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.
A B Waxman, O Einarsson, T Seres, R G Knickelbein, J B Warshaw, R Johnston, R J Homer, J A Elias
Title and authors | Publication | Year |
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NOX4 Mediates Epithelial Cell Death in Hyperoxic Acute Lung Injury Through Mitochondrial Reactive Oxygen Species
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In vitro airway models from mice, rhesus macaques, and humans maintain species differences in xenobiotic metabolism and cellular responses to naphthalene.
Kelty J, Kovalchuk N, Uwimana E, Yin L, Ding X, Van Winkle L |
American journal of physiology. Lung cellular and molecular physiology | 2022 |
Oxygen-Saturation Targets for Critically Ill Adults Receiving Mechanical Ventilation.
Semler MW, Casey JD, Lloyd BD, Hastings PG, Hays MA, Stollings JL, Buell KG, Brems JH, Qian ET, Seitz KP, Wang L, Lindsell CJ, Freundlich RE, Wanderer JP, Han JH, Bernard GR, Self WH, Rice TW |
The New England journal of medicine | 2022 |
Interleukin-11 receptor subunit α-1 is required for maximal airway responsiveness to methacholine after acute exposure to ozone.
Johnston RA, Atkins CL, Siddiqui SR, Jackson WT, Mitchell NC, Spencer CY, Pilkington AW 4th, Kashon ML, Haque IU |
American Journal of Physiology - Regulatory, Integrative and Comparative Physiology | 2022 |