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Query: UMLS:C0242706 (hyperoxia)
 5,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

IL-1 and TNF are important mediators in the inflammatory response, and have been associated with endothelial cell damage in the lung. TNF and IL-1 cell-mediated injury has been proposed to occur through an increase in intracellular oxygen free radical production. However, these cytokines have also been shown to protect the lung from hyperoxia-mediated oxidant injury. In this paper we evaluated the response of the antioxidant enzymes, MnSOD and Cu/ZnSOD to IL-1, TNF, and LPS in both rat pulmonary artery and microvascular endothelial cells. These mediators produced an increase in MnSOD but not Cu/ZnSOD expression in both rat pulmonary endothelial cells. An additive effect was observed with co-treatment by the cytokines with LPS. The MnSOD mRNA induction is dependent upon a transcriptional event, but did not require de novo protein synthesis.
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PMID:Regulation of manganese superoxide dismutase: IL-1 and TNF induction in pulmonary artery and microvascular endothelial cells. 138 89

Treatment with endotoxin protects rats against lung injury during hyperoxia (greater than 98% oxygen at 1 atmosphere absolute for 60 h). This study demonstrates that serum from endotoxin-treated donor rats also protects recipients from oxygen toxicity. Rats treated with serum from saline-treated donors were not protected, and protection was not explained by residual endotoxin in protective sera. Unlike endotoxin-protected rats (where lung antioxidant enzyme activity is elevated after hyperoxia), postexposure superoxide dismutase (SOD) and catalase (CAT) activities in the lungs of serum-protected rats were not affected. Levels of tumor necrosis factor (TNF) and interleukin 1 (IL-1) in protective sera were increased. This study demonstrates that increases in lung SOD and CAT activity are not required for endotoxin protection from hyperoxia and suggests that TNF and IL-1 may participate in the mechanism of endotoxin protection.
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PMID:Endotoxin protection of rats from pulmonary oxygen toxicity: possible cytokine involvement. 231 67

Rats injected with interleukin-1 (10 micrograms) and tumor necrosis factor (10 micrograms) and then exposed continuously to hyperoxia (greater than 99% O2, 1 atm) survived longer, had increased lung reduced/oxidized glutathione ratios, smaller pleural effusions, less pulmonary hypertension and improved arterial blood gases. The percentage of animals surviving for 72 hours in hyperoxia increased from 8% to 94%. Although relatively small increases in glutathione redox cycle enzymes occurred four and sixteen hours following cytokine injection, dramatic increases in all major antioxidant enzymes including superoxide dismutase, glucose-6-phosphate dehydrogenase, glutathione reductase, glutathione peroxidase, and catalase had occurred following 72 hours of exposure to hyperoxia. The protective effect of IL-1 + TNF against lethal pulmonary O2 toxicity could be partially inhibited by pre-injection of lysine acetylsalicylate or, less effectively, of ibuprofen. Recent studies have suggested that both IL-1 and TNF can induce manganese (mitochondrial) superoxide dismutase mRNA and protein synthesis in a variety of cell types. Preliminary studies suggest that IL-1 alone, in ample dosage, can provide protection against lethal pulmonary O2 toxicity. Future studies should be directed toward identification of acute phase changes in lung antioxidant enzymes, surfactant proteins and/or lipid components, enzymes needed for synthesis of surfactant phospholipids, and/or other protective proteins. Additional work also needs to be done in identifying the lung cell types in which early enzyme induction occurs. These studies should provide a better understanding of mechanisms whereby protection against pulmonary O2 toxicity can occur. An understanding of the molecular mechanisms inducing protective proteins should lead to more precise pharmacologic control of these processes.
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PMID:Protection against pulmonary oxygen toxicity by interleukin-1 and tumor necrosis factor: role of antioxidant enzymes and effect of cyclooxygenase inhibitors. 251 82

