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Protection against pulmonary oxygen toxicity by interleukin-1 and tumor necrosis factor: Role of antioxidant enzymes and effect of cyclooxygenase inhibitors

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Biotherapy

Abstract

Rats injected with interleukin-1 (10 μg) and tumor necrosis factor (10 μg) and then exposed continuously to hyperoxia (> 99% O2, 1 atm) survived longer, had increased lung reduced/oxidized glutathione ratios, smaller pleural effusions, less pulmonary hypertension and improv+++ed 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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Authors and Affiliations

  1. Department of Pediatrics, Webb-Waring Lung Institute, 80262, Denver, CO, USA

    Carl W. White & Pietro Ghezzi

  2. Department of Experimental Medicine, Webb-Waring Lung Institute, 80262, Denver, CO, USA

    Carl W. White & Pietro Ghezzi

  3. The Children's Hospital, University of Colorado Health Sciences Center, 80262, Denver, CO, USA

    Carl W. White & Pietro Ghezzi

  4. Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy

    Carl W. White & Pietro Ghezzi

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  1. Carl W. White
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White, C.W., Ghezzi, P. Protection against pulmonary oxygen toxicity by interleukin-1 and tumor necrosis factor: Role of antioxidant enzymes and effect of cyclooxygenase inhibitors. Biotherapy 1, 361–367 (1989). https://doi.org/10.1007/BF02171012

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