Boelsterli, Urs Alex; Chan, Eli; Zhang Qiang; Wang, J.-C.; Ee, Pui Lai Rachel; Koh, H.L.; Huang Min; Zhou Shufeng

    2006-01-01

    Diarrhea is a common dose-limiting toxicity associated with cancer chemotherapy, in particular for drugs such as irinotecan (CPT-11), 5-fluouracil, oxaliplatin, capecitabine and raltitrexed. St. John's wort (Hypericum perforatum, SJW) has anti-inflammatory activity, and our preliminary study in the rat and a pilot study in cancer patients found that treatment of SJW alleviated irinotecan-induced diarrhea. In the present study, we investigated whether SJW modulated various pro-inflammatory cytokines including interleukins (IL-1β, IL-2, IL-6), interferon (IFN-γ) and tumor necrosis factor-α (TNF-α) and intestinal epithelium apoptosis in rats. The rats were treated with irinotecan at 60 mg/kg for 4 days in combination with oral SJW or SJW-free control vehicle at 400 mg/kg for 8 days. Diarrhea, tissue damage, body weight loss, various cytokines including IL-1β, IL-2, IL-6, IFN-γ and TNF-α and intestinal epithelial apoptosis were monitored over 11 days. Our studies demonstrated that combined SJW markedly reduced CPT-11-induced diarrhea and intestinal lesions. The production of pro-inflammatory cytokines such as IL-1β, IFN-γ and TNF-α was significantly up-regulated in intestine. In the mean time, combined SJW significantly suppressed the intestinal epithelial apoptosis induced by CPT-11 over days 5-11. In particular, combination of SJW significantly inhibited the expression of TNF-α mRNA in the intestine over days 5-11. In conclusion, inhibition of pro-inflammatory cytokines and intestinal epithelium apoptosis partly explained the protective effect of SJW against the intestinal toxicities induced by irinotecan. Further studies are warranted to explore the potential for STW as an agent in combination with chemotherapeutic drugs to lower their dose-limiting toxicities

  8. Effect of Shenkang injection combined with hemodialysis treatment on renal function, renal anemia and cytokine levels in patients with chronic renal failure

    Directory of Open Access Journals (Sweden)

    Rui Liu

    2016-10-01

    Full Text Available Objective: To study the effect of Shenkang injection combined with hemodialysis treatment on renal function, renal anemia and cytokine levels in patients with chronic renal failure. Methods: A total of 68 patients with chronic renal failure who received hemodialysis treatment in our hospital during between October 2013 and February 2016 were selected and randomly divided into two groups, the observation group received Shenkang injection treatment in the process of dialysis, and the control group only received conventional symptomatic and supportive treatment. 8 weeks after treatment, serum was collected to determine the levels of renal function indexes, nutritional status indexes, anemia indexes and cytokines, and urine was collected to determine renal function indexes. Results: β2-MG, UA, Cr, phosphorus, IL-17, IL-23, CTGF, TGF-β1, FGF-2 and FGF-23 levels in serum as well as NGAL, KIM-1 and RBP levels in urine of observation group were significantly lower than those of control group, and TP, Alb, PA, calcium, Hb, EPO, Fe, TRF and FER levels in serum were significantly higher than those of control group. Conclusion: Shenkang injection combined with hemodialysis treatment helps to improve renal function, nutritional status and renal anemia, and reduce the synthesis of inflammation and renal interstitial fibrosis-related cytokines in patients with chronic renal failure.

  9. Activation of Human Peripheral Blood Eosinophils by Cytokines in a Comparative Time-Course Proteomic/Phosphoproteomic Study.

    Science.gov (United States)

    Soman, Kizhake V; Stafford, Susan J; Pazdrak, Konrad; Wu, Zheng; Luo, Xuemei; White, Wendy I; Wiktorowicz, John E; Calhoun, William J; Kurosky, Alexander