Pretreatment with the combination of tumor necrosis factor/cachectin (TNF/C) and interleukin 1 (IL-1) increased glucose-6-phosphate dehydrogenase (G6PDH), glutathione reductase (GR), glutathione peroxidase (GPX), catalase (CAT), and superoxide dismutase (SOD) activities in lungs of rats continuously exposed to hyperoxia for 72 h, a time when all untreated rats had already died. Pretreatment with TNF/C and IL-1 also increased, albeit slightly, lung G6PDH and GR activities of rats exposed to hyperoxia for 4 or 16 h. By comparison, no differences occurred in lung antioxidant enzyme activities of TNF/C and IL-1- or saline-pretreated rats exposed to hyperoxia for 36 or 52 h; the latter is a time just before untreated rats began to succumb during exposure to hyperoxia. The results raise the possibility that TNF/C and IL-1 treatment can increase lung antioxidant enzyme activities and that increased lung antioxidant enzymes may contribute to the increased survival of TNF/C and IL-1-pretreated rats in hyperoxia for greater than 72 h.
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PMID:Cytokines increase rat lung antioxidant enzymes during exposure to hyperoxia. 265 81

Ventilator-induced lung injury in children and adults is characterized by an initial inflammatory phase. To investigate whether the inflammatory cytokine, IL-1, plays a role in this process, a rabbit model of ventilator-induced injury was created. Animals maintained under pentobarbital anesthesia were primed for injury by undergoing lung lavage with 22 mL/kg of saline and then ventilated for 8 h with either FIO2 0.21 and normal pressures or FIO2 1.0 and high ventilator pressures. The animals exposed to hyperoxia/hyperventilation demonstrated a greater increase in lung lavage neutrophil counts and a higher histological injury score, as well as a faster decline in oxygenation compared to the control animals. A third group of rabbits received 800 micrograms of recombinant IL-1 receptor antagonist after lung lavage and prior to the exposure to FIO2 1.0 and high ventilator pressures. These animals had significantly lower concentrations of albumin and elastase and lower neutrophil counts in their lungs after the 8-h ventilatory period compared to hyperoxia/hyperventilation rabbits. IL-1 blockade had no effect on the decline in dynamic compliance and oxygenation seen in saline-treated hyperoxic/hyperventilated rabbits. IL-1 is a mediator of acute inflammation due to ventilator-induced lung injury.
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PMID:Effect of IL-1 blockade on inflammatory manifestations of acute ventilator-induced lung injury in a rabbit model. 777 27

A broad array of oxidative stresses modulates gene expression in a variety of mammalian cells. One goal of this review was to characterize cellular responses to oxidative injury, how these processes are regulated, and the outcome for a particular cell or tissue. Many genes induced in response to specific oxidant stresses have been identified and include transcription factors, replication proteins, proteases, protease inhibitors, proteins affecting cell proliferation and various antioxidants, i.e. heme oxygenase, MT, and MnSOD. The latter enzyme is induced after a number of cytokines and oxidant stresses including hyperoxia and mineral dusts causing inflammation. Moreover, increases in mRNA levels of TNF and IL-1, cytokines inducing MnSOD, are observed after exposure to UV and ionizing radiation. Since increased electron flow could lead to generation of more AOS within mitochondria, increased levels of MnSOD might be necessary to maintain normal functioning of the mitochondria after oxidative stress. Alterations in cell growth are intrinsically related to the pathogenesis of many diseases. Paradoxically, some of the responses of cells to oxidative stress reflect cytotoxicity and cytostasis, whereas others result in increased cell proliferation. For example, induction of gadd genes observed after oxidative stress is related to growth arrest of cells, a response which might enable the cell to repair oxidative damage prior to replication. This phenomenon might prevent fixation of mutations associated with oxidative DNA damage. On the other hand, increased mRNA expression and activity of ODC, observed after exposure of cells to UV or asbestos is associated with increased cell proliferation. In addition, increased mRNA expression of cellular proto-oncogenes observed after exposure to oxidants could also be related to increased DNA synthesis or proliferation. Figure 5 provides a general scheme of cell responses to oxidative stress and possible ramifications. AOS can react with a number of target molecules including proteins, lipids, and DNA. These interactions elicit a number of signals including activation of gene regulatory factors (transcription factors) which in turn activate oxidative stress-responsive genes or regulons. Consequently, a number of proteins are produced with distinctive functions including DNA repair enzymes, antioxidants, proteases inhibitors, cytokines and proteins affecting cell proliferation. These cellular responses to AOS can lead to restoration of normal cellular function and adaptation to oxidative stress, cell death or aberrant proliferation. It is the latter two responses which can lead to a variety of disease states including cancer.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Cell and tissue responses to oxidative damage. 837 69

