Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Etiological evidence, indicating the relationships between the onset of malignant lymphoma and pre-existing chronic inflammation, has been accumulated. For the autonomous growth of malignant tumor, genetic lesions, such as chromosomal aberrations, amplification of oncogenes, and mutations of genes involved in the cell cycle regulation, must be essential. However, how the inflammation promotes the accumulation of genetic lesions and induces the autonomous growth of lymphoid cells remains unclear. Reactive oxygen species released by polymorphonuclear leukocytes and macrophages are factors causing DNA damage in the foci of inflammation, and thus could play a role in lymphomagenesis. The xanthine/xanthine oxidase (X/XOD) system produces a mixture of hydrogen peroxide and superoxide anion extracellularly, and thus serves as an in vitro source of reactive oxygen species. Cell death of lymphoblastoid cell lines (LCLs) was induced with X/XOD treatment in a dose-dependent manner. DNA fragmentation, which is the characteristic feature of apoptosis, was observed in LCLs at 4-8 hours after X/XOD treatment. Among cytokines such as interleukin-6 (IL-6), IL-10, and interferon-gamma, only pretreatment with IL-6 gave LCLs the resistance to X/XOD-induced cell death in a dose-dependent manner. The proportion of apoptotic cells in X/XOD-treated LCL culture was decreased with IL-6 pretreatment by quantification with flow cytometric analysis. Treatment of LCLs with IL-6 for 48 hours up-regulated bcl-2 mRNA expression. Furthermore, the LCLs repeatedly treated with X/XOD and cultured with or without IL-6 showed many more structural abnormalities of chromosomes than those without X/XOD treatment. Colony forming efficiency of X/XOD-treated LCLs with IL-6 was significantly higher than those without IL-6, and even relatively higher than LCLs without X/XOD treatment. IL-6 could support the survival of non-neoplastic B cells and accelerate the malignant transformation of B lineage cells in inflammatory lesions.
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PMID:Induction of chromosomal aberrations and growth-transformation of lymphoblastoid cell lines by inhibition of reactive oxygen species-induced apoptosis with interleukin-6. 1083 Jul 83

Available data suggest that repeated concurrent exposure to haematite (Fe(2)O(3)) and benzo[A]pyrene (B[A]P) results in a decreased latency and an increased incidence of lung tumours in rodents compared to exposure to B[A]P alone. Moreover, the reactive oxygen species (ROS) formed by the lung cells themselves and/or by activated inflammatory cells may possibly contribute to the development of pulmonary disorders such as cancer formation. In order to investigate the precise role of iron in the injury induced by B[A]P-coated onto Fe(2)O(3) particles, we tend to address the hypothesis that Fe(2)O(3) and B[A]P, alone or in association, can induce oxidative stress conditions (malondialdehyde) and/or inflammatory reactions (interleukin-6) and thereby disrupt the proteinase/anti-proteinase balance (cathepsins B and L, polynuclear neutrophil (PNN) elastase, alpha-1 proteinase inhibitor (alpha(1)PI) and its inhibitory capacity) in the rat respiratory tract. Thus, Fe(2)O(3) or B[A]P-coated onto Fe(2)O(3) particles produce oxidative stress conditions through not only iron-catalysed oxidative reactions but also inflammatory processes. However, B[A]P initiates only inflammatory responses. These pollutants generate increased levels of proteases and decrease the concentrations of free alpha(1)PI. There is also a clear relationship between the partial inactivation of alpha(1)PI and the occurrence of ROS after exposure to Fe(2)O(3), alone or as a carrier of B[A]P. Hence, the proteinase/anti-proteinase balance might be more disrupted by Fe(2)O(3) or B[A]P-coated onto Fe(2)O(3) particles than by B[A]P alone. These results suggest a mechanism that can explain why B[A]P-coated onto Fe(2)O(3) particles are more injurious than B[A]P alone.
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PMID:Modification of the proteinase/anti-proteinase balance in the respiratory tract of Sprague-Dawley rats after single intratracheal instillation of benzo[A]pyrene-coated onto Fe(2)O(3) particles. 1094 2

