Endotoxin protection of rats from pulmonary oxygen toxicity: possible cytokine involvement

1990 ◽  
Vol 68 (2) ◽  
pp. 549-553 ◽  
Author(s):  
J. T. Berg ◽  
R. C. Allison ◽  
V. R. Prasad ◽  
A. E. Taylor
Keyword(s):  
Superoxide Dismutase ◽  
Enzyme Activity ◽  
Tumor Necrosis Factor ◽  
Lung Injury ◽  
Antioxidant Enzyme ◽  
Tumor Necrosis ◽  
Interleukin 1 ◽  
Oxygen Toxicity ◽  
Antioxidant Enzyme Activity ◽  
Necrosis Factor

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.

Molecular basis for tumor necrosis factor-induced increase in pulmonary superoxide dismutase activities

1990 ◽  
Vol 259 (6) ◽  
pp. L506-L512 ◽  
Author(s):  
M. F. Tsan ◽  
J. E. White ◽  
C. Treanor ◽  
J. B. Shaffer
Keyword(s):  
Superoxide Dismutase ◽  
Enzyme Activity ◽  
Tumor Necrosis Factor ◽  
Molecular Basis ◽  
Tumor Necrosis ◽  
Oxygen Toxicity ◽  
Specific Protein ◽  
Antioxidant Enzyme Activities ◽  
Tracheal Insufflation ◽  
Necrosis Factor

Tracheal insufflation of tumor necrosis factor (TNF) enhances pulmonary antioxidant enzyme activities and protects rats against oxygen toxicity (J. Appl. Physiol. 68: 1211–1219, 1990). We now report that tracheal insufflation of TNF selectively induced pulmonary Mn-superoxide dismutase (SOD) mRNA in normoxia- and hyperoxia-exposed rats, leading to increased amounts of Mn-SOD specific protein and enzyme activity. Tracheal insufflation of TNF had no effect on the levels of pulmonary Cu,Zn-SOD mRNA or specific protein. Hyperoxia alone also selectively induced pulmonary Mn-SOD mRNA. However, the hyperoxia-induced increase in Mn-SOD mRNA was not associated with an increase in Mn-SOD specific protein or enzyme activity. The results suggest that the increased pulmonary Mn-SOD in TNF-insufflated rats may contribute to the TNF-induced protection against oxygen toxicity.

Cytokines increase rat lung antioxidant enzymes during exposure to hyperoxia

1989 ◽  
Vol 66 (2) ◽  
pp. 1003-1007 ◽  
Author(s):  
C. W. White ◽  
P. Ghezzi ◽  
S. McMahon ◽  
C. A. Dinarello ◽  
J. E. Repine
Keyword(s):  
Superoxide Dismutase ◽  
Antioxidant Enzymes ◽  
Antioxidant Enzyme ◽  
Enzyme Activities ◽  
Tumor Necrosis ◽  
Interleukin 1 ◽  
Antioxidant Enzyme Activities ◽  
Rat Lung ◽  
Glucose 6 Phosphate Dehydrogenase ◽  
Necrosis Factor

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.

Effects of recombinant human superoxide dismutase on tumor necrosis factor-induced lung injury in awake sheep

1993 ◽  
Vol 74 (6) ◽  
pp. 2641-2648 ◽  
Author(s):  
T. Amari ◽  
K. Kubo ◽  
T. Kobayashi ◽  
M. Sekiguchi
Keyword(s):  
Pulmonary Hypertension ◽  
Superoxide Dismutase ◽  
Tumor Necrosis Factor ◽  
Lung Injury ◽  
Superoxide Anion ◽  
Tumor Necrosis ◽  
Late Phase ◽  
Sod Activity ◽  
Lung Lymph ◽  
Necrosis Factor

Tumor necrosis factor alpha (TNF) is a mediator of acute lung injury after endotoxemia, but the precise mechanism of TNF-induced lung injury remains unclear. To clarify the role of oxygen radicals, especially superoxide anion, in TNF-induced lung injury, we examined the effects of recombinant human superoxide dismutase (rhSOD; 4,200 U/mg) on lung physiological and biochemical changes after TNF infusion in awake sheep (n = 17). We prepared chronically instrumented sheep for lung lymph collection and hemodynamic monitoring. Recombinant human TNF (3.5 micrograms/kg iv) induced a biphasic response in awake sheep. Pulmonary hypertension peaked within 15 min of initiation of TNF and remained elevated for 3 h, followed by increased lung vascular permeability. rhSOD attenuated the pulmonary hypertension in both early and late phases but caused no change in the timing or magnitude of lung fluid balance changes during the late phase. Thromboxane A2 (thromboxane B2) and prostacyclin (6-ketoprostaglandin F1 alpha) metabolite levels in plasma and lymph increased after the TNF infusion, and rhSOD attenuated these changes. The intravenous infusion of rhSOD resulted in the appearance of significant levels of SOD activity in both plasma and lung lymph before and after TNF infusion. These findings suggest that superoxide anion may be implicated in the pathogenesis of the pulmonary hypertension induced by TNF in sheep.