    2017-08-04

    Activated eosinophils contribute to airway dysfunction and tissue remodeling in asthma and thus are considered to be important factors in asthma pathology. We report here comparative proteomic and phosphoproteomic changes upon activation of eosinophils using eight cytokines individually and in selected cytokine combinations in time-course reactions. Differential protein and phosphoprotein expressions were determined by mass spectrometry after 2-dimensional gel electrophoresis (2DGE) and by LC-MS/MS. We found that each cytokine-stimulation produced significantly different changes in the eosinophil proteome and phosphoproteome, with phosphoproteomic changes being more pronounced and having an earlier onset. Furthermore, we observed that IL-5, GM-CSF, and IL-3 showed the greatest change in protein expression and phosphorylation, and this expression differed markedly from those of the other five cytokines evaluated. Comprehensive univariate and multivariate statistical analyses were employed to evaluate the comparative results. We also monitored eosinophil activation using flow cytometry (FC) analysis of CD69. In agreement with our proteomic studies, FC indicated that IL-5, GM-CSF, and IL-3 were more effective than the other five cytokines studied in stimulating a cell surface CD69 increase indicative of eosinophil activation. Moreover, selected combinations of cytokines revealed proteomic patterns with many proteins in common with single cytokine expression patterns but also showed a greater effect of the two cytokines employed, indicating a more complex signaling pathway that was reflective of a more typical inflammatory pathology.

  10. Comparison of ophthalmic sponges and extraction buffers for quantifying cytokine profiles in tears using Luminex technology.

    Science.gov (United States)

    Inic-Kanada, Aleksandra; Nussbaumer, Andrea; Montanaro, Jacqueline; Belij, Sandra; Schlacher, Simone; Stein, Elisabeth; Bintner, Nora; Merio, Margarethe; Zlabinger, Gerhard J; Barisani-Asenbauer, Talin

    2012-01-01

    proinflammatory cytokines, Th1/Th2 distinguishing cytokines, nonspecific acting cytokines, and chemokines. WE DEMONSTRATED THE FOLLOWING: (i) 25 cytokines/chemokines expressed highly variable interactions with buffers and matrices. Several buffers enabled recovery of similar cytokine values (regulated and normal T cell expressed and secreted [RANTES], interleukin [IL]-13, IL-6, IL-8, IL-2R, and granulocyte-macrophage colony-stimulating factor [GM-CSF]); others were highly variable (monocyte chemotactic protein-1 [MCP-1], monokine induced by interferon-gamma [MIG], IL-1β, IL-4, IL-7, and eotaxin). (ii) Various extraction buffers displayed significantly different recovery rates on the same sponge for the same cytokine/chemokine. (iii) The highest recovery rates were obtained with the Merocel ophthalmic sponge except for tumor necrosis factor-α: the Weck-Cel ophthalmic sponge showed the best results, either with cytokine standards loaded onto sponges or with tears collected from the inner canthus of the eye, using the sponge. (iv) IL-5, IL-10, and interferon-α were not detected in any tear sample from four normal human subjects. Twenty-two cytokines/chemokines that we detected were extracted from the Merocel sponge to a satisfactory recovery percentage. The recovery of IL-7 was significantly lower in the extracted Merocel sponge compared to the diluted tear samples. The cytokine/chemokine extraction from tears showed the same pattern of extraction that we observed for extracting the standards. Simultaneous measurement of various cytokines using ophthalmic sponges yielded diverse results for various cytokines as the level of extraction differs noticeably for certain cytokines. A second set of controls (standard curves "with sponges") should be used to delineate the extent of extraction for each cytokine to be analyzed. Many cytokines/chemokines were detected in tear samples collected with the Merocel sponge, including many that have been implicated in ocular surface disease

  11. Comparison of ophthalmic sponges and extraction buffers for quantifying cytokine profiles in tears using Luminex technology

    Science.gov (United States)

    Inic-Kanada, Aleksandra; Nussbaumer, Andrea; Montanaro, Jacqueline; Belij, Sandra; Schlacher, Simone; Stein, Elisabeth; Bintner, Nora; Merio, Margarethe; Zlabinger, Gerhard J.