Particle size distribution is a major determinant of particle clearance by the mononuclear phagocytic system and the potential for concomitant activation of resident macrophages. To test the safety of a second-generation perflubron-based emulsion (60% perfluorocarbon [PFC] wt/vol; Oxygent [Alliance Pharmaceutical Corp., San Diego, CA]) with a small mean particle size, two parallel, randomized, double-blinded, placebo-controlled studies were conducted in 48 healthy volunteers (n = 24 per study). The study described herein focuses on safety concerning immune function. The primary endpoint was defined prospectively as delayed hypersensitivity skin test responses with lymphocyte proliferative responses to mitogenic stimulation providing a secondary measure for changes in cell-mediated immunity. Subjects received either perflubron emulsion IV (1.2 g PFC/kg or 1.8 g PFC/kg) or saline (3 mL/kg) control. Perflubron emulsion had no effect on delayed hypersensitivity skin reactions, lymphocyte proliferative potential, circulating immunoglobulins, complement activation, or plasma levels of the inflammatory cytokines, tumor necrosis factor-alpha, interleukin-1 alpha, and interleukin-1 beta. Perflubron emulsion was generally well tolerated, although there was a dose-dependent increase in minor flu-like symptoms in the perflubron treatment groups at 24 h after dosing. Increased serum levels of interleukin-6 were observed in those subjects exhibiting febrile responses. The clinical safety profile of perflubron emulsion supports its continued investigation as a temporary oxygen carrier in surgical patients to reduce exposure to allogeneic blood transfusion.
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PMID:Randomized safety studies of intravenous perflubron emulsion. II. Effects on immune function in healthy volunteers. 1100 31

Acute lung injury models demonstrate that high-frequency oscillatory ventilation (HFOV) improves lung function, mechanics, and histopathology with reduced inflammatory mediators. Neither human HFOV trials nor premature animal studies have adequately evaluated these factors during prolonged HFOV. The objective of this study was to compare the effect of prolonged HFOV with low tidal volume (VT) positive pressure ventilation (LV-PPV) in an immature baboon model for neonatal chronic lung disease (CLD). After administration of prenatal steroids, 18 baboons were delivered by cesarean section at 125 d (term = 185 d), treated with exogenous surfactant, then randomized to either HFOV or LV-PPV by 5 min age. Animals were maintained on oxygen on an "as needed" basis and on nutritional support for 1 to 2 mo. Serial pulmonary function testing (PFT) was performed. Tracheal aspirates were analyzed for interleukin-6 (IL-6), IL-8, tumor necrosis factor-alpha (TNF-alpha), IL-1beta, and IL-10. Lungs were inflation fixed for morphometric analyses. From 12 h through 10 d age, HFOV animals had consistently lower fraction of inspired oxygen (FI(O(2))) and higher a/ A ratio. Pulmonary mechanics were significantly improved in HFOV animals at nearly every time point analyzed from 12 h to 28 d. There were no consistent differences in tracheal IL-6, TNF-alpha, IL-1beta, or IL-10 after 24 h age. Higher tracheal IL-8 values and macrophage/monocyte numbers were found in LV-PPV animals after 1 wk and 3 to 4 wk ventilation. Both groups exhibited pulmonary pathologic lesions found in extremely immature humans, including alveolar hypoplasia, variable saccular wall fibrosis, and minimal airway disease. HFOV animals had significantly better lung inflation patterns by panel of standards analysis. Early, prolonged HFOV significantly improved early lung function with sustained improvement in pulmonary mechanics out to 28 d. Immature baboons managed with HFOV had less pulmonary inflammation in the hyaline membrane disease (HMD) recovery phase. Though enhanced alveolization was not observed, HFOV for 1 to 2 mo resulted in consistently more uniform lung inflation than LV-PPV.
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PMID:High-frequency oscillatory ventilation: effects on lung function, mechanics, and airway cytokines in the immature baboon model for neonatal chronic lung disease. 1106 28

Reactive oxygen intermediates (ROIs) are important mediators of a variety of pathological processes, including inflammation and ischemia/reperfusion injury. Cytokines and chemokines are detected at mRNA level in human and animal ischemic brains. This suggests that hypoxia/reoxygenation may induce cytokine production through generation of ROIs. In this study, we investigated the cytokine induction and inhibition by antioxidants in rat cortical mixed glial cells exposed to in vitro ischemia-like insults (hypoxia plus glucose deprivation). The results showed that interleukin-6 (IL-6) mRNA and protein, but not tumor necrosis factor-alpha (TNF-alpha) or interleukin-1beta (IL-1beta), were induced during hypoxia/hypoglycemia followed by reoxygenation in the mixed glial cells. The accumulation of IL-6 mRNA was induced as early as 15 min after hypoxia/hypoglycemia and its level was further increased after subsequent reoxygenation. Among the antioxidants studied, only resveratrol suppressed IL-6 gene expression and protein secretion in mixed glial cultures under hypoxia/hypoglycemia followed by reoxygenation. These findings suggest that resveratrol might be useful in treating ischemic-induced inflammatory processes in stroke.
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PMID:Resveratrol inhibits interleukin-6 production in cortical mixed glial cells under hypoxia/hypoglycemia followed by reoxygenation. 1110 30