Acute lung injury is a frequent and treatment-limiting consequence of therapy with hyperoxic gas mixtures. To determine if IL-11 is protective in oxygen toxicity, we compared the effects of 100% O2 on transgenic mice that overexpress IL-11 in the lung and transgene (-) controls. IL-11 markedly enhanced survival in 100% O2 with 100% of transgene (-) animals dying within 72-96 h and > 90% of transgene (+) animals surviving for more than 10 d. This protection was associated with markedly diminished alveolar-capillary protein leak, endothelial and epithelial membrane injury, lipid peroxidation, and pulmonary neutrophil recruitment. Significant differences in copper zinc superoxide dismutase and catalase activities were not noted and the levels of total, reduced and oxidized glutathione were similar in transgene (+) and (-) animals. Glutathione reductase, glutathione peroxidase, and manganese superoxide dismutase activities were slightly higher in transgene (+) as versus (-) mice after 100% O2 exposure, and IL-11 diminished hyperoxia-induced expression of IL-1 and TNF. Hyperoxia also caused cell death with DNA fragmentation in the lungs of transgene (-) animals and IL-11 markedly diminished this cell death response. These studies demonstrate that IL-11 markedly diminishes hyperoxic lung injury. They also demonstrate this protection is associated with small changes in lung antioxidants, diminished hyperoxia-induced IL-1 and TNF production, and markedly suppressed hyperoxia-induced DNA fragmentation.
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PMID:Targeted lung expression of interleukin-11 enhances murine tolerance of 100% oxygen and diminishes hyperoxia-induced DNA fragmentation. 957 62

Retinopathy of prematurity (ROP) is characterized by inhibition of the growth of the retinal vessels and subsequent neovascularization. Pharmacologic doses of glucocorticoids are known to decrease growth and to suppress inflammation. The aim of the present study was to investigate whether hyperoxia and/or glucocorticoid affect the growth of the retinal vessels and the expression of the anti-inflammatory cytokine IL-1 receptor antagonist (IL-1ra). The following treatments were given to newborn rabbits during the rapid growth of retinal vessels: 1) placebo and room air (n = 14); 2) dexamethasone (Dx) at 1 mg/kg/d during d 3 to 8 and room air (n = 14); 3) placebo and 100% oxygen (d 3 to 7) (n = 14); 4) Dx and O2 (n = 16). On d 12, the eyes were studied for retinal vessel length and vascular surface area from India ink-perfused vessels. When indicated, retinas were harvested on d 7 and studied for the expression of IL-1ra mRNA using Northern blot analysis. Hyperoxia decreased the length and area of the retinal vessel complexes (p < 0.01) and induced neovascularization in three of eight animals (38%). Dx decreased the length and area (p < 0.01) and tended to increase the tortuosity of the retinal vessels. Dx did not potentiate the hyperoxia-induced suppression of retinal vessel growth and prevented the hyperoxia-induced neovascularization (p = 0.04). Hyperoxia inhibited the expression of IL-1ra mRNA, whereas Dx ameliorated the hyperoxia-induced suppression of IL-1ra. According to present results, glucocorticoid decreases the retinal vessel growth and may decrease the hyperoxia-induced neovascularization. We propose that immature and damaged retinal vessels are affected by pharmacologic dosage of glucocorticoid.
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PMID:Hyperoxia and glucocorticoid modify retinal vessel growth and interleukin-1 receptor antagonist in newborn rabbits. 1008 47