    2012-01-01

    measurement of proinflammatory cytokines, Th1/Th2 distinguishing cytokines, nonspecific acting cytokines, and chemokines. Results We demonstrated the following: (i) 25 cytokines/chemokines expressed highly variable interactions with buffers and matrices. Several buffers enabled recovery of similar cytokine values (regulated and normal T cell expressed and secreted [RANTES], interleukin [IL]-13, IL-6, IL-8, IL-2R, and granulocyte-macrophage colony-stimulating factor [GM-CSF]); others were highly variable (monocyte chemotactic protein-1 [MCP-1], monokine induced by interferon-gamma [MIG], IL-1β, IL-4, IL-7, and eotaxin). (ii) Various extraction buffers displayed significantly different recovery rates on the same sponge for the same cytokine/chemokine. (iii) The highest recovery rates were obtained with the Merocel ophthalmic sponge except for tumor necrosis factor-α: the Weck-Cel ophthalmic sponge showed the best results, either with cytokine standards loaded onto sponges or with tears collected from the inner canthus of the eye, using the sponge. (iv) IL-5, IL-10, and interferon-α were not detected in any tear sample from four normal human subjects. Twenty-two cytokines/chemokines that we detected were extracted from the Merocel sponge to a satisfactory recovery percentage. The recovery of IL-7 was significantly lower in the extracted Merocel sponge compared to the diluted tear samples. The cytokine/chemokine extraction from tears showed the same pattern of extraction that we observed for extracting the standards. Conclusions Simultaneous measurement of various cytokines using ophthalmic sponges yielded diverse results for various cytokines as the level of extraction differs noticeably for certain cytokines. A second set of controls (standard curves “with sponges”) should be used to delineate the extent of extraction for each cytokine to be analyzed. Many cytokines/chemokines were detected in tear samples collected with the Merocel sponge, including many that have been

  12. Effect of Semen on Vaginal Fluid Cytokines and Secretory Leukocyte Protease Inhibitor

    Directory of Open Access Journals (Sweden)

    Kathy J. Agnew

    2008-01-01

    Methods: 138 pregnant women had vaginal fluid collected for Gram stain, acid phosphatase detection by colorimetric assay, and interleukin 1-Beta, interleukin-6, interleukin-8, and secretory leukocyte protease inhibitor measurement by enzyme immunoassay. Results for women with and without acid phosphatase were compared by Mann-Whitney test. Results: of 138 subjects, 28 (20% had acid phosphatase detected; of these, only 19 (68% reported recent intercourse and 3 (11% had sperm seen on Gram stain. There were no significant differences in proinflammatory cytokine concentrations; however, secretory leukocyte protease inhibitor concentrations were significantly higher among women with acid phosphatase. Conclusions: proinflammatory cytokine measurement does not appear to be affected by the presence of semen, but secretory leukocyte protease inhibitor is significantly higher when semen is present. Detection of semen by acid phosphatase was associated with higher vaginal SLPI concentrations, however, the presence of semen did not appear to influence vaginal proinflammatory cytokine concentrations.

  13. Cytokines and Pancreatic β-Cell Apoptosis

    DEFF Research Database (Denmark)

    Berchtold, L A; Prause, M; Størling, J

    2016-01-01

    The discovery 30 years ago that inflammatory cytokines cause a concentration, activity, and time-dependent bimodal response in pancreatic β-cell function and viability has been a game-changer in the fields of research directed at understanding inflammatory regulation of β-cell function and survival...... and the causes of β-cell failure and destruction in diabetes. Having until then been confined to the use of pathophysiologically irrelevant β-cell toxic chemicals as a model of β-cell death, researchers could now mimic endocrine and paracrine effects of the cytokine response in vitro by titrating concentrations...... of local, chronic islet inflammation. Since then, numerous studies have clarified how these bimodal responses depend on discrete signaling pathways. Most interest has been devoted to the proapoptotic response dependent upon mainly nuclear factor κ B and mitogen-activated protein kinase activation, leading...

  14. Progress of inflammatory cytokines in glaucoma

    Directory of Open Access Journals (Sweden)

    Ping Hu

    2015-12-01

    Full Text Available Glaucomais a group of diseases characterized by optic nerve damage and visual field defect, and pathological high intraocular pressure is a risk factor for glaucoma. Glaucoma is affected by the interaction of multiple genes and environmental factors, and inflammation may be involved in the pathogenesis of glaucoma. A great deal of studies have confirmed that high expression of connective tissue growth factor(CTGF, tumor necrosis factor-α(TNF-α, interleukins(ILs, nuclear factor-kappa B(NF-κBand various cytokines in the aqueous humor of patients with glaucoma, which have a close correlation with pathogenesis of glaucoma.This article reviews the progress of inflammatory cytokines and their relationship with glaucoma.

  15. Cytokines and the anorexia of infection: potential mechanisms and treatments.

    Science.gov (United States)

    McCarthy, D O

    2000-04-01

    Anorexia during infection is thought to be mediated by immunoregulatory cytokines such as interleukins 1 and 6 and tumor necrosis factor. This article reviews the potential mechanisms of action by which these cytokines are thought to suppress food intake during infection and examines the proposition that blocking of cytokine activity might be one approach to improving food intake of the infected host.

  16. 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...