Protection against oxygen toxicity by tracheal insufflation of endotoxin: role of Mn SOD and alveolar macrophages

1994 ◽  
Vol 266 (1) ◽  
pp. L38-L45 ◽  
Author(s):  
G. Tang ◽  
J. T. Berg ◽  
J. E. White ◽  
P. D. Lumb ◽  
C. Y. Lee ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Alveolar Macrophages ◽  
Tumor Necrosis ◽  
Manganese Superoxide Dismutase ◽  
Interleukin 1 ◽  
Oxygen Toxicity ◽  
Adult Rats ◽  
Manganese Superoxide ◽  
Tracheal Insufflation ◽  
Necrosis Factor

Endotoxin and the cytokines, tumor necrosis factor and interleukin-1, are known to protect adult rats against O2 toxicity. However, whether the effect of endotoxin is mediated through its direct effect on lung cells or through cytokines is not clear. In this study, we demonstrated that endotoxin at a dosage of 5 micrograms/rat (14-20 micrograms/kg) attenuated O2-induced pulmonary injury and markedly prolonged the survival of rats exposed to 100% O2. Endotoxin was more protective when given by intratracheal insufflation or intravenous injection than by intraperitoneal injection. The endotoxin-induced O2 tolerance was associated with a selective enhancement of pulmonary manganese superoxide dismutase, but not Cu,Zn SOD, mRNA. In addition, depletion of 84% rat alveolar macrophages by liposome-encapsulated dichloromethylene diphosphonate, resulted in a marked reduction (86%) of endotoxin-induced release of tumor necrosis factor into the alveolar space. However, endotoxin was still protective in these alveolar macrophage-depleted animals.

Ablation of tumor necrosis factor receptor type I (p55) alters oxygen-induced lung injury

2000 ◽  
Vol 278 (5) ◽  
pp. L1082-L1090 ◽  
Author(s):  
Gloria S. Pryhuber ◽  
David P. O'Brien ◽  
Raymond Baggs ◽  
Richard Phipps ◽  
Heidie Huyck ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Lung Injury ◽  
Tumor Necrosis ◽  
Oxygen Toxicity ◽  
Intercellular Adhesion Molecule ◽  
Type I ◽  
Intratracheal Administration ◽  
Tnf Α ◽  
Early Survival ◽  
Necrosis Factor

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)-α is induced in lungs exposed to high concentrations of oxygen; however, its contribution to hyperoxia-induced lung injury remains unclear. Both TNF-α 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)-1β, IL-1 receptor antagonist, chemokine macrophage inflammatory protein (MIP)-1β, MIP-2, interferon-γ-induced protein-10 (IP-10), and monocyte chemoattractant protein (MCP)-1 mRNA in response to intratracheal administration of recombinant murine TNF-α. However, IL-1β, IL-6, macrophage migration inhibitory factor, MIP-1α, 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-α receptor function will not protect against pulmonary oxygen toxicity.

Induction of pulmonary Mn superoxide dismutase mRNA by interleukin-1

1994 ◽  
Vol 266 (6) ◽  
pp. L664-L671 ◽  
Author(s):  
J. E. White ◽  
M. F. Tsan
Keyword(s):  
Superoxide Dismutase ◽  
Enzyme Activity ◽  
Tumor Necrosis ◽  
Actinomycin D ◽  
Interleukin 1 ◽  
Transcriptional Level ◽  
Mrna Synthesis ◽  
Beta Actin ◽  
Actin Mrna ◽  
Necrosis Factor

We have previously demonstrated that intratracheal (IT) but not intraperitoneal (IP) administration of 5 micrograms tumor necrosis factor (TNF) or interleukin-1 (IL-1) selectively enhances pulmonary Mn superoxide dismutase (Mn SOD) mRNA, leading to increased Mn SOD protein and enzyme activity, and protects rats against O2 toxicity. In this study, we demonstrated that enhancement of pulmonary Mn SOD mRNA by TNF or IL-1 was highly dependent on the route of administration. IT insufflation of 5 micrograms TNF or IL-1 selectively enhanced levels of pulmonary but not splenic or renal Mn SOD mRNA. In contrast, IP or intravenous (i.v.) administration of TNF (5 micrograms) or IL-1 (5, 20, or 50 micrograms) had little or no effect on levels of Mn SOD mRNA in the lung, spleen, or kidney. Both TNF and IL-1, whether given by IT, IP, or i.v. administration, had no effect on levels of Cu, Zn SOD mRNA. IP administration of 2 mg/kg actinomycin D 2 h before IT insufflation of IL-1 paradoxically increased the level of pulmonary Mn SOD mRNA without affecting the level of Cu,Zn SOD or beta-actin mRNA in IL-1-treated rats. Nuclear runoff transcription assay revealed that IT insufflation of IL-1 enhanced the rate on MN SOD but not Cu,Zn SOD mRNA synthesis. We conclude that IL-1-induced increase in pulmonary Mn SOD mRNA is at least in part regulated at the transcriptional level.

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