Hyperoxic lung injury, believed to be mediated by reactive oxygen species, inflammatory cell activation, and release of cytotoxic cytokines, complicates the care of many critically ill patients. The cytokine tumor necrosis factor (TNF)-alpha is induced in lungs exposed to high concentrations of oxygen; however, its contribution to hyperoxia-induced lung injury remains unclear. Both TNF-alpha treatment and blockade with anti-TNF antibodies increased survival in mice exposed to hyperoxia. In the current study, to determine if pulmonary oxygen toxicity is dependent on either of the TNF receptors, type I (TNFR-I) or type II (TNFR-II), TNFR-I or TNFR-II gene-ablated [(-/-)] mice and wild-type control mice (WT; C57BL/6) were studied in >95% oxygen. There was no difference in average length of survival, although early survival was better for TNFR-I(-/-) mice than for either TNFR-II(-/-) or WT mice. At 48 h of hyperoxia, slightly more alveolar septal thickening and peribronchiolar and periarteriolar edema were detected in WT than in TNFR-I(-/-) lungs. By 84 h of oxygen exposure, TNFR-I(-/-) mice demonstrated greater alveolar debris, inflammation, and edema than WT mice. TNFR-I was necessary for induction of cytokine interleukin (IL)-1beta, IL-1 receptor antagonist, chemokine macrophage inflammatory protein (MIP)-1beta, MIP-2, interferon-gamma-induced protein-10 (IP-10), and monocyte chemoattractant protein (MCP)-1 mRNA in response to intratracheal administration of recombinant murine TNF-alpha. However, IL-1beta, IL-6, macrophage migration inhibitory factor, MIP-1alpha, MIP-2, and MCP-1 mRNAs were comparably induced by hyperoxia in TNFR-I(-/-) and WT lungs. In contrast, mRNA for manganese superoxide dismutase and intercellular adhesion molecule-1 were induced by hyperoxia only in WT mice. Differences in early survival and toxicity suggest that pulmonary oxygen toxicity is in part mediated by TNFR-I. However, induction of specific cytokine and chemokine mRNA and lethality in response to severe hyperoxia was independent of TNFR-I expression. The current study supports the prediction that therapeutic efforts to block TNF-alpha receptor function will not protect against pulmonary oxygen toxicity.
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PMID:Ablation of tumor necrosis factor receptor type I (p55) alters oxygen-induced lung injury. 1078 41

Interleukins (IL) are part of the group of immune mediators known as cytokines. IL are produced by many different cells and possess a wide spectrum of biological activities. This review will be focused on the role of IL-1 to 6, 8, 10-13 as it pertains to the effects of hyperoxia on the adult and newborn lung in animal models. Hyperoxic exposure to the adult and newborn lung had variable effects on the expression of IL-1alpha and IL-1beta. Increased IL-6 levels were seen in adult lungs by day 3 and in the newborn lungs by day 10 of exposure to hyperoxia. IL-8 also peaked around day 10 in the newborn lung but there were no significant changes in IL-10. Pretreatment with IL-1, endotoxin, rhSOD, lidocaine, lisofylline, pentoxifylline and overexpression of IL-6, 11, and 13 seemed to attenuate hyperoxic lung injury in the adult. This protection was accompanied by increased pulmonary MnSOD, VEGF expression and decreased apoptosis. It is clear that IL have a significant role to play in hyperoxic lung injury. Increased IL expression and release has a cascade effect and appears to predate the influx of inflammatory cells. There are significant differences in the type and timing of IL expression and release in the adult and newborn lung in response to hyperoxia. Designing a therapeutic approach to counteract oxygen toxicity in the immature lung first needs understanding of the unique responses in the newborn.
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PMID:Developmental differences in the role of interleukins in hyperoxic lung injury in animal models. 1210 29


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