Journal of Applied Physiology, Vol 72, Issue 5 1902-1907, Copyright © 1992 by American Physiological Society

ARTICLES

Role of tumor necrosis factor in oxygen toxicity

J. C. Jensen, H. W. Pogrebniak, H. I. Pass, C. Buresh, M. J. Merino, D. Kauffman, D. Venzon, H. N. Langstein and J. A. Norton
Surgical Metabolism and Thoracic Oncology Sections, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.

mRNA from lungs of mice exposed to high-dose oxygen (greater than 95%) for 3 days demonstrated increased expression of the genes for tumor necrosis factor (TNF), interleukin-1, and interleukin-6 compared with mRNA from lungs of mice exposed to room air. Daily treatment of mice exposed to high-dose oxygen with an antibody to TNF improved survival compared with mice receiving a similar dose of control immunoglobulin G. Pretreatment of mice with repetitive sublethal intraperitoneal doses of recombinant human TNF for 3 days or a single intravenous dose followed by exposure to high-dose oxygen afforded a significant survival advantage compared with high-dose oxygen-exposed mice pretreated with vehicle or interleukin-1. The repetitive intraperitoneal TNF pretreatment reduced the development of interstitial pneumonitis, pulmonary edema, and lung weight gain associated with oxygen toxicity and enhanced expression of the gene for the free radical protective enzyme manganous superoxide dismutase in lung tissue, a gene that is augmented as mice are exposed to high-dose oxygen. Furthermore a single intravenous dose of TNF 24 h after oxygen exposure was still protective. The results suggest that the toxicity of oxygen therapy can be partially ameliorated by either treatment with anti-TNF antibody or pretreatment and early treatment with TNF. These findings are consistent with the hypothesis that oxygen exposure induces TNF, which causes part of the toxicity of high-dose oxygen, and that pretreatment or early treatment with TNF induces the gene for an enzyme that recently has been shown to be very effective in protecting mice from the toxicity of oxygen.

This article has been cited by other articles:

				R. Choo-Wing, J. H. Nedrelow, R. J. Homer, J. A. Elias, and V. Bhandari Developmental differences in the responses of IL-6 and IL-13 transgenic mice exposed to hyperoxia Am J Physiol Lung Cell Mol Physiol, July 1, 2007; 293(1): L142 - L150. [Abstract] [Full Text] [PDF]

				V. Bhandari, R. Choo-Wing, R. J. Homer, and J. A. Elias Increased Hyperoxia-Induced Mortality and Acute Lung Injury in IL-13 Null Mice J. Immunol., April 15, 2007; 178(8): 4993 - 5000. [Abstract] [Full Text] [PDF]

				M. Yamada, H. Kubo, S. Kobayashi, K. Ishizawa, and H. Sasaki Interferon-{gamma}: a key contributor to hyperoxia-induced lung injury in mice Am J Physiol Lung Cell Mol Physiol, November 1, 2004; 287(5): L1042 - L1047. [Abstract] [Full Text] [PDF]

				C. Nara, K. Tateda, T. Matsumoto, A. Ohara, S. Miyazaki, T. J. Standiford, and K. Yamaguchi Legionella-induced acute lung injury in the setting of hyperoxia: protective role of tumour necrosis factor-{alpha} J. Med. Microbiol., August 1, 2004; 53(8): 727 - 733. [Abstract] [Full Text] [PDF]

				C. E. O. Baleeiro, S. E. Wilcoxen, S. B. Morris, T. J. Standiford, and R. Paine III Sublethal Hyperoxia Impairs Pulmonary Innate Immunity J. Immunol., July 15, 2003; 171(2): 955 - 963. [Abstract] [Full Text] [PDF]

				S. Perkowski, J. Sun, S. Singhal, J. Santiago, G. D. Leikauf, and S. M. Albelda Gene Expression Profiling of the Early Pulmonary Response to Hyperoxia in Mice Am. J. Respir. Cell Mol. Biol., June 1, 2003; 28(6): 682 - 696. [Abstract] [Full Text] [PDF]

				C. Barazzone and C. W. White Mechanisms of Cell Injury and Death in Hyperoxia . Role of Cytokines and Bcl-2 Family Proteins Am. J. Respir. Cell Mol. Biol., May 1, 2000; 22(5): 517 - 519. [Full Text]

				N. S. Ward, A. B. Waxman, R. J. Homer, L. L. Mantell, O. Einarsson, Y. Du, and J. A. Elias Interleukin-6-Induced Protection in Hyperoxic Acute Lung Injury Am. J. Respir. Cell Mol. Biol., May 1, 2000; 22(5): 535 - 542. [Abstract] [Full Text]

				G. S. Pryhuber, D. P. O'Brien, R. Baggs, R. Phipps, H. Huyck, I. Sanz, and M. H. Nahm Ablation of tumor necrosis factor receptor type I (p55) alters oxygen-induced lung injury Am J Physiol Lung Cell Mol Physiol, May 1, 2000; 278(5): L1082 - L1090. [Abstract] [Full Text] [PDF]

				C. L. S. George, G. Fantuzzi, S. Bursten, L. Leer, and E. Abraham Effects of lisofylline on hyperoxia-induced lung injury Am J Physiol Lung Cell Mol Physiol, May 1, 1999; 276(5): L776 - L785. [Abstract] [Full Text] [PDF]

				L. L. MANTELL, S. HOROWITZ, J. M. DAVIS, and J. A. KAZZAZ Hyperoxia-induced Cell Death in the Lung-the Correlation of Apoptosis, Necrosis, and Inflammation Ann. N.Y. Acad. Sci., January 1, 1999; 887(1): 171 - 180. [Abstract] [Full Text] [PDF]

				K. J. Haley, K. Patidar, F. Zhang, R. L. Emanuel, and M. E. Sunday Tumor necrosis factor induces neuroendocrine differentiation in small cell lung cancer cell lines Am J Physiol Lung Cell Mol Physiol, August 1, 1998; 275(2): L311 - L321. [Abstract] [Full Text] [PDF]

				N. Hussain, F. Wu, C. Christian, and M. J. Kresch Hyperoxia inhibits fetal rat lung fibroblast proliferation and expression of procollagens Am J Physiol Lung Cell Mol Physiol, October 1, 1997; 273(4): L726 - L732. [Abstract] [Full Text] [PDF]