  17. 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

  18. Dietary Fructo-Oligosaccharides Attenuate Early Activation of CD4+ T Cells Which Produce both Th1 and Th2 Cytokines in the Intestinal Lymphoid Tissues of a Murine Food Allergy Model.

    Science.gov (United States)

    Tsuda, Masato; Arakawa, Haruka; Ishii, Narumi; Ubukata, Chihiro; Michimori, Mana; Noda, Masanari; Takahashi, Kyoko; Kaminogawa, Shuichi; Hosono, Akira

    2017-01-01

    Fructo-oligosaccharides (FOS) are prebiotic agents with immunomodulatory effects involving improvement of the intestinal microbiota and metabolome. In this study, we investigated the cellular mechanisms through which FOS modulate intestinal antigen-specific CD4+ T cell responses in food allergy, using OVA23-3 mice. OVA23-3 mice were fed an experimental diet containing either ovalbumin (OVA) or OVA and FOS for 1 week. Body weight and mucosal mast cell protease 1 in the serum were measured as the indicator of intestinal inflammation. Single-cell suspensions were prepared from intestinal and systemic lymphoid tissues for cellular analysis. Cytokine production was measured by ELISA. Activation markers and intracellular cytokines in CD4+ T cells were analyzed by flow cytometry. Activated CD4+ T cells were purified to examine cytokine production. Dietary intake of FOS provided moderate protection from the intestinal inflammation induced by the OVA-containing diet. FOS significantly reduced food allergy-induced Th2 cytokine responses in intestinal tissues but not in systemic tissues. FOS decreased OVA diet-induced IFN-γ+IL-4+ double-positive CD4+ T cells and early-activated CD45RBhighCD69+CD4+ T cells in the mesenteric lymph nodes. Furthermore, we confirmed that these CD45RBhighCD69+CD4+ T cells are able to produce high levels of IFN-γ and moderate level of IL-4, IL-10, and IL-13. Dietary intake of FOS during the development of food allergy attenuates the induction of intestinal Th2 cytokine responses by regulating early activation of naïve CD4+ T cells, which produce both Th1 and Th2 cytokines. Our results suggest FOS might be a potential food agent for the prevention of food allergy by modulating oral sensitization to food antigens. © 2017 S. Karger AG, Basel.

  19. Cytokines in the physiopathology of depression

    OpenAIRE

    María Belén Paredes; María Eugenia Sulen

    2018-01-01

    This paper presents a bibliographical review on the relevance of the possible role of cytokines in depression. There is a consideration of the existing approaches to detection and diagnosis of depression; they are classified according to different criteria such as design methodologies and applications. Although the etiology of depression is still an issue, the focus of this paper is to highlight the various studies regarding the interactions of the immune system and brain activity linked to d...

  20. Association of Inflammatory Cytokines with Traditional and ...

    African Journals Online (AJOL)

    Annals of Medical and Health Sciences Research | Sep-Oct 2014 | Vol 4 ... and TNF‑α in study population were 11.7 (9.7) mg/l, 64.5 (75.2) pg/ml, and 25.3 ... cytokines also interact with various metabolic factors which are ..... European Prospective Investigation into Cancer and ... nutrition and role of one‑carbon metabolism.

  1. Proinflammatory Cytokines in Prostate Cancer Development and Progression Promoted by High-Fat Diet

    Directory of Open Access Journals (Sweden)

    Hua Xu

    2015-01-01

    Full Text Available Background. We aimed to examine whether proinflammatory cytokines participated in prostate cancer (PCa development and progression promoted by high-fat diet (HFD. Methods. TRAMP (transgenic adenocarcinoma mouse prostate mice were randomly divided into two groups: normal diet group and HFD group. Mortality rate and tumor formation rate were examined. TRAMP mice were sacrificed and sampled on the 20th, 24th, and 28th week, respectively. Levels of proinflammatory cytokines, including IL-1α, IL-1β, IL-6, and TNF-α, were tested by FlowCytomix. Prostate tissue of TRAMP mice was used for histology study. Results. A total of 13 deaths of TRAMP mice were observed, among which 3 (8.33% were from the normal diet group and 10 (27.78% from the HFD group. The mortality rate of TRAMP mice from HFD group was significantly higher than that of normal diet group (P=0.032. Tumor formation rate at 20th week of age of HFD group was significantly higher than that of normal diet group (P=0.045. Proinflammatory cytokines levels, including IL-1α, IL-1β, IL-6, and TNF-α, were significantly higher in HFD TRAMP mice. Conclusions. HFD could promote TRAMP mouse PCa development and progression with elevated proinflammatory cytokines levels. Proinflammatory cytokines could contribute to PCa development and progression promoted by HFD.