The aim of this study was to define the inflammatory changes occurring in the lungs of infants at risk for bronchopulmonary dysplasia (BPD) over the first 28 days of life, and to define an optimal strategy for steroids therapy in the prevention of BPD. We measured levels of interleukin-6 (IL-6) and interleukin-1 beta (IL-1beta) in tracheal aspirate (TA) samples and blood of premature infants with severe respiratory distress syndrome RDS (n = 45) on the first day of life prior to initiation of surfactant therapy and on days 5-7, 12-14, 19-21, and 26-28. Levels of IL-6 and IL-1beta were determined with a commercially available enzyme-linked immunoassay. Logistic regression analyses were performed in order to examine differences in trends in levels of IL-6 and IL-1beta between groups of infants. Infants were divided into group I (n = 30, FiO(2) < or = 0.35 at 28 days) and group II (n = 15, FiO(2) > 0.35 based on their likelihood of developing BPD at 36 weeks postconceptional age (PCA). The infants were comparable with respect to mean ( +/- SEM) birth weight (895 +/- 33 g vs. 900 +/- 40 g), gestational age (27 +/- 0.38 weeks vs. 27 +/- 0.54 weeks), and severity of respiratory illness at entry into the study (mean airway pressure: 12 +/- 1 cmH(2)O vs. 12 +/- 1 cmH(2)O, and oxygen index: 15 +/- 2 vs. 19 +/- 4) (group I vs. group II, respectively). Logistic regression analyses failed to reveal any significant differences in linear trends of levels of IL-6 and IL-1beta in TA samples between both groups of infants. No particular pattern of change in levels of IL-6 or IL-1beta could be identified among groups of infants. Levels of IL-6 and IL-1beta in TA samples on the first day of life failed to predict the need for FiO(2) > 0.35 at 28 days of age. We could not identify an increasing trend or a specific pattern of changes in postnatal levels of IL-6 or IL-1beta in TA samples of infants who were at greater risk of developing BPD at 36 weeks PCA compared to infants who were not.
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PMID:Serial changes in levels of IL-6 and IL-1beta in premature infants at risk for bronchopulmonary dysplasia. 1127 35

The generation of reactive oxygen species (free radicals) is an important factor in the development and maintenance of rheumatoid arthritis in humans and animal models. One source of free radicals is nitric oxide produced within the synoviocytes and chondrocytes and giving rise to the highly toxic radical peroxynitrite. Several cytokines, including tumour necrosis factor-alpha (TNFalpha) are involved in the formation of free radicals, partly by increasing the activity of nitric oxide synthase. Indeed, nitric oxide may mediate some of the deleterious effects of cytokines on bone resorption. Aspirin, tetracyclines, steroids and methotrexate can suppress nitric oxide synthase. Dietary antioxidants include ascorbate and the tocopherols and beneficial effects of high doses have been reported especially in osteoarthritis. There is also evidence for beneficial effects of beta-carotene and selenium, the latter being a component of the antioxidant enzyme glutathione peroxidase. The polyunsaturated fatty acids (PUFA) include the n-3 compounds, some of which are precursors of eicosanoid synthesis, and the n-6 group which can increase formation of the pro-inflammatory cytokines TNFalpha and interleukin-6, and of reactive oxygen species. Some prostaglandins, however, suppress cytokine formation, so that n-3 PUFA often oppose the inflammatory effects of some n-6-PUFA. gamma-linolenic acid (GLA) is a precursor of prostaglandin E1, a fact which may account for its reported ability to ameliorate arthritic symptoms. Fish oil supplements, rich in n-3 PUFA such as eicosapentaenoic acid have been claimed as beneficial in rheumatoid arthritis, possibly by suppression of the immune system and its cytokine repertoire. Some other oils of marine origin (e.g. from the green-lipped mussel) and a range of vegetable oils (e.g. olive oil and evening primrose oil) have indirect anti-inflammatory actions, probably mediated via prostaglandin E1. Overall, there is a growing scientific rationale for the use of dietary supplements as adjuncts in the treatment of inflammatory disorders such as rheumatoid arthritis and osteoarthritis.
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PMID:Antioxidants and fatty acids in the amelioration of rheumatoid arthritis and related disorders. 1129 72