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

    Science.gov (United States)

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

    2013-09-01

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

  3. Agmatine Reverses Sub-chronic Stress induced Nod-like Receptor Protein 3 (NLRP3) Activation and Cytokine Response in Rats.

    Science.gov (United States)

    Sahin, Ceren; Albayrak, Ozgur; Akdeniz, Tuğba F; Akbulut, Zeynep; Yanikkaya Demirel, Gulderen; Aricioglu, Feyza

    2016-10-01

    The activation of Nod-like receptor protein 3 (NLRP3) has lately been implicated in stress and depression as an initiator mechanism required for the production of interleukin (IL)-1β and IL-18. Agmatine, an endogenous polyamine widely distributed in mammalian brain, is a novel neurotransmitter/neuromodulator, with antistress, anxiolytic and antidepressant-like effects. In this study, we examined the effect of exogenously administered agmatine on NLRP3 inflammasome pathway/cytokine responses in rats exposed to restraint stress for 7 days. The rats were divided into three groups: stress, stress+agmatine (40 mg/kg; i.p.) and control groups. Agmatine significantly down-regulated the gene expressions of all stress-induced NLRP3 inflammasome components (NLRP3, NF-κB, PYCARD, caspase-1, IL-1β and IL-18) in the hippocampus and prefrontal cortex (PFC) and reduced pro-inflammatory cytokine levels not only in both brain regions, but also in serum. Stress-reduced levels of IL-4 and IL-10, two major anti-inflammatory cytokines, were restored back to normal by agmatine treatment in the PFC. The findings of the present study suggest that stress-activated NLRP3 inflammasome and cytokine responses are reversed by an acute administration of agmatine. Whether antidepressant-like effect of agmatine can somehow, at least partially, be mediated by the inhibition of NLRP3 inflammasome cascade and relevant inflammatory responses requires further studies in animal models of depression. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  4. Regulation and function of interleukin-36 cytokines.

    Science.gov (United States)

    Bassoy, Esen Yonca; Towne, Jennifer E; Gabay, Cem

    2018-01-01

    The interleukin (IL)-36 cytokines include 3 agonists, IL-36α, IL-36β, and IL-36γ that bind to a common receptor composed of IL-36R and IL-1RAcP to stimulate inflammatory responses. IL-36Ra is a natural antagonist that binds to IL-36R, but does not recruit the co-receptor IL-1RAcP and does not stimulate any intracellular responses. The IL-36 cytokines are expressed predominantly by epithelial cells and act on a number of cells including immune cells, epithelial cells, and fibroblasts. Processing of the N-terminus is required for full agonist or antagonist activity for all IL-36 members. The role of IL-36 has been extensively demonstrated in the skin where it can act on keratinocytes and immune cells to induce a robust inflammatory response that has been implicated in psoriatic disorders. Emerging data also suggest a role for this cytokine family in pulmonary and intestinal physiology and pathology. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Cytokine Tuning of Intestinal Epithelial Function

    Directory of Open Access Journals (Sweden)

    Caroline Andrews

    2018-06-01

    Full Text Available The intestine serves as both our largest single barrier to the external environment and the host of more immune cells than any other location in our bodies. Separating these potential combatants is a single layer of dynamic epithelium composed of heterogeneous epithelial subtypes, each uniquely adapted to carry out a subset of the intestine’s diverse functions. In addition to its obvious role in digestion, the intestinal epithelium is responsible for a wide array of critical tasks, including maintaining barrier integrity, preventing invasion by microbial commensals and pathogens, and modulating the intestinal immune system. Communication between these epithelial cells and resident immune cells is crucial for maintaining homeostasis and coordinating appropriate responses to disease and can occur through cell-to-cell contact or by the release or recognition of soluble mediators. The objective of this review is to highlight recent literature illuminating how cytokines and chemokines, both those made by and acting on the intestinal epithelium, orchestrate many of the diverse functions of the intestinal epithelium and its interactions with immune cells in health and disease. Areas of focus include cytokine control of intestinal epithelial proliferation, cell death, and barrier permeability. In addition, the modulation of epithelial-derived cytokines and chemokines by factors such as interactions with stromal and immune cells, pathogen and commensal exposure, and diet will be discussed.

  6. Detection of cytokine expression patterns in the peripheral blood of patients with acute leukemia by antibody microarray analysis.

    Science.gov (United States)

    Li, Qing; Li, Mei; Wu, Yao-hui; Zhu, Xiao-jian; Zeng, Chen; Zou, Ping; Chen, Zhi-chao

    2014-04-01

    The cytokines of acute leukemia (AL) patients have certain expression patterns, forming a complex network involved in diagnosis, progression, and prognosis. We collected the serum of different AL patients before and after complete remission (CR) for detection of cytokines by using an antibody chip. The expression patterns of cytokines were determined by using bioinformatics computational analysis. The results showed that there were significant differences in the cytokine expression patterns between AL patients and normal controls, as well as between acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). In confirmatory test, ELISA revealed the expression of uPAR in AL. Moreover, the bioinformatic analysis showed that the differentially expressed cytokines among the AL groups were involved in different biological behaviors and were closely related with the development of the disease. It was concluded that the cytokine expression pattern of AL patients is significantly different from that of healthy volunteers. Also, differences of cytokine expression patterns exist between AML and ALL, and between before and after CR in the same subtype of AL, which holds important clinical significance for revealing disease progression.

  7. Cytokine Immunopathogenesis of Enterovirus 71 Brain Stem Encephalitis

    Directory of Open Access Journals (Sweden)

    Shih-Min Wang

    2012-01-01

    Full Text Available Enterovirus 71 (EV71 is one of the most important causes of herpangina and hand, foot, and mouth disease. It can also cause severe complications of the central nervous system (CNS. Brain stem encephalitis with pulmonary edema is the severe complication that can lead to death. EV71 replicates in leukocytes, endothelial cells, and dendritic cells resulting in the production of immune and inflammatory mediators that shape innate and acquired immune responses and the complications of disease. Cytokines, as a part of innate immunity, favor the development of antiviral and Th1 immune responses. Cytokines and chemokines play an important role in the pathogenesis EV71 brain stem encephalitis. Both the CNS and the systemic inflammatory responses to infection play important, but distinctly different, roles in the pathogenesis of EV71 pulmonary edema. Administration of intravenous immunoglobulin and milrinone, a phosphodiesterase inhibitor, has been shown to modulate inflammation, to reduce sympathetic overactivity, and to improve survival in patients with EV71 autonomic nervous system dysregulation and pulmonary edema.

  8. Cytokines in immunogenic cell death: Applications for cancer immunotherapy.

    Science.gov (United States)

    Showalter, Anne; Limaye, Arati; Oyer, Jeremiah L; Igarashi, Robert; Kittipatarin, Christina; Copik, Alicja J; Khaled, Annette R

    2017-09-01

    Despite advances in treatments like chemotherapy and radiotherapy, metastatic cancer remains a leading cause of death for cancer patients. While many chemotherapeutic agents can efficiently eliminate cancer cells, long-term protection against cancer is not achieved and many patients experience cancer recurrence. Mobilizing and stimulating the immune system against tumor cells is one of the most effective ways to protect against cancers that recur and/or metastasize. Activated tumor specific cytotoxic T lymphocytes (CTLs) can seek out and destroy metastatic tumor cells and reduce tumor lesions. Natural Killer (NK) cells are a front-line defense against drug-resistant tumors and can provide tumoricidal activity to enhance tumor immune surveillance. Cytokines like IFN-γ or TNF play a crucial role in creating an immunogenic microenvironment and therefore are key players in the fight against metastatic cancer. To this end, a group of anthracyclines or treatments like photodynamic therapy (PDT) exert their effects on cancer cells in a manner that activates the immune system. This process, known as immunogenic cell death (ICD), is characterized by the release of membrane-bound and soluble factors that boost the function of immune cells. This review will explore different types of ICD inducers, some in clinical trials, to demonstrate that optimizing the cytokine response brought about by treatments with ICD-inducing agents is central to promoting anti-cancer immunity that provides long-lasting protection against disease recurrence and metastasis. Copyright © 2017. Published by Elsevier Ltd.

  9. Therapeutic Touch Has Significant Effects on Mouse Breast Cancer Metastasis and Immune Responses but Not Primary Tumor Size.

    Science.gov (United States)

    Gronowicz, Gloria; Secor, Eric R; Flynn, John R; Jellison, Evan R; Kuhn, Liisa T

    2015-01-01

    Evidence-based integrative medicine therapies have been introduced