Growing evidence obtained in recent years indicates that anaphylatoxin C5a receptors (C5aR) are not restricted to myeloid cells but are also expressed on nonmyeloid cells in different tissues such as brain, lung, skin and liver. In contrast to its well-defined systemic functions, the actions of anaphylatoxins in these organs are poorly characterized. The liver can be a primary target organ for the C5a anaphylatoxin since the liver is directly connected to the gut, via the mesenteric veins and portal vein which is a main source of complement activating lipopolysaccharides (LPS). In the normal rat liver, the C5aR is only expressed by nonparenchymal cells, i.e. strongly by Kupffer cells (KC) and hepatic stellate cells (HSC) and weakly by sinusoidal endothelial cells (SEC), but not expressed by the parenchymal hepatocytes (HC). Accordingly, direct effects of C5a were only found in the C5aR-expressing KC and HSC: C5a induced the release of prostanoids from KC and HSC and enhanced the LPS-dependent release of interleukin-6 from KC. These soluble mediators indirectly influenced effector functions of the C5aR-free HC. C5a enhanced the glycogen phosphorylase activity and thus the glucose output from HC indirectly via prostanoids released from KC and HSC. Glucose can serve as an energy substrate as well as an electron donor for the synthesis of reactive oxygen intermediates by KC. Moreover, C5a also enhanced transcription of the gene for the type-2 acute phase protein alpha 2-macroglobulin in HC indirectly by increasing LPS-dependent IL-6 release from KC. Under pathological conditions, C5aR was found to be upregulated in various organs including the liver. Simulation of inflammatory conditions by treatment of rats with IL-6, a main inflammatory mediator in the liver, caused a de novo expression of functional C5aR in HC. In livers of IL-6-treated rats, C5a initiated glucose output from HC and perhaps other HC-specific defense reactions directly without the intervention of soluble mediators from nonparenchymal cells.
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PMID:Functions of anaphylatoxin C5a in rat liver: direct and indirect actions on nonparenchymal and parenchymal cells. 1136 31

This study was designed to examine the relationship between seasonal changes in training and competition load, and changes in leukocyte subsets, stress hormones, and interleukin-6 (IL-6) in response to a standardised bout of endurance exercise. In addition, changes in mood states were monitored. Ten male, international Nordic skiers, age 20-29, maximal oxygen uptake 70-82 ml x kg(-1) x min(-1) performed the same incremental treadmill tests to exhaustion at the same time of day (+/-1 h), during the competitive season (in-season HI test) and the recovery season (off-season LO test). The subject filled out a training and competition log (TC score) for three weeks prior to each test and a 65-item Profile of Mood State (POMS) test on arrival at the laboratory. Venous blood for haematological, hormonal, and IL-6 analysis was drawn before and at 0, 15, 30, 60, 120 and 240 min after the test. TC score was more than twice as high during the competitive season (16.0 +/- 3.9) compared to the off-season period (7.0 +/- 4.4). An ANOVA procedure for repeated measures showed no difference in exercise induced changes in concentrations of neutrocytes, lymphocytes, epinephrine, ACTH or cortisol between the in-season HI and off-season LO tests; however, norepinephrine and the IL-6 concentrations were elevated at the in-season HI test compared to the off-season LO test. There were no significant differences in POMS global mood score or sub-scores between the in-season HI and the off-season LO tests. Thus, in a group of elite Nordic skiers, we conclude that a doubling of the training and competition load during the winter season does not alter the leukocyte and stress hormone responses to an incremental exercise test to exhaustion.
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PMID:No effect of seasonal variation in training load on immuno-endocrine responses to acute exhaustive exercise. 1137 27

Photodynamic therapy (PDT), utilizing a photosensitizer and visible light, causes localized oxidative damage. With the mitochondrial photosensitizer Pc 4, PDT induces apoptosis, yet its molecular targets are not known. Here, the anti-apoptotic protein Bcl-2 is shown to be highly sensitive to PDT, as judged on Western blots by the disappearance of anti-Bcl-2-reactive material from the position of the native 26 kDa protein. The loss of Bcl-2 was PDT dose dependent and was observed for both endogenous and overexpressed Bcl-2 in several cell lines, immediately after PDT, and with chilled cells. It was accompanied by a trace of a 23-kDa cleavage product as well as high-molecular weight products that may result from photochemical crosslinking. PDT-induced Bcl-2 loss occurred in MCF-7 cells that do not express caspase-3 or in the presence of protease inhibitors, but was prevented, along with the induction of apoptosis, by the singlet oxygen scavenger L-histidine. Loss of FLAG-Bcl-2 was observed with both anti-FLAG and anti-Bcl-2 antibodies, indicating loss of native protein rather than simple BCL-2-epitope destruction. Photochemical damage was not observed in Bcl-x(L), Bax, Bad, the voltage-dependent anion channel, or the adenine nucleotide translocator. Therefore, Bcl-2 is one target of PDT with Pc 4, and PDT damage to Bcl-2 contributes to its efficient induction of apoptosis.
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PMID:Photochemical destruction of the Bcl-2 oncoprotein during photodynamic therapy with the phthalocyanine photosensitizer Pc 4. 1142 92


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